SII-SWORD/CoKE huggingface dataset:
Nickel ABC transporter, permease subunit NikB (Nickel_NikB)
Type: Family

This entry includes NikB from E.coli and related sequences mainly from gammaprotebacteria and bacilli.

This family consists of the NikB family of nickel ABC transporter permeases. The NikABCDE uptake system that contains this protein also contain a homologous permease subunit NikC . Based on sequence similarity, NikA is the periplasmic binding protein, NikB and NikC are the membrane components, and NikD and NikE are the ATP-binding components of the ABC transporter. Nickel is used in cells as part of urease or certain hydrogenases or superoxide dismutases. To avoid nickel toxicity, the synthesis of the Nik system is tightly controlled by the nickel-responsive repressor NikR .
Type IV secretion system, VirB5 (T4SS_VirB5)
Type: Family

This entry contains VirB5, a protein that is involved in the type IV DNA secretion systems typified by the Agrobacterium Ti plasmid vir system where it interacts with several other proteins essential for proper pilus formation . VirB5 is homologous to the IncN (N-type) conjugation system protein TraC as well as the P-type protein TrbJ and the F-type protein TraE .
Protocatechuate 4,5-dioxygenase, alpha subunit (PCA_LigA)
Type: Family

Protocatechuate (PCA) 4,5-dioxygenase is the first enzyme in the PCA 4,5-cleavage pathway that is an alternative to PCA 3,4-cleavage and PCA 2,3 cleavage pathways . PCA is an intermediate in the breakdown of lignin (hence the gene symbol ligA) and other compounds. It is composed of A and B subunits that form a tetramer . Members of this family are the alpha chain of PCA 4,5-dioxygenase, or the equivalent domain of a fusion protein.

PCA 4,5-dioxygenase is one of the aromatic ring opening dioxygenases which play key roles in the degradation of aromatic compounds. As a member of the Class III extradiol dioxygenase family, LigAB uses a non-heme Fe(II) to cleave aromatic rings between a hydroxylated carbon and an adjacent non-hydroxylated carbon .
Nickel-responsive transcriptional regulator NikR, proteobacteria (Nickel_NikR_proteobac)
Type: Family

The members of this entry from Escherichia coli, Pseudomonas putida, and Brucella melitensis, are found associated with a nickel ABC transporter operon that acts to import nickel for use as a cofactor in urease or hydrogenase. These proteins, with characterised nickel-binding and DNA-binding domains, act as nickel-responsive transcriptional regulators .
Tol-Pal system, TolA (Tol-Pal_TolA)
Type: Family

Tol proteins are involved in the translocation of group A colicins. Colicins are bacterial protein toxins, which are active against Escherichia coli and other related species. TolA is anchored to the cytoplasmic membrane by a single membrane spanning segment near the N terminus, leaving most of the protein exposed to the periplasm .

TolA couples the inner membrane complex of itself with TolQ and TolR to the outer membrane complex of TolB and OprL (also called Pal). Most of the length of the protein consists of low-complexity sequence that may differ in both length and composition from one species to another, complicating efforts to discriminate TolA (the most divergent gene in the tol-pal system) from paralogs such as TonB. Selection of members of the seed alignment and criteria for setting scoring cut-offs are based largely on conserved operon structure. The Tol-Pal complex is required for maintaining outer membrane integrity, and is also involved in transport (uptake) of colicins and filamentous DNA, and implicated in pathogenesis . Transport is energized by the proton motive force. TolA is an inner membrane protein that interacts with periplasmic TolB and with outer membrane porins OmpC, PhoE and LamB.
Cell division coordinator CpoB, C-terminal (CpoB_C)
Type: Domain

Members of this protein family are the product of one of seven genes regularly clustered in operons to encode the proteins of the tol-pal system, which is critical for maintaining the integrity of the bacterial outer membrane. The gene for this periplasmic protein has been designated orf2 and ybgF, which is then renamed CpoB (Coordinator of PG synthesis and OM constriction, associated with PBP1B). All members of the seed alignment were from unique tol-pal gene regions from completed bacterial genomes. The architecture of this protein is a signal sequence, a low-complexity region usually rich in Asn and Gln, and a well-conserved region with tandem repeats that resemble the tetratricopeptide (TPR) repeat, involved in protein-protein interaction .

