SII-SWORD/CoKE huggingface dataset:
GCM, small domain (GCM_small)
Type: Homologous_superfamily

GCM transcription factors are a family of proteins which contain a GCM motif. The GCM motif is a domain that has been identified in proteins belonging to a family of transcriptional regulators involved in fundamental developmental processes which comprise Drosophila melanogaster GCM and its mammalian homologues . In GCM transcription factors the N-terminal moiety contains a DNA-binding domain of 150 residues. Sequence conservation is highest in this GCM domain. In contrast, the C-terminal moiety contains one or two transactivating regions and is only poorly conserved.

The GCM motif has been shown to be a DNA binding domain that recognises preferentially the nonpalindromic octamer 5'-ATGCGGGT-3' . The GCM motif contains many conserved basic amino acid residues, seven cysteine residues, and four histidine residues . The conserved cysteines are involved in shaping the overall conformation of the domain, in the process of DNA binding and in the redox regulation of DNA binding . The GCM domain is a new class of Zn-containing DNA-binding domain with no similarity to any other DNA-binding domain . The GCM domain consists of a large and a small domain tethered together by one of the two Zn ions present in the structure. The large and the small domains comprise five-and three-stranded β-sheets, respectively, with three small helical segments packed against the same side of the two β-sheets. The GCM domain exercises a novel mode of sequence-specific DNA recognition, where the five-stranded β-pleated sheet inserts into the major groove of the DNA. Residues protruding from the edge strand of the β-pleated sheet and the following loop and strand contact the bases and backbone of both DNA strands, providing specificity for its DNA target site.

This superfamily represents the small domain found in the GCM motif.
Peptide-N-glycosidase F, N-terminal domain superfamily (PngaseF_N_sf)
Type: Homologous_superfamily

This superfamily represents a domain with an eight-stranded antiparallel β-jelly roll configuration, with the β-strands arranged into two sheets. It is similar in topology to many viral capsid proteins, as well as lectins and several glucanases. This domain allows the protein to bind sugars and catalyses the complete removal of N-linked oligosaccharide chains from glycoproteins .
Major vault protein repeat domain superfamily (MVP_rep_sf)
Type: Homologous_superfamily

This superfamily represents a repeated domain found in the amino terminal half of the Major Vault Protein (MVP). Vaults are one of the largest cytoplasmic ribonucleoprotein particles, found in numerous eukaryotic species. The cellular function carried out by these ribonucleoproteins remains unclear, although roles in multidrug resistance and innate immunity have been suggested . The primary sequence of MVP consists of seven short sequence repeats of ~55 amino acid residues followed by a central region and a coiled-coil protein association domain, which mediates the interactions between MVP molecules .
Kinase associated-1 domain superfamily, fungal (KA1_sf_fungal)
Type: Homologous_superfamily

This superfamily represents a domain found at the C terminus of yeast septin-associated kinases (Kcc4, Gin4 and Hsl1). It is a membrane association domain that binds acidic phospholipids. The structure of this domain includes two interacting α helices that lie on the concave surface of a five-stranded antiparallel β-sheet .
Dam replacing family, catalytic PD-(D/E)XK domain (DRP_PD-(D/E)XK_dom)
Type: Homologous_superfamily

Dam-replacing protein (DRP) is a restriction endonuclease that is flanked by pseudo-transposable small repeat elements. The replacement of Dam-methylase by DRP allows phase variation through slippage-like mechanisms in several pathogenic isolates of Neisseria meningitidis .

This superfamily represents the Dam-replacing catalytic domain. It has the typical PD-(D/E)XK-fold, found in various nucleases (CL0236).
Orbivirus VP4 core, C-terminal (Orbi_VP4_C)
Type: Homologous_superfamily

Orbivirus are double stranded RNA retroviruses of which the Bluetongue virus (BTV) is a member. The core of BTV is a multienzyme complex composed of two major proteins (VP7 and VP3) and three minor proteins (VP1, VP4 and VP6) in addition to the viral genome. VP4 has been shown to perform all RNA capping activities and has both methyltransferase type 1 and type 2 activities associated with it .

This superfamily represents the C-terminal domain (also called GT domain) of the Orbivirus VP4 core protein. Structurally, this domain consists of 6 α helices .
Catechol 1,2-dioxygenase multimerisation domain (1_2-CTD_multi_dom)
Type: Homologous_superfamily

This superfamily represents the N-terminal region (multimerisation domain) of Catechol 1,2-dioxygenase proteins. This region is always found adjacent to the dioxygenase domain.

