SII-SWORD/CoKE huggingface dataset:
Developmental pluripotency-associated protein 2/4, C-terminal domain (Dppa2/4_C_dom)
Type: Domain

This domain has been characterised in the finding of a developmental pluripotency associated gene (Dppa) in the lower vertebrate Xenopus laevis . Previous to this discovery, Dppa genes were known only in higher vertebrates.
Developmental pluripotency-associated protein 2/4, central domain (Dppa2/4_central_dom)
Type: Domain

Developmental pluripotency associated genes (Dppa) in lower vertebrates have remained undetected until the discovery of a Dppa homologue in Xenopus laevis . This entry represents a central domain of Dppa 2/4.
Tocopherol cyclase (Tocopherol_cyclase)
Type: Family

This family contains tocopherol cyclases. These enzymes are involved in the synthesis of tocopherols and tocotrienols (vitamin E) .
Polycomb-like MTF2 factor 2, C-terminal domain (Mtf2_C_dom)
Type: Domain

Mammalian Polycomb-like gene MTF2/PCL2 forms a complex with Polycomb repressive complex-2 (PRC2) and collaborates with PRC1 to achieve repression of Hox gene expression . The human MTF2 gene is expressed in three splicing variants, each of them contains the short C-terminal domain defined here.
Lysine-2,3-aminomutase, C-terminal domain (LAM_C_dom)
Type: Domain

This domain is found in the C-terminal of lysine-2,3-aminomutase (LAM) and is involved in dimerisation . LAM catalyses the interconversion of L-alpha-lysine and L-beta-lysine, which proceeds by migration of the amino group from C2 to C3 concomitant with cross-migration of the 3-pro-R hydrogen of L-alpha-lysine to the 2-pro-R position of L-beta-lysine.
Spi protease inhibitor (Spi_Prtas-inh)
Type: Domain

This domain family includes the protease inhibitor Spi. The domain is also found in the pro-peptides of streptopain (SpeB). SpeB is produced as a 43kDa pre-pro-protein, which is secreted via the recently described Sec secretory pathway Exportal. There is tight coupling between this inhibitor and its associated protease: the gene for the inhibitor Spi is located directly downstream from the gene for the streptococcal cysteine protease SpeB, and the sequence of the inhibitor is very similar to that of the SpeB propeptide. This is an example of an inhibitor molecule that is a structural homologue of the cognate propeptide, and is genetically linked to the protease gene .
Antitoxin SpoIISB (Antitoxin_SpoIISB)
Type: Family

Members of this family act as antitoxins. They bind to the SpoIISA toxin . They are disordered proteins which adopt structure only when bound to SpoIISA .
Tc3 transposase, DNA binding domain (Tc3_transposase_DNA-bd_dom)
Type: Domain

Tc3 is transposase with a specific DNA-binding domain which contains three α-helices, two of which form a helix-turn-helix motif which makes four base-specific contacts with the major groove. The N terminus makes contacts with the minor groove. There is a base specific recognition between Tc3 and the transposon DNA. The DNA binding domain forms a dimer in which each monomer binds a separate transposon end. This implicates that the dimer has a role in synapsis and is necessary for the simultaneous cleavage of both transposon termini .
Phosphatase RapC/F inhibitor (PhrC_PhrF)
Type: Family

In the field of cell-cell communication, an emerging class of extracellular signalling peptides that function intracellularly has been identified in Gram-positive bacteria. One illustrative member of this group is the Phr family of extracellular signaling peptides of Bacillus subtilis. The Phr signalling peptides are secreted by the bacterium, and then, despite the presence of intracellular peptidases, they are actively transported into the cell where they interact with intracellular receptors to regulate gene expression. The intracellular receptors are members of a family of aspartyl-phosphate phosphatases, the Rap phosphatases. These phosphatases cause the dephosphorylation of response regulator proteins, ubiquitous regulatory proteins in bacteria. Immediately downstream of the genes for the Rap phosphatases are the genes for the Phr peptides, forming rap phr signalling cassettes. There are at least seven rap phr signalling cassettes in B. subtilis, and the genome sequence of other Gram-positive, endospore-forming bacteria suggests that similar cassettes may also function in these bacteria. In B. subtilis, the rap phr cassettes regulate sporulation, genetic competence, and genes comprising the quorum response (i.e. the response to high cell density) .

