SII-SWORD/CoKE huggingface dataset:
Halobacterial output domain 1 (HalOD1)
Type: Domain

HalOD1 (Halobacterial output domain 1) is a protein domain that is specific for haloarchaea and their viruses. It is found in a stand-alone version and also in combination with response regulator receiver domain (

) and other domains . This domain is found in DdfA (HVO_2176, such as

), from Haloferax sp., which has been associated with signal transduction pathways, suggesting a potential role in signal cascades that regulate cell-shape determination .
Restriction endonuclease, SH3 domain (SH3_17)
Type: Domain

This is an N-terminal β-barrel domain found in the Hpy99I protomer region. Hpy99I is a type II restriction endonuclease (REase) found in the gastric pathogen Helicobacter pylori. The β-barrel domain has the SH3-domain fold. Deletion of the β-barrel domain drastically reduced the activity of Hpy99I .
Cytosolic carboxypeptidase, N-terminal (Pepdidase_M14_N)
Type: Domain

This entry corresponds to the N-terminal domain of Burkholderia cenocepacia M14-type cytosolic carboxypeptidase. The N-terminal domain folds into a nine-stranded antiparallel β sandwich . This domain is specific to CCP proteins and is absent in other carboxypeptidases. It has been hypothesised that the N-terminal domain might contribute to folding, might have a regulatory function and/or might be involved in binding other proteins.
T3SS EscN ATPase, C-terminal (T3SS_ATPase_C)
Type: Domain

This is the C-terminal domain of the EscN protein family of ATPases that form part of the Type III secretion system (T3SS) present in Escherichia coli. T3SS is a macromolecular complex that creates a syringe-like apparatus extending from the bacterial cytosol across three membranes to the eukaryotic cytosol. This process is essential for pathogenicity. EscN is a functionally unique ATPase that provides an inner-membrane recognition gate for the T3SS chaperone-virulence effector complexes as well as a potential source of energy for their subsequent secretion. The C-terminal domain of T3SS ATPases mediates binding with multiple contact points along the chaperone .
Bacterial archaeo-eukaryotic release factor family 6 (BaeRF_family6)
Type: Domain

This is a domain found in 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 .
Phage spike trimer (Phage_spike)
Type: Domain

Bacteriophages penetrate the host cell membrane using their tail to inject genetic material into the host . In this penetration process, they use central spike domain located beneath their baseplate . The spike domain folds as a trimeric iron-binding structure . This entry contains three copies of the repeat unit.
Ubiquitous surface protein adhesin repeat (UspA1_rep)
Type: Repeat

The UspA1 head domain is globally similar to other structures of TAA head domains and comprises a trimeric left-handed parallel β-roll, which is formed from 14 repeating 14-16 residue segments that form a ladder of β-strand coils . This entry represents a single repeat unit of the β-ladder.
Large polyvalent protein associated domain 30 (LPD30)
Type: Domain

This is an α and β fold domain that is found in polyvalent proteins of conjugative elements .
Sulfotransferase, S. mansonii-type (Sulfotransfer_4)
Type: Family

This family of proteins are distantly related to sulfotransferase enzymes, mainly found in fungi and platyhelminthes. In S. mansonii, it has been shown to be involved in resistance to oxamniquine and to have sulfotransferase activity . This entry also includes Ava biosynthesis cluster protein M from Aspergillus versicolor, which is part of the cluster that mediates the biosynthesis of a highly modified cyclo-arginine-tryptophan dipeptide (cRW) .
Galactose mutarotase-like fold domain (Gal_mutarotas_3)
Type: Domain

This domain is found in endo-alpha-N-acetylgalactosaminidase present in Streptococcus pneumoniae. Endo-alpha-N-acetylgalactosaminidase is a cell surface-anchored glycoside hydrolase involved in the breakdown of mucin type O-linked glycans. The domain, known as domain 2, exhibits strong structural similarlity to the galactose mutarotase-like fold but lacks the active site residues. Domains, found in a number of glycoside hydrolases, structurally similar to domain 2 confer stability to the multidomain architectures .
Arginine decarboxylase, helical bundle domain (Arg_decarb_HB)
Type: Domain

