The SEP (after shp1, eyc and p47) domain is an eukaryotic domain, which occurs frequently and mainly in single units. Almost all proteins containing a SEP domain are succeeded closely by a UBX domain (see
). The function of the SEP domain is as yet unknown but it has been proposed to act as a reversible competitive inhibitor of the lysosomal cysteine protease cathepsin L [
,
].The sructure of the SEP domain comprises a β-sheet composed of four
strands, and two α-helices. One side of the β-sheet faces alpha1 and alpha2. The longer helix alpha1 packs against the four-stranded β-sheet, where as the shorter helix alpha2 is located at one edge of the globular structure formed by alpha1 and the four stranded beta sheet. A number of highly conserved hydrophobic residues are present in the SEP domain, which are predominantly buried and form the hydrophobic core [,
].Some proteins known to contain a SEP domain are listed below:- Eukaryotic NSFL1 cofactor p37 (or p97 cofactor p37), an adapter protein required for Golgi and endoplasmic reticulum biogenesis. It is involved in Golgi and endoplasmic reticulum maintenance during interphase and in their reassembly at the end of mitosis.
- Eukaryotic NSFL1 cofactor p47 (or p97 cofactor p47), a major adaptor molecule of the cytosolic AAA-type ATPase (ATPases associated with various cellular activities) p97. p47 is required for the p97-regulated membrane reassembly of the endoplasmic reticulum (ER), the nuclear envelope and the Golgi apparatus.
- Vertebrate UBX domain-containing protein 4 (UBXD4).
- Plant UBA and UBX domain-containing protein.
- Saccharomyces cerevisiae (Baker's yeast) UBX domain-containing protein 1 or Suppressor of high-copy PP1 protein (shp1), the homologue of p47.
- Drosophila melanogaster (Fruit fly) eyes closed (eyc).
This entry includes Ubiquitin fusion degradation protein Ufd1 from fungi and Ufd1-like proteins from animals and plants. Ufd1 is part of the Ufd1-Npl4 complex that functions as the substrate-recruiting cofactor for Cdc48 segregase. The Cdc48-Ufd1-Npl4 complex is involved in degradation of misfolded ER proteins [
]. The Ufd1-Npl4 complex has been found to recruit Cdc48 to ubiquitylated CMG (Cdc45-MCM-GINS) helicase at the end of chromosome replication, thereby driving the disassembly reaction [].In humans, Npl4-Ufd1 acts as a cofactor in reducing antiviral innate immune responses by facilitating proteasomal degradation of RIG-I (a viral RNA sensor) [
].
This entry represents a domain found towards the N terminus of the 90kDa subunit of transcription factor IIIC (also known as subunit 9 in yeast [
]). The whole subunit is involved in RNA polymerase III-mediated transcription. It is possible that this N-terminal domain interacts with TFIIIC subunit 8 [].
This entry represents the copper-containing enzyme laccase (
), often present in mutiple copies in a single plant species, and additional, uncharacterised, closely related plant proteins termed laccase-like multicopper oxidases. These enzymes show considerable sequence similarity to the L-ascorbate oxidases (
). Laccases are enzymes of rather broad specificity, acting on both o- and p-quinols, and often acting also on aminophenols and phenylenediamine [
].
Alkaline phosphatase D (PhoD) [
] catalyses the reaction: phosphate monoester + H(2)O = an alcohol + phosphate. PhoD is similar to Ca(2+)-dependent phospholipase D [], which catalyses the hydrolysis of the ester bond between the phosphatidic acid and alcohol moieties of phospholipids [,
].PhoD (also known as alkaline phosphatase D/APaseD in Bacillus subtilis) is a secreted phosphodiesterase encoded by phoD of the Pho regulon in Bacillus subtilis. PhoD homologs are found in prokaryotes, eukaryotes, and archaea. PhoD contains a twin arginine (RR) motif and is transported by the Tat (Twin-arginine translocation) translocation pathway machinery (TatAyCy) [
,
,
,
]. Proteins containing this domain also includes the Fusarium oxysporum Fso1 protein []. PhoD belongs to the metallophosphatase (MPP) superfamily. MPPs are functionally diverse, but all share a conserved domain with an active site consisting of two metal ions (usually manganese, iron, or zinc) coordinated with octahedral geometry by a cage of histidine, aspartate, and asparagine residues. The MPP superfamily includes: Mre11/SbcD-like exonucleases, Dbr1-like RNA lariat debranching enzymes, YfcE-like phosphodiesterases, purple acid phosphatases (PAPs), YbbF-like UDP-2,3-diacylglucosamine hydrolases, and acid sphingomyelinases (ASMases). The conserved domain is a double β-sheet sandwich with a di-metal active site made up of residues located at the C-terminal side of the sheets. This domain is thought to allow for productive metal coordination [
].
The chloroplast genomes of most higher plants contain two giant open reading frames designated ycf1 and ycf2. TIC214 is encoded by ycf1. In chloroplasts, Tic214, Tic100, Tic56, and Tic20-I form stable 1-MD TIC complexes, which were shown to associate with preproteins. TIC214 is involved in protein precursor import into chloroplasts [
]. This entry also includes some uncharacterised mitochondrial genome proteins, such as AtMg00370.
This domain is found in plant proteins such as respiratory burst NADPH oxidase proteins which produce reactive oxygen species as a defence mechanism. It tends to occur to the N terminus of an EF-hand (
), which suggests a direct regulatory effect of Ca2+ on the activity of the NADPH oxidase in plants [
].
This calcineurin-like phosphoesterase domain can be found in some of the bacterial UDP-2,3-diacylglucosamine hydrolases (lpxH), archaeal DNA double-strand break repair protein Mre11 and the N-terminal of the nuclease SbcCD subunit D from bacteria. It can also be found in the eukaryotic vacuolar protein sorting-associated protein 29 (VPS29).
Members of this largely uncharacterised family share a motif approximating DXH(X25)GDXXD(X25)GNHD as found in several phosphoesterases, including the nucleases SbcD and Mre11, and a family of uncharacterised archaeal putative phosphoesterases. In this family, the His residue in GNHD portion of the motif is not conserved. The member MJ0936, one of two from Methanocaldococcus jannaschii (Methanococcus jannaschii), was shown [
] to act on model phosphodiesterase substrates; a divalent cation was required. This entry also represents Vps29 which is part of the retromer complex in yeast [].This entry also includes vacuolar protein sorting-associated protein 29 (vps29), which is an essential component of the retromer complex, a conserved complex required in endosome-to-Golgi retrograde transport [
].
This entry represents Vacuolar protein sorting-associated 29 (Vps29) from animals, yeasts and plants. Vps29 is an essential component of the retromer complex, a conserved complex required in endosome-to-Golgi retrograde transport [
].
Leucine-rich repeats (LRR) consist of 2-45 motifs of 20-30 amino acids in length that generally folds into an arc or horseshoe shape [
]. LRRs occur in proteins ranging from viruses to eukaryotes, and appear to provide a structural framework for the formation of protein-protein interactions [,
].Proteins containing LRRs include tyrosine kinase receptors, cell-adhesion molecules, virulence factors, and extracellular matrix-binding glycoproteins, and are involved in a variety of biological processes, including signal transduction, cell adhesion, DNA repair, recombination, transcription, RNA processing, disease resistance, apoptosis, and the immune response [,
].Sequence analyses of LRR proteins suggested the existence of several different subfamilies of LRRs. The significance of this classification is that repeats from different subfamilies never occur simultaneously and have most probably evolved independently. It is, however, now clear that all major classes of LRR have curved horseshoe structures with a parallel beta sheet on the concave side and mostly helical elements on the convex side. At least six families of LRR proteins, characterised by different lengths and consensus sequences of the repeats, have been identified. Eleven-residue segments of the LRRs (LxxLxLxxN/CxL), corresponding to the β-strand and adjacent loop regions, are conserved in LRR proteins, whereas the remaining parts of the repeats (herein termed variable) may be very different. Despite the differences, each of the variable parts contains two half-turns at both ends and a "linear"segment (as the chain follows a linear path overall), usually formed by a helix, in the middle. The concave face and the adjacent loops are the most common protein interaction surfaces on LRR proteins.
3D structure of some LRR proteins-ligand complexes show that the concave surface of LRR domain is ideal for interaction with α-helix, thus supporting earlier conclusions that the elongated and curved LRR structure provides an outstanding framework for achieving diverse protein-protein interactions []. Molecular modeling suggests that the conserved pattern LxxLxL, which is shorter than the previously proposed LxxLxLxxN/CxL is sufficient to impart the characteristic horseshoe curvature to proteins with 20- to 30-residue repeats []. This entry includes some LRRs that fail to be detected by the
model.
This entry contains 2-phospho-L-lactate transferase (CofD), phosphoenolpyruvate transferase and related sequences. CofD catalyses the fourth step in the biosynthesis of coenzyme F420, which is the transfer of the 2-phospholactate moiety from lactyl (2) diphospho-(5') guanosine (LPPG) to 7,8-didemethyl-8-hydroxy-5-deazariboflavin (FO) with the formation of the L-lactyl phosphodiester of 7,8-didemethyl-8-hydroxy-5-deazariboflavin (F420-0) and GMP. F420 is a flavin derivative found in methanogens, Mycobacteria, and several other lineages. This enzyme is characterised so far in Methanocaldococcus jannaschii (Methanococcus jannaschii) [
,
] but appears restricted to F420-containing species and is predicted to carry out the same function in these other species. CofD monomer contains twelve β-strands, seven of them forming a Rossmann fold, and thirteen α-helices [].