The Phr genes are processed, probably by a single processing event that cleaves off the C-terminal pentapeptide. These pentapeptides inhibit specific phosphatases that are regulators of response regulator transcription factors. The PhrA (ARNQT) and PhrE (SRNVT) peptides inhibit the RapA and RapE phosphatases, respectively, whose activity is directed toward the Spo0F approximately P intermediate response regulator of the sporulation phosphorelay; while the PhrC (ERGMT) peptide inhibits the RapC protein acting on the ComA response regulator for competence with regard to DNA transformation .

PhrF (RapF inhibitor) and PhrC (RapC) stimulate ComA-dependent gene expression to different levels and are both required for full expression of genes activated by ComA, which activates the expression of genes involved in competence development and the production of several secreted products .
Nuclear receptor repeat (Nuclear_receptor_repeat)
Type: Repeat

This is a repeat involved in dimerisation of nuclear receptors proteins and in transcriptional regulation in general. It contains a Leu-Xaa-Xaa-Leu-Leu motif which has been characterised for the orphan nuclear receptor Dax-1, which represses the constitutively expressed protein Ad4BP/SF-1. The LXXLL motif plays in important role in binding of Dax-1 to Ad4BP/SF-1 .
Kinesin-associated microtubule-binding domain (Kinesin-assoc_MT-bd_dom)
Type: Domain

This domain, found in kinesin and kinesin-like proteins, binds to microtubules .
LssY-like C-terminal domain (LssY-like-C_dom)
Type: Domain

This domain is found at the C terminus of Legionella LssY proteins, which may be a part of the type I secretion system . The domain is functionally uncharacterised. There are two completely conserved residues (P and W) that may be functionally important.
Phostensin/Taperin N-terminal domain (Phostensin/Taperin_N_dom)
Type: Domain

Phostensin has been identified as a PP1 regulatory protein binding protein. This domain is N-terminal to the PP1- and SH3-binding regions, though may carry an additional SH3-binding motif. It is likely that phostensin targets PP1 to the F-actin cytoskeleton . Phostensin binds to actin and decreases the elongation and depolymerisation rates of actin filament pointed ends .

This domain is also found in the taperin, which is a PP1 binding protein that is ancestrally related to phostensin. Taperin has a role in sound perception .
Tubulin-like (Tubulin-like)
Type: Family

Many of the residues conserved in tubulin are also highly conserved in this family.
NVEALA protein (NVEALA)
Type: Family

This family of proteins is functionally uncharacterised. They are found in bacteria and are typically between 75 and 92 amino acids in length. They contain a conserved NVEALA sequence motif.
Putative motility protein (YjfB_motility)
Type: Family

This family of proteins is regulated in B. subtilis by SigD , and is likely to be involved in motility or flagellin production. Proteins in this family are approximately 60 amino acids in length, and contain two highly conserved asparagine residues.
Phostensin/Taperin PP1-binding domain (Phostensin/Taperin_PP1-bd_dom)
Type: Domain

Phostensin has been identified as a PP1 regulatory protein, binding PP1 at the KISF motif found in this domain. This domain also appears to carry an incomplete SH3-binding domain PxRxP further upstream. It is likely that phostensin targets PP1 to the F-actin cytoskeleton . Phostensin binds to actin and decreases the elongation and depolymerisation rates of actin filament pointed ends .

This domain is also found in the taperin, which is a PP1 binding protein that is ancestrally related to phostensin. Taperin has a role in sound perception .
Sensor N-terminal transmembrane domain (Sensor_TM1)
Type: Domain

This domain is found at the N terminus of the sensor component of the two-component regulatory system. It includes a transmembrane region and part of the periplasmic region, which is likely to be involved in stimulus sensing .
Phosphoprotein P soyouz module (Soyouz_module)
Type: Domain

The soyouz module moiety is the N-terminal region of the phosphoprotein (P) from the subfamily Paramyxovirinae of the family Paramyxoviridae viruses. The main genera in this subfamily include the Rubulaviruses, avulaviruses, respiroviruses, henipaviruses, and morbilliviruses, all of which are enveloped viruses with a non-segmented, negative, single-stranded RNA genome encapsidated by the nucleoprotein (N) within a helical nucleocapsid .

