Visual pigments [
,
] are the light-absorbing molecules that mediate vision. They consist of an apoprotein, opsin, covalently linked to the chromophore cis-retinal. Vision is effected through the absorption of a photon by cis-retinal which is isomerised to trans-retinal. This isomerisation leads to a change of conformation of the protein. Opsins are integral membrane proteins with seven transmembrane regions that belong to family 1 of G-protein coupled receptors.In vertebrates four different pigments are generally found. Rod cells, which mediate vision in dim light, contain the pigment rhodopsin. Cone cells, which function in bright light, are responsible for colour vision and contain three or more colour pigments (for example, in mammals: red, blue and green).By contrast with vertebrate rhodopsin, which is found in rod cells, insect photoreceptors are found in the ommatidia that comprise the compound eyes. Each Drosophila eye has 800 ommatidia, each of which contains 8 photoreceptor cells (designated R1-R8): R1-R6 are outer cells, while R7 and R8
are inner cells. Opsins RH3 and RH4 are sensitive to UV light [,
,
]. In Drosophila, the eye is composed of 800 facets or ommatidia. Each ommatidium contains eight photoreceptor cells (R1-R8): the R1 to R6 cells are outer cells, R7 and R8 inner cells. Each of the three types of cells (R1-R6, R7 and R8) expresses a specific opsin.Proteins evolutionary related to opsins include:Squid retinochrome, also known as retinal photoisomerase, which converts various isomers of retinal into 11-cis retinal.Mammalian opsin 3 (Encephalopsin) that may play a role in encephalic photoreception.Mammalian opsin 4 (Melanopsin) that may mediate regulation of circadian rhythms and acute suppression of pineal melatonin.Mammalian retinal pigment epithelium (RPE) RGR [
], a protein that may also act in retinal isomerisation.
Major Histocompatibility Complex (MHC) glycoproteins are heterodimeric cell surface receptors that function to present antigen peptide fragments to T cells responsible for cell-mediated immune responses. MHC molecules can be subdivided into two groups on the basis of structure and function: class I molecules present intracellular antigen peptide fragments (~10 amino acids) on the surface of the host cells to cytotoxic T cells; class II molecules present exogenously derived antigenic peptides (~15 amino acids) to helper T cells. MHC class I and II molecules are assembled and loaded with their peptide ligands via different mechanisms. However, both present peptide fragments rather than entire proteins to T cells, and are required to mount an immune response.Class II MHC glycoproteins are expressed on the surface of antigen-presenting cells (APC), including macrophages, dendritic cells and B cells. MHC II proteins present peptide antigens that originate extracellularly from foreign bodies such as bacteria. Proteins from the pathogen are degraded into peptide fragments within the APC, which sequesters these fragments into the endosome so they can bind to MHC class II proteins, before being transported to the cell surface. MHC class II receptors display antigens for recognition by helper T cells (stimulate development of B cell clones) and inflammatory T cells (cause the release of lymphokines that attract other cells to site of infection) [
].MHC class II molecules are comprised of two membrane-spanning chains, alpha and beta, of similar size. Both chains consist of two globular domains (N- and C-terminal), and a transmembrane segment to anchor them to the membrane [
]. A groove in the structure acts as the peptide-binding site.This superfamily represents the N-terminal domain of both the alpha and beta chains, which share the same α-helical/β-sheet fold, where the α-helical and β-sheet regions are segregated.
This group of enzymes belongs to the GHMP kinase domain superfamily. GHMP kinases are a unique class of ATP-dependent enzymes (the abbreviation of which refers to the original members: galactokinase, homoserine kinase, mevalonate kinase, and phosphomevalonate kinase) [
]. Enzymes belonging to this superfamily contain three well-conserved motifs, the second of which has the typical sequence Pro-X-X-X-Gly-Leu-X-Ser-Ser-Ala and is involved in ATP binding []. The phosphate binding loop in GHMP kinases is distinct from the classical P-loops found in many ATP/GTP binding proteins. The bound ADP molecule adopts a rare syn conformation and is in the opposite orientation from those bound to the P-loop-containing proteins []. GHMP kinases display a distinctly bilobal appearance with their N-terminal subdomains dominated by a mixed β-sheet flanked on one side by α-helices and their C-terminal subdomains containing a four stranded anti-parallel β-sheet [,
,
,
].Aneurinibacillus thermoaerophilus protein has been characterised as a D-glycero-D-manno-heptose 7-phosphate kinase that adds phosphate group to C-1 of D-glycero-D-manno-heptose 7-phosphate [
], and has been called GmhB or HddA. Note that HddA is the preferred name for this protein because the name GmhB has also been used for the D-glycero-D-manno-heptose 1,7-bisphosphate phosphatase, [
,
]. This enzyme catalyses a step in the biosynthesis of the nucleotide-activated form GDP-D-glycero-D-manno-heptose [] and is encoded by the heptose operon [].D-glycero-D-manno-heptose is a constituent of lipopolysaccharide (LPS) cores of Gram-negative bacteria, and also a component of the S-layer glycoprotein of the Gram-positive bacterium Aneurinibacillus thermoaerophilus. The principal architecture of S-layer glycoproteins resembles that of the LPS of Gram-negative bacteria and comparable pathways are used for the biosynthesis of these similar glycoconjugates [
].WcbL of Burkholderia pseudomallei is also involved in the synthesis of an LPS (type I O-polysaccharide moieties) [
].LmbP is thought to belong to the lincomycin-production gene cluster of Streptomyces lincolnensis [
].
Major Histocompatibility Complex (MHC) glycoproteins are heterodimeric cell surface receptors that function to present antigen peptide fragments to T cells responsible for cell-mediated immune responses. MHC molecules can be subdivided into two groups on the basis of structure and function: class I molecules present intracellular antigen peptide fragments (~10 amino acids) on the surface of the host cells to cytotoxic T cells; class II molecules present exogenously derived antigenic peptides (~15 amino acids) to helper T cells. MHC class I and II molecules are assembled and loaded with their peptide ligands via different mechanisms. However, both present peptide fragments rather than entire proteins to T cells, and are required to mount an immune response.Class II MHC glycoproteins are expressed on the surface of antigen-presenting cells (APC), including macrophages, dendritic cells and B cells. MHC II proteins present peptide antigens that originate extracellularly from foreign bodies such as bacteria. Proteins from the pathogen are degraded into peptide fragments within the APC, which sequesters these fragments into the endosome so they can bind to MHC class II proteins, before being transported to the cell surface. MHC class II receptors display antigens for recognition by helper T cells (stimulate development of B cell clones) and inflammatory T cells (cause the release of lymphokines that attract other cells to site of infection) [
].MHC class II molecules are comprised of two membrane-spanning chains, alpha and beta, of similar size. Both chains consist of two globular domains (N- and C-terminal), and a transmembrane segment to anchor them to the membrane [
]. A groove in the structure acts as the peptide-binding site.This entry represents the N-terminal domain (also called beta-1 domain) of the beta chain.
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 domain contains eight conserved cysteine residues that bind to two zinc ions. The CXXC domain is found in a variety of chromatin-associated proteins. This domain binds to non-methylated CpG dinucleotides. The domain is characterised by two CGXCXXC repeats. The RecQ helicase has a single repeat that also binds to zinc, but this has not been included in this family. The DNA binding interface has been identified by NMR [
].
BAG domains are present in Bcl-2-associated athanogene 1 and silencer of death domains. The BAG proteins are modulators of chaperone activity, they bind to HSP70/HSC70 proteins and promote substrate release. The proteins have anti-apoptotic activity and increase the anti-cell death function of BCL-2 induced by various stimuli. BAG-1 binds to the serine/threonine kinase Raf-1 or Hsc70/Hsp70 in a mutually exclusive interaction. BAG-1 promotes cell growth by binding to and stimulating Raf-1 activity. The binding of Hsp70 to BAG-1 diminishes Raf-1 signalling and inhibits subsequent events, such as DNA synthesis, as well as arrests the cell cycle. BAG-1 has been suggested to function as a molecular switch that encourages cells to proliferate in normal conditions but become quiescent under a stressful environment [
,
].BAG-family proteins contain a single BAG domain, except for human BAG-5 which has four BAG repeats [
]. The BAG domain is a conserved region located at the C terminus of the BAG-family proteins that binds the ATPase domain of Hsc70/Hsp70. The BAG domain is evolutionarily conserved, and BAG domain containing proteins have been described and/or proven in a variety of organisms including Mus musculus (Mouse), Xenopus spp., Drosophila spp., Bombyx mori (Silk moth), Caenorhabditis elegans, Saccharomyces cerevisiae (Baker's yeast), Schizosaccharomyces pombe (Fission yeast), and Arabidopsis thaliana (Mouse-ear cress).The BAG domain has 110-124 amino acids and is comprised of three anti-parallel α-helices, each approximately 30-40 amino acids in length. The first and second helices interact with the serine/threonine kinase Raf-1 and the second and third helices are the sites of the BAG domain interaction with the ATPase domain of Hsc70/Hsp70. Binding of the BAG domain to the ATPase domain is mediated by both electrostatic and hydrophobic interactions in BAG-1 and is energy requiring.
E2 is an early regulatory protein found in the dsDNA papillomaviruses. The viral genome is a 7.9-kb circular DNA that codes for at least eight early and two late (capsid) proteins. The products of the early genes E6 and E7 are oncoproteins that destabilise the cellular tumour suppressors p53 and pRB. The product of the E1 gene is a helicase necessary for viral DNA replication. The products of the E2 gene play key roles in the regulation of viral gene transcription and DNA replication. During early stages of viral infection, the
E2 protein represses the transcription of the oncogenes E6 and E7, reintroduction of E2 into cervical cancer cell-lines leads to repression of E6/E7 transcription, stabilisation of the tumour suppressor p53, andcell-cycle arrest at the G1 phase of the cell cycle. E2 can also induce apoptosis by a p53-independent mechanism. E2 proteins from all papillomavirus strains bind a consensus palindromic sequence ACCgNNNNcGGT present in multiple copies in the regulatory region. It can either activate or repress transcription, depending on E2RE's position with regard to proximal promoter elements. Repression occurs by sterically hindering the assembly of the transcription initiation complex. The E2 protein is composed of a C-terminal DNA-binding domain and an N-terminal trans-activation domain. E2 exists in solution and binds to DNA as a dimer The E2-DNA binding domain forms a dimeric β-barrel, with each subunit contributing an anti-parallel 4-stranded β-sheet "half-barrel"[
,
]. The topology of each subunit is beta1-1-beta2-beta3-2-beta4. Helix 1 is the recognition helix housing all of the amino acid residues involved in direct DNA sequence specification. Upon dimerisation, strands beta2 and beta4 at the edges of each subunit participate in a continuous hydrogen-bonding network, which results in an 8-stranded β-barrel. The dimer interface is extensive, made up of hydrogen bondsbetween subunits and a substantial hydrophobic β-barrel core.
ABC transporter type 1, transmembrane domain superfamily
Type:
Homologous_superfamily
Description:
ABC transporters belong to the ATP-Binding Cassette (ABC) superfamily, which uses the hydrolysis of ATP to energise diverse biological systems. ABC transporters minimally consist of two conserved regions: a highly conserved ATP binding cassette (ABC) and a less conserved transmembrane domain (TMD). These can be found on the same protein or on two different ones. Most ABC transporters function as a dimer and therefore are constituted of four domains, two ABC modules and two TMDs.ABC transporters are involved in the export or import of a wide variety of substrates ranging from small ions to macromolecules. The major function of ABC import systems is to provide essential nutrients to bacteria. They are found only in prokaryotes and their four constitutive domains are usually encoded by independent polypeptides (two ABC proteins and two TMD proteins). Prokaryotic importers require additional extracytoplasmic binding proteins (one or more per systems) for function. In contrast, export systems are involved in the extrusion of noxious substances, the export of extracellular toxins and the targeting of membrane components. They are found in all living organisms and in general the TMD is fused to the ABC module in a variety of combinations. Some eukaryotic exporters encode the four domains on the same polypeptide chain [
].The ATP-Binding Cassette (ABC) superfamily forms one of the largest of all protein families with a diversity of physiological functions [
]. Several studies have shown that there is a correlation between the functional characterisation and the phylogenetic classification of the ABC cassette [,
]. More than 50 subfamilies have been described based on a phylogenetic and functional classification [,
,
]; (for further information see http://www.tcdb.org/tcdb/index.php?tc=3.A.1).This entry represents the transmembrane domain in cases where the TMD and ABC region are found in the same protein, and corresponds to ABC type 1 from Transporter Classification Database (http://www.tcdb.org/tcdb/index.php?tc=3.A.1).
