SII-SWORD/CoKE huggingface dataset:
Adhesin operon regulatory protein (Adhesin_operon_reg_prot)
Type: Family

Proteins in this family include PapB, DaaA, FanA, FanB and AfaA.

P pili, or fimbriae, are ~68A in diameter and 1 micron in length, the bulk of which is a fibre composed of the main structural protein PapA . At its tip, the pilus is terminated by a fibrillum consisting of repeating units of the PapE protein. This, in turn, is topped by the adhesins, PapF and PapG, both of which are needed for receptor binding. The tip fibrillum is anchored to the main PapA fibre by the PapK pilus-adaptor protein. PapH, an outer membrane protein, then anchors the entire rod in the bacterial envelope . A cytoplasmic chaperone (PapD) assists in assembling the monomers of the macromolecule in the membrane.
Type IV secretion system CagX conjugation protein (IVSec_CagX)
Type: Family

Helicobacter pylori makes use of a type IV secretion system similar in mechanism to the conjugation machine of Agrobacterium tumefaciens . These machines secrete three different types of substrate: DNA conjugation intermediates, as in A. tumefaciens; multimeric proteins such as the pertussis toxin of Bordetella pertussis; and the CagA protein of H. pylori. CagA has been linked to the more severe forms of gastric ulcers and duodenal cancers . Both CagA and the secretion system apparatus are encoded in the large pathogenicity island, termed cag , possessed by the malignant disease-causing type I bacterial strains.

CagX is found on this pathogenicity island; mutants lacking the gene fail to induce pathogenicity in an infected mouse model. CagX is thought to play a role in the process of conjugation .
Glyoxalase/fosfomycin resistance/dioxygenase domain (Glyas_Fos-R_dOase_dom)
Type: Domain

Glyoxalase I (

) (lactoylglutathione lyase) catalyzes the first step of the glyoxal pathway. S-lactoylglutathione is then converted by glyoxalase II to lactic acid . Glyoxalase I is an ubiquitous enzyme which binds one mole of zinc per subunit. The bacterial and yeast enzymes are monomeric while the mammalian one is homodimeric. The sequence of glyoxalase I is well conserved.

The domain represented by this entry is found in glyoxalase I and in other related proteins, including fosfomycin resistance proteins FosB , FosA , FosX and dioxygenases (eg. 4-hydroxyphenylpyruvate dioxygenase).
Glyoxalase I (Glyoxalase_1)
Type: Family

Glyoxalase I (lactoylglutathione lyase) catalyzes the first step of the glyoxal pathway in the following reaction:

glutathione + methylglyoxal = (R)-S-lactoylglutathione

S-lactoylglutathione is then converted by glyoxalase II to lactic acid . Glyoxalase I is a ubiquitous enzyme which binds one mole of zinc per subunit. The bacterial and yeast enzymes are monomeric while the mammalian one is homodimeric. The sequence of glyoxalase I is well conserved. In bacteria and mammals the enzyme is a protein of about 130 to 180 residues while in fungi it is about twice as long. In these organisms the enzyme is built out of the tandem repeat of a homologous domain.
Methylglyoxal synthase (Methylgl_synth)
Type: Family

Methylglyoxal synthase (MGS) catalyses the conversion of dihydroxyacetone phosphate (DHAP) to methylglyoxal and phosphate:

Glycerone phosphate = methylglyoxal + phosphate

The first part of the catalytic mechanism is believed to be similar to TIM (triosephosphate isomerase) in that both enzymes utilise DHAP to form an ene-diolate phosphate intermediate. In MGS, the second catalytic step is characterised by the elimination of phosphate and collapse of the enediolate to form methylglyoxal instead of reprotonation to form the isomer glyceraldehyde 3-phosphate, as in TIM. This is the first reaction in the methylglyoxal bypass of the Embden-Myerhoff glycolytic pathway and is believed to provide physiological benefits under non-ideal growth conditions in bacteria . MGS is a small protein of about 13 to 17kDa. An aspartate residue is involved in the catalytic mechanism .
Aminoacyl-tRNA synthetase, class II (D/K/N) (Aa-tRNA-synt_II)
Type: Domain

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 .