This entry represents a helical bundle domain found between the two enzymatic domains of the arginine decarboxylases .
D-ribitol-5-phosphate cytidylyltransferase, C-terminal (ISPD_C)
Type: Domain

This domain is located at the C-terminal region of ISPD (isoprenoid synthase domain containing protein). Structural homologs can be found in two distinct alpha/beta protein families including the seven-stranded NAD(P) (H)-dependent short-chain dehydrogenases/reductases and five-stranded response regulator proteins involved in bacterial sensing systems .
PatG, C-terminal (PatG_C)
Type: Domain

This is the C-terminal domain of Prochloron sp. PatG, which processes the precursor peptide to yield the cyclic Patellamide. The C-terminal domain of PatG is 56% structurally homologous to the C-terminal domain of PatA .
Large ribosomal subunit protein uL10-like, insertion domain (Ribosomal_uL10-like_insert)
Type: Domain

This is an insertion domain found in archaeal and eukaryotic large ribosomal subunit protein uL10 (previously known as P0 homologue (L10E) and in ribosome assembly factor MRT4, a nuclear paralogue of these proteins .
N-terminal PilZ-like domain (PilZN1)
Type: Domain

This domain is found in PilZ domain-containing proteins from Deltaproteobacteria, such as

from Geobacter sulfurreducens. This domain is located N-terminal to a canonical PilZ domain, with a PilZ-related structure comprising the β-barrel fold, lacking the C-terminal α-helix and both c-d-GMP-binding motifs . This domain also has a N-terminal loop that forms a short α-helix (3 residues) .
Alpha-2-macroglobulin, MG1 domain (A2MG_MG1)
Type: Domain

Alpha-2-macroglobulins (A2Ms) are plasma proteins that trap and inhibit a broad range of proteases and are major components of the eukaryotic innate immune system. However, A2M-like proteins were identified in pathogenically invasive bacteria and species that colonize higher eukaryotes. Bacterial A2Ms are located in the periplasm where they are believed to provide protection to the cell by trapping external proteases through a covalent interaction with an activated thioester. This domain is found on the N-terminal region in A2Ms in bacteria. Structure analysis of Salmonella enterica ser A2Ms (SA-A2Ms) show that they are composed of 13 domains, all of which fold as variants of β sandwiches with the exception of the TED, which consists of 14 α helices. Most of the β sandwich domains appear to serve a structural role and are referred to as the macroglobulin-like (MG) domains. This is the MG1 domain which is the farthest from the body of the structure. It is normally anchored to the inner membrane in vivo and connected to MG2 by a flexible linker .
Myosin X, N-terminal SH3 domain (MyoX_N_SH3)
Type: Domain

This is the N-terminal SH3 domain found in myosin X, which is essential for neuritogenesis, wound healing, cancer metastasis and some pathogenic infections. Myosin X is required for filopodia formation and extension .
E3 ubiquitin-protein ligase RNF31, PUB domain (RNF31_PUB)
Type: Domain

This is a PUB domain (PNGase/UBA-or UBX-containing domain), found in E3 ubiquitin-protein ligase RNF31, also known as Ring finger protein 31 and HOIL-1-interacting protein (HOIP) . RNF31/HOIP has been shown to contribute to inborn human immunity disorders, in which RNF31/HOIP missense mutation at PUB domain gives rise to the de-stabilized LUBAC complex (linear ubiquitin chain assembly complex) and subsequently causes the auto-inflammation and immunodeficiency. In addition, RNF31 is reported to modify ERK and JNK pathways leading to cisplatin resistance . Functional studies indicate that HOIP and OTULIN interact and act as a bimolecular editing pair for linear ubiquitin signals where the HOIP-PUB domain binds to the PUB interacting motif (PIM) of OTULIN and the chaperone VCP/p9. This interaction plays an important role where the HOIP binding to OTULIN is required for the recruitment of OTULIN to the TNF receptor complex and to counteract HOIP-dependent activation of the NF-KB pathway .
Histidine kinase receptor ArcB, transmembrane domain (HKR_ArcB_TM)
Type: Domain

