SII-SWORD/CoKE huggingface dataset:
Vibrio cholerae neuraminidase, lectin-like domain (VCNA_lectin-like_dom)
Type: Domain

These lectin-like domains is are found in Vibrio cholerae neuraminidase (VCNA). This enzyme plays a significant role in the pathogenesis of cholera by removing sialic acid from higher order gangliosides to unmask GM1, the receptor for cholera toxin. The domains flank a central β-propeller catalytic domain. They are thought to be involved in binding sialic acid, helping to target the enzyme to sialic acid-rich environments and thereby enhancing its catalytic efficiency .
Cytokinin dehydrogenase 1, FAD/cytokinin binding domain (Cytokinin_DH_FAD/cytokin-bd)
Type: Domain

This domain adopts an α+β sandwich structure with an antiparallel β-sheet, in a ferredoxin-like fold. It is predominantly found in plant cytokinin dehydrogenase 1, where it is capable of binding both FAD and cytokinin substrates. The substrate displays a 'plug-into-socket' binding mode that seals the catalytic site and precisely positions the carbon atom undergoing oxidation in close contact with the reactive locus of the flavin .
DNA topoisomerase I, N-terminal, viral (TopoI_N_vir)
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 I topoisomerases are ATP-independent enzymes (except for reverse gyrase), and can be subdivided according to their structure and reaction mechanisms: type IA (Topo IA; bacterial and archaeal topoisomerase I, topoisomerase III and reverse gyrase) and type IB (Topo IB; eukaryotic topoisomerase I and topoisomerase V). These enzymes are primarily responsible for relaxing positively and/or negatively supercoiled DNA, except for reverse gyrase, which can introduce positive supercoils into DNA. This function is vital for the processes of replication, transcription, and recombination. Unlike Topo IA enzymes, Topo IB enzymes do not require a single-stranded region of DNA or metal ions for their function. The type IB family of DNA topoisomerases includes eukaryotic nuclear topoisomerase I, topoisomerases of poxviruses, and bacterial versions of Topo IB . They belong to the superfamily of DNA breaking-rejoining enzymes, which share the same fold in their C-terminal catalytic domain and the overall reaction mechanism with tyrosine recombinases . The C-terminal catalytic domain in topoisomerases is linked to a divergent N-terminal domain that shows no sequence or structure similarity to the N-terminal domains of tyrosine recombinases .

This entry represents a domain predominantly found in viral DNA topoisomerase I, a type IB enzyme. This domain assumes a β(2)-α-β-α-β(2) fold, with a left-handed crossover between strands β2 and β3 .
Clathrin, heavy chain, linker, core motif (Clathrin_H-chain_linker_core)
Type: Domain

Proteins synthesized on the ribosome and processed in the endoplasmic reticulum are transported from the Golgi apparatus to the trans-Golgi network (TGN), and from there via small carrier vesicles to their final destination compartment. These vesicles have specific coat proteins (such as clathrin or coatomer) that are important for cargo selection and direction of transport . Clathrin coats contain both clathrin (acts as a scaffold) and adaptor complexes that link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. The two major types of clathrin adaptor complexes are the heterotetrameric adaptor protein (AP) complexes, and the monomeric GGA (Golgi-localising, Gamma-adaptin ear domain homology, ARF-binding proteins) adaptors .

Clathrin is a trimer composed of three heavy chains and three light chains, each monomer projecting outwards like a leg; this three-legged structure is known as a triskelion . The heavy chains form the legs, their N-terminal β-propeller regions extending outwards, while their C-terminal α-α-superhelical regions form the central hub of the triskelion. Peptide motifs can bind between the β-propeller blades. The light chains appear to have a regulatory role, and may help orient the assembly and disassembly of clathrin coats as they interact with hsc70 uncoating ATPase . Clathrin triskelia self-polymerise into a curved lattice by twisting individual legs together. The clathrin lattice forms around a vesicle as it buds from the TGN, plasma membrane or endosomes, acting to stabilise the vesicle and facilitate the budding process . The multiple blades created when the triskelia polymerise are involved in multiple protein interactions, enabling the recruitment of different cargo adaptors and membrane attachment proteins .

