SII-SWORD/CoKE huggingface dataset:
PIK3AP1, Toll/interleukin-1 receptor domain (PIK3AP1_TIR)
Type: Domain

This is a Toll/interleukin-1 receptor (TIR) domain found in the N-terminal region of B-cell adaptor for phosphoinositide 3-kinase (PIK3AP1 or BCAP). BCAP functions in linking the B-cell receptor (BCR) and the co-receptor CD19 to the activation of PI3K via interaction with the SH2 domains on the regulatory p85 subunit. BCAP TIR associates with the MAL/TIRAP adaptor and the TIR domains of Toll-like receptors (TLRs) .
PSA endolysin, cell wall binding domain (PSA_CBD)
Type: Domain

This is the C-terminal domain of bacteriophage PSA endolysin. The C-terminal domain is the cell wall-binding domain (CBD) which is composed of two structurally homologous subdomains. CBD comprises two copies of a β-barrel-like folds, which are held together by means of swapped β-strands. The observed structure of the CBD sub-domains from Listeriaphage endolysin (N-acetyl-muramoyl-l-alanine amidase), could be the result of either a gene duplication during evolution of the CBD or the pick-up of another functionally equivalent coding sequence, followed by swapping of the respective ancestral leading β-strands .
Carbohydrate binding module family 35 (CBM35)
Type: Domain

This entry represents carbohydrate-binding module family 35

. This domain is found in several prokaryotic proteins, including Cthe_3141 from Acetivibrio thermocellus 9 (

). It has specificity for delta4,5-anhydrogalacturonic acid (d4,5-GalA), a signature molecule for plant cell wall degradation. Its crystal structure shows a jelly roll/β-sandwich fold with 2 antiparallel sheets made of 4 and 5 antiparallel β-strands . It is also found at the end of a family of putative glycosyl hydrolases.
Polycomb repressive complex 2 subunit EZH1/EZH2, tri-helical domain (PRC2_HTH_1)
Type: Domain

This domain can be found in the polycomb repressive complex 2 (PRC2) subunits EZH1 and EZH2. Three core subunits make up the catalytic core of PRC2: EZH1 or EZH2, the zinc-finger containing SUZ12 and EED. Polycomb complexes maintain repressive chromatin states by silencing gene expression. PRC2 does this by methylating lysine 27 of histone H3 . This domain makes up part of the N-lobe which consists of EED and the N-terminal region of EZH2, and is involved in regulation .
30K viral movement protein, core domain (30K_MP_core)
Type: Domain

This entry represents the core domain found in viral movement proteins (MP) of the 30K type. The core domain is conserved among MPs of 30K sharing the same predicted secondary structure which consists of 1 α-helix and 7 predicted β-strands. The only sequence feature common to all 30K MPs is a short region between β-strands 1 and 2, which contains several conserved hydrophobic positions, and a nearly-invariant aspartate which constitutes the sequence signature of the superfamily. This signature aspartate has a conserved role in essential for viral cell-to-cell movement .
Reovirus sigma C capsid protein triple beta spiral (Reo_sigmaC_M)
Type: Domain

This short region forms a triple β-spiral structural motif .
DR2241, 4Fe-4S iron-sulfur cluster binding domain (DR2241_Fer4)
Type: Domain

This is the C-terminal domain found in Deinococcus radiodurans protein DR2241 (a Ribosomal protein S2-related protein). This domain has been shown to harbour the sequence motifs CxxC and CxxxC which bind a [4Fe-4S] iron-sulphur cluster. Together with the preceding domain, it is heavily involved in the tetramer formation .
MftR, C-terminal (MftR_C)
Type: Domain

This domain is found at the C terminus of TetR like transcription factors including the Mycofactin biosynthesis transcription factor.
VEGFR-2, transmembrane domain (VEGFR-2_TMD)
Type: Domain

This is a transmembrane domain (TMD) of vascular endothelial growth factor receptor 2 which regulates blood vessel homeostasis. Transmembrane signalling by receptor tyrosine kinases (RTKs) requires specific orientation of the intracellular kinase domains in active receptor dimers. Two mutants in VEGFR-2 TMD showed constitutive kinase activity, suggesting that precise TMD orientation is mandatory for kinase activation. Scanning mutagenesis and structural analysis indicated that introducing two polar amino acids in distinct positions of the TMD (G770E/F777E and I771E/L778E mutations) reorients transmembrane helices and leads to stable dimer formation. Therefore, it has been suggested that the transition between the inactive and the active dimeric state of VEGFR-2 implicates alternative dimeric TMD conformations .

