SII-SWORD/CoKE huggingface dataset:
Type VIII secretion system, CsgF (T8SS_CsgF)
Type: Family

The extracellular nucleation-precipitation (ENP) pathway or Type VIII secretion system (T8SS) in Gram-negative (diderm) bacteria is responsible for the secretion and assembly of prepilins for fimbiae biogenesis, the prototypical curli. Besides the T2SS that can be involved in the assembly of prototypical Type 4 pilus, the T4SS that can be involved in the biogenesis of the prototypical pilus T, the T3SS involved in the assembly of the injectisome and the T7SS involved in the formation of the prototypical Type 1 pilus, the T8SS differs in that fibre-growth occurs extracellularly. The curli, also called thin aggregative fimbriae (Tafi), are the only fimbriae dependent on the T8SS. Tafi were first identified in Salmonella spp and the controlling operon termed agf; however subsequent isolation of the homologous operon in E coli led to its being called csg. In the absence of extracellular polysaccharides Tafi appear curled, although when expressed with such polysaccharides their morphology appears as a tangled amorphous matrix . CsgF is one of three putative curli assembly factors appearing to act as a nucleator protein. Unlike eukaryotic amyloid formation, curli biogenesis is a productive pathway requiring a specific assembly machinery .
Protein of unknown function DUF2471 (DUF2471)
Type: Family

The function of this family is unknown. Members all come from Burkholderia spp. A number of proteins in this entry, including

, are annotated as serine/threonine-protein kinases.
Protein of unknown function DUF2474 (DUF2474)
Type: Family

This family of short proteins has no known function.
Plasmid conjugative transfer protein PilI (Plasmid_conjug_transfer_PilI)
Type: Domain

The thin pilus of plasmid R64 belongs to the type IV family and is required for liquid matings. PilI is one of 14 genes that have been identified as being involved in the biogenesis of the R64 thin pilus . According to structure prediction, proteins in this family adopt a compact domain composed of five β strands and an α helix between strands two and three.
Plasmid conjugative transfer entry exclusion protein TraS (Eex_TraS)
Type: Family

Entry exclusion (Eex) is a process which prevents redundant transfer of DNA between donor cells. TraS is a protein involved in Eex. It blocks redundant conjugative DNA synthesis and transport between donor cells, and it is suggested that TraS interferes with a signalling pathway that is required to trigger DNA transfer . TraS on the recipient cell is known to form an interaction with TraG on the donor cell .
Conjugative transposon, TraO (Conjug_transposon_Tra0)
Type: Family

This is a family of conjugative transposon proteins.
Curli assembly protein CsgE (Curli_CsgE)
Type: Family

Curli are a class highly aggregated surface fibres that are part of a complex extracellular matrix. They promote biofilm formation in addition to other activities. CsgE is a non-structural protein involved in curli biogenesis . CsgE forms an outer membrane complex with the curli assembly proteins CsgG and CsgF .
Spore coat protein CotE (Spore_coat_CotE)
Type: Family

CotE is a morphogenic protein that is required for the assembly of the outer coat of the endospore and spore resistance to lysozyme . CotE also regulates the expression of cotA, cotB, cotC and other genes encoding spore outer coat proteins . The timing of cotE expression has been shown in Bacillus subtilis to affect spore coat morphology but not lysozyme resistance .
Ciliary microtubule inner protein 2A-C-like domain (CMI2A-C-like_dom)
Type: Domain

This entry represents a domain found in a group of eukaryotic proteins, including human Ciliary microtubule inner protein 2A-C-like (CMI2A-C-like). CMI2B/C are microtubule inner proteins (MIPs) that form part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating . This domain is a tubulin-binding domain. Some proteins in this group contain multiple copies of this domain.
Proline-rich protein 23 (PRR23)
Type: Family

This entry represents proline-rich protein 23 (PRR23) family. The funciton of this family is not clear.
Uncharacterised protein family UPF0574 (UPF0574)
Type: Family

This is a family of proteins with no known function. The family is rich in proline residues.
Alpha-galactosidase, NEW3 domain (A-galactase_NEW3)
Type: Domain

This domain has been named NEW3, but its function is not known. It is found on proteins which are bacterial galactosidases .
DNA integrity scanning, DisA, linker region (DNA_integrity_scan_DisA_link)
Type: Domain

