SII-SWORD/CoKE huggingface dataset:
Vps53, C-terminal domain superfamily (Vps53_C_sf)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain of vacuolar protein sorting-associated protein 53 (Vps53), which is part of the of the GARP (Golgi-associated retrograde protein) complex involved in retrograde transport from early and late endosomes to late Golgi . Budding yeast Vps53 is involved in retrograde transport from early and late endosomes to late Golgi by linking the vesicle through the t-SNARE Tgl1 to the Golgi, leading to the membrane fusion between late Golgi and endosomal vesicles .
Golgi phosphoprotein 3-like domain superfamily (GPP34-like_sf)
Type: Homologous_superfamily

This superfamily represents a domain found in several eukaryotic GPP34 like proteins. GPP34 (also known as golgi phosphoprotein 3) localises to the Golgi complex and is conserved from Saccharomyces cerevisiae to humans. The cytosolically exposed location of GPP34 predicts a role for a novel coat protein in Golgi trafficking . The budding yeast GPP34 homologue, also known as Vps74, is a phosphatidylinositol-4-phosphate-binding protein that links Golgi membranes to the cytoskeleton and may participate in the tensile force required for vesicle budding from the Golgi .
Nitrate reductase beta, C-terminal domain superfamily (Nitr_red_bet_C_sf)
Type: Homologous_superfamily

This superfamily represents a domain found near the C terminus of the respiratory nitrate reductase beta chain. The nitrate reductase complex is a dimer of heterotrimers each consisting of an alpha, beta and gamma chain. This domain plays a role in the interactions between subunits and shielding of the Fe-S clusters .
Lytic exoenzyme, target recognition domain superfamily (Lytic_exo_TRD_sf)
Type: Homologous_superfamily

This entry represents a domain found downstream the catalytic domain of various lytic enzymes, such as peptidase M23 and phage lysins. The domain is composed of strands of antiparallel β sheet with one short α helix at the C-terminal end .
PA2222-like domain superfamily (PA2222-like_sf)
Type: Homologous_superfamily

This superfamily of proteins with unknown function appears to be restricted to Pseudomonas.
NapC/NirT cytochrome c superfamily (NapC/NirT_cytc_sf)
Type: Homologous_superfamily

This entry represents the NapC/NirT-type cytochrome c superfamily . Some members, such as NapC and NirT, bind four haem groups, while others, such as TorC, bind five haems.
Putative ECF-type sigma factor negative effector (ECF_sigma_eff)
Type: Homologous_superfamily

This domain is found in uncharacterised proteins, including putative ECF-type sigma factor negative effectors from Bacillus.
Ribbon-helix-helix domain superfamily (RHH_sf)
Type: Homologous_superfamily

A number of bacterial proteins contain this ribbon-helix-helix domain, which is likely to be DNA-binding.
SCAN domain superfamily (SCAN_sf)
Type: Homologous_superfamily

A number of C2H2-zinc finger proteins contain a highly conserved N-terminal motif termed the SCAN (named after SRE-ZBP, CTfin51, AW-1 and Number 18 cDNA) domain. The SCAN domain has been shown to be able to mediate homo- and hetero-oligomerisation . These proteins can either activate or repress transcription, although isolated recombinant SCAN domains do not modulate significantly the transcription . In addition to these zinc finger transcription factors, an isolated SCAN domain without adjacent zinc finger motifs has been identified in some proteins . It has been noted that the SCAN domain resembles a domain-swapped version of the C-terminal domain of the HIV capsid protein .

The SCAN domain is enriched in hydrophobic and negatively charged residues with a L-X(6)-L motif at its core. This core is flanked by A, E, L, M, H and C residues that are frequently found in α-helices . Predictions of the secondary structure of the domain suggest the presence of at least three α-helices that are separated from one another by short looped regions bounded by proline residues . It has been shown to be a selective oligomerization domain that mediates homotypic and heterotypic interactions between SCAN box containing proteins .
SopA-like, catalytic domain superfamily (SopA-like_catalytic_sf)
Type: Homologous_superfamily

This domain is found in the Escherichia coli Type III secretion effector proteins SopA and NleL . These proteins have been shown to act as E3 ubiquitin ligase enzymes. This domain contains the active site cysteine residue.
Bd37, core domain superfamily (Bd37_core_sf)
Type: Homologous_superfamily

This entry represents the core domain of Bd37, a surface antigen of B. divergens which is GPI-anchored at the surface of the merozoite. The structure of the domain consists of mainly α folds and has three sub domains .
Ndc80 domain superfamily (Ndc80_sf)
Type: Homologous_superfamily

