SII-SWORD/CoKE huggingface dataset:
Ornithine uptake porin CarO (CarO_OMP)
Type: Family

This entry represents Ornithine uptake porin CarO from Acinetobacter baumannii (

) (

), also known as carbapenem-associated resistance protein , and similar sequences from gammaproteobacteria. The outer membrane porin CarO is of clinical interest because of its role in allowing entry of carbapenem antibiotics and its variability from strain to strain. CarO should not be confused with Omp33-36, an essentially unrelated outer membrane protein that is similar in size and that also affects carbapenem susceptibility .
Sigma(X)-activator ComW (SigmaX_act_ComW)
Type: Family

This entry represents the pneumococcal DNA-binding protein ComW. This protein is found exclusively in Streptococcus. It is critical for natural transformation and interacts with the σ factor (σX), that is a master regulator for competence . Together, ComW and σX facilitate expression of the genes required for DNA uptake and genetic recombination. ComW interacts with DNA, in a sequence independent manner and this DNA-binding activity is important for transformation in pneumococcus .
DotG/IcmE-like, C-terminal domain (DotG/IcmE-like_C)
Type: Domain

This entry contains DotG/IcmE, a homologue of VirB10 which forms part of the core complex in Type IV secretion system (T4SS). The Dot/Icm system is a T4SS found in the pathogens Legionella and Coxiella and the conjugative apparatus of IncI plasmids; T4SS is employed by pathogenic bacteria to export virulence DNAs and/or proteins directly from the bacterial cytoplasm into the host cell. Similar to T4SS VirB/D components, the Legionella Dot/Icm secretion apparatus contains a critical five-protein sub-assembly that forms the membrane-spanning 'core-complex' (CC), around which all other components assemble. This transmembrane connection is mediated by protein dimer pairs consisting of two inner membrane proteins, DotF and DotG, each independently associating with DotH/DotC/DotD in the outer membrane .
Venus Flytrap-like (PfVFT1-like)
Type: Family

This entry represents the Venus Flytrap protein PfVFT1 from Plasmodium falciparum and similar proteins from Apicomplexa. PfVFT1 is a highly immunogenic protein, but its biological role in the Plasmodium falciparum parasite is unknown. It is a parasite-specific antigen expressed by the P. falciparum 3D7 strain in both sexual and asexual stages and was identified as a major candidate for inclusion in a multicomponent blood stage malaria vaccine. Bioinformatic analysis predicts a signal peptide with no identifiable membrane anchors suggesting that it coordinates a membrane-associated partner to enable surface localisation. Fractionation of detergent-resistant membranes showed that PfVFT1 clusters with GPI-anchored parasite proteins including Pf38, Pf92, Pf113, PfMSP-1, PfMSP-4, PfASP, and PfRAMA .
Outer membrane lipoprotein Omp10-like (Omp10-like)
Type: Family

This entry represents the Outer membrane lipoprotein omp10 from Brucella abortus (

) and similar sequences mainly found in alphaproteobacteria . The deletion of Omp10 in Brucella significantly reduces survival in mice and results in growth defects in minimal medium. However, it does not show impairment in intracellular growth in vitro . However, the specific function of Omp10 is unknown.
Anti-CRISPR type II subtype A6-like (AcrIIA6-like)
Type: Domain

AcrIIA6 is an anti-CRISPR (Acr) protein which was discovered via a self-targeting method that inhibits the type II-A CRISPR-Cas system (Csy) . It is the largest known type II-A Acr, and it contains a helix-turn-helix (HTH) motif that is part of its dimerisation interface. AcrIIA6 inhibits target DNA binding to Cas9 via an allosteric mechanism and can induce Cas9 dimerisation. The protospacer adjacent motif (PAM) and AcrIIA6 recognition sites are structurally close and allosterically linked. AcrIIA6 affects Cas9 conformational dynamics associated with PAM binding. Almost all type II Acrs characterised to date directly interact with the Cas9 endonuclease, although by distinct mechanisms. Anti-CRISPRs are small proteins which are the natural inhibitors for CRISPR-Cas systems; encoded on bacterial and archaeal viruses, they allow the virus to evade host CRISPR-Cas systems . The CRISPR-Cas-mediated adaptive immune response can be divided into three steps, including the acquisition of spacer derived from invading nucleic acids, crRNA processing, and target degradation. Theoretically, Acr proteins could suppress any step to disrupt the CRISPR-Cas system. Acr proteins are diverse with no common sequence or structural motif, and they inhibit a wide range of CRISPR-Cas systems with various inhibition mechanisms. CRISPR-Cas systems are divided into two classes (1 and 2) and six types (class 1: types I, III and IV; class 2: types II, V and VI) . Acr families are named for their type and subtype which are numbered sequentially as they are discovered .
HTH-type transcriptional regulator LrpA1 (LrpA1)
Type: Family

