SII-SWORD/CoKE huggingface dataset:
Aspartate-semialdehyde dehydrogenase (Asp_semialdehyde_DH)
Type: Family

This entry represents the entire asparate-semialdehyde dehydrogenase family.

Aspartate-semialdehyde dehydrogenase (

), the second enzyme in the aspartate pathway, converts aspartyl phosphate to aspartate-semialdehyde, the branch point intermediate between the lysine and threonine/methionine pathways. Based on sequence alignments, the aspartate-semialdehyde dehydrogenase family appears to have at least three distinct subfamilies. Most studies have been performed on enzymes isolated from Gram-negative bacteria . The N-terminal domain forms the active site and NADP-binding pocket, while C-terminal domain is primarily involved in hydrophobic intersubunit contacts. The catalytic mechanism involves the formation of a covalent thioester acyl-enzyme intermediate mediated through nucleophilic attack by an active site cysteine residue on the substrate aspartyl phosphate. Release of inorganic phosphate is followed by hydride transfer from NADPH to yield the product. The recently described archaeal structure suggests that the two subgroups of aspartate semi-aldehyde dehydrogenase share similar structures and have an identical catalytic mechanism, despite their relatively low sequence identity . Unlike the bacterial enzymes, the archaeal enzyme utilised both NAD and NADP as cofactor.

Bacteria, plants and fungi metabolise aspartic acid to produce four amino acids -lysine, threonine, methionine and isoleucine -in a series of reactions known as the aspartate pathway. Additionally, several important metabolic intermediates are produced by these reactions, such as diaminopimelic acid, an essential component of bacterial cell wall biosynthesis, and dipicolinic acid, which is involved in sporulation in Gram-positive bacteria. Members of the animal kingdom do not posses this pathway and must therefore acquire these essential amino acids through their diet. Research into improving the metabolic flux through this pathway has the potential to increase the yield of the essential amino acids in important crops, thus improving their nutritional value. Additionally, since the enzymes are not present in animals, inhibitors of them are promising targets for the development of novel antibiotics and herbicides. For more information see .
Alkyl hydroperoxide reductase subunit F (Alkyl_hydroperoxide_Rdtase_suF)
Type: Family

Alkyl hydroperoxide reductase subunit F (AhpF) is a homodimeric flavoenzyme which catalyzes the NADH-dependent reduction of the peroxiredoxin AhpC, which then reduces hydrogen peroxide and organic hydroperoxides. AhpF contains an NTD containing two contiguous TRX-fold subdomains similar to Pyrococcus furiosus protein disulfide oxidoreductase (PfPDO). It also contains a catalytic core similar to TRX reductase containing FAD and NADH binding domains with an active site disulfide . The NAD(P)H binding domain of AhpF may act to resolve the disulphide which forms after oxidation of the active site cysteine in AphC . This protein contains two paired conserved cysteine motifs, CxxC and CxHCDGP.
Arylsulfatase (Arylsulfatase)
Type: Family

Arylsulphatase from the multicellular green flagellate Volvox carteri is a 649 amino acid polypeptide . Like arylsulphatases in other organisms, it occurs in the periplasm. In Pseudomonas aeruginosa PAO1, however, this enzyme does not appear to be periplasmic or membrane-associated .

The synthesis of arylsufatase is repressed when sulphate, cysteine or thiocyanate is the only source for growth. A post-translational protein modification where a cysteine is replaced by a serinesemialdehydepresence has been described in two human sulphatases and in V. carteri. This modification is required for the catalytic activity of sulphatases and may be present in all sulphatases of eukaryotic origin .
tRNA-cytidine(32) 2-sulfurtransferase (tRNA_Cyd_32_2_STrfase)
Type: Family

This entry represents tRNA-cytidine(32) 2-sulfurtransferase (also known as 2-thiocytidine tRNA biosynthesis protein, TtcA) and its homologues.

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction . These proteins differ widely in size and oligomeric state, and have limited sequence homology . The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric . Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices , and are mostly dimeric or multimeric, containing at least three conserved regions . However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c .

tRNA-cytidine(32) 2-sulfurtransferase (also known as 2-thiocytidine tRNA biosynthesis protein TtcA) is required for the thiolation of cytidine in position 32 of tRNA, to form 2-thiocytidine (s(2)C32). The modified nucleoside 2-thiocytidine (s(2)C) has so far been found in tRNA from archaea and bacteria. The TtcA protein family is characterised by the existence of both a PP-loop and a Cys-X(1)-X(2)-Cys motif in the central region of the protein but can be divided into two distinct groups based on the presence and location of additional Cys-X(1)-X(2)-Cys motifs in terminal regions of the sequence. Mutant analysis showed that both cysteines in this central conserved Cys-X(1)-X(2)-Cys motif are required for the formation of s(2)C .
Chromosome partition protein MukB (MukB)
Type: Family