This entry represents a domain found in the kinetochore protein Ndc80. Ndc80 acts as a component of the NMS (Ndc80-MIND-Spc7) super complex which has a role in kinetochore function during late meiotic prophase and throughout the mitotic cell cycle. It has been shown that Ndc80 from yeast is part of a complex called the Ndc80p complex . The four Ndc80 complex subunits associate as two rod-like heterodimers (Ndc80:Nuf2 and Spc24:Spc25) . This complex is thought to bind to the microtubules of the spindle.
Atg6/Beclin C-terminal domain superfamily (Atg6/Beclin_C_sf)
Type: Homologous_superfamily

In yeasts, vacuolar protein sorting-associated protein 30 (Vps30), also known as autophagy-related protein 6 (Atg6), is a common component of two distinct phosphatidylinositol 3-kinase complexes. In complex I, Atg14 links Vps30 to Vps34 lipid kinase and plays a specific role in autophagy, while in complex II, Vps38 links Vps30 to Vps34 and plays an important role in vacuolar protein sorting . The C-terminal of Vps30 contains a globular fold comprised of three β-sheet-α-helix repeats (also known as β-α repeated, autophagy-specific (BARA) domain) and is required for autophagy through the targeting of complex I to the pre-autophagosomal structure. The N-terminal of Vps30 is required for vacuolar protein sorting .
Nuf2, N-terminal domain superfamily (Nuf2_N_sf)
Type: Homologous_superfamily

This superfamily represents a domain found at the N terminus of the Kinetochore protein Nuf2, which is part of the Ndc80 complex. This domain fold as a CH domain consisting of a four-helix bundle containing the parallel helices alphaA, alphaC, alphaE, and alphaG, similar to that in Ndc80. These CH domains from Nuf2 and Ndc80 forms the globular rod at one end the complex . The ability of the Ndc80 complex to bind microtubules resides on the tightly packed CH domains from Nuf2 and Ndc80 . This complex binds to the spindle and is required for chromosome segregation and spindle checkpoint activity .
Floricaula/leafy, C-terminal domain superfamily (Floricaula/leafy_C_sf)
Type: Homologous_superfamily

This domain is found in various plant development proteins which are homologues of floricaula (FLO) and Leafy (LFY) proteins which are floral meristem identity proteins. Mutations in the sequences of these proteins affect flower and leaf development. LFY is a plant-specific transcription factor (TF) essential for flower development. It is one of the few master regulators of flower development, as it integrates environmental and endogenous signals to orchestrate the whole floral network. Transcription factors such as LFY recognize short DNA motifs primarily through their DNA-binding domain. Upon binding to short stretches of DNA called cis-elements or TF binding sites (TFBS), they regulate gene expression.

This entry represents the DNA binding domain found in C-terminal of LFY proteins in plants. Structure-function studies have demonstrated that LFY binds semi-palindromic 19-bp DNA elements through its highly conserved C-terminal DBD, a unique helix-turn-helix fold that by itself dimerizes on DNA .
UreF domain superfamily (UreF_sf)
Type: Homologous_superfamily

This superfamily represents the urease accessory protein, UreF. The urease enzyme (urea amidohydrolase) hydrolyses urea into ammonia and carbamic acid . UreF is proposed to modulate the activation process of urease by eliminating the binding of nickel irons to noncarbamylated protein .
Ndc10, domain 2 superfamily (Ndc10_dom2_sf)
Type: Homologous_superfamily

This entry represents the second of five domains on the Kluyveromyces lactis Ndc10 protein . Each subunit of the Ndc10 dimer binds a separate fragment of DNA, suggesting that Ndc10 stabilises a DNA loop at the centromere. Proteins containing this domain also include Cbf2 from S. cerevisiae. S. cerevisiae Ndc10 (also known as Cbf2) is a component of the centromere DNA-binding protein complex CBF3, which is essential for chromosome segregation and movement of centromeres along microtubules . The structure of the protein shows that it can be divided in the two α-helical N- and C-lobes. The N-lobe consists of an antiparallel four-helix bundle with a central β-sheet which is involved in DNA binding .
Telomere resolvase ResT/TelK, catalytic domain superfamily (ResT/TelK_cat_sf)
Type: Homologous_superfamily

