SII-SWORD/CoKE huggingface dataset:
STAT, EF-hand fold domain (EF-hand_12)
Type: Domain

This domain is found in Dd-STATa, a STAT protein (signal transducer and activator of transcription A) which transcriptionally regulates cellular differentiation in Dictyostelium discoideum. The EF-hand domains are predicted to contain several basic residues that lie close to the DNA backbone .
3'-5' exonuclease C-terminal domain (Exo_C)
Type: Domain

This domain is found just after the C-terminal region of the HRDC domain (

) in 3'-5' exonuclease proteins. The domain is carried by species such as Streptomyces griseoaurantiacus and Streptomyces albulus.
Hydrogen maturase F dimerization domain (HydF_dimer)
Type: Domain

This domain is found in Hydrogen maturase F (HydF) present in Thermotoga neapolitana. HydF is a GTPase, containing an FeS cluster-binding motif, that is able to are able to activate HydA produced so that HydA can drive the reversible reduction of protons to molecular H2. This domain, referred to as domain II, is responsible for HydF dimerization through the formation of a continuous β-sheet comprising eight β-strands from two monomers .
HU domain fused to wHTH, Ig, or Glycine-rich motif (HU-HIG)
Type: Domain

This entry represents the HU domains predominantly observed in the bacteroidetes lineage with a predicted role in recognition and possible interception of the DNA of parasitic elements, a counter-conflict strategy preventing incorporation of these elements into the host genome .
Embryo surrounding factor 1, brassicaceae (ESF1_brassicaceae)
Type: Domain

This entry represents a domain found in ESF1 (Embryo surrounding factor 1), a protein found in Arabidopsis thaliana and other brassicaceae. Maternally contributed central cell ESF1 peptides play an important role in suspensor formation and pro-embryo development. The biological activity of ESF1 depends on structural topology, which is stabilized by disulfide bonds .
Phosphoribosylformylglycinamidine synthase, linker domain (PurL_linker)
Type: Domain

This is the linker domain found in Formylglycinamide ribonucleotide amidotransferase (FGAR-AT), also known as Phosphoribosylformylglycinamidine synthase (

), PurL and formylglycinamidine ribonucleotide (FGAM) synthase. This enzyme catalyzes the ATP-dependent conversion of formylglycinamide ribonucleotide (FGAR) and glutamine to formylglycinamidine ribonucleotide (FGAM), ADP, Pi, and glutamate in the fourth step of the purine biosynthetic pathway. The structure analysis of Salmonella typhimurium FGAR-AT reveals that this linker domain is made up of a long hydrophilic belt with an extended conformation .
ArlS, sensor domain (ArlS_N)
Type: Domain

This entry represents the N-terminal extracellular sensor domain of the ArlS protein from S. aureus. ArlS is a member of the two-component regulatory system ArlS/ArlR involved in the regulation of adhesion, autolysis, multidrug resistance and virulence . It recognises LL-37 antimicrobial peptide (Matilla et. al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).
SKICH domain (SKICH)
Type: Domain

The SKICH domains of SKIP and PIPP mediate plasma membrane localisation . The functions of the SKICH domains of NDP52 and CALCOCO1 are not known.
YfiR, C-terminal (YfiR_C)
Type: Domain

This entry represents the C-terminal domain present in Yfir transcription regulator proteins found in Bacillus subtilis . TetR regulates the expression of the membrane-associated tetracycline resistance protein, TetA, which exports the tetracycline antibiotic out of the cell before it can attach to the ribosomes and inhibit protein synthesis . TetR blocks transcription from the genes encoding both TetA and TetR in the absence of antibiotic. The C-terminal domain is multi-helical and is interlocked in the homodimer with the helix-turn-helix (HTH) DNA-binding domain .

