SII-SWORD/CoKE huggingface dataset:
VTC domain superfamily (VTC_sf)
Type: Homologous_superfamily

This superfamily comprises the catalytic tunnel domain of VTC (Vacuolar transporter chaperone). These transmembrane domains participate in the transport of polyP across the membrane .
Outer membrane protein assembly factor BamC, C-terminal (BamC_C)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain of outer membrane protein (OMP) assembly factor BamC, a component of the essential five-protein β-barrel assembly machinery (BAM) in E. coli . This BAM complex is responsible for recognition and assembly of outer membrane β-barrel proteins, although BamC is not essential for its functionality . BamC, together with the other two non-essential protein assembly factors BamE and BamB, express a rather unspecific influence on the stability of the complex and the kinetic folding of selected OMP proteins.
BamC has evolved through the gene duplication of two conserved domains known to mediate protein interactions in structurally related complexes.
Serine carboxypeptidase S28, SKS domain (Ser_carbopepase_S28_SKS)
Type: Homologous_superfamily

Serine carboxypeptidase S28 family comprises carboxypeptidase PRCP and the aminopeptidase DPP7 . The cap domain (SKS) is formed by 11 α-helices and two strands interconnected by loops. It contains four disulphide bonds which are assumed to be involved in stabilising the structure. The SKS domain is a rare fold possibly present only in the S28 serine peptidase family .
tRNA-dihydrouridine(16) synthase, C-terminal (DusC_C)
Type: Homologous_superfamily

Dihydrouridine (D) is a highly conserved modified base found in tRNAs from all domains of life. D is formed by reduction of the carbon-carbon double bond at positions 5 and 6 of the uridine base by dihydrouridine synthases (Dus), and is mostly found in the D-loop of tRNAs for which it is named .

DusC is composed of two domains: an N-terminal catalytic domain and a C-terminal tRNA-binding domain .
The C-terminal tRNA-binding domain is formed by four parallel helices. This domain is commonly found in Dus-family proteins and is responsible for binding to the substrate tRNA. The role of dihydrouridine in tRNA is predicted to increase conformational flexibility of the tRNA.
Zinicin-like metallopeptidase type 2, N-terminal (Zinicin_2_N)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain found in proteins with a conserved HEXXH motif, suggesting they are putative peptidases of zincin fold . Structurally, this domain consists of 4 α helices and 2 β strands.
ATP12, ATP synthase F1-assembly protein, N-terminal (ATP12_ATP_synth-F1-assembly_N)
Type: Homologous_superfamily

This superfamily represents the N-terminal "wrist" domain of ATP12 ATPases which are required for the assembly of mitochondrial ATP synthase in all eukaryotes. The eukaryotic proteins include yeast Atp12 and mammalian homologue ATPAF2 (ATP synthase mitochondrial F1 complex assembly factor 2) , which are required for assembly of the mitochondrial F1-ATPase.
Regulatory protein YycH/YycI , domain 2 (YycH/YycI_2)
Type: Homologous_superfamily

This entry represents domain 2 found in YycH and YycI proteins which share the same structural fold . Both YycH and YycI are always found in pair on the chromosome, downstream of the essential histidine kinase YycG. Additionally, both proteins share a function in regulating the YycG kinase with which they appear to form a ternary complex. Lastly, the two proteins always contain an N-terminal transmembrane helix and are localized to the periplasmic space as shown by PhoA fusion studies.

YycI and YycH proteins interact to control the activity of the YycG kinase. Both YycI and YycH proteins are localized outside the cytoplasm and attached to the membrane by an N-terminal transmembrane sequence. Bacterial two-hybrid data showed that the YycH, YycI, and the kinase YycG form a ternary complex. The data suggest that YycH and YycI control the activity of YycG in the periplasm and that this control is crucial in regulating important cellular processes .
F-actin-capping protein subunit alpha/beta, domain 2 (CapZ_alpha/beta_2)
Type: Homologous_superfamily

The F-actin capping protein binds in a calcium-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends. Unlike gelsolin and severin this protein does not sever actin filaments. The F-actin capping protein is a heterodimer composed of two unrelated subunits: alpha (

) and beta (

). Neither of the subunits shows sequence similarity to other filament-capping proteins .

