SII-SWORD/CoKE huggingface dataset:
Ribonucleotide reductase, stirrup (RNR_stirrup)
Type: Domain

The Stirrup domain, found in the prokaryotic protein ribonucleotide reductase, has a molecular mass of 9kDa and is folded into an α/β structure. It allows for binding of the reductase to DNA via electrostatic interactions, since it has a predominance of positive charges distributed on its surface .
PI-PfuI intein endonuclease, subdomain (PI-PfuI_intein_endonucl_subdom)
Type: Domain

Ribonucleotide reductase from Pyrococcus species has been shown to contain two inteins, PI-PfuI and PI-PfuII. The endonuclease domain from the PI-PfuI intein (also known as Vitamin B12-dependent ribonucleoside-diphosphate reductase) is composed of two subdomains, each of which assumes an α-β-β-α-β-β-α-α topology. The four stranded β-sheet forms a saddle-shaped surface and assembles together through an interface made of α-helices. The presence of 14 basic residues on the surface of the β-sheets suggests that this large groove may be involved in DNA binding . This entry represents the endonuclease subdomain found towards the N terminus.
Bacteriophage PP7 capsid (Phage_PP7_CP)
Type: Family

This entry represents the capsid protein (CP) of Pseudomonas phage PP7. CP adopts a secondary structure consisting of a six stranded β sheet and an α helix .
Thrombomodulin-like, EGF-like (Tme5_EGF-like)
Type: Domain

This domain adopts a fold similar to other EGF domains, with a flat major and a twisted minor β sheet. Disulphide pairing, however, is not of the usual 1-3, 2-4, 5-6 type; rather 1-2, 3-4, 5-6 pairing is found. Its extended major sheet (strands beta-2 and beta-3 and the connecting loop) projects into thrombin's active site groove. This domain is required for interaction of thrombomodulin with thrombin, and subsequent activation of protein-C .
Haemadin (Haemadin)
Type: Family

Members of this family adopt a secondary structure consisting of five short β-strands (beta1-beta5), which are arranged in two antiparallel distorted sheets formed by strands beta1-beta4-beta5 and beta2-beta3 facing each other. This β-sandwich is stabilised by six enclosed cysteines arranged in a [1-2, 3-5, 4-6] disulphide pairing resulting in a disulphide-rich hydrophobic core that is largely inaccessible to bulk solvent. The close proximity of disulphide bonds [3-5] and [4-6] organises haemadin into four distinct loops. The N-terminal segment of this domain binds to the active site of thrombin, inhibiting it .
Beta-adaptin appendage, C-terminal subdomain (B-adaptin_app_sub_C)
Type: Domain

This entry represents a subdomain of the appendage (ear) domain of beta-adaptin. This domain has a three-layer arrangement, α-β-α, with a bifurcated antiparallel β-sheet . This domain is required for binding to clathrin, and its subsequent polymerisation. Furthermore, a hydrophobic patch present in the domain also binds to a subset of D-phi-F/W motif-containing proteins that are bound by the alpha-adaptin appendage domain (epsin, AP180, eps15) .
Growth hormone/erythropoietin receptor, ligand binding (Growth/epo_recpt_lig-bind)
Type: Domain

Members of this entry include the growth hormone and erythropoietin receptors. The latter interacts with erythropoietin (EPO), with subsequent initiation of the downstream chain of events associated with binding of EPO to the receptor, including EPO-induced erythroblast proliferation and differentiation through induction of the JAK2/STAT5 signalling cascade. The domain adopts a secondary structure composed of a short amino-terminal helix, followed by two β-sandwich regions .
EF-hand domain, type 1 (EF-hand_dom_typ1)
Type: Domain

Like other EF hand domains, this domain forms a helix-loop-helix motif, though since it does not contain the canonical pattern of calcium binding residues found in many EF hand domains, it does not bind calcium ions. The main function of this domain is the provision of specificity in beta-dystroglycan recognition, though in dystrophin it serves an additional role: stabilisation of the WW domain (