After cytochrome c is synthesized in the cytoplasm as apocytochrome c, it is transported through the outer mitochondrial membrane to the intermembrane space, where haem is covalently attached by thioester bonds to two cysteine residues located in the cytochrome c centre. Cytochrome c is required during oxidative phosphorylation as an electron shuttle between Complex III (cytochrome c reductase) and IV (cytochrome c oxidase). In addition, cytochrome c is involved in apoptosis in more complex organisms such as Xenopus, rats and humans. Cellular stress can induce cytochrome c release from the mitochondrial membrane. In mammals, cytochrome c triggers the assembly of the apoptosome, consisting of cytochrome c, Apaf-1 and dATP, which activates caspase-9, leading to cell death [,
]. There are several different members of the cytochrome c family with different functional roles, for instance cytochrome c549 is associated with photosystem II []. The known structures of c-type cytochromes have six different classes of fold. Of these, four are unique to c-type cytochromes [
,
]. The consensus sequence for the cytochrome c centre is Cys-X-X-Cys-His, where the histidine residue is one of the two axial ligands of the haem iron []. This arrangement is shared by all proteins known to belong to the cytochrome c family, which presently includes both mono-haem proteins and multi-haem proteins. This entry represents mono-haem cytochrome c proteins (excluding class II and f-type cytochromes), such as cytochromes c, c1, c2, c5, c555, c550 to c553, c556, and c6.Cytochrome c-type centres are also found in the active sites of many enzymes, including cytochrome cd1-nitrite reductase as the N-terminal haem c domain, in quinoprotein alcohol dehydrogenase as the C-terminal domain, in Quinohemoprotein amine dehydrogenase A chain as domains 1 and 2, and in the cytochrome bc1 complex as the cytochrome bc1 domain.
The B30.2 domain was first identified as a protein domain encoded by an exon (named B30-2) in the Homo sapiens class I major histocompatibility complex region [
], whereas the SPRY domain was first identified in a Dictyostelium discoideum kinase splA and mammalian calcium-release channels ryanodine receptors []. B30.2 domain consists of PRY and SPRY subdomains. The SPRY domains (after SPla and the RYanodine Receptor) are shorter at the N terminus than the B30.2 domains. The ~200-residue B30.2/SPRY (for B30.2 and/or SPRY) domain is present in a large number of proteins with diverse individual functions in different biological processes. The B30.2/SPRY domain in these proteins is likely to function through protein-protein interaction [].The N-terminal ~60 residues of B30.2/SPRY domains are poorly conserved and, as a consequence, a new domain name PRY was coined for a group of similar sequence segments N-terminal to the SPRY domains [
]. The B30.2/SPRY domain contains three highly conserved motifs (LDP, WEVE and LDYE) []. TheB30.2/SPRY domain adopts a highly distorted, compact β-sandwich fold with two additional short β-helices at the N terminus. The β-sandwich of the B30.2/SPRY domain consists of two layers of β-sheets: sheet A composed of eight strands and sheet B composed of seven strands. All the β-strands are in antiparallel arrangement [
]. The 5th β-strand corresponding to WEVE motif []. Both the N- and C-terminal ends of the B30.2/SPRY domains in general are close to each other [].Tripartite motif-containing proteins (TRIMs) play a variety roles in innate immunity. TRIM14 is a noncanonical TRIM that lacks an E3 ubiquitin ligase RING domain. It is involved in type I IFN signaling in innate immunity [
,
,
]. This entry represents the PRY/SPRY domain of TRIM14.
This entry includes proteins with a radical SAM domain and a radical SAM C-terminal extension domain. One such protein is elongator complex protein 3 (ELP3): the catalytic histone acetyltransferase subunit of the RNA polymerase II elongator complex, which is itself part of the RNA polymerase II (RNAPII) holoenzyme responsible for transcriptional elongation [
]. A bacterial ELP3 homologue known as tRNA uridine(34) acetyltransferase, reflecting its role in mediating the formation of carboxymethyluridine in the wobble base at position 34 in tRNAs is also included in this family []. This entry also includes protein YhcC from Escherichia coli , which binds an [4Fe-4S] cluster, coordinated with three cysteines and an exchangeable S-adenosyl-L-methionine. YhcC cleaves S-adenosyl-L-methionine into methionine and 5'-deoxyadenosine []. This entry also includes archaeosine synthase subunit beta (RaSEA) from archaea, it is a SAM enzyme which plays a role in the synthesis of archaeosine []. Uncharacterised homologues are known from bacteria, archaea and eukaryotes.ELP3 is required for the complex integrity and for the association of the complex with nascent RNA transcript [
]. ELP3 is thought to act as a highly conserved histone acetyltransferase (HAT) capable of acetylating core histones in vitro, however, it is clearly a multi-domain protein. The HAT activity is thought to be present only in the C-terminal GNAT domain (histone acyltransferase domain) []. Studies suggest that both the histone acetyltransferase and radical S-adenosylmethionine domains are essential for function, although the exact role of the Radical SAM domain is still unclear []. The radical SAM domain is important for the structural integrity of the protein complex, as in yeast (previously demonstrated) []. However, an alternative may be that ELP3 binds ands cleave SAM, as seen in the archaea M. jannaschii. It has also been shown in previous studies that the mouse ELP3 does not require the histone acyltransferase domain for zygotic paternal genome demethylation [].
All eukaryotic cells are surrounded by a plasma membrane, and they also
contain multiple membrane-based organelles and structures inside cells. Thusmembrane remodeling is likely to be important for most cellular activities and
development. The Bin-Amphiphysin-Rvs (BAR) domain superfamily of proteins hasbeen found to play a major role in remodeling cellular membranes linked with
organelle biogenesis, membrane trafficking, cell division, cell morphology andcell migration. The BAR domain superfamily of proteins is evolutionarily
conserved with representative members present from yeast to man. Currentlythere are three distinct families of BAR domain proteins: classical BAR, F-BAR (FCH-BAR e.g., Fes/CIP4 homology BAR e.g., Toca-1) and I-
BAR (inverse-BAR e.g., IRSp53). The classical BAR, F-BAR, and I-BAR domainsare structurally similar homodimeric modules with antiparallel arrangement of
monomers [,
].The F-BAR domain is emerging as an important player in membrane remodeling
pathways. F-BAR domain proteins couple membrane remodeling with actin dynamicsassociated with endocytic pathways and filopodium formation. F-BAR domain
containing proteins can be categorized into five sub-families based on theirphylogeny which is consistent with the additional protein domains they
possess, for example, RhoGAP domains, Cdc42 binding sites,SH2 domains, SH3 domains and tyrosine
kinase domains [].The N-terminal part (about one third) of the F-BAR domain was previously
characterised as an FCH (FER-CIP4 homology) domain. However, the region ofsequence similarity extends to an adjacent region with a coiled-coil (CC)
structure. Hence, the F-BAR domain (FCH+CC, ~300 amino acids) has also beencalled extended FC (EFC) domain. The F-BAR domain plays a role in dimerization
and membrane phospholipid binding. It binds specifically to certain kinds oflipids and acts as a a dimeric membrane-binding curvature effector [
,
,
].The F-BAR domain is composed of five helices. Its structure is composed of a
short N-terminal helix, three long α-helices, and a short C-terminal helixfollowed by an extended peptide of 17 amino acids [
,
].
Amphiphysins belong to the expanding BAR (Bin-Amphiphysin-Rvsp) family proteins, all members of which share a highly conserved N-terminal BAR domain, which has predicted coiled-coil structures required for amphiphysin dimerisation and plasma membrane interaction [
]. Almost all members also share a conserved C-terminal Src homology 3 (SH3) domain, which mediates their interactions with the GTPase dynamin and the inositol-5'-phosphatase synaptojanin 1 in vertebrates and with actin in yeast. The central region of all these proteins is most variable. In mammals, the central region of amphiphysin I and amphiphysin IIa contains a proline-arginine-rich region for endophilin binding and a CLAP domain, for binding to clathrin and AP-2. The interactions mediated by both the central and C-terminal domains are believed to be modulated by protein phosphorylation [
,
].Amphiphysins are proteins involved in clathrin-mediated endocytosis clathrin-mediated endocytosis, actin function, and signalling pathways [
,
].Amphiphysin 1 was first identified in 1992 as a brain protein that was partially-associated with synaptic vesicles. Following its cloning, it was also realised to be a human auto-antigen that is detected in a rare neurological disease, Stiff-Man Syndrome, and also in certain types of cancer [
]. Amphiphysin 1 senses and facilitates membrane curvature to mediate synaptic vesicles invagination and fission during newly retrieved presynaptic vesicle formation and also acts as a linker protein binding with dynamin, clathrin, Amphiphysin II, and other dephosphins in the clathrin-coated complex. Amphiphysin 1 is cleaved an asparagine endopeptidase (AEP), which generates a fragment that increases with aging. This fragment disrupts the normal endocytic function of Amphiphysin 1, leading to synaptic dysfunction, as it activates CDK5 inducing tau hyperphosphorylation. Therefore, Amphiphysin 1 posttranslational modification contributes to pathogenesis of Alzheimer's disease, being the AEP a therapeutic target [].
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 (predicted) zinc finger is found in the bassoon and piccolo proteins, both of which are components of the presynaptic cytoskeletal matrix (PCM) assembled at the active zone of neurotransmitter release, where Piccolo plays a role in the trafficking of synaptic vesicles (SVs) [,
,
]. The Piccolo zinc fingers were found to interact with the dual prenylated rab3A and VAMP2/Synaptobrevin II receptor PRA1. There are eight conserved cysteines in Piccolo-type zinc fingers, suggesting that they coordinates two zinc ligands.
Major Histocompatibility Complex (MHC) glycoproteins are heterodimeric cell surface receptors that function to present antigen peptide fragments to T cells responsible for cell-mediated immune responses. MHC molecules can be subdivided into two groups on the basis of structure and function: class I molecules present intracellular antigen peptide fragments (~10 amino acids) on the surface of the host cells to cytotoxic T cells; class II molecules present exogenously derived antigenic peptides (~15 amino acids) to helper T cells. MHC class I and II molecules are assembled and loaded with their peptide ligands via different mechanisms. However, both present peptide fragments rather than entire proteins to T cells, and are required to mount an immune response.Class II MHC glycoproteins are expressed on the surface of antigen-presenting cells (APC), including macrophages, dendritic cells and B cells. MHC II proteins present peptide antigens that originate extracellularly from foreign bodies such as bacteria. Proteins from the pathogen are degraded into peptide fragments within the APC, which sequesters these fragments into the endosome so they can bind to MHC class II proteins, before being transported to the cell surface. MHC class II receptors display antigens for recognition by helper T cells (stimulate development of B cell clones) and inflammatory T cells (cause the release of lymphokines that attract other cells to site of infection) [
].MHC class II molecules are comprised of two membrane-spanning chains, alpha and beta, of similar size. Both chains consist of two globular domains (N- and C-terminal), and a transmembrane segment to anchor them to the membrane [
]. A groove in the structure acts as the peptide-binding site.This entry represents the N-terminal domain (also called alpha-1 domain) of the alpha chain.
