SII-SWORD/CoKE huggingface dataset:
XaxAB toxin subunit B-like (XaxB-like)
Type: Family

This entry represents the binary toxin xaxAB subunit B and its homologues. Xax was discovered in entomopathogenic Xenorhabdus nematophila (

) and it is a binary pore-forming toxin (α-PFT) encoded by two genes xaxA and xaxB with a maximum hemolytic activity obtained with equimolar concentrations of the two proteins .

The toxin orthologue YaxAB from Yersinia enterocolitica (

), also member of this family, was structurally characterised . The crystal structure of YaxB shown an atypical fold, comprising a head domain reminiscent of ClyA family of α-PFTs and pronounced coiled-coil and foot domains unique to the YaxAB system. The pore complex assembled in decamer of dimers (20-mer) arrangement of its two components.
NadS-like (NadS-like)
Type: Family

This entry represents NadS from Escherichia coli (

) and similar proteins predominantly found in gammaproteobacteria. Members of this family often carry a Cro/C1-type helix-turn-helix domain (

).
EHMT1/2, cysteine-rich region (EHMT_CRR)
Type: Domain

This is a cysteine-rich region (CRR) found in the centre of these sequences, which is unique to EHTM1/2 and mediates protein-protein interactions and recruitment of the methyltransferases to specific sites in chromatin . This domain adopts an unusual compact fold with four bound zinc atoms that contains an embedded RING domain, which represents a novel zinc-binding motif.

This entry includes Histone-lysine N-methyltransferase EHMT1 and Histone-lysine N-methyltransferase EHMT2 (

). EHMT1 and EHMT2 mono- and dimethylate 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin . H3K9me is a specific tag for repression of epigenetic transcription, recruiting HP1 proteins to methylated histones. EHMT1 also methylates 'Lys-27' of histone H3 (H3K27me), but weakly , while EHMT2 also monomethylates 'Lys-56' of histone H3 (H3K56me1) during the G1 phase of the cell cycle , and methylates 'Lys-27' of histone H3 (H3K27me) . EHMT1 and EHMT2 also dimethylate other proteins, including 'Lys-373' of p53 .

EHMT1 forms a heterodimer with EHMT2 , and is a component of the E2F6.com-1 complex in G0 phase . EHMT1 and EHMT2 contain ankyrin repeats (eight and seven ankyrin repeats, respectively), which bind the monomethylated RELA subunit of NF-kappa-B, a SET domain which interacts with WIZ , and a pre-SET domain that binds three zinc ions via cysteine residues .
Peptidoglycan-binding domain, phiBT1-type (PG_bind_dom_phiBT1-type)
Type: Domain

This entry represents a peptidoglycan-binding domain that occurs once or twice at the C-terminal end of a group of proteins mainly from actinomycetes, including cell wall amidases and in putative lysins, such as

from Streptomyces phage phiBT1 . It shows apparent homology to

.
Cortex morphogenetic protein CmpA (CmpA)
Type: Family

This entry represents CmpA (cortex morphogenetic protein A) found firmicutes, a small protein (37 amino acids) involved in endospore formation. CmpA participates in a quality-control pathway that selectively removes defective sporulating cells through regulated cell death. It acts as an adaptor that delivers SpoIVA to the ClpXP proteolytic machinery for degradation, specifically in cells that improperly assemble the spore envelope . This protein ensures proper spore envelope assembly .
GHMP kinase GYDIA-like (GHMP_GYDIA-like)
Type: Family

The GHMP kinase family is named for galactokinase (G), homoserine kinase (H), mevalonate kinase (M), and phosphomevalonate kinase (P). This entry represents an uncharacterised protein family mainly found in bacteroidetes, that is closely related to mevalonate kinase (

). Members show several distinctive nearly invariant motifs, including WGLG[ST]SSTL, GGSGYDIA (for which the family is named), and SLGAWGGF.
Uncharacterised protein family PxxKW (PxxKW_fam)
Type: Family

This entry represents an uncharacterised protein family, these proteins are approximately 90 amino acids in length and are predominantly found in Deltaproteobacteria. The proteins that constitute this family contain four invariant Cys residues. They possess a number of conserved motifs including CxGC, PxxKW (for which the family is named after), CNxATH, and NP[LI]KASKR near the C terminus.
PSP1-like (PSP1-like)
Type: Family