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].Ribosomal protein L34 is one of the proteins from the large subunit of the prokaryotic ribosome. It is a small basic protein of 44 to 51 amino-acid residues [
]. L34 belongs to a family of ribosomal proteins which, on the basis of sequence similarities, groups: Eubacterial L34, Red algal chloroplast L34 and Cyanelle L34.
The THO complex (THOC) is involved in transcription elongation and mRNA export from the nucleus [
]. This entry represents the subunit THOC7, which is found in higher eukaryotes, and the non-homologous subunit Mft1 found in yeast. Mft1 is a component the THO subcomplex of the TREX complex, which operates in coupling transcription elongation to mRNA export [
]. The THO complex is recruited to transcribed genes and moves along the gene with the elongating polymerase during transcription []. THO is important for stabilising nascent RNA in the RNA polymerase II elongation complex by preventing formation of DNA:RNA hybrids behind the elongating polymerase []. It functions in cotranscriptional formation of an export-competent messenger ribonucleoprotein particle (mRNP) by facilitating the loading of ATP-dependent RNA helicase Sub2 and the mRNA export factor Yra1 along the nascent mRNA []. In mammals, the THO complex specifically associates with spliced mRNA and not with unspliced pre-mRNA. It is recruited to spliced mRNAs by a transcription-independent mechanism. It binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export [
,
].
This entry represents part of a family of closely related, thiamine pyrophosphate-dependent enzymes includes indolepyruvate decarboxylase (IPDC,
)[
,
], pyruvate decarboxylase (PDC, ) [
], branched-chain alpha-ketoacid decarboxylase, etc []. PDC catalyses the conversion of pyruvate to acetaldehyde and CO2 in alcoholic fermentation. IPDC plays a role in the indole-3-pyruvic acid (IPA) pathway in plants and various plant-associated bacteria, it catalyses the decarboxylation of IPA to IAA. Also belonging to this entry is Mycobacterium tuberculosis alpha-keto acid decarboxylase (MtKDC) which participates in amino acid degradation via the Ehrlich pathway [], and Lactococcus lactis branched-chain keto acid decarboxylase (KdcA) an enzyme identified as being involved in cheese ripening, which exhibits a very broad substrate range in the decarboxylation and carboligation reactions [].
A number of enzymes require thiamine pyrophosphate (TPP) (vitamin B1) as a cofactor. It has been shown [] that some of these enzymes are structurally related. There are two different functional modules in the thiamin diphosphate-binding fold, the pyridine-binding (Pyr) and pyrophosphate-binding (PP) modules. This represents the N-terminal TPP-binding domain that in some members has been described as the Pyr-binding module.
The NAF domain is a 24 amino acid domain that is found in a plant-specific subgroup of serine-threonine protein kinases (CIPKs), that interact with calcineurin B-like calcium sensor proteins (CBLs). Whereas the N-terminal part of CIPKs comprises a conserved catalytic domain typical of Ser-Thr kinases, the much less conserved C-terminal domain appears to be unique to this subgroup of kinases. The only exception is the NAF domain that forms an 'island of conservation' in this otherwise variable region. The NAF domain has been named after the prominent conserved amino acids Asn-Ala-Phe. It represents a minimum protein interaction module that is both necessary and sufficient to mediate the interaction with the CBL calcium sensor proteins [
].The secondary structure of the NAF domain is currently not known, but secondary structure computation of the C-terminal region of Arabidopsis thaliana CBL-interacting protein kinase 1 revealed a long helical structure [
].
The NAF domain is a 24 amino acid domain that is found in a plant-specific subgroup of serine-threonine protein kinases (CIPKs), that interact with calcineurin B-like calcium sensor proteins (CBLs). Whereas the N-terminal part of CIPKs comprises a conserved catalytic domain typical of Ser-Thr kinases, the much less conserved C-terminal domain appears to be unique to this subgroup of kinases. The only exception is the NAF domain that forms an 'island of conservation' in this otherwise variable region. The NAF domain has been named after the prominent conserved amino acids Asn-Ala-Phe. It represents a minimum protein interaction module that is both necessary and sufficient to mediate the interaction with the CBL calcium sensor proteins [
].The secondary structure of the NAF domain is currently not known, but secondary structure computation of the C-terminal region of Arabidopsis thaliana CBL-interacting protein kinase 1 revealed a long helical structure [
].The NAF domain has also been named FISL motif for its conserved amino acid residues [
].
This group of proteins consists of several eukaryotic splicing factor 3B subunit 1 proteins, which associate with p14 through a C terminus β-strand that interacts with beta-3 of the p14 RNA recognition motif (RRM) β-sheet, which is in turn connected to an α-helix by a loop that makes extensive contacts with both the shorter C-terminal helix and RRM of p14. This subunit is required for 'A' splicing complex assembly (formed by the stable binding of U2 snRNP to the branchpoint sequence in pre-mRNA) and 'E' splicing complex assembly [].
This family contains polyketide cylcases/dehydrases which are enzymes involved in polyketide synthesis. It also includes other proteins of the START superfamily [
].
This family contains several phospholipase-like proteins from Arabidopsis thaliana and other members of the Streptophyta which are homologous to PEARLI 4.
Gcd14, also known as Trm61, is the catalytic subunit of tRNA (adenine-N(1)-)-methyltransferase [
,
], which is required for 1-methyladenosine modification and maturation of initiator methionyl-tRNA [].
Initiation factor 3 (IF-3) (gene infC) is one of the three factors required for the initiation of protein biosynthesis in bacteria. IF-3 is thought to function as a fidelity factor during the assembly of the ternary initiation complex which consist of the 30S ribosomal subunit, the initiator tRNA and the messenger RNA. IF-3 is a basic protein that binds to the 30S ribosomal subunit [
]. The chloroplast initiation factor IF-3(chl) is a protein that enhances the poly(A,U,G)-dependent binding of the initiator tRNA to chloroplast ribosomal 30s subunits in which the central section is evolutionary related to the sequence of bacterial IF-3 [
].
Initiation factor 3 (IF-3) (gene infC) is one of the three factors required for the initiation of protein biosynthesis in bacteria. IF-3 is thought to function as a fidelity factor during the assembly of the ternary initiation complex which consist of the 30S ribosomal subunit, the initiator tRNA and the messenger RNA. IF-3 is a basic protein that binds to the 30S ribosomal subunit [
]. The chloroplast initiation factor IF-3(chl) is a protein that enhances the poly(A,U,G)-dependent binding of the initiator tRNA to chloroplast ribosomal 30s subunits in which the central section is evolutionary related to the sequence of bacterial IF-3 [
].
Initiation factor 3 (IF-3) (gene infC) is one of the three factors required for the initiation of protein biosynthesis in bacteria. IF-3 is thought to function as a fidelity factor during the assembly of the ternary initiation complex which consist of the 30S ribosomal subunit, the initiator tRNA and the messenger RNA. IF-3 is a basic protein that binds to the 30S ribosomal subunit []. The chloroplast initiation factor IF-3(chl) is a protein that enhances the poly(A,U,G)-dependent binding of the initiator tRNA to chloroplast ribosomal 30s subunits in which the central section is evolutionary related to the sequence of bacterial IF-3 [
].
The proteins in this entry are functionally uncharacterised.The entry contains the Escherichia coli (strain K12) protein YjgA (
),
which has been shown to comigrate with the mature 50S ribosome subunit. Therefore it either represents a novel ribosome-associated protein or
it is associated with a different oligomeric complex that comigrates with ribosomal particles [
].
The THUMP domain (named afterTHioUridine synthases, RNA Methylases and Pseudouridine
synthases) is a module of 100-110 amino acid residues which is involvedRNA metabolism. It is shared by enzymes involved in at least three unrelated types of RNA-modification, namely methylation, pseudouridylation and thiouridylation. The THUMP domain can occur in stand-alone form or in association with a variety of catalytic domains, like
methylase, pseudo U-synthase or rhodanese. THUMP is anancient domain that apparently evolved prior to the divergence of the primary divisions of
life. It was initially predicted to have RNA-binding capacity but it was shown later that it associates with the adjacent FLD domain () to display the RNA-binding ability, leading to the delivery of a variety of RNA modification enzymes to their targets. The domain adopts an α/β fold, with two helices packed against a β-sheet [
,
,
,
].Some proteins known to contain a THUMP domain are listed below:Bacterial and archaeal thiI-like 4-thiouridine synthases (also known as tRNA sulfurtransferases or Thiamine biosynthesis protein ThiI).Bacterial, archaeal and eukaryotic RNA methyltransferases.Archaeal pseudouridine synthases (PSUSs).Several uncharacterised proteins.
Pterin 4 alpha carbinolamine dehydratase is also known as DCoH. DCoH is the dimerisation cofactor of hepatocyte nuclear factor 1 (HNF-1) that functions as both a transcriptional coactivator and a pterin dehydratase [
]. X-ray crystallographic studies have shown that the ligand binds at four sites per tetrameric enzyme, with little apparent conformational change in the protein.
