SII-SWORD/CoKE huggingface dataset:
VapC-like Sll0205 protein, PIN domain (PIN_Sll0205)
Type: Domain

This entry represents the virulence associated protein C (VapC)-like PIN (PilT N terminus) domain of the Synechocystis sp. (strain PCC 6803) Sll0205 protein and other uncharacterised homologues. They are similar to the PIN domains of the Mycobacterium tuberculosis VapC and Neisseria gonorrhoeae FitB toxins of the prokaryotic toxin/antitoxin operons, VapBC and FitAB, respectively, which are believed to be involved in growth inhibition by regulating translation. These toxins are nearly always co-expressed with an antitoxin, a cognate protein inhibitor, forming an inert protein complex. Disassociation of the protein complex activates the ribonuclease activity of the toxin by an, as yet undefined mechanism . VapC-like PIN domains are homologues of flap endonuclease-1 (FEN1)-like PIN domains, but lack the extensive arch/clamp region and the H3TH (helix-3-turn-helix) domain, an atypical helix-hairpin-helix-2-like region, seen in FEN1-like PIN domains . PIN domains within this subgroup contain four highly conserved acidic residues. These putative active site residues are thought to bind Mg2+ and/or Mn2+ ions and be essential for single-stranded ribonuclease activity .
YchF, N-terminal (YchF_N)
Type: Domain

YchF is a member of the Obg family, which includes four other subfamilies of GTPases: Obg, DRG, Ygr210, and NOG1. Obg is an essential gene that is involved in DNA replication in C. crescentus and Streptomyces griseus and is associated with the ribosome. Several members of the family, including YchF, possess the TGS domain related to the RNA-binding proteins. Experimental data and genomic analysis suggest that YchF may be part of a nucleoprotein complex and may function as a GTP-dependent translational factor .

This entry represents the N-terminal domain of YchF and homologues.
Pseudouridine synthase Pus3-like (Pus3-like)
Type: Family

This group consists of eukaryotic pseudouridine synthases similar to S. cerevisiae Pus3p. Pseudouridine synthases catalyze the isomerization of specific uridines in an RNA molecule to pseudouridines (5-ribosyluracil, psi) . No cofactors are required. S. cerevisiae Pus3p makes psi38 and psi39 in tRNAs . Mouse Pus3 has been shown to makes psi38 and, possibly also psi 39, in tRNAs . Psi38 and psi39 are highly conserved in tRNAs from eubacteria, archea and eukarya .
Pseudouridine synthase PUS1/ PUS2-like (PUS1/PUS2-like)
Type: Family

This group consists of eukaryotic pseudouridine synthases similar to Saccharomyces cerevisiae Pus1 and Pus2 . Pseudouridine synthases catalyze the isomerization of specific uridines in an RNA molecule to pseudouridines (5-ribosyluracil, psi) . No cofactors are required. S. cerevisiae Pus1 catalyzes the formation of psi34 and psi36 in the intron-containing tRNAIle, psi35 in the intron-containing tRNATyr, psi27 and/or psi28 in several yeast cytoplasmic tRNAs and, psi44 in U2 small nuclear RNA (U2 snRNA) . The presence of the intron is required for the formation of psi 34, 35 and 36. In addition S. cerevisiae PUS1 makes are psi 26, 65 and 67. C. elegans Pus1 does not modify psi44 in U2 snRNA . Mouse Pus1 makes psi27/28 in pre- tRNASer , tRNAVal and tRNAIle, psi 34/36 in tRNAIle and, psi 32 and potentially 67 in tRNAVal. Psi44 in U2 snRNA and psi32 in tRNAs are highly phylogenetically conserved. Psi 26,27,28,34,35,36,65 and 67 in tRNAs are less highly conserved. Mouse Pus1p regulates nuclear receptor activity through pseudouridylation of Steroid Receptor RNA Activator . Missense mutation in human PUS1 causes mitochondrial myopathy and sideroblastic anemia (MLASA) .
Elongation factor Tu (EF-Tu), GTP-binding domain (EF-Tu_GTP-bd)
Type: Domain

This entry represents the GTP-binding domain found in translation elongation factor EF-Tu and its homologues from bacteria, mitochondria, and chloroplasts . EF-Tu is one of several GTP-binding translation factors found in the larger family of GTP-binding elongation factors. The eukaryotic counterpart, eukaryotic translation elongation factor 1 (eEF-1 alpha), is excluded from this entry. EF-Tu is one of the most abundant proteins in bacteria, as well as one of the most highly conserved, and in a number of species the gene is duplicated with identical function. When bound to GTP, EF-Tu can form a complex with any (correctly) aminoacylated tRNA except those for initiation and for selenocysteine, in which case EF-Tu is replaced by other factors. Transfer RNA is carried to the ribosome in these complexes for protein translation .
HPS/KGPDC domain (HPS/KGPDC)
Type: Domain

