The light-harvesting complex (LHC) consists of chlorophylls A and B and the chlorophyll A-B binding protein. LHC functions as a light receptor that captures and delivers excitation energy to photosystems I and II with which it is closely associated. Under changing light conditions, the reversible phosphorylation of light harvesting chlorophyll a/b binding proteins (LHCII) represents a system for balancing the excitation energy between the two photosystems [
].The N terminus of the chlorophyll A-B binding protein extends into the stroma where it is involved with adhesion of granal membranes and photo-regulated by reversible phosphorylation of its threonine residues [
]. Both these processes are believed to mediate the distribution of excitation energy between photosystems I and II.This family also includes the photosystem II protein PsbS, which plays a role in energy-dependent quenching that increases thermal dissipation of excess absorbed light energy in the photosystem [
].
This family consists of several peroxisomal biogenesis factor 11 (PEX11) proteins from several eukaryotic species. The PEX11 peroxisomal membrane proteins promote peroxisome division in multiple eukaryotes [
]. PEX11 genes in rice have diversification not only in sequences but also in expression patterns under normal and various stress conditions [].
This entry represents a group of cys-rich proteins, including cornifelin and PLAC8 from animals, MCA (MID1-COMPLEMENTING ACTIVITY) and PCR (PLANT CADMIUM RESISTANCE) from Arabidopsis and cell number regulators from maize [
,
].Cornifelin is part of the insoluble cornified cell envelope (CE) of stratified squamous epithelia [
,
]. PLAC8 is required for white adipocyte differentiation in vitro and cell number control in vivo [].Plant transports in this entry include MCA1, MCA2 and PCR1-12. MCA1 and MCA2 mediate Ca2+ uptake [
,
,
], while PCR2 is a zinc exporter involved in both zinc extrusion and long-distance zinc transport [].
The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme [
]. RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, Sigma70 (gene rpoD; major sigma factor) and Sigma54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.
This entry represents region 2 (sigma2 domain) found in several sigma factors, often in conjunction with sigma3 and sigma4 domains (
). This region is present in Sigma70 [
], Sigma28 (FliA), SigA [], SigR and RpoE. The sigma2 domain has a conserved 4-helical core, and often a variable insert subdomain.
The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme [
]. RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.With regard to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of promoters recognised by the major sigma factors [
,
]. The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. All plastid sigma factors belong to the superfamily of sigmaA/sigma70 and have sequences homologous to the conserved regions 1.2, 2, 3, and 4 of bacterial sigma factors [
].Region 2 of sigma-70 is the most conserved region of the entire protein. All members of this class of sigma-factor contain region 2. The high conservation is due to region 2 containing both the -10 promoter recognition helix and the primary core RNA polymerase binding determinant. The core-binding helix, interacts with the clamp domain of the largest polymerase subunit, beta prime [
,
]. The aromatic residues of the recognition helix, found at the C terminus of this domain are thought to mediate strand separation, thereby allowing transcription initiation [,
].
The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme [
]. RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.With regard to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of promoters recognised by the major sigma factors [
,
]. The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. All plastid sigma factors belong to the superfamily of sigmaA/sigma70 and have sequences homologous to the conserved regions 1.2, 2, 3, and 4 of bacterial sigma factors [
].Region 3 forms a discrete compact three helical domain within the sigma-factor. Region is not normally involved in the recognition of promoter DNA, but in some specific bacterial promoters containing an extended -10 promoter element, residues within region 3 play an important role. Region 3 primarily is involved in binding the core RNA polymerase in the holoenzyme [
].
The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme [
]. RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.With regard to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of promoters recognised by the major sigma factors [
,
]. The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. All plastid sigma factors belong to the superfamily of sigmaA/sigma70 and have sequences homologous to the conserved regions 1.2, 2, 3, and 4 of bacterial sigma factors [
].Each sigma2 domain is composed of a bundle of three α-helices that is virtually identical in all structures analyzed to date [
]. The second helix of this bundle is a major point for contact with a coiled-coil domain in the beta' subunit of the core RNA polymerase complex. The third helix of the bundle includes conserved residues along one face that are involved in DNA melting and in recognition of the -10 promoter element. The sigma3 domain, which is less conserved between members of the sigma70 family is also a three-helix domain, the first helix of which contains the residues implicated in contacting DNA upstream of extended -10 promoters. The sigma4, domain has two pairs of alpha helices; the carboxy-terminal pair forms a helix-turn-helix motif that contacts the promoter DNA in the region from -30 to -38.
The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme [
]. RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.With regard to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of promoters recognised by the major sigma factors [
,
]. The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. All plastid sigma factors belong to the superfamily of sigmaA/sigma70 and have sequences homologous to the conserved regions 1.2, 2, 3, and 4 of bacterial sigma factors [
].This entry represents regions 3 and 4 (or sigma3 and sigma4 domains) found in several sigma factors, often in conjunction with the sigma2 domain (
). Both regions 3 and 4 are present in Sigma70 [
], Sigma28 (FliA), and SigA [], while region4 is also found in SigmaF [] and RpoE. Regions 3 and 4 have a nucleotide-binding 3-helical core structure, consisting of a closed or partly open bundle with a right-handed twist. Some other nucleotide-binding proteins are thought to contain domains with a similar topology.
The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme [
]. RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.With regard to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of promoters recognised by the major sigma factors [
,
]. The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. All plastid sigma factors belong to the superfamily of sigmaA/sigma70 and have sequences homologous to the conserved regions 1.2, 2, 3, and 4 of bacterial sigma factors [
].Region 4 of sigma-70 like sigma-factors is involved in binding to the -35 promoter element via a helix-turn-helix motif [
]. Due to the way Pfam works, the threshold has been set artificially high to prevent overlaps with other helix-turn-helix families. Therefore there are many false negatives.
The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme [
]. RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.With regard to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of promoters recognised by the major sigma factors [
,
]. The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. All plastid sigma factors belong to the superfamily of sigmaA/sigma70 and have sequences homologous to the conserved regions 1.2, 2, 3, and 4 of bacterial sigma factors [
].This entry is found in all varieties of the sigma-70 type sigma factors, including the ECF subfamily. A number of sigma factors have names with a different number than 70 (i.e. sigma-38), but in fact, all except for the Sigma-54 family (
) are included within this entry.
This domain is found at the C terminus of topoisomerase I. DNA topoisomerase I (
) [
,
,
,
] is one of the two types of enzyme that catalyze the interconversion of topological DNA isomers. Type I topoisomerases act by catalyzing the transient breakage of DNA, one strand at a time, and the subsequent rejoining of the strands. When a eukaryotic type 1 topoisomerase breaks a DNA backbone bond, it simultaneously forms a protein-DNA link where the hydroxyl group of a tyrosine residue is joined to a 3'-phosphate on DNA, at one end of the enzyme-severed DNA strand. In eukaryotes and poxvirus topoisomerases I, there are a number of conserved residues in the region around the active site tyrosine [].
DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single- or double-strand breaks, crossing the strands through one another, then resealing the breaks [
]. These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis [,
]. DNA topoisomerases are divided into two classes: type I enzymes (; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (
; topoisomerases II, IV and VI) break double-strand DNA [
].Type I topoisomerases are ATP-independent enzymes (except for reverse gyrase), and can be subdivided according to their structure and reaction mechanisms: type IA (Topo IA; bacterial and archaeal topoisomerase I, topoisomerase III and reverse gyrase) and type IB (Topo IB; eukaryotic topoisomerase I and topoisomerase V). These enzymes are primarily responsible for relaxing positively and/or negatively supercoiled DNA, except for reverse gyrase, which can introduce positive supercoils into DNA. This function is vital for the processes of replication, transcription, and recombination. Unlike Topo IA enzymes, Topo IB enzymes do not require a single-stranded region of DNA or metal ions for their function. The type IB family of DNA topoisomerases includes eukaryotic nuclear topoisomerase I, topoisomerases of poxviruses, and bacterial versions of Topo IB []. They belong to the superfamily of DNA breaking-rejoining enzymes, which share the same fold in their C-terminal catalytic domain and the overall reaction mechanism with tyrosine recombinases [,
]. The C-terminal catalytic domain in topoisomerases is linked to a divergent N-terminal domain that shows no sequence or structure similarity to the N-terminal domains of tyrosine recombinases [,
].DNA topoisomerase I (
) [
,
,
,
] is one of the two types of enzyme that catalyze the interconversion of topological DNA isomers. Type I topoisomerases act by catalyzing the transient breakage of DNA, one strand at a time, and the subsequent rejoining of the strands. When a eukaryotic type 1 topoisomerase breaks a DNA backbone bond, it simultaneously forms a protein-DNA link where the hydroxyl group of a tyrosine residue is joined to a 3'-phosphate on DNA, at one end of the enzyme-severed DNA strand. In eukaryotes and poxvirus topoisomerases I, there are a number of conserved residues in the region around the active site tyrosine [].
DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single- or double-strand breaks, crossing the strands through one another, then resealing the breaks [
]. These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis [,
]. DNA topoisomerases are divided into two classes: type I enzymes (; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (
; topoisomerases II, IV and VI) break double-strand DNA [
].Type I topoisomerases are ATP-independent enzymes (except for reverse gyrase), and can be subdivided according to their structure and reaction mechanisms: type IA (Topo IA; bacterial and archaeal topoisomerase I, topoisomerase III and reverse gyrase) and type IB (Topo IB; eukaryotic topoisomerase I and topoisomerase V). These enzymes are primarily responsible for relaxing positively and/or negatively supercoiled DNA, except for reverse gyrase, which can introduce positive supercoils into DNA. This function is vital for the processes of replication, transcription, and recombination. Unlike Topo IA enzymes, Topo IB enzymes do not require a single-stranded region of DNA or metal ions for their function. The type IB family of DNA topoisomerases includes eukaryotic nuclear topoisomerase I, topoisomerases of poxviruses, and bacterial versions of Topo IB [
]. They belong to the superfamily of DNA breaking-rejoining enzymes, which share the same fold in their C-terminal catalytic domain and the overall reaction mechanism with tyrosine recombinases [,
]. The C-terminal catalytic domain in topoisomerases is linked to a divergent N-terminal domain that shows no sequence or structure similarity to the N-terminal domains of tyrosine recombinases [,
].This family of DNA topoisomerase I enzymes includes both type IA enzymes from bacteria and type IB enzymes from eukaryotes and viruses.Human topoisomerase I has been shown to be inhibited by camptothecin (CPT), a plant alkaloid with antitumour activity [
]. The crystal structures of human topoisomerase I comprising the core and carboxyl-terminal domains in covalent and noncovalent complexes with 22-base pair DNA duplexes reveal an enzyme that "clamps"around essentially B-form DNA. The core domain and the first eight residues of the carboxyl-terminal domain of the enzyme, including the active-site nucleophile tyrosine-723, share significant structural similarity with the bacteriophage family of DNA integrases. A binding mode for the anticancer drug camptothecin has been proposed on the basis of chemical and biochemical information combined with the three-dimensional structures of topoisomerase I-DNA complexes [
].Vaccinia virus, a cytoplasmically-replicating poxvirus, encodes a type I DNA topoisomerase that is biochemically similar to eukaryotic-like DNA topoisomerases I, and which has been widely studied as a model topoisomerase. It is the smallest topoisomerase known and is unusual in that it is resistant to the potent chemotherapeutic agent camptothecin. The crystal structure of an amino-terminal fragment of vaccinia virus DNA topoisomerase I shows that the fragment forms a five-stranded, antiparallel β-sheet with two short α-helices and connecting loops. Residues that are conserved between all eukaryotic-like type I topoisomerases are not clustered in particular regions of the structure [].