), enhancing dystroglycan binding .
EF-hand domain, type 2 (EF-hand_dom_typ2)
Type: Domain

Like other EF hand domains, this domain forms a helix-loop-helix motif, though since it does not contain the canonical pattern of calcium binding residues found in many EF hand domains, it does not bind calcium ions. The main function of this domain is the provision of specificity in beta-dystroglycan recognition, though in dystrophin it serves an additional role: stabilisation of the WW domain (

), enhancing dystroglycan binding .
Malto-oligosyltrehalose trehalohydrolase, archaeal, C-terminal (Maltooligo_trehalose_arc_C)
Type: Domain

This C-terminal domain is found in the prokaryotic protein glycosyltrehalose trehalohydrolase; it assumes a gamma-crystallin-type fold with a five-stranded anti-parallel β-sheet that packs against the C-terminal side of a β-α barrel. The domain is common to family 13 glycosidases and typically contains a five to ten strand β-sheet, however its precise fold varies .
Translation machinery associated TMA7 (TMA7)
Type: Family

TMA7 plays a role in protein translation. Deletions of the TMA7 gene results in altered protein synthesis rates .
Bud22 domain (Bud22_dom)
Type: Domain

This entry represents a domain found in the fungal Bud22 protein and the animal SRFB1 (serum response factor-binding protein 1) protein. Budding yeast Bud22 is required for rRNA maturation and ribosomal subunit biogenesis . SRFB1 may be involved in regulating transcriptional activation of cardiac genes during the aging process and may play a role in biosynthesis and/or processing of SLC2A4 in adipose cells .
Recombination protein 107 (Rec107)
Type: Family

Rec107 forms part of a complex (Rec107-Mei4-Rec114) that is required for meiotic double strand DNA break formation. Rec107 increases in abundance and is phosphorylated during the prophase phase of cell division . Rec107 is not required for mitosis and mitotic DNA repair mechanisms .
Heat-stable enterotoxin B, secretory (STb_secrete)
Type: Family

Members of this family assume a helical secondary structure, with two α helices forming a disulphide cross-linked α-helical hairpin. The disulphide bonds are crucial for the toxic activity of the protein, and are required for maintenance of the tertiary structure, and subsequent interaction with the particulate form of guanylate cyclase, increasing cyclic GMP levels within the host intestinal epithelial cells .
Streptomyces killer toxin-like, beta/gamma crystallin (Sklp_toxin_b/g_crystallin)
Type: Domain

This domain consists of a beta-gamma-crystallin fold , wherein nine β-strands are connected by loop, and are separated into two sheets, each sheet forming the Greek key motif. The two Greek key motifs face each other in the global topology. The three-dimensional structure of the molecule is a 'sandwich'-shaped β-barrel structure: hydrophobic side-chains are packed in the large interface area of the β-sheets. In Streptomyces killer toxin-like protein domain confers a cytocidal effect to the toxin, causing cell death in both budding and fission yeasts, and morphological changes in yeasts and filamentous fungi . This domain is also found in chitin-biding antifungal proteins .
CheY binding (CheY-binding)
Type: Domain

The CheY binding domain is found in the response regulator histidine kinase CheA. It adopts a secondary structure consisting of an open-face β/α sandwich, with four antiparallel β-strands and two α-helices. It binds to a corresponding domain on CheY, with subsequent phosphorylation of the CheY Asp57 residue, and activation of CheY, which then affects flagellar rotation .
Cdc6, C-terminal (Cdc6_C)
Type: Domain