This entry represents the core motif for the α-helical zigzag linker region connecting the conserved N-terminal β-propeller region to the C-terminal α-α-superhelical region in clathrin heavy chains .
GTP-binding protein OBG, C-terminal (OCT_dom)
Type: Domain

Obg subfamily proteins (also known as ObgE, YhbZ and CgtA) are conserved P- loop GTPases, that are involved in a wide range of cellular processes, including sporulation, cellular differentiation, ribosome assembly, DNA replication, chromosome segregation, and stringent response in eubacteria and plant chloroplasts. Obg subfamily proteins have three domains: the Obg fold, the G domain, and the Obg C-terminal (OCT) domain. A potential role of the OCT domain in the regulation of the nucleotide-binding state has been suggested . The OCT domain structure contains a four-stranded β-sheet and three α-helices flanked by an additional β-strand .
Beta-trefoil DNA-binding domain (Beta-trefoil_DNA-bd_dom)
Type: Domain

This DNA-binding domain adopts a β-trefoil fold, that is, a capped β-barrel with internal pseudo threefold symmetry. In the DNA-binding protein LAG-1, it also is the site of mutually exclusive interactions with NotchIC (and the viral protein EBNA2) and corepressors (SMRT/N-Cor and CIR) .
RBP-J/Cbf11/Cbf12, DNA binding (RBP-J/Cbf11/Cbf12_DNA-bd)
Type: Domain

This domain is found in RBP-J from human and Cbf11/Cbf12 from fission yeast. These proteins function as transcription factors . This domain adopts a β sandwich structure, with nine strands in two β-sheets, in a Greek-key topology, and allow for DNA binding .
Hepsin, SRCR domain (Hepsin-SRCR_dom)
Type: Domain

This entry represents the extracellular domain of the serine protease hepsin. The domain is formed primarily by three elements of regular secondary structure: a 12-residue α helix, a twisted five-stranded antiparallel β sheet, and a second, two-stranded, antiparallel sheet. The two β-sheets lie at roughly right angles to each other, with the helix nestled between the two, adopting an SRCR fold. The exact function of this domain has not been identified, though it probably may serve to orient the protease domain or place it in the vicinity of its substrate .
Rubisco LSMT, substrate-binding domain (Rubisco_LSMT_subst-bd)
Type: Domain

This domain adopts a multihelical structure, with an irregular array of long and short α-helices. It allows binding of the protein to substrate, such as the N-terminal tails of histones H3 and H4 and the large subunit of the Rubisco holoenzyme complex .
DNA partition complex, ParG (DNA_partition_ParG)
Type: Family

This entry represents plasmid partition proteins; it adopts a ribbon-helix-helix fold, with a core of four α-helices. The proteins are an essential component of the DNA partition complex of the multi drug resistance plasmid TP228 .
Pertussis toxin, subunit S4 (Pertussis_toxin_subS4)
Type: Family

Members of this family of Bordetella pertussis toxins adopt a structure consisting of an OB fold, with a closed or partly opened β-barrel in a Greek-key topology .
Pertussis toxin, subunit S5 (Pertussis_toxin_subS5)
Type: Family

Members of this family of Bordetella pertussis toxins adopt a structure consisting of an OB fold, with a closed or partly opened β-barrel in a Greek-key topology .
Erythronolide synthase EryA2, docking domain (EryA2_docking)
Type: Domain

This domain is found at the C-terminal end of Erythronolide synthase EryA2 from Saccharopolyspora erythraea and similar sequences from actinomycetes. EryA2 is involved in the biosynthesis of antibiotic erythromycin via the biosynthesis of its aglycone precursor, 6-deoxyerythronolide B (6-dEB) .

Docking domains are found in prokaryotic erythronolide synthase. They adopt a structure consisting of a bundle of four α-helices, and mediate homodimerisation of the protein, stabilising the resulting complex .
Transcription regulator MerR, DNA binding (Tscrpt_reg_MerR_DNA-bd)
Type: Domain

This entry represents a DNA-binding domain of the transcriptional regulator MerR and similar sequences predominantly found in bacteria. It adopts a structure consisting of a core of three α-helices, with an architecture that is similar to that of the 'winged helix' fold .
Phosphoinositide-specific phospholipase C, EF-hand-like domain (PLC_EF-hand-like)
Type: Domain

This domain is predominantly found in the enzyme phosphoinositol-specific phospholipase C. It adopts a structure consisting of a core of four α-helices, in an EF like fold, and is required for functioning of the enzyme .
XPC-binding domain (XPC-bd)
Type: Domain