TetR family regulators are involved in the transcriptional control of multidrug efflux pumps, pathways for the biosynthesis of antibiotics, response to osmotic stress and toxic chemicals, control of catabolic pathways, differentiation processes, and pathogenicity . The TetR proteins identified in multiple genera of bacteria and archaea share a common helix-turn-helix (HTH) structure in their DNA-binding domain. However, TetR proteins can work in different ways: they can bind a target operator directly to exert their effect (e.g. TetR binds Tet(A) gene to repress it in the absence of tetracycline), or they can be involved in complex regulatory cascades in which the TetR protein can either be modulated by another regulator or TetR can trigger the cellular response .
Peptidase S41, N-terminal (Pept_S41_N)
Type: Domain

This domain is found in the N-terminal region of proteins carrying the peptidase S41 domain in Bacteroidetes.
DprA, winged helix domain (DprA_WH)
Type: Domain

This winged helix domain is found in the DprA protein .

DprA is a new member of the recombination-mediator protein family, dedicated to natural bacterial transformation . In Helicobacter pylori, DprA is required for natural chromosomal and plasmid transformation . It has now been shown that DprA binds cooperatively to single-stranded DNA (ssDNA) and interacts with RecA. In the process, DprA-RecA-ssDNA filaments are produced and these filaments catalyse the homology-dependent formation of joint molecules. While the Escherichia coli SSB protein limits access of RecA to ssDNA, DprA alleviates this barrier . DprA has a role not only in ensuring production of transformants via interaction with RecA, it is also involved in competence shut-off via interaction with ComE .
Desmoplakin, SH3 domain (Desmoplakin_SH3)
Type: Domain

This entry represents the SH3 domain found in Desmoplakin and related proteins .

Desmoplakin (DP) is an integral part of desmosomes, where it links desmosomal cadherins to the intermediate filaments. The N-terminal region of DP contains a plakin domain common to members of the plakin family. Plakin domains contain multiple copies of spectrin repeats (SRs). Spectrin repeats (SRs) consist of three α-helices (A, B, and C) that form an antiparallel triple-helical bundle .
Phenylalanyl tRNA synthetase beta chain, core domain (PheRS_beta_core)
Type: Domain

This entry represents the core domain found in the beta chain of phe tRNA synthetase .

Phenylalanyl-tRNA synthetase (PheRS) belongs to class II aminoacyl-tRNA synthetases (aaRS) based upon its structure. While class II aaRSs generally aminoacylate the 3'-OH ribose of the appropriate tRNA, PheRS is an exception in that it attaches the amino acid at the 2'-OH group, like class I aaRSs. PheRS is an alpha-2/beta-2 tetramer. While the alpha chain contains a catalytic core domain, the beta chain has a non-catalytic core domain .
MalT-like TPR region (TPR_MalT)
Type: Domain

This entry contains a series of TPR repeats found in HTH-type transcriptional regulator MalT and related proteins .
Polyketide synthase dimerisation element domain (PKS_DE)
Type: Domain

This is the dimerisation element domain found in bacterial modular polyketide synthase ketoreductases . The dimerization element (DE) domain is located N-terminal to the ketoreductase (KR) domain (

). The DE domain is necessary for KR function, presumably because the dimeric DE orients the KR domains for optimal activity within a module .
Nicotinate phosphoribosyltransferase C-terminal domain (NAPRTase_C)
Type: Domain

Nicotinate phosphoribosyltransferase (

) is the rate limiting enzyme that catalyses the first reaction in the NAD salvage synthesis. This domain is found at the C terminus of some nicotinate phosphoribosyltransferase enzymes. The function of this domain is uncertain.
CdiA, C-terminal tRNase domain (CdiA_C_tRNase)
Type: Domain

This entry represents the C-terminal tRNase domain of CdiA a type II toxin/immunity protein complex which can be found in B. pseudomallei isolate E479. The C-terminal tRNase domain has an α/β-fold characteristic of PD(D/E)XK nucleases. The PD(D/E)XK superfamily includes most restriction endonucleases and other enzymes involved in DNA recombination and repair .
Pyruvate dehydrogenase E1 component, middle domain (PDH_E1_M)
Type: Domain