This entry represents the beta subunit (CAPZB) and alpha subunit (CAPZA) domain 2, whose sequence is well conserved in eukaryotic species . In Drosophila, mutations of the alpha and beta subunits cause actin accumulation and subsequent retinal degeneration . In humans, CAPZB is part of the WASH complex that controls the fission of endosomes .
Vacuolar protein sorting-associated protein IST1-like (IST1-like)
Type: Homologous_superfamily

The endosomal sorting complex required for transport (ESCRT) machinery functions in several important eukaryotic cellular processes such as MVB (multivesicular body) formation. The AAA-ATPase Vps4 catalyzes disassembly of the ESCRT-III complex and may regulate membrane deformation and vesicle scission as well. Ist1 acts as a negative regulator of the MVB pathway by binding to the N-terminal MIT (microtubule interacting and transport) domain of Vps4 through its C-terminal region, with its 15 amino acids bearing strong homology to a conserved sequence motif called MIM1 (MIT interacting motif 1 ). This MIT domain is found in various proteins and enzymes including ubiquitin hydrolases proteases, ATPases (Spastin and VPS4 proteins) and ATPase activators (Vta1p/LIP5) .
Fimbrillin-like 1, N-terminal (Mfa-like_1_N)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain of fimbrillin proteins found by clustering human gut metagenomic sequences . Analysis of structural comparisons shows this proteins to be part of the FimbA (CL0450) superfamily of adhesin components or fimbrillins.
Peptidase M60, enhancin-like domain 3 (Pep_M60_3)
Type: Homologous_superfamily

The peptidase family M60 domain belongs to the Merops zincin superfamily of zinc-requiring metalloproteases (clan MA, subclan MA(E)). The peptidase family M60 domain contains the metal-binding consensus motif HExxH. The two histidine residues are ligands of the catalytic Zn(2) and the glutamic acid residue is involved in nucleophilic attack. An additional conserved glutamic acid is found approximately 20 residues from the first histidine within the metal-binding motif. The second conserved glutamic acid potentially acts as a third proteous Zn(2) ligand. The peptidase family M60 domain targets complex host glycoproteins, such as mucins .

This superfamily represents the third domain of peptidases that contain a zinc metallopeptidase motif (HEXXHX(8,28)E) and possess mucinase activity .
Amino acid transporter heavy chain SLC3A2 (SLC3A2)
Type: Family

Heteromeric amino acid transporters (HATs) are composed of two subunits, a heavy (SLC3 family) and a light subunit [SLC7 or L-type amino acid transporter (LAT) family] linked by a conserved disulfide bridge . HATs are amino acid exchangers, and the transport activity resides in the light subunit. The heavy chain of the surface antigen 4F2 (4F2hc), also known as amino acid transporter heavy chain SLC3A2, is a HAT heavy subunit . 4F2hc controls the cell surface expression as well as the membrane topology of the 4F2 heterodimer .

SLC3A2 is essential for plasma membrane localization, stability, and the transport activity of SLC7A5 and SLC7A8 . It forms heterodimers with SLC7 family transporters (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A10 and SLC7A11), a group of amino-acid antiporters . The heterodimer with SLC7A11 functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane .
GpdQ, beta-strand dimerisation domain (GpdQ_beta-strand)
Type: Homologous_superfamily

Glycerophosphodiesterase (GDPD) from Enterobacter aerogenes, GpdQ, is a promiscuous binuclear metallohydrolase that belongs to a diverse family of metallo-phosphoesterases . It plays a role in catalysing the hydrolysis of mono-, di- and triester substrates, including some organophosphate pesticides and products of the degradation of nerve agents .

This superfamily represents the dimerisation domain of GpdQ, consisting of a pair of two-stranded antiparallel β-sheets and a short β-strand in the loop between the sheets, joining the β-sandwiches from each subunit. A disjointed single β-sandwich is formed across the length of the dimer. The fold of this domain consists of a pair of two-stranded β-sheets from each chain, longer than the β-sheets from the α/β sandwich domain, with a shorter third strand from each chain not directly contributing to the dimer interface.
Inactive peptidyl-prolyl cis-trans isomerase FKBP6/shutdown (FKBP6/shu)
Type: Family

This entry includes FKBP6 from mammals and protein shutdown (shu) from flies. FKBP6 is a testis-sperm specific protein that belongs to the immunophilins FKBP family known to be involved in meiosis, calcium homeostasis, clathrin-coated vesicles, and membrane fusions . FKBP6 contains a PPIase FKBP-type domain and a TPR domain. However, it is inactive as an isomerase and associates with Hsp90 via its TPR domain . Protein shutdown is essential for the formation of germline cysts during oogenesis and is a component of the Drosophila piRNA biogenesis machinery . This entry also includes the FKBP6 homologue found in Dictyostelium discoideum.
GpdQ, catalytic alpha/beta sandwich domain (GpdQ_catalytic)
Type: Homologous_superfamily

Glycerophosphodiesterase (GDPD) from Enterobacter aerogenes, GpdQ, is a promiscuous binuclear metallohydrolase that belongs to a diverse family of metallo-phosphoesterases . It plays a role in catalysing the hydrolysis of mono-, di- and triester substrates, including some organophosphate pesticides and products of the degradation of nerve agents .