MukB is a 170kDa protein that is involved in ATP-dependent chromosome partitioning during cell division in Escherichia coli . Its domain structure is reminiscent of the eukaryotic motor proteins kinesin and myosin . MukB, like SMC (structural maintenance of chromosomes) proteins with which it shares function, has a dimeric structure and similar domain architecture . It is a filamentous protein with globular domains at the ends, and also having DNA binding and nucleotide binding abilitiesIt forms a homodimer with a rod-and-hinge structure with a pair of large, C-terminal globular domains at one end and a pair of small, N-terminal globular domains at the other . The N-terminal domain carries a putative Walker A nucleotide-binding region and the C-terminal domain has been shown to bind to DNA .
Peptidase M54, archaemetzincin, archaeal/bacterial (Pept_M54_archaemetzncn_arc/bac)
Type: Family

This entry represents the archaeal zinc-dependent peptidases and homologous bacterial sequences that belong to the MEROPS peptidase family M54, more commonly known as the archaemetzincins.

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .
8-oxoguanine DNA glycosylase/AP lyase Ogg (DNA_glyclase/AP_lyase_Ogg)
Type: Family

This entry represents bifunctional, thermostable 8-oxoguanine DNA glycosylase/DNA lyase enzymes (OGG or OG glycosylases), which are involved in base excision repair of DNA damaged by oxidation or by mutagenic agents . Most damage to bases in DNA is repaired by the base excision repair pathway . These enzymes have both DNA glycosylase activity (

) and AP lyase activity (

). OGG1 enzymes are active only towards the removal of 8-oxoguanine .
Pirin (Pirin)
Type: Family

Eukaryotic pirins are highly conserved nuclear proteins that may function as transcriptional regulators with a role in apoptosis . Prokaryotic homologues have also been identified. Both bacterial and human pirins have been shown to possess quercetinase activity , although this is not universally true for all family members - YhaK (

), for example, displays no such enzymatic activity .

Pirin is composed of two structurally similar domains arranged face to face. Although the two domains are similar, the C-terminal domain of pirin differs from the N-terminal domain as it does not contain a metal binding site and its sequence does not contain the conserved metal-coordinating residues .

Pirin is considered a member of the cupin superfamily on the basis of primary sequence and structural similarity. The presence of a metal binding site in the N-terminal β-barrel of pirin, may be significant in its interaction with Bcl-3 and nuclear factor I (NFI) and role in regulating NF-kappaB transcription factor activity .
ATPase, PP-loop, MJ1638-related (ATPase_PP-loop_MJ1638)
Type: Family

The PP-loop motif appears to be a modified version of the P-loop of nucleotide binding domain that is involved in phosphate binding . Named PP-motif, since it appears to be a part of a previously uncharacterised ATP pyrophophatase domain. ATP sulfurylases, Escherichia coli NtrL, and Bacillus subtilis OutB consist of this domain alone. In other proteins, the pyrophosphatase domain is associated with amidotransferase domains (type I or type II), a putative citrulline-aspartate ligase domain or a nitrilase/amidase domain.

PP-loop ATPases are part of the HUP domain class (after HIGH-signature proteins, UspA, and PP-ATPase), along with the nucleotide-binding domains of class I aminoacyl-tRNA synthetases, UspA protein (USPA domains), photolyases, and electron transport flavoproteins (ETFP). The HUP domain is a distinct class of α/β domain .

This group represents MJ1638-type predicted PP-loop ATPases.
Opacity-associated protein B (OapB)
Type: Family

This group represents an opacity-associated protein B .
SRP-independent targeting protein 3 (SND3_fun)
Type: Family

SRP-independent targeting protein 3 (SND3, previously known as PHO88) is localized to the endoplasmic reticulum (ER). SND3 works together with SND1 and SND2; these proteins function in parallel with the SRP and GET pathways to target a broad range of substrates to the ER. The SND proteins constitute an alternative targeting route to the ER . SND3/PHO88 was first identified as a Saccharomyces cerevisiae protein involved in inorganic phosphate transport .
Midasin (Midasin)
Type: Family

Midasin (MDN1, REA1) is a is a member of the AAA(+) family of ATPases. It is a nuclear chaperone required for maturation and nuclear export of pre-60S ribosome subunits .
DNA-damage-repair/toleration protein, DRT102 (DRT102)
Type: Family

Plants employ DNA-damage-repair/toleration (DRT) activities to resist UV radiation. This family represents DNA-damage-repair/toleration protein DRT102 .
Biotinidase-like, eukaryotic (Biotinidase-like_euk)
Type: Family