This domain is also found in Protein W and V .
Plant viral polyprotein P1, serine peptidase domain (P1_Ser_Pept_dom)
Type: Domain

This entry represents the serine peptidase at the N terminus of P1 protein of the Potyviridae polyproteins. The catalytic triad in P1 from the ssRNA positive-strand Brome streak mosaic rymovirus, is His-311, Asp-322 and Ser-355 .
ToxN/AbiQ toxin (ToxN/AbiQ_toxin)
Type: Family

ToxN acts as a toxin, it is part of a type III toxin-antitoxin system. It acts as a ribosome independent endoribonuclease. It interacts with, and is inhibited by, the RNA antitoxin, ToxI . Three ToxN monomers bind to three ToxI monomers to create a trimeric ToxN-ToxI complex .
Regulatory protein YrvL (YrvL)
Type: Family

YrvL prevents expression and activity of the YrvI sigma factor. It may function as an anti-sigma factor .
Cep57 centrosome localisation domain (Cep57_CLD)
Type: Domain

The CLD or centrosome localisation domain of Cep57 is found at the N terminus, and lies approximately between residues 58 and 239. This region lies within the first α-helical coiled-coil segment of Cep57, and localises to the centrosome internally to gamma-tubulin, suggesting that it is either on both centrioles or on a centromatrix component . This N-terminal region can also multimerise with the N terminus of other Cep57 molecules.
Stage V sporulation protein AE (SpoVAE)
Type: Family

This entry represents stage V sporulation protein AE .
Phage protein (N4 Gp49/phage Sf6 gene 66) family (Phage_gp49_66)
Type: Family

This family of phage proteins is functionally uncharacterised. The family includes bacteriophage Sf6 gene 66 (

) as well as phage N4 GP49 protein (

). Proteins in this family are typically between 87 and 154 amino acids in length. There is a conserved NGF sequence motif.
Cold-inducible protein YdjO (YdjO)
Type: Family

This family includes the B. subtilis YdjO protein (

), which is functionally uncharacterised. Note - this is not a homologue of E. coli YdjO (

). B. subtilis YdjO is cold-inducible . Its expression is induced by the extracytoplasmic function sigma factor sigma-W .
Putative membrane protein YuiB (YuiB)
Type: Family

This family of bacterial proteins is functionally uncharacterised. Proteins in this family are approximately 100 amino acids in length. There is a conserved FGIGF sequence motif, and many members are putative membrane proteins.
YIEGIA protein (YIEGIA)
Type: Family

This family includes the B. subtilis YphB protein (

), which is functionally uncharacterised (note - this is not a homologue of E. coli YphB). Its expression is regulated by the sporulation transcription factor sigma-F, however it is not essential for sporulation or germination . Proteins in this family are typically between 276 and 300 amino acids in length and contain a conserved YIEGIA motif.
Stimulus-sensing domain (Stimulus_sens_dom)
Type: Domain

This domain is found in the periplasmic region of the sensor component of the two-component regulatory system. The periplasmic region is likely to be involved in stimulus sensing .
Bacterial virulence factor lipase, N-terminal domain (Lipase_bact_N)
Type: Domain

This domain is found in bacterial sequences, and is typically between 258 and 271 amino acids in length. There are two conserved sequence motifs: DGT and DGWST. The domains occurs in the N-terminal region of bacterial virulence factor lipase. The N-terminal region contains a potential signalling sequence .
HmuY protein (HmuY)
Type: Family

HmuY is a novel heme-binding protein that recruits heme from host carriers and delivers it to its cognate outer-membrane transporter, the TonB-dependent receptor HmuR. This family of proteins is found in bacteria. Proteins in this family are typically between 214 and 278 amino acids in length.
Minor type IV pilin, PilX-like (Pilin_PilX-like)
Type: Family

PilX is a protein from Neissaria meningitidis which is crucial for the formation of bacterial aggregates and adhesion to human cells . The structure of PilX is similar to all pilins as it has the common α/β roll fold. PilX subunits have surface-exposed motifs which are thought to stabilise bacterial aggregates against pilus retraction. It also illustrates how a minor pilus component can modulate the virulence properties of pili which have a simple composition and structure .
YodL-like (YodL-like)
Type: Family

This family is found in bacteria, and is approximately 100 amino acids in length. There are two completely conserved residues (Y and D) that may be functionally important.
YHYH domain (YHYH_dom)
Type: Domain

This domain is found in bacterial, eukaryotic and viral sequences. It contains a conserved YHYH sequence motif.
PPC89 centrosome localisation domain (PPC89_CLD)
Type: Domain