Proteins containing this domain also include VEGFR-1 and VEGFR-3 from animals and VEGFR-4 (also known as kdrl) from zebrafish .
Proline utilization A proline dehydrogenase N-terminal domain (PRODH)
Type: Domain

This is the N-terminal domain found in Proline utilization A (PutA) proteins. Proline utilization A (PutA) is a flavoprotein that has mutually exclusive roles as a transcriptional repressor of the put regulon and a membrane-associated enzyme that catalyzes the oxidation of proline to glutamate . The N-terminal region carries the flavoenzyme proline dehydrogenase (PRODH) domain which catalyzes the 2-electron oxidation of proline with the concomitant reduction of a flavin cofactor .
Carbon monoxide dehydrogenase subunit alpha ,N-terminal (CODH_A_N)
Type: Domain

Acetyl-coenzyme A (CoA) synthase/carbon monoxide dehydrogenase (ACS/CODH) is a bifunctional enzyme that catalyzes the reversible reduction of CO2 to CO (CODH activity). This entry is for the N-terminal domain found in ACS/CODH subunit alpha .
Exo-beta-D-glucosaminidase, Ig-fold domain (Ig_GlcNase)
Type: Domain

This domain can be found in 2 glycoside hydrolase subfamily of beta-glucosaminidases (

) such as CsxA, from Amycolatopsis orientalis that has exo-beta-D-glucosaminidase (exo-chitosanase) activity . It has an immunoglobulin-like topology.
Major tropism determinant, N-terminal domain (Mtd_N)
Type: Domain

This is the N-terminal domain of major tropism determinant (Mtd), a retroelement-encoded receptor-binding protein. Mtd-N forms a three-fold symmetric β-prism. This resembles the pseudo three-fold-symmetric β-prisms of monocot lectins, but lacks residues in these lectins identified as binding carbohydrates. The β-prism and β-sandwich domains reinforce overall trimeric assembly and therefore may have indirect roles in stabilizing the backbone of the variable region .
Flax-rust effector AvrM, N-terminal domain (AvrM_N)
Type: Domain

This is the N-terminal domain found in AvrM present in Melampsora lini. AvrM is a secreted effector protein that can internalize into plant cells in the absence of pathogens, binds to phosphoinositides and results in effector-triggered immunity. This domain is related to the WY domain core in oomycete effectors .
4'-phosphopantetheinyl transferase, N-terminal domain (4PPT_N)
Type: Domain

This entry represents the N-terminal domain from 4'- phosphopantetheinyl transferase enzymes. This domain is structurally related to the 4'-phosphopantetheinyl transferase domain (

) with which it forms a pseudodimeric arrangement .

This domain can also be found in enterobactin synthase component D (EntD), which forms part of the enterobactin-synthetase enzyme complex. It plays an essential role in the assembly of the enterobactin by catalyzing the transfer of the 4'-phosphopantetheine (Ppant) moiety from coenzyme A to the apo-domains of both EntB (ArCP domain) and EntF (PCP domain) to yield their holo-forms which make them competent for the activation of 2,3-dihydroxybenzoate (DHB) and L-serine, respectively . Deletion studies involving EntD- mutants have shown that it is essential for virulence .
Pre-SET CXC domain (Pre-SET_CXC)
Type: Domain

This domain is found to the N terminus of the SET domain in the EZH2 protein . It is a zinc binding domain.
PGM1 C-terminal domain (PGM1_C)
Type: Domain

