SII-SWORD/CoKE huggingface dataset:
TCP-1-like chaperonin intermediate domain superfamily (TCP-1-like_intermed_sf)
Type: Homologous_superfamily

Chaperonins are large cylindrical structures that transiently enclose a partially folded polypeptide and allow it to continue folding in a sequestered environment. Chaperonins are grouped into two families: group I chaperonins, found in eubacteria (e.g. GroEL in Escherichia coli) and eukaryotic organelles of eubacterial descent (e.g. Cpn60 in mitochondria and chloroplasts), and group II chaperonins, found in archaea and the eukaryotic cytosol (CCT or TCP-1 complex) . Both groups share a common monomer architecture of three domains: an equatorial domain that carries ATPase activity, an intermediate domain, and an apical domain, involved in substrate binding .

This superfamily represents the intermediate domain of type II chaperonins.
Baseplate structural protein Gp9/Gp10 middle domain superfamily (Gp9/Gp10_mid_dom_sf)
Type: Homologous_superfamily

This superfamily represents the middle domain found in baseplate structural protein Gp9 and Gp10 of bacteriophage T4.

The Bacteriophage T4 is a double-stranded, structurally complex virus that infects Escherichia coli. Gene product 9 (Gp9) connects the long tail fibres to the baseplate, and triggers baseplate reorganisation and tail contraction after virus attachment to the host cell. The Gp9 protein forms a homotrimer, with each monomer having three domains: the N-terminal α-helical domain forms a triple coiled coil, the middle domain is a mixed, seven-stranded β sandwich with a unique fold, and the C-terminal domain is a eight-stranded β-sandwich with similarity to jellyroll viral capsid protein structures . The flexible loops that occur between domains may enable the conformational changes necessary during infection.

Together with gp11, gp10 initiates the assembly of wedges that then go on to associate with a hub to form the viral baseplate .
Baseplate structural protein Gp9 C-terminal domain superfamily (Gp9_C_dom_sf)
Type: Homologous_superfamily

The Bacteriophage T4 is a double-stranded, structurally complex virus that infects Escherichia coli. Gene product 9 (Gp9) connects the long tail fibres to the baseplate, and triggers baseplate reorganisation and tail contraction after virus attachment to the host cell. The Gp9 protein forms a homotrimer, with each monomer having three domains: the N-terminal α-helical domain forms a triple coiled coil, the middle domain is a mixed, seven-stranded β sandwich with a unique fold, and the C-terminal domain is a eight-stranded β-sandwich with similarity to jellyroll viral capsid protein structures . The flexible loops that occur between domains may enable the conformational changes necessary during infection.

This superfamily represents the Gp9 C-terminal domain.
GroEL-like equatorial domain superfamily (GROEL-like_equatorial_sf)
Type: Homologous_superfamily

Chaperonins are large cylindrical structures that transiently enclose a partially folded polypeptide and allow it to continue folding in a sequestered environment. Chaperonins are grouped into two families: group I chaperonins, found in eubacteria (e.g. GroEL in Escherichia coli) and eukaryotic organelles of eubacterial descent (e.g. Cpn60 in mitochondria and chloroplasts), and group II chaperonins, found in archaea and the eukaryotic cytosol (CCT or TCP-1 complex) . Both groups share a common monomer architecture of three domains: an equatorial domain that carries ATPase activity, an intermediate domain, and an apical domain, involved in substrate binding .

This superfamily represents the equatorial domain.
Glycosyl hydrolase family 95, N-terminal domain (GH95_N_dom)
Type: Domain

This domain is found towards the N terminus of alpha-L-fucosidases, which are members of the glycosyl hydrolase family 95 .
P-loop containing nucleoside triphosphate hydrolase (P-loop_NTPase)
Type: Homologous_superfamily

The P-loop NTPase fold is the most prevalent domain of the several distinct nucleotide-binding protein folds.

The most common reaction catalysed by enzymes of the P-loop NTPase fold is the hydrolysis of the beta-gamma phosphate bond of a bound nucleoside triphosphate (NTP). The energy from NTP hydrolysis is typically utilised to induce conformational changes in other molecules, which constitutes the basis of the biological functions of most P-loop NTPases. P-loop NTPases show substantial substrate preference for either ATP or GTP .
CRISPR-associated protein Csx1, C-terminal (CRISPR-assoc_Csx1_C)
Type: Homologous_superfamily

CRISPRs (clustered regularly interspaced short palindromic repeat) and CRISPR-associated (CAS) genes comprise an adaptive immune system that provides protection against mobile genetic elements (viruses, transposable elements and conjugative plasmids). Although many different Cas protein families have been identified, the exact functions of most of their constituents are still unknown.