The DisA protein is a bacterial checkpoint protein that dimerises into an octameric complex. The protein consists of three distinct domains. the first, N-terminal region, from 1-145 is globular and is represented by

; the next 146-289 residues is this domain that consists of an elongated bundle of three α-helices (α6, α10, and α11), one side of which carries an additional three helices (α7-9), thus forming a spine like-linker between domains 1 and 3. The C-terminal residues of domain 3 (

), represent the specific DNA-binding domain. The octameric complex thus has structurally linked nucleotide-binding and DNA-binding HhH domains and the nucleotide-binding domains are bound to a cyclic di-adenosine phosphate such that DisA is a specific di-adenylate cyclase. The di-adenylate cyclase activity is strongly suppressed by binding to branched DNA, but not to duplex or single-stranded DNA, suggesting a role for DisA as a monitor of the presence of stalled replication forks or recombination intermediates via DNA structure-modulated c-di-AMP synthesis .
Spindle body associated protein, C-terminal domain (Spindle_body_associated_C_dom)
Type: Domain

This C-terminal domain of spindle-body-associated protein Sfi1 has an important role to play in the bridge-splitting during bi-polar spindle assembly, and this separation event possibly requires interaction with integral components of the nuclear envelope, such as the Mps2-Bbp1 complex . Centrally to this domain is a region carrying centrin-binding repeats with repeating units containing tryptophan,

.
Putative transmembrane family 234 (TMEM234)
Type: Family

TMEM234 is a family of putative inner membrane proteins. Many bacterial members are annotated as putative L-Ara4N-phosphoundecaprenol flippase subunit ArnE, and as inner membrane proteins. They may be transporters of the multi-drug-resistant superfamily.
Endo-1,3(4)-beta-glucanase 1, carbohydrate binding (Eng1_septum)
Type: Domain

This is a carbohydrate binding domain found in Schizosaccharomyces pombe endo-1,3(4)-beta-glucanase 1 (Eng1). It is required for septum localisation .
Lipoprotein LpqB, beta-propeller domain, C-terminal (Lipoprotein_LpqB_C)
Type: Domain

The Gmad1 domain is found associated with

, in bacterial spore formation. It is predicted to have a β-propeller fold and to have a passive binding role rather than a catalytic function owing to the low number of conserved hydrophilic residues.
Bacterial spore germination, immunoglobulin-like domain (Gmad2_Ig-like_dom)
Type: Domain

This domain is found linked to

in some bacterial proteins. It is predicted to contain an immunoglobulin-like all-β fold .
Protein of unknown function DUF2478 (DUF2478)
Type: Family

This is a family of hypothetical bacterial proteins encoded in the vicinity of molybdenum ABC transporter gene-products MobA, MobB and MobC. However the function could not be confirmed.
BppU, N-terminal (BppU_N)
Type: Domain

This is the N-terminal domain of baseplate upper proteins (BppU, also known as ORF48) which is found in bacteriophages. The N-terminal domain exhibits a β-sandwich immunoglobulin fold .
Protein of unknown function DUF2480 (DUF2480)
Type: Family

All the members of this family are uncharacterised proteins, but the environment in which they are found on the bacterial genome suggests a function as a glucose-6-phosphate isomerase (

). This could not, however, be confirmed.
Bacteriophage A118, Gp45 (Phage_A118_Gp45)
Type: Family

The proteins in this entry represents Gp45 in Listeria phage A118 (Bacteriophage A118) and related proteins; Gp45 is thought to have a function in the phage tail-fibre system.
Protein of unknown function DUF2481 (DUF2481)
Type: Family

This is a hypothetical protein family homologous to Lmo2305 in Bacteriophage A118 systems.
Protein of unknown function DUF2482 (DUF2482)
Type: Family

This entry represents a group of phage proteins with unknown function.
Protein of unknown function DUF2483 (DUF2483)
Type: Family

This is a family of unknown function is found in tailed bacteriophages and suspected prophages found in Firmicutes.
Protein of unknown function DUF2484 (DUF2484)
Type: Family

A role of this family in UDP-N-acetylenolpyruvoylglucosamine reductase, as MurB, could not be confirmed.
ESAT-6 secretion machinery protein EssA/YueC (EssA/YueC)
Type: Family

Mycobacterium tuberculosis secretes ESAT-6, a virulence factor belonging to the WXG100 family. Other Gram-positive human pathogens belonging to the phylum Firmicutes, e.g. Staphylococcus aureus, also secrete immune potent WXG100 proteins. S. aureus secretes ESAT-6-like proteins EsxA and EsxB. In S.aureus the WXG100 protein secretion system seems to be encoded by a locus of eight ORFs, called ess (eSAT-6 secretion system) . This locus encodes, amongst several other proteins, EssA, a protein predicted to possess one transmembrane domain. Due to its predicted membrane location and its absolute requirement for WXG100 protein secretion, it has been speculated that EssA could form a secretion apparatus. Proteins homologous to EssA are absent from mycobacteria .