Phage integrases are enzymes that mediate unidirectional site-specific recombination between two DNA recognition sequences, the phage attachment site, attP, and the bacterial attachment site, attB []. Integrases may be grouped into two major families, the tyrosine recombinases and the serine recombinases, based on their mode of catalysis. Tyrosine family integrases, such as Bacteriophage lambda integrase, utilise a catalytic tyrosine to mediate strand cleavage, tend to recognise longer attP sequences, and require other proteins encoded by the phage or the host bacteria.The 356 amino acid lambda integrase consists of two domains: an N-terminal domain that includes residues 1-64 and is responsible for binding the arm-type sites of attP, and a C-terminal domain (CTD) that binds the lower affinity core-type sites and contains the catalytic site. The CTD can be further divided into the core-type binding domain (residues 65-169) and the catalytic core domain (170-356), the later representing this entry. The catalytic core adopts an alpha3-beta3-alpha4 fold, where one side of the beta sheet is exposed.The recombinases Cre from phage P1, XerD from Escherichia coli and Flp from yeast are members of the tyrosine recombinase family, and have a two-domain motif resembling that of lambda integrase, as well as sharing a conserved binding mechanism [
]. The structural fold of their catalytic core domains resemble that of Lambda integrase.The catalytic core of the eukaryotic DNA topoisomerase I shares significant structural similarity with the bacteriophage family of DNA integrases [
]. Topoisomerases I promote the relaxation of DNA superhelical tension by introducing a transient single-stranded break in duplex DNA and are vital for the processes of replication, transcription and recombination.
DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single- or double-strand breaks, crossing the strands through one another, then resealing the breaks [
]. These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis [
,
]. DNA topoisomerases are divided into two classes: type I enzymes (; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (
; topoisomerases II, IV and VI) break double-strand DNA [
].Type I topoisomerases are ATP-independent enzymes (except for reverse gyrase), and can be subdivided according to their structure and reaction mechanisms: type IA (Topo IA; bacterial and archaeal topoisomerase I, topoisomerase III and reverse gyrase) and type IB (Topo IB; eukaryotic topoisomerase I and topoisomerase V). These enzymes are primarily responsible for relaxing positively and/or negatively supercoiled DNA, except for reverse gyrase, which can introduce positive supercoils into DNA. This function is vital for the processes of replication, transcription, and recombination. Unlike Topo IA enzymes, Topo IB enzymes do not require a single-stranded region of DNA or metal ions for their function. The type IB family of DNA topoisomerases includes eukaryotic nuclear topoisomerase I, topoisomerases of poxviruses, and bacterial versions of Topo IB [
]. They belong to the superfamily of DNA breaking-rejoining enzymes, which share the same fold in their C-terminal catalytic domain and the overall reaction mechanism with tyrosine recombinases [,
]. The C-terminal catalytic domain in topoisomerases is linked to a divergent N-terminal domain that shows no sequence or structure similarity to the N-terminal domains of tyrosine recombinases [,
].This entry represents the N-terminal DNA-binding domain found in eukaryotic topoisomerase I, which is a type IB enzymes. To cleave the DNA backbone, these enzymes must make a transient phosphotyrosine bond. The N-terminal domain of human topoisomerase I is thought to coordinate the restriction of free strand rotation during the topoisomerisation step of catalysis. A conserved tryptophan residue may be important for the DNA-interaction ability of the N-terminal domain [
]. Human topoisomerase I has been shown to be inhibited by camptothecin (CPT), a plant alkaloid with antitumour activity. A binding mode for the anticancer drug camptothecin has been proposed on the basis of chemical and biochemical information combined with the three-dimensional structures of topoisomerase I-DNA complexes [].
DNA topoisomerase I, DNA binding, N-terminal domain 1
Type:
Homologous_superfamily
Description:
DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single- or double-strand breaks, crossing the strands through one another, then resealing the breaks [
]. These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis [,
]. DNA topoisomerases are divided into two classes: type I enzymes (; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (
; topoisomerases II, IV and VI) break double-strand DNA [
].Type I topoisomerases are ATP-independent enzymes (except for reverse gyrase), and can be subdivided according to their structure and reaction mechanisms: type IA (Topo IA; bacterial and archaeal topoisomerase I, topoisomerase III and reverse gyrase) and type IB (Topo IB; eukaryotic topoisomerase I and topoisomerase V). These enzymes are primarily responsible for relaxing positively and/or negatively supercoiled DNA, except for reverse gyrase, which can introduce positive supercoils into DNA. This function is vital for the processes of replication, transcription, and recombination. Unlike Topo IA enzymes, Topo IB enzymes do not require a single-stranded region of DNA or metal ions for their function. The type IB family of DNA topoisomerases includes eukaryotic nuclear topoisomerase I, topoisomerases of poxviruses, and bacterial versions of Topo IB [
]. They belong to the superfamily of DNA breaking-rejoining enzymes, which share the same fold in their C-terminal catalytic domain and the overall reaction mechanism with tyrosine recombinases [,
]. The C-terminal catalytic domain in topoisomerases is linked to a divergent N-terminal domain that shows no sequence or structure similarity to the N-terminal domains of tyrosine recombinases [,
].This entry represents a structural motif, consisting of an orthogonal α-helical topology that forms the N-terminal DNA-binding domain of certain eukaryotic topoisomerase I (type IB) enzymes. To cleave the DNA backbone, these enzymes must make a transient phosphotyrosine bond. The N-terminal domain of human topoisomerase I is thought to coordinate the restriction of free strand rotation during the topoisomerisation step of catalysis. A conserved tryptophan residue may be important for the DNA-interaction ability of the N-terminal domain [
]. Human topoisomerase I has been shown to be inhibited by camptothecin (CPT), a plant alkaloid with antitumour activity. A binding mode for the anticancer drug camptothecin has been proposed on the basis of chemical and biochemical information combined with the three-dimensional structures of topoisomerase I-DNA complexes [].
DNA topoisomerase I, DNA binding, N-terminal domain 2
Type:
Homologous_superfamily
Description:
DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single- or double-strand breaks, crossing the strands through one another, then resealing the breaks [
]. These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis [,
]. DNA topoisomerases are divided into two classes: type I enzymes (; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (
; topoisomerases II, IV and VI) break double-strand DNA [
].Type I topoisomerases are ATP-independent enzymes (except for reverse gyrase), and can be subdivided according to their structure and reaction mechanisms: type IA (Topo IA; bacterial and archaeal topoisomerase I, topoisomerase III and reverse gyrase) and type IB (Topo IB; eukaryotic topoisomerase I and topoisomerase V). These enzymes are primarily responsible for relaxing positively and/or negatively supercoiled DNA, except for reverse gyrase, which can introduce positive supercoils into DNA. This function is vital for the processes of replication, transcription, and recombination. Unlike Topo IA enzymes, Topo IB enzymes do not require a single-stranded region of DNA or metal ions for their function. The type IB family of DNA topoisomerases includes eukaryotic nuclear topoisomerase I, topoisomerases of poxviruses, and bacterial versions of Topo IB [
]. They belong to the superfamily of DNA breaking-rejoining enzymes, which share the same fold in their C-terminal catalytic domain and the overall reaction mechanism with tyrosine recombinases [,
]. The C-terminal catalytic domain in topoisomerases is linked to a divergent N-terminal domain that shows no sequence or structure similarity to the N-terminal domains of tyrosine recombinases [,
].This entry represents a structural motif, consisting of a complex alpha/beta topology that forms the N-terminal DNA-binding domain of certain eukaryotic topoisomerase I (type IB) enzymes. To cleave the DNA backbone, these enzymes must make a transient phosphotyrosine bond. The N-terminal domain of human topoisomerase I is thought to coordinate the restriction of free strand rotation during the topoisomerisation step of catalysis. A conserved tryptophan residue may be important for the DNA-interaction ability of the N-terminal domain [
]. Human topoisomerase I has been shown to be inhibited by camptothecin (CPT), a plant alkaloid with antitumour activity. A binding mode for the anticancer drug camptothecin has been proposed on the basis of chemical and biochemical information combined with the three-dimensional structures of topoisomerase I-DNA complexes [].
DNA topoisomerase I, catalytic core, eukaryotic-type
Type:
Domain
Description:
DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single- or double-strand breaks, crossing the strands through one another, then resealing the breaks [
]. These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis [,
]. DNA topoisomerases are divided into two classes: type I enzymes (; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (
; topoisomerases II, IV and VI) break double-strand DNA [
].Type I topoisomerases are ATP-independent enzymes (except for reverse gyrase), and can be subdivided according to their structure and reaction mechanisms: type IA (Topo IA; bacterial and archaeal topoisomerase I, topoisomerase III and reverse gyrase) and type IB (Topo IB; eukaryotic topoisomerase I and topoisomerase V). These enzymes are primarily responsible for relaxing positively and/or negatively supercoiled DNA, except for reverse gyrase, which can introduce positive supercoils into DNA. This function is vital for the processes of replication, transcription, and recombination. Unlike Topo IA enzymes, Topo IB enzymes do not require a single-stranded region of DNA or metal ions for their function. The type IB family of DNA topoisomerases includes eukaryotic nuclear topoisomerase I, topoisomerases of poxviruses, and bacterial versions of Topo IB [
]. They belong to the superfamily of DNA breaking-rejoining enzymes, which share the same fold in their C-terminal catalytic domain and the overall reaction mechanism with tyrosine recombinases [,
]. The C-terminal catalytic domain in topoisomerases is linked to a divergent N-terminal domain that shows no sequence or structure similarity to the N-terminal domains of tyrosine recombinases [,
].This entry represents the catalytic core of eukaryotic and viral topoisomerase I (type IB) enzymes, which occurs near the C-terminal region of the protein.Human topoisomerase I has been shown to be inhibited by camptothecin (CPT), a plant alkaloid with antitumour activity [
]. The crystal structures of human topoisomerase I comprising the core and carboxyl-terminal domains in covalent and noncovalent complexes with 22-base pair DNA duplexes reveal an enzyme that "clamps"around essentially B-form DNA. The core domain and the first eight residues of the carboxyl-terminal domain of the enzyme, including the active-site nucleophile tyrosine-723, share significant structural similarity with the bacteriophage family of DNA integrases. A binding mode for the anticancer drug camptothecin has been proposed on the basis of chemical and biochemical information combined with the three-dimensional structures of topoisomerase I-DNA complexes [
].Vaccinia virus, a cytoplasmically-replicating poxvirus, encodes a type I DNA topoisomerase that is biochemically similar to eukaryotic-like DNA topoisomerases I, and which has been widely studied as a model topoisomerase. It is the smallest topoisomerase known and is unusual in that it is resistant to the potent chemotherapeutic agent camptothecin. The crystal structure of an amino-terminal fragment of vaccinia virus DNA topoisomerase I shows that the fragment forms a five-stranded, antiparallel β-sheet with two short α-helices and connecting loops. Residues that are conserved between all eukaryotic-like type I topoisomerases are not clustered in particular regions of the structure [
].
DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single- or double-strand breaks, crossing the strands through one another, then resealing the breaks [
]. These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis [,
]. DNA topoisomerases are divided into two classes: type I enzymes (; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (
; topoisomerases II, IV and VI) break double-strand DNA [
].Type I topoisomerases are ATP-independent enzymes (except for reverse gyrase), and can be subdivided according to their structure and reaction mechanisms: type IA (Topo IA; bacterial and archaeal topoisomerase I, topoisomerase III and reverse gyrase) and type IB (Topo IB; eukaryotic topoisomerase I and topoisomerase V). These enzymes are primarily responsible for relaxing positively and/or negatively supercoiled DNA, except for reverse gyrase, which can introduce positive supercoils into DNA. This function is vital for the processes of replication, transcription, and recombination. Unlike Topo IA enzymes, Topo IB enzymes do not require a single-stranded region of DNA or metal ions for their function. The type IB family of DNA topoisomerases includes eukaryotic nuclear topoisomerase I, topoisomerases of poxviruses, and bacterial versions of Topo IB [
]. They belong to the superfamily of DNA breaking-rejoining enzymes, which share the same fold in their C-terminal catalytic domain and the overall reaction mechanism with tyrosine recombinases [,
]. The C-terminal catalytic domain in topoisomerases is linked to a divergent N-terminal domain that shows no sequence or structure similarity to the N-terminal domains of tyrosine recombinases [,
].This entry represents the C-terminal region of DNA topoisomerase I enzymes from eukaryotes (type IB enzymes). This region covers both the catalytic core and the DNA-binding domains.Human topoisomerase I has been shown to be inhibited by camptothecin (CPT), a plant alkaloid with antitumour activity [
]. The crystal structures of human topoisomerase I comprising the core and carboxyl-terminal domains in covalent and noncovalent complexes with 22-base pair DNA duplexes reveal an enzyme that "clamps"around essentially B-form DNA. The core domain and the first eight residues of the carboxyl-terminal domain of the enzyme, including the active-site nucleophile tyrosine-723, share significant structural similarity with the bacteriophage family of DNA integrases. A binding mode for the anticancer drug camptothecin has been proposed on the basis of chemical and biochemical information combined with the three-dimensional structures of topoisomerase I-DNA complexes [
].
DNA topoisomerase I, catalytic core, alpha/beta subdomain
Type:
Homologous_superfamily
Description:
DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single- or double-strand breaks, crossing the strands through one another, then resealing the breaks [
]. These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis [,
]. DNA topoisomerases are divided into two classes: type I enzymes (; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (
; topoisomerases II, IV and VI) break double-strand DNA [
].Type I topoisomerases are ATP-independent enzymes (except for reverse gyrase), and can be subdivided according to their structure and reaction mechanisms: type IA (Topo IA; bacterial and archaeal topoisomerase I, topoisomerase III and reverse gyrase) and type IB (Topo IB; eukaryotic topoisomerase I and topoisomerase V). These enzymes are primarily responsible for relaxing positively and/or negatively supercoiled DNA, except for reverse gyrase, which can introduce positive supercoils into DNA. This function is vital for the processes of replication, transcription, and recombination. Unlike Topo IA enzymes, Topo IB enzymes do not require a single-stranded region of DNA or metal ions for their function. The type IB family of DNA topoisomerases includes eukaryotic nuclear topoisomerase I, topoisomerases of poxviruses, and bacterial versions of Topo IB [
]. They belong to the superfamily of DNA breaking-rejoining enzymes, which share the same fold in their C-terminal catalytic domain and the overall reaction mechanism with tyrosine recombinases [,
]. The C-terminal catalytic domain in topoisomerases is linked to a divergent N-terminal domain that shows no sequence or structure similarity to the N-terminal domains of tyrosine recombinases [,
].This entry represents the alpha/beta subdomain that comprises part of the catalytic core of eukaryotic and viral topoisomerase I (type IB) enzymes, which occurs near the C-terminal region of the protein.
DNA topoisomerase I, catalytic core, alpha-helical subdomain, eukaryotic-type
Type:
Homologous_superfamily
Description:
DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single- or double-strand breaks, crossing the strands through one another, then resealing the breaks [
]. These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis [,
]. DNA topoisomerases are divided into two classes: type I enzymes (; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (
; topoisomerases II, IV and VI) break double-strand DNA [
].Type I topoisomerases are ATP-independent enzymes (except for reverse gyrase), and can be subdivided according to their structure and reaction mechanisms: type IA (Topo IA; bacterial and archaeal topoisomerase I, topoisomerase III and reverse gyrase) and type IB (Topo IB; eukaryotic topoisomerase I and topoisomerase V). These enzymes are primarily responsible for relaxing positively and/or negatively supercoiled DNA, except for reverse gyrase, which can introduce positive supercoils into DNA. This function is vital for the processes of replication, transcription, and recombination. Unlike Topo IA enzymes, Topo IB enzymes do not require a single-stranded region of DNA or metal ions for their function. The type IB family of DNA topoisomerases includes eukaryotic nuclear topoisomerase I, topoisomerases of poxviruses, and bacterial versions of Topo IB [
]. They belong to the superfamily of DNA breaking-rejoining enzymes, which share the same fold in their C-terminal catalytic domain and the overall reaction mechanism with tyrosine recombinases [,
]. The C-terminal catalytic domain in topoisomerases is linked to a divergent N-terminal domain that shows no sequence or structure similarity to the N-terminal domains of tyrosine recombinases [,
].This superfamily represents the α-helical subdomain that comprises part of the catalytic core of eukaryotic and viral topoisomerase I (type IB) enzymes, which occurs near the C-terminal region of the protein.Human topoisomerase I has been shown to be inhibited by camptothecin (CPT), a plant alkaloid with antitumour activity [
]. The crystal structures of human topoisomerase I comprising the core and carboxyl-terminal domains in covalent and noncovalent complexes with 22-base pair DNA duplexes reveal an enzyme that "clamps"around essentially B-form DNA. The core domain and the first eight residues of the carboxyl-terminal domain of the enzyme, including the active-site nucleophile tyrosine-723, share significant structural similarity with the bacteriophage family of DNA integrases. A binding mode for the anticancer drug camptothecin has been proposed on the basis of chemical and biochemical information combined with the three-dimensional structures of topoisomerase I-DNA complexes [
].Vaccinia virus, a cytoplasmically-replicating poxvirus, encodes a type I DNA topoisomerase that is biochemically similar to eukaryotic-like DNA topoisomerases I, and which has been widely studied as a model topoisomerase. It is the smallest topoisomerase known and is unusual in that it is resistant to the potent chemotherapeutic agent camptothecin. The crystal structure of an amino-terminal fragment of vaccinia virus DNA topoisomerase I shows that the fragment forms a five-stranded, antiparallel β-sheet with two short α-helices and connecting loops. Residues that are conserved between all eukaryotic-like type I topoisomerases are not clustered in particular regions of the structure [
].
Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [
,
,
,
,
]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few []. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target. This entry represents the zinc finger domain found in RanBP2 proteins. Ran is an evolutionary conserved member of the Ras superfamily that regulates all receptor-mediated transport between the nucleus and the cytoplasm. Ran binding protein 2 (RanBP2) is a 358kDa nucleoporin located on the cytoplasmic side of the nuclear pore complex which plays a role in nuclear protein import [
]. RanBP2 contains multiple zinc fingers which mediate binding to RanGDP [].
DNA-directed RNA polymerases
(also known as DNA-dependent RNA polymerases) are responsible for the polymerisation of ribonucleotides into a sequence complementary to the template DNA. In eukaryotes, there are three different forms of DNA-directed RNA polymerases transcribing different sets of genes. Most RNA polymerases are multimericenzymes and are composed of a variable number of subunits. The core RNA polymerase complex consists of five subunits (two alpha, one beta, one beta-prime and one omega) and is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme [
]. The core RNA polymerase complex forms a "crab claw"-like structure with an internal channel running along the full length [
]. The key functional sites of the enzyme, as defined by mutational and cross-linking analysis, are located on the inner wall of this channel.RNA synthesis follows after the attachment of RNA polymerase to a specific site, the promoter, on the template DNA strand. The RNA synthesis process continues until a termination sequence is reached. The RNA product, which is synthesised in the 5' to 3' direction, is known as the primary transcript.
Eukaryotic nuclei contain three distinct types of RNA polymerases that differ in the RNA they synthesise:RNA polymerase I: located in the nucleoli, synthesises precursors of most ribosomal RNAs.RNA polymerase II: occurs in the nucleoplasm, synthesises mRNA precursors. RNA polymerase III: also occurs in the nucleoplasm, synthesises the precursors of 5S ribosomal RNA, the tRNAs, and a variety of other small nuclear and cytosolic RNAs. Eukaryotic cells are also known to contain separate mitochondrial and chloroplast RNA polymerases. Eukaryotic RNA polymerases, whose molecular masses vary in size from 500 to 700kDa, contain two non-identical large (>100kDa) subunits and an array of up to 12 different small (less than 50kDa) subunits.The phage-type enzymes are a family of single chain polymerases found in bacteriophages and mitochondria [
,
].
UAS is a domain of unknown function found in FAF1 proteins (FAS-associated factor 1) and in other
proteins, many of which are described as having no known function.
The UBX domain is found in ubiquitin-regulatory proteins, which are members of the ubiquitination pathway, as well as a number of other proteins including FAF-1 (FAS-associated factor 1), the human Rep-8 reproduction protein and several hypothetical proteins from yeast. The function of the UBX domain is not known although the fragment of avian FAF-1 containing the UBX domain causes apoptosis of transfected cells.
O-Glycosyl hydrolases (
) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families [
,
]. This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.Glycoside hydrolase family 35 (
) comprises enzymes with only one known activity; beta-galactosidase (
).
Mammalian beta-galactosidase is a lysosomal enzyme (gene GLB1) which cleaves the terminal galactose from gangliosides, glycoproteins, and glycosaminoglycans and whose deficiency is the cause of the genetic disease Gm(1) gangliosidosis (Morquio disease type B).
Many calcium-binding proteins belong to the same evolutionary family and share a type of calcium-binding domain known as the EF-hand. This type of domain consists of a twelve residue loop flanked on both sides by a twelve residue α-helical domain. In an EF-hand loop the calcium ion is coordinated in a pentagonal bipyramidal configuration. The six residues involved in the binding are in positions 1, 3, 5, 7, 9 and 12; these residues are denoted by X, Y, Z, -Y, -X and -Z. The invariant Glu or Asp at position 12 provides two oxygens for liganding Ca (bidentate ligand). Ca2 binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers [,
,
,
,
].
Many calcium-binding proteins belong to the same evolutionary family and share a type of calcium-binding domain known as the EF-hand. This type of domain consists of a twelve residue loop flanked on both sides by a twelve residue α-helical domain. In an EF-hand loop the calcium ion is coordinated in a pentagonal bipyramidal configuration. The six residues involved in the binding are in positions 1, 3, 5, 7, 9 and 12; these residues are denoted by X, Y, Z, -Y, -X and -Z. The invariant Glu or Asp at position 12 provides two oxygens for liganding Ca (bidentate ligand). Ca2 binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers [
,
,
,
,
].This signature pattern includes the complete EF-hand loop as well as the first residue which follows the loop and which seem to always be hydrophobic. Note: positions 1 (X), 3 (Y) and 12 (-Z) are the most conserved. The 6th residue in an EF-hand loop is, in most cases a Gly, but the number of exceptions to this 'rule' has gradually increased, therefore, this signature pattern includes all the different residues which have been shown to exist in this position in functional Ca-binding sites. The pattern is known, in some cases, to miss one of the EF-hand regions in some proteins with multiple EF-hand domains.
This domain superfamily consists of a duplication of two EF-hand units, where each unit is composed of two helices connected by a twelve-residue calcium-binding loop. The calcium ion in the EF-hand loop is coordinated in a pentagonal bipyramidal configuration. Many calcium-binding proteins contain an EF-hand type calcium-binding domain [
,
]. These include: calbindin D9K, S100 proteins such as calcyclin, polcalcin phl p 7 (a calcium-binding pollen allergen), osteonectin, parvalbumin, calmodulin [] family of proteins (troponin C, caltractin, cdc4p, myosin essential chain, calcineurin, recoverin, neurocalcin), plasmodial-specific CaII-binding protein Cbp40, penta-EF-Hand proteins [] (sorcin, grancalcin, calpain), as well as multidomain proteins such as phosphoinositide-specific phospholipase C, dystrophin, Cb1 and alpha-actinin. The fold consists of four helices and an open array of two hairpins.