Histidine kinase receptors (HKRs) are part of a two-component system, in which an HKR in the bacterial inner membrane transmits a signal to a response regulator located in the cytoplasm. This is a trans-membrane domain (TM) found in ArcB (class 2, aerobic respiratory control sensor). ArcB has two TM helices connected by a short periplasmic loop. TM domain structures suggests a loose helical packing which provides an inherent flexibility in the TM domains and that this is perhaps essential to the mechanism of signal transduction across the membrane .
Murine leukemia virus integrase, C-terminal (MLVIN_C)
Type: Domain

This is the C-terminal domain (CTD) which can be found in murine leukemia virus (MLV) integrase (IN) proteins. This domain interacts with the bromo and extraterminal (BET) proteins through the ET domain. This interaction provides a structural basis for global in vivo integration-site preferences and disruption of this interaction through truncation mutations affects the global targeting profile of MLV. This domain consists of an SH3 fold followed by a long unstructured tail .
Hydrogen maturase F, tetramerization domain (HydF_tetramer)
Type: Domain

This entry represents the C-terminal domain of Hydrogen maturase F (HydF) from Thermotoga neapolitana. HydF is a GTPase that contains an FeS cluster-binding motif and is able to activate HydA production. This domain is known as domain III and is primarily responsible for homotetramer formation. Interactions between the two FeS cluster-binding domains are the interactions between the β2 strands, the initial part of the long loop that connects strand β2 to strand β3, and the loop that connects strand β1 to helix α3. There are three highly conserved cysteine residues (Cys-302, Cys-353, and Cys-356) that represent the FeS cluster-binding site which form a superficial pocket .
Neurabin-1/2, PDZ domain (Neurabin-1/2_PDZ)
Type: Domain

This entry represents the PDZ domain found in neurabin and spinophilin proteins . The PDZ domain in spinophilin mediates its interaction with protein phosphatase PP1 .
Fanconi anemia core complex-associated protein 24, pseudonuclease domain (PND)
Type: Domain

This entry represents the pseudonuclease domain (PND) from the FANCM protein . This domain is part of the PD(D/E)XK superfamily but does not appear to have a full set of catalytic residues .
SPIN-DOC-like, zinc-finger (SPIN-DOC_Znf-C2H2)
Type: Domain

This is a zinc finger domain C2H2 type which can be found in SPIN1 docking protein (SPIN-DOC). SPIN-DOC is a Spindlin1 (SPIN1) regulator that directly binds and strongly disrupts its histone methylation reading ability, causing it to disassociate from chromatin . Proteins containing this domain also include Epm2aip1, which is a glycogen synthase (GS)-associated protein. In the absence of Epm2aip1, the sensitivity of the liver to insulin, in which GS is a principal actor, is impaired .
HMG domain-containing protein 3, CxC4 like cysteine cluster (HMGXB3_CxC4)
Type: Domain

This entry represents a predicted Zinc chelating domain found in HMGXB3 (HMG-box containing 3), a protein involved in a range of cellular processes including cell migration and proliferation . This domain is N-terminal to the KDZ transposase domain .
Bacterial HORMA domain (Bact_HORMA)
Type: Domain

This entry represents the HORMA domain found in bacterial proteins from the cyclic-oligonucleotide-based anti-phage signalling system (CBASS), such us CD-NTase-associated protein 7 from Pseudomonas aeruginosa (Cap7, also known as Bacterial HORMA2 sensor protein), which is part of the type III-CBASS. CBSSs are a family of defence systems against bacteriophages which are ancestry related with the cGAS-STING innate immune pathway in animals. CBASSs are composed of an oligonucleotide cyclase, which generates signalling cyclic oligonucleotides in response to phage infection, and an effector that is activated by the cyclic oligonucleotides and promotes cell death . Cap7 is essential for phage defence and it is the sensor protein in the type III-CBASS. It binds to a closure peptide (consensus Glu-Val-Met-Glu-Phe-Asn-Pro), and forms the CdnD:Cap7:Cap8 complex, which allows it to activate the oligonucleotide cyclase CdnD for second messenger synthesis. The oligonucleotide cyclase becomes active only when physically bound by the HORMA-domain protein .
Cell division control protein 13, OB2 domain (Cdc13_OB2)
Type: Domain