This entry represents HTH-type transcriptional regulator LrpA1 from Halobacterium salinarum and similar proteins specific to halobacteria. LrpA1 functions as a transcription factor, overseeing the regulation of genes associated with amino acid metabolism. It suppresses the aspB3 gene, responsible for encoding an aspartate transaminase, particularly in the presence of L-aspartate. Additionally, it influences the basal transcriptional regulator TfbB. Furthermore, LrpA1 demonstrates binding activity to its own promoter .
Holdfast anchor protein HfaD (Holdfast_HfaD)
Type: Family

This entry represents the Holdfast attachment protein D (HfaD,

) from Caulobacter vibrioides and related proteins from alphaproteobacteria. HfaD is involved in attachment of the holdfast to the cell. The holdfast is a structure that allows the bacteria to firmly adheres to surfaces. The holdfast biosynthesis and secretion machinery are encoded by two major loci, hfsEFGH and hfsDABC. The hfsDAB genes encode a secretion protein complex believed to span the inner and outer membrane of the cell envelope. Deletion of any of the components of this complex results in holdfast shedding and decreased adherence and biofilm formation .
Holdfast anchoring protein HfaB (Holdfast_HfaB)
Type: Family

This entry represents the Holdfast attachment protein B (HfaB,

) from Caulobacter vibrioides and related proteins from alphaproteobacteria. HfaB is involved in attachment of the holdfast to the cell. The holdfast is a structure that allows the bacteria to firmly adheres to surfaces. The holdfast biosynthesis and secretion machinery are encoded by two major loci, hfsEFGH and hfsDABC. The hfsDAB genes encode a secretion protein complex believed to span the inner and outer membrane of the cell envelope. Deletion of any of the components of this complex results in holdfast shedding and decreased adherence and biofilm formation . HfaB may be involved in the positive regulation of hfaC.
Stress response protein AzuC (AzuC)
Type: Family

This entry represents AzuC protein (

) from Escherichia coli and related proteins mainly from Enterobacteria. AzuC is a basic, extremely small protein (28 amino acids in Escherichia coli K-12) whose expression is repressed by cyclic AMP response protein (CRP) and stimulated by acidic pH . ArcA was shown to activate the operons encoding yccB and ybgT .
Ribonuclease HI, halobacteria (RnhA-like_halobact)
Type: Family

This entry represents Ribonuclease HI from Halobacterium salinarum (known as RnhA) (

) (

) and similar proteins specific to halobacteria species. RnhA is an enzymatic nuclease with a specific role in the degradation of RNA within RNA-DNA hybrids. Its mode of action suggests exonucleolytic activity in the context of RNA/DNA hybrids. Furthermore, RnhA exhibits endonucleolytic capabilities, playing a crucial role in the removal of RNA primers associated with the Okazaki fragments during the synthesis of the lagging strand .
Phosphomevalonate decarboxylase (MvaD-like)
Type: Family

This family includes Phosphomevalonate decarboxylase from Haloferax volcanii (MvaD) and similar enzymes responsible for the decarboxylation of mevalonate monophosphate from halophilic archaea. MvaD catalyses the decarboxylation of mevalonate 5-phosphate (MVAP) to isopentenyl phosphate (IP). It functions in an alternate mevalonate (MVA) pathway leading to isopentenyl diphosphate (IPP), a key precursor for the biosynthesis of isoprenoid compounds such as archaeal membrane lipids .
Putative surface-exposed virulence protein BigA (BigA)
Type: Family

This entry represents the putative surface-exposed virulence protein BigA from Salmonella typhimurium (

) and related Salmonella species.