This superfamily represents a C-terminal domain found in CAS proteins of the Csx1 family. The C-terminal domain of Csx1 proteins is greatly diversified, in contrast to the conserved N-terminal domain, which appears to play a common role in the homodimerisation of the protein .
DNA polymerase lambda lyase domain superfamily (DNA_pol_lamdba_lyase_dom_sf)
Type: Homologous_superfamily

DNA polymerase lambda is a repair polymerase that has both DNA polymerase and terminal transferase activities. It has 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity . Structural modeling suggests that pol lambda contains the palm, fingers, thumb, and lyase domains present in pol beta, as well as an additional N-terminal BRCT domain and a serine-proline-rich linker that are presumably involved in protein-protein interactions .

This superfamily represents the lyase domain of pol lambda which is also known as the 8kDa domain .
ADP-ribosylation factor-binding protein GGA1-3 (GGA1-3)
Type: Family

This family represents GGAs (Golgi-associated, gamma-adaptin homologous, ARF-interacting proteins) family which includes GGA1, GGA2 and GGA3. They are adaptor proteins that play a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes . They mediate the ARF-dependent recruitment of clathrin to the TGN and binds ubiquitinated proteins and membrane cargo molecules with a cytosolic acidic cluster-dileucine (DXXLL) motif and they also regulate retrograde transport of phosphorylated form of BACE1 from endosomes to the trans-Golgi network . These proteins have a multidomain structure consisting of an N-terminal VHS domain linked by a short proline-rich linker to a GAT (GGA and TOM) domain, which is followed by a long flexible linker to the C-terminal appendage, GAE (Gamma-Adaptin Ear) domain .
Glucose Oxidase, domain 2 (Glucose_Oxidase_domain_2)
Type: Homologous_superfamily

This superfamily represents a structurally irregular domain of glucose oxidase. It is a subdomain of the FAD ADP-binding domain represented by

. The FAD-binding domain forms the α-β fold typical of dinucleotide binding proteins .
TOM1-like protein 1, GAT domain (TOM1L1_GAT_dom)
Type: Domain

TOM1-like protein 1 (TOM1L1) is an adapter protein involved in signaling pathways. It interacts with the SH2 and SH3 domains of various signaling proteins when it is phosphorylated. TOM1L1 promotes activation of Src family tyrosine kinase Fyn, possibly by disrupting intramolecular SH3-dependent interactions . It has been implicated in multivesicular body (MVB) formation, viral egress from the cell, and cytokinesis. Its amplification enhances the metastatic progression of ERBB2-positive breast cancers .

This entry represents the canonical GAT domain of TOM1L1. It is a monomeric three-helix bundle that binds ubiquitin . It is also responsible for the interaction with Toll-interacting protein (Tollip) .
TOM1-like protein 2, VHS domain (TOM1L2_VHS_dom)
Type: Domain

Target of Myb1 (TOM1)-like 2 (TOM1L2) has a probable role in protein transport . It acts as a negative regulator of growth factor-induced Src mitogenic signaling .

This entry represents the N-terminal VHS (Vps27p/Hrs/Stam) domain of TOM1L2, which is found next to the GAT domain. The VHS domain has a superhelical structure similar to the structure of the ARM repeats .
Visual pigments (opsins) retinal binding site (Retinal_BS)
Type: Binding_site

Visual pigments are the light-absorbing molecules that mediate vision. They consist of an apoprotein, opsin, covalently linked to the chromophore cis-retinal. Vision is effected through the absorption of a photon by cis-retinal which is isomerised to trans-retinal. This isomerisation leads to a change of conformation of the protein. Opsins are integral membrane proteins with seven transmembrane regions that belong to family 1 of G-protein coupled receptors.

In vertebrates four different pigments are generally found. Rod cells, which mediate vision in dim light, contain the pigment rhodopsin. Cone cells, which function in bright light, are responsible for colour vision and contain three or more colour pigments (for example, in mammals: red, blue and green).