Dioxygenases catalyse the incorporation of both atoms of molecular oxygen into substrates using a variety of reaction mechanisms. Cleavage of aromatic rings is one of the most important functions of dioxygenases, which play key roles in the degradation of aromatic compounds. The substrates of ring-cleavage dioxygenases can be classified into two groups according to the mode of scission of the aromatic ring. Intradiol enzymes use a non-haem Fe(III) to cleave the aromatic ring between two hydroxyl groups (ortho-cleavage), whereas extradiol enzymes (

) use a non-haem Fe(II) to cleave the aromatic ring between a hydroxylated carbon and an adjacent non-hydroxylated carbon (meta-cleavage) . These two subfamilies differ in sequence, structural fold, iron ligands, and the orientation of second sphere active site amino acid residues.

Enzymes that belong to the intradiol family include catechol 1,2-dioxygenase (1,2-CTD) (

); protocatechuate 3,4-dioxygenase (3,4-PCD) (

); and chlorocatechol 1,2-dioxygenase (

) .
Beta-1,3-glucan-binding protein, N-terminal domain superfamily (BGBP_N_sf)
Type: Homologous_superfamily

Beta 1,3-glucan recognition proteins (GRP, also called Gram-negative bacteria binding proteins or GNBPs) have specific affinity for beta 1,3-glucan, a component on the surface of fungi and bacteria. Beta-GRP (beta-1,3-glucan recognition protein) is one of several pattern recognition receptors (PRRs), also referred to as biosensor proteins, that complexes with pathogen-associated beta-1,3-glucans and then transduces signals necessary for activation of an appropriate innate immune response. They are present in insects and lack all catalytic residues .

BGRP consists of a well conserved N-terminal domain and a C-terminal beta-1,3-glucanase-like domain . The N-terminal domain of BGRP plays a critical role for the detection of pathogen. In contrast, the C-terminal glucanase-like domain has neither glucanase activity, nor affinity with the beta-1,3-glucan .

This superfamily represents a domain is found at the N terminus of beta-1,3-glucan-binding proteins (BGRP-N). Structurally, BGRP-N has an immunoglobulin-like β-sandwich fold composed of two antiparallel β-sheets containing three and five β-strands .
Viral ssDNA binding protein, head domain (Viral_ssDBP_head)
Type: Homologous_superfamily

This entry includes the major DNA-binding protein (DBP, UL57 or ICP8) from Herpesviruses. DBP binds single-stranded DNA, and the region encompassing residues 368-902 contains the DNA-binding site . UL5, UL8 and UL52 genes encode an essential heterotrimeric DNA helicase-primase that is responsible for concomitant DNA unwinding and primer synthesis at the viral DNA replication fork. DBP may stimulate DNA unwinding and enable bypass of cisplatin damaged DNA by recruiting the helicase-primase to the DNA . DBP helps initiate DNA replication by binding to the origin-binding protein (UL9) . It also reorganizes the host nucleus leading to the formation of prereplicative sites and replication compartments .

This superfamily represents the head domain found in Viral ssDNA-binding protein. The head domain interacts with the C-terminal domain (CTD) of the protein and gives the CTD structure. The CTD is involved in increasing the ssDNA binding protein's cooperativity when binding ICP8, which is believed to stimulate helicase activity. Structurally, this domain consists of 8 α helices .
PvsD/AcsD-like, thumb domain, helical bundle (PvsD/AcsD-like_thumb_helix)
Type: Homologous_superfamily

The achromobactin synthetase protein D (AcsD) monomer can be decomposed into three domains that resemble a cupped hand (thumb domain 1, palm domain 2 and fingers domain 3). The Domain 1 (thumb) is a three helix bundle flanked by a four stranded anti-parallel β-sheet that forms the dimer interface. Domain 2 bridges domain 1 to domain 3 and comprises a four-helix bundle sandwiched between a three-stranded antiparallel β-sheet and a two-stranded antiparallel β-sheet. Domain 3 is connected to domain 1 by a 31-residue extended loop (L4), it comprises 182 residues folded in a twisted eight-stranded antiparallel β-sheet interspersed with five α-helices and extended loops .

This superfamily represents the helix bundle of the vibrioferrin amide bond forming protein PvsD, AcsD and related proteins, thumb domain.
PvsD/AcsD-like, thumb domain, four stranded beta-sheet (PvsD/AcsD-like_thumb_beta)
Type: Homologous_superfamily

The achromobactin synthetase protein D (AcsD) monomer can be decomposed into three domains that resemble a cupped hand (thumb domain 1, palm domain 2 and fingers domain 3). The Domain 1 (thumb) is a three helix bundle flanked by a four stranded anti-parallel β-sheet that forms the dimer interface. Domain 2 bridges domain 1 to domain 3 and comprises a four-helix bundle sandwiched between a three-stranded antiparallel β-sheet and a two-stranded antiparallel β-sheet. Domain 3 is connected to domain 1 by a 31-residue extended loop (L4), it comprises 182 residues folded in a twisted eight-stranded antiparallel β-sheet interspersed with five α-helices and extended loops .