This entry represents a domain found in 3-keto-L-gulonate 6-phosphate decarboxylase (KGPDC) and D-arabino-3-hexulose-6-phosphate synthase (HPS). In some bacteria and archaea HPS is found as part of the bifunctional enzyme Fae/Hps . KGPDC catalyzes the formation of L-xylulose 5-phosphate and carbon dioxide from 3-keto-L-gulonate 6-phosphate as part of the anaerobic pathway for L-ascorbate utilization in some eubacteria. HPS catalyzes the formation of D-arabino-3-hexulose-6-phosphate from D-ribulose 5-phosphate and formaldehyde in microorganisms that can use formaldehyde as a carbon source. Both catalyze reactions that involve the Mg2+-assisted formation and stabilization of 1,2-enediolate reaction intermediates .
Methionyl-tRNA formyltransferase, N-terminal domain (Met-tRNA-FMT_N)
Type: Domain

This entry represents the methionyl-tRNA formyltransferase (Met-tRNA-FMT), N-terminal formyltransferase domain.

Met-tRNA-FMT transfers a formyl group from N-10 formyltetrahydrofolate to the amino terminal end of a methionyl-aminoacyl-tRNA acyl moiety, yielding formyl-Met-tRNA. Formyl-Met-tRNA plays an essential role in protein translation initiation by forming a complex with IF2. The formyl group plays a dual role in the initiator identity of N-formylmethionyl-tRNA by promoting its recognition by IF2 and by impairing its binding to EFTU-GTP. The N-terminal domain contains a Rossmann fold and it is the catalytic domain of the enzyme .
Methanocaldococcus jannaschii dihydropteroate synthase-like, MBL-fold metallo hydrolase domain (DHPS-like_MBL-fold)
Type: Domain

Proteins containing this domain includes Methanocaldococcus jannaschii 7,8-dihydropterin-6-methyl-4-(beta-D-ribofuranosyl)-aminobenzene-5'-phosphate synthase (EC 2.5.1.15), a folate biosynthetic enzyme also known as dihydropteroate synthase and 7,8 dihydropteroate synthase . Proteins containing this domain also include Thermoanaerobacter tengcongensis Tflp, which is a ferredoxin-like protein . These proteins belong to the MBL-fold metallo-hydrolase superfamily which is comprised mainly of hydrolytic enzymes which carry out a variety of biological functions .
PTS system lactose-specific EIICB component, IIB domain (PTS_IIB)
Type: Domain

This entry represents the IIB domain found in subunit IIB of enzyme II (EII) of the lactose-specific phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) from Firmicutes as well as Actinobacteria . In this system, EII is a lactose-specific permease with two cytoplasmic domains (IIA and IIB) and a transmembrane channel IIC domain. The IIC and IIB domains are expressed as a single protein from the lac operon. The IIB domain fold includes a central four-stranded parallel open twisted β-sheet flanked by α-helices on both sides . The seven major PTS systems with this IIB fold include lactose, chitobiose/lichenan, ascorbate, galactitol, mannitol, fructose, and a sensory system with similarity to the bacterial bgl system .
Vitamin K epoxide reductase, Actinobacteria-type (VKOR_Actinobacteria)
Type: Domain

Proteins containing this domain include vitamin K epoxide reductase (VKOR) mostly present in actinobacteria. VKOR (also named VKORC1) is an integral membrane protein that catalyzes the reduction of vitamin K 2,3-epoxide and vitamin K to vitamin K hydroquinone, an essential co-factor subsequently used in the γ-carboxylation of glutamic acid residues in blood coagulation enzymes. All homologues of VKOR contain an active site CXXC motif, which is switched between reduced and disulfide-bonded states during the reaction cycle . In some bacterial homologues, the VKOR domain is fused with domains of the thioredoxin family of oxidoreductases which may function as redox partners in initiating the reduction cascade .
Class II Histidinyl-tRNA synthetase (HisRS)-like catalytic core domain (HisRS-like_core)
Type: Domain