Cdc13 is an essential yeast protein required for telomere length regulation and genome stability. Cdc13, like a number of single-stranded telomere binding proteins, consists of several oligonucleotide-oligosaccharide binding (OB) folds. These folds potentially arise from evolutionary gene duplication and are involved in multiple functions, including nucleic acid and protein binding and Cdc13 dimerization. This entry represents the OB2 domain, second OB-fold counting from the N terminus of Cdc13. Biochemical assays indicate OB2 is not involved in telomeric DNA or Stn1 binding. However, disruption of the OB2 dimer in full-length Cdc13 affects Cdc13-Stn1 association, leading to telomere length deregulation, increased temperature sensitivity, and Stn1 binding defects. Hence it is suggested that the dimerization of the OB2 domain of Cdc13 is required for proper Cdc13, Stn1, Ten1 (CST) assembly and productive telomere capping .
Large polyvalent protein-associated domain 5 (LPD5)
Type: Domain

This domain is predicted to be an enzymatic alpha beta domain . It is often found N-terminal to a metallopeptidase domain in polyvalent proteins. The domain contains a conserved aspartate, lysine, and two arginine residues.
Cry35Ab1 , HTH C-terminal domain (Cry35Ab1_HTH)
Type: Domain

This is the C-terminal domain found in Bacillus subtilis YefC and Bacillus thuringiensis protein Cry35Ab1 (an insecticidal protein). The domain has three helices held in a hydrophobic core, the first two form a typical helix-loop-helix whilst the third helix is perpendicular. The domain is structurally homologous to BinB and proteins containing similar β-trefoil lectin-like domains. The domain is not required for insecticidal activity or for immuno-reactivity and its function is likely to be to bind to WCR brush border membrane vesicles .
Csd3, N-terminal (Csd3_N)
Type: Domain

Csd3 (also known as HdpA) is a bi-functional enzyme with delta, delta-endopeptidase activity and delta, delta-carboxypeptidase activity. The N-terminal domain is also known as domain 1 and is composed of an α/β fold consisting of a five-stranded antiparallel β-sheet and three short α-helices. Domain 1 blocks the active-site cleft of the LytM domain, with the protruding helix alpha-3 contributing to the Zn2+ coordination sphere. The fold of domain 1 is very remotely related to monellin/cystatin superfamily proteins, some of which act as inhibitors of cysteine peptidases .
LasR-specific antiactivator QslA (QslA)
Type: Domain

This domain is found in QslA from Pseudomonas aeruginosa. QslA is an antiactivator which binds to the transcription factor LasR, disrupting its dimerization and preventing LasR from binding to target DNA. QslA forms a dimer that interacts with the ligand-binding domain in LasR .
TIAM1, CC-Ex domain (TIAM1_CC-Ex)
Type: Domain

Tiam1 is a guanine exchange factor (GEF) for CDC42 and the Rho-family GTPase Rac1, which plays an important role in cell-matrix adhesion and in cell migration . Tiam1 is involved in multiple steps of tumorigenesis .