This superfamily represents the four stranded β-sheet of the vibrioferrin amide bond forming protein PvsD, AcsD and related proteins, thumb domain.
DNA polymerase alpha, subunit B, N-terminal domain superfamily (DNA_pol_alpha_B_N_sf)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain of subunit B of DNA polymerase alpha-primase, an enzyme which is essential for DNA replication in higher eukaryotes as it initiates synthesis on both leading and lagging strand single-stranded DNA templates. It consists of a primase heterodimer that synthesises RNA primers, a DNA polymerase that extends them, and a fourth subunit, p68 (also termed B-subunit), which is believed to regulate the whole complex. This domain docks on the SV40 helicase and activates the viral primosome .
Large ribosomal subunit protein mL64 domain superfamily (Ribosomal_mL64_sf)
Type: Homologous_superfamily

This superfamily represents a domain found in the large ribosomal subunit protein mL64, also known as Growth arrest and DNA damage-inducible proteins-interacting protein 1 and CRIF1 . These proteins act as negative regulators of G1 to S cell cycle phase progression by inhibiting cyclin-dependent kinases. Inhibitory effects are additive with GADD45 proteins but occur also in the absence of GADD45 proteins. Furthermore, they act as a repressor of the orphan nuclear receptor NR4A1 by inhibiting AB domain-mediated transcriptional activity . They may be involved in the hormone-mediated regulation of NR4A1 transcriptional activity.

Structurally, this domain consists of 4 α helices.
Phosphoprotein, C-terminal domain, viral (Phosphoprotein_C_viral)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain of the phosphoprotein from vesiculoviruses, which are ssRNA negative-strand rhabdoviruses. It is known as the phosphoprotein or P protein . This protein may be part of the RNA dependent RNA polymerase complex . The phosphorylation states of this protein may regulate the transcription and replication complexes .

Structurally, the C-terminal domain consists of 2 strands and 5 helices.
CFA/I fimbrial subunit E, adhesin domain (CfaE_adhesin)
Type: Homologous_superfamily

CfaE, the tip adhesin of enterotoxigenic Escherichia coli colonisation factor antigen I fimbriae (CFA/I), initiates binding of this enteropathogen to the small intestine. It comprises a stacked N-terminal β-sandwich adhesin domain (AD) and a C-terminal pilin domain (PD), with the putative receptor-binding pocket at one pole and an equatorial interdomain interface .

This superfamily represents the adhesin domain of CfaE, homologous to the pilus biogenesis initiator protein CbID and the major pilin subunits of CS pili.
Antitoxin VbhA domain superfamily (VbhA_sf)
Type: Homologous_superfamily

VbhT is a bacterial Fic protein of the mammalian pathogen B. schoenbuchensis. It is composed of an N-terminal FIC domain and a C-terminal BID domain. FIC domains are known to catalyse adenylylation (also called AMPylation). This entry represents VbhA, an antitoxin that binds FIC domain (filamentation induced by cyclic AMP) of VbhT and inhibits its activity. It inhibits the adenylylation activity of VbhT by positioning close to the putative ATP-binding site, hence competing with ATP binding .

Structurally, VbhA consists of 3 α helices.
TBC1 domain family member 7, domain 2 (TBC1D7_dom2)
Type: Homologous_superfamily

TBC1D7 is part of the TSC1-TSC2-TBC1D7 complex that serves as a negative regulator of the mechanistic target of rapamycin complex 1 that controls cell growth in response to environmental cues . TBC1D7 helps to stabilize the TSC1-TSC2 complex through its direct interaction with TSC1. Homozygous inactivation of TBC1D7 causes intellectual disability and megaencephaly .

This superfamily represents the second out of three domains found in TBC1D7. Structurally, this domain consists of 4 α helices.
Phospholipase B-like, domain 1 (PLipase_B-like_dom1)
Type: Homologous_superfamily

Phospholipase B (PLB) catalyses the hydrolytic cleavage of both acylester bonds of glycerophospholipids. This family of PLB enzymes has been identified in mammals, flies and nematodes but not in yeast . In Drosophila this protein was named LAMA for laminin ancestor since it is expressed in the neuronal and glial precursors that surround the lamina .