Escherichia CpoB coordinates PBP1B and the Tol machines to maintain cell envelope integrity during division .
Tol-Pal system, TolQ (Tol-Pal_TolQ)
Type: Family

TolQ is one of the essential components of the Tol-Pal system. Together with TolR, it harnesses proton motive force to energize TolA, which spans the periplasm to reach the complex of TolB and Pal at the outer member. The tol-pal system proves to be important for maintaining outer membrane integrity . Gene pairs similar to the TolQ and TolR gene pair often number several per genome, but this entry describes TolQ specifically, as found in tol-pal operons. A close homologue, excluded from this entry, is ExbB of the ExbB/ExbD/TonB protein complex, which powers transport of siderophores and vitamin B12 across the bacterial outer membrane. The Tol-Pal system is exploited by colicin and filamentous phage DNA to enter the cell . It is also implicated in pathogenesis in several bacterial species .
TonB-system energizer ExbB type-1 (TonB_ExbB_1)
Type: Family

This entry describes ExbB proteins, part of the MotA/TolQ/ExbB protein family. The paired proteins MotA and MotB, TolQ and TolR, and ExbB and ExbD harness the proton-motive force to drive the flagellar motor, energize the Tol-Pal system, or energize TonB, respectively. Tol-Pal and TonB are both active at the outer membrane. Genomes may have many different TonB-dependent receptors, of which many of those characterised are involved in siderophore transport across the outer membrane.

In E. coli, ExbB together with the ExbD and TonB proteins is involved in energy-coupled transport across the outer membrane .
4-carboxy-4-hydroxy-2-oxoadipate aldolase/oxaloacetate decarboxylase (LigK_PcmE)
Type: Family

4-Hydroxy-4-methyl-2-oxoglutarate (HMG)/4-carboxy-4-hydroxy-2-oxoadipate (CHA) aldolases are class II (divalent metal ion dependent) pyruvate aldolases from the meta cleavage pathways of protocatechuate and gallate . This enzyme of the protocatechuate 4,5-cleavage pathway converts its substrate to pyruvate plus oxaloacetate. Protocatechuate is an intermediate in many pathways for degrading aromatic compounds, including lignin and fluorene. LigK gene has been shown to be, not only a 4-carboxy-4-hydroxy-2-oxoadipate aldolase but also the enzyme of the following step, oxaloacetate decarboxylase .
Tol-Pal system-associated acyl-CoA thioesterase (Tol-Pal_acyl-CoA_thioesterase)
Type: Family

The tol-pal system consists of five critical genes. Inner membrane proteins TolQ and TolR convert proton motive force to energy that is transduced through TolA to an outer membrane complex of TolB and Pal. The system is known to be required to maintain outer membrane integrity. In a system with several homologous parts, ExbB and ExbD transduces energy through TonB to a variety of outer membrane proteins, many of which are siderophore receptors. The tol-pal system therefore may also be involved in transport. This family consists of a protein nearly always found in operons with the genes of the tol-pal system. The significance of this thioesterase to the tol-pal system is unclear, but either of two observations may be relevant. First, Pal, or peptidoglycan-associated lipoprotein, has a conserved N-terminal cleavage and acylation that makes it a lipoprotein. Second, the tol-pal system is implicated not only in the import of certain organics but also in the maintenance of outer membrane integrity (by an unknown mechanism) .
Tol-Pal system protein TolB (Tol-Pal_TolB)
Type: Family