The yeast polymerase suppressor 1 (PSP1) protein partially suppresses mutations in DNA polymerases alpha and delta . The C-terminal half of PSP1 contains a domain, which is also found in several hypothetical proteins from both eukaryotic (fungal) and prokaryotic sources, such as Bacillus subtilis YaaT protein (also known as RicT), which was first thought to play a significant role in phosphorelay during initiation of sporulation. However, YaaT/RicT belongs to a iron-sulfur containing regulatory complex that is conserved also in many non-sporulating species, together with homologs of YmcA (RicA) and YlbF (RicF) . It is possible that the yaaT protein is also related to DNA replication .
Transposase for transposon Tn5-like (Tn5p-like)
Type: Family

This entry represents transposase for transposon Tn5 from Escherichia coli (also known as TnpA) and similar bacterial proteins. TnpA mediates transposition of transposon Tn5 by a 'cut and paste' mechanism .
Organoarsenical effux MFS transporter ArsJ (MFS_ArsJ)
Type: Family

ArsJ regularly is encoded next to a glyceraldehyde-3-phosphate dehydrogenase that can synthesize 1-arseno-3-phosphoglycerate in the presence of arsenate, and appears to provide arsenate resistance by exporting that organoarsenical compound before it spontaneously dissociates into arsenate and 3-phosphoglycerate .
Sensor histidine kinase RegB (RegB)
Type: Family

This family represents a redox-responsive histidine kinase, RegB/PrrB, found in alphaproteobacteria, which shows strong sequence conservation, including the notable motif [VA]AAAAHELGTPxTI. It always acts as a partner to an ActR/PrrA/RegA family global response regulator transcription factor in a two-component sensory transduction system. Lineage-specific names and gene symbols given to this histidine kinase reflect downstream regulator changes such as entry into stationary phase, anaerobic expression of photosynthesis genes, and survival of exposure to low pH .
Radical SAM STM4011-like (Radical_SAM_STM4011-like)
Type: Family

This entry represents a group of bacterial putative radical SAM proteins, including STM4011 from Salmonella typhimurium (

), whose function is unknown. Members are somewhat variable in architecture.
ActR/PrrA/RegA redox response regulator transcription factor (ActR_PrrA_rreg)
Type: Family

ActR, PrrA, and RegA are examples of lineage-specific names given to a response regulator transcription factor that acts as a global regulator and belongs to a sensor-regulator pair with ActS/PrrB/RegB respectively, that is highly conserved in the alphaproteobacteria. Examples of this regulator include ActR (acid tolerance regulator) in Sinorhizobium meliloti , stationary phase response regulator SpdR in Caulobacter crescentus (also known as C. vibroides) , and RegA, member of the two-component regulatory system RegB/RegA involved in transactivating anaerobic expression of the photosynthetic apparatus .
YHYH domain, bacterial (YHYH_dom_bact)
Type: Domain

This entry represents a domain that contain a specific form of the YHYH motif. It is located near the N terminus of a protein just after a signal peptide region. The domain has two characteristic motifs, GxC and YH[YC]H, separated by a short spacer region of variable length. A different type of YHYH that locates more C-terminal in the protein sequences, and is repeated, is described by

.
Virulence factor SrfA-like (SrfA-like)
Type: Family

This entry represents a group of proteins mainly found in gammaproteobacteria, including the virulence factor SrfA (SsrAB regulated factor A) from Salmonella typhimurium (

), a secreted effector whose mechanism of secretion is not known. SrfA belongs to a set of three SsrAB regulated factors, along with SrfB and SrfC. Operons related to srfABC are widely distributed in proteobacteria, suggesting coordinated action, and the three proteins appear able to form a complex .
Peroxide/acid stress response protein YhcN-like (Stress_YhcN-like)
Type: Family

This entry represents YhcN from Escherichia coli and similar proteins predominantly found in enterobacteria. YhcN is involved in the stress response of E. coli to hydrogen peroxide, cadmium, acid and biofilm formation .
Tryptophan ABC transporter substrate-binding TrpX-like (ABC_SBP_TrpX-like)
Type: Family

This entry represents a group of putative ABC transporter substrate binding proteins from firmicutes, including

from Streptococcus pyogenes (TrpX), part of a tryptophan uptake system. TrpX plays a crucial role for metabolic adaptation and growth during infection .
LapA-like, retention module (LapA-like_RM)
Type: Domain

This entry represents the N-terminal retention module found in giant adhesin LapA of Pseudomonas fluorescens , the ice-binding giant adhesin of an Antarctic bacterium and other very large repetitive proteins from proteobacteria with C-terminal regions that make them substrates for type I secretion systems.
Uncharacterised protein STM4014-like (STM4014-like)
Type: Family

This entry represents a group of bacterial proteins that contain an ATP-grasp fold subdomain, including STM4014 from Salmonella typhimurium (