The ELO family consist of eukaryotic integral membrane proteins involved in fatty acid elongation. This family consist of:Mammalian proteins ELOVL1 to ELOVL7 [
,
]. These proteins catalyse the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle, each of them has a specific substrate specificity and physiological functions.Yeast ELO1, ELO2 and ELO3 [
,
]. They are components of a microsomal membrane-bound long-chain fatty acid elongation system.Caenorhabditis elegans hypothetical protein C40H1.4.Caenorhabditis elegans hypothetical protein D2024.3.This group of eukaryotic integral membrane proteins are evolutionary related and have from 290 to 435 amino acid residues. Structurally, they seem to be formed of three sections: a N-terminal region with two transmembrane domains, a central hydrophilic loop and a C-terminal region that contains from one to three transmembrane domains. Members of this family are involved in long chain fatty acid elongation systems that produce the 26-carbon precursors for ceramide and sphingolipid synthesis []. Yeast ELO3 () affects plasma membrane H+-ATPase activity, and may act on a glucose-signalling pathway that controls the expression of several genes that are transcriptionally regulated by glucose such as PMA1 [
]. It plays an important role in lipotoxic cell death induced by oleic acid through maintaining a balanced fatty acid composition in the plasma membrane []. Mammalian ELOVLs are also associated with known pathologies. ELOVL1 catalyses elongation of saturated and monounsaturated C22-C26-VLCFAs, and dominant mutations cause ichthyosis, hypomyelination of the central white matter that leads to spastic paraplegia and central nystagmus and optic atrophy [], dominant ELOVL4 mutations cause a juvenile macular dystrophy (Stargardt disease-3) and Elovl4 knockout mice die soon after birth due to a deficiency in skin barrier formation. Studies in Elovl6-null mice have revealed that ELOVL6 is involved in an obesity-induced insulin resistance and ELOVL7 is involved in prostate cancer growth [].
After cytochrome c is synthesized in the cytoplasm as apocytochrome c, it is transported through the outer mitochondrial membrane to the intermembrane space, where haem is covalently attached by thioester bonds to two cysteine residues located in the cytochrome c centre. Cytochrome c is required during oxidative phosphorylation as an electron shuttle between Complex III (cytochrome c reductase) and IV (cytochrome c oxidase). In addition, cytochrome c is involved in apoptosis in more complex organisms such as Xenopus, rats and humans. Cellular stress can induce cytochrome c release from the mitochondrial membrane. In mammals, cytochrome c triggers the assembly of the apoptosome, consisting of cytochrome c, Apaf-1 and dATP, which activates caspase-9, leading to cell death [
,
]. There are several different members of the cytochrome c family with different functional roles, for instance cytochrome c549 is associated with photosystem II []. The known structures of c-type cytochromes have six different classes of fold. Of these, four are unique to c-type cytochromes [
,
]. The consensus sequence for the cytochrome c centre is Cys-X-X-Cys-His, where the histidine residue is one of the two axial ligands of the haem iron []. This arrangement is shared by all proteins known to belong to the cytochrome c family, which presently includes both mono-haem proteins and multi-haem proteins. This entry represents mono-haem cytochrome c proteins (excluding class II and f-type cytochromes), such as cytochromes c, c1, c2, c5, c555, c550 to c553, c556, and c6.Cytochrome c-type centres are also found in the active sites of many enzymes, including cytochrome cd1-nitrite reductase as the N-terminal haem c domain, in quinoprotein alcohol dehydrogenase as the C-terminal domain, in Quinohemoprotein amine dehydrogenase A chain as domains 1 and 2, and in the cytochrome bc1 complex as the cytochrome bc1 domain.
Methyl-accepting chemotaxis protein, four helix bundle domain superfamily
Type:
Homologous_superfamily
Description:
This entry represents a four-helix bundle that operates as a ubiquitous sensory module in prokaryotic signal-transduction, which is known as four-helix bundles methyl-accepting chemotaxis protein (4HB_MCP) domain. The 4HB_MCP is always found between two predicted transmembrane helices indicating that it detects only extracellular signals. In many cases the domain is associated with a cytoplasmic HAMP domain suggesting that most proteins carrying the bundle might share the mechanism of transmembrane signalling which is well-characterised in E coli chemoreceptors [
].Methyl-accepting chemotaxis proteins (MCPs) are a family of bacterial receptors that mediate chemotaxis to diverse signals, responding to changes in the concentration of attractants and repellents in the environment by altering swimming behaviour [
]. Environmental diversity gives rise to diversity in bacterial signalling receptors, and consequently there are many genes encoding MCPs []. For example, there are four well-characterised MCPs found in Escherichia coli: Tar (taxis towards aspartate and maltose, away from nickel and cobalt), Tsr (taxis towards serine, away from leucine, indole and weak acids), Trg (taxis towards galactose and ribose) and Tap (taxis towards dipeptides). MCPs share similar topology and signalling mechanisms. MCPs either bind ligands directly or interact with ligand-binding proteins, transducing the signal to downstream signalling proteins in the cytoplasm. MCPs undergo two covalent modifications: deamidation and reversible methylation at a number of glutamate residues. Attractants increase the level of methylation, while repellents decrease it. The methyl groups are added by the methyl-transferase cheR and are removed by the methylesterase cheB. Most MCPs are homodimers that contain the following organisation: an N-terminal signal sequence that acts as a transmembrane domain in the mature protein; a poorly-conserved periplasmic receptor (ligand-binding) domain; a second transmembrane domain; and a highly-conserved C-terminal cytoplasmic domain that interacts with downstream signalling components. The C-terminal domain contains the glycosylated glutamate residues.
BAG domains are present in Bcl-2-associated athanogene 1 and silencer of death domains. The BAG proteins are modulators of chaperone activity, they bind to HSP70/HSC70 proteins and promote substrate release. The proteins have anti-apoptotic activity and increase the anti-cell death function of BCL-2 induced by various stimuli. BAG-1 binds to the serine/threonine kinase Raf-1 or Hsc70/Hsp70 in a mutually exclusive interaction. BAG-1 promotes cell growth by binding to and stimulating Raf-1 activity. The binding of Hsp70 to BAG-1 diminishes Raf-1 signalling and inhibits subsequent events, such as DNA synthesis, as well as arrests the cell cycle. BAG-1 has been suggested to function as a molecular switch that encourages cells to proliferate in normal conditions but become quiescent under a stressful environment [,
].BAG-family proteins contain a single BAG domain, except for human BAG-5 which has four BAG repeats [
]. The BAG domain is a conserved region located at the C terminus of the BAG-family proteins that binds the ATPase domain of Hsc70/Hsp70. The BAG domain is evolutionarily conserved, and BAG domain containing proteins have been described and/or proven in a variety of organisms including Mus musculus (Mouse), Xenopus spp., Drosophila spp., Bombyx mori (Silk moth), Caenorhabditis elegans, Saccharomyces cerevisiae (Baker's yeast), Schizosaccharomyces pombe (Fission yeast), and Arabidopsis thaliana (Mouse-ear cress).The BAG domain has 110-124 amino acids and is comprised of three anti-parallel α-helices, each approximately 30-40 amino acids in length. The first and second helices interact with the serine/threonine kinase Raf-1 and the second and third helices are the sites of the BAG domain interaction with the ATPase domain of Hsc70/Hsp70. Binding of the BAG domain to the ATPase domain is mediated by both electrostatic and hydrophobic interactions in BAG-1 and is energy requiring.
Positive-stranded RNA (+RNA) viruses that belong to the order Nidovirales infect a wide range of vertebrates (families Arteriviridae and Coronaviridae) or invertebrates (Mesoniviridae and Roniviridae). Examples of nidoviruses with high economic and societal impact are the arterivirus porcine reproductive and respiratory syndrome virus (PRRSV) and the zoonotic coronaviruses (CoVs) causing severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and Covid-19 (SARS-CoV-2) in humans. In all nidoviruses, at least two-thirds of the capacity of the polycistronic genome is occupied by the two large open reading frames (ORFs; 1a and 1b) that together constitute the replicase gene. The two polyproteins produced, pp1a (ORF1a-encoded) and pp1ab (ORF1a/ORF1b-encoded), are processed to a dozen or more proteins by the virus main protease (3CLpro, encoded in ORF1a) with possible involvement of other protease(s). These and other proteins form a membrane-bound replication-transcription complex (RTC) that invariably includes two key ORF1b-encoded subunits: the RNA-dependent RNA polymerase (RdRp) and a superfamily 1 helicase domain (HEL1), which is fused with a multinuclear Zn-binding domain (ZBD). The RNA-dependent RNA polymerase (RdRp) domain of nidoviruses resides in a cleavage product of the replicase polyprotein named non- structural protein (nsp) 12 in coronaviruses and nsp9 in arteriviruses. In all nidoviruses, the C-terminal RdRp domain is linked to a conserved N-terminal domain, which has been coined NiRAN (nidovirus RdRp-associated nucleotidyl transferase). The NiRAN domain has an essential nucleotidylation activity and its potential functions in nidovirus replication may include RNA ligation, protein-primed RNA synthesis, and the guanylyl-transferase function that is necessary for mRNA capping [
,
,
,
,
].The NiRAN domain is characterised by an α+β fold composed of eight α-helices and a five stranded β-sheet. In addition, an N-terminal β-hairpin interacts with the palm subdomain of the RdRp domain [
,
].
This is a family of glycine cleavage H-proteins, part of the glycine cleavage system (GCS) found in bacteria, archaea, and the mitochondria of eukaryotes. GCS is a multienzyme complex consisting of 4 different components (P-, H-, T- and L-proteins) which catalyzes the oxidative cleavage of glycine [
]. The H-protein shuttles the methylamine group of glycine from the P-protein (glycine dehydrogenase) to the T-protein (aminomethyltransferase) via a lipoyl group, attached to a completely conserved lysine residue [].
This superfamily represents the N-terminal OB domain found in NigD-like proteins. Proteins containing this domain are mostly found in Bacteroides species, including NigD. They are typically between 234 and 260 amino acids in length and possess an N-terminal lipoprotein attachment site. NigD is a protein found in the Nig operon that encodes a bacteriocin called nigrescin. It has been suggested that NigD may be the immunity protein for nigrescin (NigC) because it is directly downstream [
].
This superfamily represents a domain found in SARS and bat coronaviruses, which is about 70 amino acids in length. PL2pro is a domain of the non-structural protein NSP3, found associated with various other coronavirus proteins due to the polyprotein nature of most viral translation. The domain performs three of the cleavages required to separate the translated polyprotein into its distinct proteins [
]. Structurally, this domain consists of two α-helices and seven β-strands arranged into an antiparallel β-sheet.
This protein is found adjacent to various classes of repetitive or low-complexity YSIRK proteins (whether unique in genome or not), in a range of species (Enterococcus faecalis X98, Ruminococcus torques, Coprobacillus sp. D7, Lysinibacillus fusiformis ZC1, Streptococcus equi subsp. equi 4047, etc). The affliated YSIRK proteins include Streptococcal protective antigen (see [
]) and proteins with the Rib/alpha/Esp surface antigen repeat (see ). The last quarter of this protein has an AraC family helix-turn-helix (HTH) transcriptional regulator domain.
This entry represents the N-terminal OB domain found in NigD-like proteins. Proteins containing this domain are mostly found in Bacteroides species, including NigD. They are typically between 234 and 260 amino acids in length and possess an N-terminal lipoprotein attachment site. NigD is a protein found in the Nig operon that encodes a bacteriocin called nigrescin. It has been suggested that NigD may be the immunity protein for nigrescin (NigC) because it is directly downstream [
].
This entry includes human E3 ubiquitin-protein ligase MARCH proteins (MARCH1/2/3/4/5/8/9/11), and virus proteins (MIR1, MIR2, LAP and VIE1) that share homology with the MARCH proteins [
,
]. Human MARCH1 mediates ubiquitination of TFRC, CD86, FAS and MHC class II proteins, such as HLA-DR alpha and beta, and promotes their subsequent endocytosis and sorting to lysosomes via multivesicular bodies [
]. Virus MIR1 has been shown to function as an E3 ubiquitin ligase for immune recognition-related molecules [].