Members of this protein family are the TolB periplasmic protein of Gram-negative bacteria. TolB is part of the Tol-Pal (peptidoglycan-associated lipoprotein) multiprotein complex, comprising five envelope proteins, TolQ, TolR, TolA, TolB and Pal, which form two complexes. The TolQ, TolR and TolA inner-membrane proteins interact via their transmembrane domains. The β-propeller domain of the periplasmic protein TolB is responsible for its interaction with Pal. TolB also interacts with the outer-membrane peptidoglycan-associated proteins Lpp and OmpA. TolA undergoes a conformational change in response to changes in the proton-motive force, and interacts with Pal in an energy-dependent manner. The C-terminal periplasmic domain of TolA also interacts with the N-terminal domain of TolB. The Tol-PAL system is required for bacterial outer membrane integrity. Escherichia coli TolB is involved in the tonB-independent uptake of group A colicins (colicins A, E1, E2, E3 and K), and is necessary for the colicins to reach their respective targets after initial binding to the bacteria. It is also involved in uptake of filamentous DNA. Study of its structure suggests that the TolB protein might be involved in the recycling of peptidoglycan or in its covalent linking with lipoproteins. The Tol-Pal system is also implicated in pathogenesis of E. coli, Haemophilus ducreyi, Salmonella enterica and Vibrio cholerae, but the mechanism(s) is unclear.
Tol-Pal system protein TolR (Tol-Pal_TolR)
Type: Family

This entry describes the inner membrane protein TolR, part of the TolR/TolQ complex that transduces energy from the proton-motive force, through TolA, to an outer membrane complex made up of TolB and Pal (peptidoglycan-associated lipoprotein). The complex is recruited to cell division sites and is required to maintain outer membrane integrity; defects may cause a defect in the import of some organic compounds. TolR is related to MotB, the peptidoglycan (PG)-binding stator protein from the flagellum, suggesting it might serve a similar role in Tol-Pal .
Peptidoglycan-associated lipoprotein, C-terminal (Pal_lipo_C)
Type: Domain

This entry represents the C-terminal domain of peptidoglycan-associated lipoprotein (Pal or OprL) of the Tol-Pal system. The system appears to be involved both in the maintenance of outer membrane integrity and in the import of certain organic molecules as nutrients . Pal contains a hydrodrophobic lipoprotein signal sequence, a conserved N-terminal cleavage and modification site, a poorly conserved low-complexity region, together comprising about 65 amino acids, and a well-conserved C-terminal domain. The entry represents only the conserved C-terminal domain.
TonB system transport protein ExbD type-1 (TonB_ExbD_1)
Type: Family

Members of this family are Gram-negative bacterial inner membrane proteins, generally designated ExbD, related to the TolR

. Members are always found next to a protein designated ExbB (

), which is related to the TolQ family (

). ExbD and ExbB together form a proton channel through which they can harness the proton-motive force to energize TonB, which in turn energizes TonB-dependent receptors in the outer membrane. TonB-dependent receptors with known specificity tend to import siderophores or vitamin B12. A TonB system and Tol-Pal system often will co-exist in a single bacterial genome.
TonB system transport protein ExbD type-2 (TonB_ExbD_2)
Type: Family

Members of this family are Gram-negative bacterial inner membrane proteins, generally designated ExbD, related to the TolR (

). Members are always encoded next to a protein designated ExbB (

), which is related to the TolQ (

). ExbD and ExbB together form a proton channel through which they can harness the proton-motive force to energize TonB, which in turn energizes TonB-dependent receptors in the outer membrane. TonB-dependent receptors with known specificity tend to import siderophores or vitamin B12. A TonB system and Tol-Pal system often will co-exist in a single bacterial genome.
TonB-system energizer ExbB type-2 (TonB_ExbB_2)
Type: Family

Members of this protein family appear to be the ExbB protein of an ExbBD proton-transporting membrane complex that, by means of TonB, energizes transport by TonB-dependent receptors. Note that this family represents one of at least two distinct groups TolQ homologues designated ExbB - see also