D-tyrosyl-tRNA(Tyr) deacylase (DTD), also known as D-aminoacyl-tRNA deacylase, is an editing enzyme that removes D-amino acids from mischarged tRNAs. Structural studies have shown various different modes of D-amino acid recognition by DTDs, suggesting an inherent plasticity that can accommodate all d-amino acids. DTDs are essentially inactive toward L-aa-tRNAs [
,
].This superfamily represents a DTD fold, consisting of a β-barrel closed on one side by a β-sheet lid [
]. The DTD fold is present across the domains of life in twodifferent functional contexts: as an N-terminal editing domain of archaeal ThrRS (Threonyl-tRNA synthetase), which specifically removes noncognate
L-serine mischarged on tRNAThr, and as a freestanding'chiral proofreading' enzyme, which removes D-amino acids from
tRNAs in bacteria and eukaryotes [].
This family consists of D-aminoacyl-tRNA deacylase DTD, also known as D-Tyr-tRNA(Tyr) deacylase. It is an enzyme that cleaves misacetylated D-aminoacyl-tRNA molecules into free tRNAs and D-amino acids [,
]. Cell growth inhibition by several D-amino acids can be explained by an in vivo production of D-aminoacyl-tRNA molecules.The enzyme is found in bacteria and in eukaryotes but not in archea. It has a beta barrel-like fold structure and forms homodimers in which two surface cavities serve as the active site for tRNA binding [
,
,
].
Ribonuclease HII, helix-loop-helix cap domain superfamily
Type:
Homologous_superfamily
Description:
This superfamily represents the helix-loop-helix cap domain of ribonuclease HII. This C-terminal domain forms a compact structure consisting of two α-helices: alpha 8 and alpha 9. Unlike the N-terminal domain, bacterial RNases HI do not possess this domain. In the full-length enzyme, the alpha9 helix is followed by 15 amino acid residues, of which conformation is likely to be flexible, as revealed from the susceptibility to trypsin digestion. It has been suggested that this domain confers substrate-specific binding capacity to the core nuclease architecture, thus accounting for the endonucleolytic specificity of the type 2 RNase H family members [
]. It also has been suggested that this domain to be involved in the interaction with the DNA/RNA hybrid [].
Whereas bacterial and archaeal RNases H2 are active as single polypeptides, the Saccharomyces cerevisiae (Baker's yeast) homologue, Rnh2Ap, when expressed in Escherichia coli, fails to produce an active RNase H2. For RNase H2 activity three proteins are required [Rnh2Ap (Rnh201p), Ydr279p (Rnh202p) and Ylr154p (Rnh203p)]. Deletion of any one of the proteins or mutations in the catalytic site in Rnh2A leads to loss of RNase H2 activity [
]. RNase H2 is an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. It participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. This entry represents the catalytic chain of RNase H2, which is found as a single polypeptide in prokaryotes and is part of a three protein complex in eukaryotes. In Saccharomyces cerevisiae (Baker's yeast) it is represented by
.
The entry represents the Rnase H type-II domain.Ribonuclease H (RNase H) (
) is a member of the ribonuclease family, which recognises and cleaves the RNA strand of RNA-DNA heteroduplexes. The enzyme is widely present in all three kingdoms of living organisms, including bacteria, archaea, and eukaryotes, and their counterpart domains are also found in reverse transcriptases (RTs) from retroviruses and retroelements [
]. RNases H are classified into two evolutionarily unrelated families, type-I and type-II RNase H, with common structural features of the catalytic domain but different range of substrates for enzymatic cleavage. There appears to be three evolutionarily distinct lineages of cellular Rnase H enzymes []. Type-I or RNase HI domains have been found in all Eukarya, one Archaea, many Eubacteria, a few non-LTR retroposons and all LTR retrotransposons. Type II enzymes consist of RNase HII (rnhB) and HIII (rnhC), which are homologous enzymes. RNase HII can be found in Archaea, Eubacteria and all Eukarya, while RNase HIII appears only in some Eubacteria. In eukaryotes and all Archaea, RNase HII enzymes may constitute the bulk of all Rnase H activity, while the reverse is true in Eubacteria like E. coli where RNase HI is the major source of RNH activity [,
,
]. All LTR retrotransposons acquired an enzymatically weak RNase H domain that is missing an important catalytic residue found in all other RNase H enzymes. Vertebrate retroviruses appear to have reacquired their RNase H domains, which are catalytically more active, but their ancestral RNase H domains (found in other LTR retrotransposons) have degenerated to give rise to the tether domain unique to vertebrate retrovirus []. Reverse transcriptase (RT) is a modular enzyme carrying polymerase and ribonuclease H (RNase H) activities in separable domains. Retroviral RNase H is synthesised as part of the POL polyprotein that contains an aspartyl protease, a reverse transcriptase, RNase H and integrase. POL polyprotein undergoes specific enzymatic cleavage to yield the mature proteins. RNAse H activity requires the presence of divalent cations (Mg2+ or Mn2+) that bind its active site. The main element of the RNase H-like catalytic core is a β-sheet comprising five β-strands, ordered 3-2-1-4-5, where the β-strand 2 is antiparallel to the other β-strands. On both sides the central β-sheet is flanked by α-helices, the number of which differs between related enzymes. The catalytic residues for RNase H enzymatic activity (three aspartic acid and one glutamic acid residue) are invariant across all RNase H domains [
,
,
,
,
,
,
].
This family includes ribonuclease HII and HIII.Ribonuclease H (RNase H) (
) is a member of the ribonuclease family, which recognises and cleaves the RNA strand of RNA-DNA heteroduplexes. The enzyme is widely present in all three kingdoms of living organisms, including bacteria, archaea, and eukaryotes, and their counterpart domains are also found in reverse transcriptases (RTs) from retroviruses and retroelements [
]. RNases H are classified into two evolutionarily unrelated families, type-I and type-II RNase H, with common structural features of the catalytic domain but different range of substrates for enzymatic cleavage. There appears to be three evolutionarily distinct lineages of cellular Rnase H enzymes []. Type-I or RNase HI domains have been found in all Eukarya, one Archaea, many Eubacteria, a few non-LTR retroposons and all LTR retrotransposons. Type II enzymes consist of RNase HII (rnhB) and HIII (rnhC), which are homologous enzymes. RNase HII can be found in Archaea, Eubacteria and all Eukarya, while RNase HIII appears only in some Eubacteria. In eukaryotes and all Archaea, RNase HII enzymes may constitute the bulk of all Rnase H activity, while the reverse is true in Eubacteria like E. coli where RNase HI is the major source of RNH activity [,
,
]. All LTR retrotransposons acquired an enzymatically weak RNase H domain that is missing an important catalytic residue found in all other RNase H enzymes. Vertebrate retroviruses appear to have reacquired their RNase H domains, which are catalytically more active, but their ancestral RNase H domains (found in other LTR retrotransposons) have degenerated to give rise to the tether domain unique to vertebrate retrovirus []. Reverse transcriptase (RT) is a modular enzyme carrying polymerase and ribonuclease H (RNase H) activities in separable domains. Retroviral RNase H is synthesised as part of the POL polyprotein that contains an aspartyl protease, a reverse transcriptase, RNase H and integrase. POL polyprotein undergoes specific enzymatic cleavage to yield the mature proteins. RNAse H activity requires the presence of divalent cations (Mg2+ or Mn2+) that bind its active site. The main element of the RNase H-like catalytic core is a β-sheet comprising five β-strands, ordered 3-2-1-4-5, where the β-strand 2 is antiparallel to the other β-strands. On both sides the central β-sheet is flanked by α-helices, the number of which differs between related enzymes. The catalytic residues for RNase H enzymatic activity (three aspartic acid and one glutamic acid residue) are invariant across all RNase H domains [
,
,
,
,
,
,
].
Rfa3 (also known as RPA14) is a component of the replication protein A (RPA) complex, which binds to and removes secondary structure from ssDNA. The RPA complex is involved in DNA replication, repair, and recombination [
].
Fatty acid desaturases are enzymes that catalyse the insertion of a double bond at the delta position of fatty acids. There seem to be two distinct families of fatty acid desaturases which do not seem to be evolutionary related.Family 1 is composed of:Stearoyl-CoA desaturase (SCD) (
) [
]. Family 2 is composed of:Bacterial fatty acid desaturases.Plant stearoyl-acyl-carrier-protein desaturase (
) [
], this enzyme catalyzes the introduction of a double bond at the delta(9) position of steraoyl-ACP to produce oleoyl-ACP. This enzyme is responsible for the conversion of saturated fatty acids to unsaturated fatty acids in the synthesis of vegetable oils.Cyanobacterial DesA [
], an enzyme that can introduce a second cis double bond at the delta(12) position of fatty acid bound to membranes glycerolipids. DesA is involved in chilling tolerance; the phase transition temperature of lipids of cellular membranes being dependent on the degree of unsaturation of fatty acids of the membrane lipids.Members of this entry are endoplasmic reticulum (ER) integral membrane proteins that share the same mushroom-like shape fold consisting of four transmembrane helices (TM1-TM4) which anchor them to the membrane, capped by a cytosolic domain containing a unique 9-10 histidine-coordinating di metal (di-iron) catalytic centre [
,
]. The structure of mouse stearoyl-CoA desaturase (SDC) revealed that TM2 and TM4 are longer than TM1 and TM3 and protrude into the cytosolic domain, providing three of the nine histidine residues that coordinate the two metal ions, while the other histidine residues are provided by the soluble domain in this enzyme [].