This entry represents one of the thiamin diphosphate-binding domains found in pyruvate dehydrogenase E1 component .
SMODS and SLOG-associating 2TM effector domain, fungi (SLATT_fungi)
Type: Domain

The SLATT domain contains two transmembrane helices. SLATT domains are generally predicted to function in bacteria as pore-forming effectors in a class of conflict systems which are reliant on the production of second messenger nucleotide or nucleotide derivatives. SLATT domains are predicted to initiate cell suicide responses upon their activation. The role of this fungal family is not yet understood, although the expansion of the family in many fungal lineages points to a potential role in conflict .
NOG1, N-terminal helical domain (NOG1_N)
Type: Domain

This domain is found at the N terminus of NOG1 GTPase proteins.

In Saccharomyces cerevisiae, the NOG1 gene has been shown to be essential for cell viability, suggesting that NOG1 may play an important role in nucleolar functions. In particular, NOG1 is believed to be functionally linked to ribosome biogenesis, which occurs in the nucleolus. In eukaryotes, NOG1 mutants were found to disrupt the biogenesis of the 60S ribosomal subunit .
Rhamnogalacturonan I lyase beta-sheet domain (RGI_lyase)
Type: Domain

This is the β-sheet domain found in rhamnogalacturonan (RG) lyases , which are responsible for an initial cleavage of the RG type I (RG-I) region of plant cell wall pectin. Polysaccharide lyase family 11 carrying this domain, such as YesW (

) and YesX (

), cleave glycoside bonds between rhamnose and galacturonic acid residues in RG-I through a beta-elimination reaction .
Beta-mannosidase, Ig-fold domain (Beta-mannosidase_Ig)
Type: Domain

This Ig-like fold domain is found in mannosidase enzymes .
Proteasomal ATPase, N-terminal OB domain (Prot_ATP_ID_OB_N)
Type: Domain

This is the interdomain (ID), oligonucleotide binding (OB) domain found at the N-terminal of proteasomal ATPase .
CbbX, AAA lid domain (AAA_lid_6)
Type: Domain

Many AAA+ proteins have a C-terminal α-helical bundle in addition to the AAA core. The functional roles of the helical bundle are varied and include the formation of a lid over the nucleotide binding site and mediation of subunit interactions in oligomeric protein complexes. This entry represents the α helical AAA+ lid domain that is found to the C terminus of AAA domains in the CfxQ/CbbX family .
ChlI/MoxR, AAA lid domain (ChlI/MoxR_AAA_lid)
Type: Domain

This entry represents the α-helical AAA+ lid domain that is found to the C terminus of AAA domains.

Proteins containing this domain include magnesium-chelatase subunits, such as ChlI and ChlD. The plant magnesium-chelatase is a complex of three subunits, CHLI, CHLD and CHLH. The reaction takes place in two steps, with an ATP-dependent activation followed by an ATP-dependent chelation step . This domain can also be found in MoxR, a putative AAA-type ATPase enzymatic complex assembly chaperone .
Bacterial SCP orthologue (SCP_3)
Type: Domain

This domain is found in MSMEG_5817 gene product from M. smegmatis. It has been shown to be vital for mycobacterial survival within host macrophages. Crystal structure revealed a Rossmann-like fold α/β two-layer sandwich forming a highly hydrophobic interface cavity and with high structural homology to the sterol carrier protein (SCP) family. Hence, it has been suggested that this domain may be involved in the interaction of apolar ligands through its hydrophobic cavity. Alanine-scanning mutagenesis of the hydrophobic cavity of MSMEG_5817 protein demonstrated that the conserved Val82 residue plays an important role in ligand binding .
Epithelial cell adhesion molecule N-terminal domain (EpCAM_N)
Type: Domain