These secondary amidases participate in vitamin recycling. Biotinidase (

) has both a hydrolase and a transferase activity. It hydrolyses free biocytin or small biotinyl-peptides produced during the proteolytic degradation of biotin-dependent carboxylases, to release free biotin (vitamin H), and it can transfer biotin to acceptor molecules such as histones. Biotinidase deficiency in humans is an autosomal recessive disorder characterised by neurological and cutaneous symptoms .
Protoglobin (Protoglobin)
Type: Family

Protoglobins (Pgbs) are single-domain globins of yet unknown biological function . Included in this subfamily are Pgbs from the strictly anaerobic methanogen Methanosarcina acetivorans (MaPgb) and from the obligate aerobic hyperthermophile Aeropyrum pernix (ApPgb).

MaPgb is a dimeric globin which in addition to the 3-on-3 helical sandwich contains an N-terminal extension. This extension, along with other Pgb-specific loops buries the heme within the protein; two orthogonal apolar tunnels grant access of small ligand molecules to the heme. Like other globins, MaPgb can bind O2, CO and NO reversibly in vitro, however it has as unusually low O2 dissociation rate, along with a large structural distortion of the heme moiety . CO binding to and dissociation from the heme occurs through biphasic kinetics. ApPgb also contains heme, and can bind O2, CO and NO . This subfamily belongs to a family which includes the globin-coupled-sensors (GCSs) and single-domain sensor globins. It has been demonstrated that Pgbs and other single-domain globins can function as sensors, when coupled to an appropriate regulator domain .
Peptidase S8A, bacillopeptidase F (Pept_S8A_Bpr)
Type: Family

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes . They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence . Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases .

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base . The geometric orientations of the catalytic residues are similar between families, despite different protein folds . The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) .

Limited proteolysis of most large protein precursors is carried out in vivo by the subtilisin-like pro-protein convertases. Many important biological processes such as peptide hormone synthesis, viral protein processing and receptor maturation involve proteolytic processing by these enzymes . The subtilisin-serine protease (SRSP) family hormone and pro-protein convertases (furin, PC1/3, PC2, PC4, PACE4, PC5/6, and PC7/7/LPC) act within the secretory pathway to cleave polypeptide precursors at specific basic sites, generating their biologically active forms. Serum proteins, pro-hormones, receptors, zymogens, viral surface glycoproteins, bacterial toxins, amongst others, are activated by this route . The SRSPs share the same domain structure, including a signal peptide, the pro-peptide, the catalytic domain, the P/middle or homo B domain, and the C terminus.

This group represents bacillopeptidase F (Bpr) an extracellular serine protease that is expressed at the beginning of the stationary phase . Members of this family belong to MEROPS peptidase family S8, subfamily S8A (subtilisin, clan SB). Bpr is required for the processing and activation of the extracellular metalloprotease (Mpr, glutamyl endopeptidase

) in Bacillus subtilis .
PHO85 cyclin 1/2/9 (PHO85_cyclin_1/2/9)
Type: Family

Pho85 is a non-essential cyclin-dependent kinase (CDK) involved in the cell cycle . Pho85 is controlled by 10 cyclins that may be grouped into 2 families according to cyclin box sequence similarity : the Pho80 family (Pho80, Pcl6, Pcl7, Pcl8, and Pcl10) and the Pcl1,2 family (Pcl1, Pcl2, Pcl5, Pcl9 and ClG1). Except Pcl5, the rest of the Plc1,2 family members show a tightly controlled cell cycle pattern of expression: Pcl9 is produced in late M phase and during early G1, Pcl2 in late M until late G1, and Pcl1 during late G1 .

This entry includes Pcl1, Pcl2 and Pcl9.
Sperm surface protein Sp17 (Sp17)
Type: Family

Sp17 was originally proposed to be a sperm-specific protein that plays a role in sperm-egg interactions by binding to the zona pellucida via two conserved heparin-binding motifs . Later, it was found expressed in other tissues and may have a regulatory role in an A-kinase anchoring protein complex .
Protease, Mu phage/prophage I type (Phage_Mu_Gp1)
Type: Family

This entry includes protease I (Gp1) from Bacteriophage Mu. It is involved in virion assembly/maturation and may cleave the portal protein to yield mature procapsids competent for DNA packaging .
ADP-ribosylarginine hydrolase (ADP-ribosylarg_hydro)
Type: Family

This enzyme catalyzes the reverse reaction of mono-ADP-ribosylation by removing ADP-ribose from arginine residues in ADP-ribosylated proteins. NAD:arginine ADP-ribosyltransferases and ADP-ribosylarginine hydrolases catalyse opposing arms of the putative ADP-ribosylation cycle.
Pyruvate decarboxylase/indolepyruvate decarboxylase-like (PDC/IPDC-like)
Type: Family