). Members of this family are proteins of unknown function, regularly found in a conserved gene neighborhood that also includes two uncharacterised radical SAM proteins.
Putative aga operon transcriptional repressor-like (AgaR-like)
Type: Family

This entry represents the putative aga operon transcriptional repressor from Escherichia coli (AgaR) and similar bacterial proteins. AgaR is a probable repressor for the aga operon for N-acetyl galactosamine transport and metabolism .
T6SS-associated TssQ-like (TssQ-like)
Type: Family

This entry represents TssQ from Bordetella bronchiseptica (

) and its homologues. TssQ is encoded within a T6SS locus but its function remains unknown . T6SS appears to constitute a phage-tail-spike-like injectisome and is required for virulence in several pathogens. It is also involved in intraspecies and interspecies bacterial interactions .
Nickel-binding protein Mua (Mua)
Type: Family

This entry represents Mua (modulator of urease activity) proteins found in the genus Helicobacter, such as

. Mua is a nickel-binding protein and its repression of urease activity correlates with nickel concentrations .
Manganase accumulation protein MntS (MntS)
Type: Family

This entry represents MntS, a small protein of about 42 amino acids from enterobacteria. This protein in known to assist bacteria in accumulating manganese when iron is limiting. It may function as a manganese chaperone, or it may inhibit manganese efflux transporters .
ORF2/OrfX-like (ORF2/OrfX-like)
Type: Family

This entry represents a family of uncharacterised proteins that occur in replication regions of a large number of Acinetobacter plasmids, including

from Acinetobacter sp. M131,

from Acinetobacter baumannii, the founding members of this family, referred to as ORF2 and OrfX . However, these proteins are not required for replication. These proteins contain an N-terminal DNA-binding helix-turn-helix domain .
TrgA (TrgA)
Type: Family

This entry represents TrgA and similar proteins mainly found in alphaproteobacteria, a protein associated with tellurium resistance. These are hydrophobic proteins, about 150 amino acids in length, probably embedded in the membrane, and possibly involved in transport .
tRNA mnm(5)s(2)U biosynthesis bifunctional protein MnmC, N-terminal (tRNA_MNMC2)
Type: Domain

This entry represents the N-terminal region, called MnmC2, of the tRNA 5-methylaminomethyl-2-thiouridine biosynthesis bifunctional protein MnmC, or of a standalone protein that performs the same methyltransferase function, in partnership with an FAD-dependent protein, or C-terminal region, called MNMC1 (

).
Fimbria major subunit Mfa1 (Mfa1_fim)
Type: Family

Members of this family are fimbrial shaft proteins (major subunit proteins), found in the Bacteroidales. This family is named for Mfa1 from Porphyromonas gingivalis , and is related to but distinct from the family of FimA from this species.

Five genes encoded by the mfa1 gene cluster form the Mfa1 fimbriae. Mfa1 constitutes the shaft, Mfa2 the anchor, and Mfa3-5 are the tip proteins of the fimbria. Mfa1, Mfa2 and Mfa3 have the same overall fold that consists of two β-sandwich domains. Upon polymerisation, the first β-strand of the shaft or tip protein is removed by indigenous proteases. The resulting void is filled by a donor-strand from another fimbrial protein .

The Mfa1 shaft protein has several distinct structural features not observed in the anchor and tip proteins and these are a metal-binding proline-rich loop and a large 63 residue long insert in the C-terminal domain. The exposed prolines on Mfa1 are likely to interact with surface proteins of other bacteria .
Phosphoethanolamine transferase EptC/CptA (EptC/CptA)
Type: Family

This entry represents a group of proteins from gammaproteobacteria, including phosphoethanolamine transferase EptC from Escherichia coli and phosphoethanolamine transferase CptA from Salmonella typhimurium. Both proteins catalyse the addition of a phosphoethanolamine moiety to the outer membrane lipopolysaccharide core . EptC also plays a role in the pathogenesis of E.coli meningitis, as it is required for invasion of E.coli K1 into brain microvascular endothelial cells (BMEC). It contributes to E.coli traversal across the blood-brain barrier .
Selenium metabolism-associated LysR-like transcriptional regulator (LysR-like_Sec_metab)
Type: Family

LysR family transcriptional regulators regularly appear encoded adjacent to selenecysteine incorporation proteins such as SelB. This protein family represents an especially well-conserved subgroup of such transcription factors from species such as Merdimonas faecis, Sellimonas intestinalis, Syntrophotalea acetylenica, and Hydrogenivirga caldilitoris .
CU044_5270-like (CU044_5270-like)
Type: Family

This entry represents a group of proteins from actinomycetes, including CU044_5270 from Streptomyces sp. (

), which often have several members per genome. Lengths average about 340 amino acids. The function is unknown.
Major capsid protein, shiphovirus-type (MCP_Sipho)
Type: Family

This entry represents phage major capsid proteins found in a large number of Siphoviridae, many of which having Gram-positive bacteria such as Mycobacterium and Gordonia as host.
Transcriptional regulatory protein WalR (WalR)
Type: Family

This entry represents Transcriptional regulatory protein WalR from Bacillus subtilis (also known as YycF) and similar proteins predominantly found in firmicutes.

