SII-SWORD/CoKE huggingface dataset:
Zinc finger, GAGA-binding factor (Znf_GAGA-bd_fac)
Type: Domain

Members of this entry bind to a 5'-GAGAG-3' DNA consensus binding site, and contain a Cys2-His2 zinc finger core as well as an N-terminal extension containing two highly basic regions. The zinc finger core binds in the DNA major groove and recognises the first three GAG bases of the consensus in a manner similar to that seen in other classical zinc finger-DNA complexes. The second basic region forms a helix that interacts in the major groove recognising the last G of the consensus, while the first basic region wraps around the DNA in the minor groove and recognises the A in the fourth position of the consensus sequence .

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.
Interleukin-4 receptor alpha, N-terminal (IL-4_rcpt-alpha_N)
Type: Domain

Interleukin-4 receptor is a type I transmembrane protein that can bind interleukin 4 and interleukin 13 to regulate IgE antibody production in B cells. Among T cells, the encoded protein also can bind interleukin 4 to promote differentiation of Th2 cells. A soluble form of the encoded protein can be produced by an alternate splice variant or by proteolysis of the membrane-bound protein, and this soluble form can inhibit IL4-mediated cell proliferation and IL5 upregulation by T-cells. Allelic variations in this gene have been associated with atopy, a condition that can manifest itself as allergic rhinitis, sinusitis, asthma, or eczema. The binding of IL-4 or IL-13 to the IL-4 receptor on the surface of macrophages results in the alternative activation of those macrophages. Alternatively activated macrophages downregulate inflammatory mediators such as during immune responses, particularly with regards to helminth infections.

This entry represents the N-terminal (extracellular) portion of interleukin-4 receptor alpha, it is related in overall topology to fibronectin type III modules and folds into a sandwich comprising seven antiparallel β sheets arranged in a three-strand and a four-strand β-pleated sheet. They are required for binding of interleukin-4 to the receptor alpha chain, which is a crucial event for the generation of a Th2-dominated early immune response .
DNA topoisomerase VI, subunit B, transducer (TopoVI_B_transducer)
Type: Domain

DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single-or double-strand breaks, crossing the strands through one another, then resealing the breaks . These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis . DNA topoisomerases are divided into two classes: type I enzymes (

; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (

; topoisomerases II, IV and VI) break double-strand DNA .

Type II topoisomerases are ATP-dependent enzymes, and can be subdivided according to their structure and reaction mechanisms: type IIA (topoisomerase II or gyrase, and topoisomerase IV) and type IIB (topoisomerase VI). These enzymes are responsible for relaxing supercoiled DNA as well as for introducing both negative and positive supercoils .

This entry represents subunit B of topoisomerase VI, an ATP-dependent type IIB enzyme. Members of this family adopt a structure consisting of a four-stranded β-sheet backed by three α-helices, the last of which is over 50 amino acids long and extends from the body of the protein by several turns. This domain has been proposed to mediate intersubunit communication by structurally transducing signals from the ATP binding and hydrolysis domains to the DNA binding and cleavage domains of the gyrase holoenzyme .
Type I cytokine receptor, cytokine-binding domain (TypeI_recpt_CBD)
Type: Domain

The alpha chain of the interleukin-6 receptor (IL-6R-alpha) consists of a signal peptide, an extracellular region, a transmembrane domain, and a short cytoplasmic domain. The extracellular region is highly modular, consisting of three domains (D1, D2, and D3). The N-terminal domain D1 is characteristic of the Ig superfamily, and domains D2 and D3 are homologous to cytokine-binding domains (CBD) consisting of two fibronectin type III (FnIII) domains .

