SII-SWORD/CoKE huggingface dataset:
[LysW]-lysine/[LysW]-ornithine hydrolase (LysK)
Type: Family

Several bacteria and archaea utilize the amino group-carrier protein, LysW, for lysine biosynthesis from alpha-aminoadipate (AAA). In some cases, such as Sulfolobus, LysW is also used to protect the amino group of glutamate in arginine biosynthesis. After LysW modification, AAA and glutamate are converted to lysine and ornithine, respectively, by a single set of enzymes with dual functions .

LysK catalyzes the release of L-lysine from [LysW]-gamma-L-lysine in the lysine biosynthetic pathway and the release of L-ornithine from [LysW]-L-ornithine in the arginine biosynthetic pathway .
CxxxxCH...CXXCH motif, Geobacter sulfurreducens (C4xCH_C2xCH_motif_GEOSU)
Type: Repeat

This motif occurs from three to eight times in eight different proteins of Geobacter sulfurreducens. The final CXXCH motif matches the cytochrome c family haem-binding site signature, suggesting that the sequence may be involved in haem-binding.
Doubled CXXCH motif (Paired_CXXCH_1)
Type: Domain

This entry represents a domain of about 41 amino acids that contains, among other motifs, two copies of the CXXCH motif associated with haem binding. Most proteins in this entry have at least three copies of this domain (i.e. at least six copies of CXXCH) and are predicted to be high molecular weight c-type cytochromes.
Lipoprotein intramolecular transacylase Lit (Lit)
Type: Family

This entry represents the lipoprotein intramolecular transacylase, Lit . Lit creates a lipoprotein that is less immunogenic, possibly enabling the bacteria to gain a foothold in the host by stealth. The crystal structure of the Lit enzyme from Bacillus cereus (

) revealed that it consists of consists of four transmembrane helices with an extracellular cap . The conserved residues map to the cap-membrane interface and they include two catalytic histidines that function to effect unimolecular transacylation. The reaction involves acyl transfer from the sn-2 position of the glyceryl moiety to the amino group on the N-terminal cysteine of the substrate via an 8-membered ring intermediate.
CRISPR-associated protein Cse3 (CRISPR-assoc_prot_Cse3)
Type: Family

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.

This entry represents the Cse3 (CRISPR/Cas Subtype Ecoli protein 3, also known as CasE) family of Cas proteins. The Thermus thermophilus HB8 family member has been crystallised and found to have a structure consisting of two domains with opposing parallel β-sheets, known as a β-sheet platform . This structure is similar to those found in the sex-lethal protein and poly(A)-binding protein and is consistent with an RNA-binding function.
CRISPR-associated protein, CXXC-CXXC (CRISPR-assoc_prot_CXXC-CXXC)
Type: Family

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.

This entry represents a conserved region from an otherwise highly divergent protein found in the Tneap subtype of CRISPR/Cas regions. This Cys-rich region features two CXXC motifs.
CGCAxxGCC motif (CGCAxxGCC_motif)
Type: Family

This entry represents a putative redox-active protein of about 140 residues, with four perfectly conserved Cys residues. It includes a CGAXXG motif. Most members are found within one or two loci of transporter or oxidoreductase genes. A member from Geobacter sulfurreducens, located in a molybdenum transporter operon, has a TAT (twin-arginine translocation) signal sequence for Sec-independent transport across the plasma membrane, a hallmark of bound prosthetic groups such as FeS clusters.
N-formyl-4-amino-5-aminomethyl-2-methylpyrimidine deformylase/Succinyl-diaminopimelate desuccinylase (ArgE/DapE)
Type: Family

This entry represents N-formyl-4-amino-5-aminomethyl-2-methylpyrimidine deformylase and succinyl-diaminopimelate desuccinylase enzymes. The former enzyme catalyses the deformylation of formylaminopyrimidine to give aminopyrimidine. The latter enzyme catalyses the hydrolysis of N-succinyl-L,L-diaminopimelic acid (SDAP), forming succinate and LL-2,6-diaminoheptanedioate (DAP), an intermediate involved in the bacterial biosynthesis of lysine and meso-diaminopimelic acid, an essential component of bacterial cell walls.
Bacteriophage lambda, Recombination protein bet (Phage_lambda_Bet)
Type: Family

This entry represents Recombination protein bet from Bacteriophage lambda (Bet, also known as red-beta). Bet functions in general recombination and in the late, rolling-circle mode of lambda DNA replication. It has a function similar to that of E.coli recT. It is a single-stranded DNA binding protein that can promote renaturation of DNA . Members of this protein family are found in tailed bacteriophagues and bacterial prophagues.
CRISPR-associated protein, MJ0385 (CRISPR-assoc_prot_MJ0385)
Type: Family

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.