HisRS is a homodimer and is responsible for the attachment of histidine to the 3' OH group of ribose of the appropriate tRNA. This domain is primarily responsible for ATP-dependent formation of the enzyme bound aminoacyl-adenylate. Class II assignment is based upon its structure and the presence of three characteristic sequence motifs . This domain is also found at the C terminus of eukaryotic GCN2 protein kinase and at the N terminus of the ATP phosphoribosyltransferase accessory subunit, HisZ. HisZ along with HisG catalyze the first reaction in histidine biosynthesis. HisZ is found only in a subset of bacteria and differs from HisRS in lacking a C-terminal anti-codon binding domain .
Cupredoxin-like protein, Cyanobacteria (Cupredoxin-like_Cyanobacteria)
Type: Domain

This entry represents a group of uncharacterised proteins from Cyanobacteria that share protein sequence similarity with cupredoxin. Cupredoxins are blue copper proteins because they have an intense blue color due to the presence of a mononuclear type 1 (T1) copper site. Structurally, the cupredoxin-like fold consists of a β-sandwich with 7 strands in 2 β-sheets, which is arranged in a Greek-key β-barrel. Some of these proteins have lost the ability to bind copper. Majority of family members contain multiple cupredoxin domain repeats; ceruloplasmin and coagulation factors V/VIII have six repeats; Laccase, ascorbate oxidase, and spore coat protein A, and multicopper oxidase CueO contain three repeats; and nitrite reductase has two repeats. Others are mono-domain cupredoxins, such as plastocyanin, pseudoazurin, plantacyanin, azurin, rusticyanin, stellacyanin, quinol oxidase and the periplasmic domain of cytochrome c oxidase subunit II .
FwdD/FmdC, molybdopterin dinucleotide-binding domain (FmdC/FwdD_MopB-bd)
Type: Domain

This entry represents the C terminus of subunit C of molybdenum formylmethanofuran dehydrogenase (FmdC) and subunit D of tungsten formylmethanofuran dehydrogenase (FwdD), and other related proteins from Archaea . Formylmethanofuran dehydrogenase catalyzes the first step in methane formation from CO2 in methanogenic archaea and some eubacteria . This domain is of the conserved molybdopterin-binding C-terminal (MopB_CT) region present in many, but not all, MopB homologues.
IS607-like transposase, catalytic domain (IS607_transposase-like)
Type: Domain

Proteins containing this domain often also contain a DNA binding domain with homology to MerR/SoxR located N-terminal to the catalytic domain. Proteins containing this domain catalyze the transposition of insertion sequence (IS) elements such as IS607 from Helicobacter and IS1535 from Mycobacterium, and similar proteins from other bacteria and several archaeal species. IS elements are DNA segments that move to new sites in prokaryotic and eukaryotic genomes causing insertion mutations and gene rearrangements . This domain belongs to a larger group of catalytic domains found in serine recombinases, which catalyze site-specific recombination of DNA molecules by a concerted, four-strand cleavage and rejoining mechanism which involves a transient phosphoserine linkage between DNA and the enzyme. They are functionally versatile and include resolvases, invertases, integrases, and transposases .
Ferritin, prokaryotic-type (Ferritin_prok)
Type: Family

This entry represents non-heme Ferritins found in archaea and bacteria. They belong to a broad superfamily of ferritin-like diiron-carboxylate proteins. The ferritin protein shell is composed of 24 protein subunits arranged in 432-point symmetry. Each protein subunit, a four-helix bundle with a fifth short terminal helix, contains a dinuclear ferroxidase centre (H type) . Unique to this group of proteins is a third metal site in the ferroxidase centre . Iron storage involves the uptake of iron (II) at the protein shell, its oxidation by molecular oxygen at the ferroxidase centres, and the movement of iron (III) into the cavity for deposition as ferrihydrite .
Aldolase FbaB-like, archaeal-type (FbaB-like)
Type: Family

This family represents class I fructose-bisphosphate aldolase DhnA/FbaB found in some bacteria and in archaea. Catalysis of the enzymes proceeds via a Schiff-base mechanism like other class I aldolases, although this subfamily is clearly divergent based on sequence similarity to other class I and class II (metal dependent) aldolase subfamilies . This entry also includes LsrF and other enzymes with high homology to class I aldolase FbaB .
Lactate-binding periplasmic protein TTHA0766 (TTHA0766)
Type: Family