Proteins in this family include WEB1 (At2g26570) and PMI15 (At5g38150) from Arabidopsis thaliana. Both Web1 and PMI15 are required for the chloroplast avoidance response under high intensity blue light. This avoidance response consists in the relocation of chloroplasts on the anticlinal side of exposed cells. Web1 acts in association with PMI2 to maintain the velocity of chloroplast photorelocation movement via cp-actin filaments regulation [
,
].
The following small plant proteins are evolutionary related:Gamma-thionins from Triticum aestivum (Wheat) endosperm (gamma-purothionins) and gamma-hordothionins from Hordeum vulgare(Barley) are toxic to animal cells and inhibit protein synthesis in cell free systems [
].A flower-specific thionin (FST) from Nicotiana tabacum (Common Tobacco)[
].Antifungal proteins (AFP) from the seeds of Brassicaceae species such as radish, mustard, turnip and Arabidopsis thaliana (Thale Cress)[
].Inhibitors of insect alpha-amylases from sorghum [
].Probable protease inhibitor P322 from Solanum tuberosum (Potato).A germination-related protein from Vigna unguiculata (Cowpea) [
].Anther-specific protein SF18 from sunflower. SF18 is a protein that contains a gamma-thionin domain at its N terminus and a proline-rich C-terminal domain.Glycine max (Soybean) sulphur-rich protein SE60 [
].Vicia faba (Broad bean) antibacterial peptides fabatin-1 and -2.In their mature form, these proteins generally consist of about 45 to 50 amino-acid residues. As shown in the following schematic representation, these peptides contain eight conserved cysteines involved in disulphide bonds.+-------------------------------------------+
| +-------------------+ || | | |
xxCxxxxxxxxxxCxxxxxCxxxCxxxxxxxxxCxxxxxxCxCxxxC| | | |
+---|----------------+ |+------------------+
'C': conserved cysteine involved in a disulphide bond.
The folded structure of Gamma-purothionin is characterised by a well-defined 3-stranded anti-parallel β-sheet and a short α-helix [
]. Three disulphide bridges are located in the hydrophobic core between the helix and sheet, forming a cysteine-stabilised α-helical motif. This structure differs from that of the plant alpha- and beta- thionins, but is analogous to scorpion toxins and insect defensins.
Knottins are small proteins characterised by a cystine-knot [
]. They constitute a large family of structurally related peptides with diverse biological functions, including inhibitors, anti-microbial peptides and toxins [].The scorpion toxin-like domain is found in a subgroup of metazoan knottins mainly from the arthropoda, which include the antibacterial defensins [
] and the scorpion alpha and beta-neurotoxins [,
]. The plant sequences include members of the gamma-thionin family, which are plant defensins that have no antifungal activity. Other members are insect alpha-amylase inhibitors, cysteine-rich antifungal proteins and proteins annotated as proteinase inhibitors; those that are characterised belong to MEROPS inhibitor family I18, clan I.
SWAP is derived from the Suppressor-of-White-APricot splicing regulator from Drosophila melanogaster. The domain is found in regulators responsible for pervasive, nonsex-specific alternative pre-mRNA splicing characteristics and has been found in splicing regulatory proteins [
]. These ancient, conserved SWAP proteins share a colinearly arrayed series of novel sequence motifs [].
The SAP motif is a 35-residue motif, which has been named after SAF-A/B,
Acinus and PIAS, three proteins known to contain it. The SAP motif is found ina variety of nuclear proteins involved in transcription, DNA repair, RNA
processing or apoptotic chromatin degradation. As the sap motif of SAF-A hasbeen shown to be essential for specific DNA binding activity, it has been
proposed that it could be a DNA-binding motif [].A multiple alignment of the SAP motif reveals a bipartite distribution of
strongly conserved hydrophobic, polar and bulky amino acids separated by aregion that contains a glycine. Secondary structure predictions suggest that
the SAP motif could form two alpha helices separated by a turn [].Some proteins known to contain a SAP motif are listed below:Vertebrate scaffold attachment factors A and B (SAF-A/B). These two
proteins are heterogeneous nuclear ribonucleoproteins (hnRNPs) that bind toAT-rich chromosomal region. It has been proposed that they couple RNA
metabolism to nuclear organisation [,
]. The SAF-A protein is cleaved bycaspase-3 during apoptosis [
].Mammalian Acinus, a protein which induces apoptotic chromatin condensation
after cleavage by caspase-3 []. Acinus also contains a RNA-recognitionmotif.
Eukaryotic proteins of the PIAS (protein inhibitor of activated STAT)
family. These proteins interact with phosphorylated STAT dimers and inhibitSTAT mediated gene activation. Deletion of the first 50 amino acid residues
containing the SAP domain allows the interaction of PIAS1 with STAT1monomer [
].Plant poly(ADP-ribose) polymerase (PARP). PARP is a nuclear protein that
catalyzes the poly(ADP-ribosyl)ation of proteins. It is involved inresponses to mild and severe oxidative stresses, by mediating DNA repair
and programmed cell death processes, respectively []. PARP is tightlybound to chromatin or nuclear matrix.
Arabidopsis thaliana Arp, an apurinic endonuclease-redox protein.Yeast THO1 protein. It could be involved in the regulation of
transcriptional elongation by RNA polymerase II [].Animal Ku70. Together with Ku86, it forms a DNA ends binding complex that
is involved in repairing DNA double-strand breaks.Yeast RAD18, a protein involved in DNA repair.Neurospora crassa UVS-2, the homologue of RAD18.
The cwf21 domain is found in proteins involved in mRNA splicing. Proteins containing this domain have been isolated as a subcomplex of the splicosome in Schizosaccharomyces pombe (Fission yeast) [
]. In yeast, this domain binds the protein Prp8p [], a large and highly conserved U5 snRNP protein which has been proposed as a protein cofactor at the spliceosomal catalytic centre [].The cwf21 domain is found in, amongst others, the small Cwc21p protein in yeast as well as in the much larger human ortholog SRm300 (serine/arginine repetitive matrix protein).
The C-terminal domain (CTD) of the large subunit of RNA polymerase II is a
platform for mRNA processing factors and links gene transcription to mRNAcapping, splicing and polyadenylation. CTD recognition is dependent on the
phosphorylation state of the CTD itself, which varies during the course oftranscription but has also been linked to the isomerization state of the CTD's
proline residues. Several RNA-processing factors recognise the CTD by means ofa conserved CTD-interacting domain (CID). Factors with CID domains include the
serine/arginine-rich-like factors SCAF4 and SCAF8, Nrd1 (which is implicatedin polyadenylation-independent RNA 3'-end formation) and Pcf11. Pcf11 is a
conserved and essential subunit of the yeast cleavage factor 1A, which isrequired for 3'-RNA processing and transcription termination [
,
].The CID domain is a right-handed superhelix of eight α-helices forming a
compact domain. The CID fold closely resembles that of VHSdomains
and is related to armadillo-repeat proteins
, except for the two amino-terminal helices. Amino acid residues
in the hydrophobic core of the domain are highly conserved across CID domains[
,
].
This family consists of several hypothetical proteins from both cyanobacteria and plants. Members of this family are typically around 250 residues in length. The function of this family is unknown but the species distribution indicates that the family may be involved in photosynthesis.
This entry contains serine endopeptidases belonging to the MEROPS peptidase family S8 (subtilisin family , clan SB). Limited proteolysis of most large protein precursors is carried out in vivo by the subtilisin-like pro-protein convertases. Many important biological processes such as peptide hormone synthesis, viral protein processing and receptor maturation involve proteolytic processing by these enzymes [
]. The subtilisin-serine protease (SRSP) family hormone and pro-protein convertases (furin, PC1/3, PC2, PC4, PACE4, PC5/6, and PC7/7/LPC) act within the secretory pathway to cleave polypeptide precursors at specific basic sites, generating their biologically active forms. Serum proteins, pro-hormones, receptors, zymogens, viral surface glycoproteins, bacterial toxins, amongst others, are activated by this route []. The SRSPs share the same domain structure, including a signal peptide, the pro-peptide, the catalytic domain, the P/middle or homo B domain, and the C terminus.
The nucleobase cation symporter 2 (NCS2) family, also known as the nucleobase ascorbate transporter(NAT) family, are a large family found in bacteria, fungi (except Saccharomyces cerevisiae), plants and mammals. Nucleobase transporter families have solute transport preferences among purines and pyrimidines. Members of this family often have overlapping but unique solute transport and binding profiles [
].
This entry includes tafazzin and its homologues, such as Taz1 from yeasts and N-acylphosphatidylethanolamine synthase from plants. Tafazzin is an enzyme involved in the cardiolipin remodelling pathway [
,
]. The phospholipid cardiolipin is an important component of the inner mitochondrial membrane that is involved in mitochondrial energy production and apoptosis []. In humans tafazzin is expressed at high levels in cardiac and skeletal muscle. As many as 10 isoforms can be present in different amounts in different tissues. Isoforms with hydrophobic N-termini are thought to be membrane anchored, while shorter forms, lacking the hydrophobic stretch, may be cytoplasmic (these latter are found in leukocytes and fibroblasts, but not in heart and skeletal muscle). A central hydrophilic domain may serve as an exposed loop that interacts with other proteins. Defects in the taz gene are the cause of Barth syndrome, a severe inherited disorder, often fatal in childhood. The disease is characterised by cardiac and skeletal myopathy, short stature and neutropenia [].In flies tafazzin is a CoA-independent, acyl-specific phospholipid transacylase with substrate preference for cardiolipin and phosphatidylcholine [
].Budding yeast Taz1 is a lyso-phosphatidylcholine acyltransferase that is required for normal phospholipid content of mitochondrial membranes, whose acyl specificity in the reaction relies on lipid chemical composition [
,
]. Arabidopsis N-acylphosphatidylethanolamine synthase (NAPE synthase, At1g78690) is an acyltransferase that catalyses the N-acylation of phosphatidylethanolamine to form N-acylphosphatidylethanolamine (N-acyl-PE) [
].
Cyclophilins exhibit peptidyl-prolyl cis-trans isomerase (PPIase) activity (
), accelerating protein folding by catalysing the cis-trans isomerisation of proline imidic peptide bonds in oligopeptides [
,
]. They also have protein chaperone-like functions [] and are the major high-affinity binding proteins for the immunosuppressive drug cyclosporin A (CSA) in vertebrates [].Cyclophilins are found in all prokaryotes and eukaryotes, and have been structurally conserved throughout evolution, implying their importance in cellular function [
]. They share a common 109 amino acid cyclophilin-like domain (CLD) and additional domains unique to each member of the family. The CLD domain contains the PPIase activity, while the unique domains are important for selection of protein substrates and subcellular compartmentalisation [].This entry represents the core β-barrel cyclophilin-like domain.
Prismane (hybrid-cluster) proteins are present in a wide range of bacteria and archaea, and are characterised by their two Fe/S centres: a [4Fe-4S] cubane cluster, and a hybrid [4Fe-2S-2O]cluster [
]. Prismane proteins contain four domains: two spectrin repeat-like 3-helical bundle domains, and two alpha/beta domains with Rossmann-fold topology. Several proteins are structurally related to Prismane, including Ni-containing carbon monoxide dehydrogenase (CODH) (lack one of the N-terminal 3-helical bundle domains), the alpha and beta subunits of bifunctional CODH, and the alpha and beta subunits of acetyl-CoA synthetase.This superfamily represents the spectrin repeat-like 3-helical bundle domains, as well as the two alpha/beta domains with Rossmann-fold topology.