This entry represents a family of Cas proteins that tends to be found near CRISPR repeats. The species range for famliy members, so far, is exclusively archaeal. It is found so far in only four different species, and includes two tandem genes in Pyrococcus furiosus DSM 3638. This family is also known as Csa4 and Cas8a2 Type I-A .
NADPH-dependent F420 reductase (NpdG)
Type: Family

Members of this family are found only in species with evidence of coenzyme F420. All members of this family are believed to act as NADPH-dependent F420 reductase. This entry includes Methanothermobacter marburgensis fno, which catalyses the reduction of NADP+ with F420H2 via hydride transfer, and the reverse reaction, i.e. the reduction of F420 with NADPH . Another member, AF_0892 from Archaeoglobus fulgidus, is essential for both the 5-deazaflavin structure and the presence of an 8-hydroxy group in the substrate .
Glycine reductase, selenoprotein B (Gly_red_sel_B)
Type: Family

Glycine reductase is a complex with two selenoprotein subunits, A and B. This entry represents the glycine reductase selenoprotein B. Closely related proteins not matched by this entry include selenoprotein B subunits of betaine reductase and sarcosine reductase. All contain selenocysteine incorporated during translation at a specific UGA codon.
Selenoprotein B, glycine/betaine/sarcosine/D-proline reductase family (Various_sel_PB)
Type: Family

This entry represents selenoprotein B of glycine reductase, sarcosine reductase, betaine reductase, D-proline reductase, and perhaps others . All members are expected to contain an internal TGA codon, encoding selenocysteine, which may be misinterpreted as a stop codon.
HisA/PriA, Actinobacteria (HisA/PriA_Actinobacteria)
Type: Family

This entry includes HisA (1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino] imidazole-4-carboxamide isomerase) and HisA homologues from Actinobacteria, known as PriA (phosphoribosyl Isomerase A). These enzymes are involved in both the histidine and tryptophan biosynthetic pathways.

In addition to their ancestral HisA activity, PriA enzymes also have a proficient N'-(5'-phosphoribosyl) anthranilate (PRA) isomerase or TrpF activity. Therefore, where a trpF gene is lacking, as in the Actinobacteria or Gram-positive eubacteria with high (G C) content, PriA participates in the biosynthesis of both L-histidine and L-tryptophan .
Shikimate kinase, archaea (SK_arc)
Type: Family

Shikimate kinase (

) catalyses the fifth step in the shikimate pathway of aromatic amino acids biosynthesis. It converts shikimate to shikimate 3-phosphate (3-phosphoshikimate). This part of the pathway leads to the biosynthesis of chorismate, the precursor of aromatic amino acids, folates, ubiquinones, and other aromatic compounds. The shikimate pathway links metabolism of carbohydrates to biosynthesis of the aromatic amino acids phenylalanine, tyrosine, tryptophan and their derivatives in microorganisms and plants . In a sequence of seven enzymatic reactions, D-erythrose 4-phosphate (E4P), an intermediate of the pentose phosphate pathway and phosphoenol pyruvate (PEP), a glycolytic intermediate, are converted to chorismate. The shikimate pathway is present in bacteria, archaea, fungi and plants. The absence of the shikimate pathway in animals makes it an attractive target for non-toxic herbicides, antimicrobial and antifungal agents.

Shikimate kinase enzymes present an example of convergent evolution via enzyme recruitment from an unrelated group. This group represents shikimate kinases of the archaeal type. Members have no sequence similarity with the typical form of shikimate kinase (

) found in bacteria and eukaryotes, but are instead distantly related to homoserine kinases, which belong to the GHMP kinase domain superfamily (GHMP = galactose, homoserine, mevalonate, and phosphomevalonate) . All known non-archaeal shikimate kinases (the typical form) belong to the non-homologous, structurally unrelated nucleoside monophosphate (NMP) kinase domain superfamily .

Nomenclature note: the name AroK is used for non-homologous shikimate kinases of both the archaeal and bacterial types.
Diaminopimelate dehydrogenase, Ddh (Diaminopimelate_DH_Ddh)
Type: Family

Two lysine biosynthesis pathways evolved separately in organisms, the diaminopimelic acid (DAP) and aminoadipic acid (AAA) pathways. The DAP pathway synthesizes L-lysine from aspartate and pyruvate, and diaminopimelic acid is an intermediate. This pathway is utilised by most bacteria, some archaea, some fungi, some algae, and plants. The AAA pathway synthesizes L-lysine from alpha-ketoglutarate and acetyl coenzyme A (acetyl-CoA), and alpha-aminoadipic acid is an intermediate. This pathway is utilised by most fungi, some algae, the bacterium Thermus thermophilus, and probably some archaea, such as Sulfolobus, Thermoproteus, and Pyrococcus. No organism is known to possess both pathways .

