SII-SWORD/CoKE huggingface dataset:
FkbH domain (FkbH_domain)
Type: Domain

This entry describes a domain of unknown function. One of proteins with this domain is a modular polyketide synthase, which is 4800 amino acids in length from Streptomyces avermitilis, where the domain is the C-terminal segment. By contrast, the FkbH protein from Streptomyces hygroscopicus (

) apparently contains only this domain. The remaining members of the family all contain an additional N-terminal domain of between 200 and 275 amino acids, which show less than 20% identity to one another. It seems likely then that these proteins are involved in disparate functions, probably the biosynthesis of different natural products. For instance, the FkbH gene is found in a gene cluster believed to be responsible for the biosynthesis of unusual 'PKS extender units' in the ascomycin pathway . This domain is composed of two parts, the first of which is a member of subfamily IIIC of the haloacid dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. All of the characterised enzymes within subfamily III are phosphatases, and all of the active site residues characteristic of HAD-superfamily phosphatases are present in this domain. The C-terminal portion of this domain is unique to this family (by BLAST).
MoaD, archaeal-type (MoaD_arc-typ)
Type: Family

Members of this family appear to be mainly archaeal and bacterial versions of MoaD, subunit 1 of molybdopterin converting factor. Small archaeal modifier protein 1 (SAM1) is a member of this family and it is involved in protein tagging in an ubiquitin-like system from archaea known as SAMPylation . It is not known whether it is implicated in the targeting of proteins to the proteasome for degradation . SAM1 is also essential for MoCo-dependent dimethyl sulphoxide reductase activity, suggesting that it functions in the sulphur-containing molybdenum cofactor (MoCo) biosynthesis .

SAM proteins, as Ub/Ubl proteins, have a β-grasp fold common to a growing superfamily of proteins involved in diverse functions. Among these functions, sulphur activation for the biosynthesis of thiamine, tungsten and molybdenum cofactors bears striking resemblance to the activation of Ub/Ubl .
Capsule biosynthesis phosphatase (EcbF_BcbF)
Type: Family

This entry describes a small family of highly conserved proteins (>60% identity). Two of these, BcbF and EcbF of Pasteurella multocida are believed to be part of the capsule polysaccharide biosynthesis machinery because they are co-transcribed from a locus devoted to that purpose . In P. multocida there are six different variant capsules (A-F), and these proteins are found only in B and E. The other two species in which this gene is (currently) found are both also pathogenic. These proteins are also members of the IIIC subfamily of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. All of the characterised enzymes within subfamily III are phosphatases, and all of the active site residues characteristic of HAD-superfamily phosphatases are present in this subfamily.
Bifunctional uridylyltransferase/uridylyl-removing enzyme (UTase/UR)
Type: Family

This entry describes GlnD, the uridylyltransferase/uridylyl-removing enzyme for signal-transduction protein PII, and acts as the sensory component of the nitrogen regulation (ntr) system . The ntr system modulates nitrogen metabolism in response to the prevailing nitrogen source and the requirements of the cell. During nitrogen fixation, ammonia and 2-oxoglutarate can be used to produce glutamate. The activity of the PII protein is stimulated by glutamine and inhibited by 2-oxoglutarate. Under glutamate-limiting conditions, PII is uridylylated by GlnD leading to the activation of glutamate synthetase and to the stimulation of NtrC-dependent promoters. Under high concentrations of fixed nitrogen, PII is de-uridylylated leading to the inactivation of the glutamate synthetase pathway and switching off NtrC-dependent promoters .

Not all homologues of PII share the property of uridylyltransferase modification on the characteristic Tyr residue (see

), but the modification site is preserved in the PII homologue of all species with a member of this family.
Methylthioadenosine phosphorylase (MTAP) (MTAP)
Type: Family

This entry represents the methylthioadenosine phosphorylase (MTAP). MTAP catalyses the reversible phosphorylation of S-methyl-5'-thioadenosine (MTA) to adenine and 5-methylthioribose-1-phosphate. It is involved in the breakdown of MTA, a major by-product of polyamine biosynthesis. It is responsible for the first step in the methionine salvage pathway after MTA has been generated from S-adenosylmethionine. It has broad substrate specificity with 6-aminopurine nucleosides as preferred substrates .
Phosphopentomutase (DeoB)
Type: Family