This is the C-terminal domain found in PGM1 present in Streptomyces cirratus. PGM1 is a gene product that links precursor peptides together to form the antibiotic Pheganomycin .
LegC3 N-terminal, Legionellaceae (LegC3_N_Legionellaceae)
Type: Domain

LegC3 (also known as Kinectin 1) is an effector protein secreted by Legionella pneumophila which is believed to act by inhibiting vacuolar fusion. The N-terminal domain of LegC3 is composed of a long discontinuous coiled-coil capped by an antiparallel four-helix bundle that is rigidly connected to the coiled-coil segment. The features responsible for fusion inhibition are located mainly within the N-terminal domain, as this domain alone is sufficient to inhibit vacuole fusion .
Rubisco accumulation factor 1, alpha-helical domain (Raf1_N)
Type: Domain

This is the N-terminal α helical domain found in Rubisco accumulation factor1 (Raf1). Raf1 from Arabidopsis thaliana consists of an N-terminal alpha-domain, a flexible linker segment and a C-terminal β-sheet domain that mediates dimerization. The α-domains mediate the majority of functionally important contacts with RbcL (Rubisco large subunits) by bracketing each RbcL dimer at the top and bottom. The alpha-domain alone is essentially inactive .
Metanogen output domain 1 (MetOD1)
Type: Domain

MetOD1 (Metanogen output domain 1) is a protein domain that is found in euryarchaeal classes Methanobacteria and Methanomicrobia, either in stand-alone form or in combination with the response regulator receiver domain (

) .
ZAP, helix turn helix N-terminal domain (ZAP_HTH)
Type: Domain

Zinc-finger antiviral protein (ZAP) is a host factor that specifically inhibits the replication of certain viruses, such as HIV-1, by targeting viral mRNA for degradation. This domain is a helix turn helix domain found at the N-terminal region constituting the top cockpit layer of the protein .
Nidovirus helicase, RING/Ubox like zinc-binding domain (Znf-RING_13)
Type: Domain

This is a zinc binding domain found in nidovirus helicase. It includes includes 12 or 13 conserved Cys/His residues. Amino acid substitutions in ZBD or the adjacent spacer that connects it to the downstream domain can profoundly affect EAV (equine arteritis virus) helicase activity and RNA synthesis, with most replacements of conserved Cys or His residues yielding replication-negative virus phenotypes .
Plexin, TIG domain 2 (TIG2_plexin)
Type: Domain

This entry represents a TIG domain found in plexin proteins. TIG domains have an Ig-like fold .
LIM interaction domain (LID)
Type: Domain

LIM-homeodomain (LIM-HD) proteins are transcription factors that are critical in the development of many cell types and tissues. The activity of LIM-HD proteins is dependent on the essential cofactor LIM domain-binding protein 1 (Ldb1). This entry represents a 30-residue LIM interaction domain (LID) that binds to the LIM domains of all LIM-HD and closely related LIM-only (LMO) proteins. Isl1 (Insulin gene enhancer protein 1) and Isl2 each contain a LID-like sequence in their C-terminal regions, the Lhx3-binding domain (LBD), which binds the LIM domains Lhx3 and Lhx4 .
Rubredoxin binding domain (Rbx-bd)
Type: Domain

This is the C-terminal domain found in rubredoxin reductase (RdxR) present in Pseudomonas aeruginosa. RdxR are important in prokaryotes as they allow for the metabolism of inert n-alkanes and RdxR is also crucial for archaea and anaerobic bacteria in the response to oxidative stress. This domain is known to recognise and bind to rubredoxin .
Csp protease B, prodomain (CspB_prodomain)
Type: Domain

Csp proteases (Csps) and the subtilase protease family Subtilases are serine proteases that contain a catalytic triad in the order of Asp, His and Ser. Structure analysis reveals that Csps are subtilisin-like proteases with two distinctive functional features: a central jellyroll domain and a retained prodomain. The prodomain adopts a similar fold to the prodomains of related subtilisin-like proteases with the C-terminal region extending deep into the catalytic cleft. However, unlike the majority of subtilisin-like proteases, the prodomain stays bound to the subtilase domain via a network of interactions that result in tighter prodomain binding relative to other subtilases. Finally the prodomain acts as both an intramolecular chaperone and an inhibitor of CspB protease activity .
Pre-PUA domain (Pre-PUA)
Type: Domain