EpCAM (epithelial cell adhesion molecule), a stem and carcinoma cell marker, is a cell surface protein involved in homotypic cell-cell adhesion via intercellular oligomerization and proliferative signalling via proteolytic cleavage. Structure analysis indicate that it is composed of three domains: N-terminal domain, Thyroglobulin type-1A (TY) domain and the C-terminal domain. This entry represents the small and compact disulphide-rich N-terminal domain of 39 amino-acid residues .
Alpha-dystroglycan N-terminal domain 2 (Alpha_DG1_N2)
Type: Domain

This is the second N-terminal domain found in alpha-Dystroglycan (DG). The murine skeletal muscle N-terminal alpha-DG region, contains two autonomous domains; the first identified as an Ig-like and the second resembling ribosomal RNA-binding proteins . This domain is similar to the small subunit ribosomal protein S6 of Thermus thermophilus (S6 domain). It is suggested that the S6 domain may be of functional relevance for LARGE (like-acetylglucosaminyltransferase) recognition along the alpha-DG maturation pathway .
Arsenite oxidase subunit AioA/Iodate reductase subunit IdrA, 3Fe-4S cluster (AioA/IdrA_3Fe-4S)
Type: Domain

Arsenite oxidase is a 100kDa molybdenum- and iron-sulfur-containing protein located on the outer surface of the inner membrane of Gram-negative organisms. The large subunit of arsenite oxidase (AioA) is similar to other members of the dimethylsulfoxide (DMSO) reductase family of molybdenum enzymes, while the small subunit contains a Rieske-type [2Fe-2S] site. The large subunit of arsenite oxidase is divided into four domains, with domain I binding the [3Fe-4S] cluster. Domain I consists of three antiparallel β-sheets and six helices. The [3Fe-4S] cluster is coordinated by the motif Cys21-X2-Cys24-X3-Cys28 near the interface with domains III and IV. A large, flattened funnel-like cavity bounded by domains I, II, and III leads to the molybdenum centre (

) located near the centre of the molecule . This domain is also found in iodate reductase subunit IdrA, the closest related member of the DMSO reductase family .
Polymerase beta, nucleotidyltransferase (Polbeta)
Type: Domain

Proteins containing this domain include a member of the nucleotidyltransferase fold found in polymorphic toxins (NTox45) and polyvalent proteins .
Nuclear pore protein Nup188, C-terminal (Nup188_C)
Type: Domain

This is C-terminal domain of Nup188. It is a right-handed arc-shaped superhelical structure built from 19 helices that form 6 helical repeats, which are stacked in regular order. The first helical pair (alpha1 and alpha2) forms a HEAT repeat followed by 5 ARM repeats .
Type ISP restriction-modification enzyme LLaBIII, C-terminal specificity domain (Type_ISP_LLaBIII_C)
Type: Domain

This is the C-terminal domain of Type ISP restriction-modification enzyme LLaBIII present in Lactococcus lactis subsp. cremoris. Type ISP restriction-modification (RM) enzymes provide a potent defence against infection by foreign and bacteriophage DNA. This domain interacts extensively with DNA and is known as the target recognition domain (TRD). TRD works by recognising 6/7 base pairs of asymmetric sequence .
Ribonuclease J, C-terminal (RNase_J_C)
Type: Domain

This domain is found at the C terminus of Ribonuclease J proteins. Its function is unknown, but deletion of this domain causes dissociation to monomers .
Caprin-1 dimerization domain (Caprin-1_dimer)
Type: Domain

This domain is found in human Caprin-1 protein. Caprin-1 plays a role in many important biological processes, including cellular proliferation, innate immune response and synaptic plasticity. This domain is found in the highly conserved homologous region 1(HR1) and is responsible for the tight homodimerization of Caprin-1 .
Bacterial archaeo-eukaryotic release factor family 11 (BaeRF_family11)
Type: Family

This entry represents a bacterial family of the archaeo-eukaryotic release factor superfamily. It is likely to play roles in biological conflicts or regulation under stress conditions at the ribosome . It has been classified as family 11 by Pfam.
Large polyvalent protein-associated domain 39 (LPD39)
Type: Domain

Polyvalent proteins are predicted to be transmitted by genomic parasites such as conjugative elements, plasmids, and phages during the initial phase of infection along with their DNA. They are typified by the presence of multiple domains with disparate activities .