Cdc6 (also known as Cell division cycle 6 or Cdc18) functions as a regulator at the early stages of DNA replication, by helping to recruit and load the Minichromosome Maintenance Complex (MCM) onto DNA and may have additional roles in the control of mitotic entry. Precise duplication of chromosomal DNA is required for genomic stability during replication. Cdc6 has an essential role in DNA replication and irregular expression of Cdc6 may lead to genomic instability. Cdc6 over-expression is observed in many cancerous lesions. DNA replication begins when an origin recognition complex (ORC) binds to a replication origin site on the chromatin. Studies indicate that Cdc6 interacts with ORC through the Orc1 subunit, and that this association increases the specificity of the ORC-origins interaction. Further studies suggest that hydrolysis of Cdc6-bound ATP promotes the association of the replication licensing factor Cdt1 with origins through an interaction with Orc6 and this in turn promotes the loading of MCM2-7 helicase onto chromatin. The MCM2-7 complex promotes the unwinding of DNA origins, and the binding of additional factors to initiate the DNA replication. S-Cdk (S-phase cyclin and cyclin-dependent kinase complex) prevents rereplication by causing the Cdc6 protein to dissociate from ORC and prevents the Cdc6 and MCM proteins from reassembling at any origin. By phosphorylating Cdc6, S-Cdk also triggers Cdc6's ubiquitination. The Cdc6 protein is composed of three domains, an N-terminal AAA+ domain with Walker A and B, and Sensor-1 and -2 motifs. The central region contains a conserved nucleotide binding/ATPase domain and is a member of the ATPase superfamily. .

The C-terminal domain of cell division control protein 6 (CDC6) assumes a winged helix fold, with a five α-helical bundle (α15-α19) structure, backed on one side by three β strands (β6-β8). It has been shown that this domain acts as a DNA-localisation factor, however its exact function is, as yet, unknown. Putative functions include: (1) mediation of protein-protein interactions and (2) regulation of nucleotide binding and hydrolysis. Mutagenesis studies have shown that this domain is essential for appropriate CDC6 activity .
K cyclin, C-terminal (K-cyclin_C)
Type: Domain

Cyclins are eukaryotic proteins that play an active role in controlling nuclear cell division cycles , and regulate cyclin dependent kinases (CDKs). Cyclins, together with the p34 (cdc2) or cdk2 kinases, form the Maturation Promoting Factor (MPF). There are two main groups of cyclins, G1/S cyclins, which are essential for the control of the cell cycle at the G1/S (start) transition, and G2/M cyclins, which are essential for the control of the cell cycle at the G2/M (mitosis) transition. G2/M cyclins accumulate steadily during G2 and are abruptly destroyed as cells exit from mitosis (at the end of the M-phase). In most species, there are multiple forms of G1 and G2 cyclins. For example, in vertebrates, there are two G2 cyclins, A and B, and at least three G1 cyclins, C, D, and E.

Cyclin homologues have been found in various viruses, including Saimiriine herpesvirus 2 (Herpesvirus saimiri) and Human herpesvirus 8 (HHV-8) (Kaposi's sarcoma-associated herpesvirus). These viral homologues differ from their cellular counterparts in that the viral proteins have gained new functions and eliminated others to harness the cell and benefit the virus .

This domain adopts a secondary structure consisting of a five α-helix cyclin fold. Interaction with cyclin dependent kinases (CDKs) at a PSTAIRE sequence motif within the catalytic cleft of CDK results in the regulation of CDK activity .
Glucan 1,4-alpha-maltotetraohydrolase, domain C (AMT4_domain_C)
Type: Domain

Glucan 1,4-alpha-maltotetraohydrolase AMT4 (

), also known as maltooligosaccharide-forming amylase (MFA), degrades starch into maltooligosaccharides. Crystal structure of AMT4 from Pseudomonas saccharophila, which shares high sequence similarity with AMT4 from P. stutzeri, revealed that it folds into three domains, domain A, B and C. This entry represents domain C, which consists of five antiparallel β-strands .
Domain of unknown function DUF1922 (DUF1922)
Type: Domain

