SII-SWORD/CoKE huggingface dataset:
Pyridoxal-dependent decarboxylase, exosortase system type 1 associated (DCO2ase_PEP1)
Type: Family

The sequences in this family contain the pyridoxal binding domain and C-terminal sheet domain of a family of Pyridoxal-dependent decarboxylases. Characterised enzymes in this family decarboxylate substrates such as ornithine, diaminopimelate and arginine.

The proteins found in tyhis entry, with the exception of those observed in certain Burkholderia species, are all found in the context of exopolysaccharide biosynthesis loci containing the exosortase/PEP-CTERM protein sorting system . More specifically, these are characteristic of the type 1 exosortase system represented by

. The substrate of these enzymes may be a precursor of the carrier or linker which is hypothesized to release the PEP-CTERM protein from the exosortase enzyme. These enzymes are apparently most closely related to the diaminopimelate decarboxylase found in

, which may suggest a similarity (or identity) of substrate.
Hydrolase, ortholog 1, exosortase system type 1 associated (Hydrolase-1_PEP)
Type: Family

This group of proteins are members of the alpha/beta hydrolase superfamily. These proteins are generally found in genomes containing the exosortase/PEP-CTERM protein export system , specifically the type 1 variant of this system described by

. When found in this context they are invariably present in the vicinity of a second, relatively unrelated enzyme (orthologue 2,

) of the same superfamily.
Hydrolase, ortholog 2, exosortase system type 1 associated (Hydrolase-2_PEP)
Type: Family

This group of proteins are members of the alpha/beta hydrolase superfamily. These proteins are generally found in genomes containing the exosortase/PEP-CTERM protein export system , specifically the type 1 variant of this system described by

. When found in this context they are invariably present in the vicinity of a second, relatively unrelated enzyme (orthologue 1,

) of the same superfamily.
Halocyanin, copper-binding domain (Halocyanin)
Type: Domain

Halocyanins are blue (type I) copper redox proteins found in halophilic archaea such as Natronomonas pharaonis (Natronobacterium pharaonis). Halocyanin from from N. pharaonis has been characterised

and shown to be a small blue copper protein with a molecular mass of about 15.5kDa . This protein, which was named halocyanin, contains one Cu2+, with a copper-binding site containing two His, one Met, and one Cys as probable ligands. It is probable that halocyanin is a peripheral membrane protein, which serves as a mobile electron carrier.

This entry represents the copper-binding domain of halocyanins. This domain is present only once in some halocyanins and is duplicated in others. It is not found in plastocyanins or certain divergent paralogs of halocyanin.
GNAT-acetyltransferase (GNAT-acetyltransferase)
Type: Family

Members of this protein family belong to the GNAT family of acetyltransferases. Each is part of a conserved three-gene cassette sparsely distributed across at least twenty different species known so far, including alpha, beta, and gamma Proteobacteria, Mycobacterium, and Prosthecochloris, which is a member of the Chlorobi. The other two members of the cassette are a probable protease and an asparagine synthetase family protein.
Asparagine synthase family amidotransferase (Asparagine_synth)
Type: Family

Members of this protein family are closely related to several isoforms of asparagine synthetase (glutamine amidotransferase) and typically have been given this name in genome annotations to date. Each is part of a conserved three-gene cassette sparsely distributed across at least twenty different species known so far, including alpha, beta, and gamma Proteobacteria, Mycobacterium, and Prosthecochloris, which is a member of the Chlorobi. The other two members of the cassette are a probable protease and a member of the GNAT family of acetyltransferases.
Glutamine synthetase, type III (Glutamine_synthetase_typeIII)
Type: Family

This family consists of the type III isozyme of glutamine synthetase (GS), originally described in Rhizobium meliloti (Sinorhizobium meliloti), where types I and II also occur . This family also includes the GSIII-like protein gamma-glutamylmethylamide synthetase, also known as glutamate--methylamine ligase .
Peptidase M42, hydrolase (Peptidase_M42_hydrolase)
Type: Family

This entry contains sequences related to MEROPS peptidase family M42, a glutamyl aminopeptidase family that also includes the cellulase CelM from Clostridium thermocellum and deblocking aminopeptidases that can remove acylated amino acids. Members of this family occur in a three gene cassette with an amidotransferase (

)in the asparagine synthase (glutamine-hydrolysing) family, and a probable acetyltransferase (