This region of the inner centromere protein has been found to be necessary and sufficient for binding to aurora-related kinase. This interaction has been implicated in the coordination of chromosome segregation with cell division in yeast [
].
Spt5p and prokaryotic NusG are shown to contain a novel 'NGN' domain. The combined NGN and KOW motif regions of Spt5 form the binding domain with Spt4 [
]. Spt5 complexes with Spt4 as a 1:1 heterodimer snf this Spt5-Spt4 complex regulates early transcription elongation by RNA polymerase II and has an imputed role in pre-mRNA processing via its physical association with mRNA capping enzymes. The Schizosaccharomyces pombe core Spt5-Spt4 complex is a heterodimer bearing a trypsin-resistant Spt4-binding domain within the Spt5 subunit [].
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].Ribosomal protein L24 is one of the proteins from the large ribosomal subunit.
L24 belongs to a family of ribosomal proteins which, on the basis of sequencesimilarities, groups:- Eubacterial L24.- Plant chloroplast L24 (nuclear-encoded).- Red algal L24.- Vertebrate L26.- Yeast L26 (YL33).- Archaebacterial HmaL24 (HL15).- A probable ribosomal protein from Sulfolobus acidocaldarius [
].
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 [,
,
,
]. Diphosphomevalonate decarboxylase (mevalonate pyrophosphate decarboxylase, (
) catalyzes the decarboxylation of mevalonate pyrophosphate to isopentyl pyrophosphate (IPP) [
], the last step in the synthesis of IPP in the mevalonate pathway. In archaea, an alternate pathway involves decarboxylation of mevalonate monophosphate instead of diphosphomevalonate []. Mevalonate is a key intermediate in the biosynthesis of sterols and non-sterol isoprenes in the mevalonate pathway. In mammals, the majority of mevalonate is converted into cholesterol.ATP + (R)-5-diphosphomevalonate = ADP + phosphate + isopentenyl diphosphate + CO2 The classical mevalonate (MVA) pathway involves decarboxylation of mevalonate diphosphate, while an alternate pathway involves decarboxylation of mevalonate monophosphate. The enzyme responsible is known as phosphomevalonate decarboxylase [].
This entry represents single domain 2Fe-2S (also called plant type) ferredoxins. In general, these occur as a single domain proteins or with a chloroplast transit peptide. In higher plants, ferredoxin is the unique soluble electron carrier protein located in the stroma, and a wide variety of essential metabolic and signalling processes depend upon the reduction by ferredoxin. Species tend to be photosynthetic, but several forms may occur in one species and individually may not be associated with photosynthesis. For instance, in Arabidopsis two ferredoxins are leaf-type that support high photosynthetic activity, while one is a root-type that is more efficiently reduced under non-photosynthetic conditions and supporting a higher activity of sulphite reduction [
].
This region is found in eukaryotes, and is typically between 182 and 199 amino acids in length. There is a single completely conserved residue R that may be functionally important. Tubulin folding cofactor D does not co-polymerise with microtubules either in vivo or in vitro, but instead modulates microtubule dynamics by sequestering beta-tubulin from GTP-bound alphabeta-heterodimers in microtubules [
].
This domain is found in FeMo cofactor biosynthesis protein NifB, PqqA peptide cyclase, Oxygen-independent coproporphyrinogen III oxidase (HemN), biotin synthase (BioB), Lipoyl synthase (LipA), Ribosomal protein S12 methylthiotransferase RimO, GTP 3',8-cyclase (MoaA) and tRNA-2-methylthio-N(6)-dimethylallyladenosine synthase (MiaB), and similar proteins found in cellular organisms. This group includes a representative in the eukaryotic elongator
subunit, Elp-3. Some members of this entry are methyltransferases [,
].
Radical SAM proteins are found in all domains of life and share an unusual Fe-S cluster associated with generation of a free radical by reductive cleavage of SAM and often provide an anaerobic or oxygen-independent mechanism that is found as an aerobic reaction in other proteins. Radical SAM proteins catalyse diverse reactions, including unusual methylations, isomerization, sulphur insertion, ring formation, anaerobic oxidation and protein radical formation. These proteins function in DNA precursor, vitamin, cofactor, antibiotic and herbicide biosynthesis and in biodegradation pathways [
,
].Radical SAM proteins share several common features, notably three strictly conserved cysteine residues generally included in the CxxxCxxC motif. These critical cysteines coordinate the unusual [4Fe-4S]2+/1+ cluster, while SAM serves as ligand for the fourth iron atom and acts as a cofactor or a cosubstrate []. The radical SAM enzymes biochemically characterised to date have in common the cleavage of the [4Fe-4S]1+-SAM complex to [4Fe-4S]2+-Met and the 5'-deoxyadenosyl radical, which abstracts a hydrogen atom from the substrate to initiate a radical mechanism [,
].The Radical SAM domain is organised in a fold related to the β-barrel or TIM barrel, in which β-strands are arranged in a barrel-like array, with peripheral helices intervening between β-strands. The [4Fe-4S] clusters and substrates are bound within the barrels, as is typical of TIM barrel enzymes [,
].
This entry represents the eukaryotic transmembrane proteins 230 and 134 (TMEM230 and 134). TMEM134 function is unknown, but it has been shown to interact with E virus ORF2 [
]. TMEM 230 is involved in trafficking and recycling of synaptic vesicles [].
The family of pyridoxal 5'-phosphate synthase subunits, known as the PdxS/SNZ family, occur in organisms in four kingdoms and form one of the most highly conserved families [
]. A PdxS/SNZ protein has a classic (beta/alpha)8-barrel fold, consisting of eight parallel β-strands alternating with eight alpha helices. PdxS subunits form two hexameric rings [
]. Proteins are involved in vitamin B6 biosynthesis.The term vitamin B6 is used to refer collectively to the compound pyridoxine
and its vitameric forms, pyridoxal, pyridoxamine, and their phosphorylated derivatives. Vitamin B6 is required by all organisms and plays an essential
role as a co-factor for enzymatic reactions. Plants, fungi, bacteria, archaebacteria, and protists synthetize vitamin B6. Animals and some highly
specialised obligate pathogens obtain it nutritionally. Vitamin B6 has two distinct biosynthetic pathways, which do not coexist in any organism. The
pdxA/pdxJ pathway, that has been extensively characterised in Escherichia coli, is found in the gamma subdivision of the proteobacteria. A second
pathway of vitamin B6 synthesis involving the pdxS/SNZ and pdxT/SNO protein families, which are completely unrelated in sequence to the pdxA/pdxJ proteins, is found in plants, fungi, protists, archaebacteria and most bacteria [,
,
].PdxS/SNZ and pdxT/SNO proteins form a complex which serves as a glutamine
amidotransferase to supply ammonia as a source of the ring nitrogen of vitamin B6 [
]. PdxT/SNO and pdxS/SNZ appear to encode respectively the glutaminase subunit, which produces ammonia from glutamine, and the synthase subunit, which combines ammonia with five- and three-carbon phosphosugars to form vitamin B6 [].
This entry corresponds to proteins having the Ysc84 actin binding domain (YAB). This 184 amino acid domain lies at the N terminus of the Saccharomyces cerevisiae (Baker's yeast) protein Ysc84 (
). It is essential for the organisation of the actin cytoskeleton, and interacts with the Arp2/3 complex [
]. Homologous domains are found across a range of species. In fungi and vertebrates the domain is at the N terminus, while there is an SH3 domain at the C terminus. In plants the domain seems to be at the C terminus and in association with a FYVE domain. Interestingly, the domain is absent in invertebrates.The domain is also found in prokaryotes, where presumable it is also involved in protein binding, perhaps to the prokaryotic homologue of actin [
].
This domain is found in bacteria and eukaryotes, and is approximately 110 amino acids in length. It is found in association with
. This domain is also present in the tau subunit before it undergoes cleavage. Domains I-III are shared between the tau and the gamma subunits, while most of the DnaB-binding Domain IV and all of the alpha-interacting Domain V are unique to tau.
This entry includes a group of choline transporter-like protein, including SLC44A1/2/3/4/5 from humans, Pns1 from budding yeasts, and Ctl1 from fission yeasts [
]. In humans, mutations of this family of proteins have been linked to several human diseases []. SLC44A1-5 are choline transporters that regulate choline transport across both the plasma membrane and the mitochondrial membrane in a Na(+)-independent manner [
,
,
].
Malectin is a membrane-anchored protein of the endoplasmic reticulum that recognises and binds Glc2-N-glycan. It carries a signal peptide from residues 1-26, a C-terminal transmembrane helix from residues 255-274, and a highly conserved central part of approximately 190 residues followed by an acidic, glutamate-rich region. Carbohydrate-binding is mediated by the four aromatic residues, Y67, Y89, Y116, and F117 and the aspartate at D186. NMR-based ligand-screening studies has shown binding of the protein to maltose and related oligosaccharides, on the basis of which the protein has been designated "malectin", and its endogenous ligand is found to be Glc2-high-mannose N-glycan [
].This entry represents a malectin domain, and can also be found in probable receptor-like serine/threonine-protein kinases from plants [
] and in proteins described as glycoside hydrolases.