The FERM domain (F for 4.1 protein, E for ezrin, R for radixin and M for moesin) is a widespread protein module involved in localising proteins to the plasma membrane [
]. FERM domains are found in a number of cytoskeletal-associated proteins that associate with various proteins at the interface between the plasma membrane and the cytoskeleton. The FERM domain is located at the N terminus of the majority of FERM-containing proteins [,
], which includes: Band 4.1, which links the spectrin-actin cytoskeleton of erythrocytes to the plasma membrane.Ezrin, a component of the undercoat of the microvilli plasma membrane.Moesin, which is probably involved in binding major cytoskeletal structures to the plasma membrane.Radixin, which is involved in the binding of the barbed end of actin filaments to the plasma membrane in the undercoat of the cell- to-cell adherens junction.Talin, a cytoskeletal protein concentrated in regions of cell-substratum contact and, in lymphocytes, of cell-cell contacts.Filopodin, a slime mold protein that binds actin and which is involved in the control of cell motility and chemotaxis.Merlin (or schwannomin).Protein NBL4.Unconventional myosins X, VIIa and XV, which are mutated in congenital deafness.Focal-adhesion kinases (FAKs), cytoplasmic protein tyrosine kinases involved in signalling through integrins.Janus tyrosine kinases (JAKs), cytoplasmic tyrosine kinases that are non-covalently associated with the cytoplasmic tails of receptors for cytokines or polypeptidic hormones.Non-receptor tyrosine-protein kinase TYK2.Protein-tyrosine phosphatases PTPN3 and PTPN4, enzyme that appear to act at junctions between the membrane and the cytoskeleton.Protein-tyrosine phosphatases PTPN14 and PTP-D1, PTP-RL10 and PTP2E.Caenorhabditis elegans protein phosphatase ptp-1.Ezrin, moesin, and radixin are highly related proteins (ERM protein family), but the other proteins in which the FERM domain is found do not share any region of similarity outside of this domain. ERM proteins are made of three domains, the FERM domain, a central helical domain and a C-terminal tail domain, which binds F-actin. The amino-acid sequence of the FERM domain is highly conserved among ERM proteins and is responsible for membrane association by direct binding to the cytoplasmic domain or tail of integral membrane proteins. ERM proteins are regulated by an intramolecular association of the FERM and C-terminal tail domains that masks their binding sites for other molecules. For cytoskeleton-membrane cross-linking, the dormant molecules becomes activated and the FERM domain attaches to the membrane by binding specific membrane proteins, while the last 34 residues of the tail bind actin filaments. Aside from binding to membranes, the activated FERM domain of ERM proteins can also bind the guanine nucleotide dissociation inhibitor of Rho GTPase (RhoDGI), which suggests that in addition to functioning as a cross-linker, ERM proteins may influence Rho signalling pathways. The crystal structure of the FERM domain reveals that it is composed of three structural modules (F1, F2, and F3) that together form a compact clover-shaped structure [
].The FERM domain has also been called the amino-terminal domain, the 30kDa domain, 4.1N30, the membrane-cytoskeletal-linking domain, the ERM-like domain, the ezrin-like domain of the band 4.1 superfamily, the conserved N-terminal region, and the membrane attachment domain [
].
The FERM domain (F for 4.1 protein, E for ezrin, R for radixin and M for moesin) is a widespread protein module involved in localising proteins to the plasma membrane [
]. FERM domains are found in a number of cytoskeletal-associated proteins that associate with various proteins at the interface between the plasma membrane and the cytoskeleton. The FERM domain is located at the N terminus of the majority of FERM-containing proteins [,
], which includes: Band 4.1, which links the spectrin-actin cytoskeleton of erythrocytes to the plasma membrane.Ezrin, a component of the undercoat of the microvilli plasma membrane.Moesin, which is probably involved in binding major cytoskeletal structures to the plasma membrane.Radixin, which is involved in the binding of the barbed end of actin filaments to the plasma membrane in the undercoat of the cell- to-cell adherens junction.Talin, a cytoskeletal protein concentrated in regions of cell-substratum contact and, in lymphocytes, of cell-cell contacts.Filopodin, a slime mold protein that binds actin and which is involved in the control of cell motility and chemotaxis.Merlin (or schwannomin).Protein NBL4.Unconventional myosins X, VIIa and XV, which are mutated in congenital deafness.Focal-adhesion kinases (FAKs), cytoplasmic protein tyrosine kinases involved in signalling through integrins.Janus tyrosine kinases (JAKs), cytoplasmic tyrosine kinases that are non-covalently associated with the cytoplasmic tails of receptors for cytokines or polypeptidic hormones.Non-receptor tyrosine-protein kinase TYK2.Protein-tyrosine phosphatases PTPN3 and PTPN4, enzyme that appear to act at junctions between the membrane and the cytoskeleton.Protein-tyrosine phosphatases PTPN14 and PTP-D1, PTP-RL10 and PTP2E.Caenorhabditis elegans protein phosphatase ptp-1.Ezrin, moesin, and radixin are highly related proteins (ERM protein family), but the other proteins in which the FERM domain is found do not share any region of similarity outside of this domain. ERM proteins are made of three domains, the FERM domain, a central helical domain and a C-terminal tail domain, which binds F-actin. The amino-acid sequence of the FERM domain is highly conserved among ERM proteins and is responsible for membrane association by direct binding to the cytoplasmic domain or tail of integral membrane proteins. ERM proteins are regulated by an intramolecular association of the FERM and C-terminal tail domains that masks their binding sites for other molecules. For cytoskeleton-membrane cross-linking, the dormant molecules becomes activated and the FERM domain attaches to the membrane by binding specific membrane proteins, while the last 34 residues of the tail bind actin filaments. Aside from binding to membranes, the activated FERM domain of ERM proteins can also bind the guanine nucleotide dissociation inhibitor of Rho GTPase (RhoDGI), which suggests that in addition to functioning as a cross-linker, ERM proteins may influence Rho signalling pathways. The crystal structure of the FERM domain reveals that it is composed of three structural modules (F1, F2, and F3) that together form a compact clover-shaped structure [
].The FERM domain has also been called the amino-terminal domain, the 30kDa domain, 4.1N30, the membrane-cytoskeletal-linking domain, the ERM-like domain, the ezrin-like domain of the band 4.1 superfamily, the conserved N-terminal region, and the membrane attachment domain [
].
The microtubule-based kinesin motors and actin-based myosin motors generate movements required for intracellular trafficking, cell division, and muscle contraction. In general, these proteins consist of a motor domain that generates movement and a tail region that varies widely from class to class and is thought to mediate many of the regulatory or cargo binding functions specific to each class of motor [
]. The Myosin Tail Homology 4 (MyTH4) domain has been identified as a conserved domain in the tail domains of several different unconventional myosins [] and a plant kinesin-like protein [], but has more recently been found in several non-motor proteins []. Although the function is not yet fully understood, there is an evidence that the MyTH4 domain of Myosin-X (Myo10) binds to microtubules and thus could provide a link between an actin-based motor protein and the microtubule cytoskeleton [].The MyTH4 domain is found in one or two copies associated
with other domains, such as myosin head, kinesin motor, FERM, PH, SH3 and IQ. The domain is predicted to be largely α-helical, interrupted by three orfour turns. The MyTH4 domain contains four highly conserved regions designated
MGD (consensus sequence L(K/R)(F/Y)MGDhP, LRDE (consensus LRDEhYCQhhKQHxxxN),RGW (consensus RGWxLh), and ELEA (RxxPPSxhELEA), where h indicates a
hydrophobic residue and x is any residue [].
This domain is a putative nucleic acid binding zinc finger and is found at the N terminus of proteins that also contain an adjacent XS domain
and in some proteins a C-terminal XH domain
[
]. Proteins containing this domain include protein SUPPRESSOR OF GENE SILENCING 3 (SGS3), which is required for post-transcriptional gene silencing and natural virus resistance [,
].
This XS (named after rice gene X and SGS3) domain is a single-stranded RNA-binding domain (RBD) and possesses a unique version of a RNA recognition motif (RRM) fold [
]. It is conserved in a family of plant proteins including gene X and SGS3. Although its function is still unknown, the plant SGS3 proteins are thought to be involved in post-transcriptional gene silencing (PTGS) pathways []. In addition, they contain a conserved aspartate residue that may be functionally important.
Sel1-like repeats are tetratricopeptide repeat sequences originally identified in a Caenorhabditis elegans receptor molecule which is a key negative regulator of the Notch pathway [
]. Mammalian homologues have since been identified although these mainly pancreatic proteins have yet to have a function assigned.
The Mlo-related proteins are a family of plant integral membrane proteins, first discovered in barley. Mutants lacking wild-type Mlo proteins show broad spectrum resistance to the powdery mildew fungus, and dysregulated cell death control, with spontaneous cell death in response to developmental or abiotic stimuli. Thus wild-type Mlo proteins are thought to be inhibitors of cell death whose deficiency lowers the threshold required to trigger the cascade of events that result in plant cell death. Mlo proteins are localized in the plasma membrane and possess seven transmembrane regions; thus the Mlo family is the only major higher plant family to possess 7 transmembrane domains. It has been suggested that Mlo proteins function as G-protein coupled receptors in plants that seems not to require heterotrimeric G proteins [
,
]; however the molecular and biological functions of Mlo proteins is still unclear.
TLC is a protein domain with at least 5 transmembrane α-helices. Lag1p and Lac1p
are essential foracyl-CoA-dependent ceramide synthesis [
], TRAM is a subunitof the translocon and the CLN8
gene is mutated in Northern epilepsy syndrome. Proteins containing this domain may possessmultiple functions such as
lipid trafficking, metabolism, or sensing. Trh homologues possess additionalhomeobox domains [
].
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [,
].L32 is a protein from the large ribosomal subunit that contains a surface-exposed globular domain and a finger-like projection that extends into the RNA core to stabilize the tertiary structure. L32 does not appear to play a role in forming the A (aminacyl), P (peptidyl) or E (exit) sites of the ribosome, but does interact with 23S rRNA, which has a "kink-turn"secondary structure motif. L32 is overexpressed in human prostate cancer and has been identified as a stably expressed housekeeping gene in macrophages of human chronic obstructive pulmonary disease (COPD) patients. In Schizosaccharomyces pombe, L32 has also been suggested to play a role as a transcriptional regulator in the nucleus. Found in archaea and eukaryotes, this protein is known as L32 in eukaryotes and L32e in archaea [
,
,
,
,
,
,
].
This superfamily represents a rubredoxin-like metal-binding fold found in ribosomal proteins L37ae, L37e, L44e and S27e. This domain contains two CX(n)C motifs (where n is usually two) [
,
].
This superfamily represents the core domain of ribosomal proteins L37ae and L37e, which share a common rubredoxin-like metal-binding fold containing two CX(n)C motifs (where n is usually two) [
].
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [,
].This ribosomal protein is found in archaebacteria and eukaryotes [
]. Ribosomal protein L37 has a single zinc finger-like motif of the C2-C2 type [].
Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [
,
,
,
,
]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few []. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target. These sequences contain a putative zinc finger domain found predominantly in plants. Arabidopsis thaliana (Mouse-ear cress) has at least 10 distinct members. Proteins containing this domain, including LRP1 (lateral root primordium 1)[
], generally share the same size, about 300 amino acids, and architecture. This 43-residue domain, and a more C-terminal companion domain of similar size, appear as tightly conserved islands of sequence similarity. The remainder consists largely of low-complexity sequence. Several animal proteins have regions with matching patterns of Cys, Gly, and His residues. But are excluded from this family because of their low similarity.