) in the GNAT family.
Peptidase M42, glutamyl aminopeptidase (Pept_M42_glutamyl_aminopept)
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 entry contains glutamyl aminopeptidases belonging to MEROPS family M42 (glutamyl aminopeptidase family, clan MH). The family includes the deblocking aminopeptidases from Pyrococcus horikoshii and related species, and endo-1,4-beta-glucanase (cellulase M) from Clostridium thermocellum.
XrtA/PEP-CTERM system amidotransferase (XrtA_amidotfase)
Type: Family

The predicted protein-sorting transpeptidase that we call exosortase (see

) has distinct subclasses that associated with different types of exopolysaccharide production loci. This entry represents a distinct clade among a set of amidotransferases largely annotated (not necessarily accurately) as glutamine-hydrolysing asparagine synthases. Members of this clade are essentially restricted to the characteristic exopolysaccharide (EPS) regions that encode the exosortase XrtA, in genomes that also have numbers of PEP-CTERM domain (

) proteins.
Exosortase 1 (Exosortase-1)
Type: Family

This entry represents predicted protein-sorting transpeptidases, called exosortases (see

), which have distinct subclasses that associate with different types of exopolysaccharide production loci. This is the most common type, exosortase 1/CrtA; it is analogous to srtA, which represents the most common type of sortase in Gram-positive bacteria.
Exosortase family protein XrtG (Exosort-XrtG)
Type: Family

Members of this protein family are found in a modest number of non-pathogenic Gram-positive bacteria, including three species of Lactococcus. Three paralogues exist in Clostridium acetobutylicum. This protein appears related to the conserved core region of a family of proposed transpeptidases, exosortase (previously EpsH), thought to act on PEP-CTERM proteins. The protein has been assigned the gene symbol XrtG (eXosoRTase family protein of Gram-positives).
XrtG-associated glycosyltransferase (XrtG-assoc_glycosyltfrase)
Type: Family

Members of this protein family are probable glycosyltransferases of family 2, whose genes are near those for the exosortase homologue XrtG (

), which is restricted to Gram-positive bacteria. Other genes in the conserved gene neighbourhood include a 6-pyruvoyl tetrahydropterin synthase homologue (

) and an uncharacterised integral membrane protein (

).
6-pyruvoyl tetrahydropterin synthase-related, bacteria (6-PTP_synth-rel_bac)
Type: Family

Members of this family are restricted to the bacteria, but resemble eukaryotic known and prokaryotic predicted 6-pyruvoyl tetrahydropterin synthases.
Exosortase 2 (Exosortase-2)
Type: Family

This entry includes predicted protein-sorting transpeptidases called exosortases (see

) which have distinct subclasses associated with different types of exopolysaccharide production loci. Members of this entry are relatively uncommon proteobacterial type designated to be type 2/XrtB. This entry includes the probable exosortase EpsH from Methylobacillus sp., a transpeptidase that recognises and modifies its substrate by proteolytic cleavage of a sorting signal . Most species encountered so far with XrtB also contain XrtA (

).
CRISPR-associated protein Csf1 (CRISPR-assoc_prot_Csf1)
Type: Family

This entry represents the Csf1 family of Cas proteins. Members of this family show up near CRISPR repeats in Acidithiobacillus ferrooxidans ATCC 23270, Azoarcus sp. (strain EbN1), and Rhodoferax ferrireducens (strain DSM 15236/ATCC BAA-621/T118). In the latter two species, the CRISPR/cas locus is found on a plasmid. This family is one of several characteristic of a type of cas gene cluster we designate Aferr after A. ferrooxidans, where it is both chromosomal and the only type of cas gene cluster found. The gene is designated csf1 (CRISPR/cas Subtype as in A. ferrooxidans protein 1), as it lies closest to the repeats.

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.
CRISPR type IV/AFERR-associated protein Csf2 (CRISPR-assoc_prot_Csf2)
Type: Family

This entry represents the Csf2 family of Cas proteins. Members of this family show up near CRISPR repeats in Acidithiobacillus ferrooxidans ATCC 23270, Azoarcus sp. (strain EbN1), and Rhodoferax ferrireducens (strain DSM 15236/ATCC BAA-621/T118). In the latter two species, the CRISPR/cas locus is found on a plasmid. This family is one of several characteristic of a type of cas gene cluster we designate Aferr after A. ferrooxidans, where it is both chromosomal and the only type of cas gene cluster found. The gene is designated csf2 (CRISPR/cas Subtype as in A. ferrooxidans protein 2), as it lies second closest to the repeats.