This superfamily describes the catalytic α/β sandwich domain, which consists of two facing β-sheets, surrounded by α-helices. The entry also contains the final helix of the domain swapped extension, which forms a 'cap' at the α/β sandwich sub-domain, which significantly narrows the entrance to the active site cavity.
S-adenosylmethionine decarboxylase, N-terminal (AdoMetDC_N)
Type: Homologous_superfamily

S-adenosylmethionine decarboxylase (AdoMetDC) catalyses the removal of the carboxylate group of S-adenosylmethionine to form S-adenosyl-5'-3-methylpropylamine which then acts as the n-propylamine group donor in the synthesis of the polyamines spermidine and spermine from putrescine.

The catalytic mechanism of AdoMetDC involves a covalently-bound pyruvoyl group. This group is post-translationally generated by a self-catalyzed intramolecular proteolytic cleavage reaction between a glutamate and a serine. This cleavage generates two chains, beta (N-terminal) and alpha (C-terminal). The N-terminal serine residue of the alpha chain is then converted by non hydrolytic serinolysis into a pyruvoyl group.

This superfamily represents the N-terminal domain of S-adenosylmethionine decarboxylase.
E3 ubiquitin-protein ligase RNF182 (RNF182)
Type: Family

RNF182 is a brain-enriched E3 ubiquitin-protein ligase that stimulates E2-dependent polyubiquitination in vitro. It is upregulated in Alzheimer"s disease (AD) brains and neuronal cells exposed to injurious insults. It interacts with ATP6V0C and promotes its degradation by the ubiquitin-proteosome pathway , suggesting a very specific role in controlling the turnover of an essential component of the neurotransmitter release machinery. It also plays a role in the inhibition of TLR-triggered innate immune response by mediating 'Lys'-48-linked ubiquitination and subsequent degradation of NF-kappa-B component RELA . RNF182 contains an N-terminal C3HC4-type RING-HC finger, and a C-terminal transmembrane domain.
S-adenosylmethionine decarboxylase, C-terminal (AdoMetDC_C)
Type: Homologous_superfamily

S-adenosylmethionine decarboxylase (AdoMetDC) catalyses the removal of the carboxylate group of S-adenosylmethionine to form S-adenosyl-5'-3-methylpropylamine which then acts as the n-propylamine group donor in the synthesis of the polyamines spermidine and spermine from putrescine.

The catalytic mechanism of AdoMetDC involves a covalently-bound pyruvoyl group. This group is post-translationally generated by a self-catalyzed intramolecular proteolytic cleavage reaction between a glutamate and a serine. This cleavage generates two chains, beta (N-terminal) and alpha (C-terminal). The N-terminal serine residue of the alpha chain is then converted by non hydrolytic serinolysis into a pyruvoyl group.

This superfamily represents the C-terminal domain of S-adenosylmethionine decarboxylase.
FhaA, N-terminal domain superfamily (FhaA_N_sf)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain found in the FHA domain-containing protein FhaA (previously known as Rv0020c) from Mycobacterium tuberculosis. The FHA (Fork Head Associated) domain is a phosphopeptide-specific binding domain that enables the protein to specifically bind to sequences containing phosphothreonine. FhaA is one of the major substrates of Ser/Thr protein kinases (STPK) and plays a role in the regulation of cell growth and peptidoglycan synthesis by binding to MviN. It may inhibit the late stages of peptidoglycan synthesis .
Lecithin retinol acyltransferase (LRAT)
Type: Family

Lecithin retinol acyltransferase (LRAT) is a retinyl ester synthase, catalyzing the formation of fatty acid retinyl esters, a crucial step in the retinoid cycle . It has been linked to early onset retinitis pigmentosa .
Cytochrome c oxidase assembly factor 6 homolog (COA6)
Type: Family

COA6 is involved in the maturation of the mitochondrial respiratory chain complex IV subunit MT-CO2/COX2 . Mutations in the COA6 gene cause cardioencephalomyopathy due to cytochrome c oxidase deficiency 4 (CEMCOX4), and an infantile disorder with a fatal course in the first weeks of life, characterised by hypertrophic cardiomyopathy, left ventricular non-compaction, lactic acidosis, metabolic hypotonia, and mitochondrial complex IV deficiency .
ADP-ribosylation factor-like protein 15 (ARL15)
Type: Family