This entry represents a group of plant proteins, including protein SHORT INTERNODES (SHI) and its paralogues from Arabidopsis. In Arabidopsis, the SHI family comprises ten members. They contain a RING finger-like zinc finger motif. SHI may act as a negative regulator of GA responses through transcriptional control binding directly to the 5'-T/GCTCTAC-3' DNA motif found in the promoter regions [
]. In rice, it regulates tillering and panicle branching by modulating SPL14/IPA1 transcriptional activity on the downstream TB1 and DEP1 target genes [].
These sequences contain a tightly conserved small domain found in SHORT INTERNODES (SHI) and related plant proteins. SHI proteins also contain a well-conserved adjacent N-terminal putative zinc finger domain (
). SHI may act as a negative regulator of GA responses through transcriptional control [
,
].
Casein kinase, a ubiquitous well-conserved protein kinase involved in cell metabolism and differentiation, is characterised by its preference for Ser or Thr in acidic stretches of amino acids. The enzyme is a tetramer of 2 alpha- and 2 beta-subunits [
,
]. However, some species (e.g., mammals) possess 2 related forms of the alpha-subunit (alpha and alpha'), while others (e.g., fungi) possess 2 related beta-subunits (beta and beta') []. The alpha-subunit is the catalytic unit and contains regions characteristic of serine/threonine protein kinases. The beta-subunit is believed to be regulatory, possessing an N-terminal auto-phosphorylation site, an internal acidic domain, and a potential metal-binding motif []. The beta subunit contains, in its central section, a cysteine-rich motif, CX(n)C, that could be involved in binding a metal such as zinc [
]. The mammalian beta-subunit gene promoter shares common features with those of other mammalian protein kinases and is closely related to the promoter of the regulatory subunit of cAMP-dependent protein kinase [].
Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process.
Protein kinases fall into three broad classes, characterised with respect to substrate specificity []:Serine/threonine-protein kinasesTyrosine-protein kinasesDual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)Protein kinase function is evolutionarily conserved from Escherichia coli to human [
]. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation []. Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [].Casein kinase, a ubiquitous, well-conserved protein kinase involved in cell metabolism and differentiation, is characterised by its preference for Ser or Thr in acidic stretches of amino acids. The enzyme is a tetramer of 2 alpha- and 2 beta-subunits [
,
]. However, some species (e.g., mammals) possess 2 related forms of the alpha-subunit (alpha and alpha'), while others (e.g., fungi) possess 2 related beta-subunits (beta and beta') []. The alpha-subunit is the catalytic unit and contains regions characteristic of serine/threonine protein kinases. The beta-subunit is believed to be regulatory, possessing an N-terminal auto-phosphorylation site, an internal acidic domain, and a potential metal-binding motif []. The beta subunit is a highly conserved protein of about 25kDa that contains, in its central section, a cysteine-rich motif, CX(n)C, that could be involved in binding a metal such as zinc []. The mammalian beta-subunit gene promoter shares common features with those of other mammalian protein kinases and is closely related to the promoter of the regulatory subunit of cAMP-dependent protein kinase [].This superfamily represents the N-terminal α-helical domain, which has an orthogonal bundle topology.
Pectate lyase
is an enzyme involved in the maceration and soft rotting of plant tissue. Pectate lyase is responsible for the eliminative cleavage of pectate, yielding oligosaccharides with 4-deoxy-alpha-D-mann-4-enuronosyl groups at their non-reducing ends. The protein is maximally expressed late in pollen development. It has been suggested that the pollen expression of pectate lyase genes might relate to a requirement for pectin degradation during pollen tube growth [
]. Some of the proteins in this family are allergens [
]. Allergies are hypersensitivity reactions of the immune system to specific substances called allergens (such as pollen, stings, drugs, or food) that, in most people, result in no symptoms. A nomenclature system has been established for antigens (allergens) that cause IgE-mediated atopic allergies in humans [WHO/IUIS Allergen Nomenclature Subcommittee King T.P., Hoffmann D., Loewenstein H., Marsh D.G., Platts-Mills T.A.E., Thomas W. Bull. World Health Organ. 72:797-806(1994)]. This nomenclature system is defined by a designation that is composed of the first three letters of the genus; a space; the first letter of the species name; a space and an arabic number. In the event that two species names have identical designations, they are discriminated from one another by adding one or more letters (as necessary) to each species designation.
The allergens in this family include allergens with the following designations: Amb a 1, Amb a 2, Amb a 3, Cha o 1, Cup a 1, Cry j 1, Jun a 1.Two of the major allergens in the pollen of short ragweed (
Ambrosia artemisiifolia) are Amb aI and Amb aII. The primary structure of Amb aII has been deduced and has been shown to share ~65% sequence identity with the Amb alpha I multigene family of allergens [
]. Members of the Amb aI/aII family include Nicotiana tabacum (Common tobacco) pectate lyase, which is similar to the deduced amino acid sequences of two pollen-specific pectate lyase genes identified in Solanum lycopersicum (Tomato) (Lycopersicon esculentum) []; Cry jI, a major allergenic glycoprotein of Cryptomeria japonica (Japanese cedar) - the most common pollen allergen in Japan []; and P56 and P59, which share sequence similarity with pectate lyases of plant pathogenic bacteria [
].
This entry represents the Toll/interleukin-1 receptor (TIR) domain, which is the conserved cytoplasmic domain of approximately 200 amino acids, found in Toll-like receptors (TLRs) and their adaptors. Proteins containing this domain can also be found in plants, where they mediate disease resistance [
], and in bacteria, where they have been associated with virulence. Interestingly, the TIR domains from proteins present in all three major domains of life have been shown to cleave nicotinamide adenine dinucleotide (NAD+). In plants, TIR domains require self-association interfaces and a putative catalytic glutamic acid that is conserved in both bacterial TIR NAD+-cleaving enzymes (NADases) and the mammalian SARM1 (sterile alpha and TIR motif containing 1) NADase for cell death induction and NAD+ cleavage activity [
,
]. It has been suggested that the primordial function of the TIR domain is the enzymatic cleavage of NAD+ and that the scaffolding function, which is best characterised in mammalian TIR domains involved in innate immunity, may be a more recent evolutionary adaptation [].Toll proteins or Toll-like receptors (TLRs) and the interleukin-1 receptor (IL-1R) superfamily are both involved in innate antibacterial and antifungal
immunity in insects as well as in mammals. These receptors share a conserved cytoplasmic domain of approximately 200 amino acids, known as the Toll/IL-1R homologous region (TIR). The similarity between TLRs and IL-1Rs is not restricted to sequence homology since these proteins also share a similar signalling pathway. They both induce the activation of a Rel type transcription factor via an adaptor protein and a protein kinase []. Interestingly, MyD88, a cytoplasmic adaptor protein found in mammals, contains a TIR domain associated to a DEATH domain [,
,
]. Besides the mammalian and Drosophila proteins, a TIR domain is also found in a number of plant cytoplasmic proteins implicated in host defense [].Site directed mutagenesis and deletion analysis have shown that the TIR domain is essential for Toll and IL-1R activities. Sequence analysis have revealed the presence of three highly conserved regions among the different members of the family: box 1 (FDAFISY), box 2 (GYKLC-RD-PG), and box 3 (a conserved W surrounded by basic residues). It has been proposed that boxes 1 and 2 are involved in the binding of proteins involved in signalling, whereas box 3 is primarily involved in directing localization of receptor, perhaps through interactions with cytoskeletal element [
].Resolution of the crystal structures of the TIR domains of human Toll-like receptors 1 and 2 has shown that they contain a central five-stranded parallel β-sheet that is surrounded by a total of five helices on both sides, with connecting loop structures [
]. The loop regions appear to play an important role in mediating the specificity of protein-protein interactions [,
].
This domain family is found in eukaryotes, and is approximately 120 amino acids in length. The family is found in association with
. There are two completely conserved residues (R and L) that may be functionally important.
ThiS (thiaminS) is a 66 aa protein involved in sulphur transfer. ThiS is coded in the thiCEFSGH operon in Escherichia coli. This family of proteins have two conserved Glycines at the COOH terminus. Thiocarboxylate is formed at the last G in the activation process. Sulphur is transferred from ThiI to ThiS in a reaction catalysed by IscS [
]. MoaD, a protein involved in sulphur transfer during molybdopterin synthesis, is about the same length and shows limited sequence similarity to ThiS. Both have the conserved GG at the COOH end [].ThiS/MoaD proteins serve as sulfur carriers in thiamine and tungsten/molybdenum cofactor biosynthesis. Proteins in this entry also include TtuB from Thermus thermophilus. TtuB functions as the sulfur donor in the sulfurtransferase reaction catalyzed by TtuA [
]. It is also required for the 2-thiolation of 5-methyluridine residue at position 54 in the T loop of tRNAs, leading to 5-methyl-2-thiouridine (m5s2U or s2T). This modification allows thermal stabilization of tRNAs in thermophilic microorganisms, and is essential for cell growth at high temperatures [].
MOCS2A is a the small subunit of the molybdopterin synthase complex that catalyses the conversion of precursor Z into molybdopterin by mediating the incorporation of 2 sulfur atoms into precursor Z to generate a dithiolene group. In the complex, MOCS2A serves as sulfur donor by being thiocarboxylated at its C terminus by UBA4 [
]. After interaction with MOCS2B, the sulfur is then transferred to precursor Z to form molybdopterin [,
].This entry represents the Molybdopterin synthase sulfur carrier subunit from eukaryotes.
This entry represents a structural domain with a beta-Grasp fold that is found in molybdopterinsynthase subunit MoaD [
], as well as in the thiamin biosynthesis sulphur carrier protein ThiS [].ThiS (thiaminS) is a 66 aa protein involved in sulphur transfer. ThiS is coded in the thiCEFSGH operon in Escherichia coli. ThiS proteins have two conserved Glycines at the COOH terminus. Thiocarboxylate is formed at the last G in the activation process. Sulphur is transferred from ThiI to ThiS in a reaction catalysed by IscS [
]. MoaD, a protein involved in sulphur transfer during molybdopterin synthesis, is about the same length and shows limited sequence similarity to ThiS. Both have the conserved GG at the COOH end.
Adenylate kinases (ADK) are phosphotransferases that catalyse the reversible reaction
AMP + MgATP = ADP + MgADP
an essential reaction for many processes in living cells. Two ADK isozymes have been identified in mammalian cells. These specifically bind AMP and favour binding to ATP over
other nucleotide triphosphates (AK1 is cytosolic and AK2 is located in the mitochondria). A third ADK has been identified in bovine heart and human cells [
], this is a mitochondrial GTP:AMP phosphotransferase, also specific for the phosphorylation of AMP, but can only use GTP or ITP as a
substrate []. ADK has also been identified in different bacterial species and in yeast [
]. Two further enzymes are known to be related to the ADK family, i.e. yeast uridine monophosphokinase and slime mold UMP-CMP kinase. Within the ADK family there are several conserved
regions, including the ATP-binding domains. One of the most conserved areas includes an Arg residue, whose modification inactivates the enzyme, together with an Asp that resides in the catalytic cleft
of the enzyme and participates in a salt bridge.In humans, nine different AK isoenzymes have been identified (AK1-9) [
].
Adenylate kinases (ADK;
) are phosphotransferases that catalyse the Mg-dependent reversible conversion of ATP and AMP to two molecules of ADP, an essential reaction for many processes in living cells. In large variants of adenylate kinase, the AMP and ATP substrates are buried in a domain that undergoes conformational changes from an open to a closed state when bound to substrate; the ligand is then contained within a highly specific environment required for catalysis. Adenylate kinase is a 3-domain protein consisting of a large central CORE domain flanked by a LID domain on one side and the AMP-binding NMPbind domain on the other [
]. The LID domain binds ATP and covers the phosphates at the active site. The substrates first bind the CORE domain, followed by closure of the active site by the LID and NMPbind domains.Comparisons of adenylate kinases have revealed a particular divergence in the active site lid. In some organisms, particularly the Gram-positive bacteria, residues in the lid domain have been mutated to cysteines and these cysteine residues (two CX(n)C motifs) are responsible for the binding of a zinc ion. The bound zinc ion in the lid domain is clearly structurally homologous to Zinc-finger domains. However, it is unclear whether the adenylate kinase lid is a novel zinc-finger DNA/RNA binding domain, or that the lid bound zinc serves a purely structural function [
].