This domain adopts a structure consisting of four α-helices, arranged in an array. It binds specifically and directly to the xeroderma pigmentosum group C protein (XPC) to initiate nucleotide excision repair .
Taq polymerase, thermostable, exonuclease region (Taq_pol_thermo_exonuc)
Type: Domain

This domain is found in prokaryotic Taq DNA polymerase (thermostable), where it assumes a ribonuclease H-like motif. The domain confers 5'-3' exonuclease activity to the polymerase .
WIBG, Mago-binding (WIBG_mago-bd)
Type: Domain

Partner of Y14 and mago (PYM, also known as WIBG) is a key regulator of the exon junction complex (EJC), a multiprotein complex that associates immediately upstream of the exon-exon junction on mRNAs and serves as a positional landmarks for the intron exon structure of genes and directs post-transcriptional processes in the cytoplasm such as mRNA export, nonsense-mediated mRNA decay (NMD) or translation .

The N-terminal domain of PYM adopts a small globular all-β-domain structure, with a three-stranded β-sheet and a contiguous β-hairpin. It binds to both Mago and Y14 .
Rhamnogalacturonase B, N-terminal (RhgB_N)
Type: Domain

This domain is found in prokaryotic enzyme rhamnogalacturonase B, it adopts a structure consisting of a β-supersandwich, with eighteen strands in two β-sheets. The exact function of the domain is unknown, but a putative role includes carbohydrate-binding .
Elongation factor P, C-terminal (Elong-fact-P_C)
Type: Domain

Elongation factor P (EF-P) stimulates the peptidyltransferase activity in the prokaryotic 70S ribosome. EF-P enhances the synthesis of certain dipeptides with N-formylmethionyl-tRNA and puromycine in vitro. EF-P binds to both the 30S and 50S ribosomal subunits. EF-P binds near the streptomycine binding site of the 16S rRNA in the 30S subunit. EF-P interacts with domains 2 and 5 of the 23S rRNA. The L16 ribosomal protein of the 50S or its N-terminal fragment are required for EF-P mediated peptide bond synthesis, whereas L11, L15, and L7/L12 are not required in this reaction, suggesting that EF-P may function at a different ribosomal site than most other translation factors. EF-P is essential for cell viability and is required for protein synthesis . EF-P is mainly present in bacteria. The EF-P homologs in archaea and eukaryotes are the initiation factors aIF5A and eIF5A, respectively. EF-P has 3 domains (domains I, II, and III). Domains II and III are S1-like domains. This entry includes domain III (the second S1 domain of EF_P). Domains II and III of have structural homology to the eIF5A domain C, suggesting that domains II and III evolved by duplication. These domains adopt an OB-fold, with five β-strands forming a β-barrel in a Greek-key topology .
Peptidase S53, activation domain (S53_propep)
Type: Domain

This domain is found at the N terminus of peptidases belonging to MEROPS peptidase family S53 (sedolisin, clan SB). The domain adopts a ferredoxin-like fold, with an α+β sandwich. Cleavage of the domain results in activation of the peptidase .
Transcription factor CEP-1, DNA-binding domain (Trans_fact_CEP1_DNA-bd)
Type: Domain

This DNA-binding domain is found in the Caenorhabditis transcription factor CEP-1, which is related to human p53. It adopts a β sandwich structure, with nine strands in two β-sheets, in a Greek-key topology .
Ubiquitin-conjugating enzyme, C-terminal fungi (UBA_C_fun)
Type: Domain

This C-terminal domain is found in ubiquitin binding proteins, it adopts a structure consisting of a three α-helix bundle. This domain is predominantly found in fungi .
Follistatin/Osteonectin EGF domain (Follistatin/Osteonectin_EGF)
Type: Domain

This domain is predominantly found in osteonectin and follistatin. They adopt an EGF-like structure . Follistatin is involved in diverse activities from embryonic development to cell secretion.
T-cell receptor alpha chain, constant domain (TCR_alpha_C)
Type: Domain