This Pre-PUA-like domain is found before the PUA domain (

) in a wide variety of proteins including eukaryotic translation initiation factor 2D (

), where it is found at the N terminus.
E3 ligase, CCCH-type zinc finger (Znf-CCCH_4)
Type: Domain

This short zinc binding domain has the pattern of three cysteines and one histidine to coordinate the zinc ion. This domain is found in a wide variety of Zinc finger CCCH containing proteins, such as E3 ligases and G patch containing proteins.
Dam-replacing protein, HTH domain (DRP_C)
Type: Domain

Dam-replacing protein (DRP) is an restriction endonuclease that is flanked by pseudo-transposable small repeat elements. The replacement of Dam-methylase by DRP allows phase variation through slippage-like mechanisms in several pathogenic isolates of Neisseria meningitidis . This domain represents the C-terminal HTH domain.
TrmO, C-terminal (TrmO_C)
Type: Domain

This domain is found at the C terminus of TrmO tRNA methyltransferase proteins . This domain has a RelE fold.
Methyltransferase EEF1AKMT1/ZCCHC4 (Mlase_EEF1AKMT1/ZCCHC4)
Type: Family

This is a protein of approximately 200 residues which is conserved from plants to humans . It contains a highly conserved QFW motif close to the N terminus and a DPPF motif in the centre. The DPPF motif is characteristic of N-6 adenine-specific DNA methylases, and this family is found in eukaryotes . Proteins in this entry include EEF1A lysine methyltransferase 1 (EEF1AKMT1) and ZCCHC4. EEF1AKMT1 is a protein-lysine methyltransferase that selectively catalyzes the trimethylation of EEF1A at 'Lys-79' . ZCCHC4 is an rRNA N6-methyltransferase that specifically methylates the adenine in position 4220 of 28S rRNA .
Glycosyl hydrolase family 92 N-terminal domain (GH92_N)
Type: Domain

This domain is found at the N terminus of family 92 glycosyl hydrolase proteins.
Cas3, C-terminal (Cas3_C)
Type: Domain

This is the C-temrinal domain of the Cas3 proteins. The C-terminal domain (CTD) is shown to completely wrap ssDNA inside the helicase. Deletion of the CTD (aa 819-924) reduced CRISPR interference. It is suggested that the CTD regulates the N-terminal HD nuclease activity by functioning as a substrate filter .
Reverse transcriptase, RNase H-like domain (RT_RNaseH)
Type: Domain

DNA polymerase and ribonuclease H (RNase H) activities allow reverse transcriptases to convert the single-stranded retroviral RNA genome into double-stranded DNA, which is integrated into the host chromosome during infection . This domain can also be found in animal retrotransposon-like proteins .

This entry represents an RNase H-like domain found in a group of reverse transcriptases, including those transcribed as part of an enzymatic polyprotein.
Bacterial archaeo-eukaryotic release factor family 12 (BaeRF_family12)
Type: Family

This is a bacterial family of the archaeo-eukaryotic release factor superfamily. Likely to play roles in biological conflicts or regulation under stress conditions at the ribosome .
VapC45, PIN like domain (VapC45_PIN-like)
Type: Domain

This is a bacterial domain of unknown function suggested to resemble PIN like domains . This domain can be found in putative ribonuclease VapC45 from Mycobacterium tuberculosis .
Integron Cassette Protein Hfx_Cass5 (Hfx_Cass5)
Type: Domain

This domain forms part of the integron cassette protein Hfx_CASS5 present in Vibrio cholerae. The structure of Hfx is a tetramer built from two domain-swapped dimers .
Viral coat protein P2, N-terminal domain (P2_N)
Type: Domain

This entry represents the N-terminal jelly roll domain of P2.