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.
CRISPR type IVassociated protein Csf3 (CRISPR-assoc_prot_Csf3)
Type: Family

This entry represents the Csf3 family of Cas proteins. Members of this family show up near CRISPR repeats in Acidithiobacillus ferrooxidans ATCC 23270, Azoarcus sp. (strain EbN1), and Rhodoferax ferrireducens (strain DSM 15236/ATCC BAA-621/T118). In the latter two species, the CRISPR/cas locus is found on a plasmid. This family is one of several characteristic of a type of cas gene cluster we designate Aferr after A. ferrooxidans, where it is both chromosomal and the only type of cas gene cluster found. The gene is designated csf3 (CRISPR/cas Subtype as in A. ferrooxidans protein 3), as it lies third closest to the repeats.

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.
CRISPR-associated DEAD/DEAH-box helicase Csf4 (CRISPR-assoc_helicase_Csf4)
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 Csf4 family of DEAD/DEAH-box helicases. Members of this Cas family show up near CRISPR repeats in Acidithiobacillus ferrooxidans ATCC 23270, Azoarcus sp. (strain EbN1), and Rhodoferax ferrireducens (strain DSM 15236/ATCC BAA-621/T118). In the latter two species, the CRISPR/cas locus is found on a plasmid. This family is one of several characteristic of a type of cas gene cluster we designate Aferr after A. ferrooxidans, where it is both chromosomal and the only type of cas gene cluster found. The gene is designated csf4 (CRISPR/cas Subtype as in A. ferrooxidans protein 1), as it lies farthest (fourth closest) from the repeats in the A. ferrooxidans genome.
Acanthamoeba polyphaga mimivirus, L690 (APMV_L690)
Type: Domain

This entry is represented by Acanthamoeba polyphaga mimivirus, L690. These proteins are uncharacterised. Members are found with a C-terminal putative exosortase interaction domain, PEP-CTERM, in Nitrosospira multiformis, Rhodoferax ferrireducens, Solibacter usitatus (strain Ellin6076), and Acidobacteria bacterium (strain Ellin345). Some members are found not to have the PEP-CTERM domain in several other species, including Burkholderia ambifaria, Gloeobacter violaceus PCC 7421, and three copies in Acanthamoeba polyphaga mimivirus (APMV).
Formylmethanofuran dehydrogenase subunit C (Formylmethanofuran_DH_suC)
Type: Domain

This entry represents the C subunit of formylmethanofuran dehydrogenase (

), which is involved in methane biosynthesis from carbon dioxide . This oxygen-labile enzyme catalyses the reversible oxidation of carbon dioxide and methanofuran (MFR) to N-formylmethanofuran (CHO-MFR). There is a tungsten-containing (Fwd) form of this enzyme and a molybdenum-containing (Fmd) form; this entry includes both forms . Formylmethanofuran dehydrogenase is composed of 5-7 subunits, of which subunit C (FwdC or FmdC) is one. The enzymes in this entry are largely from archaeal species. Nomenclature in some bacteria may reflect inclusion of the formyltransferase described by

as part of the complex.
Triphosphoribosyl-dephospho-CoA synthase CitG (TriPribosyl-deP-CoA_syn_CitG)
Type: Family

Triphosphoribosyl-dephospho-CoA is transferred to, and becomes the prosthetic group of, the respective acyl carrier protein subunits of both citrate lyase and malonate decarboxylase. Members of this protein family are triphosphoribosyl-dephospho-CoA synthases specifically from citrate lyase systems . CitG sometimes occurs as a fusion protein with CitX. CitX transfers the prosthetic group 2'-(5''-triphosphoribosyl)-3'-dephospho-CoA to the citrate lyase gamma chain, an acyl carrier protein.
3-hexulose-6-phosphate isomerase (PHI/rmpB)
Type: Family

6-phospho 3-hexuloisomerase (PHI, also known as rmpB) is part of the ribulose monophosphate (RuMP) pathway, which in one direction removes the toxic metabolite formaldehyde by assimilation into fructose-6-phosphate . In the other direction, in species lacking a complete pentose phosphate pathway, the RuMP pathway yields ribulose-5-phosphate, necessary for nucleotide biosynthesis, at the cost of also yielding formaldehyde. These latter species tend usually have a formaldehyde-activating enzyme to attach formaldehyde to the C1 carrier tetrahydromethanopterin.
3-hexulose-6-phosphate synthase (3-hexulose-6-phosphate_synth)
Type: Domain