CBS domains are evolutionarily conserved structural domains found in a variety of non functionally-related proteins from all kingdoms of life. These domains pair together to form a intramolecular dimeric structure (CBS pair), termed Bateman domain [
,
,
,
]. CBS domains have been shown to bind mainly ligands with an adenosyl group such as AMP, ATP and S-AdoMet, but may also bind metal ions, or nucleic acids [,
]. Hence, they play an essential role in the regulation of the activities of numerous proteins, and mutations in them are associated with several hereditary diseases [,
,
]. CBS domains are found attached to a wide range of other protein domains suggesting that CBS domains may play a regulatory role making proteins sensitive to adenosyl-carrying ligands. The region containing the CBS domains in cystathionine-beta synthase is involved in regulation by S-AdoMet []. CBS domain pairs from AMPK bind AMP or ATP []. The CBS domains from IMPDH, which bind ATP, have shown to have a role in the regulation of adenylate nucleotide synthesis [,
].
Chloride channels (CLCs) constitute an evolutionarily well-conserved family of voltage-gated channels that are structurally unrelated to the other known voltage-gated channels. They are found in organisms ranging from bacteria to yeasts and plants, and also to animals. Their functions in higher animals likely include the regulation of cell volume, control of electrical excitability and trans-epithelial transport [
].The first member of the family (CLC-0) was expression-cloned from the electric organ of Torpedo marmorata [
], and subsequently nine CLC-like proteins have been cloned from mammals. They are thought to function as multimers of two or more identical or homologous subunits, and they have varying tissue distributions and functional properties. To date, CLC-0, CLC-1, CLC-2, CLC-4 and CLC-5 have been demonstrated to form functional Cl- channels; whether the remaining isoforms do so is either contested or unproven. One possible explanation for the difficulty in expressing activatable Cl- channels is that some of the isoforms may function as Cl- channels of intracellular compartments, rather than of the plasma membrane. However, they are all thought to have a similar transmembrane (TM) topology, initial hydropathy analysis suggesting 13 hydrophobic stretches long enough to form putative TM domains []. Recently, the postulated TM topology has been revised, and it now seems likely that the CLCs have 10 (or possibly 12) TM domains, with both N- and C-termini residing in the cytoplasm [].A number of human disease-causing mutations have been identified in the genes encoding CLCs. Mutations in CLCN1, the gene encoding CLC-1, the major skeletal muscle Cl- channel, lead to both recessively and dominantly-inherited forms of muscle stiffness or myotonia [
]. Similarly, mutations in CLCN5, which encodes CLC-5, a renal Cl- channel, lead to several forms of inherited kidney stone disease []. These mutations have been demonstrated to reduce or abolish CLC function.
Chloride channels (CLCs) constitute an evolutionarily well-conserved family of voltage-gated channels that are structurally unrelated to the other known voltage-gated channels. They are found in organisms ranging from bacteria to yeasts and plants, and also to animals. Their functions in higher animals likely include the regulation of cell volume, control of electrical excitability and trans-epithelial transport [
].The first member of the family (CLC-0) was expression-cloned from the electric organ of Torpedo marmorata [
], and subsequently nine CLC-like proteins have been cloned from mammals. They are thought to function as multimers of two or more identical or homologous subunits, and they have varying tissue distributions and functional properties. To date, CLC-0, CLC-1, CLC-2, CLC-4 and CLC-5 have been demonstrated to form functional Cl- channels; whether the remaining isoforms do so is either contested or unproven. One possible explanation for the difficulty in expressing activatable Cl- channels is that some of the isoforms may function as Cl- channels of intracellular compartments, rather than of the plasma membrane. However, they are all thought to have a similar transmembrane (TM) topology, initial hydropathy analysis suggesting 13 hydrophobic stretches long enough to form putative TM domains []. Recently, the postulated TM topology has been revised, and it now seems likely that the CLCs have 10 (or possibly 12) TM domains, with both N- and C-termini residing in the cytoplasm [].A number of human disease-causing mutations have been identified in the genes encoding CLCs. Mutations in CLCN1, the gene encoding CLC-1, the major skeletal muscle Cl- channel, lead to both recessively and dominantly-inherited forms of muscle stiffness or myotonia [
]. Similarly, mutations in CLCN5, which encodes CLC-5, a renal Cl- channel, lead to several forms of inherited kidney stone disease []. These mutations have been demonstrated to reduce or abolish CLC function.This superfamily represents the core domain of the cholide ion channel.
A number of formyl transferases belong to this group. Methionyl-tRNA formyltransferase transfers a formyl group onto the amino terminus of the acyl moiety of the methionyl minoacyl-tRNA. The formyl group appears to play a dual role in the initiator identity of N-ormylmethionyl-tRNA by promoting its recognition by IF2 and by impairing its binding to EFTU-GTP. Formyltetrahydrofolate dehydrogenase produces formate from formyl-tetrahydrofolate. This is the N-terminal domain of these enzymes and is found upstream of the C-terminal domain (
).
The trifunctional glycinamide ribonucleotide synthetase-aminoimidazole ribonucleotide synthetase-glycinamide ribonucleotide transformylase catalyses the second, third and fifth steps in de novo purine biosynthesis. The glycinamide ribonucleotide transformylase belongs to this group.
Glutamate, leucine, phenylalanine, valine and tryptophan dehydrogenases are structurally and functionally related. They contain a Gly-rich region containing a conserved Lys residue, which has been implicated in the catalytic activity, in each case a reversible oxidative deamination reaction.Glutamate dehydrogenases (
,
, and
) (GluDH) are enzymes that catalyse the NAD- and/or NADP-dependent reversible deamination of L-glutamate into alpha-ketoglutarate [
,
]. GluDH isozymes are generally involved with either ammonia assimilation or glutamate catabolism. Two separate enzymes are present in yeasts: the NADP-dependent enzyme, which catalyses the amination of alpha-ketoglutarate to L-glutamate; and the NAD-dependent enzyme, which catalyses the reverse reaction [] - this form links the L-amino acids with the Krebs cycle, which provides a major pathway for metabolic interconversion of alpha-amino acids and alpha- keto acids []. In rice, glutamate dehydrogenase 3 is mitochondrial.Leucine dehydrogenase (
) (LeuDH) is a NAD-dependent enzyme that catalyses the reversible deamination of leucine and several other aliphatic amino acids to their keto analogues [
]. Each subunit of this octameric enzyme from Bacillus sphaericus contains 364 amino acids and folds into two domains, separated by a deep cleft. The nicotinamide ring of the NAD+ cofactor binds deep in this cleft, which is thought to close during the hydride transfer step of the catalytic cycle.Phenylalanine dehydrogenase (
) (PheDH) is na NAD-dependent enzyme that catalyses the reversible deamidation of L-phenylalanine into phenyl-pyruvate [
].Valine dehydrogenase (
) (ValDH) is an NADP-dependent enzyme that catalyses the reversible deamidation of L-valine into 3-methyl-2-oxobutanoate [
].L-tryptophan dehydrogenase catalyses the reversible oxidative deamination of L-tryptophan to indole-3-pyruvate in the presence of NAD+ [
,
].
Glutamate, leucine, phenylalanine, valine and tryptophan dehydrogenases are structurally and functionally related. They contain a Gly-rich region containing a conserved Lys residue, which has been implicated in the catalytic activity, in each case a reversible oxidative deamination reaction.Glutamate dehydrogenases (
,
, and
) (GluDH) are enzymes that catalyse the NAD- and/or NADP-dependent reversible deamination of L-glutamate into alpha-ketoglutarate [
,
]. GluDH isozymes are generally involved with either ammonia assimilation or glutamate catabolism. Two separate enzymes are present in yeasts: the NADP-dependent enzyme, which catalyses the amination of alpha-ketoglutarate to L-glutamate; and the NAD-dependent enzyme, which catalyses the reverse reaction [] - this form links the L-amino acids with the Krebs cycle, which provides a major pathway for metabolic interconversion of alpha-amino acids and alpha- keto acids []. In rice, glutamate dehydrogenase 3 is mitochondrial.Leucine dehydrogenase (
) (LeuDH) is a NAD-dependent enzyme that catalyses the reversible deamination of leucine and several other aliphatic amino acids to their keto analogues []. Each subunit of this octameric enzyme from Bacillus sphaericus contains 364 amino acids and folds into two domains, separated by a deep cleft. The nicotinamide ring of the NAD+ cofactor binds deep in this cleft, which is thought to close during the hydride transfer step of the catalytic cycle.Phenylalanine dehydrogenase (
) (PheDH) is na NAD-dependent enzyme that catalyses the reversible deamidation of L-phenylalanine into phenyl-pyruvate [
].Valine dehydrogenase (
) (ValDH) is an NADP-dependent enzyme that catalyses the reversible deamidation of L-valine into 3-methyl-2-oxobutanoate [
].L-tryptophan dehydrogenase catalyses the reversible oxidative deamination of L-tryptophan to indole-3-pyruvate in the presence of NAD+ [
,
].This entry represents the dimerisation region of these enzymes.
Glutamate, leucine, phenylalanine, valine and tryptophan dehydrogenases are structurally and functionally related. They contain a Gly-rich region containing a conserved Lys residue, which has been implicated in the catalytic activity, in each case a reversible oxidative deamination reaction.Glutamate dehydrogenases (
,
, and
) (GluDH) are enzymes that catalyse the NAD- and/or NADP-dependent reversible deamination of L-glutamate into alpha-ketoglutarate [
,
]. GluDH isozymes are generally involved with either ammonia assimilation or glutamate catabolism. Two separate enzymes are present in yeasts: the NADP-dependent enzyme, which catalyses the amination of alpha-ketoglutarate to L-glutamate; and the NAD-dependent enzyme, which catalyses the reverse reaction [] - this form links the L-amino acids with the Krebs cycle, which provides a major pathway for metabolic interconversion of alpha-amino acids and alpha- keto acids []. In rice, glutamate dehydrogenase 3 is mitochondrial.Leucine dehydrogenase (
) (LeuDH) is a NAD-dependent enzyme that catalyses the reversible deamination of leucine and several other aliphatic amino acids to their keto analogues [
]. Each subunit of this octameric enzyme from Bacillus sphaericus contains 364 amino acids and folds into two domains, separated by a deep cleft. The nicotinamide ring of the NAD+ cofactor binds deep in this cleft, which is thought to close during the hydride transfer step of the catalytic cycle.Phenylalanine dehydrogenase (
) (PheDH) is na NAD-dependent enzyme that catalyses the reversible deamidation of L-phenylalanine into phenyl-pyruvate [
].Valine dehydrogenase (
) (ValDH) is an NADP-dependent enzyme that catalyses the reversible deamidation of L-valine into 3-methyl-2-oxobutanoate [
].L-tryptophan dehydrogenase catalyses the reversible oxidative deamination of L-tryptophan to indole-3-pyruvate in the presence of NAD+ [
,
].This entry represents the C-terminal domain of these proteins.