This entry represents a family of animal proteins, including human ADP-ribosylation factor-like protein 15 (ARL15). The function of ARL15 is not clear.
AT-rich interactive domain-containing protein 4 (ARID4)
Type: Family

This entry includes ARID4 (AT-rich interactive domain-containing protein 4, or At3g43240) from Arabidopsis. Its function is not clear.
Histone-lysine N-methyltransferase SETD2, animal (SETD2_animal)
Type: Family

SETD2 is a histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate . It is required for DNA double-strand break repair and activation of the p53-mediated checkpoint . SETD2-inactivation has been linked to tumour development . SETD2 also methylates alpha-tubulin at lysine 40, the same lysine that is marked by acetylation on microtubules. Methylation of microtubules occurs during mitosis and cytokinesis and can be ablated by SETD2 deletion, which causes mitotic spindle and cytokinesis defects, micronuclei, and polyploidy . Moreover, SETD2 is also involved in interferon-alpha-induced antiviral defense by mediating both monomethylation of STAT1 at 'Lys-525' and catalyzing H3K36me3 on promoters of some interferon-stimulated genes (ISGs) to activate gene transcription .
NarX-like, N-terminal domain superfamily (NarX-like_N_sf)
Type: Homologous_superfamily

This domain is found N-terminal in histidine kinase NarX and other sensor proteins. NarX is a histidine kinase receptor that responds to nitrate and nitrite to effect regulation of anaerobic respiration in various bacteria . Structurally, the Narx sensor domain is a dimer of four-helix bundles, related by a quasi two-fold axis of symmetry running roughly parallel to the long axes of the helices .
tRNA methyltransferase, Trm1, C-terminal (tRNA_met_Trm1_C)
Type: Homologous_superfamily

Trm1 (

) dimethylates a single guanine residue at position 26 of a number of tRNAs using S-adenosyl-L-methionine as donor of the methyl groups . In Saccharomyces cerevisiae, Trm1 is required for the modification of both mitochondrial and cytoplasmic tRNAs . This family also includes the related TRMT1-like protein from Mus musculus, which may play a role in motor coordination and exploratory behaviour , and similar mammal sequences.

This superfamily represents the C terminus of Trm1. This domain is characterised by the presence zinc-cysteine cluster where a zinc atom is bound to four cysteine residues and functions as a structural element that holds the tRNA-binding site between the N- and C-terminal domains .
Antirestriction domain superfamily (Antirestriction_sf)
Type: Homologous_superfamily

This superfamily includes various protein that are involved in antirestriction. The ArdB protein efficiently inhibits restriction by members of the three known families of type I systems of Escherichia coli .
Proto-chlorophyllide reductase, C-terminal (P-CP_red_C)
Type: Homologous_superfamily

This domain superfamily is found in bacteria and plant chloroplast proteins. It often appears at the C-terminal of nitrogenase component 1 type oxidoreductases and sometimes independently in bacterial proteins such as the proto-chlorophyllide reductase subunit B of the cyanobacterium Synechocystis.
Ufd1-like, Nn domain (Ufd1-like_Nn)
Type: Homologous_superfamily

This entry includes Ubiquitin fusion degradation protein Ufd1 from fungi and Ufd1-like proteins from animals and plants.

Ufd1 is part of the Ufd1-Npl4 complex that functions as the substrate-recruiting cofactor for Cdc48 segregase. The Cdc48-Ufd1-Npl4 complex is involved in degradation of misfolded ER proteins . The Ufd1-Npl4 complex has been found to recruit Cdc48 to ubiquitylated CMG (Cdc45-MCM-GINS) helicase at the end of chromosome replication, thereby driving the disassembly reaction .

In humans, Npl4-Ufd1 acts as a cofactor in reducing antiviral innate immune responses by facilitating proteasomal degradation of RIG-I (a viral RNA sensor) .

The Ufd1 N-terminal fragment is composed of two readily identifiable subdomains designated as Nn and Nc subdomains. The Nn subdomain adapts a double-psi β-barrel fold, and the Nc subdomain has a mixed α/β roll structure . This superfamily represents the Nn domain found in Ufd1 proteins.
Glycosyl hydrolase 115 superfamily (GH115_sf)
Type: Homologous_superfamily

Glycosyl hydrolase family 115 (GH115) members are alpha-glucuronidases that catalyses the cleavage of 4-O-methyl D-glucuronic acid side chains from native xylan polysaccharides (

) . Family GH115 appears to be restricted to Archaea,
Bacteria, and Fungi . This entry includes Schizophyllum commune Agu1 protein (

) and SpGlcA115A (

) from Streptomyces pristinaespiralis .