By contrast with vertebrate rhodopsin, which is found in rod cells, insect photoreceptors are found in the ommatidia that comprise the compound eyes. Each Drosophila eye has 800 ommatidia, each of which contains 8 photoreceptor cells (designated R1-R8): R1-R6 are outer cells, while R7 and R8 are inner cells. Opsins RH3 and RH4 are sensitive to UV light . In Drosophila, the eye is composed of 800 facets or ommatidia. Each ommatidium contains eight photoreceptor cells (R1-R8): the R1 to R6 cells are outer cells, R7 and R8 inner cells. Each of the three types of cells (R1-R6, R7 and R8) expresses a specific opsin.

Proteins evolutionary related to opsins include:

Squid retinochrome, also known as retinal photoisomerase, which converts various isomers of retinal into 11-cis retinal.

Mammalian opsin 3 (Encephalopsin) that may play a role in encephalic photoreception.

Mammalian opsin 4 (Melanopsin) that may mediate regulation of circadian rhythms and acute suppression of pineal melatonin.

Mammalian retinal pigment epithelium (RPE) RGR , a protein that may also act in retinal isomerisation.

The attachment site for retinal in the above proteins is a conserved lysine residue in the middle of the seventh transmembrane helix.
Protein kinase C, eta (PKC_eta)
Type: Family

Protein kinase C, eta type is a member of the novel protein kinase C (nPKC) family. It is involved in the regulation of cell differentiation in keratinocytes and pre-B cell receptor . PKC eta also mediates regulation of epithelial tight junction integrity and foam cell formation . In addition, it is required for glioblastoma proliferation and apoptosis prevention in MCF-7 cells.

PKC is a family of serine- and threonine-specific protein kinases that depend on lipids for activity. They can be activated by calcium but have a requirement for the second messenger diacylglycerol . Members of this family play key regulatory roles in various cellular processes. Currently, there are ten isoforms of PKC which can be classified into classical (alpha, beta I, beta II, gamma), novel (delta, epsilon, eta, theta) and atypical (zeta, iota/lambda) types based on their primary structure and biochemical characteristics . All PKCs contain a C-terminal kinase domain and an N-terminal regulatory domain.

The N-terminal regulatory domain of nPKC consists of a C2 domain follows by a double C1 domain (C1A and C1B). The C2 domain does not respond to calcium which makes nPKC diacylglycerol-sensitive but calcium-independent .
Deoxyguanosinetriphosphate triphosphohydrolase, C-terminal (dGTP_triphosphohydrolase_C)
Type: Homologous_superfamily

This superfamily represents a domain found at the C terminus of deoxyguanosine triphosphate triphosphohydrolase (dGTPase), an enzyme that releases inorganic triphosphate from GTP . dGTPase preferentially hydrolyses dGTP over the other canonical NTPs .
Lipoxygenase, domain 3 (Lipoxygenase_dom_3)
Type: Homologous_superfamily

This superfamily represents a domain found in lipoxygenases.

Lipoxygenases ([ec:1.13.11.-]) are a class of iron-containing dioxygenases which catalyses the hydroperoxidation of lipids, containing a cis,cis-1,4-pentadiene structure. They are common in plants where they may be involved in a number of diverse aspects of plant physiology including growth and development, pest resistance, and senescence or responses to wounding. Plants express a variety of cytosolic isozymes as well as what seems to be a chloroplast isozyme .

The iron atom in lipoxygenases is bound by four ligands, three of which are histidine residues . Six histidines are conserved in all lipoxygenase sequences, five of them are found clustered in a stretch of 40 amino acids. This region contains two of the three iron-ligands; the other histidines have been shown to be important for the activity of lipoxygenases.
Homing endonuclease (Homing_endonucl)
Type: Homologous_superfamily

Homing endonucleases are rare-cutting enzymes encoded by inteins and introns. They are found inserted within host genes in eukaryotes, bacteria, archaebacteria and viruses . By making a site-specific double-strand break in the intronless or inteinless alleles, these nucleases create recombinogenic ends which engage in a gene conversion process that duplicates the intron or intein . There are four families of homing endonucleases classified by the conserved sequence motifs LAGLIDADG, GIY-YIG, H-N-H and His-Cys box . Endonucleases of the DOD family contain one or two copies of the 10-residue sequence known as a dodecapeptide or LAGLIDADG motif. LAGLIDADG endonucleases are either monomers, such as I-SceI, that are composed of two pseudo symmetric subdomains, or homodimers, such as I-CreI. In both cases, the LAGLIDADG endonuclease folds into a β-saddle architecture, a common motif for nucleic acid binding proteins .

