SII-SWORD/CoKE huggingface dataset:
Fas-binding factor 1, C-terminal (FBF1_C)
Type: Domain

This entry represents a domain found at the C-terminal end of human Fas-binding factor 1 (FBF1) (

) and similar animal sequences. FBF1 is a keratin-binding protein required for epithelial cell polarisation. It is involved in apical junction complex (AJC) assembly via its interaction with PARD3 and required for ciliogenesis .

Intraflagellar transport (IFT) machinery is required for the assembly and maintenance of cilia. Fas-binding factor 1 (FBF1) is a transition fibre protein required for the ciliary import of assembled IFT particles at the ciliary base . FBF1, also known as albatross, has also being shown to be involved in regulating polarization in epithelial cells .
Fatty acid synthase, pseudo-KR domain (FAS_pseudo-KR)
Type: Domain

Fatty acid synthase is a multifunctional enzyme that catalyses the de novo biosynthesis of long-chain saturated fatty acids, starting from acetyl-CoA and malonyl-CoA in the presence of NADPH . This entry represents the pseudo-ketoreductase (pseudo-KR) domain which is catalytically inactive and supports the integrity of the active KR domain .
Formamidopyrimidine-DNA glycosylase, C-terminal domain (FPG_C)
Type: Domain

This entry represents a small C-terminal zinc finger domain found in a small subset of viral Formamidopyrimidine-DNA glycosylase (FPG) enzymes (such as:

) .
Selenocysteine-specific elongation factor, 3rd domain (eEFSec_III)
Type: Domain

This domain is found in Selenocysteine-specific elongation factor from humans (eEFSec) (

) and similar sequences mainly found in animals. eEFSec is a translation factor necessary for the incorporation of selenocysteine into proteins. This protein adopts a chalice-like structure composed of four domains. This entry represents the third domain, which shows seven antiparallel β-strands and a long α-helix .
Selenocysteine-specific elongation factor, C-terminal RIFT domain (eEFSec_C)
Type: Domain

This entry represents the C-terminal RIFT β barrel domain found in human Selenocysteine-specific elongation factor (eEFSec) (

) and similar sequences mainly found in animals. Selenocysteine is the only proteinogenic amino acid encoded by a recoded in-frame UGA codon that does not operate as the canonical opal stop codon. A specialised translation elongation factor, eEFSec in eukaryotes and SelB in prokaryotes, promotes selenocysteine incorporation into selenoproteins .
ECT2, PH domain (ECT2_PH)
Type: Domain

ECT2 (Epithelial Cell Transforming Sequence 2) is a guanine nucleotide exchange factor (GEF) that catalyses the exchange of GDP for GTP. It is a cell cycle regulator that plays key roles in cytokinesis . ECT2 contains triple copies of the BRCT domain (BRCT0 (

), BRCT1 and BRCT2 (

) at the N-terminal, separated from the C-terminal DH (

) and PH domains by a linker of about 100 residues. This entry represents the PH domain . The BRCT and DH-PH domains mediate intra-molecular interactions that restrains ETC2 activity during interphase.
ECT2, BRCT0 domain (ECT2_BRCT0)
Type: Domain

ECT2 (Epithelial Cell Transforming Sequence 2) is a guanine nucleotide exchange factor (GEF) that catalyses the exchange of GDP for GTP. It is a cell cycle regulator that plays key roles in cytokinesis [1-4]. ECT2 contains triple copies of the BRCT domain (BRCT0, BRCT1 (

) and BRCT2 (

) at the N-terminal, separated from the C-terminal DH (

) and PH (

) domains by a linker of about 100 residues. This entry represents the first BRCT domain, BRCT0 . The BRCT and DH-PH domains mediate intra-molecular interactions that restrains ETC2 activity during interphase.
HTH-type transcriptional regulator EthR, C-terminal domain (EthR_C)
Type: Domain

HTH-type transcriptional regulator EthR (

) is involved in the repression of the monooxygenase EthA which is responsible of the formation of the active metabolite of ethionamide (ETH). It is responsible for the low sensitivity of the human pathogen Mycobacterium tuberculosis to ethionamide. It consists of a DNA-binding HTH domain at the N-terminal (

) and a C-terminal helical domain that binds its ligand (this entry) .
ETF-QO/FixC, ubiquinone-binding (ETF-QO/FixC_UQ-bd)
Type: Domain

Electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) is a a 4Fe4S flavoprotein located in the inner mitochondrial membrane and catalyses ubiquinone (UQ) reduction. It forms a single structural domain with three functional regions (that bind FAD, the 4Fe4S cluster, and UQ) which are closely packed and share structural elements . This domain includes the residues involved in UQ binding . This domain is also found in FixC proteins from bacteria (

], which share similarities with ETF-QO .
BDLP-like, helical domain (BDLP-like_hel)
Type: Domain

This entry represents the helical region from Bacterial dynamin-like protein (BDLP,

) from Nostoc punctiforme and similar large GTPases with multidomain architectures mainly found in cyanobacteria. BDLP is a dynamin-related GTPase probably involved in membrane remodelling . This region covers the middle and GED domains which mediate extensive protein-protein contacts .
Cytoplasmic dynein 2 heavy chain 1, AAA+ ATPase domain (DYNC2H1_AAA_dom)
Type: Domain

This domain is found in Cytoplasmic dynein 2 heavy chain 1 from humans (DYNC2H1) and similar sequences mainly found in animals. Dynein-2 is essential for the dynamic remodelling of the ciliary proteome and is associated with human skeletal ciliopathies. DYNC2H1, one of its specific components, is the motor-domain- containing heavy chain. This protein consists of a compact N-terminal region, an elongated tail and a C-terminal AAA motor domain. There are two copies of this protein in the complex, each adopting a different configuration, which contributes to the asymmetry of Dynein-2. This entry covers one of the six motor's ring AAA domains (ATPases associated with various cellular activities) .
DZF domain, N-terminal (DZF_dom_N)
Type: Domain

This entry represents the N-terminal mixed α/β region of the DZF domain, which contains a central anti-parallel β-sheet . It is usually found in combination with

. Members of this entry are found exclusively in metazoa.

The DZF domain (domain associated with zinc fingers) is a dimerisation domain found in :

Interleukin enhancer-binding factor 3 (also known as Nuclear factor of activated T-cells 90 kDa, NF90, DRBP76 or NFAR), contains two double-stranded RNA-binding motifs (dsRBMs) and interacts with highly structured RNAs as well as the dsRNA-activated protein kinase (PKR).

Interleukin enhancer-binding factor 2 (also known as NF45), which appears to function predominantly as a heterodimeric complex with NF90.

Spermatid perinuclear RNA-binding protein (SPNR, also known as STRBP), a testes specific paralogue of NF90.

Zinc finger RNA-binding protein (Zfr).

Nuclear factors NF90 and NF45 form a protein complex involved in a variety of cellular processes and are thought to affect gene expression both at the transcriptional and translational level. In addition, this complex affects the replication of several viruses through direct interactions with viral RNA. NF90 and NF45 dimerise through their common DZF domain. The DZF domain shows structural similarity to the template-free nucleotidyltransferase family of RNA modifying enzymes. However, the lack of conserved catalytic residues suggests that the DZF domain encodes a 'pseudotransferase' that is no longer able to catalyse transfer of nucleotides.

The DZF dimerisation domain form an oblong structure with a flat face on one side and a curved face on the other. The DZF domain is bipartite and characterised by an N-terminal mixed α/β region that contains a central anti-parallel β-sheet and a C-terminal α-helical region. The overall structure has a pseudo two-fold rotational symmetry.

The central β-sheet forms the base of a cleft between the N- and C-terminal halves while dimerisation is mediated by the α-helices at the C terminus .
DZF domain, C-terminal (DZF_dom_C)
Type: Domain

This entry represents the C-terminal α-helical region of the DZF domain .
The function of this domain is unknown . It is usually found in combination with

. Members of this entry are found exclusively in metazoa.

The DZF domain (domain associated with zinc fingers) is a dimerisation domain found in :

Interleukin enhancer-binding factor 3 (also known as Nuclear factor of activated T-cells 90 kDa, NF90, DRBP76 or NFAR), contains two double-stranded RNA-binding motifs (dsRBMs) and interacts with highly structured RNAs as well as the dsRNA-activated protein kinase (PKR).

Interleukin enhancer-binding factor 2 (also known as NF45), which appears to function predominantly as a heterodimeric complex with NF90.

Spermatid perinuclear RNA-binding protein (SPNR, also known as STRBP), a testes specific paralogue of NF90.

Zinc finger RNA-binding protein (Zfr).