This is a predicted enzymatic α-helical domain that is associated with polyvalent proteins of phages and prophages .
Tyrosinase, C-terminal (Tyrosinase_C)
Type: Domain

This is the C-terminal domain of Tyrosinase present in Aspergillus oryzae. Tyrosinase is a dinuclear copper monooxygenase/oxidase that plays a crucial role in the melanin pigment biosynthesis. The C-terminal domain is referred to as the shielding domain as it prohibits substrate access to the enzyme-active site and blocks the oxidase/oxygenase activity to avoid undesirable intracellular reactions of highly reactive quinonoid products. This means the domain may play an important role in regulating the enzyme activity. Two of the three cysteines (Cys522, and Cys525) that play a significant role in the copper incorporation process belong to the C-terminal domain .
CALCOCO1/2, zinc finger UBZ1-type (CALCOCO1/2_Zn_UBZ1)
Type: Domain

The ubiquitin-binding zinc finger (UBZ) is a type of zinc-coordinating β-β-α fold domain found mainly in proteins involved in DNA repair and transcriptional regulation. UBZ domains coordinate a zinc ion with cysteine or histidine residues; depending on their amino acid sequence, UBZ domains are classified into several families . Type 1 UBZs are CCHH-type zinc fingers found in tandem UBZ domains of TAX1-binding protein 1 (TAX1BP1) , type 2 UBZs are CCHC-type zinc fingers found in FAAP20 which is a subunit of the Fanconi anemia (FA) core complex , type 3 UBZs are CCHH-type zinc fingers found only in the Y-family translesion polymerase eta , and type 4 UBZs are CCHC-type zinc fingers found in Y-family translesion polymerase kappa, Werner helicase-interacting protein 1 (WRNIP1), and Rad18 .

This entry represents the UBZ1 type zinc finger domain found in calcium-binding and coiled-coil domain 1/2 (CALCOCO1/2), tax-binding protein 1 and protein spindle-F.

This domain is a typical C2H2-type zinc finger which specifically recognizes mono-ubiquitin or poly-ubiquitin chain. The overall ubiquitin-binding mode utilizes the C-terminal α-helix to interact with the solvent-exposed surface of the central β-sheet of ubiquitin, similar to that observed in the RABGEF1/Rabex-5 or POLN/Pol-eta zinc finger .

CALCOCO2 (also known as NDP25) is an ubiquitin-binding autophagy receptor involved in the selective autophagic degradation of invading pathogens . Tax binding protein 1 is a ubiquitin binding protein and protein spindle-F plays a role in oocyte axis determination and microtubule organization during oogenesis in Drosophila .
HTH-type transcriptional repressor KstR, C-terminal (KstR_C)
Type: Domain

This entry represents the C-terminal domain present the transcriptional regulator KstR that regulates a large set of genes responsible for cholesterol catabolism. This is important for Mycobacterium tuberculosis during infection, both at an early stage in the macrophage phagosome and later within the necrotic granuloma .

TetR family regulators are involved in the transcriptional control of multidrug efflux pumps, pathways for the biosynthesis of antibiotics, response to osmotic stress and toxic chemicals, control of catabolic pathways, differentiation processes, and pathogenicity . The TetR proteins identified in overm ultiple genera of bacteria and archaea share a common helix-turn-helix (HTH) structure in their DNA-binding domain. However, TetR proteins can work in different ways: they can bind a target operator directly to exert their effect (e.g. TetR binds Tet(A) gene to repress it in the absence of tetracycline), or they can be involved in complex regulatory cascades in which the TetR protein can either be modulated by another regulator or TetR can trigger the cellular response . TetR regulates the expression of the membrane-associated tetracycline resistance protein, TetA, which exports the tetracycline antibiotic out of the cell before it can attach to the ribosomes and inhibit protein synthesis . TetR blocks transcription from the genes encoding both TetA and TetR in the absence of antibiotic. The C-terminal domain is multi-helical and is interlocked in the homodimer with the helix-turn-helix (HTH) DNA-binding domain .
ZIC protein, zinc finger domain (Znf_ZIC)
Type: Domain