Proteins in this entry are 3-hexulose-6-phosphate synthase (HPS), or the HPS domain of a fusion protein. This enzyme is part of the ribulose monophosphate (RuMP) pathway, which in one direction removes the toxic metabolite formaldehyde by assimilation into fructose-6-phosphate. In the other direction, in species lacking a complete pentose phosphate pathway, the RuMP pathway yields ribulose-5-phosphate, necessary for nucleotide biosynthesis, at the cost of also yielding formaldehyde. These latter species tend usually have a formaldehyde-activating enzyme to attach formaldehyde to the C1 carrier tetrahydromethanopterin. In these species, the enzyme is viewed as a lyase rather than a synthase and is called D-arabino 3-hexulose 6-phosphate formaldehyde lyase. Note that there is some overlap in specificity with the Escherichia coli enzyme 3-keto-L-gulonate 6-phosphate decarboxylase.
Malonate decarboxylase, McdH subunit (Malonate_deCOase_MdcHsu)
Type: Family

The McdH subunit of malonate decarboxylase is a malonyl-CoA:ACP transacylase . It initiates the activation of malonate decarboxylase by malonyl-transfer to an acetylated phosphoribosyl dephospho-CoA prosthetic group on the acyl carrier subunit.
Triphosphoribosyl-dephospho-CoA synthase (TriPribosyl-deP-CoA_syn)
Type: Family

Triphosphoribosyl-dephospho-CoA synthase (MdcB; (

) acts in cofactor biosynthesis, preparing the coenzyme A derivative that becomes attached to the malonate decarboxylase acyl carrier protein (or delta subunit) . The closely related protein CitG of citrate lyase produces the same molecule, but the two families are nonetheless readily separated.
Biotin-independent malonate decarboxylase, beta subunit (Malonate_beta)
Type: Family

Members of this protein family are the beta subunit of malonate decarboxylase. Malonate decarboxylase may be a soluble enzyme, or linked to membrane subunits and active as a sodium pump. In the malonate decarboxylase complex, the beta subunit appears to act as a malonyl-CoA decarboxylase .
Phosphoribosyl-dephospho-CoA transferase (Holo-ACP_synthase)
Type: Family

Members of this protein family are the phosphoribosyl-dephospho-CoA transferase specific to the malonate decarboxylase system. This enzyme can also be designated holo-ACP synthase (

). The corresponding component of the citrate lyase system, CitX, shows little or no sequence similarity to this family.

Malonate decarboxylase, like citrate lyase, has a unique acyl carrier protein subunit with a prosthetic group derived from, and distinct from, coenzyme A.
Malonate decarboxylase, carboxybiotin decarboxylase subunit, Na+ transporting (Malonate_biotin)
Type: Family

Malonate decarboxylase can be a soluble enzyme, or a sodium ion-translocating with additional membrane-bound components. Members of this protein family are integral membrane proteins required to couple decarboxylation to sodium ion export. This family belongs to a broader family of sodium ion-translocating decarboxylase beta subunits.
Alkyl hydroperoxide reductase subunit C (AhpC)
Type: Family

This peroxiredoxin (AhpC, alkylhydroperoxide reductase subunit C) is one subunit of a two-subunit complex with subunit F(

). Usually these are found as an apparent operon. The gene has been characterised in Bacteroides fragilis where it is important in oxidative stress defence. This gene contains two invariant cysteine residues, one near the N terminus and one near the C terminus, each followed immediately by a proline residue.

This entry also includes PrxU, a selenocysteine-containing peroxiredoxin.
Cytochrome c-type biogenesis protein CcmI (Cyt_c_biogenesis_CcmI)
Type: Domain

This TPR repeat-containing protein is the CcmI protein (also called CycH) of c-type cytochrome biogenesis. CcmI is thought to act as an apo-cytochrome c chaperone. This entry describes the N-terminal region.
Alkyl hydroperoxide reductase F subunit homogue, putative (AhpF_homologue_put)
Type: Family

This family of thioredoxin reductase homologues is found adjacent to the alkylhydroperoxide reductase C subunit predominantly in cases where there is only one C subunit in the genome and that genome is lacking the F subunit partner (AhpF). Subunit F is also a thioredoxin reductase homologue (