This entry describes bacterial phosphopentomutase. This protein is involved in the purine and pyrimidine salvage pathway of nucleotide synthesis. It catalyses a phosphotransfer on ribose and deoxyribose, converting D-ribose 1-phosphate to D-ribose 5-phosphate, and 2-deoxy-D-ribose 1-phosphate to 2-deoxy-D-ribose 5-phosphate .
Oxidoreductase alpha (molybdopterin) subunit (Mopterin_OxRdtse_a_bac)
Type: Family

This entry includes a well-defined clade of molybdopterin-dependent formate dehydrogenases, bacterial type . It represents the alpha subunit, which contains a molybdopterin cofactor and generally associate with two other subunits which contain iron-sulphur clusters and cytochromes. This entry also includes protein YdeP from Escherichia coli and assimilatory nitrate reductase from Haloferax mediterranei .
Ni-containing CO dehydrogenase (CODH)
Type: Family

This entry describes the Ni-containing carbon monoxide dehydrogenase (CODH) family (

). These enzymes reversibly oxidise CO to CO(2), and play key roles in the energy-yielding pathways of various autotrophic anaerobes, allowing these organisms to grow with CO as the sole carbon source . The active sites of these enzymes contain Ni-iron-sulphur (NiFeS) clusters. This family also includes the CODH subunit of bifunctional CODH/acetyl-CoA synthetase (CODH/ACS), which contains two Ni-containing active sites to catalyse the formation of acetyl-CoA from CO(2)-derived CO .

CODH is related to hybrid cluster proteins (HCP, or prismane) (

), a complex whose activity is not yet fully described; the hybrid Fe-S cluster in HCPs is similar to the NiFeS cluster in CODH .
Hydroxylamine reductase (Hydroxylam_reduct)
Type: Family

Hybrid cluster proteins (HCP, or Prismane) have been identified in bacteria, archaea and eukaryotic protozoa. No specific function has yet been assigned to these proteins, but it may involve oxidoreductase enzymatic activity. These proteins contain one 4Fe-4S cluster, and one hybrid 4Fe-2O-2S cluster, the latter being similar to the Ni-Fe-S cluster found in carbon monoxide dehydrogenase enzymes (

) .

This subfamily is heterogeneous with respect to the presence or absence of a region of about 100 amino acids not far from the N terminus of the protein. Members have been described as monomeric. The general function is unknown, although members from E. coli and several other species have hydroxylamine reductase activity. Members are found in various bacteria, in Archaea, and in several parasitic eukaryotes: Giardia intestinalis, Trichomonas vaginalis, and Entamoeba histolytica.
MTA/SAH nucleosidase (MTA_SAH_Nsdase)
Type: Family

This entry represents the enzyme 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTA/SAH nucleosidase) (

) which acts on its two substrates at the same active site. This enzyme is involved in the recycling of the components of S-adenosylmethionine after it has donated one of its two non-ribose sulphur ligands to an acceptor. In the case of 5'-methylthioadenosine this represents the first step of the methionine salvage pathway in bacteria . This enzyme is essential for bacterial metabolism, while is absent in mammals, showing potential for antibiotic design .
5-methylthioadenosine/S-adenosylhomocysteine nucleosidase, putative (MTA_SAH_nuc_hyp)
Type: Family

This entry represents the enzyme 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase, which acts on its two substrates at the same active site , and similar sequences mainly found in alphaproteobacteria. This group of sequences is related but distinct to

. This enzyme is involved in the recycling of the components of S-adenosylmethionine after it has donated one of its two non-ribose sulphur ligands to an acceptor. In the case of 5'-methylthioadenosine this represents the first step of the methionine salvage pathway in bacteria .
Periplasmic nitrate reductase, large subunit (Periplasm_NO3_reductase_lsu)
Type: Family

This entry represents the large subunit of a family of nitrate reductases found in proteobacteria which are localised to the periplasm. This subunit binds molybdopterin and contains a twin-arginine motif at the N terminus. The protein associates with NapB, a soluble haem-containing protein and NapC, a membrane-bound cytochrome c. The periplasmic nitrate reductases are not involved in the assimilation of nitrogen, and are not directly involved in the formation of electrochemical gradients (i.e. respiration) either. Rather, the purpose of this enzyme is either dissimilatory (i.e. to dispose of excess reductive equivalents) or indirectly respiratory by virtue of the consumption of electrons derived from NADH via the proton translocating NADH dehydrogenase. The enzymes from Ralstonia eutropha (Alcaligenes eutrophus) and Paracoccus pantotrophus (Thiosphaera pantotropha) have been characterised. In Escherichia coli (as well as other organisms) this gene is part of a large nitrate reduction operon (napFDAGHBC).
Type II secretion system protein GspI (T2SS_protein-GspI)
Type: Family

GspI is a pseudopilin component of the type II secretion system (T2SS). It contains the prepilin signal sequences . In Pseudomonas aeruginosa GspI homologue, known as XcpV, has been suggested to be the central component and initiator of pseudopilus formation .