This superfamily represents the homing endonuclease domain.
Stannin superfamily (Stannin_sf)
Type: Homologous_superfamily

Stannin (SNN) is a mitochondrial membrane protein that plays a role in the toxic effects of organotins . TMT (trimethyltin), an organotin compound extensive used in industry and agriculture, can cause injury to specific regions of the brain. Stannin is expressed in the TMT-damaged neuronal cells and may be involved in mitochondria-mediated apoptosis in these cells . The structure of stannin is composed of three domains: a single transmembrane helix, a linker and a distorted cytoplasmic helix .
Protein kinase C, delta (PKC_delta)
Type: Family

Protein kinase C, delta type is a member of the novel protein kinase C (nPKC) family. PKC delta plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis , but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death . PKC delta is also involves in tumor suppression , required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses .

PKC is a family of serine- and threonine-specific protein kinases that depend on lipids for activity. They can be activated by calcium but have a requirement for the second messenger diacylglycerol . Members of this family play key regulatory roles in various cellular processes. Currently, there are ten isoforms of PKC which can be classified into classical (alpha, beta I, beta II, gamma), novel (delta, epsilon, eta, theta) and atypical (zeta, iota/lambda) types based on their primary structure and biochemical characteristics . All PKCs contain a C-terminal kinase domain and an N-terminal regulatory domain.

The N-terminal regulatory domain of nPKC consists of a C2 domain follows by a double C1 domain (C1A and C1B). The C2 domain does not respond to calcium which makes nPKC diacylglycerol-sensitive but calcium-independent .
Small ribosomal subunit protein uS13, C-terminal (Rbsml_uS13_C)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain in proteins of the ribosomal protein family uS13 (previously known as S13).

Ribosomal protein uS13 is one of the proteins from the small ribosomal subunit. In Escherichia coli, uS13 is known to be involved in binding fMet-tRNA and, hence, in the initiation of translation. It is a basic protein of 115 to 177 amino-acid residues that contains three helices and a β-hairpin in the core of the protein, forming a helix-two turns-helix (H2TH) motif, and a non-globular C-terminal extension. This family of ribosomal proteins is present in prokaryotes, eukaryotes and archaea .
Ecotin, C-terminal (Ecotin_C)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain of ecotin, a general inhibitor of pancreatic serine proteases .

Proteins containing this domain include members from the protease inhibitor I11 (ecotin) family. Ecotins are dimeric periplasmic proteins from Escherichia coli and related Gram-negative bacteria that have been shown to be potent inhibitors of many trypsin-fold serine proteases of widely varying substrate specificity, which belong to MEROPS peptidase family S1 (

) . Phylogenetic analysis suggested that ecotin has an exogenous target, possibly neutrophil elastase. Ecotin from E. coli, Yersinia pestis, and Pseudomonas aeruginosa, all species that encounter the mammalian immune system inhibit neutrophil elastase strongly while ecotin from the plant pathogen Pantoea citrea inhibits neutrophil elastase 1000-fold less than the others .
Protective antigen, heptamerisation domain (PA_heptamer_dom)
Type: Domain

This entry represents pat of domain 2 of PA and similar proteins from firmicutes.

Protective antigen (PA) is the central component of the three-part protein toxin secreted by Bacillus anthracis, the organism responsible for anthrax. Homologues of PA have been found in several spore-forming Gram-positive bacteria, and share the ability to translocate toxic enzymes into the host cytosol. The PA monomer is organised mainly into antiparallel β-sheets and has four domains: an N-terminal domain (domain 1,

) containing two calcium ions and the cleavage site for activating proteases; a heptamerisation domain (domain 2,

and

) containing a large flexible loop implicated in membrane insertion; a small domain with several key residues for oligomerisation (domain 3,

); and a C-terminal receptor-binding domain (domain 4,

) .
Protective antigen, domain 4 (PA_dom_4)
Type: Homologous_superfamily

This entry represents domain 4 of PA and similar sequences from Bacillus.