This superfamily represents the domain 1 of phospholipase B. Structurally, this domain consists of 4 anti-parallel β sheets and a small α helix.
Phospholipase B-like, domain 2 (PLipase_B-like_dom2)
Type: Homologous_superfamily

Phospholipase B (PLB) catalyses the hydrolytic cleavage of both acylester bonds of glycerophospholipids. This family of PLB enzymes has been identified in mammals, flies and nematodes but not in yeast . In Drosophila this protein was named LAMA for laminin ancestor since it is expressed in the neuronal and glial precursors that surround the lamina .

This superfamily represents the domain 2 of phospholipase B. Structurally, this domain consists of 4 α helices.
Phospholipase B-like, domain 3 (PLipase_B-like_dom3)
Type: Homologous_superfamily

Phospholipase B (PLB) catalyses the hydrolytic cleavage of both acylester bonds of glycerophospholipids. This family of PLB enzymes has been identified in mammals, flies and nematodes but not in yeast . In Drosophila this protein was named LAMA for laminin ancestor since it is expressed in the neuronal and glial precursors that surround the lamina .

This superfamily represents the domain 3 of phospholipase B.
DNA packaging protein FI, C-terminal domain (Packaging_FI_C)
Type: Homologous_superfamily

DNA packaging protein FI is a two-domain protein required for efficient DNA packaging and in lambda bacteriophage head assembly. This entry represents the C-terminal domain responsible for the head binding activity . It adopts a β-strand fold, presents several unstructured regions and a conserved EEE sequence motif.
TPA1/Ofd1, C-terminal (TPA1/Ofd1_C)
Type: Homologous_superfamily

This superfamily entry represents the C-terminal domain of Ofd1 (oxoglutarate and iron-dependent oxygenase, from Schizosaccharomyces pombe), a prolyl 4-hydroxylase-like 2-oxoglutarate-Fe(II) dioxygenase that accelerates the degradation of Sre1N (the N-terminal transcription factor domain of Sre1) in the presence of oxygen . The domain is conserved from yeasts to humans and was also characterised in S. cerevisiae Tpa1 . Yeast Sre1 is the orthologue of mammalian sterol regulatory element binding protein (SREBP), and it responds to changes in oxygen-dependent sterol synthesis as an indirect measure of oxygen availability. However, unlike the prolyl 4-hydroxylases that regulate mammalian hypoxia-inducible factor, Ofd1 uses multiple domains to regulate Sre1N degradation by oxygen; the Ofd1 N-terminal dioxygenase domain is required for oxygen sensing and this Ofd1 C-terminal domain accelerates Sre1N degradation in yeasts .
PvsD/AcsD-like, palm domain, helix bundle (PvsD/AcsD-like_palm_helix)
Type: Homologous_superfamily

The achromobactin synthetase protein D (AcsD) monomer can be decomposed into three domains that resemble a cupped hand (thumb domain 1, palm domain 2 and fingers domain 3). The Domain 1 (thumb) is a three helix bundle flanked by a four stranded anti-parallel β-sheet that forms the dimer interface. Domain 2 bridges domain 1 to domain 3 and comprises a four-helix bundle sandwiched between a three-stranded antiparallel β-sheet and a two-stranded antiparallel β-sheet. Domain 3 is connected to domain 1 by a 31-residue extended loop (L4), it comprises 182 residues folded in a twisted eight-stranded antiparallel β-sheet interspersed with five α-helices and extended loops .

This superfamily represents the helix bundle of the vibrioferrin amide bond forming protein PvsD and achromobactin synthetase protein D (AcsD) palm domain. The secondary structure elements of the palm domain are interspersed with long loops, two of which, L9 and L10, point upwards from the palm and contain three absolutely conserved residues H444, N447 and D464 as well as N509 which is found only in type A and B enzymes .
Interleukin-17 receptor A/B, FnIII-like domain 2 superfamily (IL17RA/B_FnIII-like_2_sf)
Type: Homologous_superfamily

The five IL-17 receptors (IL17RA-IL17RE) exhibit considerable sequence divergence between one another, but all appear to contain extracellular domains composed of fibronectin type-III (FnIII) domains, and cytoplasmic SEF/IL-17R (SEFIR) domains that show loose homology to Toll/IL-1R (TLR) domains.