The type II secretion system (T2SS) is one of several extracellular secretion systems in gram-negative bacteria. It delivers toxins and a range of hydrolytic enzymes including proteases, lipases and carbohydrate-active enzymes to the cell surface or extracellular space . T2SS systems are composed of 11 to 15 different proteins, which are generally called GspA to GspO and GspS. The T2SS spans the two bacterial membranes and ensures secretion of folded proteins across the outer membrane pore formed by GspD. The inner membrane complex contains GspC, GspL, GspM, and GspF. The cytoplasmic domains of GspL and GspF interact with an ATPase, GspE. GspE is thought to energize the formation of a short pseudopilus by several pilin-like proteins, GspG to GspK . GspD has been shown to interact with the inner membrane component GspC .
Type II secretion system protein GspG (Type2_sec_GspG)
Type: Family

GspG is the major pseudopilin of the type 2 secretion systems (T2SSs). The N-terminal hydrophobic helices of the GspG subunits arrange within the core of the pseudopilus, with the C-terminal domains and the Ca2+-binding sites located at the surface. The structure of GspG (also known as PulG) has been revealed .

The type II secretion system (T2SS) is one of several extracellular secretion systems in gram-negative bacteria. It delivers toxins and a range of hydrolytic enzymes including proteases, lipases and carbohydrate-active enzymes to the cell surface or extracellular space . T2SS systems are composed of 11 to 15 different proteins, which are generally called GspA to GspO and GspS. The T2SS spans the two bacterial membranes and ensures secretion of folded proteins across the outer membrane pore formed by GspD. The inner membrane complex contains GspC, GspL, GspM, and GspF. The cytoplasmic domains of GspL and GspF interact with an ATPase, GspE. GspE is thought to energize the formation of a short pseudopilus by several pilin-like proteins, GspG to GspK . GspD has been shown to interact with the inner membrane component GspC .
Type II secretion system protein GspJ (T2SS_protein-GspJ)
Type: Family

This family of proteins represents GspJ which is targeted to the membrane of Escherichia coli. GspJ forms a complex with GspI and GspK, which is part of the type 2 secretion system, involved in the translocation of proteins across the outer membrane of E.coli. The GSPK-I-J complex has quasi-helical characteristics .

The type II secretion system (T2SS) is one of several extracellular secretion systems in gram-negative bacteria. It delivers toxins and a range of hydrolytic enzymes including proteases, lipases and carbohydrate-active enzymes to the cell surface or extracellular space . T2SS systems are composed of 11 to 15 different proteins, which are generally called GspA to GspO and GspS. The T2SS spans the two bacterial membranes and ensures secretion of folded proteins across the outer membrane pore formed by GspD. The inner membrane complex contains GspC, GspL, GspM, and GspF. The cytoplasmic domains of GspL and GspF interact with an ATPase, GspE. GspE is thought to energize the formation of a short pseudopilus by several pilin-like proteins, GspG to GspK . GspD has been shown to interact with the inner membrane component GspC .
Phage replisome organiser, N-terminal domain (Phage_rep_org__N)
Type: Domain

This entry represents the N-terminal domain of a small family of phage proteins. The proteins in this group contain a region of low-complexity sequence that reflects DNA direct repeats able to function as an origin of phage replication. The low-complexity region is adjacent to this N-terminal domain.
HTH-type transcriptional regulator Rgg, C-terminal domain (Transcription_activator_Rgg_C)
Type: Domain

This domain is found at the C-terminal of HTH-type transcriptional regulator Rgg (also called RopB) from Streptococcus gordonii, and similar proteins predominantly found in Firmicutes. Rgg is a peptide pheromone receptor that directly binds pheromones transported to the cytosol. The large C-terminal repeat domain contains five HTH folds and a capping helix that form a right-handed superhelical structure, resembling a TPR domain superhelix . This domain is found associated with the N-terminal helix-turn-helix DNA-binding domain