Protective antigen (PA) is the central component of the three-part protein toxin secreted by Bacillus anthracis, the organism responsible for anthrax. Homologues of PA have been found in several spore-forming Gram-positive bacteria, and share the ability to translocate toxic enzymes into the host cytosol. The PA monomer is organised mainly into antiparallel β-sheets and has four domains: an N-terminal domain (domain 1,

) containing two calcium ions and the cleavage site for activating proteases; a heptamerisation domain (domain 2,

and

) containing a large flexible loop implicated in membrane insertion; a small domain with several key residues for oligomerisation (domain 3,

); and a C-terminal receptor-binding domain (domain 4,

) .
MAP kinase activated protein kinase, C-terminal (MAPKAPK_C)
Type: Homologous_superfamily

This superfamily represent the C-terminal domain of the MAP kinase activated protein kinases (MAPKAPKs). Proteins containing this domain include Mapkapk2 and Mapkapk3. They are mainly involved in post-transcriptional regulation of gene expression and play an role in inflammation and cancer .
Isopenicillin N synthase-like superfamily (IPNS-like_sf)
Type: Homologous_superfamily

Isopenicillin N synthase (IPNS) catalyses conversion of the linear tripeptide delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV) to isopenicillin N (IPN), the central step in biosynthesis of the beta-lactam antibiotics . IPNS is a nonhaem-Fe2+-dependent enzyme. It belongs to a class of nonhaem Fe2+-containing enzymes which includes 2-oxoglutarate-dependent dioxygenases, 2-oxoglutarate-dependent hydroxy- lases, and enzymes involved in ethylene formation and anthocyaninidin biosynthesis.

The IPNS structure shows that the active site is buried within the hydrophobic pocket of an eight-stranded jelly roll barrel .
DNA-binding protein H-NS-like, C-terminal domain (H-NS_C_dom)
Type: Domain

This entry represents the C-terminal domain of the H-NS DNA binding protein. It is composed of an antiparallel β-sheet, an α-helix and a 3 (10)-helix which form a hydrophobic core, stabilising the whole structure. This domain has been found to bind to DNA .

The histone-like nucleoid-structuring (H-NS) protein is a DNA-binding protein implicated in transcriptional repression (silencing) as well as in bacterial chromosome organisation . H-NS binds tightly to AT-rich dsDNA, increases its thermal stability and inhibits transcription. It also binds to ssDNA and RNA but with a much lower affinity .
Variant surface glycoprotein C-terminal domain superfamily (VSG_C_dom_sf)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain of variant surface glycoproteins. This domain consists of a short α-helix followed by a single turn of 3(10)-helix and connected by a short loop to a small anti-parallel β-sheet and then a longer α-helix at the C terminus . The function of the domain is not clear.
Short tail fibre protein, C-terminal (Short_tail_fibre_C)
Type: Domain

This entry represents the C-terminal domain of the bacteriophage T4 short tail fibre.

During virus attachment, Bacteriophage T4 binds Escherichia coli with its long tail fibres and then binds irreversibly to the lipopolysaccharides component on the cell surface using its short tail fibres . The short tail fibres are composed of a single protein, gp12. The C-terminal domain of gp12 is a receptor-binding domain consisting of three extensively intertwined monomers .
5-keto-4-deoxyuronate isomerase, N-terminal (KduI_N)
Type: Homologous_superfamily

The enzyme 5-keto-4-deoxyuronate isomerase (KduI), also known as 4-deoxy-L-threo-5-hexosulose-uronate ketol-isomerase 2, is part the bacterial metabolic pathway that uses pectin as a carbon source. It catalyses the interconversion of 5-keto-4-deoxyuronate and 2,5-diketo-3-dexoygluconate. KduI is a metalloprotein structurally homologous to members of the cupin superfamily . The KduI subunit consists of two similar halves comprised of 12 β-strands. This superfamily represents the N-terminal domain.
Alpha-ketoglutarate-dependent dioxygenase AlkB-like (AlkB-like)
Type: Domain

This superfamily brings together catalytic domains found in Alpha-ketoglutarate-dependent dioxygenase AlkB-like DNA/RNA demethylases.

AlkB is a DNA repair enzyme that removes methyl adducts and some larger alkylation lesions from endocyclic positions on purine and pyrimidine bases. It is a dioxygenase that requires molecular oxygen, alpha-ketoglutarate and iron .

The catalytic core of AlkB is homologous to other Fe-2OG dioxygenases . Two discrete global conformations have been observed for AlkB, differing in accessibility of a putative oxygen-diffusion tunnel .
Arabinofuranosyltransferase, domain 1 (EmbABC_dom1)
Type: Homologous_superfamily

Arabinosyltransferases EmbA, EmbB and EmbC are known to be involved in arabinogalactan (AG) and lipoarabinomannan (LAM) biosynthesis in mycobacteria. Synthesis of LAM, but not AG, ceases after inactivation of EmbC, while the arabinan of AG is affected by EmbA or EmbB disruption . The arabinans of the mycobacterial cell wall are key structural and immunological polymers.