All proteins in this family for which functions are known are components of a multiprotein complex used for targeting nucleotide excision repair to specific parts of the genome. Rad23 contains a ubiquitin-like domain that interacts with catalytically active proteasomes and two ubiquitin
(Ub)-associated (UBA) sequences that bind Ub. Rad23 interacts with ubiquitinated cellular proteins through thesynergistic action of its UBA domains. In
humans, Rad23 complexes with the XPC protein.
This domain adopts a structure consisting of four α-helices, arranged in an array. It binds specifically and directly to the xeroderma pigmentosum group C protein (XPC) to initiate nucleotide excision repair [
].
Glycolipid transfer protein (GLTP) is a cytosolic protein that catalyses the intermembrane transfer of glycolipids such as glycosphingolipids, glyceroglycolipids, and possibly glucosylceramides, but not of phospholipids. The GLTP protein consists of a single domain with a multi-helical structure consisting of two layers of orthogonally packed helices [
,
]. The GLTP domain is also found in trans-Golgi network proteins involved in Golgi-to-cell-surface membrane traffic [
].
This entry represents the copper-containing enzyme L-ascorbate oxidase (
), also called ascorbase. These enzymes are found in flowering plants, and show greater sequence similarity to a family of laccases (
) from plants than to other known ascorbate oxidases.
Association with the SNF1 complex (ASC) domain is found in the Sip1/Sip2/Gal83/AMPKbeta subunits of the SNF1/AMP-activated protein kinase (AMPK) complex [
]. SNF1/AMPK are heterotrimeric enzymes composed of a catalytic alpha-subunit, a regulatory gamma-subunit and a regulatory/targeting beta-subunit []. Saccharomyces cerevisiae encodes three beta-subunit genes, Sip1, Sip2 and Gal83 [,
]. The beta-subunits function as target selective adaptors that recruit the catalytic kinase and regulator Snf4/gamma-subunits. The ASC domain is required for interaction with Snf4 [,
].The SNF1 kinase complex is required for transcriptional, metabolic, and developmental adaptations in response to glucose limitation [
,
]. As glucose levels decrease, Snf1 is activated and promotes the use of alternative carbon sources.
This domain is found in all 24 mce genes associated with the four mammalian cell entry (mce) operons of Mycobacterium tuberculosis and MlaD proteins from other Actinomycetales [
,
]. The archetype (mce1A, Rv0169), was isolated as being necessary for colonisation of, and survival within, the macrophage []. The domain is also found in: Chloroplast Ycf22 and related cyanobacterial homologues, the majority of which have an N-terminal transmembrane domain and are putative ABC transporters.
Proteobacterial homologues, which include MlaD, PqiB, YrbD, YebT, VpsC and Ttg2C. MlaD is part of the ABC transporter complex MlaFEDB that actively prevents phospholipid accumulation at the cell surface []. MlaFEDB complex is composed of two ATP-binding proteins (MlaF), two transmembrane proteins (MlaE), two cytoplasmic solute-binding proteins (MlaB) and a probable periplamic solute-binding protein (MlaD). Through the Mla pathway, Gram-negative bacteria maintains lipid asymmetry in the outer membrane by retrograde trafficking of phospholipids from the outer membrane to the inner membrane [].
Members of this family are metallothioneins. These
proteins are cysteine rich proteins that bind to heavymetals. Members of this family appear to be closest to
Class II metallothioneins.
Members of this eukaryotic family are part of the group II chaperonin complex called CCT (chaperonin containing TCP-1 or Tailless Complex Polypeptide 1) or TRiC [
,
]. Chaperonins are involved in productive folding of proteins []. They share a common general morphology, a double toroid of 2 stacked rings. The archaeal equivalent group II chaperonin is often called the thermosome []. Both the thermosome and the TCP-1 family of proteins are weakly, but significantly [], related to the cpn60/groEL chaperonin family (see ).
The TCP-1 protein was first identified in mice where it is especially abundant in testis but present in all cell types. It has since been found and characterised in many other animal species, as well as in yeast, plants and protists. The TCP1 complex has a double-ring structure with central cavities where protein folding takes place [
]. TCP-1 is a highly conserved protein of about 60kDa (556 to 560 residues) which participates in a hetero-oligomeric 900kDa double-torus shaped particle [] with 6 to 8 other different, but homologous, subunits []. These subunits, the chaperonin containing TCP-1 (CCT) subunit beta, gamma, delta, epsilon, zeta and eta are evolutionary related to TCP-1 itself [,
]. Non-native proteins are sequestered inside the central cavity and folding is promoted by using energy derived from ATP hydrolysis [,
,
]. The CCT is known to act as a molecular chaperone for tubulin, actin and probably some other proteins [,
].This family consists exclusively of the CCT eta chain (part of a paralogous family) from animals, plants, fungi, and other eukaryotes.
Chaperonins are large cylindrical structures that transiently enclose a partially folded polypeptide and allow it to continue folding in a sequestered environment. Chaperonins are grouped into two families: group I chaperonins, found in eubacteria (e.g. GroEL in Escherichia coli) and eukaryotic organelles of eubacterial descent (e.g. Cpn60 in mitochondria and chloroplasts), and group II chaperonins, found in archaea and the eukaryotic cytosol (CCT or TCP-1 complex) [
,
]. Both groups share a common monomer architecture of three domains: an equatorial domain that carries ATPase activity, an intermediate domain, and an apical domain, involved in substrate binding [,
].This superfamily represents the intermediate domain of type II chaperonins.
It has been observed that the identity of N-terminal residues of a protein is
related to the half life of the protein. This observation yields a rule,called the N-end rule [
]. Similar but distinct versions of the N-end rule operate in all organisms examined, from mammals to fungi and bacteria. Ineukaryotes, the N-end rule pathway is a part of the ubiquitin degradation
system. Some proteins that have a very short half life contain a specificmotif at their N terminus, the N-degron. It consists of a destabilising
N-terminal residue and an internal Lys, which is the site of poly-Ub chain[
,
].The UBR1 protein was shown to bind specifically to proteins bearing N-terminal
residues that are destabilising according to the N-end rule, but not tootherwise identical proteins bearing stabilising N-terminal residues [
]. UBR1 contains an N-terminal conserved region (the UBR-type zinc finger) which is also found in various proteins implicated in N-degron recognition. The UBR-type zinc finger defines a unique E3 class, most likely N-degron specific [].
The maoC gene is part of an operon with maoA which is involved in the synthesis of monoamine oxidase [
]. The MaoC protein shares similarity with a region found in a wide variety of enzymes, such as peroxisomal hydratase-dehydrogenase-epimerase and fatty acid synthase beta subunit. A deletion mutant of the C-terminal 271 amino acids in peroxisomal hydratase-dehydrogenase-epimerase (), corresponding to the MaoC domain, abolished its 2-enoyl-CoA hydratase activity, suggesting that this region may be a hydratase enzyme [
]. Several bacterial proteins that are composed solely of this domain have (R)-specific enoyl-CoA hydratase activity [].
3-oxo-5-alpha-steroid 4-dehydrogenases,
catalyse the conversion of 3-oxo-5-alpha-steroid + acceptor to 3-oxo-delta(4)-steroid + reduced acceptor. The steroid 5-alpha-reductase enzyme is responsible for the formation of dihydrotestosterone, this hormone promotes the differentiation of male external genitalia and the prostate during foetal development [
]. In humans mutations in this enzyme can cause a form of male pseudohermaphorditism in which the external genitalia and prostate fail to develop normally. A related steroid reductase enzyme, DET2, is found in plants such as Arabidopsis. Mutations in this enzyme cause defects in light-regulated development []. This domain is present in both type 1 and type 2 [] forms.This domain is also found in polyprenol reductase (SRD5A3;
), which is reduces the alpha-isoprene unit of polyprenol to form dolichol. Dolichol is required for the synthesis of a dolichol-linked monosaccharide and the oligosaccharide precursor used for N-glycosylation [
].Another enzyme with this domain is very-long-chain enoyl-CoA reductase (TECR;
), which catalyzes the last of the four reactions of the long-chain fatty acids elongation cycle by reducing the trans-2,3-enoyl-CoA fatty acid intermediate to an acyl-CoA that can be further elongated by entering a new cycle of elongation [
].
This family consists of the wound-inducible basic proteins from plants. The metabolic activities of plants are dramatically altered upon mechanical injury or pathogen attack. A large number of proteins accumulates at wound or infection sites, such as the wound-inducible basic proteins. These proteins are small, 47 amino acids in length, has no signal peptides and are hydrophilic and basic [
].