).
Cytochrome c-type biogenesis protein CcsA (Cyt_c_biogenesis_CcsA)
Type: Family

The CcsA protein family represents one of two essential proteins in system II c-type cytochrome biogenesis . Additional proteins tend to be part of the system but can often be replaced by chemical reductants such as dithiothreitol. These proteins are often named CcsB in Bordetella and some other bacteria, ResC in Bacillus (where there is additional N-terminal sequence), while chloroplast proteins are consistently named CcsA.
Cytochrome c nitrate reductase biogenesis protein NrfE (CytC_NO3Rdtase_biogenesis_NrfE)
Type: Family

Members of this protein family closely resemble the CcmF protein of the CcmABCDEFGH system, or system I, for c-type cytochrome biogenesis (

). Members are found, as a rule, next to closely related paralogues of CcmG and CcmH and always located near other genes associated with the cytochrome c nitrite reductase enzyme complex. As a rule, members are found in species that also encode bona fide members of the CcmF, CcmG, and CcmH families.
Cytochrome c-type protein NrfB (Cyt_c_NrfB)
Type: Family

Members of this protein family each contain five copies of the CXXCH haem-binding motif, and represent the NrfB component of the multi-subunit enzyme, cytochrome c nitrite reductase.
Formate-dependent nitrite reductase complex, subunit NrfF (For-dep_Cytc_NO2Rdtase_NrfF)
Type: Domain

The genes NrfE, NrfF, and NrfG are required for the formate-dependent nitrite reduction pathway, which involves at least two C-type cytochrome proteins, NrfA and NrfB. The NrfE, NrfF, and NrfG genes (haem lyase complex) are involved in the maturation of a special C-type cytochrome, apocytochrome C (apoNrfA), to cytochrome C (NrfA) by transferring a haem to the unusual haem binding motif of the Cys-Trp-Ser-Cys-Lys sequence in apoNrfA protein .
NrfD (NrfD)
Type: Family

Members of this protein family are NrfD, a highly hydrophobic protein encoded in the nrf operon, which encodes cytochrome c nitrite reductase. This multiple haem-containing enzyme can reduce nitrite to ammonia. Members belong to a broader protein family, which also contains an NrfD-related subunit of polysulphide reductase.
Cytochrome c nitrite reductase, Fe-S protein (Cyt_c_NO2Rdtase_NrfC)
Type: Family

Members of this protein family are the Fe-S protein, NrfC, of the cytochrome c nitrite reductase system for which the pentaheme cytochrome c protein, NrfB (family

) is an unambiguous marker. Members of this protein family show similarity to other ferredoxin-like proteins, including a subunit of polysulphide reductase.
3-oxoacyl-[acyl-carrier-protein] synthase 2 (3-oxoacyl-ACP_synth-2)
Type: Family

3-oxoacyl-[acyl-carrier-protein] synthase 2 (KAS-II, FabF) is involved in the condensation step of fatty acid biosynthesis in which the malonyl donor group is decarboxylated and the resulting carbanion used to attack and extend the acyl group attached to the acyl carrier protein . Most genomes encoding fatty acid biosynthesis contain a number of condensing enzymes, often of all three types: 1, 2 and 3. Synthase 2 is mechanistically related to synthase 1 (KAS-I, FabB) containing a number of absolutely conserved catalytic residues in common . This model is based primarily on genes which are found in apparent operons with other essential genes of fatty acid biosynthesis ((

). The large gap between the trusted cut-off and the noise cut-off contains many genes which are not found adjacent to genes of the fatty acid pathway in genomes that often also contain a better hit to this model. These genes may be involved in other processes such as polyketide biosyntheses. Some genomes contain more than one above-trusted hit to this model which may result from recent paralogous expansions. Second hits to this model which are not next to other fatty acid biosynthesis genes may be involved in other processes. FabB sequences should fall well below the noise cut-off of this model.
Enoyl-(acyl-carrier-protein) reductase II, putative (Enoyl_ACP_red-II_put)
Type: Family

This oxidoreductase of the 2-nitropropane dioxygenase family is commonly found in apparent operons with genes involved in fatty acid biosynthesis. Furthermore, this genomic context generally includes fabG, 3-oxoacyl-[ACP] reductase, and lacks the fabI enoyl-[ACP] reductase.