This entry represents the CC and Ex subdomain found in the PH-CC-Ex globular domain of the Tiam1 and Tiam2 proteins (T-lymphoma invasion and metastasis). The CC subdomain forms an antiparallel coiled coil with two long α-helices, together with the C-terminal Ex subdomain they form a small globular domain comprising three α-helices. The CC subdomain of the Tiam2 PHCCEx domain follows the C-terminal alpha1 helix of the PH subdomain through a four-residue linker .
Cas9, WED domain (Cas9_WED_dom)
Type: Domain

This domain, known as the wedge (WED) domain, can be found in Cas9 from Staphylococcus aureus. Cas9 cleaves double-stranded DNA targets with a protospacer adjacent motif (PAM) and complementarity to the guide RNA. The Cas9 WED domain has a fold comprising a twisted five-stranded β sheet flanked by four α helices, and is responsible for the recognition of the distorted repeat: anti-repeat duplex. WED domains are responsible for the recognition of single-guide RNA scaffolds .
GshAB, ATP-grasp-like domain (GshAB_ATP-grasp)
Type: Domain

Glutathione biosynthesis is achieved in most organisms via a conserved two-step approach relying on the capacity of two independent and unrelated ligases to perform peptide synthesis coupled to ATP hydrolysis. In a first and rate-limiting step, gamma-glutamylcysteine ligase (gamma-ECL) (or GshA;

) uses l-glutamate and l-cysteine to form gamma-glutamylcysteine (gamma-EC), which, in a second step, is condensed with glycine to glutathione by glutathione synthetase (GS) (or GshB;

). However, several pathogenic and free-living bacteria carry out glutathione biosynthesis based on a single enzyme that catalyses both the gamma-ECL and the GS reactions. Such bifunctional glutathione-synthesizing enzymes have been termed gamma-GCS-GS, GshF or GshAB . Hybrid GshF contains a typical gammaproteobacterial gamma-ECL fused to an ATP-grasp-like domain . The ATP-grasp-like module is responsible for the ensuing formation of glutathione from gamma-glutamylcysteine and glycine. The ATP-grasp-like domain has an antiparallel β-sheet in the GshF structures in contrast to all structurally characterised members of the ATP-grasp superfamily .
SipA, vinculin binding site (SipA_VBS)
Type: Conserved_site

This motif includes the three vinculin binding sites found in the Shigella SipA/IpaA protein . Proteins containing this site also include some proteins from Chlamydia species.
Phenylalanine--tRNA ligase beta subunit, B1 domain (PhetRS_B1)
Type: Domain

This is the N-terminal domain found in phenylalanine--tRNA ligase beta subunit .
N-formyltransferase dimerization C-terminal domain (N_formyltrans_C)
Type: Domain

This is the C-terminal domain of N-formyltransferase from Francisella tularensis. N-formylated sugars are observed on O-antigens of pathogenic Gram-negative bacteria. This C-terminal domain is responsible for dimerisation. In particular, the β hairpin motif present in the domain helps create a subunit-subunit interface. The dimeric interface is characterised by a hydrophobic patch formed by Ile 195, Leu 197, Val 201, Met 203, Ile 207, Phe 223, Val 231, Val 233, Leu 235, and Leu 237 from both monomers .
Leucine zipper with capping helix domain (LZ3wCH)
Type: Domain

This domain is found at the C-terminal region of Hop2 and Mnd1 proteins. In meiotic DNA recombination, the Hop2-Mnd1 complex promotes Dmc1-mediated single-stranded DNA (ssDNA) invasion into homologous chromosomes to form a synaptic complex. Hop2 (for homologous pairing; also known as TBPIP) is expressed specifically during meiosis, same as Mnd1 (for meiotic nuclear divisions 1). The C-terminal region of both Hop2 and Mnd1, folds into three α-helices that are interrupted by two short non-helical regions. These α-helices of the two proteins together form a parallel coiled coil that provides the major interface for heterodimer formation. The non-helical regions form substantially kinked junctions between adjacent leucine zippers: the LZ1-LZ2 and LZ2-LZ3 junctions.This domain is the C-terminal segment of Hop2 and Mnd1 which folds back onto the C-terminal leucine zipper (LZ3) to form a helical bundle-like structure, hence designated LZ3wCH (for LZ3 with capping helices). The LZ3wCH region plays a role in interacting with the Dmc1 nucleofilament .
Transcription factor Tfb2, C-terminal domain (Tfb2_C)
Type: Domain