. Each group associates with a distinct group of ExbD proteins, and a single species may have two ExbB/ExbD/TonB systems.
CRISPR-associated protein Cas6/Cmx6 (CRISPR-assoc_prot_Cas6/Cmx6)
Type: Family

Members of this entry are designated type I-MYXAN CRISPR-associated protein Cas6/Cmx6 and resemble the Cas6 proteins described by

in having a C-terminal motif GXGXXXXXGXG, where the single X of each GXG is hydrophobic and the spacer XXXXX has at least one Lys or Arg. Examples are found in cas gene operons of CRISPR regions in Anabaena variabilis (strain ATCC 29413/PCC 7937), Leptospira interrogans, Gemmata obscuriglobus UQM 2246, and twice in Myxococcus xanthus (strain DK 1622). Oddly, an orphan member is found in Thiobacillus denitrificans (strain ATCC 25259), whose genome does not seem to contain other evidence of CRISPR repeats or cas genes.

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.
Conserved hypothetical protein CHP02808 (CHP02808)
Type: Family

This very small protein (about 46 amino acids) consists largely of a single predicted membrane-spanning region. It is found in Photobacterium profundum SS9 and in three species of Vibrio, always near periplasmic nitrate reductase genes, but far from the periplasmic nitrate reductase genes in Aeromonas hydrophila ATCC 7966.
Phasin, subfamily 3 (Phasin_subfam-3)
Type: Family

Phasins (or granule-associate proteins) are surface proteins found covering Polyhydroxyalkanoate (PHA) storage granules in bacteria. Polyhydroxyalkanoates are linear polyesters produced by bacterial fermentation of sugar or lipids for the purpose of storing carbon and energy, and are accumulated as intracellular granules by many bacteria under unfavorable conditions, enhancing their fitness and stress resistance . The layer of phasins stabilises the granules and prevents coalescence of separated granules in the cytoplasm and nonspecific binding of other proteins to the hydrophobic surfaces of the granules. For example, in Ralstonia eutropha (strain ATCC 17699/H16/DSM 428/Stanier 337) (Cupriavidus necator (strain ATCC 17699 / H16 / DSM 428 / Stanier 337)), the major surface protein of polyhydroxybutyrate (PHB) granules is phasin PhaP1(Reu), which occurs along with three homologues (PhaP2, PhaP3, and PhaP4) that have the capacity to bind to PHB granules but are present at minor levels . These four phasins lack a highly conserved domain but share homologous hydrophobic regions.

Members of this entry are encoded in polyhydroxyalkanoic acid storage system regions in a number of Vibrio species, including Vibrio cholerae V52, Photobacterium profundum SS9, Acinetobacter sp., and Aeromonas hydrophila. Members appear distantly related to the phasin family, see:

and

.
Putative formate dehydrogenase, TAT signal-containing (Formate_DH_TAT-contain)
Type: Family

Members of this uncharacterised protein family are all small, extending 70 or fewer residues from their respective likely start codon. All have the twin-arginine-dependent transport (TAT) signal sequence at the N terminus and a conserved 20-residue C-terminal region that includes the motif Y-[HRK]-X-[TS]-X-H-[IV]-X-X-[YF]-Y. The TAT signal sequence suggests a bound cofactor. All members are encoded near genes for subunits of format dehydrogenase, and may themselves be a subunit or accessory protein of another protein complex.
Fatty acid response transcription factor FadR (FA-response_TF_FadR)
Type: Family

Members of this entry are transcriptional regulators of fatty acid metabolism (FadR), including both biosynthesis and beta-oxidation reactions, which are found exclusively in a subset of Gamma proteobacteria with strictly one copy per genome. Proteins have an N-terminal DNA-binding domain and a less well conserved C-terminal long chain acyl-CoA-binding domain. FadR when expressed in Escherichia coli shows differences in regulatory response and fatty acid binding profiles. All members of this entry are expected to have the same function.
PfaD-like, TIM-barrel domain (PfaD-like_TIM-barrel)
Type: Domain

The protein PfaD is part of a four-gene locus, similar to polyketide biosynthesis systems, which is responsible for omega-3 polyunsaturated fatty acid biosynthesis in several high pressure and/or cold-adapted bacteria. Several other members of the entry are found in loci presumed to act in polyketide biosynthesis per se .