This entry represents a domain consisting of a β-sheet region followed by an α-helix. The β-sheet region contains a CXCX...XCXC sequence with Cys residues located in two proximal loops and pointing towards each other. The precise function of these proteins is unknown .
Domain of unknown function DUF1923 (DUF1923)
Type: Domain

This domain is found in maltosyltransferases, adopting a secondary structure that consists of eight antiparallel β-strands forming an open-sided 'jelly roll' Greek key β-barrel. Their exact function is, as yet, unknown .
SsuA/THI5-like (SsuA/THI5)
Type: Domain

This domain is found in NMT1/THI5 family proteins. These proteins are proposed to be required for the biosynthesis of the pyrimidine moiety of thiamine . This domain is also found in aliphatic sulfonates-binding protein SsuA, which is part of a transport system for aliphatic sulfonates .
Adhesion molecule, immunoglobulin-like (Adhes-Ig-like)
Type: Domain

This domain is found in mucosal vascular addressin cell adhesion molecule 1 proteins (MAdCAM-1). These are cell adhesion molecules expressed on the endothelium in mucosa that guide the specific homing of lymphocytes into mucosal tissues. MAdCAM-1 belongs to a subclass of the immunoglobulin superfamily (IgSF), the members of which are ligands for integrins . The crystal structure of this domain has been reported; it adopts an immunoglobulin-like β-sandwich structure, with seven strands arranged in two β-sheets in a Greek-key topology .
Protein of unknown function DUF1924, Cytochrome c-type protein SHP-like (DUF1924_SHP)
Type: Family

This family of proteins includes Cytochrome c-type proteins from proteobacteria, such as Cytochrome c-type protein SHP from Rhodobacter sphaeroides (

), a high-spin cytochrome able to transiently bind oxygen during autoxidation. It is organized into a series of four α-helices and extended loop configuration, showing structural similarity to the class I cytochromes c. It has been suggested that SHP could reduce a small ligand, but its function is still unknown .
Cyclomaltodextrinase, N-terminal (Cyc-maltodext_N)
Type: Domain

This domain is found at the N terminus of cyclomaltodextrinase. The domain assumes a β-sandwich structure composed of the eight antiparallel β-strands. A ten residue linker is also present at the C-terminal end, which connects the N-terminal domain to a distal domain in the protein. This domain participates in oligomerisation of the protein, wherein the N-terminal domain of one subunit contacts the active centre of the other subunit, and is also required for binding of cyclodextrin to substrate . Proteins containing this domain also include neopullulanase SusA from Bacteroides thetaiotaomicron. SusA cleaves 1,4-alpha-glucosidic linkages in starch to produce disaccharides or trisaccharides in starch degradation .
MIF4G-like, type 1 (MIF4G-like_typ-1)
Type: Domain

This entry represents an MIF4G-like domain. MIF4G domains share a common structure but can differ in sequence. This entry is designated "type 1", and is found in nuclear cap-binding proteins and eIF4G.

The MIF4G domain is a structural motif with an ARM (Armadillo) repeat-type fold, consisting of a 2-layer α/α right-handed superhelix. Proteins usually contain two or more structurally similar MIF4G domains connected by unstructured linkers. MIF4G domains are found in several proteins involved in RNA metabolism, including eIF4G (eukaryotic initiation factor 4-gamma), eIF-2b (translation initiation factor), UPF2 (regulator of nonsense transcripts 2), and nuclear cap-binding proteins (CBP80, CBC1, NCBP1), although the sequence identity between them may be low .
Bacteriophage T4, Gp12 (Phage_T4_Gp12)
Type: Domain

This domain adopts a right-handed triple-stranded β-helix fold, and is found in the central region of the phage short tail fibre protein Gp12 .
MIF4G-like, type 2 (MIF4G-like_typ-2)
Type: Domain

This entry represents an MIF4G-like domain. MIF4G domains share a common structure but can differ in sequence. This entry is designated "type 2", and is found in nuclear cap-binding proteins and eIF4G.