Ubiquinol-cytochrome C reductase hinge domain superfamily
Type:
Homologous_superfamily
Description:
The ubiquinol-cytochrome C reductase complex (cytochrome bc1 complex) is a respiratory multienzyme complex [
]. The bc1 complex contains 11 subunits; 3 respiratory subunits (cytochrome B, cytochrome C1, Rieske protein), 2 core proteins and 6 low molecular weight proteins. This family represents the 'hinge' protein of the complex which is thought to mediate formation of the cytochrome c1 and cytochrome c complex. Proteins in this entry from an α-helical hairpin.This entry represents the structural domain superfamily.
This protein contains several bacterial RmuC DNA recombination proteins. The function of the RMUC protein is unknown but it is suspected that it is either a structural protein that protects DNA against nuclease action, or is itself involved in DNA cleavage at the regions of DNA secondary structures [
]. Proteins in this family are predicted to contain a central endonuclease-like fold domain, surrounded by coiled coils, consistent with a direct role in DNA cleavage [,
].
Plenty of SH3 domains protein 2 (POSH2 also known as SH3 domain-containing RING finger protein 3 or putative E3 ubiquitin-protein ligase SH3RF2) contains the Src homology 3 (SH3) domains and a RING finger domain which confers E3 ligase activity to the protein. It belongs to the POSH family, which includes POSH1, POSH2 and POSH3 [
]. POSH2 interacts with GTP-loaded Rac1, which is a small signaling G protein [].This entry represents the third SH3 domain of SH3RF2.
This UBA domain is found in sequestosome-1 (SQSTM) and similar proteins [
].Sequestosome-1 (SQSTM), also known as ubiquitin-binding protein p62, is a widely expressed multifunctional cytoplasmic protein that is able to noncovalently bind ubiquitin and several signaling proteins, suggesting a regulatory role connected to the ubiquitin-proteasome pathway. It functions as a scaffolding protein that regulates a diverse range of signaling pathways [
]. It plays a critical role in cell's selective autophagy and oxidative stress response.
Proteins containing this region are predicted secretins, that is, outer membrane pore proteins associated with delivery of proteins from the periplasm to the outside of the cell. Related proteins include the GspD type II secretion family, the YscC/HrcC family type III secretion family, and the PilQ type IV pilus formation family. These proteins are found in gene clusters associated with MSHA (mannose-sensitive haemagglutinin) and related pili, and appear to be the secretin of this pilus system.
This entry contains a functionally uncharacterised region belonging to the Git3 G-protein coupled receptor. Git3 is one of six proteins required for glucose-triggered adenylate cyclase activation, and is a G protein-coupled receptor responsible for the activation of adenylate cyclase through Gpa2 - heterotrimeric G protein alpha subunit, part of the glucose-detection pathway. Git3 contains seven predicted transmembrane domains, a third cytoplasmic loop and a cytoplasmic tail [
]. This is the conserved N-terminal domain of the member proteins.
This family includes NudC (nuclear distribution gene C), NudC-like (NudCL) [
], NudC-like 2/NudC domain-containing protein 2 (NudCL2/NUDCD2)[], NudC domain-containing protein 3, and NudC domain protein BOBBER from plants []. All members of the NudC family share a conserved p23 domain, which possesses chaperone activity both in conjunction with and independently of heat shock protein 90 (Hsp90) []. NudC proteins play multiple roles in cell cycle progression, cell migration, inflammatory response, platelet production, carcinogenesis [,
].
Members of this protein family are the precursors of a family of small bacteriocins (i.e. microcins) with thiopeptide type modifications, a highly modified subclass of heterocycle-containing peptide antibiotics. Members tend to be found clustered in genomes with proteins recognised by and proteins/domains annotated as lantibiotic dehydratase (
,
), and with a cyclodehydratase/docking protein fusion protein characteristic of heterocycle formation. Members with known function block translation by inhibiting translation factor activity [
,
,
,
].
The ezrin-radixin-moesin (ERM) protein family link actin filaments of cell surface structures to the plasma membrane, using a C-terminal F-actin binding segment and an N-terminal FERM domain, a common membrane binding module [
]. ERM proteins are highly related members of the larger protein 4.1 superfamily. The sole Drosophila ERM protein, Moesin, functions in maintaining epithelial integrity by regulating cell-signalling events that affect actin organisation and polarity [].This superfamily represents the actin-binding tail domain of ERM proteins.
This entry represents the Ninja family of proteins, which play a role in stress-related and growth-related signalling cascades [
]. In Arabidopsis thaliana, Ninja (also known as AFP homologue 2, At4g28910) is a negative regulator of jasmonate responses. Through protein Ninja, Jasmonate ZIM-domain (JAZ) repressor proteins recruit the Groucho/Tup1-type co-repressor TOPLESS (TPL) and TPL-related proteins (TPRs) []. Ninja-family proteins AFP1 and AFP4 have been shown to act as negative regulators of the abscisic acid (ABA) response [].
This entry represents the AAA-lid domain found in MCM proteins.MCM proteins are DNA-dependent ATPases required for the initiation of
eukaryotic DNA replication [,
,
]. In eukaryotes there is a family of six proteins, MCM2 to MCM7. They were first identified in yeast where most of them have adirect role in the initiation of chromosomal DNA replication by interacting directly with autonomously replicating sequences (ARS). They were thus called minichromosome maintenance proteins, MCM proteins [
].
This family consists of mammalian Ameloblastin precursor (Amelin) proteins. Matrix proteins of tooth enamel consist mainly of amelogenin but also of non-amelogenin proteins, which, although their volumetric percentage is low, have an important role in enamel mineralization. One of the non-amelogenin proteins is ameloblastin, also known as amelin and sheathlin. Ameloblastin (AMBN) is one of the enamel sheath proteins which is thought to have a role in determining the prismatic structure of growing enamel crystals [
].
This domain contains one highly conserved negatively charged residue and one highly conserved positively charged residue that are probably important for the function of these proteins. Proteins containing this domain include the yeast nuclear export factor Sac3 [
], and mammalian GANP/MCM3-associated protein, which facilitates the nuclear localisation of MCM3, a protein that associates with chromatin in the G1 phase of the cell-cycle []. It also includes yeast Thp3 (THO-related protein 3), which may have a role in transcription elongation [
].
The many bacterial transcription regulation proteins which bind DNA through a
'helix-turn-helix' motif can be classified into subfamilies on the basis ofsequence similarities. One of these subfamilies, called 'iclR', groups several proteins including:
gylR, a possible activator protein for the gylABX glycerol operon in
Streptomyces.iclR, the repressor of the acetate operon (also known as glyoxylate bypass
operon) in Escherichia coli and Salmonella typhimurium. These proteins have
a Helix-Turn-Helix motif at the N terminus that is similar to that of other DNA-binding proteins [].
This entry represents a domain found in KaiC, which is a core component of the KaiBC clock protein complex that constitutes the main circadian regulator in cyanobacteria [
]. The circadian clock protein KaiC, is encoded in the kaiABC operon that controls circadian rhythms and may be universal in Cyanobacteria. Each member contains two copies of this domain, which is alsofound in other proteins. KaiC performs autophosphorylation and acts as its own transcriptional repressor.
Proteins containing this domain also include some eukaryotic proteins.
Type I protein secretion is a system in some Gram-negative bacteria to export proteins (often proteases) across both inner and outer membranes to the extracellular medium. PrtD, an ABC transporter, is one of three proteins of the type I secretion apparatus, which assemble with PrtE and PrtF to form the complex required for protein secretion [
]. Targeted proteins are not cleaved at the N terminus, but rather carry signals located toward the extreme C terminus to direct type I secretion.
This superfamily represents the peptidyl-prolyl cis-trans isomerase domain found in a wide range of proteins, including trigger factor [
,
], FK506-binding proteins [,
], proteins from the parvulin family such as Par10 from E.coli, Pin1 and Par14 from human or Pin from plants [], chaperone SurA [,
] and foldase protein PrsA []. This domain catalyses cis/trans isomerization of peptidyl-prolyl bonds, which is often rate-limiting for protein folding.This domain consists of a flattened β-barrel of four/six-stranded, antiparallel sheets, surrounded by four/six α-helices.
E3 ubiquitin-protein ligase SH3RF2, second SH3 domain
Type:
Domain
Description:
SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation [
]. It may also play a role in cardiac functions together with protein phosphatase 1 []. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This entry represents the second SH3 domain of SH3RF2.
This entry represents a domain found tandemly duplicated in two proven archaeal S-layer glycoproteins, MA0829 from Methanosarcina acetivorans C2A and MM1976 from Methanosarcina mazei Go1 [
], as well as in several paralogues of those L-layer proteins from both species. Members of the family show regions of local similarity to another known family of archaeal S-layer proteins (). Some members of this family, including the proven S-layer proteins, have the archaeosortase A target motif, PGF-CTERM (
), at the protein C terminus.
This protein domain is found at the C-terminal end of the Tankyrase binding protein in eukaryotes. The precise function of this protein is still unknown. However, it is known that interacts with the enzyme tankyrase, a telomeric poly(ADP-ribose) polymerase, by binding to it. Tankyrin catalyses poly(ADP-ribose) chain formation onto proteins. More specifically, it binds to the ankyrin domain in tankyrase [
]. The protein domain is approximately 170 amino acids in length and contains two conserved sequence motifs: FPG and LKA.
The Flagellar/Hr/Invasion Proteins Export Pore (FHIPEP) family [
,
] consists of a number of proteins that constitute the type III secretion (or signal peptide-independent) pathway apparatus [,
]. This mechanism translocates proteins lacking an N-terminal signal peptide across the cell membrane in one step, as it does not require an intermediate periplasmic process to cleave the signal peptide. It is a common pathway amongst Gram-negative bacteria for secreting toxic and flagellar proteins.This superfamily represents the domain 1 found in FHIPEP protein.
The Flagellar/Hr/Invasion Proteins Export Pore (FHIPEP) family [
,
] consists of a number of proteins that constitute the type III secretion (or signal peptide-independent) pathway apparatus [,
]. This mechanism translocates proteins lacking an N-terminal signal peptide across the cell membrane in one step, as it does not require an intermediate periplasmic process to cleave the signal peptide. It is a common pathway amongst Gram-negative bacteria for secreting toxic and flagellar proteins.This superfamily represents the domain 3 found in FHIPEP protein.
The Flagellar/Hr/Invasion Proteins Export Pore (FHIPEP) family [
,
] consists of a number of proteins that constitute the type III secretion (or signal peptide-independent) pathway apparatus [,
]. This mechanism translocates proteins lacking an N-terminal signal peptide across the cell membrane in one step, as it does not require an intermediate periplasmic process to cleave the signal peptide. It is a common pathway amongst Gram-negative bacteria for secreting toxic and flagellar proteins.This superfamily represents the domain 4 found in FHIPEP protein.
This family contains protein-histidine N-methyltransferases (also known as DORA reverse strand protein DREV) that specifically catalyse 1-methylhistidine (pros-methylhistidine) methylation of target proteins, such as S100A9, NDUFB3, SLC39A5, SLC39A7, ARMC6 and DNAJB12 [
,
]. They mediate methylation of proteins with a His-x-His (HxH) motif (where 'x' is preferably a small amino acid), in which the 1-methylhistidine modification may affect the binding of zinc and other metals []. These proteins constitute the main methyltransferase for the 1-methylhistidine modification in cell [].
Pigment precursor permease/Protein ATP-binding cassette sub-family G
Type:
Family
Description:
This family includes pigment precursor permeases (protein white, brown and scarlet) from flies and ATP-binding cassette sub-family G member 1 (ABCG1) from mammals. The fly pigment precursor permeases are membrane-spanning proteins necessary for the transport of pigment precursor into pigment cells responsible for eye colour. White protein dimerises with brown protein for the transport of guanine and with scarlet protein for the transport of tryptophan [
].ABCG1 is an ABC half transporter that facilitates efflux excess cholesterol from macrophages [
,
].