Structurally, this domain superfamily consists of 8 β strands and 8 α helices arranged into a TIM barrel. Within GH115, this particular superfamily functions as a catalytic domain.
Ubiquitin-activating enzyme E1, FCCH domain superfamily (E1_FCCH_sf)
Type: Homologous_superfamily

This domain is found in the ubiquitin-activating E1 (Ub-E1) family enzymes. It is one of the catalytic cysteine half-domains of Ub-E1. The catalytic cysteine half-domains contain the E1 active site cysteine, and are known as FCCH and SCCH, for 'first' and 'second' catalytic cysteine half-domain, respectively .

Structurally, the FCCH domain is composed of 7 anti-parallel β sheets and 2 α helices.
Malonyl-CoA decarboxylase, C-terminal catalytic domain superfamily (Malonyl_CoA_deC_C_sf)
Type: Homologous_superfamily

This superfamily represents the C-terminal catalytic domain of Malonyl-CoA decarboxylase (MCD), enzyme which catalyzes the conversion of malonyl-CoA to acetyl-CoA and CO2 and is localized in peroxisomes, and more abundantly in the cytoplasm. MCD is found from bacteria to humans and it has important roles in regulating fatty acid metabolism and food intake. This catalytic domain shares unexpected structural homology to the GCN5-related N-acetyltransferase (GNAT) superfamily .
Alphavirus E2 glycoprotein, domain A (Alphavir_E2_A)
Type: Homologous_superfamily

Alphaviruses are enveloped RNA viruses that use arthropods such as mosquitoes for transmission to their vertebrate hosts, and include Semliki Forest and Sindbis viruses . Alphaviruses consist of three structural proteins: the core nucleocapsid protein C, and the envelope proteins P62 and E1 (

) that associate as a heterodimer. The viral membrane-anchored surface glycoproteins are responsible for receptor recognition and entry into target cells through membrane fusion. The proteolytic maturation of P62 into E2 and E3 (

) causes a change in the viral surface. Together the E1, E2, and sometimes E3 glycoprotein "spikes" form an E1/E2 dimer or an E1/E2/E3 trimer, where E2 extends from the centre to the vertices, E1 fills the space between the vertices, and E3, if present, is at the distal end of the spike . Upon exposure of the virus to the acidity of the endosome, E1 dissociates from E2 to form an E1 homotrimer, which is necessary for the fusion step to drive the cellular and viral membranes together . This entry represents the alphaviral E2 glycoprotein. The E2 glycoprotein functions to interact with the nucleocapsid through its cytoplasmic domain, while its ectodomain is responsible for binding a cellular receptor.

The E2 glycoproteins interact with the nucleocapsid through its cytoplasmic domain, while its ectodomain is responsible for binding a cellular receptor. This is an all beta protein belonging to the immunoglobulin superfamily, with three immunoglobulin domains labelled A, B and C in amino- to carboxy-terminal order.

This superfamily represents the N-terminal domain, known as domain A, of the alphavirus E2 glycoprotein and which is found at the centre of the protein .
Alphavirus E2 glycoprotein, domain B (Alphavir_E2_B)
Type: Homologous_superfamily

Alphaviruses are enveloped RNA viruses that use arthropods such as mosquitoes for transmission to their vertebrate hosts, and include Semliki Forest and Sindbis viruses . Alphaviruses consist of three structural proteins: the core nucleocapsid protein C, and the envelope proteins P62 and E1 (

) that associate as a heterodimer. The viral membrane-anchored surface glycoproteins are responsible for receptor recognition and entry into target cells through membrane fusion. The proteolytic maturation of P62 into E2 and E3 (

) causes a change in the viral surface. Together the E1, E2, and sometimes E3 glycoprotein "spikes" form an E1/E2 dimer or an E1/E2/E3 trimer, where E2 extends from the centre to the vertices, E1 fills the space between the vertices, and E3, if present, is at the distal end of the spike . Upon exposure of the virus to the acidity of the endosome, E1 dissociates from E2 to form an E1 homotrimer, which is necessary for the fusion step to drive the cellular and viral membranes together . This entry represents the alphaviral E2 glycoprotein. The E2 glycoprotein functions to interact with the nucleocapsid through its cytoplasmic domain, while its ectodomain is responsible for binding a cellular receptor.

The E2 glycoproteins interact with the nucleocapsid through its cytoplasmic domain, while its ectodomain is responsible for binding a cellular receptor. This is an all beta protein belonging to the immunoglobulin superfamily, with three immunoglobulin domains labelled A, B and C in amino- to carboxy-terminal order.

This superfamily represents the central domain, known as domain B, of the alphavirus E2 glycoprotein.