This is the C-terminal domain of transcription factor Tfb2 present in Saccharomyces cerevisiae. Tfb2 is known as p52 in humans. The interaction between p8-Tfb5 and p52-Tfb2 has a key role in the maintenance of the transcription factor TFIIH architecture and TFIIHs function in nucleotide-excision repair (NER) pathway. The C-terminal domain of Tfb2 is thought to have a crucial role in DNA repair .
DNA polymerase delta subunit, OB-fold domain (DNA_pol_D_N)
Type: Domain

The eukaryotic DNA polymerase delta (Pol delta) participates in genome replication, homologous recombination, DNA repair and damage tolerance . Human Pol delta consists of four subunits: p125, p50, p66 and p12. The first three subunits correspond to the three subunits of S. cerevisiae Pol delta. p50 serves as a scaffold for the assembly of Pol delta by interacting simultaneously with all of the other three subunits. This entry corresponds to the OB fold domain found in the p50 subunit.
AFL, C-terminal (AFL_C)
Type: Domain

This domain is found in Archaeoglobus fulgidus lipase (AFL). The domain consists of a layer of seven β-sheet. When the domain is combined with the proximal domain, which is also a layer of seven β-sheet, they form a β sandwich. The combination of these two domains is known as the C-terminal domain. It is likely that the C-terminal domain plays an important role in substrate specificity, catalytic efficiency but also attributes partly to AFLs stability .
Tyrosine kinase receptor A, transmembrane domain (TrkA_TMD)
Type: Domain

Tyrosine kinase receptor A (also known as Neurotrophic tyrosine kinase receptor type 1 and High affinity nerve growth factor receptor), consists of 796 amino acids and can be divided in the extracellular ligand-binding domain, the trans-membrane domain (TMD), and the intracellular tyrosine kinase domain . This domain is the TMD of TrkA which has shown to be involved in the interaction with amyloid precursor protein (APP) .
Atg29, N-terminal (Atg29_N)
Type: Domain

This is the N-terminal domain found in fungal Atg proteins such as Atg29. In yeast, the induction of autophagy begins at a single perivacuolar site that is proximal to the vacuole, called the phagophore assembly site (PAS) . Atg17-Atg29-Atg31 complex (Atg1 complex) formation is a prerequisite for PAS assembly. Functional analysis indicate that the N-terminal half Atg29 can bind Atg31 .
Tyrosine-protein kinase receptor Ret, cadherin like domain 3 (Ret_CLD3)
Type: Domain

RET is a single transmembrane-spanning receptor tyrosine kinase (RTK) that plays critical roles in the development of vertebrates. Structural analysis indicate that RET contains four consecutive cadherin-like domains (CLD). This entry relates to CLD3. Classical cadherin calcium-coordinating motifs can be found between CLD2 and CLD3 .
TraI, 2B/2B-like domain (TraI_2B)
Type: Domain

This is the 2B and 2B-like sub-domain found in TraI, a relaxase of F-family plasmids. It contains four domains: a trans-esterase domain that executes the nicking and covalent attachment of the T-strand to the relaxase, a vestigial helicase domain (carrying the 2B/2B-like sub-domain) that operates as an ssDNA-binding domain, an active 5' to 3' helicase domain, and a C-terminal domain that functions as a recruitment platform for relaxosome components.
Agarase, CBM-like domain (Agarase_CBM)
Type: Domain

This is the N-terminal CBM-like domain found in exo-beta-agarase proteins from the marine microbe Saccharophagus degradans. This enzyme catalyzes a critical step in the metabolism of agarose by S. degradans through cleaving agarose oligomers into neoagarobiose products that can be further processed into monomers. The CBM-like domain is structurally very similar to some CBM domains. A loop in the CBM-like domain is involved in forming the roof of the active site channel. The contribution of the CBM-like domain to formation of the active site of the enzyme supports a role in substrate recognition explaining the exo-mode of beta-agarase action .