This entry represents the constant domain of the alpha chain of alpha/beta T-cell antigen receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are composed of alpha and beta, or gamma and delta, polypeptide chains with variable (V) and constant (C) regions. alpha/beta TCRs recognise antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. The antigen binding site is formed by the variable domains of the alpha and beta chains, located at the N terminus of each chain . alpha/beta TCRs recognise antigens differently from gamma/delta TCRs.
Endonuclease VIII-like 1, DNA binding (Endonuclease-VIII_DNA-bd)
Type: Domain

This domain is predominantly found in Endonuclease VIII-like 1 proteins and adopts a glucocorticoid receptor-like fold. Structural analysis reveals a zincless finger motif that is required for glycosylase activity .
Interferon/interleukin receptor domain (Interferon/interleukin_rcp_dom)
Type: Domain

Proteins with this domains have a secondary structure consisting of seven β-strands arranged in an immunoglobulin-like β-sandwich, in a Greek-key topology. They include interferon receptors, tissue factor proteins and interleukin receptors.
Chs5p-Arf1p binding (ChAPs)
Type: Family

ChAPs (Chs5p-Arf1p-binding proteins) are required for the export of specialised cargo from the Golgi. They physically interact with Chs3, Chs5 and the small GTPase Arf1, and they also form interactions with each other .
NADH pyrophosphatase-like, N-terminal (NADH_PPase-like_N)
Type: Domain

This entry represents the N-terminal domain found in NADH pyrophosphatase, which has a rudiment Nudix fold according to SCOP. This domain is also found in Nudix hydrolases, such as NudC, which has been shown to act as a NAD decapping enzyme .
Zinc ribbon, NADH pyrophosphatase (Znr_NADH_PPase)
Type: Domain

This domain has a zinc ribbon structure and is found in proteins such as NAD-capped RNA hydrolases and NAD(P)H pyrophosphatases. It is often found between two NUDIX domains.
Fumarylacetoacetase, N-terminal (Fumarylacetoacetase_N)
Type: Domain

Fumarylacetoacetase (

; also known as fumarylacetoacetate hydrolase or FAH) catalyses the hydrolytic cleavage of a carbon-carbon bond in fumarylacetoacetate to yield fumarate and acetoacetate as the final step in phenylalanine and tyrosine degradation . This is an essential metabolic function in humans, the lack of FAH causing type I tyrosinaemia, which is associated with liver and kidney abnormalities and neurological disorders . The enzyme mechanism involves a catalytic metal ion, a Glu/His catalytic dyad, and a charged oxyanion hole . FAH folds into two domains: an N-terminal domain SH3-like β-barrel, and a C-terminal with an unusual fold consisting of three layers of β-sheet structures .

This entry represents the N-terminal domain of fumarylacetoacetase. This domain adopts a structure consisting of an SH3-like barrel .
Transposase-like, Mu, C-terminal (Transposase-like_Mu_C)
Type: Domain

This domain is found in various prokaryotic integrases and transposases. It adopts a β-barrel structure with Greek-key topology .
Tectiviridae, minor capsid (Tecti-min-caps)
Type: Family

Members of this family form the minor capsid protein of various Tectiviridae .
XLF-like, N-terminal (XLF-like_N)
Type: Domain

This entry represents the N-terminal domain of human Non-homologous end-joining factor 1 (NHEJ1 or XLF), Xrcc4-like factor 1 from Schizosaccharomyces pombe (Xlf1) and similar sequences from fungi and animals.

XLF (also called Cernunnos) is involved in DNA nonhomologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination. XLF and XRCC4 form long helical protein filaments suitable for DNA end protection and alignment to facilitate DNA double strand break repair . It directly interacts with the XRCC4-Ligase IV complex and siRNA-mediated downregulation of XLF in human cell lines leads to radio-sensitivity and impaired DNA non-homologous end-joining . XLF is the human orthologue of fission yeast Xrcc4-like factor 1 .
KCNMB2, ball/chain domain (KCNMB2_ball_chain_dom)
Type: Domain

This domain is found in the cytoplasmic N terminus of KCNMB2, the beta-2 subunit of large conductance calcium and voltage-activated potassium channels. It is responsible for the fast inactivation of these channels .
Cortexillin, coiled coil (Cortexillin-I_CC)
Type: Domain

This domain is predominantly found in the actin-bundling protein cortexillin I and II from Dictyostelium discoideum (Slime mold). The domain has a structure consisting of an 18-heptad-repeat α-helical coiled-coil, and is a prerequisite for the assembly of Cortexillin I .
TACI, cysteine-rich domain (TACI_Cys-rich-dom)
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.