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 .
Hemolectin/hemocytin (Hml)
Type: Family

This group represents arthropod hemolectin/hemocytin, which are proteins with structural similarity to the human von Willebrand factor , each containing a single proteinase inhibitor domain homologue related to MEROPS proteinase inhibitor family I8 (clan IA).
DNA repair protein Rev1 (REV1)
Type: Family

Rev1 is a deoxycytidyl transferase involved in translesion DNA synthesis (TLS) pathway to bypass DNA lesions during replication . During TLS, Y-family DNA polymerase (Poleta, Polkappa, Poliota and Rev1) incorporates a nucleotide opposite the DNA lesion, and then Polzeta (consitst of Rev3 and Rev7) carries out primer extension. Rev1 is a unique member of the Y polymerase family, since its catalytic activity is limited to DNA-dependent, deoxycytidyl transferase activity .
Bifunctional ribulose 5-phosphate reductase/CDP-ribitol pyrophosphorylase (CDP-ribitol_syn)
Type: Family

This group represents a bifunctional ribulose 5-phosphate reductase/CDP-ribitol pyrophosphorylase. It catalyzes the NADPH-dependent reduction of D-ribulose 5-phosphate to D-ribitol 5-phosphate and the further reaction of D-ribitol 5-phosphate with CTP to form CDP-ribitol .
Glycine/sarcosine/betaine reductase complex, protein C, alpha subunit (Gly_reductase_pC_asu)
Type: Family

This group represents a glycine/sarcosine/betaine reductase complex, component C, alpha subunit. Please see the following relevant references: .
Fucose-1-phosphate guanylyltransferase (Fucose-1-phosphate_GuaTrfase)
Type: Family

This group represents fucose-1-phosphate guanylyltransferase. Please see the following relevant reference: .
ATPase, PP-loop, MJ1599-related (ATPase_PP-loop_MJ1599)
Type: Family

The PP-loop motif appears to be a modified version of the P-loop of nucleotide binding domain that is involved in phosphate binding . Named PP-motif, since it appears to be a part of a previously uncharacterised ATP pyrophophatase domain. ATP sulfurylases, Escherichia coli NtrL, and Bacillus subtilis OutB consist of this domain alone. In other proteins, the pyrophosphatase domain is associated with amidotransferase domains (type I or type II), a putative citrulline-aspartate ligase domain or a nitrilase/amidase domain.

PP-loop ATPases are part of the HUP domain class (after HIGH-signature proteins, UspA, and PP-ATPase), along with the nucleotide-binding domains of class I aminoacyl-tRNA synthetases, UspA protein (USPA domains), photolyases, and electron transport flavoproteins (ETFP). The HUP domain is a distinct class of α/β domain .

This entry represents MJ1599-type predicted PP-loop ATPases.
ATPase, PP-loop, MJ1016-related (ATPase_PP-loop_MJ1016)
Type: Family

The PP-loop motif appears to be a modified version of the P-loop of nucleotide binding domain that is involved in phosphate binding . Named PP-motif, since it appears to be a part of a previously uncharacterised ATP pyrophophatase domain. ATP sulfurylases, Escherichia coli NtrL, and Bacillus subtilis OutB consist of this domain alone. In other proteins, the pyrophosphatase domain is associated with amidotransferase domains (type I or type II), a putative citrulline-aspartate ligase domain or a nitrilase/amidase domain.

PP-loop ATPases are part of the HUP domain class (after HIGH-signature proteins, UspA, and PP-ATPase), along with the nucleotide-binding domains of class I aminoacyl-tRNA synthetases, UspA protein (USPA domains), photolyases, and electron transport flavoproteins (ETFP). The HUP domain is a distinct class of α/β domain .

This entry represents MJ1016-type predicted PP-loop ATPases.
Cytochrome c prime (Cyt_c_prime)
Type: Family

Cytochromes c (cytC) can be defined as electron-transfer proteins having one or several haem c groups, bound to the protein by one or, more generally, two thioether bonds involving sulphydryl groups of cysteine residues. The fifth haem iron ligand is always provided by a histidine residue. CytC possess a wide range of properties and function in a large number of different redox processes. Ambler recognised four classes of cytC.

Class II includes the high-spin cytC' and a number of low-spin cytochromes, e.g. cyt c-556. The haem-attachment site is close to the C terminus. The cytC' are capable of binding such ligands as CO, NO or CN(-), albeit with rate and equilibrium constants 100 to 1,000,000-fold smaller than other high-spin haemoproteins . This, coupled with its relatively low redox potential, makes it unlikely that cytC' is a terminal oxidase. Thus cytC' probably functions as an electron transfer protein .