This entry includes a lactate binding TRAP transporter TTHA0766 and related proteins . TRAP transporters are a large family of solute transporters ubiquitously found in bacteria and archaea. They are comprised of a periplasmic substrate-binding protein (SBP; often called the P subunit) and two unequally sized integral membrane components: a large transmembrane subunit involved in the translocation process (the M subunit) and a smaller membrane of unknown function (the Q subunit). The driving force of TRAP transporters is provided by electrochemical ion gradients (either protons or sodium ions) across the cytoplasmic membrane, rather than ATP hydrolysis. This substrate-binding domain belongs to the type 2 periplasmic binding fold protein superfamily (PBP2). The PBP2 proteins are typically comprised of two globular subdomains connected by a flexible hinge and bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap .
Alpha-keto acid binding periplasmic protein (TakP/all3028)
Type: Family

This entry includes TRAP transporters that binds to ketoacids such as pyruvate and alpha-ketobutyrate, xylulose, and other unknown ligands . TRAP transporters are a large family of solute transporters ubiquitously found in bacteria and archaea. They are comprised of a periplasmic substrate-binding protein (SBP; often called the P subunit) and two unequally sized integral membrane components: a large transmembrane subunit involved in the translocation process (the M subunit) and a smaller membrane of unknown function (the Q subunit). The driving force of TRAP transporters is provided by electrochemical ion gradients (either protons or sodium ions) across the cytoplasmic membrane, rather than ATP hydrolysis. This substrate-binding domain belongs to the type 2 periplasmic binding fold protein superfamily (PBP2). The PBP2 proteins are typically comprised of two globular subdomains connected by a flexible hinge and bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap .
CTP:phosphocholine cytidylyltransferase domain (CCT)
Type: Domain

This entry represents the catalytic domain of CTP:phosphocholine cytidylyltransferase (CCT) . It is also found in CTP:phosphoethanolamine cytidylyltransferase (ECT). ECT is composed of two tandem cytidylyltransferase (CT) domains; this entry corresponds the N-terminal CT domain, which is known to contribute to its catalytic activity . CCT catalyzes the condensation of CTP and phosphocholine to form CDP-choline as the rate-limiting and regulatory step in the CDP-choline pathway. Similarly, ECT catalyzes the condensation of CTP and ethanolamine to form CDP-ethanolamine.
Type I (cytosolic) L-asparaginase (L-asparaginase_I)
Type: Family

Asparaginases (amidohydrolases,

) are enzymes that catalyze the hydrolysis of asparagine to aspartic acid and ammonia. In bacteria, there are two classes of amidohydrolases. This entry represents type I L-asparaginases, which are highly specific for asparagine and localized in the cytosol . Type I L-asparaginase acts as a dimer . A conserved threonine residue is thought to supply the nucleophile hydroxy-group that attacks the amide bond. Many bacterial L-asparaginases have both L-asparagine and L-glutamine hydrolysis activities, to a different degree, and some of them are annotated as asparaginase/glutaminase . One example of an enzyme with no L-glutaminase activity is the type I L-asparaginase from Wolinella succinogenes .
Acyl-CoA dehydrogenase family member 10/11, N-terminal (ACAD10_11_N)
Type: Domain

This entry represents the N-terminal domains of vertebrate ACAD10 and ACAD11, and similar uncharacterised bacterial and eukaryotic proteins. ACADs are a family of flavoproteins that are involved in the beta-oxidation of fatty acyl-CoA derivatives. ACAD deficiency can cause metabolic disorders including muscle fatigue, hypoglycemia, and hepatic lipidosis. There are at least 11 distinct ACADs, some of which show distinct substrate specificities to either straight-chain or branched-chain fatty acids . ACAD10 is widely expressed in human tissues and highly expressed in liver, kidney, pancreas, and spleen. ACAD10 and ACAD11 are both significantly expressed in human brain tissues . They contain a long N-terminal domain with similarity to phosphotransferases with a Protein Kinase fold, which is absent in other ACADs. They may exhibit multiple functions in acyl-CoA oxidation pathways. ACAD11 utilises substrates with carbon chain lengths of 20 to 26, with optimal activity towards C22CoA. ACAD10 may be associated with an increased risk in type II diabetes .
N-Acetyl-L-glutamate kinase, cyclic (NAGK-C)
Type: Family

The cyclic N-Acetyl-L-glutamate kinase (NAGK-C) catalyzes the phosphorylation of the γ-COOH group of N-acetyl-L-glutamate (NAG) by ATP in the second step of arginine biosynthesis found in some bacteria and photosynthetic organisms using the non-acetylated, cyclic route of ornithine biosynthesis. In this pathway, glutamate is first N-acetylated and then phosphorylated by NAGK to give phosphoryl NAG, which is converted to NAG-ornithine. There are two variants of the arginine biosynthesis pathway. In the cyclic one, typified by Thermotoga maritima and Pseudomonas aeruginosa, the acetyl group is recycled by reversible transacetylation from acetylornithine to glutamate. The phosphorylation of NAG by NAGK is feedback inhibited by arginine. In photosynthetic organisms, NAGK is the target of the nitrogen-signaling protein PII. Hexameric formation of NAGK domains appears to be essential to both arginine inhibition and NAGK-PII complex formation .
GPAT/DHAPAT, acyltransferase domain (GPAT/DHAPAT_LPLAT)
Type: Domain