This is the second of two fibronectin-type domains on interleukin-17 receptor proteins A and B . These two fibronectin-type domains are linked and together bind two molecules of IL-17 at one of its receptor-binding interfaces. This allows the other interface to bind to another receptor, thus allowing the IL-17 family of homodimeric cytokines to coordinate two different receptors .
Hri1, N-terminal domain superfamily (Hri1_N_sf)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain of Saccharomyces cerevisiae's Hri1 (Hrr25-interacting protein 1, YLR301w), a non-essential protein named for its interaction with the yeast protein kinase Hrr25. It has also been shown to interact with Sec72p, although it does not seem to be involved in protein translocation into the ER. This N-terminal domain of Hri1p contains a tandem repeat of a structural unit that forms a β-barrel with structural similarity to nitrobindin. It is involved in homodimerization and it may also contain a ligand binding site .
Birnavirus VP3, domain 1 (Birna_VP3_dom1)
Type: Homologous_superfamily

Birnavirus VP3 is involved in virus morphogenesis. It interacts with the structural protein VP2, with the double-stranded RNA genome, and with the virus-encoded, RNA-dependent RNA polymerase (RdRP), VP1, playing a role in both viral capsid formation, recruitment of VP1 into the capsid and encapsidation of the viral genome.

This superfamily represents domain 1 of the multifunctional birnavirus protein VP3. This domain's fold lacks significant homologies with any other protein domains of known structure.
Birnavirus VP3, domain 2 (Birna_VP3_dom2)
Type: Homologous_superfamily

Birnavirus VP3 is involved in virus morphogenesis. It interacts with the structural protein VP2, with the double-stranded RNA genome, and with the virus-encoded, RNA-dependent RNA polymerase (RdRP), VP1, playing a role in both viral capsid formation, recruitment of VP1 into the capsid and encapsidation of the viral genome.

This superfamily represents domain 2 of the multifunctional birnavirus protein VP3. The fold of this domain shows significant structural similarities with different transcription regulation factors which suggests it mediates interaction with both the genome and RdRP .
Pre-hexon-linking protein IIIa, N-terminal (Hex_IIIa_N)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain of pre-hexon-linking protein IIIa.

The major capsid protein of the adenovirus strain is also known as a hexon. This entry represents protein IIIa, which is a hexon-associated protein that is likely to participate in vertex stabilisation and genome packaging. It stabilises vertices by tethering the penton bases to neighbouring peripentonal hexons, and lashes peripentonal hexons to the neighbouring hexons through its interaction with hexon-linking protein. During virus assembly, it seems to play a role in packaging of viral DNA via its interaction with packaging protein 3 .
LuxQ periplasmic domain, N-terminal subdomain (LuxQ-periplasm_N)
Type: Homologous_superfamily

LuxQ is a sensor histidine kinase involved in quorum sensing in the marine bacterium Vibrio harveyi. Quorum sensing is a process of bacterial cell-cell communication driven by secreted signaling molecules called autoinducers such as AI-2. The receptor for this autoinducer is LuxPQ, formed as a result of the association between LuxQ and LuxP, a periplasmic binding protein, through the cited periplasmic domain of LuxQ .

This superfamily shares the N-terminal structure of the periplasmic domain in LuxQ.
Erythrocyte binding antigen 175, C-terminal domain superfamily (EBA-175_C_sf)
Type: Homologous_superfamily

EBA-175 is involved in the formation of a tight junction. This necessary step in invasion is required for replication and proliferation of the parasite in the bloodstream of its vertebrate host. This superfamily represents the C-terminal region VI, which is a cysteine rich domain essential for EBA-175 trafficking. The structure is a homodimer that contains a five-α-helical core stabilised by four disulphide bridges .
KRIT, N-terminal NPxY motif-rich domain superfamily (NUDIX_sf)
Type: Homologous_superfamily

This domain is found in higher eukaryotes at the N terminus of KRIT1 or Krev interaction trapped proteins. KRIT1 is a 736 amino acid protein that contains three regions, an N-terminal NPxY motif-rich region, an ankyrin repeat domain (ARD) and a band four-point-one, ezrin, radixin, moesin (FERM) domain. The N-terminal region of KRIT1 contains three NPxY-like motifs and can bind ICAP1 (integrin cytoplasmic-associated protein 1 (ICAP1). In the absence of KRIT1, ICAP1 binds via its C-terminal PH/PTB fold domain to the integrin beta-1 cytoplasmic tail. Binding of KRIT1 to ICAP1 via this domain out-competes the binding of ICAP1 to integrin cytoplasmic tails such that ICAP1 is sequestered in the nucleus. Integrin activation is thus prevented. KRIT1 does not include the canonical "Nudix box" motif or other Nudix motifs but does, however, very clearly adopt a Nudix fold with a central β-sheet flanked by two α-helices .