.
Uridine phosphorylase (Uridine_phosphorylase)
Type: Family

This entry represents a family of bacterial and archaeal uridine phosphorylases unrelated to the mammalian enzymes of the same name. The Escherichia coli , Salmonella and Klebsiella genes have been characterised. Sequences from Clostridium, Streptomyces, Treponema, Aeropyrum and Pyrobaculum are also included in this family, but it does not include related sequences from Halobacterium, which are more distantly related and represent enzymes with a slightly different substrate specificity. Also distantly related is a clade of archaeal sequences which are related to the DeoD family of inosine phosphorylases (

) as they are to these uridine phosphorylases. This clade includes a characterised protein from Sulfolobus solfataricus which has been misnamed as a methylthioadenosine phosphorylase, but which acts on inosine and guanosine - it is unclear whether uridine has been evaluated as a substrate .
Uridine phosphorylase, eukaryotic (Uridine_phosphorylase_euk)
Type: Family

This entry represents a clade of mainly eukaryotic uridine phosphorylases. Uridine phosphorylase (UP) catalyzes the reversible phosphorolysis of uracil ribosides and analogous compounds to their respective nucleobases and ribose 1-phosphate. Human UPP1 has a role in the activation of pyrimidine nucleoside analogues used in chemotherapy, such as 5-fluorouracil . This subfamily belongs to the nucleoside phosphorylase-I (NP-I) family, whose members accept a range of purine nucleosides as well as the pyrimidine nucleoside uridine. The NP-I family is distinct from nucleoside phosphorylase-II, which belongs to a different structural family.
Non-ribosomal peptide synthase (NRPS_synth)
Type: Domain

This entry represents a region of 171 amino acids long and contains three very highly conserved regions. At the N terminus is a nearly invariant lysine (position 11) followed by xxxRxxPxxGxGYG in which the proline and the first glycine are invariant. This is followed approximately 22 residues later by the motif FNYLG. Near the C terminus of the domain is the sequence TxSD where the serine and aspartate are nearly invariant. This domain appears to be located immediately downstream from a condensation domain (

), and is followed primarily by the end of the molecule or another condensation domain (or, in a few cases, it is followed by

, an AMP-binding module). The converse is not true,

domains are not always followed by this domain, which implicates this domain in possible post-condensation modification events.

This region has so far been found in a variety of peptide synthases including

Bacitracin synthetase 1

Gramicidin S synthetase 1

Linear gramicidin synthetase subunit A

Surfactin synthetase subunit 1

Tyrocidine synthetase 1

It is also found in Vanchrobactin synthetase VabF which is involved in the synthesis of the siderophore vanchrobactin .
Methylmalonate-semialdehyde dehydrogenase (MeMal-semiAld_DH)
Type: Family

Methylmalonate-semialdehyde dehydrogenase (MMSDH,

) catalyses the irreversible NAD+- and CoA-dependent oxidative decarboxylation of methylmalonate semialdehyde to propionyl-CoA. Methylmalonate-semialdehyde dehydrogenase has been characterised in both prokaryotes and eukaryotes , functioning as a mammalian tetramer and a bacterial homodimer. Although similar in monomeric molecular mass and enzymatic activity, the N-terminal sequence in Pseudomonas aeruginosa does not correspond with the N-terminal sequence predicted for rat liver. Sequence homology to a variety of prokaryotic and eukaryotic aldehyde dehydrogenases places MMSDH in the aldehyde dehydrogenase (NAD+) superfamily making MMSDH's CoA requirement unique among known ALDHs. Methylmalonate semialdehyde dehydrogenase is closely related to betaine aldehyde dehydrogenase, 2-hydroxymuconic semialdehyde dehydrogenase, and class 1 and 2 aldehyde dehydrogenase .
5,10-methenyltetrahydromethanopterin hydrogenase (HMD_)
Type: Family

The N(5),N(10)-methylenetetrahydromethanopterin dehydrogenase system of methanogenic archaea is composed of H2-forming methylenetetrahydromethanopterin dehydrogenase (Hmd,

) and F420-dependent methylenetetrahydromethanopterin dehydrogenase (

) . Hmd is an iron-sulphur-cluster-free enzyme that contains an intrinsic CO ligand bound to iron . The Hmd enzymes can be divide into two distinct subgroups: one has been experimentally characterised as H2-forming N(5),N(10)-methenyltetrahydromethanopterin dehydrogenase (Hmd or HmdI), and the other one contains isozymes that have not been experimentally characterised (HmdII and HmdIII). Because all three isozyme forms are present in each of the corresponding sequenced genomes, it has been suggested that HmdII and HmdIII may not exhibit Hmd activity and may have a different biological function .