This entry includes the asparagine, aspartic acid and lysine tRNA synthetases.
OB-fold nucleic acid binding domain, AA-tRNA synthetase-type (NA-bd_OB_tRNA)
Type: Domain

The OB-fold (oligonucleotide/oligosaccharide-binding fold) is found in all three kingdoms and its common architecture presents a binding face that has adapted to bind different ligands. The OB-fold is a five/six-stranded closed β-barrel formed by 70-80 amino acid residues. The strands are connected by loops of varying length which form the functional appendages of the protein. The majority of OB-fold proteins use the same face for ligand binding or as an active site. Different OB-fold proteins use this 'fold-related binding face' to, variously, bind oligosaccharides, oligonucleotides, proteins, metal ions and catalytic substrates.
Cyclin, C-terminal domain (Cyclin_C-dom)
Type: Domain

Cyclins are eukaryotic proteins that play an active role in controlling nuclear cell division cycles , and regulate cyclin dependent kinases (CDKs). Cyclins, together with the p34 (cdc2) or cdk2 kinases, form the Maturation Promoting Factor (MPF). There are two main groups of cyclins, G1/S cyclins, which are essential for the control of the cell cycle at the G1/S (start) transition, and G2/M cyclins, which are essential for the control of the cell cycle at the G2/M (mitosis) transition. G2/M cyclins accumulate steadily during G2 and are abruptly destroyed as cells exit from mitosis (at the end of the M-phase). In most species, there are multiple forms of G1 and G2 cyclins. For example, in vertebrates, there are two G2 cyclins, A and B, and at least three G1 cyclins, C, D, and E.

Cyclin homologues have been found in various viruses, including Saimiriine herpesvirus 2 (Herpesvirus saimiri) and Human herpesvirus 8 (HHV-8) (Kaposi's sarcoma-associated herpesvirus). These viral homologues differ from their cellular counterparts in that the viral proteins have gained new functions and eliminated others to harness the cell and benefit the virus .

This is the C-terminal domain of cyclins.
Prolyl-tRNA editing protein, YbaK/EbsC (Prolyl-tRNA_editing_YbaK/EbsC)
Type: Family

This entry represents the YbaK family, bacterial proteins whose full length sequence is homologous to an insertion domain in proline--tRNA ligases. They deacylate mischarged tRNAs.

YbaK functions in trans to edit the amino acid from incorrectly charged Cys-tRNA(Pro) via a Cys-tRNA(Pro) deacylase activity . YbaK has also been shown to hydrolyse glycyl-tRNA's, alanyl-tRNA's, seryl-tRNA's, and prolyl-tRNA's . This family also includes

(EbsC) and ProX. EbsC affects the expression of a receptor called binding substance, that mediates mating aggregate formation in Enterococcus faecalis . It could be a regulatory protein that suppresses the function or expression of ebsA and/or ebsMB. ProX functions in trans to edit the amino acid moiety from incorrectly charged Ala-tRNA(Pro) .
4-oxalocrotonate tautomerase-like domain (4-OT-like_dom)
Type: Domain

4-oxalocrotonate tautomerase (4-OT, also known as 2-hydroxymuconate tautomerase) is an enzyme that converts 2-hydroxymuconate to the α-β-unsaturated ketone, 2-oxo-3-hexenedioate . This enzyme forms part of a bacterial metabolic pathway that oxidatively catabolizes toluene, o-xylene, 3-ethyltoluene, and 1,2,4-trimethylbenzene into intermediates of the citric acid cycle. With a monomer size of just 62 amino acid residues, the 4-Oxalocrotonate tautomerase is one of the smallest enzyme subunits known . However, in solution, the enzyme forms a hexamer of six identical subunits, so the active site may be formed by amino acid residues from several subunits . This enzyme is also unusual in that it uses a proline residue at the amino terminus as an active site residue.