This entry represents glutamate dehydrogenases (GDH). The tertiary structure have been solved for the GDHs from Thermotoga maritima and Pyrococcus furiosus, both of which are thermostable because of an ion-pair network in the hinge region [
]. Some GDHs are NADP-specific, such as GdhA from Escherichia coli, which catalyzes the reversible oxidative deamination of glutamate to alpha-ketoglutarate and ammonia [,
]. In eukaryotes, NADP-dependent GDHs may be mitochondrial, such as GluD from Dictyostelium discoideum [].
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].This model decribes bacterial and chloroplast ribosomal protein L22
Ribosomal protein L22 (L17 in eukaryotes) is a core protein of the large ribosomal subunit. It is the only ribosomal protein that interacts with all six domains of 23S rRNA, and is one of the proteins important for directing the proper folding and stabilizing the conformation of 23S rRNA. L22 is the largest protein contributor to the surface of the polypeptide exit channel, the tunnel through which the polypeptide product passes. L22 is also one of six proteins located at the putative translocon binding site on the exterior surface of the ribosome [
,
].Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].
Protein phosphatase inhibitor 2 (IPP-2) is a phosphoprotein conserved among all eukaryotes, and it appears in both the nucleus and cytoplasm of tissue culture cells [
]. Protein phosphatase inhibitor 2 family member C (PPP1R2C) has been shown to inhibit the catalytic subunit of PP1 [].
Methylation at CpG dinucleotide, the most common DNA modification in
eukaryotes, has been correlated with gene silencing associated with variousphenomena such as genomic imprinting, transposon and chromosome X inactivation, differentiation, and cancer. Effects of DNA methylation are mediated through proteins which bind to symmetrically methylated CpGs. Such proteins contain a specific domain of ~70 residues, the methyl-CpG-binding domain (MBD), which is linked to additional domains associated with chromatin, such as the bromodomain, the AT hook motif,the SET domain, or the PHD finger. MBD-containing proteins appear to act as structural proteins, which recruit a variety of histone deacetylase (HDAC) complexes and chromatin remodelling factors, leading to chromatin compaction and, consequently, to transcriptional repression. The MBD of MeCP2, MBD1, MBD2, MBD4 and BAZ2 mediates binding to DNA, in case of MeCP2, MBD1 and MBD2 preferentially to methylated CpG. In case of human MBD3 and SETDB1 the MBD has been shown to mediate protein-protein interactions [
,
].The MBD folds into an alpha/beta sandwich structure comprising a layer of
twisted beta sheet, backed by another layer formed by the alpha1 helix and ahairpin loop at the C terminus. These layers are both amphipathic, with the alpha1 helix and the beta sheet lying parallel and the hydrophobic faces tightly packed against each other. The beta sheet is composed of two long inner strands (beta2 and beta3) sandwiched by two shorter outer strands (beta1 and beta4) [
].
Cytochrome b5 is a membrane-bound hemoprotein which acts as an electron carrier for several membrane-bound oxygenases [
]. There are two homologous forms of b5, one found in microsomes and one found in the outer membrane of mitochondria. Two conserved histidine residues serve as axial ligands for the heme group. The structure of a number of oxidoreductases consists of the juxtaposition of a heme-binding domain homologous to that of b5 and either a flavodehydrogenase or a molybdopterin domain. These enzymes are:Lactate dehydrogenase (EC 1.1.2.3) [
], an enzyme that consists of a flavodehydrogenase domain and a heme-binding domain called cytochrome b2.Nitrate reductase (EC 1.7.1.-), a key enzyme involved in the first step of nitrate assimilation in plants, fungi and bacteria [
]. Consists of a molybdopterin domain, a heme-binding domain called cytochrome b557, as well as a cytochrome reductase domain.Sulfite oxidase (EC 1.8.3.1) [
], which catalyzes the terminal reaction in the oxidative degradation of sulfur-containing amino acids. Also consists of a molybdopterin domain and a heme-binding domain.Yeast acyl-CoA desaturase 1 (EC 1.14.19.1; gene OLE1). This enzyme contains a C-terminal heme-binding domain.Yeast Scs7 (YMR272c), a sphingolipid alpha-hydroxylase.Proteins containing a cytochrome b5-like domain also include:TU-36B, a Drosophila muscle protein of unknown function [
].Fission yeast hypothetical protein SpAC1F12.10c (C1F12.10c).Yeast Irc21 (YMR073c), a putative protein with unknown function.
This entry represents the katanin p80 WD40 repeat-containing subunit B1. The microtubule-severing protein katanin consists of a heterodimer of 60 and 80kDa subunits. p60 has microtubule-stimulated ATPase and microtubule-severing activities, while p80 is a novel protein containing WD40 repeats, which are frequently involved in protein-protein interactions.Katanin p80 WD40-containing subunit B1 may act to target p60 to sites of action such as the centrosome []. Microtubule severing may promote rapid reorganisation of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. There is also evidence that katanin localises at the leading edge of migratory cells and trims microtubules at their dynamic plus ends [].The C-terminal domain of p80 katanin binds microtubules in vitro, while the N-terminal WD40 domain acts as a negative regulator of microtubule disassembly activity [
].
This entry represents the C-terminal domain of katanin 80kDa subunit. Katanin is a microtubule-severing protein consist of a 60kDa ATPase subunit (katanin-p60) and a 80kDa subunit (katanin-p80) [
]. Katanin-p80is composed of an N-terminal WD40 repeat domain, a central proline-rich domain and a C-terminal domain required for dimerisation with the catalytic katanin-p60. The katanin complex associates with a specific subregion of the mitotic spindle leading to increased microtubule disassembly and targeting of katanin-p60 to the spindle poles [
]. It was suggested that katanin is targeted to spindle poles through a combination of direct microtubule binding by the katanin-p60 and through interactions between the WD40 domain and an unknown protein [].
Lipoyl synthase is an iron-sulphur protein [
]. It is localised to mitochondria in yeast and Arabidopsis [,
]. It generates lipoic acid, a thiol antioxidant that is linked to a specific Lys as prosthetic group for the pyruvate and alpha-ketoglutarate dehydrogenase complexes and the glycine-cleavage system.
Electron transport accessory-like domain superfamily
Type:
Homologous_superfamily
Description:
The electron transport accessory proteins adopt the beta topology of an SH3 domain, with a partly opened beta barrel and a 3-10 helical turn interrupting the last strand. Other proteins displaying this topology include R67 dihydrofolate reductase, which catalyses the hydration of nitriles to amides [
], photosystem I accessory proteins (PsaE), which participate in cyclic electron transport and modulate the interaction of photosystem I with ferrodoxin [], the alpha chain of ferrodoxin thioredoxin reductase (FTR), which is involved in the regulation of the activity of chloroplast enzymes [], and the beta chain of nitrile hydratase, which confers trimethoprim-resistance to R67-expressing bacteria [].
Ferredoxin thioredoxin reductase is a [4FE-4S] protein which plays an important role in the ferredoxin/thioredoxin regulatory chain. It converts an electron signal (photoreduced ferredoxin) to a thiol signal (reduced thioredoxin), regulating enzymes by reduction of specific disulphide groups. It catalyses the light-dependent activation of several photosynthesis enzymes. Ferredoxin thioredoxin reductase is a heterodimer of subunit a and subunit b. Subunit a is the variable subunit, and b is the catalytic chain [,
]. This entry represents a domain found in the variable or alpha subunit of this group of ferredoxin thioredoxin reductases predominantly found in cyanobacteria and plants. In some members this is the only domain present in the protein, while in others it is located at the C-terminal end of the sequence.
This entry represents cleavage and polyadenylation specificity factor subunit 5, also known as the cleavage and polyadenylation specificity factor 25kDa subunit. These proteins are a component of the cleavage factor Im (CFIm) complex involved in pre-mRNA 3' end processing [
]. CFIm may also play a role in regulation of poly(A) site selection [].
This domain is known as the MPN domain [
], PAD-1-like domain [], JABP1 domain [] or JAMM domain []. Proteins with this domain include proteasome regulatory subunits, eukaryotic initiation factor 3 (eIF3) subunits and regulators of transcription factors. They are metalloenzymes that function as the ubiquitin isopeptidase/deubiquitinase in the ubiquitin-based signalling and protein turnover pathways in eukaryotes []. Versions of the domain in prokaryotic cognates of the ubiquitin-modification pathway are predicted to have a similar role [].The archaeal (H. volcanii) JAMM domain containing protein, HvJAMM1, cleaves ubiquitin-like small archaeal modifier proteins (SAMP1/2) from protein conjugates [
]. The bacterial JAMM domain containing protein QbsD from Pseudomonas fluorescens cleaves the C-terminal amino acid residues of the sulfur carrier protein QbsE prior to the formation of the carboxy-terminal thiocarboxylate [].
This domain is found at the C terminus of many regulatory proteins, including the yeast proteasomal subunit Rpn11 and eukaryotic initiation factor 3 subunit F (eIF3f). The Rpn11 C-terminal domain is necessary for normal mitochondrial morphology and function and is thought to regulate the mitochondrial fission and tubulation processes [
]. The eIF3f C-terminal domain is critical for proper eIF3f activity in skeletal muscle through its interaction with mTOR (also known as FRAP, RAFT1 or RAPT) [,
].
The GOLD (for Golgi dynamics) domain is a protein module found in severaleukaryotic Golgi and lipid-traffic proteins. It is typically between 90 and
150 amino acids long. Most of the size difference observed in the GOLD-domainsuperfamily is traceable to a single large low-complexity insert that is seen
in some versions of the domain. With the exception of the p24 proteins, whichhave a simple architecture with the GOLD domain as their only globular domain, all other GOLD-domain proteins contain additional conserved globular domains. In these proteins, the GOLD domain co-occurs with lipid-, sterol- or fatty acid-binding domains such as PH, CRAL-TRIO, FYVE oxysterol binding- and acyl CoA-binding
domains, suggesting that these proteins may interact with membranes. The GOLDdomain can also be found associated with a RUN domain, which
may have a role in the interaction of various proteins with cytoskeletalfilaments. The GOLD domain is predicted to mediate diverse protein-protein
interactions []. A secondary structure prediction for the GOLD domain reveals that it is likelyto adopt a compact all-β-fold structure with six to seven strands. Most of
the sequence conservation is centred on the hydrophobic cores that supportthese predicted strands. The predicted secondary-structure elements and the
size of the conserved core of the domain suggests that it may form a beta-sandwich fold with the strands arranged in two beta sheets stacked on each
other [].Some proteins known to contain a GOLD domain are listed below:Eukaryotic proteins of the p24 family.Animal Sec14-like proteins. They are involved in secretion.Human Golgi resident protein GCP60. It interacts with the Golgi integral
membrane protein Giantin.Yeast oxysterol-binding protein homologue 3 (OSH3).
This entry represents a group of plant-specific O-fucosyltransferases and their homologues [
]. O-fucosyltransferase-like proteins are GDP-fucose dependent enzymes with similarities to the family 1 glycosyltransferases (GT1). They are soluble ER proteins that may be proteolytically cleaved from a membrane-associated preprotein, and are involved in the O-fucosylation of protein substrates, the core fucosylation of growth factor receptors, and other processes [,
].
This is a family of conserved proteins representing the enzyme responsible for adding O-fucose to EGF (epidermal growth factor-like) repeats. Six highly conserved cysteines are present as well as a DXD-like motif (ERD), conserved in mammals, Drosophila, and Caenorhabditis elegans. Both features are characteristic of several glycosyltransferase families. The enzyme is a membrane-bound protein released by proteolysis and, as for most glycosyltransferases, is strongly activated by manganese [
].
Thimet oligopeptidase and neurolysin are closely related zinc-dependent metallopeptidases that metabolize small bioactive peptides. They cleave many substrates at the same sites, but they recognise different positions on others [
].This entry represents the up-down alpha bundle domain found at the N terminus of these and related M3 peptidases.