P2 (30.2kDa) is the major outer-coat protein of the marine lipid-containing bacteriophage PM2. Each subunit of P2 is composed of two β-barrel jelly rolls, disposed normally to the surface of the capsid, which lend pseudo-6-fold symmetry to the molecules, facilitating their close packing within the capsid. There is a Ca2+ ion located between the two β barrels of P2 that helps PM2 molecular organisation .
SbsC C-terminal domain (S-layer_SbsC_C)
Type: Domain

This is the C-terminal domain found in bacterial cell surface layer protein SbsC which can be found in species such as Geobacillus stearothermophilus. The C-terminal domain is the third and last triple-helical bundle and adopts a canonical coiled-coil structure. A similar overall arrangement of antiparallel triple-helical bundles has been found in the cytoskeletal protein spectrin (2SPC).
Collagenase ColG-like, catalytic helper subdomain (ColG_subdomain)
Type: Domain

This is the catalytic helper subdomain found in collagenase G from Clostridium histolyticum. This domain is indispensable for proper folding and full peptidase activity .
Eis-like, acetyltransferase domain (Acetyltransf_17)
Type: Domain

N-acetyltransferases catalyse the transfer of acetyl groups from acetyl-CoA to arylamines. This acetyltransferase (GNAT) domain is found in Eis from Mycobacterium and other N-acetyltransferases still uncharacterised.
JAK1-3/TYK2, pleckstrin homology-like domain (JAK1-3/TYK2_PHL_dom)
Type: Domain

This entry represents the pleckstrin homology-like (PHL) subdomain found in JAK1-3/TYK2 proteins. PHL (residues 283-419) together with the N-terminal ubiquitin-like subdomain (residues 36-111) and an acyl-coenzyme A binding protein-like subdomain (residues 148-282), associate into a canonical tri-lobed FERM domain .

Janus kinases (JAKs) are tyrosine kinases that function in membrane-proximal signalling events initiated by a variety of extracellular factors binding to cell surface receptors . Many type I and II cytokine receptors lack a protein tyrosine kinase domain and rely on JAKs to initiate the cytoplasmic signal transduction cascade. Ligand binding induces oligomerisation of the receptors, which then activates the cytoplasmic receptor-associated JAKs. These subsequently phosphorylate tyrosine residues along the receptor chains with which they are associated. The phosphotyrosine residues are a target for a variety of SH2 domain-containing transducer proteins. Amongst these are the signal transducers and activators of transcription (STAT) proteins, which, after binding to the receptor chains, are phosphorylated by the JAK proteins. Phosphorylation enables the STAT proteins to dimerise and translocate into the nucleus, where they alter the expression of cytokine-regulated genes. This system is known as the JAK-STAT pathway.

Four mammalian JAK family members have been identified: JAK1, JAK2, JAK3, and TYK2. They are relatively large kinases of approximately 1150 amino acids, with molecular weights of ~120-130kDa. Their amino acid sequences are characterised by the presence of 7 highly conserved domains, termed JAK homology (JH) domains. The C-terminal domain (JH1) is responsible for the tyrosine kinase function. The next domain in the sequence (JH2) is known as the tyrosine kinase-like domain, as its sequence shows high similarity to functional kinases but does not possess any catalytic activity. Although the function of this domain is not well established, there is some evidence for a regulatory role on the JH1 domain, thus modulating catalytic activity. The N-terminal portion of the JAKs (spanning JH7 to JH3) is important for receptor association and non-catalytic activity, and consists of JH3-JH4, which is homologous to the SH2 domain, and lastly JH5-JH7, which is a FERM domain.
Bacterial dipeptidyl-peptidase SH3 domain (SH3_16)
Type: Domain

This is the first of two N-terminal bacterial SH3 (SH3b) domains found in bacterial dipeptidyl-peptidases VI such as gamma-D-glutamyl-L-diamino acid endopeptidases. The first SH3b domain plays an important role in defining substrate specificity by contributing to the formation of the active site, such that only murein peptides with a free N-terminal alanine are allowed .
RuvC endonuclease subdomain 3 (RuvC_III)
Type: Domain