WalR is a member of the two-component regulatory system WalK/WalR involved in the regulation of the ftsAZ operon, the yocH, ykvT, cwlO, lytE, ydjM, yjeA, yoeB genes and the tagAB and tagDEF operons. It is essential for cell wall metabolism . In Streptococcus pneumoniae, this protein inhibits transcription of fabT, probably acting in an unphosphorylated form, thereby playing a role in the regulation of fatty acid biosynthesis . WalR belongs to the OmpR family of response regulators, which are characterised by a REC domain and a winged helix-turn-helix effector domain involved in DNA binding .
Surface protein Hvo_1808-like (Hvo_1808-like)
Type: Family

This entry represents a small family of secreted proteins from halophilic archaea . Members of this family has either lipoprotein signal peptide at the N terminus, or a PGF-CTERM sorting signal at the C terminus, but never both. These types of sorting signals are processed in a way that, after their removal, a lipid moiety is left at the new terminus that anchors the protein in the plasma membrane.

The central region of these proteins has a weak sequence similarity and is predicted to adopt the structure of metalloproteases ('zincins') catalytic domain. Residues that constitute the active site of 'zincins' are also conserved across the members of this family.
Cell wall-active antibiotic response protein LiaF, C-terminal domain (LiaF_C)
Type: Domain

This entry represents the conserved C-terminal domain of LiaF (called VraT in Staphylococcus), an additional key component of the histidine kinase LiaS and response regulator LiaR system. The system responds to cell envelop stress in the Firmicutes, and plays a role in resistance to cell wall-targeting antibiotics .
Peptidase C45-like (C45_proenzyme-like)
Type: Family

Members of this family include hydrolases and N-acyltransferases that belong to the Ntn (N-terminal nucleophile) hydrolase family. Members have an invariant Cys residue required both for autoproteolytic processing into alpha and beta chains and for activity. Members of this entry are described by MEROPs as a cysteine protease, family C45, because of its autoproteolytic activity. Characterised members include TAN from Drosophila, which removes beta-alanine from both carcinine and N-beta-alanyl dopamine , and isopenicillin-N N-acyltransferase from various fungi. The latter has been heavily studied because of its role in penicillin biosynthesis . This entry also includes uncharacterised proteins from archaea, such as AF_0267 from Archaeoglobus fulgidus and proteins dcd1A/B from Dictyostelium discoideum.
Putative cytokinetic ring protein SteA-like (Put_SteA-like)
Type: Family

This entry represents a group of proteins mainly found in actinobacteria and firmicutes. Members of this family on membrane proteins from Actinobacteria have been reported to be SteA (Sensitive To Ethambutol A), a cytokinetic ring protein that partners with SteB and contributes to proper cell division . A region of these proteins show sequence similarity to the catalytic domain of thiamine pyrophosphokinases.
Transcriptional repressor SdpR-like (SdpR-like_repress)
Type: Family

This entry represents the transcriptional repressor SdpR from Bacillus subtilis and similar bacterial sequences. SdpR represses the transcription of the sdpIR operon and of several other operons that probably contribute to delaying commitment to sporulation. Transcription factors in this family resemble metalloregulatory transcriptional repressors such as ArsR, SmtB, CadX, ZiaR, etc., but may lack the key metal-binding residues .
ISNCY transposase (ISNCY_transpos)
Type: Family

The ISNCY insertion sequence family, as defined by ISFinder, encodes several apparently unrelated families of transposases. Members of this family, predominantly found in proteobacteria, resemble the transposases of ISNCY family elements such as transposase for insertion sequence IS1202 from Streptococcus pneumoniae.
Integral membrane protein BPSS1780-like (BPSS1780-like)
Type: Family

This entry represents a group of poorly characterised integral membrane proteins mainly from gamma/betaproteobacteria, including BPSS1780 from Burkholderia pseudomallei (

) and BTH_II0599 from Burkholderia thailandensis (

). BTH_II0599 probably transports the toxic C-terminal region of CdiA-2 from B.pseudomallei strain 1026b across the inner membrane to the cytoplasm, where CdiA has a toxic effect .
Type IX secretion system, outer membrane channel protein PorV (T9SS_OM_PorV)
Type: Family