Telomere resolvase ResT (protelomerase) catalyses the conversion of linear double-stranded DNA into hairpin telomeres . This entry represents the catalytic domain of ResT and TelK .
RTP801-like, C-terminal domain superfamily (RTP801-like_C_sf)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain of RTP801 (also known as REDD1), the protein product of a hypoxia-inducible factor 1 (HIF-1)- responsive gene . It is thought to be involved in various cellular processes . Both RTP801 and RTP801-like (REDD2) work downstream of AKT and upstream of TSC2 to inhibit mTOR, a serine/threonine kinase that plays an essential role in cell growth control . Overexpression of RTP801 causes the apoptosis- resistant phenotype in cycling cells, and apoptosis sensitivity in growth arrested cells . Two members of this superfamily expressed by Drosophila melanogaster, Scylla (

) and Charybde (

), are designated as Hox targets .
DUF2267 superfamily (DUF2267_sf)
Type: Homologous_superfamily

This entry contains proteins that have no known function.
Channel forming colicin, C-terminal domain superfamily (Channel_colicin_C_sf)
Type: Homologous_superfamily

Colicins are plasmid-encoded polypeptide toxins produced by and active against Escherichia coli and closely related bacteria. Colicins are released into the environment to reduce competition from other bacterial strains. Colicins bind to outer membrane receptors, using them to translocate to the cytoplasm or cytoplasmic membrane, where they exert their cytotoxic effect, including depolarisation of the cytoplasmic membrane, DNase activity, RNase activity, or inhibition of murein synthesis.

Channel-forming colicins (colicins A, B, E1, Ia, Ib, and N) are transmembrane proteins that depolarize the cytoplasmic membrane, leading to dissipation of cellular energy . These colicins contain at least three domains: an N-terminal translocation domain responsible for movement across the outer membrane and periplasmic space; a central domain responsible for receptor recognition; and a C-terminal cytotoxic domain responsible for channel formation in the cytoplasmic membrane .

This entry represents the C-terminal cytotoxic domain, which has a globin-like fold with additional helices at either end.
Inositol polyphosphate kinase superfamily (IPK_sf)
Type: Homologous_superfamily

Inositol phosphates (IPs) act as signalling messengers to regulate various cellular processes such as growth. This entry includes a group of inositol polyphosphate kinase, including inositol polyphosphate multikinase Arg82 and Inositol hexakisphosphate/inositol heptakisphosphate kinase Kcs1 from budding yeast. They play important roles in vacuole biogenesis and the cell's response to certain environmental stresses. The kinase activity of Arg82 and Kcs1 is required for the production of soluble inositol phosphates . Independently of its catalytic activity, Arg82 is crucial for assembling the Arg80-Mcm1 protein complex at the promoter region of genes involved in arginine metabolism .

This entry also includes human inositol hexakisphosphate kinase 1/2/3 (IP6K1/2/3), inositol polyphosphate multikinase (IPMK) and inositol-trisphosphate 3-kinase A/B/C (IP3KA/B/C) . They are involved in inositol phosphate biosynthesis . Independently of its catalytic activity, IPMK mediates the activation of mammalian target of rapamycin (mTOR) in response to essential amino acids [

. Crystallographic analysis showed that the disordered domains of IPMK modulates its kinase activity .
Cse2 superfamily (Cse2_sf)
Type: Homologous_superfamily

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.

This superfamily represents Cse2 of Cas proteins, a novel family of endoribonucleases that cleaves single-stranded RNAs preferentially within U-rich regions, including Cse2 from Thermus thermophilus . These proteins are found in the CRISPR/Cas subtype Ecoli regions of many bacteria (most of which are mesophiles), and not in Archaea . This is also known as Cse2 Type I-E .
Peptidoglycan hydrolase Gp5 superfamily (Gp5_sf)
Type: Homologous_superfamily

This superfamily represents the P5 murein endopeptidase from Pseudomonas phage phi6. P5 murein endopeptidase has lytic activity against several Gram-negative bacteria . It is thought that the enzyme cleaves the cell wall peptide bridge formed by meso-2,6-diaminopimelic acid and D-Alanine.
DVA-1 superfamily (DVA-1_sf)
Type: Homologous_superfamily

The polyprotein allergens from certain nematoda, such as ABA-1 from Ascari and DvA-1 from Dictyocaulus viviparus, are lipid-binding proteins comprising multiple tandem repeats of this domain .
SAP30, C-terminal domain superfamily (SAP30_C_sf)
Type: Homologous_superfamily

SAP30 is a subunit of the histone deacetylase complex. This C-terminal domain of the SAP30 proteins appears to be the binding region for Sin3 .
YmfJ/YflH superfamily (YmfJ/YflH_sf)
Type: Homologous_superfamily