This entry also includes tautomerase PptA, a 4-OT homologue .
Acetate/propionate kinase (Ac/propionate_kinase)
Type: Family

This entry represents proteins which transfer phosphate from ATP to a short chain aliphatic acid. For example, Acetate kinase catalyses the reaction ATP + acetate = ADP + acetyl phosphate and propionate kinase which utilizes propionate as substrate .
Peptide chain release factor 1 (RF-1)
Type: Family

This entry represents peptide chain release factor 1 (PrfA, RF-1), and excludes the related peptide chain release factor 2 (PrfB, RF-2). RF-1 helps recognise and terminate translation at UAA and UAG stop codons . This entry also includes chloroplast release factor APG3, which is an orthologue of E. coli RF1 and is essential for chloroplast development. APG3 could complement E. coli RF1 mutants, but not RF2 mutants, indicating that AP3 may function as RF1 in E. coli, showing specificity of stop codon recognition .
Peptide chain release factor 2 (PrfB)
Type: Family

Peptide chain release factors (RFs) are required for the termination of protein biosynthesis . At present two classes of RFs can be distinguished. Class I RFs bind to ribosomes that have encountered a stop codon at their decoding site and induce release of the nascent polypeptide. Class II RFs are GTP-binding proteins that interact with class I RFs and enhance class I RF activity. In prokaryotes there are two class I RFs that act in a codon specific manner : RF-1 (gene prfA) mediates UAA and UAG-dependent termination while RF-2 (gene prfB), which is represented by this entry, mediates UAA and UGA-dependent termination. RF-1 and RF-2 are structurally and evolutionary related proteins which have been shown to be part of a larger family.

This entry represents peptide chain release factor 2 (PrfB, RF-2). It also includes chloroplastic release factor PrfB, which is required for the proper translation and stability of UGA-containing transcripts in chloroplasts .
NanQ anomerase/TabA/YiaL family (NanQ/TabA/YiaL)
Type: Family

This protein family consists of bacterial proteins. N-acetylneuraminate anomerase NanQ (NanQ, previously known as YhcH) plays a role in sialic acid catabolism by opening both the alpha- and beta-forms of N-acetylneuraminate (sialic acid; Neu5Ac) to provide aceneuramate, the preferred substrate for the sialic acid aldolase (NanA) . TabA (YjgK), also included in this entry, influences biofilm formation by toxin-antitoxin systems .
Phosphoesterase MJ0037 (Pesterase_MJ0037)
Type: Family

This entry represents a group of poorly uncharacterised archaeal proteins, such as MJ0037 from Methanocaldococcus jannaschii, that share a motif approximating DXH(X25)GDXXD(X25)GNHD as found in several phosphoesterases, including the nucleases SbcD and Mre11. SbcD is a subunit of the SbcCD nuclease of Escherichia coli that can cleave DNA hairpins to unblock stalled DNA replication.
ABC transporter, permease protein DrrB/DrrC (ABC_transpt_DrrB/DrrC)
Type: Family

DrrB and DrrC are part of the ABC transporter complex drrABC involved in doxorubicin and daunorubicin resistance . The members of this family are found mainly in mycobacteria. They are paralogous to proteins of the resistance efflux system of Streptomyces peucetius . In mycobacteria this pump confers resistance towards a broad range of structurally unrelated antibiotics .
F420H(2)-dependent quinone reductase (F420H2_quin_Rdtase)
Type: Family

This entry represents a family of proteins found in paralogous families in the genera Mycobacterium and Streptomyces. Seven members are in Mycobacterium tuberculosis. Member protein Rv3547 has been characterised as a deazaflavin-dependent nitroreductase . Rv1558 is an F420H(2)-dependent quinone reductase involved in oxidative stress protection .
UDP-galactopyranose mutase (UDP-GALP_mutase)
Type: Family