This domain corresponds to the D2 domain in IL-6R-alpha and is also found in other members of the type I cytokine receptor family.
Cyclin domain, herpesvirus (Cyclin_dom_herpesvir)
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 entry represents a domain found in a family of viral cyclins that specifically activate CDK6 of host cells to a very high degree . This domain adopts a helical structure consisting of five α-helices, with one helix surrounded by the others.
Flavocytochrome c sulphide dehydrogenase, flavin-binding (FlavoCytC_S_DH_flav-bd)
Type: Domain

This entry represents the flavin-binding domain of flavocytochrome c sulphide dehydrogenase (FCSD), enzymes found in sulphur-oxidising bacteria such as the purple phototrophic bacteria Chromatium vinosum . These enzymes are complexes of flavoprotein and a dihaem cytochrome that carry out hydrogen sulphide-dependent cytochrome C reduction. The dihaem cytochrome folds into two domains, each of which resembles mitochondrial cytochrome c, with the two haem groups bound to the interior of the subunit. The flavoprotein subunit has a glutathione reductase-like fold consisting of a beta(3,4)-α(3) core, and an α+β sandwich. The active site of the flavoprotein subunit contains a catalytically important disulphide bridge located above the pyrimidine portion of the flavin ring . Electrons are transferred from the flavin to one of the haem groups in the cytochrome. This entry represents a flavoprotein domain required for binding to flavin, and subsequent electron transfer.
Ribosomal protein Rsm22-like (Ribosomal_Rsm22-like)
Type: Family

Rsm22 is a mitochondrial ribosome (mitoribosome) assembly factor . It retains the characteristic folding and ability to bind S-adenosyl-L-methionine, but it probably lost its methyltransferase activity . In Schizosaccharomyces pombe (Fission yeast), Rsm22 is tandemly fused to Cox11 (a factor required for copper insertion into cytochrome oxidase) and the two proteins are proteolytically cleaved after import into the mitochondria . Rsm22 is also known as Ribosome assembly protein METTL17 in mammals. This entry consists of mitochondrial Rsm22 and homologous sequences from eukaryotes and bacteria.

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Sucrose phosphorylase, C-terminal (Suc_Porlyase_C)
Type: Domain

This domain is C-terminal to the catalytic sucrose phosphorylase β/α barrel domain. It adopts a β-sandwich fold, with Greek-key topology and is functionally uncharacterised .
Mycoplasma arthritidis-derived mitogen (M_arthritidis-der_mitogen)
Type: Family

Mycoplasma arthritidis-derived mitogen (MA-Mit) adopts a completely α-helical structure consisting of ten α-helices arranged in two orthogonal bundles. MA-Mit is a superantigen that can activate large fractions of T cells bearing particular TCR V-beta elements. Two MA-Mit molecules form an asymmetric dimer and cross-link two MHC antigens to form a dimerised MA-Mit-MHC complex .
Smaug, PHAT analogous topology (PHAT_dom)
Type: Domain

The PHAT (pseudo-HEAT analogous topology) domain assumes a structure consisting of a layer of three parallel helices packed against a layer of two antiparallel helices, into a cylindrical shaped five-helix bundle. It is found in the RNA-binding protein Smaug, where it is essential for high-affinity RNA binding . Smaug is a translation regulator that binds to the 3'-UTR of specific mRNAs such as nanos (nos) and prevents their translation .
Domain of unknown function DUF1965 (DUF1965)
Type: Domain

Members of this family of fungal domains adopt a structure that consists of an α/β motif. Their exact function has not, as yet, been determined .
tRNA nucleotidyltransferase, substrate binding (tRNA_NucTransf2)
Type: Domain

This domain adopts a structure consisting of a five helical bundle core. It is predominantly found in Archaeal tRNA nucleotidyltransferases, following the catalytic nucleotidyltransferase domain .
DNA primase/polymerase, bifunctional, N-terminal (DNA_primase/pol_bifunc_N)
Type: Domain

Members of this family adopt a structure consisting of a core of antiparallel β sheets. They are found in various bacterial hypothetical proteins, and have been shown to harbour both primase and polymerase activities .
P22 tailspike C-terminal domain (P22_tailspike_C)
Type: Domain

The tailspike protein of Salmonella bacteriophage P22 is a viral adhesion protein that mediates attachment of the viral protein to host cell-surface lipopolysaccharide. The tailspike protein displays both receptor binding and destroying properties, inactivating the receptor by endoglycosidase activity. P22 tailspike is a homotrimer composed of 666 amino acid polypeptide chains. P22 tailspike consists of three main structural elements: the head-binding domain at the N terminus, the β-helix in the centre of the protein, and the β-prism and caudal fin at the C terminus . The P22 tailspike protein contains similar structural elements to pectin lyase . The binding of the disaccharide product occurs within a positively charged cleft formed by loops extending from the surface of the β-helix structure. Amino acid residues responsible for recognition of the disaccharide, as well as potential catalytic residues, have been identified .