This entry represents a group of proteins mainly found in bacteroidetes, including PorV from the oral pathogen Porphyromonas gingivalis (

), an outer membrane β-barrel protein that is a component of the type IX secretion system (T9SS) needed to process a subset of T9SS substrates. PorV is a paralog of PorQ .
SWFGD domain (SWFGD_dom)
Type: Domain

This entry represents a small (29 amino acids long) uncharacterised domain that is named after its conserved SWFGD motif. This domain is found in protein sequences containing a DUF2171 domain (

) or a BON domain (

), suggesting a possible involvement in attachment to phospholipid membranes. Two copies of the SWFGD domain may be found in a single protein.
Peptidase C45 (Peptidase_C45)
Type: Family

This entry represents hydrolases and N-acyltransferases that belong to the Ntn (N-terminal nucleophile) hydrolase family, described by MEROPs as a cysteine protease, family C45, because of its autoproteolytic activity. Members have an invariant Cys residue required both for autoproteolytic processing into alpha and beta chains and for activity. Characterised members include TAN from Drosophila, which removes beta-alanine from both carcinine and N-beta-alanyl dopamine , and isopenicillin-N N-acyltransferase from various fungi. The latter has been heavily studied because of its role in penicillin biosynthesis .
Protein phosphatase CheZ (CheZ_Pase)
Type: Family

This entry represents protein phosphatase CheZ. CheZ family members are broadly distributed and play significant roles in chemotaxis systems in Gram-negative bacteria. This phosphatase efficiently dephosphorylates proteins from the chemotaxis system CheY(HP) and CheAY, and has additional weak activity on CheV2 . It was shown that in Helicobacter pylori, the CheZ phosphatase localises to the bacterial pole and its localisation depends on the interactions with ChePep chemotaxis protein .
DCD1A/B-like (DCD1A/B-like)
Type: Family

This entry represents a group of poorly characterised proteins found in bacteria, some archaea and microscopic eukaryotes, such as proteins dcd1A/B from Dictyostelium discoideum. They may contain a cysteine protease-like domain.
Peptidase C69, dipeptidase A-like (C69_dipept_A-like)
Type: Family

This family represents bacterial dipeptidases from MEROPS C69 family (subfamily 001,

) , such as dipeptidase A from Lactobacillus helveticus, which hydrolyzes a wide range of dipeptides but is unable to hydrolyze dipeptides containing proline .
Cyclic GMP-AMP synthase (GAMP_synthase)
Type: Family

This entry represents the bacterial cyclic GMP-AMP synthase family. The cyclic GMP-AMP synthase (cGAS)-STING pathway is a central component of the cell-autonomous innate immune system in animals . The cGAS protein is a sensor of cytosolic viral DNA and, upon sensing DNA, it produces a cyclic GMP-AMP (cGAMP) signalling molecule that binds to the STING protein and activates the immune response. The production of cGAMP has also been detected in bacteria and cGAMP signalling is part of a common antiphage defence system . Phage infection triggers the production of cGAMP, which activates the phospholipase, leading to a loss of membrane integrity and to cell death before completion of phage reproduction.
Integration host factor, actinobacterial-type (IHF_actinobact)
Type: Family

Members of this family are nucleoid-associated dsDNA-binding proteins called integration host factor (mIHF in mycobacteria (

) and sIHF in streptomycetes) because of similarities in cellular role, not in sequence, to the integration host factor proteins of Escherichia coli. Actinobacterial-type IHF actually shows more sequence similarity to 30S ribosomal subunit protein S13 . Some members are fused to an additional guanylate kinase domain. mIHF is essential for survival of the human pathogen Mycobacterium tuberculosis and its NMR spectroscopy revealed mIHF as a globular protein with a protruding α-helix and a disordered N-terminal similar to sHIF .
Lipoprotein YgdI/YgdR-like, SH3-like domain (YgdI/YgdR-like_SH3-like)
Type: Domain

This entry represents the SH3-like domain of small bacterial lipoproteins, including YgdI and YgdR from E. coli, whose function is unknown.
Periplasmic metallochaperone CueP-like (CueP-like)
Type: Family

This entry represents CueP and its homologues, a copper-binding periplasmic metallochaperone identified in Salmonella enterica serovar Typhimurium (

). CueP has been implicated in the transfer of copper ions to SodCII in the periplasm. Its crystal structure has been determined, revealing a V-shaped dimeric structure . Each monomer is composed of two domains, N-terminal α/β domain and a C-terminal Ig-like domain. Many members of this family, although not CueP itself, are lipoproteins.