Nuclear factors NF90 and NF45 form a protein complex involved in a variety of cellular processes and are thought to affect gene expression both at the transcriptional and translational level. In addition, this complex affects the replication of several viruses through direct interactions with viral RNA. NF90 and NF45 dimerise through their common DZF domain. The DZF domain shows structural similarity to the template-free nucleotidyltransferase family of RNA modifying enzymes. However, the lack of conserved catalytic residues suggests that the DZF domain encodes a 'pseudotransferase' that is no longer able to catalyse transfer of nucleotides.

The DZF dimerisation domain form an oblong structure with a flat face on one side and a curved face on the other. The DZF domain is bipartite and characterised by an N-terminal mixed α/β region that contains a central anti-parallel β-sheet and a C-terminal α-helical region. The overall structure has a pseudo two-fold rotational symmetry.

The central β-sheet forms the base of a cleft between the N- and C-terminal halves while dimerisation is mediated by the α-helices at the C terminus .
Ell binding protein Ebp1, C-terminal (Ebp1_C)
Type: Domain

This entry represents the conserved C-terminal domain of Ell binding protein 1 (Ebp1) from Schizosaccharomyces pombe (

), which is distantly related to AFF family of proteins from metazoans. This domain is known as AFF4 C-terminal homology domain (CHD) or C-terminal signature sequence (CSS) . The function of Ebp1 is not clear. It colocalises with Ell1 and Eaf1, being part of the SEC-like complex that regulates Pol II transcription . This domain is found in several species from actinomycetes, but not in S. cerevisiae .
Enhancer of mRNA-decapping protein 4, C-terminal (EDC4_C)
Type: Domain

Enhancer of mRNA-decapping protein 4 (EDC4, also known as Ge-1), is a regulator of mRNA decapping to function in the mRNA P-bodies within the cytoplasm. It has been shown to interact with mTORC1 , coenzyme A synthase and MARF1 . It is also involved in the regulation of immune system . This is the C-terminal domain which is necessary and sufficient for P-body targeting and in plants, it also mediates DCP1 and DCP2 interaction, as well as self-association . It adopts an helical-repeat fold similar to that of ARM/HEAT repeat proteins.
Edema factor, alpha-helical domain (EF_HD)
Type: Domain

This domain is found in Edema factor (EF, also known as Calmodulin-sensitive adenylate cyclase), the exotoxin with adenylyl cyclase activity produced by Bacillus anthracis to increase the concentration of cyclic AMP in infected host cells and disrupt intracellular signalling pathways. EF consists of four domains: a PA-binding domain (PABD), two adenylate cyclase domains (ACD) and a helical domain (HD, this entry). HD moves and forms a large clamp that almost completely encircles EF's activator calmodulin (CaM), naturally present in host cells, stabilising a disordered loop and leading to enzyme activation .
Zinc transporter ZIP4/12, EF-hand (ZIP4_12_EF-hand)
Type: Domain

This entry represents an EF-hand-like domain found in a group of Zip zinc transporters from vertebrates, including human Zinc transporter ZIP4/12 . ZIP12 may play a role in neurulation and neurite extension. It may also be involved in maintaining intracellular zinc content at levels that reduce the inhibitory effects of rises in oxidative stress on spermatogonia and spermatozoa viability during spermatogenesis .
Ubiquitin carboxyl-terminal hydrolase 38-like, N-terminal domain (Usp38-like_N)
Type: Domain

This domain is found at the N-terminal end of Ubiquitin carboxyl-terminal hydrolase 38 from humans (Usp38) and similar proteins predominantly found in vertebrates. Usp38 is a deubiquitinating enzyme that plays a role in various cellular processes, including DNA repair, cell cycle regulation, and immune response . This domain forms ARM repeats. It is often associated to

.
UV-stimulated scaffold protein A, N-terminal alpha-solenoid repeats (UVSSA_N_a-solenoid_rpt)
Type: Repeat

This entry represents the N-terminal set of alpha solenoid repeats found in UV-stimulated scaffold protein A (UVSSA) and related proteins from eukaryotes. UVSSA is involved in transcription-coupled nucleotide excision repair, a mechanism that rapidly removes RNA polymerase II-blocking lesions from the transcribed strand of active genes .
ATP-dependent DNA helicase uvsW, N-terminal (UvsW_N)
Type: Domain