Aconitase (aconitate hydratase;
) is an iron-sulphur protein that contains a [4Fe-4S]-cluster and catalyses the interconversion of isocitrate and citrate via a cis-aconitate intermediate. Aconitase functions in both the TCA and glyoxylate cycles, however unlike the majority of iron-sulphur proteins that function as electron carriers, the [4Fe-4S]-cluster of aconitase reacts directly with an enzyme substrate. In eukaryotes there is a cytosolic form (cAcn) and a mitochondrial form (mAcn) of the enzyme. In bacteria there are also 2 forms, aconitase A (AcnA) and B (AcnB). Several aconitases are known to be multi-functional enzymes with a second non-catalytic, but essential function that arises when the cellular environment changes, such as when iron levels drop [,
]. Eukaryotic cAcn and mAcn, and bacterial AcnA have the same domain organisation, consisting of three N-terminal alpha/beta/alpha domains, a linker region, followed by a C-terminal 'swivel' domain with a beta/beta/alpha structure (1-2-3-linker-4), although mAcn is smaller than cAcn. However, bacterial AcnB has a different organisation: it contains an N-terminal HEAT-like domain, followed by the 'swivel' domain, then the three alpha/beta/alpha domains (HEAT-4-1-2-3) [].Eukaryotic cAcn enzyme balances the amount of citrate and isocitrate in the cytoplasm, which in turn creates a balance between the amount of NADPH generated from isocitrate by isocitrate dehydrogenase with the amount of acetyl-CoA generated from citrate by citrate lyase. Fatty acid synthesis requires both NADPH and acetyl-CoA, as do other metabolic processes, including the need for NADPH to combat oxidative stress. The enzymatic form of cAcn predominates when iron levels are normal, but if they drop sufficiently to cause the disassembly of the [4Fe-4S]-cluster, then cAcn undergoes a conformational change from a compact enzyme to a more open L-shaped protein known as iron regulatory protein 1 (IRP1; or IRE-binding protein 1, IREBP1) [,
]. As IRP1, the catalytic site and the [4Fe-4S]-cluster are lost, and two new RNA-binding sites appear. IRP1 functions in the post-transcriptional regulation of genes involved in iron metabolism - it binds to mRNA iron-responsive elements (IRE), 30-nucleotide stem-loop structures at the 3' or 5' end of specific transcripts. Transcripts containing an IRE include ferritin L and H subunits (iron storage), transferrin (iron plasma chaperone), transferrin receptor (iron uptake into cells), ferroportin (iron exporter), mAcn, succinate dehydrogenase, erythroid aminolevulinic acid synthetase (tetrapyrrole biosynthesis), among others. If the IRE is in the 5'-UTR of the transcript (e.g. in ferritin mRNA), then IRP1-binding prevents its translation by blocking the transcript from binding to the ribosome. If the IRE is in the 3'-UTR of the transcript (e.g. transferrin receptor), then IRP1-binding protects it from endonuclease degradation, thereby prolonging the half-life of the transcript and enabling it to be translated [
].IRP2 is another IRE-binding protein that binds to the same transcripts as IRP1. However, since IRP1 is predominantly in the enzymatic cAcn form, it is IRP2 that acts as the major metabolic regulator that maintains iron homeostasis [
]. Although IRP2 is homologous to IRP1, IRP2 lacks aconitase activity, and is known only to have a single function in the post-transcriptional regulation of iron metabolism genes []. In iron-replete cells, IRP2 activity is regulated primarily by iron-dependent degradation through the ubiquitin-proteasomal system.Bacterial AcnB is also known to be multi-functional. In addition to its role in the TCA cycle, AcnB was shown to be a post-transcriptional regulator of gene expression in Escherichia coli and Salmonella enterica [
,
]. In S. enterica, AcnB initiates a regulatory cascade controlling flagella biosynthesis through an interaction with the ftsH transcript, an alternative RNA polymerase sigma factor. This binding lowers the intracellular concentration of FtsH protease, which in turn enhances the amount of RNA polymerase sigma32 factor (normally degraded by FtsH protease), and sigma32 then increases the synthesis of chaperone DnaK, which in turn promotes the synthesis of the flagellar protein FliC. AcnB regulates the synthesis of other proteins as well, such as superoxide dismutase (SodA) and other enzymes involved in oxidative stress.3-isopropylmalate dehydratase (or isopropylmalate isomerase;
) catalyses the stereo-specific isomerisation of 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate. This enzyme performs the second step in the biosynthesis of leucine, and is present in most prokaryotes and many fungal species. The prokaryotic enzyme is a heterodimer composed of a large (LeuC) and small (LeuD) subunit, while the fungal form is a monomeric enzyme. Both forms of isopropylmalate are related and are part of the larger aconitase family [
]. Aconitases are mostly monomeric proteins which share four domains in common and contain a single, labile [4Fe-4S]cluster. Three structural domains (1, 2 and 3) are tightly packed around the iron-sulphur cluster, while a fourth domain (4) forms a deep active-site cleft. The prokaryotic enzyme is encoded by two adjacent genes, leuC and leuD, corresponding to aconitase domains 1-3 and 4 respectively [
,
]. LeuC does not bind an iron-sulphur cluster. It is thought that some prokaryotic isopropylamalate dehydrogenases can also function as homoaconitase , converting cis-homoaconitate to homoisocitric acid in lysine biosynthesis [
]. Homoaconitase has been identified in higher fungi (mitochondria) and several archaea and one thermophilic species of bacteria, Thermus thermophilus []. It is also found in the higher plant Arabidopsis thaliana, where it is targeted to the chloroplast [].This superfamily represents the 'swivel' domain found at the C-terminal of eukaryotic mAcn, cAcn/IPR1 and IRP2, and bacterial AcnA, but in the N-terminal region following the HEAT-like domain in bacterial AcnB. This domain has a three layer beta/beta/alpha structure, and in cytosolic Acn is known to rotate between the cAcn and IRP1 forms of the enzyme. This domain is also found in the small subunit of isopropylmalate dehydratase (LeuD).
Aconitase (aconitate hydratase;
) is an iron-sulphur protein that contains a [4Fe-4S]-cluster and catalyses the interconversion of isocitrate and citrate via a cis-aconitate intermediate. Aconitase functions in both the TCA and glyoxylate cycles, however unlike the majority of iron-sulphur proteins that function as electron carriers, the [4Fe-4S]-cluster of aconitase reacts directly with an enzyme substrate. In eukaryotes there is a cytosolic form (cAcn) and a mitochondrial form (mAcn) of the enzyme. In bacteria there are also 2 forms, aconitase A (AcnA) and B (AcnB). Several aconitases are known to be multi-functional enzymes with a second non-catalytic, but essential function that arises when the cellular environment changes, such as when iron levels drop [
,
]. Eukaryotic cAcn and mAcn, and bacterial AcnA have the same domain organisation, consisting of three N-terminal alpha/beta/alpha domains, a linker region, followed by a C-terminal 'swivel' domain with a beta/beta/alpha structure (1-2-3-linker-4), although mAcn is smaller than cAcn. However, bacterial AcnB has a different organisation: it contains an N-terminal HEAT-like domain, followed by the 'swivel' domain, then the three alpha/beta/alpha domains (HEAT-4-1-2-3) [].Eukaryotic cAcn enzyme balances the amount of citrate and isocitrate in the cytoplasm, which in turn creates a balance between the amount of NADPH generated from isocitrate by isocitrate dehydrogenase with the amount of acetyl-CoA generated from citrate by citrate lyase. Fatty acid synthesis requires both NADPH and acetyl-CoA, as do other metabolic processes, including the need for NADPH to combat oxidative stress. The enzymatic form of cAcn predominates when iron levels are normal, but if they drop sufficiently to cause the disassembly of the [4Fe-4S]-cluster, then cAcn undergoes a conformational change from a compact enzyme to a more open L-shaped protein known as iron regulatory protein 1 (IRP1; or IRE-binding protein 1, IREBP1) [,
]. As IRP1, the catalytic site and the [4Fe-4S]-cluster are lost, and two new RNA-binding sites appear. IRP1 functions in the post-transcriptional regulation of genes involved in iron metabolism - it binds to mRNA iron-responsive elements (IRE), 30-nucleotide stem-loop structures at the 3' or 5' end of specific transcripts. Transcripts containing an IRE include ferritin L and H subunits (iron storage), transferrin (iron plasma chaperone), transferrin receptor (iron uptake into cells), ferroportin (iron exporter), mAcn, succinate dehydrogenase, erythroid aminolevulinic acid synthetase (tetrapyrrole biosynthesis), among others. If the IRE is in the 5'-UTR of the transcript (e.g. in ferritin mRNA), then IRP1-binding prevents its translation by blocking the transcript from binding to the ribosome. If the IRE is in the 3'-UTR of the transcript (e.g. transferrin receptor), then IRP1-binding protects it from endonuclease degradation, thereby prolonging the half-life of the transcript and enabling it to be translated [
].IRP2 is another IRE-binding protein that binds to the same transcripts as IRP1. However, since IRP1 is predominantly in the enzymatic cAcn form, it is IRP2 that acts as the major metabolic regulator that maintains iron homeostasis [
]. Although IRP2 is homologous to IRP1, IRP2 lacks aconitase activity, and is known only to have a single function in the post-transcriptional regulation of iron metabolism genes []. In iron-replete cells, IRP2 activity is regulated primarily by iron-dependent degradation through the ubiquitin-proteasomal system.Bacterial AcnB is also known to be multi-functional. In addition to its role in the TCA cycle, AcnB was shown to be a post-transcriptional regulator of gene expression in Escherichia coli and Salmonella enterica [
,
]. In S. enterica, AcnB initiates a regulatory cascade controlling flagella biosynthesis through an interaction with the ftsH transcript, an alternative RNA polymerase sigma factor. This binding lowers the intracellular concentration of FtsH protease, which in turn enhances the amount of RNA polymerase sigma32 factor (normally degraded by FtsH protease), and sigma32 then increases the synthesis of chaperone DnaK, which in turn promotes the synthesis of the flagellar protein FliC. AcnB regulates the synthesis of other proteins as well, such as superoxide dismutase (SodA) and other enzymes involved in oxidative stress.3-isopropylmalate dehydratase (or isopropylmalate isomerase;
) catalyses the stereo-specific isomerisation of 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate. This enzyme performs the second step in the biosynthesis of leucine, and is present in most prokaryotes and many fungal species. The prokaryotic enzyme is a heterodimer composed of a large (LeuC) and small (LeuD) subunit, while the fungal form is a monomeric enzyme. Both forms of isopropylmalate are related and are part of the larger aconitase family [
]. Aconitases are mostly monomeric proteins which share four domains in common and contain a single, labile [4Fe-4S]cluster. Three structural domains (1, 2 and 3) are tightly packed around the iron-sulphur cluster, while a fourth domain (4) forms a deep active-site cleft. The prokaryotic enzyme is encoded by two adjacent genes, leuC and leuD, corresponding to aconitase domains 1-3 and 4 respectively [
,
]. LeuC does not bind an iron-sulphur cluster. It is thought that some prokaryotic isopropylamalate dehydrogenases can also function as homoaconitase , converting cis-homoaconitate to homoisocitric acid in lysine biosynthesis [
]. Homoaconitase has been identified in higher fungi (mitochondria) and several archaea and one thermophilic species of bacteria, Thermus thermophilus []. It is also found in the higher plant Arabidopsis thaliana, where it is targeted to the chloroplast [].This superfamily represents a domain with an alpha/beta/alpha topology. This structural domain usually occurs in triplicate, with domains 1 and 3 being the most closely related since they share the same pseudo 2-fold symmetry. This entry represents domain 2. This triple domain region is found at the N-terminal of eukaryotic mAcn, cAcn/IPR1 and IRP2, and bacterial AcnA, but in the C-terminal of bacterial AcnB; in each case, this region binds the [4Fe-4S]-cluster.
Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha, subdomain 1/3
Type:
Homologous_superfamily
Description:
Aconitase (aconitate hydratase;
) is an iron-sulphur protein that contains a [4Fe-4S]-cluster and catalyses the interconversion of isocitrate and citrate via a cis-aconitate intermediate. Aconitase functions in both the TCA and glyoxylate cycles, however unlike the majority of iron-sulphur proteins that function as electron carriers, the [4Fe-4S]-cluster of aconitase reacts directly with an enzyme substrate. In eukaryotes there is a cytosolic form (cAcn) and a mitochondrial form (mAcn) of the enzyme. In bacteria there are also 2 forms, aconitase A (AcnA) and B (AcnB). Several aconitases are known to be multi-functional enzymes with a second non-catalytic, but essential function that arises when the cellular environment changes, such as when iron levels drop [
,
]. Eukaryotic cAcn and mAcn, and bacterial AcnA have the same domain organisation, consisting of three N-terminal alpha/beta/alpha domains, a linker region, followed by a C-terminal 'swivel' domain with a beta/beta/alpha structure (1-2-3-linker-4), although mAcn is smaller than cAcn. However, bacterial AcnB has a different organisation: it contains an N-terminal HEAT-like domain, followed by the 'swivel' domain, then the three alpha/beta/alpha domains (HEAT-4-1-2-3) [].Eukaryotic cAcn enzyme balances the amount of citrate and isocitrate in the cytoplasm, which in turn creates a balance between the amount of NADPH generated from isocitrate by isocitrate dehydrogenase with the amount of acetyl-CoA generated from citrate by citrate lyase. Fatty acid synthesis requires both NADPH and acetyl-CoA, as do other metabolic processes, including the need for NADPH to combat oxidative stress. The enzymatic form of cAcn predominates when iron levels are normal, but if they drop sufficiently to cause the disassembly of the [4Fe-4S]-cluster, then cAcn undergoes a conformational change from a compact enzyme to a more open L-shaped protein known as iron regulatory protein 1 (IRP1; or IRE-binding protein 1, IREBP1) [,
]. As IRP1, the catalytic site and the [4Fe-4S]-cluster are lost, and two new RNA-binding sites appear. IRP1 functions in the post-transcriptional regulation of genes involved in iron metabolism - it binds to mRNA iron-responsive elements (IRE), 30-nucleotide stem-loop structures at the 3' or 5' end of specific transcripts. Transcripts containing an IRE include ferritin L and H subunits (iron storage), transferrin (iron plasma chaperone), transferrin receptor (iron uptake into cells), ferroportin (iron exporter), mAcn, succinate dehydrogenase, erythroid aminolevulinic acid synthetase (tetrapyrrole biosynthesis), among others. If the IRE is in the 5'-UTR of the transcript (e.g. in ferritin mRNA), then IRP1-binding prevents its translation by blocking the transcript from binding to the ribosome. If the IRE is in the 3'-UTR of the transcript (e.g. transferrin receptor), then IRP1-binding protects it from endonuclease degradation, thereby prolonging the half-life of the transcript and enabling it to be translated [].IRP2 is another IRE-binding protein that binds to the same transcripts as IRP1. However, since IRP1 is predominantly in the enzymatic cAcn form, it is IRP2 that acts as the major metabolic regulator that maintains iron homeostasis [
]. Although IRP2 is homologous to IRP1, IRP2 lacks aconitase activity, and is known only to have a single function in the post-transcriptional regulation of iron metabolism genes []. In iron-replete cells, IRP2 activity is regulated primarily by iron-dependent degradation through the ubiquitin-proteasomal system.Bacterial AcnB is also known to be multi-functional. In addition to its role in the TCA cycle, AcnB was shown to be a post-transcriptional regulator of gene expression in Escherichia coli and Salmonella enterica [
,
]. In S. enterica, AcnB initiates a regulatory cascade controlling flagella biosynthesis through an interaction with the ftsH transcript, an alternative RNA polymerase sigma factor. This binding lowers the intracellular concentration of FtsH protease, which in turn enhances the amount of RNA polymerase sigma32 factor (normally degraded by FtsH protease), and sigma32 then increases the synthesis of chaperone DnaK, which in turn promotes the synthesis of the flagellar protein FliC. AcnB regulates the synthesis of other proteins as well, such as superoxide dismutase (SodA) and other enzymes involved in oxidative stress.3-isopropylmalate dehydratase (or isopropylmalate isomerase;
) catalyses the stereo-specific isomerisation of 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate. This enzyme performs the second step in the biosynthesis of leucine, and is present in most prokaryotes and many fungal species. The prokaryotic enzyme is a heterodimer composed of a large (LeuC) and small (LeuD) subunit, while the fungal form is a monomeric enzyme. Both forms of isopropylmalate are related and are part of the larger aconitase family [
]. Aconitases are mostly monomeric proteins which share four domains in common and contain a single, labile [4Fe-4S]cluster. Three structural domains (1, 2 and 3) are tightly packed around the iron-sulphur cluster, while a fourth domain (4) forms a deep active-site cleft. The prokaryotic enzyme is encoded by two adjacent genes, leuC and leuD, corresponding to aconitase domains 1-3 and 4 respectively [
,
]. LeuC does not bind an iron-sulphur cluster. It is thought that some prokaryotic isopropylamalate dehydrogenases can also function as homoaconitase , converting cis-homoaconitate to homoisocitric acid in lysine biosynthesis [
]. Homoaconitase has been identified in higher fungi (mitochondria) and several archaea and one thermophilic species of bacteria, Thermus thermophilus []. It is also found in the higher plant Arabidopsis thaliana, where it is targeted to the chloroplast [].This superfamily represents a domain with an alpha/beta/alpha topology. This structural domain usually occurs in triplicate, with domains 1 and 3 being the most closely related since they share the same pseudo 2-fold symmetry. This entry represents domains 1 and 3. This triple domain region is found at the N-terminal of eukaryotic mAcn, cAcn/IPR1 and IRP2, and bacterial AcnA, but in the C-terminal of bacterial AcnB; in each case, this region binds the [4Fe-4S]-cluster. This triple domain region is also found in the large subunit of isopropylmalate dehydratase (LeuC).
Traffic through the yeast Golgi complex depends on a member of the syntaxin family of SNARE proteins, Sed5, present in early Golgi cisternae. Got1 is thought to facilitate Sed5-dependent fusion events [
]. This is a family of sequences derived from eukaryotic proteins. They are similar to a region of a SNARE-like protein required for traffic through the Golgi complex, SFT2 protein () [
]. This is a conserved protein with four putative transmembrane helices, thought to be involved in vesicular transport in later Golgi compartments [].
This domain is found in sodium, potassium, and calcium ion channels proteins. The proteins have 6 transmembrane helices in which the last two helices flank a loop which determines ion selectivity. In some Na channel proteins the domain is repeated four times, whereas in others (e.g. K channels) the protein forms a tetramer in the membrane. A bacterial structure of the protein is known for the last two helices but is not included in the Pfam family due to it lacking the first four helices.
Gingipains are proteinases from Porphyromonas gingivalis, a major pathogen associated with chronic periodontitis. They belong to MEROPS peptidase family C25. There are three types: Arg-specific proteinases RgpA, and RgpB, and the Lys-specific proteinase Kgp. All three gingipain precursors contain a propeptide of around 200 amino acids in length that is removed during maturation. It has been shown that gingipain propeptides are capable of inhibiting their mature cognate proteinases [
]. Proteins homologous to the gingipain precursor are known from many other bacteria, some archaea and some eukaryotes.
Members of this protein family are sortase enzymes, cysteine transpeptidases involved in protein sorting activities. Members of this family tend to be found in proteobacteria, rather than in Gram-positive bacteria where sortases attach proteins to the Gram-positive cell wall or participate in pilin cross-linking. Many species with this sortase appear to contain a signal target sequence, a protein with a Vault protein inter-alpha-trypsin domain and a von Willebrand factor type A domain, encoded by an adjacent gene. These sortases are designated subfamily 6 [
].
Gingipains are proteinases from Porphyromonas gingivalis, a major pathogen associated with chronic periodontitis. They belong to MEROPS peptidase family C25. There are three types: Arg-specific proteinases RgpA, and RgpB, and the Lys-specific proteinase Kgp. All three gingipain precursors contain a propeptide of around 200 amino acids in length that is removed during maturation. It has been shown that gingipain propeptides are capable of inhibiting their mature cognate proteinases [
]. Proteins homologous to the gingipain precursor are known from many other bacteria, some archaea and some eukaryotes.
Reoviruses are double-stranded RNA viruses that lack a membrane envelope. Their capsid is organised in two concentric icosahedral layers: an inner core and an outer capsid layer. The outer capsid is made up of the major proteins mu1 and sigma3, and the minor protein sigma1. The inner core structure is composed of the major core proteins lambda1 and sigma2, core spike protein lambda2, and minor core proteins lambda3 and mu2. The inner core encases the 10 segments of double-stranded RNA (dsRNA) which comprise the genome [
].
Secretion of protein products occurs by a number of different pathways in bacteria. One of these pathways known as the type V pathway was first described for the IgA1 protease [
]. The protein component that mediates secretion through the outer membrane is contained within the secreted protein itself, hence the proteins secreted in this way are called autotransporters [,
]. This superfamily represents the pectate Lyase C-like domain found in autotransporters. This domain can also be found in phage P22 tail spike protein.
This family of archaebacterial proteins, formerly known as DUF114, has been found to be a serine dehydrogenase proteinase distantly related to ClpP proteinases that belong to the serine proteinase superfamily. The family belong to MEROPS peptidase family S49; they are mostly unassigned peptidases but include the archaean signal peptide peptidase 1 [
]. The family has a catalytic triad of Ser, Asp, His residues, which shows an altered residue ordering compared with the ClpP proteinases but similar to that of the carboxypeptidase clan [
].
Members of group of are outer membrane proteins from the TolC family within the RND (Resistance-Nodulation-cell Division) efflux systems. These proteins, unlike the NodT family, appear not to be lipoproteins. All are believed to participate in type I protein secretion, an ABC transporter system for protein secretion without cleavage of a signal sequence, although they may, like TolC, participate also in the efflux of smaller molecules as well [
]. This family includes the well-documented examples TolC (Escherichia coli), PrtF (Erwinia), and AprF (Pseudomonas aeruginosa) [].
The macrolide antibiotic rapamycin and the cytosol protein FKBP12 can form a complex which specifically inhibits the TORC1 complex, leading to growth arrest. The FKBP12-rapamycin complex interferes with TORC1 function by binding to the FKBP12-rapamycin binding domain (FRB) of the Tor proteins. This superfamily represents the FRB domain [
,
]. Proteins containing this domain include Tor proteins which are serine/threonine kinases conserved from fungi to humans. While higher eukaryotes such as humans possess a single Tor protein, yeasts contain two (Tor1 and Tor2) [].
In the Actinobacteria, as shown for Mycobacterium tuberculosis, some proteins are modified by ligation between an ε-amino group of a lysine side chain and the C-terminal carboxylate of the ubiquitin-like protein Pup. This modification leads to protein degradation by the archaeal-like proteasome found in the Actinobacteria. Members of this protein family belong to the AAA family of ATPases and tend to be clustered with the genes for Pup, the Pup ligase PafA, and structural components of the proteasome. This protein forms hexameric rings with ATPase activity.
Calponin is a smooth muscle-specific, actin-, tropomyosin- and calmodulin-binding protein believed to be involved in regulation or modulation of contraction [
,
]. Interaction of the protein with actin inhibits actomyosin MgATPase activity. Multiple isoforms are found in smooth muscle []. Calponin is a basic protein of ~34kDa []. The protein contains three repeats of a well-conserved 26-residue domain (see ).
This entry also includes LIM and calponin homology domains-containing protein 1 (LIMCH1), which contains a LIM zinc-binding domain and a CH (calponin-homology) domain.
This entry represents a domain that cover most of the length of DMP19 from Neisseria meningitidis (NMB0541, ) and similar proteins. DMP19 is a DNA mimic protein able to prevent the transcription factor NHTF from binding to a recognition box, playing a role in the gene regulation in the bacterial nitrogen response. DMP19 is an acidic protein with an all-α structure. The protein adopts a dimeric configuration and its surface-charge distribution reveals a dsDNA-like topology [
]. This domain is also found in other bacterial uncharacterised proteins.