This entry represents the C-terminal domain of the tailspike protein.
Major allergen I polypeptide chain 2-like (CH2-like)
Type: Family

This entry includes major allergen I polypeptide chain 2 (Fel d 1 chain 2) from cat and related proteins, such as SCGB2B from mice.

Allergies are hypersensitivity reactions of the immune system to specific substances called allergens (such as pollen, stings, drugs, or food) that, in most people, result in no symptoms. A nomenclature system has been established for antigens (allergens) that cause IgE-mediated atopic allergies in humans. The nomenclature system uses the first three letters of the genus, followed by the first letter of the species name, followed by a number (additional letters can be added to the name as required to discriminate between similar designations).

Fel d 1 is allergen 1 from Felis silvestris catus (Cat), which is an important agent in human allergic reactions . The protein is expressed in saliva and sebaceous glands. The complete primary structure of Fel d 1 has been determined . The allergen is tetrameric glycoprotein consisting of two disulphide-linked heterodimers of chains 1 and 2, which have been shown to be encoded by different genes. Fel d 1 chains 1 and 2 share structural similarity with uteroglobin, a secretoglobin superfamily member; chain 2 is a glycoprotein with N-linked oligosaccharides.

SCGB2B is an androgen-binding protein that plays a role in mate selection in mice .
Pollen allergen ole e 6 (Pollen_allergen_ole-e-6)
Type: Family

This entry represents pollen allergens, such as ole-e-6, a small acidic protein from Olea europaea (Common olive) which mediates olive allergy. Members of this family have an α-helical hairpin structure cross-linked by three disulphides, followed by a long, unstructured C-terminal tail .
FokI, cleavage domain (FokI_cleavage_dom)
Type: Domain

Type IIS restriction endonuclease FokI (

) is a member of an unusual class of bipartite restriction enzymes that recognises the double-stranded DNA sequence 5'-GGATG-3' and cleave DNA phosphodiester groups 9 base pairs away on this strand and 13 base pairs away on the complementary strand . FokI contains amino- and carboxy-terminal domains corresponding to the DNA-recognition and cleavage functions, respectively.

The recognition domain is made of three smaller subdomains (D1, D2 and D3) which are evolutionarily related to the helix-turn-helix-containing DNA-binding domain of the catabolite gene activator protein CAP .

This entry represents the C-terminal cleavage domain of FokI, which adopts a structure consisting of an α/β/α core containing a five-stranded β-sheet .
F1 capsule antigen (Caf1)
Type: Family

Members of this family represent the F1 capsule antigen Caf1 synthesised by the Yersinia pestis bacteria. They adopt a structure consisting of a seven strands arranged in two β-sheets, in a Greek-key topology, and mediate targeting of the bacterium to sites of infection .
Tumour necrosis factor receptor 13C, TALL-1 binding domain (TNFR_13C_TALL-1-bd)
Type: Domain

Cytokines can be grouped into a family on the basis of sequence, functional and structural similarities . Tumor necrosis factor (TNF) (also known as TNF-alpha or cachectin) is a monocyte-derived cytotoxin that has been implicated in tumour regression, septic shock and cachexia . The protein is synthesised as a prohormone with an unusually long and atypical signal sequence, which is absent from the mature secreted cytokine . A short hydrophobic stretch of amino acids serves to anchor the prohormone in lipid bilayers . Both the mature protein and a partially-processed form of the hormone are secreted after cleavage of the propeptide .

There are a number of different families of TNF, but all these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognised by their specific receptors.

The domain represented by this entry is predominantly found in the tumour necrosis factor receptor superfamily member 13c, BAFF-R and is required for binding to tumour necrosis factor ligand TALL-1 .
BCMA, TALL-1 binding (BCMA_Tall-1-bd)
Type: Domain

Cytokines can be grouped into a family on the basis of sequence, functional and structural similarities . Tumor necrosis factor (TNF) (also known as TNF-alpha or cachectin) is a monocyte-derived cytotoxin that has been implicated in tumour regression, septic shock and cachexia . The protein is synthesised as a prohormone with an unusually long and atypical signal sequence, which is absent from the mature secreted cytokine . A short hydrophobic stretch of amino acids serves to anchor the prohormone in lipid bilayers . Both the mature protein and a partially-processed form of the hormone are secreted after cleavage of the propeptide .