There four known variations of the DAP pathway in bacteria: the succinylase, acetylase, aminotransferase, and dehydrogenase pathways. These pathways share the steps converting L-aspartate to L-2,3,4,5- tetrahydrodipicolinate (THDPA), but the subsequent steps leading to the production of meso-diaminopimelate, the immediate precursor of L-lysine, are different .

The succinylase pathway acylates THDPA with succinyl-CoA to generate N-succinyl-LL-2-amino-6-ketopimelate and forms meso-DAP by subsequent transamination, desuccinylation, and epimerization. This pathway is utilised by proteobacteria and many firmicutes and actinobacteria.

The acetylase pathway is analogous to the succinylase pathway but uses N-acetyl intermediates. This pathway is limited to certain Bacillus species, in which the corresponding genes have not been identified.

The aminotransferase pathway converts THDPA directly to LL-DAP by diaminopimelate aminotransferase (DapL) without acylation. This pathway is shared by cyanobacteria, Chlamydia, the archaeon Methanothermobacter thermautotrophicus, and the plant Arabidopsis thaliana.

The dehydrogenase pathway forms meso-DAP directly from THDPA, NADPH, and NH4 _ by using diaminopimelate dehydrogenase (Ddh). This pathway is utilised by some Bacillus and Brevibacterium species and Corynebacterium glutamicum.

Most bacteria use only one of the four variants, although certain bacteria, such as C. glutamicum and Bacillus macerans, possess both the succinylase and dehydrogenase pathways.

This entry represents the diaminopimelate dehydrogenase enzyme which provides an alternate (shortcut) route of lysine biosynthesis in Corynebacterium, Bacterioides, Porphyromonas and other species. The enzyme from Corynebacterium glutamicum (Brevibacterium flavum) has been crystallized and characterised .
IMP cyclohydrolase (IMP_cyclohydrolase)
Type: Family

This entry represents IMP cyclohydrolase, which catalyses the cyclisation of 5-formylamidoimidazole-4-carboxamide ribonucleotide to inosine monophosphate (IMP), a reaction which is important in de novo purine biosynthesis in archaeal species . This single domain protein is arranged to form an overall fold that consists of a four-layered α-β-β-α core structure. The two antiparallel β-sheets pack against each other and are covered by α-helices on one face of the molecule. The protein is structurally similar to members of the N-terminal nucleophile (NTN) hydrolase superfamily. A deep pocket was in fact found on the surface of IMP cyclohydrolase in a position equivalent to that of active sites of NTN-hydrolases, but an N-terminal nucleophile could not be found. Therefore, it is thought that this enzyme is structurally but not functionally similar to members of the NTN-hydrolase family .

In bacteria this step is catalysed by a bifunctional enzyme (purH).
2-succinylbenzoate--CoA ligase (MenE)
Type: Family

This entry represents the enzyme O-succinylbenzoate-CoA ligase (MenE), which is involved in the fourth step of the menaquinone (vitamin K2) biosynthesis pathway. In bacteria, menaquinone is used during fumarate reduction in anaerobic respiration. In green sulphur bacteria and heliobacteria, menaquinones are thought to be used as a loosely bound secondary electron acceptor in the photosynthetic reaction centre. In cyanobacteria, the product of the menaquinone pathway is phylloquinone (2-methyl-3-phytyl-1,4-naphthoquinone), a molecule used exclusively as an electron transfer cofactor in Photosystem (PS) I .
Serine-protein kinase RsbW (RsbW)
Type: Family

This entry describes the serine-protein kinase RsbW also known as the anti-sigma B factor. Sigma B controls the general stress regulon in B subtilis and is activated by cell stresses such as stationary phase and heat shock. RsbW binds to sigma B and prevents formation of the transcription complex at the promoter . RsbV (anti-anti-sigma factor) binds to RsbW to inhibit association with sigma B, however RsbW can phosphorylate RsbV, causing disassociation of the RsbV/RsbW complex . Low ATP level or environmental stress causes the dephosphorylation of RsbV .
Anti-sigma F factor (Anti-sigma_F)
Type: Family