UDP-galactopyranose mutase (

) is involved in the conversion of UDP-GALP into UDP-GALF through a 2-keto intermediate, and contains FAD as a cofactor. The gene is known as glf, ceoA, and rfbD. It is known experimentally in Escherichia coli, Mycobacterium tuberculosis, and Klebsiella pneumoniae.
Aspartate racemase (Asp_race)
Type: Family

Asparate racemases (

) and some close homologues of function are related to the more common glutamate racemases, but form a distinct evolutionary branch . Members of this family are the aspartate racemase-related subset of amino acid racemases. Aspartate racemases act as homodimers and catalyse the conversion of L-aspartate to D-aspartate. The structure of aspartate racemase from
Pyrococcus horikoshii
has been solved .
Glycerate kinase (Glycerate_kinase)
Type: Family

This family includes glycerate kinase 2 (

), which catalyses the phosphorylation of (R)-glycerate to 3-phospho-(R)-glycerate in the presence of ATP. There are two glycerate kinases in E. coli, known as GKI and GKII and GKII is encoded by glxK .
Ribosomal RNA large subunit methyltransferase RlmN/Cfr (rRNA_lsu_MTrfase_RlmN/Cfr)
Type: Family

This entry represents the RlmN family, that includes dual-specificity RNA methyltransferase RlmN and ribosomal RNA large subunit methyltransferase Cfr.

Dual-specificity RNA methyltransferase RlmN specifically methylates position 2 of adenine 2503 in 23S rRNA . This nucleotide is located in a functionally important region of the ribosome, at the entrance to the nascent peptide exit tunnel, and may thus be involved in the interaction with the nascent peptide. It also methylates position 2 of adenine 37 in tRNAs. Unmodified tRNA is not a suitable substrate for RlmN, which suggests that RlmN works in a late step during tRNA maturation .

Ribosomal RNA large subunit methyltransferase Cfr specifically methylates position 8 of adenine 2503 in 23S rRNA. It can also methylate position 2 of A2503 after the primary methylation is complete, to form 2,8-dimethyladenosine. Cfr confers antibiotic resistance in bacteria. The antibiotic resistance is provided by methylation at the 8 position and is independent of methylation at the 2 position of A2503 .
RNA methyltransferase TrmJ/LasT (RNA_MeTrfase_TrmJ/LasT)
Type: Family

This entry includes TrmJ and LasT from E.coli. TrmJ is a tRNA methyltransferase that catalyzes the formation of 2'O-methylated cytidine (Cm32) or 2'O-methylated uridine (Um32) at position 32 in tRNA . The function of LasT is not clear.
Nucleoside diphosphate pyrophosphatase (NDP_pyrophosphatase)
Type: Family

This entry describes a family of proteins which appear to catalyse the hydrolysis of phosphorus-containing acid anhydrides such as nucleoside diphosphate, for example ADP-mannose and UDP-glucose . Some of these enzymes play a key role in glycogen biosynthesis.
Toxin-antitoxin system, YafQ-like toxin (Toxin_YafQ-like)
Type: Family

YafQ is a ribosome-associated endoribonuclease that serves as part of a toxin-antitoxin system, for which DinJ is the antidote component . It associates with the ribosome and blocks translation elongation through sequence-specific and frame-dependent mRNA cleavage .
Peptidase M50, putative membrane-associated zinc metallopeptidase (Pept_M50_Zn)
Type: Family

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 .

This family contains putative zinc metallopeptidases belonging to MEROPS peptidase family M50 (S2P protease family, clan MM). The N-terminal region of contains a perfectly conserved motif HEXGH, where the Glu is the active site and the His residues coordinate the metal cation.