Bacillus subtilis secretes the WXG100 virulence factor homologue YukE. YeuC has been shown to be required for YukE export within a nonessential Esat-6 protein secretion system (ESX or Ess) in B. subtilis. It is suggested to be part of the yuk/yue locus encoding the proteins involved in this ESX .
NAD(P)H-quinone oxidoreductase subunit M (NdhM)
Type: Family

The NADH dehydrogenase I complex shuttles electrons from an unknown electron donor, via FMN and iron-sulphur (Fe-S) centres, to quinones in the respiratory and/or the photosynthetic chain. The immediate electron acceptor for the enzyme in plants is believed to be plastoquinone. The NADH dehydrogenase I complex couples the redox reaction to proton translocation, and thus conserves the redox energy in a proton gradient.

This entry represents subunit M of the NADH dehydrogenase I complex in cyanobacteria and plant chloroplasts .
Phage tail assembly chaperone protein Gp14 (Phage_TAC_8)
Type: Family

This phage protein family is expressed from within a cluster of tail- and base plate-producing genes . It is a family of tail assembly chaperone proteins .
Protein of unknown function DUF2486 (DUF2486)
Type: Family

This family is made up of members from various Burkholderia spp. The function is unknown.
PBSX phage terminase small subunit-like, N-terminal domain (XtmA-like_N)
Type: Domain

This entry represents the N-terminal domain of PBSX phage terminase small subunit from Bacillus subtilis (XtmA) mainly found in firmicutes and some species of tailed bacteriophages. Members of this group share protein sequence similarity with the phage terminase small subunit.

Packaging of double-stranded viral DNA concatemers requires interaction of the prohead with virus DNA. This process is mediated by a phage-encoded DNA recognition and terminase protein. The terminase enzymes described so far are hetero-oligomers composed of a small and a large subunit. The small terminase subunit is thought to form a nucleoprotein structure that helps to position the terminase large subunit at the packaging initiation site .
Gp23 (Gp23)
Type: Family

This entry represents the major tail subunit protein, Gp23 of Listeria. Its function is unclear.
Toxin co-regulated pilus biosynthesis protein Q, C-terminal (Pilus_synth_Q_C)
Type: Domain

The toxin-coregulated pilus (TCP) of Vibrio cholerae and the soluble TcpF protein that is secreted via the TCP biogenesis apparatus are essential for intestinal colonisation in the disease of cholera. TCP fibres are homopolymers of TcpA pilin, encoded by the first gene in the tcp biogenesis operon. TcpQ is part of an outer membrane complex of the TCP biogenesis apparatus, comprised of TcpC and TcpQ. TcpQ is required for proper localisation of TcpC to the outer membrane .
Generative cell specific-1/HAP2 domain (HAP2/GCS1_dom)
Type: Domain

The gene encoding Arabidopsis HAP2 is allelic with GCS1 (Generative cell-specific protein 1). HAP2 is expressed only in the haploid sperm and is required for efficient guidance of the pollen tube to the ovules. In Arabidopsis the protein is a predicted membrane protein with an N-terminal secretion signal, a single transmembrane domain and a C-terminal histidine-rich domain . HAP2-GCS1 is found from plants to lower eukaryotes and is necessary for the fusion of the gametes in fertilisation. It is involved in a novel mechanism for gamete fusion where a first species-specific protein binds male and female gamete membranes together after which a second, broadly conserved protein, either directly or indirectly, causes fusion of the two membranes together. The broadly conserved protein is represented by this HAP2-GCS1 domain, conserved from plants to lower eukaryotes . In Plasmodium berghei the protein is expressed only in male gametocytes and gametes, having a male-specific function during the interaction with female gametes, and being indispensable for parasite fertilisation. The gene in plants and eukaryotes might well have originated from acquisition of plastids from red algae .
Domain of unknown function DUF2510 (DUF2510)
Type: Domain