Cas9 proteins are abundant across the bacterial kingdom, but vary widely in both sequence and size. All known Cas9 enzymes contain an HNH domain that cleaves the DNA strand complementary to the guide RNA sequence (target strand), and a RuvC nuclease domain required for cleaving the noncomplementary strand (non-target strand), yielding double-strand DNA breaks (DSBs). The crystal structures of type II-A and II-C Cas9 proteins highlight the features in Cas9 enzymes that support their function as RNA-guided endonucleases. Cas9 enzymes adopt a bilobed architecture composed of a nuclease lobe containing juxtaposed RuvC and HNH nuclease domains and a variable α-helical lobe likely to be involved in nucleic acid binding. The RuvC domain is made up of three discontinuous segments (RuvC-I to RuvC-III), with the HNH domain inserted between the second and the third segments. The RuvC domain forms the structural core of the nuclease lobe, a six-stranded β sheet surrounded by four α helices, with all three conserved subdomains (I, II, III) contributing catalytic residues to the active site .
DNTTIP1, dimerisation domain (DNTTIP1_dimer)
Type: Domain

This is the N-terminal domain of DNTTIP1, a protein that forms part of a novel histone deacetylase complex present in Homo sapiens. Histone deacetylase complexes comprise DNTTIP1, histone deacetylase (HDAC) and the repressor protein MIDEAS. The acetylation of histone tails plays a critical role in determining the accessibility of chromatin to transcriptional regulators and RNA polymerase complexes. This N-terminal domain is responsible for dimerization of histone deacetylase 1(HDAC1). The N-terminal domain also interacts and mediates the assembly of the HDAC1- MIDEAS complex .
5'-3' exoribonuclease 1, SH3-like domain (SH3_12)
Type: Domain

This is the C-terminal SH3-like domain which can be found in the exoribonuclease Xrn1. Xrn1 is a 175kDa processive exoribonuclease that is conserved from yeast to mammals which targets cytoplasmic RNA substrates marked by a 5' monophosphate for processive 5'-to-3' degradation. The Sh3-like domain in Xrn1 lacks the canonical SH3 residues normally involved in binding proline-rich peptide motifs and instead engages in non-canonical interactions with the catalytic domain. Additionally it is essential in maintaining the structural integrity of Xrn1, since partial truncation of this domain in yeast Xrn1 yields an inactive protein. There is a long loop projecting from the SH3-like domain that contacts the PAZ/Tudor domain, occluding the functional surface that binds RNA or peptide motifs containing methylated arginines, respectively, in canonical PAZ and Tudor domain .
XIAP-associated factor 1, C-terminal (XAF1_C)
Type: Domain

XIAP-associated factor 1 (XAF1) is a 301-amino acid interferon (INF)-inducible pro-apoptotic protein. This entry represents the C-terminal domain which is functionally identified as XIAP(RING)-binding domain of XAF1 .
FHOD1, N-terminal GTPase-binding domain (FHOD1_GBD_N)
Type: Domain

This is the N-terminal GTPase-binding domain (GBD) of the formin homology domain-containing proteins (FHOD). This GBD is recruited by Rac and Ras GTPases in cells and plays an essential role for FHOD1-mediated actin remodelling and transcriptional activation, localizes to specific GTPases in cells, and binds to GTPases in vitro. It exhibits structural similarity to the ubiquitin superfold as found, for example, in the Ras-binding domains of c-Raf1 or PI3 kinase, but contains an unusual loop that inserts into the first FH3 repeat .
PNK, FHA domain (FHA_2)
Type: Domain

This entry represents a divergent FHA domain which in human PNK (polynucleotide kinase 3'-phosphatase) binds to phosphorylated segment of XRCC1 .
Importin repeat 6 (Importin_rep_6)
Type: Repeat

The importin subunit beta-3 has a superhelical structure composed of tandem repeats structurally similar to HEAT repeats . This entry represents two consecutive repeat units.
Focal adhesion kinase, N-terminal (FADK_N)
Type: Domain

This entry represents the FERM N-terminal domain found in focal adhesion kinases .