The family of bacterial and plant proteins also includes a region that hits the PDZ domain (

), found in a number of proteins targeted to the membrane by binding to a peptide ligand . The family includes EcfE, which is a homologue of human site-2 protease (S2P), a membrane-bound zinc metalloprotease involved in regulated intramembrane proteolysis. In Escherichia coli EcfE activates the sigma(E) pathway of stress response through a site-2 cleavage of anti-sigma(E), RseA.
Large ribosomal subunit protein uL18, bacterial-type (Ribosomal_uL18_bac-type)
Type: Family

This entry represents the ribosomal protein uL18 from bacteria and chloroplasts. The archaebacterial type is not included in this family.

The large ribosomal subunit protein uL18 is an essential component of the large subunit LSU, which is required in its formation and stabilisation. The LSU contains the ribosomal catalytic site termed the peptidyl transferase centre (PTC), which catalyses the formation of peptide bonds, thereby polymerising the amino acids delivered by tRNAs into a polypeptide chain. Additionally, uL18 is essential for binding and coordinating 5S rRNA into the ribosome, a key step in ribosome biogenesis and assembly .

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 .
Signal-recognition particle receptor FtsY (SR_rcpt_FtsY)
Type: Family

FtsY is involved in targeting and insertion of nascent membrane proteins into the cytoplasmic membrane. It acts as a receptor for the complex formed by the signal recognition particle (SRP) and the ribosome-nascent chain (RNC). In E. coli, interaction with SRP-RNC leads to the transfer of the RNC complex to the Sec translocase for insertion into the membrane, the hydrolysis of GTP by both Ffh and FtsY, and the dissociation of the SRP-FtsY complex into the individual components .
Glutamate racemase (Glu_race)
Type: Family

Glutamate racemase (

) provides the (R)-glutamic acid required for cell wall biosynthesis. It converts L-glutamate to D-glutamate during peptidoglycan biosynthesis. The most closely related proteins differing in function are aspartate racemases.
Hydrogenase maturation factor HypB (Hyd_mat_HypB)
Type: Family

The hydrogenase accessory protein HypB is a GTP hydrolase required for assembly of the nickel metallocentre of hydrogenase . In Helicobacter pylori, HypB is also required for maturation of urease . The homologue guanidine hydrolase-activating protein B (GhaB) is involved in the maturation of the nickel-dependent guanidine hydrolase GdmH; it is required for nickel insertion into the metal centre of GdmH .
Nicotinate-nucleotide pyrophosphorylase (NadC)
Type: Family

Nicotinate-nucleotide pyrophosphorylase (

), also known as quinolinate phosphoribosyltransferase (decarboxylating), catalyses the conversion of nicotinate D-ribonucleotide, pyrophosphate and carbon dioxide into pyridine-2,3-dicarboxylate and 5-phospho-alpha-D-ribose 1-diphosphate. This enzyme is a type II phosphoribosyltransferase which provides the
de novo
source of nicotinate mononucleotide (NAMN) for NAD biosynthesis in both prokaryotes and eukaryotes .

Structural studies have shown that the active form of this enzyme is a homodimer with an unsual fold . The N-terminal forms a mixed α/β domain, while the C-terminal region forms a multi-stranded, open α/β-barrel. The active site is found at the C-terminal ends of the β-strands of the α/β-barrel, and is bordered by the N-terminal domain of the second subunit of the dimer. It contains several conserved charged residues thought to be important determinants of substrate binding and catalysis.
Protein Iojap/ribosomal silencing factor RsfS (Iojap/RsfS/C7orf30)
Type: Family

This entry includes Iojap protein from plants, the ribosomal silencing factor RsfS (also known as RsfA) from bacteria and its homologue, C7orf30, from animals.
Ribosome-binding ATPase YchF/Obg-like ATPase 1 (ATPase_YchF/OLA1)
Type: Family

E. coli ribosome-binding ATPase YchF is an ATPase that binds to both the 70S ribosome and the 50S ribosomal subunit in a nucleotide-independent manner . The mammalian homologue of YchF has been termed OLA1, for Obg-like ATPase 1 . These proteins bind and hydrolyse ATP more efficiently than GTP, therefore their name. ATPase activity is a general feature of the YchF subfamily of Obg-like GTPases .