This entry represents proteins with unknown function includind uncharacterised proteins YmfJ and YflH. The superfamily appears to be restricted to Firmicutes.
ATPase inhibitor subunit zeta superfamily (ATPase_inh_sub_z_sf)
Type: Homologous_superfamily

This entry represents zeta-subunits, which are found in alpha-proteobacterial F1F0-ATPase regulatory proteins. The zeta subunit is a potent inhibitor of the alpha-proteobacterial F1FO-ATPase. The inhibitory region resides in the first 14 N-terminal residues of the protein, which protrude from the 4-α-helix bundle structure of the isolated zeta subunit .
SLBP, RNA-binding domain superfamily (SLBP_RNA_bind_sf)
Type: Homologous_superfamily

This entry represents the RNA-binding domain of histone RNA hairpin-binding protein, also known as SLBP . Proteins containing this domain include SLBP1 and SLBP2 from Xenopus laevis.

SLBP1 binds the 5' side of the stem-loop structure of replication-dependent histone pre-mRNAs and contributes to efficient 3'-end processing by stabilising the complex between histone pre-mRNA and U7 small nuclear ribonucleoprotein (snRNP), via the histone downstream element (HDE) . It plays an important role in targeting mature histone mRNA from the nucleus to the cytoplasm and to the translation machinery. It stabilises mature histone mRNA and could be involved in cell-cycle regulation of histone gene expression .
STAT1, C-terminal domain superfamily (STAT1_C_sf)
Type: Homologous_superfamily

This entry represents the C-terminal domain of STAT1, which selectively binds the TAZ2 domain of CRB (CREB-binding protein) . This group of eukaryotic proteins is approximately 20 amino acids in length, and is found in association with

,

,

,

. By binding to CRB, it becomes a transcriptional activator and can initiate transcription of certain genes.
Antitoxin ParD superfamily (ParD_sf)
Type: Homologous_superfamily

ParD is the antitoxin of a bacterial toxin-antitoxin gene pair. The cognate toxin is ParE in

. The superfamily contains several related antitoxins from Cyanobacteria, Proteobacteria and Actinobacteria. Antitoxins of this class carry an N-terminal ribbon-helix-helix domain, RHH, that is highly conserved across all type II bacterial antitoxins, which dimerises with the RHH domain of a second VapB molecule. A hinge section follows the RHH, with an additional pair of flexible α helices at the C terminus. This C terminus is the toxin-binding region of the dimer, and so is specific to the cognate toxin, whereas the RHH domain has the specific function of lying across the RNA-binding groove of the toxin dimer and inactivating the active-site - a more general function of all type II antitoxins .
CcmH/CycL/Ccl2/NrfF domain superfamily (CcmH/CycL/NrfF/Ccl2_sf)
Type: Homologous_superfamily

This superfamily represents a domain found in NrfF, CcmH and Ccl2. CcmH is part of the CcmFH complex, which is the system I holocytochrome c synthetase . NrfF is not required for the biogenesis of c-type cytochromes .
Daxx, N-terminal domain superfamily (Daxx_N_sf)
Type: Homologous_superfamily

The Daxx protein (also known as death domain-associated protein 6) is thought to play a role in apoptosis. Daxx forms a complex with Axin . Daxx is a scaffold protein shown to play diverse roles in transcription and cell cycle regulation. This N-terminal domain folds into a left-handed four-helix bundle (H1, H2, H4, H5) that binds to the N-terminal residues of the tumour-suppressor Rassf1C .
Alpha-glycerophosphate oxidase, C-terminal domain superfamily (DAO_C_sf)
Type: Homologous_superfamily

This entry represents the C-terminal cap domain of alpha-glycerophosphate oxidase, also known as glycerol-3-phosphate oxidase (

) . This domain shows an overall negative electrostatic surface, thought to be involved in substrate recognition.
SASP, alpha/beta-type superfamily (SASP_sf_alpha/beta)
Type: Homologous_superfamily

Small, acid-soluble spore proteins (SASP or ASSP) are proteins bound to the spore DNA of bacteria of the genera Bacillus, Thermoactynomycetes, and Clostridium . They are double-stranded DNA-binding proteins that cause DNA to change to an A-like conformation. They protect the DNA backbone from chemical and enzymatic cleavage and are thus involved in dormant spore's high resistance to UV light. SASP are degraded in the first minutes of spore germination and provide amino acids for both new protein synthesis and metabolism.