This entry represents the C-terminal domain of Polyunsaturated fatty acid synthase subunit B/C (PFA2/3) and polyketide biosynthesis proteins BaeE, PksE and ThaF.
Sugar isomerase, AgaS (Sugar_isomerase_AgaS)
Type: Family

Some members of this protein family are found in genic regions associated with N-acetyl-galactosamine and galactosamine utilisation and are suggested to be isomerases . Proteins in this entry include Escherichia coli AgaS, which is suggested to be a Gam-6-P deaminase/isomerase in the Aga/Gam pathway .
Omega-3 polyunsaturated fatty acid synthase-like (Omega3_polyunsat_FA_synth-like)
Type: Domain

This entry represents a group of proteins based on a PfaB protein family. The protein PfaB family is part of a four-gene locus, which is similar to polyketide biosynthesis systems, responsible for omega-3 polyunsaturated fatty acid biosynthesis in several high pressure and/or cold-adapted bacteria. The fairly permissive trusted cut off set for this HMM allows detection of homologues encoded near homologues to other proteins of the locus: PfaA, PfaC, and/or PfaD. The likely role in every case is either polyunsaturated fatty acid or polyketide biosynthesis.
Alcohol dehydrogenase, zinc-binding type 1 (ADH_Zn_typ-1)
Type: Family

Members of this entry form a distinct subset of the larger family of oxidoreductases that includes zinc-binding alcohol dehydrogenases and NADPH:quinone reductases. Some current members of this entry carry designations as putative alginate lyase, however none have been characterised as such.
Alcohol dehydrogenase class III (ADH_3)
Type: Family

Class III alcohol dehydrogenases (ADH3) (

) tend to show poor activity for ethanol among their various substrate alcohols. They catalyze the oxidation and reduction of a wide variety of substrates that include S-(hydroxymethyl)glutathione (HMGSH), S-nitrosoglutathione, and long chain primary alcohols and aldehydes . The enzyme was previously designated as glutathione-dependent formaldehyde dehydrogenase, as it acts as a HMGSH dehydrogenase (

). ADH3 oxidizes HMGSH to S-formylglutathione, which is then hydrolyzed to glutathione and formate by a hydrolase . S-(hydroxymethyl)glutathione can form spontaneously from formaldehyde and glutathione, and constitutes a cellular strategy for sequestering and metabolizing highly toxic formaldehyde .
Formaldehyde dehydrogenase, glutathione-independent (HCHO_DH_non_GSH)
Type: Family

Members of this entry represent a distinct clade within the larger family of zinc-dependent dehydrogenases of medium chain alcohols. This entry includes the so-called glutathione-dependent formaldehyde dehydrogenase. Members of this entry have a tightly bound NAD that can act as a true cofactor, rather than a co-substrate in dehydrogenase reactions and in dismutase reactions for some aldehydes. The name given to this family, however, is formaldehyde dehydrogenase, glutathione-independent.
Glutathione-dependent formaldehyde-activating enzyme (Formald_GSH)
Type: Family

This entry represents glutathione-dependent formaldehyde-activating enzyme, also known as S-(hydroxymethyl)glutathione synthase, an enzyme that converts glutathione and formaldehyde into S-(hydroxymethyl)glutathione. The reaction of glutathione and formaldehyde to form S-(hydroxymethyl)glutathione occurs naturally, but this enzyme speeds its formation in some species as part of a pathway of formaldehyde detoxification .
S-formylglutathione hydrolase (S-formylglutathione_hydrol)
Type: Family