ATP synthase, F0 complex, subunit C, DCCD-binding site
Type:
Binding_site
Description:
Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP. There are several different types of transmembrane ATPases, which can differ in function (ATP hydrolysis and/or synthesis), structure (e.g., F-, V- and A-ATPases, which contain rotary motors) and in the type of ions they transport [
,
]. The different types include:F-ATPases (ATP synthases, F1F0-ATPases), which are found in mitochondria, chloroplasts and bacterial plasma membranes where they are the prime producers of ATP, using the proton gradient generated by oxidative phosphorylation (mitochondria) or photosynthesis (chloroplasts).V-ATPases (V1V0-ATPases), which are primarily found in eukaryotes and they function as proton pumps that acidify intracellular compartments and, in some cases, transport protons across the plasma membrane []. They are also found in bacteria [].A-ATPases (A1A0-ATPases), which are found in Archaea and function like F-ATPases, though with respect to their structure and some inhibitor responses, A-ATPases are more closely related to the V-ATPases [
,
].P-ATPases (E1E2-ATPases), which are found in bacteria and in eukaryotic plasma membranes and organelles, and function to transport a variety of different ions across membranes.E-ATPases, which are cell-surface enzymes that hydrolyse a range of NTPs, including extracellular ATP.F-ATPases (also known as ATP synthases, F1F0-ATPase, or H(+)-transporting two-sector ATPase) (
) are composed of two linked complexes: the F1 ATPase complex is the catalytic core and is composed of 5 subunits (alpha, beta, gamma, delta, epsilon), while the F0 ATPase complex is the membrane-embedded proton channel that is composed of at least 3 subunits (A-C), with additional subunits in mitochondria. Both the F1 and F0 complexes are rotary motors that are coupled back-to-back. In the F1 complex, the central gamma subunit forms the rotor inside the cylinder made of the alpha(3)beta(3) subunits, while in the F0 complex, the ring-shaped C subunits forms the rotor. The two rotors rotate in opposite directions, but the F0 rotor is usually stronger, using the force from the proton gradient to push the F1 rotor in reverse in order to drive ATP synthesis [
]. These ATPases can also work in reverse in bacteria, hydrolysing ATP to create a proton gradient.Subunit C (also called subunit 9, or proteolipid) is found in the F0 complex of F-ATPases. Ten C subunits form an oligomeric ring that makes up the F0 rotor. The flux of protons through the ATPase channel drives the rotation of the C subunit ring, which in turn is coupled to the rotation of the F1 complex gamma subunit rotor due to the permanent binding between the gamma and epsilon subunits of F1 and the C subunit ring of F0. The sequential protonation and deprotonation of Asp61 of subunit C is coupled to the stepwise movement of the rotor [
]. Structurally, subunit c consists of two long terminal hydrophobic regions, which probably span the membrane, and a central hydrophilic region. N,N'-dicyclohexylcarbodiimide (DCCD) can bind covalently to subunit c and thereby abolish the ATPase activity. DCCD binds to a specific glutamate or aspartate residue which is located in the middle of the second hydrophobic region near the C terminus of the protein. This entry represents the site that includes the DCCD-binding residue.
Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP. There are several different types of transmembrane ATPases, which can differ in function (ATP hydrolysis and/or synthesis), structure (e.g., F-, V- and A-ATPases, which contain rotary motors) and in the type of ions they transport [
,
]. The different types include:F-ATPases (ATP synthases, F1F0-ATPases), which are found in mitochondria, chloroplasts and bacterial plasma membranes where they are the prime producers of ATP, using the proton gradient generated by oxidative phosphorylation (mitochondria) or photosynthesis (chloroplasts).V-ATPases (V1V0-ATPases), which are primarily found in eukaryotes and they function as proton pumps that acidify intracellular compartments and, in some cases, transport protons across the plasma membrane [
]. They are also found in bacteria [].A-ATPases (A1A0-ATPases), which are found in Archaea and function like F-ATPases, though with respect to their structure and some inhibitor responses, A-ATPases are more closely related to the V-ATPases [
,
].P-ATPases (E1E2-ATPases), which are found in bacteria and in eukaryotic plasma membranes and organelles, and function to transport a variety of different ions across membranes.E-ATPases, which are cell-surface enzymes that hydrolyse a range of NTPs, including extracellular ATP.The F-ATPases (or F1F0-ATPases) and V-ATPases (or V1V0-ATPases) are each composed of two linked complexes: the F1 or V1 complex contains the catalytic core that synthesizes/hydrolyses ATP, and the F0 or V0 complex that forms the membrane-spanning pore. The F- and V-ATPases all contain rotary motors, one that drives proton translocation across the membrane and one that drives ATP synthesis/hydrolysis [
,
].In V-ATPases, there are three proteolipid subunits (c, c' and c'') that form part of the proton-conducting pore, each containing a buried glutamic acid residue that is essential for proton transport, and together they form a hexameric ring spanning the membrane [
,
]. Structurally, the c subunits consist of a two antiparallel transmembrane helices. Both helices of one c subunit are connected by a loop on the cytoplasmic side [
].This entry represents the V-ATPase proteolipid subunit C like domain found in the V-ATPase proteolipid subunit C and the F-ATP synthase subunit C.
Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP. There are several different types of transmembrane ATPases, which can differ in function (ATP hydrolysis and/or synthesis), structure (e.g., F-, V- and A-ATPases, which contain rotary motors) and in the type of ions they transport [,
]. The different types include:F-ATPases (ATP synthases, F1F0-ATPases), which are found in mitochondria, chloroplasts and bacterial plasma membranes where they are the prime producers of ATP, using the proton gradient generated by oxidative phosphorylation (mitochondria) or photosynthesis (chloroplasts).V-ATPases (V1V0-ATPases), which are primarily found in eukaryotes and they function as proton pumps that acidify intracellular compartments and, in some cases, transport protons across the plasma membrane [
]. They are also found in bacteria [].A-ATPases (A1A0-ATPases), which are found in Archaea and function like F-ATPases, though with respect to their structure and some inhibitor responses, A-ATPases are more closely related to the V-ATPases [
,
].P-ATPases (E1E2-ATPases), which are found in bacteria and in eukaryotic plasma membranes and organelles, and function to transport a variety of different ions across membranes.E-ATPases, which are cell-surface enzymes that hydrolyse a range of NTPs, including extracellular ATP.F-ATPases (also known as ATP synthases, F1F0-ATPase, or H(+)-transporting two-sector ATPase) (
) are composed of two linked complexes: the F1 ATPase complex is the catalytic core and is composed of 5 subunits (alpha, beta, gamma, delta, epsilon), while the F0 ATPase complex is the membrane-embedded proton channel that is composed of at least 3 subunits (A-C), with additional subunits in mitochondria. Both the F1 and F0 complexes are rotary motors that are coupled back-to-back. In the F1 complex, the central gamma subunit forms the rotor inside the cylinder made of the alpha(3)beta(3) subunits, while in the F0 complex, the ring-shaped C subunits forms the rotor. The two rotors rotate in opposite directions, but the F0 rotor is usually stronger, using the force from the proton gradient to push the F1 rotor in reverse in order to drive ATP synthesis [
]. These ATPases can also work in reverse in bacteria, hydrolysing ATP to create a proton gradient.This entry represents subunit C (also called subunit 9, or proteolipid) found in the F0 complex of F-ATPases. Ten C subunits form an oligomeric ring that makes up the F0 rotor. The flux of protons through the ATPase channel drives the rotation of the C subunit ring, which in turn is coupled to the rotation of the F1 complex gamma subunit rotor due to the permanent binding between the gamma and epsilon subunits of F1 and the C subunit ring of F0. The sequential protonation and deprotonation of Asp61 of subunit C is coupled to the stepwise movement of the rotor [
].
Globins are haem-containing proteins involved in binding and/or transporting oxygen. They belong to a very large and well studied family that is widely distributed in many organisms [
]. Globins have evolved from a common ancestor and can be divided into three groups: single-domain globins, and two types of chimeric globins, flavohaemoglobins and globin-coupled sensors. Bacteria have all three types of globins, while archaea lack flavohaemoglobins, and eukaryotes lack globin-coupled sensors []. Several functionally different haemoglobins can coexist in the same species. The major types of globins include:Haemoglobin (Hb): tetramer of two alpha and two beta chains, although embryonic and foetal forms can substitute the alpha or beta chain for ones with higher oxygen affinity, such as gamma, delta, epsilon or zeta chains. Hb transports oxygen from lungs to other tissues in vertebrates [
]. Hb proteins are also present in unicellular organisms where they act as enzymes or sensors [].Myoglobin (Mb): monomeric protein responsible for oxygen storage in vertebrate muscle [
].Neuroglobin: a myoglobin-like haemprotein expressed in vertebrate brain and retina, where it is involved in neuroprotection from damage due to hypoxia or ischemia [
]. Neuroglobin belongs to a branch of the globin family that diverged early in evolution. Cytoglobin: an oxygen sensor expressed in multiple tissues. Related to neuroglobin [
].Erythrocruorin: highly cooperative extracellular respiratory proteins found in annelids and arthropods that are assembled from as many as 180 subunit into hexagonal bilayers [
].Leghaemoglobin (legHb or symbiotic Hb): occurs in the root nodules of leguminous plants, where it facilitates the diffusion of oxygen to symbiotic bacteriods in order to promote nitrogen fixation.Non-symbiotic haemoglobin (NsHb): occurs in non-leguminous plants, and can be over-expressed in stressed plants [
].Flavohaemoglobins (FHb): chimeric, with an N-terminal globin domain and a C-terminal ferredoxin reductase-like NAD/FAD-binding domain. FHb provides protection against nitric oxide via its C-terminal domain, which transfers electrons to haem in the globin [
].Globin-coupled sensors: chimeric, with an N-terminal myoglobin-like domain and a C-terminal domain that resembles the cytoplasmic signalling domain of bacterial chemoreceptors. They bind oxygen, and act to initiate an aerotactic response or regulate gene expression [
,
]. Protoglobin: a single domain globin found in archaea that is related to the N-terminal domain of globin-coupled sensors [].Truncated 2/2 globin: lack the first helix, giving them a 2-over-2 instead of the canonical 3-over-3 α-helical sandwich fold. Can be divided into three main groups (I, II and II) based on structural features [
].This domain superfamily is found in the entire globin family of proteins, including the microbial globins [
].