The MIF4G domain is a structural motif with an ARM (Armadillo) repeat-type fold, consisting of a 2-layer α/α right-handed superhelix. Proteins usually contain two or more structurally similar MIF4G domains connected by unstructured linkers. MIF4G domains are found in several proteins involved in RNA metabolism, including eIF4G (eukaryotic initiation factor 4-gamma), eIF-2b (translation initiation factor), UPF2 (regulator of nonsense transcripts 2), and nuclear cap-binding proteins (CBP80, CBC1, NCBP1), although the sequence identity between them may be low .
Lyase, N-terminal (Lyase_N)
Type: Domain

This entry represents a domain predominantly found in chondroitin ABC lyase I, adopting a jelly-roll fold topology consisting of a two-layered bent β-sheet sandwich with one short α-helix. The convex β sheet is composed of five antiparallel strands, whilst the concave β-sheet contains five antiparallel β-strands with a loop between two consecutive strands folding back onto the concave surface. This domain is required for binding of the protein to long glycosaminoglycan chains .
Lyase, catalytic (Lyase_catalyt)
Type: Domain

This domain is predominantly found in chondroitin ABC lyase I, adopting a helical structure, with fifteen α-helices which are at least two turns long and several short helical turns. The bulk of the domain is formed by ten α-helices forming five hairpin-like pairs and arranged into an incomplete toroid, the (α/α)5 fold. Additionally, two long and two short α-helices at the N terminus of the domain wrap around the toroid. At the C-terminal end of the toroid there is one additional short α-helix. This domain is required for degradation of polysaccharides containing 1,4-beta-D-hexosaminyl and 1,3-beta-D-glucoronosyl or 1,3-alpha-L-iduronosyl linkages to disaccharides containing 4-deoxy-beta-D-gluc-4-enuronosyl groups .
Alpha-amylase/4-alpha-glucanotransferase, central domain (A-amylase/a-glucTrfase_central)
Type: Domain

Alpha-amylase is classified as family 13 (

) of the glycosyl hydrolases and is present in archaea, bacteria, fungi, plants and animals. Alpha-amylase is an essential enzyme in alpha-glucan metabolism, acting to catalyse the hydrolysis of alpha-1,4-glucosidic bonds of glycogen, starch and related polysaccharides. Although all alpha-amylases possess the same catalytic function, they can vary with respect to sequence. In general, they are composed of three domains: a TIM barrel containing the active site residues and chloride ion-binding site (domain A), a long loop region inserted between the third β-strand and the α-helix of domain A that contains calcium-binding site(s) (domain B), and a C-terminal β-sheet domain that appears to show some variability in sequence and length between amylases (domain C) . Amylases have at least one conserved calcium-binding site, as calcium is essential for the stability of the enzyme. The chloride-binding functions to activate the enzyme, which acts by a two-step mechanism involving a catalytic nucleophile base (usually an Asp) and a catalytic proton donor (usually a Glu) that are responsible for the formation of the beta-linked glycosyl-enzyme intermediate.

This entry represents a domain found in prokaryotic alpha-amylase (

) and 4-alpha-glucanotransferase (

). It is adjacent to the C-terminal domain (see

). This domain adopts an immunoglobulin/albumin-binding domain-like fold, with a bundle of three α-helices . The exact function of this domain is, as yet, unknown.
Alpha-amylase/4-alpha-glucanotransferase, C-terminal (A-amylase/a-glucTrfase_C)
Type: Domain