BigA is an autotransporter protein characterised by a C-terminal outer membrane barrel (

) that facilitates the transport of its passenger domain across the membrane. The N-terminal region contains a variable passenger domain, which is translocated through the barrel. After export, the passenger domain may undergo auto-catalytic cleavage, cleavage by an external protease, or remain uncleaved, depending on the specific protein .
Nickel-binding protein HpnL (HpnL)
Type: Family

This entry represents the Hpn-like protein HpnL, or Hpn-2, including founding member HP1432 from Helicobacter pylori (

). HpnL is a histidine and glutamine-rich metal-binding polypeptide that binds nickel, among other metals . It may help deliver sequestered nickel for the biosynthesis of urease, which is critical to the survival of Helicobacter pylori during exposures to strongly acidic conditions. This protein is a paralogue to the histidine-rich nickel storage protein Hpn (e.g. HP1427) . Both nickel-binding proteins are expressed in response to nickel, under control of the regulator NikR .

Members of this family are found exclusively in Helicobacter.
Type V CRISPR-associated protein Cas12k (V_Cas12k)
Type: Family

This entry represents the Type V CRISPR-associated protein Cas12k and related proteins from cyanobacteria. Cas12k is the large effector protein of type V-K CRISPR systems, which belong to the class 2 systems. Cas12k has also been known as C2c5, and type V-K as type V-U5 .
Peptide resistance ABC transporter activity modulator VraH (VraH)
Type: Family

This entry represents VraH protein mainly found in Staphylococcus. VraH is a component of VraDEH system that confers a high-level resistance against daptomycin and gallidermin and enhances pathogenicity .
Sensor-kinase BvgS-like, first periplasmic domain (BvgS-like_periplasmic1)
Type: Domain

This entry represents the first of the two tandem periplasmic solute-binding domains of Virulence sensor protein BvgS from Bordetella pertussis and related proteins mainly found in proteobacteria. These domains are homologous to bacterial periplasmic-binding proteins (PBPs), a transmembrane region followed successively by a cytoplasmic PAS (Per/ARNT/SIM), a histidine-kinase (HK), a receiver and a histidine phosphotransfer (Hpt) domains. The sensor protein BvgS can autophosphorylate and phosphorylate the response regulator BvgA. The BvgAS phosphorelay controls the expression of virulence factors in response to certain environmental stimuli in Bordetella pertussis. Its close homologue from Escherichia coli Sensor protein EvgS appear to be involved in the transcriptional regulation of drug efflux pumps. This domain of BvgS belongs to the type 2 periplasmic-binding fold protein (PBP2) superfamily, whose members are involved in chemotaxis and uptake of nutrients and other small molecules from the extracellular space as a primary receptor .

PBP2 typically comprises two globular subdomains connected by a flexible hinge and bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two receptor cytoplasmically-located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energised by ATP hydrolysis .
Sensor-kinase BvgS-like, second periplasmic domain (BvgS-like_periplasmic2)
Type: Domain

This entry represents the second of the two tandem periplasmic solute-binding domains of Virulence sensor protein BvgS from Bordetella pertussis and related proteins mainly found in proteobacteria. These domains are homologous to bacterial periplasmic-binding proteins (PBPs), a transmembrane region followed successively by a cytoplasmic PAS (Per/ARNT/SIM), a histidine-kinase (HK), a receiver and a histidine phosphotransfer (Hpt) domains. The sensor protein BvgS can autophosphorylate and phosphorylate the response regulator BvgA. The BvgAS phosphorelay controls the expression of virulence factors in response to certain environmental stimuli in Bordetella pertussis. Its close homologue from Escherichia coli Sensor protein EvgS appear to be involved in the transcriptional regulation of drug efflux pumps. This domain of BvgS belongs to the type 2 periplasmic-binding fold protein (PBP2) superfamily, whose members are involved in chemotaxis and uptake of nutrients and other small molecules from the extracellular space as a primary receptor .

PBP2 typically comprises two globular subdomains connected by a flexible hinge and bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two receptor cytoplasmically-located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energised by ATP hydrolysis .
Glutamate [NMDA] receptor subunit 1-like, ligand-binding domain (NMDA1-like_ligand-bd)
Type: Domain