Globins are haem-containing proteins involved in binding and/or transporting oxygen. They belong to a very large and well studied family that is widely distributed in many organisms [
]. Globins have evolved from a common ancestor and can be divided into three groups: single-domain globins, and two types of chimeric globins, flavohaemoglobins and globin-coupled sensors. Bacteria have all three types of globins, while archaea lack flavohaemoglobins, and eukaryotes lack globin-coupled sensors []. Several functionally different haemoglobins can coexist in the same species. The major types of globins include:Haemoglobin (Hb): tetramer of two alpha and two beta chains, although embryonic and foetal forms can substitute the alpha or beta chain for ones with higher oxygen affinity, such as gamma, delta, epsilon or zeta chains. Hb transports oxygen from lungs to other tissues in vertebrates [
]. Hb proteins are also present in unicellular organisms where they act as enzymes or sensors [].Myoglobin (Mb): monomeric protein responsible for oxygen storage in vertebrate muscle [
].Neuroglobin: a myoglobin-like haemprotein expressed in vertebrate brain and retina, where it is involved in neuroprotection from damage due to hypoxia or ischemia [
]. Neuroglobin belongs to a branch of the globin family that diverged early in evolution. Cytoglobin: an oxygen sensor expressed in multiple tissues. Related to neuroglobin [
].Erythrocruorin: highly cooperative extracellular respiratory proteins found in annelids and arthropods that are assembled from as many as 180 subunit into hexagonal bilayers [
].Leghaemoglobin (legHb or symbiotic Hb): occurs in the root nodules of leguminous plants, where it facilitates the diffusion of oxygen to symbiotic bacteriods in order to promote nitrogen fixation.Non-symbiotic haemoglobin (NsHb): occurs in non-leguminous plants, and can be over-expressed in stressed plants [
].Flavohaemoglobins (FHb): chimeric, with an N-terminal globin domain and a C-terminal ferredoxin reductase-like NAD/FAD-binding domain. FHb provides protection against nitric oxide via its C-terminal domain, which transfers electrons to haem in the globin [
].Globin-coupled sensors: chimeric, with an N-terminal myoglobin-like domain and a C-terminal domain that resembles the cytoplasmic signalling domain of bacterial chemoreceptors. They bind oxygen, and act to initiate an aerotactic response or regulate gene expression [
,
]. Protoglobin: a single domain globin found in archaea that is related to the N-terminal domain of globin-coupled sensors [
].Truncated 2/2 globin: lack the first helix, giving them a 2-over-2 instead of the canonical 3-over-3 α-helical sandwich fold. Can be divided into three main groups (I, II and II) based on structural features [
].This superfamily represents proteins with a globin-like fold consisting of six helices in a partly opened, folded leaf topology, as well as the truncated globins that lack the initial helix. This includes both the globins themselves, and the phycocyanin-like phycobilisome proteins (phycocyanin, allophycocyanin, phycoerythrin and phycoerythrocyanin). Phycobilisome proteins are oligomers of two different types of globin-like subunits that contain two extra helices at the N terminus, and which are use to bind a bilin chromophore. They occur in red algae and cyanobacteria, where they are used for light-harvesting [
].
Globins are haem-containing proteins involved in binding and/or transporting oxygen. They belong to a very large and well studied family that is widely distributed in many organisms [
]. Globins have evolved from a common ancestor and can be divided into three groups: single-domain globins, and two types of chimeric globins, flavohaemoglobins and globin-coupled sensors. Bacteria have all three types of globins, while archaea lack flavohaemoglobins, and eukaryotes lack globin-coupled sensors []. Several functionally different haemoglobins can coexist in the same species. The major types of globins include:Haemoglobin (Hb): tetramer of two alpha and two beta chains, although embryonic and foetal forms can substitute the alpha or beta chain for ones with higher oxygen affinity, such as gamma, delta, epsilon or zeta chains. Hb transports oxygen from lungs to other tissues in vertebrates [
]. Hb proteins are also present in unicellular organisms where they act as enzymes or sensors [].Myoglobin (Mb): monomeric protein responsible for oxygen storage in vertebrate muscle [
].Neuroglobin: a myoglobin-like haemprotein expressed in vertebrate brain and retina, where it is involved in neuroprotection from damage due to hypoxia or ischemia [
]. Neuroglobin belongs to a branch of the globin family that diverged early in evolution. Cytoglobin: an oxygen sensor expressed in multiple tissues. Related to neuroglobin [
].Erythrocruorin: highly cooperative extracellular respiratory proteins found in annelids and arthropods that are assembled from as many as 180 subunit into hexagonal bilayers [
].Leghaemoglobin (legHb or symbiotic Hb): occurs in the root nodules of leguminous plants, where it facilitates the diffusion of oxygen to symbiotic bacteriods in order to promote nitrogen fixation.Non-symbiotic haemoglobin (NsHb): occurs in non-leguminous plants, and can be over-expressed in stressed plants [
].Flavohaemoglobins (FHb): chimeric, with an N-terminal globin domain and a C-terminal ferredoxin reductase-like NAD/FAD-binding domain. FHb provides protection against nitric oxide via its C-terminal domain, which transfers electrons to haem in the globin [
].Globin-coupled sensors: chimeric, with an N-terminal myoglobin-like domain and a C-terminal domain that resembles the cytoplasmic signalling domain of bacterial chemoreceptors. They bind oxygen, and act to initiate an aerotactic response or regulate gene expression [
,
]. Protoglobin: a single domain globin found in archaea that is related to the N-terminal domain of globin-coupled sensors [
].Truncated 2/2 globin: lack the first helix, giving them a 2-over-2 instead of the canonical 3-over-3 α-helical sandwich fold. Can be divided into three main groups (I, II and II) based on structural features [
].This entry covers most of the globin family of proteins, but it omits some bacterial globins and the protoglobins.
The U2 small nuclear ribonucleoprotein auxiliary factor (U2AF) is a heterodimeric splicing factor composed of a large and a small subunit [
]. The large U2AF subunit recognises the intronic polypyrimidine tract, a sequence located adjacent to the 3' splice site that serves as an important signal for both constitutive and regulated pre-mRNA splicing. The small subunit interacts with the 3' splice site dinucleotide AG and is essential for regulated splicing. The subunits shuttle continuously between the nucleus and the cytoplasm via a mechanism that involves carrier receptors and is independent of binding to mRNA. Both subunits contain an arginine/serine-rich (RS) domain, which acts as a nuclear localisation signal.Furthermore, the presence of an RS domain on either subunit is sufficient to trigger the nucleocytoplasmic import of the heterodimeric complex [
,
,
].The human form of the U2 auxiliary factor small subunit, hU2AF35, contains a degenerate RNA recognition motif (RRM) and a C-terminal RS domain. Mutations in this protein alters U2AF1 function affects the alternative splicing of target genes associated with myelodysplastic syndrome (MDS) [
]. The murine form has been shown to be genomically imprintedwith monoallelic expression from the paternal allele. However, this is not the case in humans [
].
This entry represents the CRA (or CT11-RanBPM) domain, which is a protein-protein interaction domain present in crown eukaryotes (plants, animals, fungi) and which is found in Ran-binding proteins such as Ran-binding protein 9 (RanBP9 or RanBPM) and RanBP10. RanBPM is a scaffolding protein important in regulating cellular function in both the immune system and the nervous system, and may act as an adapter protein to couple membrane receptors to intracellular signaling pathways. This domain is at the C terminus of the proteins and is the binding domain for the CRA motif, which is comprised of approximately 100 amino acids at the C-terminal of RanBPM. It was found to be important for the interaction of RanBPM with Fragile X messenger ribonucleoprotein 1 (FMRP/FMR1), but its functional significance has yet to be determined [
].
Acetolactate synthase, large subunit, biosynthetic
Type:
Family
Description:
Two groups of proteins form acetolactate from two molecules of pyruvate. The type of acetolactate synthase described in this entry also catalyzes the formation of acetohydroxybutyrate from pyruvate and 2-oxobutyrate, an early step in the branched chain amino acid biosynthesis; it is therefore also termed acetohydroxyacid synthase. In bacteria, this catalytic chain is associated with a smaller regulatory chain in an alpha2/beta2 heterotetramer. Acetolactate synthase is a thiamine pyrophosphate enzyme. In this type, FAD and Mg++ are also found. Several isozymes of this enzyme are found in Escherichia coli (strain K12), one of which contains a frameshift in the large subunit gene and is not expressed.
A number of enzymes require thiamine pyrophosphate (TPP) (vitamin B1) as a cofactor. It has been shown [
] that some of these enzymes are structurally related. This entry represents the DHS-like NAD/FAD-binding domain of TPP enzymes, which contains a 2-fold Rossman fold.
A number of enzymes require thiamine pyrophosphate (TPP) (vitamin B1) as a cofactor. It has been shown [
] that some of these enzymes are structurally related. The thiamin diphosphate-binding fold comprises two different functional modules, the pyridine-binding (Pyr) and pyrophosphate-binding (PP) modules. This represents the TPP binding domain which localizes at the C-terminal of TPP enzymes and in some members has been described as the PP-binding module.