There are two distinct families of SASP: the α/β type and the gamma-type. Alpha/beta SASP are small proteins of about sixty to seventy amino acid residues that are generally coded by a multigene family. The N terminus of alpha/beta SASP contains the site which is cleaved by a SASP-specific protease that acts during germination while the C terminus and is probably involved in DNA-binding.
AraC-like superfamily (AraC-like_sf)
Type: Homologous_superfamily

This superfamily consists of several hypothetical bacterial proteins of around 180 residues in length. The function of this superfamily is unknown.
Envelope glycoprotein M superfamily, flavivirus (Env_glycoprot_M_sf_flavivir)
Type: Homologous_superfamily

Flaviviruses are small enveloped viruses with virions comprised of three proteins called C, M and E . The envelope glycoprotein M is made as a precursor, called prM. The precursor portion of the protein is the signal peptide for the proteins entry into the membrane. prM is cleaved to form M in a late-stage cleavage event. Associated with this cleavage is a change in the infectivity and fusion activity of the virus.
HNS-dependent expression A/B superfamily (HdeA/HdeB_sf)
Type: Homologous_superfamily

HNS (histone-like nucleoid structuring)-dependent expression A (HdeA) protein is a stress response protein found in highly acid resistant bacteria such as Shigella flexneri and Escherichia coli, but which is lacking in mildly acid tolerant bacteria such as Salmonella . HdeA is one of the most abundant proteins found in the periplasmic space of E. coli, where it is one of a network of proteins that confer an acid resistance phenotype essential for the pathogenesis of enteric bacteria . HdeA is thought to act as a chaperone, functioning to prevent the aggregation of periplasmic proteins denatured under acidic conditions. The HNS protein, a chromatin-associated protein that influences the gene expression of several environmentally-induced target genes, represses the expression of HdeA. HdeB, which is encoded within the same operon, may form heterodimers with HdeA. HdeA is a single domain α-helical protein with an overall fold that is similar to the fold of the N-terminal subdomain of the GluRS anticodon-binding domain.

This superfamily represents HdeA and HdeB which are also known as acid stress chaperones.
YmgD domain superfamily (YmgD_sf)
Type: Homologous_superfamily

This superfamily represents a domain found in bacterial proteins. They are approximately 110 amino acids in length.
HeLo domain superfamily (HeLo_sf)
Type: Homologous_superfamily

This N-terminal domain, HeLo, has a prion-inhibitory effect in cis on its own prion-forming domain (PFD) and in trans on HET-s prion propagation . The domain is found exclusively in the fungal kingdom. Its structure, as it occurs in the heterokaryon incompatibility proteins HET-s and HET-S proteins, consists of two bundles of α-helices that pack into a single globular domain . The domain boundary determined from its structure and from protease-resistance experiments overlaps with the C-terminal prion-forming domain of HET-s . The HeLo domains of HET-s and HET-S are very similar and their few differences (and not the prion-forming domains) determine the compatibility-phenotype of the fungi in which the proteins are expressed.

The mechanism of the HeLo domain-function in heterokaryon-incompatibility is still under investigation, however the HeLo domain is found in similar protein architectures as other cell death and apoptosis-inducing domains. The only other HeLo protein to which a function has been associated is LopB from Leptosphaeria maculans . Although its specific role in L. maculans is unknown, LopB- mutants have impaired ability to form lesions on oilseed rape. The HeLo domain is not related to the HET domain (

) which is another domain involved in heterokaryon incompatibility.
CagS superfamily (CagS_sf)
Type: Homologous_superfamily

This superfamily represents CAG pathogenicity island protein 13 (CagS) from Helicobacter pylori. The gene lies just downstream of the cluster whose protein-products resemble those of the Vibrio proteins that form the structural core of T4SS. The exact function of CagS is not known . This superfamily consists of four α-helices.
StbB superfamily (StbB_sf)
Type: Homologous_superfamily

This entry represents the plasmid stability protein (StbB) which is conserved in the Enterobacteriales. It is a putative plasmid stability protein in that it is expressed from the operon involved in stability, but its actual function has not yet been characterised but it may be involved in the control of plasmid partition.
RFXAP, C-terminal domain superfamily (RFXAP_C_sf)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain of RFXAP (regulatory factor X-associated protein) that binds to RFXANK , the ankyrin-repeat regulatory factor X protein. RFXAP is part of the RFX complex, mutants of either RFXAP or RFXANK protein fail to bind to each other. RFX5 binds only to the RFXANK-RFXAP scaffold and not to either protein alone, and neither the scaffold nor RFX5 alone can bind DNA. The binding of the RFXANK-RFXAP scaffold to RFX5 leads to a conformational change in the latter that exposes the DNA-binding domain of RFX5. The DNA-binding domain of RFX5 anchors the RFX complex to MHC class II X and S promoter boxes .