This entry represents the ligand binding domain of Glutamate [NMDA] receptor subunit 1 from Drosophila melanogaster (NMDA1), also known as the NR1 subunit of ionotropic NMDA (N-methyl-D-aspartate) glutamate receptor, and similar animal proteins. NMDA1, a member of the type 2 periplasmic binding fold protein superfamily, is an essential channel-forming subunit of the NMDA receptor. This protein plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. It mediates neuronal functions in glutamate neurotransmission. It plays a role in associative learning and in long-term memory consolidation . The functional NMDA receptor is a heterotetramer composed of two NR1 and two NR2 (A, B, C, and D) or of NR3 (A and B) subunits. NR1/NR3 receptors are calcium-impermeable and unaffected by ligands acting at the NR2 glutamate-binding site. The ionotropic N-methyl-d-asparate (NMDA) subtype of glutamate receptors serves critical functions in neuronal development, functioning, and degeneration in the mammalian central nervous system .
Glutamate [NMDA] receptor subunit 1-like, N-terminal LIVBP-like domain (NMDA1-like_N)
Type: Domain

This entry represents N-terminal leucine-isoleucine-valine-binding protein (LIVBP)-like domain of Glutamate [NMDA] receptor subunit 1 from Drosophila melanogaster (NMDA1), also known as the NR1 subunit of ionotropic NMDA (N-methyl-D-aspartate) glutamate receptor, and similar animal proteins. NMDA1, a member of the type 2 periplasmic binding fold protein superfamily, is an essential channel-forming subunit of the NMDA receptor. This protein plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. It mediates neuronal functions in glutamate neurotransmission. It plays a role in associative learning and in long-term memory consolidation . The functional NMDA receptor is a heterotetramer composed of two NR1 and two NR2 (A, B, C, and D) or of NR3 (A and B) subunits. NR1/NR3 receptors are calcium-impermeable and unaffected by ligands acting at the NR2 glutamate-binding site. These proteins serve critical functions in neuronal development, functioning, and degeneration in the mammalian central nervous system .
ROK, conserved site (ROK_cs)
Type: Conserved_site

This entry represents a conserved region found in the ROK (Repressor, ORF, Kinase) family. The domain common to the family members consists of about 300 residues with highly conserved central part rich of glycine residues.

A family of bacterial proteins has been described which groups transcriptional repressors, sugar kinases and yet uncharacterised open reading frames . This family, known as ROK (Repressor, ORF, Kinase) includes the xylose operon repressor, xylR, from Bacillus subtilis, Lactobacillus pentosus and Staphylococcus xylosus; N-acetylglucosamine repressor, nagC, from Escherichia coli; glucokinase

from Streptomyces coelicolor; fructokinase

from Pediococcus pentosaceus, Streptococcus mutans and Zymomonas mobilis; allokinase

and mlc from E. coli; and E. coli hypothetical proteins yajF and yhcI and the corresponding Haemophilus influenzae proteins. The repressor proteins (xylR and nagC) from this family possess an N-terminal region not present in the sugar kinases and which contains an helix-turn-helix DNA-binding motif.
Type II secretion system minor pseudopilin GspH (TypeII_GspH)
Type: Family

This entry represents type II secretion system protein H (GspH) found predominantly in gammaproteobacteria. The proteins of the type II secretion system (T2SS) are named Gsp in general and Eps in V. cholerae. EpsH is a GspH homologue and one of the minor pseudopilin components of the T2SS. This protein has been structurally characterised . It adopts an α/β structure, in which a hydrophobic helix is cradled by a pair of four-stranded antiparallel β-sheets.

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 .
NOTCH1 EGF-like calcium-binding domain (NOTCH1_EGF-like)
Type: Domain

This entry represents the EGF-like domains found in Neurogenic locus notch homolog protein 1 (NOTCH1) and related proteins such as protein kinase C-binding protein NELL2, Uromodulin and others. The EGF-like domains in NOTCH1 perform multiple functions and constitute crucial elements of the Notch signalling system. They play a role in dimer formation. They also serve as a protection against proteases, including TNF-alpha converting enzyme, which prevents Notch1 from ligand-independent activation .
Scytalone dehydratase-like (Scytalone_dh)
Type: Domain

This entry represents a domain found as standalone in Scytalone dehydratase (SDH) and in combination with amidase domain (

) in Scytalone dehydratase-like protein Arp1.

SDH is a member of the group of enzymes involved in fungal melanin biosynthesis . It was first identified in a phytopathogenic fungus, Magnaporthe grisea (Rice blast fungus), which causes rice blast disease . Scytalone dehydratase is a molecular target of inhibitor design efforts aimed at protecting rice plants from fungal disease .