There are a number of different families of TNF, but all these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognised by their specific receptors.

Members of this entry, which are predominantly found in the tumour necrosis factor receptor superfamily member 17, BCMA, are required for binding to tumour necrosis factor ligand TALL-1 .
Glycosyl transferase 64 domain (GT64_dom)
Type: Domain

Members of this family catalyse the transfer reaction of N-acetylglucosamine and N-acetylgalactosamine from the respective UDP-sugars to the non-reducing end of [glucuronic acid]beta 1-3[galactose]beta 1-O-naphthalenemethanol, an acceptor substrate analog of the natural common linker of various glycosylaminoglycans. They are also required for the biosynthesis of heparan-sulphate .
Immunomodulatory protein FIP-Fve, fungal (Immunomodulatory_FIP-Fve_fun)
Type: Family

FIP-Fve (Fungal Immunomodulatory Protein Fve) is a major fruiting body protein from Flammulina velutipes, a mushroom possessing immunomodulatory activity . It stimulates lymphocyte mitogenesis, suppresses systemic anaphylaxis reactions and oedema, enhances transcription of IL-2, IFN-gamma and TNF-alpha, and haemagglutinates red blood cells. It appears to be a lectin with specificity for complex cell-surface carbohydrates. Fve adopts a tertiary structure consisting of an immunoglobulin-like β-sandwich, with seven strands arranged in two β sheets, in a Greek-key topology. It forms a non-covalently linked homodimer containing no Cys, His or Met residues; dimerisation occurs by 3-D domain swapping of the N-terminal helices and is stabilised predominantly by hydrophobic interactions .
Alpha-amylase, domain C (A_amylase_C_dom)
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 domain is found at the C-terminal of various fungal alpha-amylase proteins. It has been identified as a secondary binding site, which might be part of a starch interaction site . It has a β-sandwich fold comprising an antiparallel β-sheet with eight strands.
Glycoside hydrolase family 38, central domain (Glyco_hydro_38_cen)
Type: Domain

This entry represents a domain found in members of the glycosyl hydrolases families 38. This domain is found in the central region that adopts a structure consisting of three α helices, in an immunoglobulin/albumin-binding domain-like fold. The domain is predominantly found in the enzyme alpha-mannosidase .

Glycoside hydrolase family 38

comprises enzymes with only one known activity; alpha-mannosidase (

) (

).

Lysosomal alpha-mannosidase is necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover. The enzyme catalyses the hydrolysis of terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides, and can cleave all known types of alpha-mannosidic linkages. Defects in the gene cause lysosomal alpha-mannosidosis (AM), a lysosomal storage disease characterised by the accumulation of unbranched oligo-saccharide chains.
Peroxisomal ATPase PEX1, N-terminal C-lobe (PEX1-N_C-lobe)
Type: Domain

The N-terminal domain of PEX1 adopts a double ψ β-barrel fold, similar in structure to the Cdc48 N-terminal domain. It has been suggested that this domain may be involved in interactions with ubiquitin, ubiquitin-like protein modifiers, or ubiquitin-like domains, such as Ubx. Furthermore, the domain may possess a putative adaptor or substrate binding site, allowing for peroxisomal biogenesis, membrane fusion and protein translocation . This domain can be subdivided in N- and C-lobes. This entry represents the C-lobe.
Peroxisomal ATPase PEX1, N-terminal N-lobe (PEX1-N-lobe)
Type: Domain

The N-terminal domain of PEX1 adopts a Cdc48 domain 2-like fold, with a β-α-β(3) arrangement. It has been suggested that this domain may be involved in interactions with ubiquitin, ubiquitin-like protein modifiers, or ubiquitin-like domains, such as Ubx. Furthermore, the domain may possess a putative adaptor or substrate binding site, allowing for peroxisomal biogenesis, membrane fusion and protein translocation . This domain can be subdivided in an N-lobe, represented in this entry, and a C-lobe .