The N-terminal region of the fission yeast spindle pole body protein PPC89 has low similarity to the human Cep57 protein. The CLD or centrosome localisation domain of Cep57 and PPC89 is found towards the N terminus of the proteins. This region localises to the centrosome internally to gamma-tubulin, suggesting that it is either on both centrioles or on a centromatrix component. This N-terminal region can also multimerise with the N terminus of other Cep57 molecules. A microtubule-binding domain is found at the C terminus.
PDZ-like domain (PDZ-like_dom)
Type: Domain

PDZ domains are found in diverse signalling proteins in bacteria, yeasts, plants, insects and vertebrates. This entry represents a PDZ-like domain found in bacterial, plant and fungal sequences.
KANL2-like, probable zinc-finger domain (Znf_KANL2-like)
Type: Domain

This domain is found in the human KAT8 regulatory NSL complex subunit 2 (KANSL2) and related proteins including INO80 complex subunit D (INO80D) and Protein SUMV-1 from C. elegans. It contains six invariant cysteine and two histidines that define a C3HC3H conserved pattern and probably are involved in zinc coordination.

KANSL2 is a non-catalytic component of the NSL histone acetyltransferase complex, a multiprotein complex that mediates histone H4 acetylation at Lys-5 and Lys-8 (H4K5ac and H4K8ac) at transcription start sites and promotes transcription initiation . KANSL2 protects the integrity of the NSL complex . KANSL2 has a pair of this domain, the second of which was found to be essential to NSL complex function .

INO80D is a member of the INO80 chromatin-modifying complex and has been shown to interact with the NSL complex .

Protein SUMV-1 is a nuclear factor that influences the activity of genes involved in vulval development . SUMV-1 physically interacts with SUMV-2 and both likely function together with MYS-2 in a nematode KAT8/MOF-like complex to antagonise the activity of the synMuv genes .
Flocculin type 3 repeat (Flocculin_t3_rpt)
Type: Repeat

This repeat is found in the Flocculation protein FLO9 (

) close to its C terminus, and in a number of other Saccharomyces proteins.
Insulin-induced protein family (INSIG_fam)
Type: Family

This family contains a number of eukaryotic Insulin-induced proteins (INSIG-1 and INSIG-2) approximately 200 residues long. INSIG-1 and INSIG-2 are found in the endoplasmic reticulum and bind the sterol-sensing domain of SREBP cleavage-activating protein (SCAP), preventing it from escorting SREBPs to the Golgi. Their combined action permits feedback regulation of cholesterol synthesis over a wide range of sterol concentrations .

The INSIG family also includes NSG1 and NSG2 (INSIG homologues 1 and 2) .
NETI protein (NETI)
Type: Family

This family includes the B. subtilis YebG protein (

), which is functionally uncharacterised (note - this is not a homologue of E. coli YebG). Proteins in this family are typically between 42 and 66 amino acids in length and contain a conserved NETI motif.
TaqI-like C-terminal specificity domain (TaqI_C)
Type: Domain

This domain is found at the C terminus of the TaqI protein and other modification methylases and is involved in DNA-binding and substrate recognition.
Trypanosome variant surface glycoprotein, B-type, N-terminal domain (Trypano_VSG_B_N_dom)
Type: Domain

This entry represents the N-terminal of B-type variant surface glycoproteins (VSG) from trypanosomal parasites.

VSG forms a coat on the surface of the parasite. The trypanosome evades the immune response of the host by expressing a series of antigenically distinct VSGs from an estimated 1000 VSG genes .
Beta-defensin domain (Beta_defensin_dom)
Type: Domain

This is a domain found in beta defensins, antimicrobial peptides implicated in the resistance of epithelial surfaces to microbial colonisation .

Defensins are 2-6kDa, cationic, microbicidal peptides active against many Gram-negative and Gram-positive bacteria, fungi, and enveloped viruses [

.

], containing three pairs of intramolecular disulphide bonds. On the basis of their size and pattern of disulphide bonding, mammalian defensins are classified into alpha, beta and theta categories. Every mammalian species explored thus far has beta-defensins. In cows, as many as 13 beta-defensins exist in neutrophils. However, in other species, beta-defensins are more often produced by epithelial cells lining various organs (e.g. the epidermis, bronchial tree and genitourinary tract).