Alpha-amylase is classified as family 13 (

) of the glycosyl hydrolases and is present in archaea, bacteria, fungi, plants and animals. Alpha-amylase is an essential enzyme in alpha-glucan metabolism, acting to catalyse the hydrolysis of alpha-1,4-glucosidic bonds of glycogen, starch and related polysaccharides. Although all alpha-amylases possess the same catalytic function, they can vary with respect to sequence. In general, they are composed of three domains: a TIM barrel containing the active site residues and chloride ion-binding site (domain A), a long loop region inserted between the third β-strand and the α-helix of domain A that contains calcium-binding site(s) (domain B), and a C-terminal β-sheet domain that appears to show some variability in sequence and length between amylases (domain C) . Amylases have at least one conserved calcium-binding site, as calcium is essential for the stability of the enzyme. The chloride-binding functions to activate the enzyme, which acts by a two-step mechanism involving a catalytic nucleophile base (usually an Asp) and a catalytic proton donor (usually a Glu) that are responsible for the formation of the beta-linked glycosyl-enzyme intermediate.

This entry represents a domain found in prokaryotic alpha-amylase (

) and 4-alpha-glucanotransferase (

). This domain adopts a β-sandwich fold, in which two layers of anti-parallel β-sheets are arranged in a nearly parallel fashion. The exact function of this domain is, as yet, unknown, however it has been proposed that it may play a role in transglycosylation reactions .
Bacteriophage T4, Gp27, baseplate hub, C-terminal (Phage_T4_Gp27_C)
Type: Domain

This domain adopts a β barrel structure with a Greek key topology, which is topologically similar to the FMN-binding split barrel. It is found at the C terminus of the Gp27 protein; a structural component of the viral baseplate .
Bacteriophage T4, Gp27, baseplate hub, N-terminal (Phage_T4_Gp27_N)
Type: Domain

This domain adopts a β barrel structure with a Greek key topology, which is topologically similar to the FMN-binding split barrel. It is found at the N terminus of the Gp27 protein; a structural component of the viral baseplate .
Quinohemoprotein amine dehydrogenase, alpha subunit, haem binding domain (QH-AmDH_asu_heme-bd_dom)
Type: Domain

Quinohemoprotein amine dehydrogenases (QHNDH)

) are enzymes produced in the periplasmic space of certain Gram-negative bacteria, such as Paracoccus denitrificans and Pseudomonas putida, in response to primary amines, including n-butylamine and benzylamine. QHNDH catalyses the oxidative deamination of a wide range of aliphatic and aromatic amines through formation of a Schiff-base intermediate involving one of the quinone O atoms . Catalysis requires the presence of a novel redox cofactor, cysteine tryptophylquinone (CTQ). CTQ is derived from the post-translational modification of specific residues, which involves the oxidation of the indole ring of a tryptophan residue to form tryptophylquinone, followed by covalent cross-linking with a cysteine residue . There is one CTQ per subunit in QHNDH. In addition to CTQ, two haem c cofactors are present in QHNDH that mediate the transfer of the substrate-derived electrons from CTQ to an external electron acceptor, cytochrome c-550 .

QHNDH is a heterotrimer of alpha, beta and gamma subunits. The alpha and beta subunits contain signal peptides necessary for the translocation of QHNDH to the periplasm. The alpha subunit is composed of four domains - domain 1 forming a dihaem cytochrome, and domains 2-4 forming antiparallel β-barrel structures; the beta subunit is a 7-bladed β-propeller that provides part of the active site; and the small, catalytic gamma subunit contains the novel cross-linked CTQ cofactor, in addition to additional thioester cross-links between Cys and Asp/Glu residues that encage CTQ. The gamma subunit assumes a globular secondary structure with two short α-helices having many turns and bends .

This entry represents the dihaem cytochrome c domain of the QHNDH alpha subunit. The domain contain two cysteine residues that are involved in thioether linkages to haem .
Quinohemoprotein amine dehydrogenase, alpha subunit domain III (QH-AmDH_asu_dom_III)
Type: Domain

Members of this family, which are predominantly found in the prokaryotic protein quinohemoprotein amine dehydrogenase, adopt an immunoglobulin-like β-sandwich fold, with seven strands arranged into two β sheets; the fold is possibly related to the immunoglobulin and/or fibronectin type III superfamilies. The precise function of this domain has not, as yet, been defined .