This entry describes proteins from bacteria, yeast, and human, with a conserved critical role in formaldehyde detoxification as S-formylglutathione hydrolase (

). Eukaryotic members, particularly the human protein, are better known as esterase D (

), an enzyme with broad specificity, although S-formylglutathione hydrolase has now been demonstrated as well.
Alcohol dehydrogenase, zinc-binding type 2 (ADH_Zn_typ-2)
Type: Family

Members of this entry form a distinct subset of the larger family of oxidoreductases that includes zinc-binding alcohol dehydrogenases and NADPH:quinone reductases. The gene neighbourhood of members of this family is not conserved and it appears that no members are characterised. Sequence alignments reveal 6 invariant cysteine residues and one invariant histidine.
Acrylyl-CoA reductase AcuI (Acrylyl-CoA_reductase_AcuI)
Type: Family

This entry represents acrylyl-CoA reductase AcuI, a subfamily of zinc-containing alcohol dehydrogenase. Acrylyl-CoA reductase AcuI catalyses the NADPH-dependent reduction of acrylyl-CoA to propanoyl-CoA .

This entry also includes quinone oxidoreductase, YhdH from Escherichia coli and YhfP from Bacillus subtilis both of which bind NADPH or NAD, but not zinc. Both proteins have been studied crystallographically for insight into function.
Quinone oxidoreductase PIG3 (Quinone_OxRdtase_PIG3)
Type: Family

Members of this family include putative quinone oxidoreductases that belong to the broader superfamily of zinc-dependent alcohol (of medium chain length) dehydrogenases. A member of this family is human quinone oxidoreductase PIG3, which is induced by p53 and may be involved in the generation of reactive oxygen species (ROS) .
Leukotriene B4 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase (PTGR1)
Type: Family

Leukotriene B4 12-hydroxydehydrogenase is an NADP-dependent enzyme of arachidonic acid metabolism, responsible for converting leukotriene B4 to the much less active metabolite 12-oxo-leukotriene B4. The BRENDA database lists leukotriene B4 12-hydroxydehydrogenase as one of the synonyms of 2-alkenal reductase (

), while

is 15-oxoprostaglandin 13-reductase.
Anaerobic ribonucleoside-triphosphate reductase activator (Anaer_RNR_activator)
Type: Family

Members of this entry represent a set of proteins related to, yet architecturally different from, the activating protein for the glycine radical-containing, oxygen-sensitive ribonucleoside-triphosphate reductase (RNR, see

). Members of this entry are found paired with members of a similarly divergent set of anaerobic ribonucleoside-triphosphate reductases. Identification of these proteins as RNR activating proteins is partly from pairing with the candidate RNR and further supported by the finding that upstream of these operons are examples of a conserved regulatory element that is found in nearly all bacteria and that occurs specifically upstream of operons for all three classes of RNR genes .
Uncharacterised domain CHP02828, putative membrane fusion protein (CHP02828_mem_fusion)
Type: Domain

Members of this entry show similarity to those in

, the membrane fusion protein (MFP) cluster 2 family, which is linked to RND transport systems.
Sporulation stage III, protein AE (Spore_III_AE)
Type: Family

This entry represents the stage III sporulation protein AE, which is encoded in a spore formation operon spoIIIAABCDEFGH under the control of sigma G . A comparative genome analysis of all sequenced genomes of Firmicutes shows that the proteins are strictly conserved among the sub-set of endospore-forming species.
Sporulation stage III, protein AG (Spore_III_AG)
Type: Family

This entry represents the stage III sporulation protein AG, which is encoded in a spore formation operon: spoIIIAABCDEFGH under the control of sigma G . A comparative genome analysis of all sequenced genomes of Firmicutes shows that the proteins are strictly conserved among the sub-set of endospore-forming species.