Proteins containing this domain are lysophospholipid acyltransferases (LPLATs) such as dihydroxyacetone phosphate acyltransferase (DHAPAT, also known as 1 glycerol-3-phosphate O-acyltransferase 1) and glycerol 3-phosphate acyltransferases GPAT1 and GPAT2 . They are acyltransferases of de novo and remodeling pathways of glycerophospholipid biosynthesis which catalyze the incorporation of an acyl group from either acylCoAs or acyl-acyl carrier proteins (acylACPs) into acceptors such as dihydroxyacetone phosphate or glycerol 3-phosphate respectively .
Formyltetrahydrofolate deformylase, C-terminal hydrolase domain (Formyl-FH4-Hydrolase_C)
Type: Domain

Formyl-FH4 Hydrolase catalyzes the hydrolysis of 10-formyltetrahydrofolate (formyl-FH4) to FH4 and formate. Formate is the substrate of phosphoribosylglycinamide transformylase for step three of de novo purine nucleotide synthesis. Formyl-FH4 hydrolase has been proposed to regulate the balance of FH4 and C1-FH4 in the cell. The enzyme uses methionine and glycine to sense the pools of C1-FH4 and FH4, respectively .
MJ0421-like THUMP domain (MJ0421-like_THUMP)
Type: Domain

Proteins containing this domain, including MJ0421 from Methanocaldococcus jannaschii
, are a group of uncharacterised archaeal proteins that contain an N-terminal THUMP domain and a C-terminal SPOUT RNA methyltransferase domain. The THUMP domain is named after thiouridine synthases, methylases and PSUSs. The domain consists of about 110 amino acid residues. It is predicted to be an RNA-binding domain and probably functions by delivering a variety of RNA modification enzymes to their targets .
N-Acetyl-L-glutamate kinase, noncyclic (NAGK-NC)
Type: Family

The noncyclic N-Acetyl-L-glutamate kinase (NAGK-NC) catalyzes the phosphorylation of the γ-COOH group of N-acetyl-L-glutamate (NAG) by ATP in the second step of microbial arginine biosynthesis using the acetylated, noncyclic route of ornithine biosynthesis. There are two variants of the arginine biosynthesis pathway. In this one, typified by the pathway in Escherichia coli, glutamate is acetylated by acetyl-CoA and acetylornithine is deacylated hydrolytically. In this pathway, feedback inhibition by arginine occurs at the initial acetylation of glutamate and not at the phosphorylation of NAG by NAGK. The Escherichia coli NAGK is a homodimer .
Peptide chain release factor 3, GTP-binding domain (RF3_GTP-bd)
Type: Domain

This entry reprsents the GTP-binding domain found in peptide chain release factor 3.
PAE1087-like, metallophosphatase domain (PAE1087_MPP)
Type: Domain

PAE1087 is an uncharacterised Pyrobaculum aerophilum protein with a metallophosphatase domain. The domain present in members of this family 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 .
N-Acetyl-L-glutamate kinase, fungal-type (NAGK-fArgBP)
Type: Domain

The N-Acetyl-L-glutamate kinase (NAGK) of the fungal arginine-biosynthetic pathway (fArgBP) is a nuclear-encoded, mitochondrial polyprotein precursor with an N-terminal NAGK (ArgB) domain (this entry), a central DUF619 domain, and a C-terminal reductase domain (ArgC, N-Acetylglutamate Phosphate Reductase, NAGPR). The precursor is cleaved in the mitochondria into two distinct enzymes (NAGK-DUF619 and NAGPR). Native molecular weights of these proteins indicate that the kinase is an octamer whereas the reductase is a dimer. This entry also includes some gammaproteobacteria (Xanthomonas and Xylella) NAG kinases with an N-terminal NAGK (ArgB) domain and a C-terminal DUF619 domain. The DUF619 domain is described as a putative distant homologue of the acetyltransferase, ArgA, predicted to function in NAG synthase association in fungi. Eukaryotic sequences have an N-terminal mitochondrial transit peptide .