This protein catalyzes the conversion of allantoin (5-ureidohydantoin) to allantoic acid by hydrolytic cleavage of the five-member hydantoin ring [
,
]. The proteins in this family are all in the vicinity of other genes involved in the processes of xanthine/urate/allantoin catabolism.
This group represents sphingolipid delta-4 desaturase (DEGS), an integral membrane protein required for sphingosine biosynthesis. It converts D-erythro-sphinganine to D-erythro-sphingosine (E-sphing-4-enine) [
]. Delta4-desaturated sphingolipids provide an early signal that triggers the entry into both meiotic and spermatid differentiation pathways during Drosophila spermatogenesis [].
This small domain appears to be specific to sphingolipid delta 4-desaturase. Sphingolipids are important membrane signalling molecules involved in many different cellular functions in eukaryotes. Sphingolipid delta 4-desaturase catalyses the formation of (E)-sphing-4-enine [
]. Some proteins with this domain have bifunctional delta 4-desaturase/C-4-hydroxylase activity. Delta 4-desaturated sphingolipids may play a role in early signalling required for entry into meiotic and spermatid differentiation pathways during Drosophila spermatogenesis [].
4Fe-4S ferredoxin, iron-sulphur binding, conserved site
Type:
Conserved_site
Description:
This entry represents a conserved site of Fe-4S ferredoxin, iron-sulphur binding domainFerredoxins are iron-sulphur proteins that mediate electron transfer in a range of metabolic reactions; they fall into several subgroups according to the nature of their iron-sulphur cluster(s) [
,
]. One group, originally found in bacteria, has been termed "bacterial-type", in which the active centre is a 4Fe-4S cluster. 4Fe-4S ferredoxins may in turn be subdivided into further groups, based on their sequence properties. Most contain at least one conserved domain, including four Cys residues that bind to a 4Fe-4S centre.
During the evolution of bacterial-type ferredoxins, intrasequence gene duplication, transposition and fusion events occured, resulting in the appearance of proteins with multiple iron-sulphur centres: e.g. dicluster-type (2[4Fe-4S]) and polyferredoxins, iron-sulphur subunits of bacterial succinate dehydrogenase/fumarate reductase, formate hydrogenlyase and formate dehydrogenase complexes, pyruvate-flavodoxin oxidoreductase, NADH:ubiquinone reductase, amongst others. In some bacterial ferredoxins, one of the duplicated domains has lost one or more of the four conserved Cys residues. These domains have either lost their iron-sulphur binding property, or bind to a 3Fe-4S centre instead of a 4Fe-4S centre. 3D structures are now known both for a number of monocluster-type [] and dicluster-type [] 4Fe-4S ferredoxins.
Ferredoxins are a group of iron-sulphur proteins which mediate electron transfer in a wide variety of metabolic reactions. Ferredoxins can be divided into several subgroups depending upon the physiological nature of the iron-sulphur cluster(s). One of these subgroups are the 4Fe-4S ferredoxins, which are found in bacteria and which are thus often referred as 'bacterial-type' ferredoxins. The structure of these proteins [
] consists of the duplication of a domain of twenty six amino acid residues; each of these domains contains four cysteine residues that bind to a 4Fe-4S centre.Several structures of the 4Fe-4S ferredoxin domain have been determined [
]. The clusters consist of two interleaved 4Fe- and 4S-tetrahedra forming a cubane-like structure, in such a way that the four iron occupy the eight corners of a distorted cube. Each 4Fe-4S is attached to the polypeptide chain by four covalent Fe-S bonds involving cysteine residues.
A number of proteins have been found [
] that include one or more 4Fe-4S binding domains similar to those of bacterial-type ferredoxins.The pattern of cysteine residues in the iron-sulphur region is sufficient to detect this class of 4Fe-4S binding proteins. This entry represents the whole domain.Note:In some bacterial ferredoxins, one of the two duplicated domains has lost one or more of the four conserved cysteines. The consequence of such variations is that these domains have either lost their iron-sulphur binding property or bind to a 3Fe-3S centre instead of a 4Fe-4S centre.
This entry represents the I subunit (one of 14 subunits, A to N) of the NADH-quinone oxidoreductase complex I (
) which generally couples NADH and ubiquinone oxidation/reduction in bacteria and mammalian mitochondria, but may act on NADPH and/or plastoquinone in cyanobacteria and plant chloroplasts. This family does not contain 'I' subunits from the closely related F420H2 dehydrogenase and formate hydrogenlyase complexes.
The carbon-nitrogen hydrolase domain is an around 265-residue domain found in numerous enzymes involved in the reduction of organic nitrogen compounds and ammonia production. Based on their sequence similarity and on the reactions
they catalyse, these enzymes can be classified into functionally distinct groups including [,
]:Nitrilases (
), which cleave various nitriles into the corresponding acids and ammonia.
Cyanide hydratase (
) of pathogenic fungi, which detoxifies HCN that is released by their hosts, cyanogenic plants, after injury.
Aliphatic amidases (
), which enable prokaryotes to use acetamides as both carbon and nitrogen source.
Beta-ureidopropionase (also known as beta-alanine synthase or N-carbamoyl-beta-alanine amino hydrolase;
), which catalyses the last step of pyrimidine catabolism.
Glutamine-dependent NAD(+) synthetase (also known as AdgA, for ammonia-dependent growth) from Rhodobacter species (
). It appears to be essential for using various amino acids as nitrogen sources.Biotinidase (
), which catalyses the hydrolysis of biocytin to biotin and lysine.
Pantetheinase (
) (Pantetheine hydrolase) (Vanin), which hydrolyzes specifically one of the carboamide linkages in D-pantetheine, thus recycling pantothenic acid (vitamin B5) and releasing cysteamine.
Apolipoprotein N-acyltransferase ([intenz:2.3.1.-]) (gene lnt), a bacterial enzyme that transfers the fatty acyl group on membrane lipoproteins.Glutamine-dependent NAD(+) synthetase (
), which catalyses the final step in NAD+ synthesis [
,
]. The carbon-nitrogen hydrolase domain is characterised by several conserved motifs, one of which contains a cysteine that is part of the catalytic site in nitrilases. Another highly conserved motif includes a glutamic acid that might also be involved in catalysis [
].
Transketolase
(TK) catalyses the reversible transfer of a
two-carbon ketol unit from xylulose 5-phosphate to an aldose receptor, such asribose 5-phosphate, to form sedoheptulose 7-phosphate and glyceraldehyde 3-
phosphate. This enzyme, together with transaldolase, provides a link betweenthe glycolytic and pentose-phosphate pathways.
TK requires thiamine pyrophosphate as a cofactor. In most sources where TK hasbeen purified, it is a homodimer of approximately 70 Kd subunits. TK sequences
from a variety of eukaryotic and prokaryotic sources [,
] show that theenzyme has been evolutionarily conserved.
In the peroxisomes of methylotrophic yeast Pichia angusta (Yeast) (Hansenula polymorpha), there is ahighly related enzyme, dihydroxy-acetone synthase (DHAS)
(also
known as formaldehyde transketolase), which exhibits a very unusualspecificity by including formaldehyde amongst its substrates.
1-deoxyxylulose-5-phosphate synthase (DXP synthase) [] is an enzyme so farfound in bacteria (gene dxs) and plants (gene CLA1) which catalyses the
thiamine pyrophosphoate-dependent acyloin condensation reaction between carbonatoms 2 and 3 of pyruvate and glyceraldehyde 3-phosphate to yield 1-deoxy-D-xylulose-5-phosphate (dxp), a precursor in the biosynthetic pathway to
isoprenoids, thiamine (vitamin B1), and pyridoxol (vitamin B6). DXP synthaseis evolutionary related to TK.
The N-terminal section, contains a histidine residue which appears to function inproton transfer during catalysis [
]. This entry represents the centralsection there are conserved acidic residues that are part of the active cleft
and may participate in substrate-binding [].This group of proteins includes transketolase enzymes
and 2-oxoisovalerate dehydrogenasebeta subunit
. Both these enzymes
utilise thiamine pyrophosphate as a cofactor, suggestingthere may be common aspects in their mechanism of catalysis.
This entry conserved acidic residues that are located in the central section, which may participate in substrate-binding [
].
Transketolase (
) (TK) catalyzes the reversible transfer of a two-carbon ketol unit from xylulose 5-phosphate to an
aldose receptor, such as ribose 5-phosphate, to form sedoheptulose 7-phosphate and glyceraldehyde 3- phosphate. Thisenzyme, together with transaldolase, provides a link between the glycolytic and pentose-phosphate pathways. TK requires
thiamine pyrophosphate as a cofactor. This group includes
two proteins from the yeast Saccharomyces cerevisiae (Baker's yeast) but excludes dihydroxyactetone synthases(formaldehyde transketolases) from various yeasts and the even more distant mammalian
transketolases. Among the family of thiamine diphosphate-dependent enzymes that includestransketolases, dihydroxyacetone synthases, pyruvate dehydrogenase E1-beta subunits, and
deoxyxylulose-5-phosphate synthases, mammalian and bacterial transketolases seem not tobe orthologous.