This is the ZF1 (Zinc Finger 1) domain found in Zic family proteins found in Eukaryotes. In humans, there are five members of the Zic family that are involved in human congenital anomalies. One of them, ZIC3, causes X-linked heterotaxy (HTX1), which is a left-right axis disturbance that manifests as variable combinations of heart malformation, altered lung lobation, splenic abnormality and gastrointestinal malrotation. Zic faily proteins contain multiple zinc finger domains (ZFD), which are generally composed of five tandemly repeated C2H2 zinc finger (ZF) motifs. Sequence comparison analysis reveal that this N-terminal ZF (ZF1) domain of the Zic zinc finger domains is unique in that it possesses more amino acid residues (6-38 amino acids) between the two cysteine residues of the C2H2 motif compared to Gli and Glis ZF1s or any of the other ZFs (ZF2-5) in the Gli/Glis/Zic superfamily of proteins. Mutations in cysteine 253 (C253S) or histidine 286 (H286R) in ZIC3 ZF1, which are found in heterotaxy patients, result in extranuclear localization of the mutant ZIC3 protein. Furthermore, mutations in the evolutionarily conserved amino acid residues (C253, W255, C268, H281 and H286) of ZF1 generally impair nuclear localization .
GNAT-like C-terminal domain (GNAT_C)
Type: Domain

This is the C-terminal domain found in N-acyltransferase (NAT) proteins present in Actinoplanes teichomyceticus. In this organism, NAT proteins are responsible for N-acylation in the synthesis of the antibiotic teicoplanin. The C-terminal domain undergoes a substantial conformational change upon binding to Acyl-CoA. The C-terminal domain is considered Gcn5-related N-acetyltransferase like (GNAT-like) but differs from the canonical GNAT fold in that it lacks the first β-strand and has an additional four α-helices .
ADAMTS, cysteine-rich domain 2 (ADAMTS_CR_2)
Type: Domain

This cysteine rich domain is found in a variety of ADAMTS peptidases.

Proteolysis of the extracellular matrix plays a critical role in establishing tissue architecture during development and in tissue degradation in diseases such as cancer, arthritis, Alzheimer's disease and a variety of inflammatory conditions . The proteolytic enzymes responsible for this process are members of diverse protease families, including the secreted zinc metalloproteases (MPs) .

ADAM-TS (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) is closely related to the ADAM family (A Disintegrin and Metalloproteinase) and is a subfamily of the MP family, consists of at least 20 members sharing a high degree of sequence similarity and conserved domain organisation . The defining domains of the ADAM-TS family are (from N- to C-termini) a pre-pro metalloprotease domain of the reprolysin type, a snake venom disintegrin-like domain, a thrombospondin type-I (TS) module, a cysteine-rich region, and a cysteine-free (spacer) domain . Domain organisation following the spacer domain C terminus shows some variability in certain ADAM-TS members, principally in the number of additional TS domains. These enzymes have a wide-spectrum role in vascular biology and cardiovascular pathophysiology .

Members of the ADAM-TS family have been implicated in a range of diseases . For instance, members of this family have been found to participate directly in processes in the central nervous system (CNS) such as the regulation of brain plasticity . ADAM-TS1 is reported to be involved in inflammation and cancer cachexia , whilst recessively inherited ADAM-TS2 mutations cause Ehlers-Danlos syndrome type VIIC, a disorder characterised clinically by severe skin fragility . ADAM-TS4 is an aggrecanase involved in arthritic destruction of cartilage .