This entry contains proteins with a CCCH-type zinc finger, which bind zinc via cysteine and histidine residues in the motif C-x8-C-x5-C-x3-H, and a C3HC4 type RING finger. Proteins with this structure include:
Pre-mRNA-splicing factor CWC24, a component of the CWC complex, which is involved in pre-mRNA splicing [
].RING finger protein 113A, an E3 ubiquitin-protein ligase that catalyzes polyubiquitination of SNRNP200/BRR2 with non-canonical 'Lys-63'-linked polyubiquitin chains [
] and CXCR4, leading to its degradation and thereby termination of CXCR4 signaling [].RING finger protein 113B, which is uncharacterized.
Proteins containing this repeat include the stress response protein Ish1 from fission yeasts and meiotic sister chromatid recombination protein 1 (Msc1) from budding yeasts. Proteins containing this repeat also include some uncharacterised proteins from Acinetobacter baumannii. Ish1 has a role in maintaining cell viability during stationary phase induced by stress response. It can be activated by the spc1 MAPK pathway [
]. Msc1 was identified in a screen for mutants that show an increase in meiotic unequal sister-chromatid recombination (SCR) [
]. Its function is not clear.
This entry represents the family E of the E2/UBC superfamily of proteins found in diverse bacteria. Analysis of the active site residues suggest that members of this family are inactive as they lack the characteristic catalytic residues of the E2 enzymes [
,
]. They are usually fused to or in the neighbourhood of a multi/poly ubiquitin domain protein. Other proteins of the ubiquitin modification pathway such as the E1 and JAB proteins are also found in its gene neighbourhood along with a distinct predicted metal-binding protein.
This entry represents the PORR (plant organelle RNA recognition domain, previously DUF860) family of proteins which localise to either mitochondria or chloroplasts, and it seems likely that most PORR proteins function in organellar RNA metabolism. Including in this family are Protein root primordium defective 1-like (RPD1) and Protein WHAT'S THIS FACTOR1 [
,
,
]. RPD1 is involved in pre-arranging the maintenance of the active cell proliferation during root primordium development []. WTF1 is a RNA-binding protein involved in the chloroplastic group II intron splicing [].
This domain occurs at the N-terminal of proteins belonging to the caudal-related homeobox protein family. This region is thought to mediate transcription activation. The level of activation caused by mouse Cdx2 (
) is affected by phosphorylation at serine 60 via the mitogen-activated protein kinase pathway [
]. Caudal family proteins are involved in the transcriptional regulation of multiple genes expressed in the intestinal epithelium, and are important in differentiation and maintenance of the intestinal epithelial lining. Caudal proteins always have a homeobox DNA binding domain ().
Amino acid permeases are integral membrane proteins involved in the transport
of amino acids into the cell. A number of such proteins have been found to beevolutionary related [
,
,
].These proteins seem to contain up to 12 transmembrane segments. The best conserved region
in this family is located in the second transmembrane segment.Spore germination protein (amino acid permease) is involved in the response to the germinative mixture of L-asparagine, glucose, fructose and potassium ions (AFFK). These proteins could be amino acid transporters.
The tumour necrosis factor (TNF) receptor associated factors (TRAFs) are major signal transducers for the TNF receptor (TNFR) superfamily and the interleukin-1 receptor/Toll-like receptor superfamily in mammals [
]. TRAFs constitute a family of genetically conserved adapter proteins found in mammals (TRAF1-6) as well as in other multicellular organisms such as Drosophila [], Caenorhabditis elegans []. TRAF2 is the prototypical member of the family. Mammalian TRAF1 and TRAF2 were the first members initially identified by their association with TNFR2. The TRAF1/TRAF2 and TRAF3/TRAF5 gene pairs may have arisen from recent independent gene duplications and to share a common ancestral gene. TRAF4 and TRAF6 precursor genes may have arisen earlier during evolution, with the divergence of the TRAF6 precursor occurring earliest of all. Except TRAF1, this PIRSF has a general domain architecture containing one N-terminal RING finger, a variable number of middle region of TRAF-type zinc finger and C2H2 type of zinc finger, and one C-terminal MATH domain. TRAF1 is unique in the family in that it lacks the N-terminal RING and zinc-finger domains [
]. This has rendered TRAF1 unable to promote TNF receptor signalling and act as a "dominant negative"TRAF [
]. Also TRAF1 is a substrate for caspases activated by TNF family death receptors []. The larger C-terminal cleaved fragment can bind to and sequester TRAF2 from TNFR1 complex, therefore modulating TNF induced NFkB activation []. A wide range of biological functions, such as adaptive and innate immunity, embryonic development, stress response and bone metabolism, are mediated by TRAFs through the induction of cell survival, proliferation, differentiation and death. TRAFs are functionally divergent from a perspective of both upstream and downstream TRAF signal transduction pathways and of signalling-dependent regulation of TRAF trafficking. Each TRAF protein interacts with and mediates the signal transduction of multiple receptors, and in turn each receptor utilises multiple TRAFs for specific functions []. About 40 interaction partners of TRAF have been described thus far, including receptors, kinases, regulators and adaptor proteins.TRAF proteins can be recruited to and activated by ligand-engaged receptors in least three distinct ways [
]. 1) Members of the TNFR superfamily that do not contain intracellular death domains, such as TNFR2 and CD40, recruit TRAFs directly via short sequences in their intracellular tails []. 2) Those that contain an intracellular death domain, such as TNFR1, first recruit an adapter protein, TRADD, via a death-domain-death-domain interaction, which then serves as a central platform of the TNFR1 signalling complex, which assembles TRAF2 and RIP for survival signalling, and FADD and caspase-8 for the induction of apoptosis. 3) Members of the IL-1R/TLR superfamily contain a protein interaction module known as the TIR domain, which recruits, sequentially, MyD88, a TIR domain and death domain containing protein, and IRAKs, adapter Ser/Thr kinases with death domains. IRAKs in turn associate with TRAF6 to elicit signalling by IL-1 and pathogenic components such as LPS. A common mechanism for the membrane-proximal event in TRAF signalling has been revealed by the conserved trimeric association in the crystal structure of the TRAF domain of TRAF2 [
].This entry represents the TNF receptor associated factors found in metazoa.
Methyl transfer from the ubiquitous S-adenosyl-L-methionine (AdoMet) to either nitrogen, oxygen or carbon atoms is frequently employed in diverse organisms ranging from bacteria to plants and mammals. The reaction is catalysed by methyltransferases (Mtases) and modifies DNA, RNA, proteins and small molecules, such as catechol for regulatory purposes. The various aspects of the role of DNA methylation in prokaryotic restriction-modification systems and in a number of cellular processes in eukaryotes including gene regulation and differentiation is well documented.Three classes of DNA Mtases transfer the methyl group from AdoMet to the target base to form either N-6-methyladenine, or N-4-methylcytosine, or C-5- methylcytosine. In C-5-cytosine Mtases, ten conserved motifs are arranged in the same order []. Motif I (a glycine-rich or closely related consensus sequence; FAGxGG in M.HhaI []), shared by other AdoMet-Mtases [], is part of the cofactor binding site and motif IV (PCQ) is part of the catalytic site. In contrast, sequence comparison among N-6-adenine and N-4-cytosine Mtases indicated two of the conserved segments [], although more conserved segments may be present. One of them corresponds to motif I in C-5-cytosine Mtases, and the other is named (D/N/S)PP(Y/F). Crystal structures are known for a number of Mtases [,
,
,
]. The cofactor binding sites are almost identical and the essential catalytic amino acids coincide. The comparable protein folding and the existence of equivalent amino acids in similar secondary and tertiary positions indicate that many (if not all) AdoMet-Mtases have a common catalytic domain structure. This permits tertiary structure prediction of other DNA, RNA, protein, and small-molecule AdoMet-Mtases from their amino acid sequences [].CheR proteins are part of the chemotaxis signaling mechanism in bacteria. Flagellated bacteria swim towards favourable chemicals and away from deleterious ones. Sensing of chemoeffector gradients involves chemotaxis receptors, transmembrane (TM) proteins that detect stimuli through their periplasmic domains and transduce the signals via their cytoplasmic domains [
]. Signalling outputs from these receptors are influenced both by the binding of the chemoeffector ligand to their periplasmic domains and by methylation of specific glutamate residues on their cytoplasmic domains. Methylation is catalysed by CheR, an S-adenosylmethionine-dependent methyltransferase [], which reversibly methylates specific glutamate residues within a coiled coil region, to form gamma-glutamyl methyl ester residues [
,
].The structure of the Salmonella typhimurium chemotaxis receptor methyltransferase CheR, bound to S-adenosylhomocysteine, has been determined to a resolution of 2.0 A [
]. The structure reveals CheR to be a two-domain protein, with a smaller N-terminal helical domain linked via a single polypeptide connection to a larger C-terminal alpha/beta domain. The C-terminal domain has the characteristics of a nucleotide-binding fold, with an insertion of a small anti-parallel β-sheet subdomain. The S-adenosylhomocysteine-binding site is formed mainly by the large domain, with contributions from residues within the N-terminal domain and the linker region [].CheR proteins are part of the chemotaxis signaling mechanism which methylates the chemotaxis receptor at specific glutamate residues. This entry refers to the C-terminal SAM-binding domain of the CherR-type MCP methyltransferases, which are found in bacteria, archaea and green plants. This entry is found in association with
.
G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups [
]. The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence []. The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) [,
,
,
,
]. GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice []. Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs [].The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices [
,
,
].Pheromones have evolved in all animal phyla, to signal sex and dominance
status, and are responsible for stereotypical social and sexual behaviour among members of the same species. In mammals, these chemical signals are believed to be detected primarily by the vomeronasal organ (VNO), a chemosensory organ located at the base of the nasal septum []. The VNO is present in most amphibia, reptiles and non-primate mammals but is absent in birds, adult catarrhine monkeys and apes []. An active role for the human VNO in the detection of pheromones is disputed; the VNO is clearly present in the foetus but appears to be atrophied or absent in adults. Three distinct families of putative pheromone receptors have been identified in the vomeronasal organ (V1Rs, V2Rs and V3Rs). All are G protein-coupled receptors but are only distantly related to the receptors of the main olfactory system, highlighting their different role [].The V1 receptors share between 50 and 90% sequence identity but have little
similarity to other families of G protein-coupled receptors. They appear tobe distantly related to the mammalian T2R bitter taste receptors and the
rhodopsin-like GPCRs []. In rat, the family comprises 30-40 genes. These are expressed in the apical regions of the VNO, in neurons expressing Gi2. Coupling of the receptors to this protein mediates inositol trisphosphate signalling []. A number of human V1 receptor homologues have also been found. The majority of these human sequences are pseudogenes [] but an apparently functional receptor has been identified that is expressed in the human olfactory system [].
Gibberellins are plant hormones which have great impact on growth signalling. DELLA proteins are transcriptional regulators of growth related proteins that lack a DNA binding domain and exert its negative regulation of gibberellin responses through interaction with other transcription factors [
]. DELLAs are downregulated when gibberellins bind to their receptor GID1 [,
], which forms a complex with DELLA proteins and signals them towards 26S proteasome. The N-terminal of DELLA proteins contains conserved DELLA and TVHYNP motifs which are important for GID1 binding and proteolysis of the DELLA proteins [,
].
This is the cytosolic domain of integral membrane proteins, such as plant OSCA1, yeast PHM7 and CSC1-like protein 1 (also known as TRANSMEMBRANE PROTEIN 63A),
[
,
]. Members of this entry are mechanosensitive calcium-permeable ion channels consisting of an N-terminal transmembrane domain (RSN1_TM), a cytosolic domain and a 7TM region at the C-terminal. Fold recognition programs consistently and with high significance predict this domain to be distantly homologous to RNA binding proteins from the RRM clan [,
]. Human CSC1-like protein 1 is involved myelin development [].
This family consists of a number of eukaryotic proteins including CXXC motif containing zinc binding protein (previously known as UPF0587 protein C1orf123). The crystal structure reveals that the protein binds a Zn2+ ion in a tetrahedral coordination with four Cys residues from two CxxC motifs. CXXC motif containing zinc binding protein was initially identified as an interaction partner for the heavy metal-associated (HMA) domain of CCS (copper chaperone for superoxide dismutase). However, it was shown that only misfolded mutant forms, lacking part of the zinc-binding sites, interact with CCS [
].