This entry describes the SpoIIAB anti-sigma F factor. Sigma F regulates spore development in B subtilis. SpoIIAB binds to sigma F, preventing formation of the transcription complex at the promoter . SpoIIAA (anti-anti-sigma F factor) binds to SpoIIAB to inhibit association with sigma F, however SpoIIAB can phosphorylate SpoIIAA, causing disassociation of the SpoIIAA/B complex . The SpoIIE phosphatase dephosphorylates SpoIIAA.
Uncharacterised peroxidase-related (Uncharacterised_peroxidase-rel)
Type: Family

Members of this family are conserved hypothetical proteins of around 200 amino acids in length. Many of them contain an akylhydroperoxidase (AhpD) domain.
o-Succinylbenzoate synthase, MenC type1 (OSB_synthase_MenC1)
Type: Family

This entry describes the enzyme o-succinylbenzoic acid synthetase (MenC) that is involved in one of the steps of the menaquinone biosynthesis pathway. The biosynthesis of menaquinone has been studied most in Escherichia coli . 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC) is dehydrated by MenC to give the aromatic compound O-succinylbenzoate (OSB) . MenC, which is a member of the enolase superfamily and x-ray structure has been determined . Many of the common names of the proteins in this family are incorrectly described as O-succinylbenzoyl-CoA synthase. Members are restricted to bacteria.
o-Succinylbenzoate synthase/NAAAR (OSBS/NAAAR)
Type: Family

This entry includes the enzyme o-succinylbenzoic acid synthetase (menC) and N-acylamino acid racemase (NAAAR, or the more general term, racemase/racemase family). MenC is involved in one of the steps of the menaquinone biosynthesis pathway. It takes 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC) and makes it into 2-succinylbenzoate. Also included are enzymes with the common name of N-acylamino acid racemase (NAAAR, or the more general term, racemase/racemase family), which refers to the enzyme's industrial application as a racemase that catalyses the racemisation of N-acylamino acids, and not to its biological function as o-succinylbenzoic acid synthetase . NAAARs act on a broad range of N-acylamino acids rather than amino acids. Enantiopure amino acids are of industrial interest as chiral building blocks for antibiotics, herbicides, and drugs. Most members of this group of o-succinylbenzoate synthases are proteins from low GC Gram-positive bacteria and archaea. menC/NAAAR is a member of the enolase superfamily, characterised by the presence of an enolate anion intermediate which is generated by abstraction of the alpha-proton of the carboxylate substrate by an active site residue and is stabilized by coordination to the essential Mg2+ ion .
1,4-Dihydroxy-2-naphthoyl-CoA synthase, MenB (DHNA-CoA_synthase_MenB)
Type: Family

This entry represents an enzyme, naphthoate synthase

, MenB or dihydroxynaphthoic acid synthetase, which is involved in the fifth step of the menaquinone biosynthesis pathway. Menaquinone (vitamin K2), is an essential quinone used in electron-transfer pathways serving as the major electron carrier during anaerobic growth. In the bacterium, the biosynthetic pathway in bacteria typically comprises 6-7 steps . Together with o-succinylbenzoate-CoA ligase (menE

), MenB takes 2-succinylbenzoate and converts it into 1,4-di-hydroxy-2-naphthoic acid (DHNA) . The conversion of o-succinylbenzoate-CoA ligase to DHNA is mediated by the enzyme DHNA synthase, which is encoded by menB .

The protein structure of naphthoate synthase has been expressed in Escherichia coli, purified and crystallised, and found to have fold characteristics of the crotonase family of enzymes, which is notable for the presence of several highly flexible regions around the active site. The C-terminal region of the protein may play a critical role both in completion of the binding pocket and in stabilisation of the hexamer, suggesting a link between oligomerisation and catalytic activity .
Sulphite reductase [NADPH] flavoprotein, alpha chain (CysJ)
Type: Family

Escherichia coli NADPH-sulphite reductase (SiR) is a multimeric hemoflavoprotein composed of eight alpha-subunits (SiR-FP) and four beta-subunits (SiR-HP) that catalyses the six electron reduction of sulphite to sulphide. This is one of several activities required for the biosynthesis of L-cysteine from sulphate. The alpha component of NADPH-sulphite reductase is a flavoprotein, the beta component is a hemoprotein . The flavoprotein component catalyses the electron flow from NADPH to FAD to FMN to the hemoprotein component.