This domain of unknown function is found in a family of proteins conserved in Actinobacteria. Many members are annotated as putative membrane proteins but this could not be confirmed.
Late embryogenesis abundant protein, LEA-18 (LEA-18)
Type: Family

This is a family of late embryogenesis-abundant proteins There is high accumulation of this protein in dry seeds, and in the roots of full-grown plants in response to dehydration and ABA (abscisic acid application) treatments . This LEA protein disappears after germination. It accumulates in growing regions of well irrigated hypocotyls and meristems suggesting a role in seedling growth resumption on rehydration . As a group the LEA proteins are highly hydrophilic, contain a high percentage of glycine residues, lack Cys and Trp residues and do not coagulate upon exposure to high temperature, and for these reasons are considered to be members of a group of proteins called hydrophilins . Expression of the protein is negatively regulated during etiolating growth, particularly in roots, in contrast to its expression patterns during normal growth .
Domain of unknown function DUF2520 (DUF2520)
Type: Domain

This presumed domain is found C-terminal to a Rossmann-like domain suggesting that these proteins are oxidoreductases.
Salivary thrombin inhibitor anophelin, mosquito (Thrombin_inhibitor_anophelin)
Type: Family

This family represents Salivary thrombin inhibitor anophelin from Anopheles albimanus and similar proteins from insects. AT is a salivary protein with anticoagulant activity that inhibits host thrombin (F2), the peptidase that is at the end of the blood coagulation cascade and which creates the clot by cleaving fibrinogen . The interaction between thrombin and fibrinogen involves two different areas of contact - via the thrombin active site and via a second substrate-binding site known as an exosite. The inhibitor acts by blocking the exosite, rather than by interacting with the active site. The inhibitors are from mosquitoes that feed on human blood and which, by inhibiting thrombin, prevent the blood from clotting and keep it flowing.
Netrin module, non-TIMP type (Netrin_module_non-TIMP)
Type: Domain

The netrin (NTR) module is an about 130-residue domain found in the C-terminal parts of netrins, complement proteins C3, C4, and C5, secreted frizzled-related proteins, and type I procollagen C-proteinase enhancer proteins (PCOLCEs), as well as in the N-terminal parts of tissue inhibitors of metalloproteinases (TIMPs). The proteins harboring the NTR domain fulfill diverse biological roles ranging from axon guidance, regulation of Wnt signalling, to the control of the activity of metalloproteinases. The NTR domain can be found associated to other domains such as CUB, WAP, Kazal, Kunitz, Ig-like, laminin N-terminal, laminin-type EGF or frizzled. The NTR domain is implicated in inhibition of zinc metalloproteinases of the metzincin family .

The NTR module is a basic domain containing six conserved cysteines, which are likely to form internal disulphide bonds, and several conserved blocks of hydrophobic residues (including an YLLLG-like motif). The NTR module consists of a β-barrel with two terminal α-helices packed side by side against the face of the β-barrel (see

) .

This entry includes most netrin modules, but excludes those found in TIMPs.
RIO-type domain (RIO_dom)
Type: Domain

This entry represents the atypical serine/threonine kinase domain found in the RIO family members and similar proteins. RIO protein family are classified as atypical serine/threonine kinases and includes Rio1, Rio2 and Rio3, highly conserved from archaea to human . They exhibit little sequence similarity with eukaryotic protein kinases, and hence, are classified as atypical protein kinases . This domain is also found at the C-terminal of EKC/KEOPS complex subunit BUD32 from Fungi and Kae1/Bud32 from archaea .

Rio1-3 have a distinct role in cytoplasmic maturation of the pre-40S pre-rRNA. Yeast Rio1 and Rio2 proteins are essential proteins that associate to ribosomal pre-40S particles and are involved in D-site cleavage in vivo . They are also required for proper cell cycle progression and chromosome maintenance, and are necessary for survival of the cells. These proteins are involved in the processing of 20 S pre-rRNA via late 18 S rRNA processing.
RIO kinase, conserved site (RIO_kinase_CS)
Type: Conserved_site

Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process.
Protein kinases fall into three broad classes, characterised with respect to substrate specificity :

Serine/threonine-protein kinases

Tyrosine-protein kinases

Dual specificity protein kinases (e.g. MEK -phosphorylates both Thr and Tyr on target proteins)

Protein kinase function is evolutionarily conserved from Escherichia coli to human . Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved , leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases .

This entry represents RIO kinase, they exhibit little sequence similarity with eukaryotic protein kinases, and are classified as atypical protein kinases . The conformation of ATP when bound to the RIO kinases is unique when compared with ePKs, such as serine/threonine kinases or the insulin receptor tyrosine kinase, suggesting that the detailed mechanism by which the catalytic aspartate of RIO kinases participates in phosphoryl transfer may not be identical to that employed in known serine/threonine ePKs. Representatives of the RIO family are present in organisms varying from Archaea to humans, although the RIO3 proteins have only been identified in multicellular eukaryotes, to date.
Phosphatidylinositol 3-/4-kinase, conserved site (PI3/4_kinase_CS)
Type: Conserved_site

Phosphatidylinositol 3-kinase (PI3-kinase) (

) is an enzyme that phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol ring. The three products of PI3-kinase - PI-3-P, PI-3,4-P(2) and PI-3,4,5-P(3) function as secondary messengers in cell signalling. Phosphatidylinositol 4-kinase (PI4-kinase) (

) is an enzyme that acts on phosphatidylinositol (PI) in the first committed step in the production of the secondary messenger inositol-1'4'5'-trisphosphate. This domain is also present in a wide range of protein kinases, involved in diverse cellular functions, such as control of cell growth, regulation of cell cycle progression, a DNA damage checkpoint, recombination, and maintenance of telomere length. Despite significant homology to lipid kinases, no lipid kinase activity has been demonstrated for any of the PIK-related kinases .

The PI3- and PI4-kinases share a well conserved domain at their C-terminal section; this domain seems to be distantly related to the catalytic domain of protein kinases . The catalytic domain of PI3/PI4KK has the typical bilobal structure that is seen in other ATP-dependent kinases, divided into an N-lobe and a C-lobe (

) . The core of this domain is the most conserved region of the PI3Ks. The N-lobe contains a five-stranded antiparallel β-sheet core flanked by a helical hairpin on one side and a helix on the other. The C-lobe contains helices, which form a helical bundle together with the N--obe helix. The helical bundle is flanked by three β-strands and a helix. Three loops are related to kinase activity, the glycine-rich G-loop, the catalytic loop and the activation loop. The G-loop has been reported to bind to the phosphate group of nucleotides .
Membrane magnesium transporter (MMgT)
Type: Family

This entry represents a family of membrane magnesium transporters (MMgT) . The proteins, MMgT1 (also known as ER membrane protein complex subunit 5) and MMgT2, are localised to the Golgi complex and post-Golgi vesicles, including the early endosomes, suggesting that they may provide regulated pathways for Mg2+ transport in the Golgi and post-Golgi organelles of epithelium-derived cells . MMgT1 is part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins and it is also involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices . MMgT1 is also required for the post-translational insertion of tail-anchored proteins in endoplasmic reticulum membranes and mediates the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology thus, controlling the topology of multi-pass membrane proteins like the G protein-coupled receptors .
Glycophorin, conserved site (Glycophorin_CS)
Type: Conserved_site

Proteins in this group are responsible for the molecular basis of the blood group antigens, surface markers on the outside of the red blood cell membrane. Most of these markers are proteins, but some are carbohydrates attached to lipids or proteins [Reid M.E., Lomas-Francis C. The Blood Group Antigen FactsBook Academic Press, London / San Diego, (1997)]. Glycophorin A (PAS-2) and glycophorin B (PAS-3) belong to the MNS blood group system and are associated with antigens that include M/N, S/s, U, He, Mi(a), M(c), Vw, Mur, M(g), Vr, M(e), Mt(a), St(a), Ri(a), Cl(a), Ny(a), Hut, Hil, M(v), Far, Mit, Dantu, Hop, Nob, En(a), ENKT, amongst others.

Glycophorin A is the major sialoglycoprotein of the erythrocyte membrane . Structurally, glycophorin A consists of an N-terminal extracellular domain, heavily glycosylated on serine and threonine residues, followed by a transmembrane region and a C-terminal cytoplasmic domain. Other glycophorins in this entry such as Glycophorin B and Glycophorin E represent minor sialoglycoproteins in the erythrocyte membrane.

This entry represents a short conserved region found in the transmebrane domain of gylcophorins.