EamA (named after the O-acetyl-serine/cysteine export gene in E. coli) domain is found in a wide range of proteins including the Erwinia chrysanthemi PecM protein, which is involved in pectinase, cellulase and blue pigment regulation, the Salmonella typhimurium PagO protein (function unknown), and some members of the solute carrier family group 35 (SLC35) nucleoside-sugar transporters. Many members of this family are classed as drug/metabolite transporters and have no known function. They are predicted to be integral membrane proteins and many of the proteins contain two copies of this domain [
].
This entry represents a group of proteins from Streptophytes, including Protein VASCULATURE COMPLEXITY AND CONNECTIVITY (also known as DEAL1), Protein DESIGUAL 2-4 (DEAL2-4) and Protein MODIFYING WALL LIGNIN-1/2 (MWL-1/2). DEAL1 is required for embryo provasculature development and cotyledon vascular complexity and connectivity [
,
]. DEAL2 and 3 ensure bilateral symmetry development and early leaf margin patterning, probably via the regulation of auxin and CUC2 distribution []. MWL1 and 2 are involved in secondary cell wall biology, specifically lignin biosynthesis []. Proteins included in this family contain a number of conserved cysteine residues.
Rhodanese, a sulphurtransferase involved in cyanide detoxification (see
) shares evolutionary relationship with a large family of proteins [
], includingCdc25 phosphatase catalytic domain.non-catalytic domains of eukaryotic dual-specificity MAPK-phosphatases.non-catalytic domains of yeast PTP-type MAPK-phosphatases.non-catalytic domains of yeast Ubp4, Ubp5, Ubp7.non-catalytic domains of mammalian Ubp-Y.Drosophila heat shock protein HSP-67BB.several bacterial cold-shock and phage shock proteins.plant senescence associated proteins.catalytic and non-catalytic domains of rhodanese (see
).
Rhodanese has an internal duplication. This domain is found as a single copy in other proteins, including phosphatases and ubiquitin C-terminal hydrolases [
].
Mandelate racemase/muconate lactonizing enzyme, conserved site
Type:
Conserved_site
Description:
Mandelate racemase
(MR) and muconate lactonizing enzyme
(MLE)
are two bacterial enzymes involved in aromatic acid catabolism. They catalyze mechanistically distinct reactions yet they are related at the level of their primary,
quaternary (homooctamer) and tertiary structures [
,
].A number of other proteins also seem to be evolutionary related to these two
enzymes. These include, various plasmid-encoded chloromuconate cycloisomerases , Escherichia coli protein rspA [
], E. coli bifunctional DGOA protein, E. coli hypothetical proteins ycjG, yfaW and yidU and a hypothetical protein from Streptomyces
ambofaciens[
].
Type-F conjugative transfer system pilin assembly thiol-disulphide isomerase TrbB
Type:
Family
Description:
This protein is part of a large group of proteins involved in conjugative transfer of plasmid DNA, specifically the F-type system. This protein has been predicted to contain a thioredoxin fold, contains a conserved pair of cysteines and has been shown to function as a thiol disulfide isomerase by complementation of an Ecoli DsbA defect [
]. The protein is believed to be involved in pilin assembly []. The protein is closely related to TraF () which is somewhat longer, lacks the cysteine motif and is apparently not functional as a disulfide bond isomerase.
The Yippee-like (YPEL) family proteins share homology to drosophila Yippee, a
zinc finger binding protein. YPEL proteins are found in essentiallly all theeukaryotes and hence they must play important roles in the maintenance of
life. Subcellular localization of all YPEL proteins to the centrosomes andthe mitotic apparatus suggest their role in the mitosis-associated function.
YPEL proteins contain a Yippee domain, which is a putative zinc-finger-like,metal-binding domain [
,
,
,
].The Yippee domain contains two cysteine pairs that are fifty-two amino acids
appart (C-X(2)-C-X(52)-C-X(2)-C) and could be part of a metal (zinc) bindingpocket [
].
Tai4 is a new form of autoimmunity protein for a type VI secretion system, T6SS. T6SS has roles in interspecies interactions, as well as higher order host-infection, by injecting effector proteins into the periplasmic compartment of the recipient cells of closely related species. Pseudomonas aeruginosa produces at least three effector proteins to other cells and thus has three specific cognate immunity proteins to protect itself. Tae4, or type VI amidase effector 4, in Enterobacter cloacae has a cognate Tai4 or type VI amidase immunity 4 protein [
].
Recoverin is a Ca(2+) -binding protein that controls phosphorylation of the visual receptor rhodopsin by inhibiting rhodopsin kinase (GRK-1) in photoreceptor cells [
,
]. It serves as a cancer-retina antigen that is expressed in retina and tumour cells and evokes antibodies and/or T cells in patients with cancer [,
].A number of other proteins including visinin, hippocalcin, neurocalcin,
S-modulin, visinin-like protein, frequenin, guanylyl cyclase-activating proteins GCAP-1 and GCAP-2 [] belong to this family. All of the family members are generally small N-myristoylated proteins containing four EF-hand calcium-binding consensus motifs.
This entry represents what appears to be a phylogenetically distinct clade, containing Escherichia coli CspD (
) and related proteobacterial proteins within the larger family of cold shock domain proteins. The gene symbol cspD may have been used independently for other subfamilies of cold shock domain proteins, such as for Bacillus subtilis CspD. These proteins typically are shorter than 70 amino acids. In E. coli, CspD is a stress response protein induced in stationary phase. This homodimer binds single-stranded DNA and appears to inhibit DNA replication [
].
Sex determination proteins are found in eukaryotes. Proteins in this family are typically between 168 and 410 amino acids in length. It plays a role in the gender determination of around 20% of all animals.In the honeybee, the mechanism of sex determination depends on the complementary sex determiner (csd) gene which produces an SR-type protein. Males are homozygous while females are homozygous for the csd gene. Heterozygosity generates an active protein which initiates female development [
]. This entry represents the N-terminal end of the sex determination protein.
Proteins in this entry include the human NEDD4 family-interacting protein 1/2 (Ndfip1 and Ndfip2) and the yeast Bsd2 metal homeostatis proteins. Ndfip1 and Ndfip2 are endosomal membrane proteins that bind to and activate members of the Nedd4 family of E3 ubiquitin ligases [
,
]. Ndfip1 plays a role in regulating metal transport in human neurons []. Bsd2 is required for the targeting of several proteins into the MVB (multivesicular body) pathway [
]. It prevents metal hyperaccumulation by exerting negative control over the Smf1 and Smf2 metal transport systems [].
This entry contains the central domain of the phosphoprotein from vesiculoviruses, which are ssRNA negative-strand rhabdoviruses. It is known as the phosphoprotein or P protein [
,
]. This protein may be part of the RNA dependent RNA polymerase complex []. The phosphorylation states of this protein may regulate the transcription and replication complexes [].The structure of this domain consists of an intertwinned homodimer of beta(2)-α-β(2) motifs arranged in three layers (beta/alpha/beta); each antiparallel β-sheet is formed by the N-terminal β-hairpin of one subunit and the C-terminal β-hairpin of the other subunit.
E3 ubiquitin-protein ligase SH3RF2, first SH3 domain
Type:
Domain
Description:
SH3RF2 is also called POSHER (POSH-eliminating RING protein) or HEPP1 (heart protein phosphatase 1-binding protein). It acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation [
]. It may also play a role in cardiac functions together with protein phosphatase 1 []. SH3RF2 contains an N-terminal RING finger domain and three SH3 domains. This entry represents the first SH3 domain, located at the N-terminal half, of SH3RF2.
Dynamin-binding protein, first N-terminal SH3 domain
Type:
Domain
Description:
Dynamin-binding protein (DNMBP, also known as Tuba) is a scaffold protein that links dynamin with actin-regulating proteins. It binds a variety of actin regulatory proteins, including N-WASP, CR16, WAVE1, WIRE, PIR121, NAP1, and Ena/VASP proteins, via a C-terminal SH3 domain [
]. It plays a critical role in ciliogenesis and nephrogenesis, most likely via Cdc42 activation [].The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles [
]. This entry represents the first N-terminal SH3 domain.
Dynamin-binding protein, second N-terminal SH3 domain
Type:
Domain
Description:
Dynamin-binding protein (DNMBP, also known as Tuba) is a scaffold protein that links dynamin with actin-regulating proteins. It binds a variety of actin regulatory proteins, including N-WASP, CR16, WAVE1, WIRE, PIR121, NAP1, and Ena/VASP proteins, via a C-terminal SH3 domain [
]. It plays a critical role in ciliogenesis and nephrogenesis, most likely via Cdc42 activation [].The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles [
]. This entry represents the second N-terminal SH3 domain.
Dynamin-binding protein, third N-terminal SH3 domain
Type:
Domain
Description:
Dynamin-binding protein (DNMBP, also known as Tuba) is a scaffold protein that links dynamin with actin-regulating proteins. It binds a variety of actin regulatory proteins, including N-WASP, CR16, WAVE1, WIRE, PIR121, NAP1, and Ena/VASP proteins, via a C-terminal SH3 domain [
]. It plays a critical role in ciliogenesis and nephrogenesis, most likely via Cdc42 activation [].The four N-terminal SH3 domains of DNMBP binds the GTPase dynamin, which plays an important role in the fission of endocytic vesicles [
]. This entry represents the third N-terminal SH3 domain.
The melanoma antigen (MAGE) protein family contains more than 25 members that share a conserved MAGE homology domain (MHD) [
].Proteins known to contain a MAGE domain are listed below:Human MAGE-A, -B and -C proteins. MAGE-A, -B and -C genes are silent in all normal tissues with the exception of testis.Human MAGE-D to -L proteins. MAGE-D to -L genes are expressed in normal adult tissues.Mouse Mage-a and -b proteins.Mouse Mage-d, -e, -g, -h, -k and -l.Mammalian Necdin. The human Necdin gene is a candidate for the Prader-Willi syndrome.
Drosophila Sfmbt (dSfmbt) is part of the Pho repressive complex (PhoRC) responsible for HOX (Homeobox) gene silencing. In this complex, Pho or Pho-like proteins bind DNA and dSfmbt binds methylated histones. dSfmbt contains a SAM (sterile alpha motif) domain and 4 MBT repeats. dSfmbt can interact with mono- and di-methylated histones H3 and H4 through the MBT repeats [
]. It also interacts with the PcG protein Scm, a related MBT-repeat protein with similar methyl-lysine binding activity [].This entry represents the SAM domain, which is a putative protein-protein interaction domain.
This is a family of bacterial proteins related to the Escherichia coli BglG protein. E. coli BglG protein mediates the positive regulation of the beta-glucoside (bgl) operon by functioning as a transcriptional antiterminator [
]. BglG is an RNA-binding protein that recognises a specific sequence located just upstream of two termination sites within the operon. The activity of bglG is suppressed by its phosphorylation [] by bglF (EII-bgl), the permease from the beta-glucoside PTS system. BglG is highly similar to other proteins, which also probably act as transcriptional antiterminators.
Proteins containing this domain form structural complexes with other known families, such as
and
. The carbon monoxide (CO) dehydrogenase of Oligotropha carboxidovorans is a heterotrimeric complex composed of a apoflavoprotein, a molybdoprotein, and an iron-sulphur protein. It can be dissociated with sodium dodecylsulphate [
]. CO dehydrogenase catalyzes the oxidation of CO according to the following equation []: CO + H2O = CO2 + 2e + 2H+ Subunit S represents the iron-sulphur protein of CO dehydrogenase and is clearly divided into a C- and an N-terminal domain, each binding a [2Fe-2S] cluster [].
Sex determination proteins are found in eukaryotes. Proteins in this family are typically between 168 and 410 amino acids in length. It plays a role in the gender determination of around 20% of all animals.In the honeybee, the mechanism of sex determination depends on the complementary sex determiner (csd) gene which produces an SR-type protein. Males are homozygous while females are homozygous for the csd gene. Heterozygosity generates an active protein which initiates female development [
]. This entry represents the C-terminal end of the sex determination protein.