This entry represents the experimentally characterised (HmdI) subgroup of the N(5),N(10)-methylenetetrahydromethanopterin dehydrogenases.
H(2)-forming methylenetetrahydromethanopterin dehydrogenase-related protein (HMDII/III)
Type: Family

This family consists of two members, designated HmdII and HmdIII, restricted to methanogens. They are homologues of the enzyme Hmd, a H2-forming N(5),N(10)-methenyltetrahydromethanopterin dehydrogenase. Because all three isozyme forms are present in each of the corresponding sequenced genomes, it has been suggested that HmdII and HmdIII may not exhibit Hmd activity and may have a different biological function . Based on its ability to bind to aminoacyl-tRNA synthetases and tRNA, a role for HmdII has been proposed as a regulator of protein synthesis that senses intracellular methylene-H4 MPT concentration .
Bacteriophage HK97-gp10, putative tail-component (HK97-gp10_tail)
Type: Family

This family is found in HK97-gp10-like phage proteins. These may be tail component proteins.
Amino acid ABC transporter, permease protein, 3-TM domain (AA_ABC_transptr_permease_3TM)
Type: Domain

ABC transporters are minimally constituted of two conserved regions: a highly conserved ATP binding cassette (ABC) and a less conserved transmembrane domain (TMD). These regions can be found on the same protein (mostly in eukaryotes and bacterial exporters) or on two different ones (mostly bacterial importers) .

This entry represents the membrane component of a group of amino acid transport systems, such as histidine transport system HisM and HisQ subunits . The region covered by this domain is predicted to contain three transmembrane helices in general. Substrate specificities attributed to permeases recognised by this entry include histidine, arginine, glutamine, glutamate, and (in Agrobacterium) the opines octopine and nopaline .
Aliphatic sulfonates-binding protein (ABC_SsuA_sub-bd)
Type: Family

Members of this family are substrate-binding periplasmic proteins of ABC transporters. This subfamily includes SsuA, a member of a transporter operon needed to obtain sulphur from aliphatic sulphonates. Related proteins include taurine (NH2-CH2-CH2-S03H) binding proteins, the probable sulphate ester binding protein AtsR, and the probable aromatic sulphonate binding protein AsfC. All these families make sulphur available when Cys and sulphate levels are low .
Taurine ABC transporter, substrate-binding protein TauA (Peri-bd_TauA)
Type: Family

This entry represents taurine-binding periplasmic protein TauA. TauA is part of tauABCD gene cluster involved in sulfonate transport in sulphate starvation condition. TauA plays a major role in ABC transport system and could be ideal candidate to serve as taurine catcher in biological fluids . The most closely related proteins outside this family are putative aliphatic sulphonate binding proteins.
Toxin CdiA-like, Filamentous hemagglutinin motif repeats (CdiA_FHA1_rpt)
Type: Repeat

This entry represents several repeats of the filamentous hemagglutinin (FHA-1) motif, which have approximately 20 amino acids. The repeats are found at the N-terminal domain of Toxin CdiA from Escherichia coli and similar proteins mostly from bacterial species, including several plant and animal pathogens. The FHA-1 repeats found in the extracellular filament of CdiA form an elongated β-helix, with each ~20-residue motif extending the helix .

CdiA is a toxic component of a toxin-immunity protein module, which functions as a cellular contact-dependent growth inhibition (CDI) system CDI modules allow bacteria to communicate with and inhibit the growth of closely related neighbouring bacteria in a contact-dependent fashion. CDI is neutralised by its cognate immunity protein CdiI, but not by non-cognate CdiI from other bacteria .

Some proteins with nuclease activity on top of the toxin activity are also included in this group, such as tRNA nuclease CdiA from Escherichia coli. This protein cleaves tRNA (CUG-Gln) in the acceptor stem between C70 and A71 [

. 16S rRNA endonuclease CdiA from Enterobacter cloacae cleaves 16S rRNA in vivo and in vitro between adenine 1493 and guanosine 1494 of E.coli 16S rRNA .
Sporulation protein YjcZ-like (YjcZ-like)
Type: Family

Endospores of B. subtilis are encased in a thick protein shell known as the spore coat. The coat's complex structure comprises an inner coat (IC) and an outer coat (OC), and includes more than 70 spore-specific proteins. This entry includes several sporulation-specific proteins including YjcZ and SscA, which is involved in spore germination and spore coat assembly .