This entry represents a cysteine-rich domain found in the TACI family of proteins. Members of this family are predominantly found in tumour necrosis factor receptor superfamily, member 13b (TACI), and are required for binding to the ligands APRIL and BAFF .
Bacteriophage P22, Gp8, scaffold (Phage_P22_Gp8_scaffold)
Type: Family

Members of this family of scaffolding proteins are produced by various bacteriophages .
MHC class II-associated invariant chain/CLIP, MHC II-interacting (MHC_II-assoc_invar/CLIP_MHC-bd)
Type: Domain

This domain is found in MHC class II-associated invariant chain (Ii), and in class II invariant chain-associated peptide (CLIP), and is required for association with class II major histocompatibility complex (MHC II) in the MHC II processing pathway . Ii plays a critical role in the assembly of the MHC, as well as in MHC II antigen processing by stabilising peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex from the endoplasmic reticulum to compartments where peptide loading of class II takes place . In antigen-presenting cells (APCs), loading of MHC II molecules with peptides is regulated by Ii, which blocks MHC II antigen-binding sites in pre-endosomal compartments . Several factors modulate the surface expression of MHC II molecules via post-Golgi mechanisms, including CLIP.

The Invariant chain contains a single transmembrane domain. Ii first assembles into a trimer and then associates with three class II alpha/beta MHC heterodimers. Although the membrane-proximal region of the Ii luminal domain is structurally disordered, the C-terminal segment of the luminal domain is largely α-helical and contains a major interaction site for the Ii trimer .
LuxQ, periplasmic domain (LuxQ-periplasm_dom)
Type: Domain

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 entry represents the periplasmic sensor domain of the prokaryotic protein LuxQ, that assumes a structure consisting of two tandem Per/ARNT/Simple-minded (PAS) folds .
FCP1-like phosphatase, C-terminal (FCP1_C)
Type: Domain

The C-terminal domain of FCP-1 is required for interaction with the carboxy terminal domain of RAP74. Interaction relies extensively on van der Waals contacts between hydrophobic residues situated within α-helices in both domains .
POU, class 2, associating factor 1 (PD-C2-AF1)
Type: Family

Members of this family are transcriptional co-activators that specifically associate with either OCT1 or OCT2, through recognition of their POU domains. They are essential for the response of B-cells to antigens and required for the formation of germinal centres .
Rabaptin, GTPase-Rab5 binding domain (Rabaptin_Rab5-bd_dom)
Type: Domain

This domain is predominantly found in Rabaptin and allows for binding to the GTPase Rab5. This interaction is necessary and sufficient for Rab5-dependent recruitment of Rabaptin5 to early endosomal membranes .
SurA N-terminal (SurA_N)
Type: Domain

The correct folding of outer membrane proteins (OMPs) in Gram-negative bacteria is facilitated by the survival protein SurA . This entry represents the helical domain found at the N-terminal of the chaperone SurA that, together with the C-terminal, forms a core domain which contains OMP binding sites. OMP binding induces conformational changes of SurA domains that protect OMPs from misfolding and aggregation . The C-terminal of the SurA protein folds back and forms part of this domain also but is not included in the current alignment.
Domain of unknown function DUF1971 (DUF1971)
Type: Domain

This uncharacterised domain is predominantly found in bacterial Tellurite resistance proteins.
Domain of unknown function DUF1972 (DUF1972)
Type: Domain

This domain is functionally uncharacterised and found in bacterial glycosyltransferases and rhamnosyltransferases.
C-myb, C-terminal (C-myb_C)
Type: Domain

This entry represents the C-terminal domain of the proto-oncogene c-myb and the viral transforming protein myb. Truncation of the domain results in 'activation' of c-myb and subsequent tumourigenesis .
Acyl-CoA dehydrogenase, C-terminal, bacterial-type (FadE_C)
Type: Domain

This entry represents a domain found at the C-terminal end of Acyl-coenzyme A dehydrogenase from Escherichia coli (FadE) and similar proteins mainly found in bacteria. FadE catalyses the dehydrogenation of acyl-coenzymes A (acyl-CoAs) to 2-enoyl-CoAs, the first step of the beta-oxidation cycle of fatty acid degradation. This domain seems to be essential for its function .