Arp1 ia a part of the Pks2 gene cluster that mediates the formation of infectious structures (appressoria), enabling these fungi to kill insects faster .
Microtubule cross-linking factor 1-3 (MTCL1-3)
Type: Family

The SOGA (suppressor of glucose by autophagy) family consists of proteins SOGA1, SOGA2, and SOGA3 (also known as Microtubule cross-linking factor 1-3). SOGA1 regulates autophagy by playing a role in the reduction of glucose production in an adiponectin-and insulin-dependent manner . SOGA1/2 are required for faithful chromosome segregation during mitosis . Members of this entry contain a long coiled-coil domain that dimerizes and holds two N-terminal domains that bind to microtubules .
CFI box-CTERM domain (CFI_box_CTERM_dom)
Type: Domain

This entry represents the long form of the CFI putative sorting signal, in which the CFI motif occurs at the start of a longer homology domain, named the CFI-box-CTERM domain. The CFI-box motif is a probable protein modification site, first modified on the Cys sidechain and then, most likely cleaved in a manner resembling the CAAX box in eukaryotes. Proteins harbouring this domain are found in prokaryotes. Most members of this group show this domain towards the C-terminal end, while Prepilin-type N-terminal cleavage/methylation domain-containing protein from Desulfatibacillum aliphaticivorans (

) has the CFI motif as the start of a longer tail region.
CmeU-like (CmeU-like)
Type: Family

This entry represents a family of proteins from Campylobacter, including CmeU from Campylobacter coli (

) .
Highly acidic protein (Highly_acidic)
Type: Family

This entry represents a family of very short highly acidic proteins from Campylobacter. Members are usually between 50 and 55 amino acids long.
Type I-Fv CRISPR-associated protein Cas7fv-like (Cas7fv-like)
Type: Family

This entry represents a family of Type I-Fv CRISPR-associated proteins from proteobacteria, including

from Shewanella putrefaciens .

Cas7fv is one of the CRISPR associated (Cas) proteins of type I-F variant CRISPR-Cas system. CRISPR (clustered regularly interspaced short palindromic repeats)-Cas modules are adaptive immune systems found in archaea and bacteria against foreign nucleic acids such as phages and plasmids via RNA-guided endonucleases. CRISPR-Cas systems are classified based on Cas protein content and arrangement in CRISPR-Cas loci into two main classes (1 and 2) and at least six types (I, II, III, IV, V, VI). Class 1 systems utilize multiple Cas proteins and CRISPR RNA (crRNA) to form an effector complex while class 2 systems employ a large, single effector with crRNA to mediate interference. Type I CRISPR-Cas systems are most widespread in nature and the Cas protein composition of the employed Cascade interference complexes differ between seven subtypes (A-F, U). Type I-F variant (I-Fv) is a subtype that rely on a minimal set of five Cas proteins and has structural differences with I-F and I-E Cascades. Double strand DNA recruitment and recognition in the type I-Fv Cascade is facilitated from the major groove side by Cas5fv instead of the large subunit Cas8 and the finger domain of Cas7fv .
Variant surface antigen A-F-like, signal domain (VlpA-F-like_signal)
Type: Domain

This entry represents the N-terminal signal domain of the lipoproteins Variant surface antigen A-F from Mesomycoplasma hyorhinis and similar sequences from the parasites mollicutes .
Cyanobacterial tandem bacteriocin (CTB)
Type: Family

This entry represents a family of cyanobacterial proteins named CTB (Cyanobacterial Tandem Bacteriocin) as multiple family members can be encoded in tandem in a single genome. Members of this family, which average about 85 amino acids in length, resemble class II bacteriocins. They show N-terminal sequence similarity to bacteriocin leader peptide domain

and lack Cys residues (enriched in lanthipeptides as well as disulfide-forming bacteriocins) almost entirely. They are encoded next to homologues of families

and

, involved in bacteriocin cleavage and export.
Auxiliary Activity family 9 (AA9)
Type: Family

Although weak endoglucanase activity has been demonstrated in several members of this family , they lack the clustered conserved catalytic acidic amino acids present in most glycoside hydrolases. Many members of this family lack measurable cellulase activity on their own, but enhance the activity of other cellulolytic enzymes. They are therefore unlikely to be true glycoside hydrolases . The substrate-binding surface of this family is a flat Ig-like fold . This family of enzymes were originally classified as glycoside hydrolases (GH61) and they have been reclassified as the Auxiliary Activity Family 9 (

, ) of CAZy.