This entry describes an NADPH-dependent sulphite reductase flavoprotein subunit alpha. It binds one FAD and one FMN as prosthetic groups and contains an NADPH-binding domain .
HflC (HflC)
Type: Family

This model characterizes proteins similar to prokaryotic HflC (High frequency of lysogenization C). Although many members of the SPFH (or band 7) superfamily are lipid raft associated, prokaryote plasma membranes lack cholesterol and are unlikely to have lipid raft domains. Individual proteins of this SPFH domain superfamily may cluster to form membrane microdomains which may in turn recruit multiprotein complexes . Escherichia coli HflC is an integral membrane protein which may localize to the plasma membrane. HflC associates with another SPFH superfamily member (HflK) to form an HflKC complex . HflKC interacts with FtsH in a large complex termed the FtsH holo-enzyme . FtsH is an AAA ATP-dependent protease which exerts progressive proteolysis against membrane-embedded and soluble substrate proteins . HflKC can modulate the activity of FtsH . HflC is considered to be a protease inhibitor and is a member of inhibitor family I87 in the MEROPS database. HHflKC plays a role in the decision between lysogenic and lytic cycle growth during lambda phage infection .
HflK (HflK)
Type: Family

The accumulation of abnormal membrane proteins is something which must be avoided in order to maintain cell viability. In Escherichia coli, the membrane-bound, ATP-dependent protease FtsH plays a central role in the degradation of these abnormal proteins . Known substrates of this protease include several lambda bacteriophage proteins, the heat-shock transcription factor sigma-32, and the unassembled form of the membrane protein SecY. While FtsH is active as a protease on its own, in vivo it forms a complex with a membrane-bound HflKC heterodimer. HflKC has a generally inhibitory effect on the protease activity of FtsH, though the mechanism of this inhibition is not known. HflK is a member of peptidase inhibitor family I87 . The HflK and HflC polypeptides are paralogous, and often encoded by tandem genes within bacterial genomes.

This entry represents the HflK subunit (MEROPS identifier I87.002) of the HflKC heterodimer.
Regulator of ribonuclease activity A (RraA)
Type: Family

The regulator of ribonuclease activity A (RraA) family includes a number of closely related sequences from bacteria and plants. The Escherichia coli member has been characterised, and its crystal structure determined . It acts as a regulator of the endonuclease RNase E (see

) by binding to it and inhibiting RNA processing .
Na(+)-translocating NADH-quinone reductase subunit C (NqrC)
Type: Family

This entry represents the NqrC subunit of the six-protein, Na(+)-pumping NADH-quinone reductase of a number of marine and pathogenic Gram-negative bacteria.
Na(+)-translocating NADH-quinone reductase subunit F (NqrF)
Type: Family

This entry represents the Na(+)-translocating E subunit from NADH:ubiquinone oxidoreductase from a number of marine and pathogenic Gram-negative bacteria .
Poly(A) polymerase I (PolA_pol_I)
Type: Family

This entry describes poly(A) polymerase I (also known as PcnB and plasmid copy number protein). These enzymes sequentially add adenosine nucleotides to the 3' end of RNAs, targeting them for degradation by the cell . This was originally described for anti-sense RNAs, but was later demonstrated for mRNAs as well . Members of this family are predominantly found in the gamma- and beta-proteobacteria, with putative members in the Chlamydiacae and Spirochetes. This family has homology to tRNA nucleotidyltransferase.
Ion-translocating oxidoreductase complex, RnfB/RsxB (Elect_transpt_cplx_RnfB/RsxB)
Type: Family

The six subunit complex RnfABCDGE in Rhodobacter capsulatus (Rhodopseudomonas capsulata) encodes an apparent NADH oxidoreductase responsible for electron transport to nitrogenase, necessary for nitrogen fixation . A closely related complex in Escherichia coli, RsxABCDGE (Reducer of SoxR), reduces the 2Fe-2S-containing superoxide sensor SoxR, active as a transcription factor when oxidised . This family of putative NADH oxidoreductase complexes exists in many of the same species as the related NQR, a Na(+)-translocating NADH-quinone reductase, but is distinct. This entry describes the B subunit.
Ion-translocating oxidoreductase complex, subunit RnfC/RsxC (Ion_transpt_RnfC/RsxC)
Type: Family

The six subunit complex RnfABCDGE in Rhodobacter capsulatus (Rhodopseudomonas capsulata) encodes an apparent NADH oxidoreductase responsible for electron transport to nitrogenase, necessary for nitrogen fixation . A closely related complex in Escherichia coli, RsxABCDGE (Reducer of SoxR), reduces the 2Fe-2S-containing superoxide sensor SoxR, active as a transcription factor when oxidized . This family of putative NADH oxidoreductase complexes exists in many of the same species as the related NQR, a Na(+)-translocating NADH-quinone reductase (

), but is distinct. This entry describes the C subunit.