Defensins are produced constitutively and/or in response to microbial products or proinflammatory cytokines. Some defensins are also called corticostatins (CS) because they inhibit corticotropin-stimulated corticosteroid production. The polar topology of defensins, with spatially separated charged and hydrophobic regions, allows them to insert themselves into the phospholipid membranes so that their hydrophobic regions are buried within the lipid membrane interior and their charged (mostly cationic) regions interact with anionic phospholipid head groups and water. Subsequently, some defensins can aggregate to form `channel-like' pores; others might bind to and cover the microbial membrane in a 'carpet-like' manner. The net outcome is the disruption of membrane integrity and function, which ultimately leads to the lysis of microorganisms. Some defensins are synthesised as propeptides which may be relevant to this process.

Human, rabbit and guinea-pig beta-defensins, as well as human beta-defensin-2 (hBD2), induce the activation and degranulation of mast cells, resulting in the release of histamine and prostaglandin D2.
NudC N-terminal domain (NudC_N_dom)
Type: Domain

Nuclear distribution gene C homologue (nudC) proteins form complexes with other nud proteins and are involved in several cellular division activities. Recently it was shown that nudC regulates platelet-activating factor (PAF) acetylhydrolase with PAF being a pro-inflammatory secondary lipidic messenger . The N terminus of nudC proteins contain a highly conserved region consisting of a predicted three helix bundle. This entry represents the N-terminal conserved domain.
Bacteriophage abortive infection AbiH (AbiH)
Type: Family

This family of proteins confers resistance to bacteriophage .
PDGLE domain (PDGLE_dom)
Type: Domain

This short presumed domain is usually found on its own. However, it is also found in the energy-coupling factor transporter substrate-capture protein NikMN, indicating it may have a role in metal transport.
RRXRR domain (RRXRR_dom)
Type: Domain

This domain is found in bacterial, eukaryotic and viral sequences, and is approximately 180 amino acids in length. It contains a conserved RRXRR motif.
Axin interactor dorsalization-associated protein, C-terminal (Aida_C)
Type: Domain

The axin interaction dorsalization-associated (Aida) protein was characterised in zebrafish as a protein that utilizes its C-terminal region to interact with axis formation inhibitor (Axin), which is a microtubule-interacting scaffold protein for several distinct signalling proteins in the Wnt cascade. The C-terminal region of the Aida protein is a distinct version of the C2 domain. This Aida-type C2 domain is found in the C-terminal region of the proteins and it is critical for interactions with cytoskeletal in the context of cellular adhesion points, thus, it is combined with diverse domains related to cytoskeletal functions, e.g. EF hands, coiled coils, IQ calmodulin-binding motifs, ankyrin repeats and myosin head motor domain, or with a second lipid-binding domain, e.g. the PH domain. The Aida-type C2 domain is found only in the metazoan, choanoflagellate, chromist and chlorophyte lineages .

This domain has predominantly a β-strand globular fold composed of an antiparallel β-sandwich with two β-sheets, and three short α-helices to stabilize the conformation .
Toxin SpoIISA, type II toxin-antitoxin system (SpoIISA_toxin)
Type: Family

SpoIISA is a toxin which causes lysis of vegetatively growing cells. It forms part of a type II toxin-antitoxin system, where the SpoIISB protein acts as an antitoxin. It is a transmembrane protein, with a cytoplasmic domain accounting for approximately two-thirds of the protein. The structure of the cytoplasmic domain resembles that of the GAF domain. SpoIISB binds to the cytoplasmic domain of SpoIISA with high affinity .
Vacuolar protein sorting-associated protein 8, central domain (Vps8_central_dom)
Type: Domain

Vps8 is one of the Golgi complex components necessary for vacuolar sorting . Eukaryotic cells contain a highly dynamic endo-membrane system, in which individual organelles keep their identity despite continuous vesicle generation and fusion. Vesicles that bud from a donor membrane are targeted and delivered to each individual organelle, where they release their cargo after fusion with the acceptor membrane. Vps8 is the core component of the endosomal tethering complex CORVET (class C core vacuole/endosome tethering). Vps8 co-operates with Vps21-GTP to mediate endosomal clustering in a reaction that is dependent on Vps3. Vps8 is the only CORVET subunit that is enriched on late endosomes, suggesting that it is a marker for the maturation of late endosomes. Late endosomes form intralumenal vesicles, and the resulting multivesicular bodies fuse with the vacuole to release their cargoes .

This entry represents the central domain of Vps8.
Stage VI sporulation protein F (SpoVIF)
Type: Family

The sporulation-specific SpoVIF (YjcC) protein of Bacillus subtilis is essential for the development of heat-resistant spores. Its expression is governed by SigK .