This entry represents the small N-terminal α/β domain of the DNA helicase UvsW from bacteriophage T4 , which consists of five β-strands and two α-helices. This domain is structurally homologous to the DNA-binding domain of the T4 transcription factor MotA, thus, it likely binds the nucleic acid substrate . Members of this group of proteins are found in tailed bacteriophages and prophages from some bacterial species.
Endo-beta-N-acetylglucosaminidase EndoS-like, Ig-like domain (EndoS-like_Ig-like)
Type: Domain

This domain is found in Endo-beta-N-acetylglucosaminidase EndoS from Streptococcus pyogenes and similar sequences predominantly found in firmicutes. EndoS is an immunomodulatory enzyme secreted by the bacteria to remove carbohydrates from IgG antibodies in a highly specific manner, which gives the pathogen a survival advantage over its host. This protein is composed of five distinct protein domains. The domain located at the base of the V-shaped EndoS structure (this entry), also named hybrid Ig domain, is composed of two subdomains. The smaller one is inserted within the loop that connects the LRR domain to the second and third β-strands of the larger subdomain. The latter is a typical Ig domain structurally similar to the interleukin-4 receptor .
V-cyclin, C-terminal domain (V-cyclin_C)
Type: Domain

This domain is found at the C-terminal end of V-cyclin from Murid herpesvirus 4 (MuHV-4,

) and similar proteins specific to herpesvirus. This domain adopts an α-helical structure . It is usually associated with

.
Minor capsid protein V18-like, jelly roll domain (V18-like_jelly_roll)
Type: Domain

This entry represents the single jelly-roll domain of Sputnik virus minor capsid proteins V18 .

Sputnik is a dsDNA virus, referred to as a virophage, that is coassembled with Mimivirus in the host amoeba. It is an icosahedral virus and its capsid contains a major protein (V20) and two minor proteins (V18/19) .
Minor capsid protein V18/19-like, jelly roll domain superfamily (V18/19-like_jelly_roll_sf)
Type: Homologous_superfamily

This entry represents the single jelly-roll domain of Sputnik virus minor capsid proteins V18 and V19 .

Sputnik is a dsDNA virus, referred to as a virophage, that is coassembled with Mimivirus in the host amoeba. It is an icosahedral virus and its capsid contains a major protein (V20) and two minor proteins (V18/19) .
VopL, C-terminal dimerization domain (VopL_VCD)
Type: Domain

The VopL C-terminal dimerization domain (VCD) is found in Vibrio parahaemolyticus protein L (VopL,

), an actin nucleation factor that induces stress fibres when injected into eukaryotic host cells. VCD shows a mainly α-helical fold, forms a U-shaped dimer and interacts with the pointed end of the actin nucleus, contributing to the nucleation activity directly .
VopL, C-terminal dimerization domain superfamily (VopL_VCD_sf)
Type: Homologous_superfamily

The VopL C-terminal dimerization domain (VCD) is found in Vibrio parahaemolyticus protein L (VopL,

), an actin nucleation factor that induces stress fibres when injected into eukaryotic host cells. VCD shows a mainly α-helical fold, forms a U-shaped dimer and interacts with the pointed end of the actin nucleus, contributing to the nucleation activity directly .
Malonyl-CoA-[acyl-carrier-protein] transacylase, small domain (VinK-like_small)
Type: Domain

This family includes Malonyl-CoA-[acyl-carrier-protein] transacylase from Streptomyces halstedii (VinK,

) and similar sequences predominantly found in actinomycetes. VinK transfers a dipeptide group between two ACPs, VinL and VinP1LdACP, in vicenistatin biosynthesis . VinK is composed of two α/β domains. This entry represents the small domain . The two conserved catalytic residues of VinK are located at the interface between the large domain and small domain .
VipE-like, N-terminal (VipE-like_N)
Type: Domain

Legionella pneumophila use the Icm/Dot type IVB secretion system to deliver into the host cell effectors that inhibit phagosome maturation and modulate host vesicle trafficking pathways. VipE (

) is one of those effectors. This entry represents the N-terminal domain of VipE that adopts an α-helical fold (

). This domain is also found in similar sequences from gammaproteobacteria.
VopS, N-terminal domain (VopS_N)
Type: Domain

This domain is found at the N-terminal end of VopS from Vibrio parahaemolyticus and similar sequences from gammaproteobacteria. VopS is an adenylyltransferase involved in virulence by provoking the disruption of Rho GTPase signalling and the inhibition of actin assembly in infected cells. This domain is required for full activity of VopS. It consists of nine α-helices .
Reelin, subrepeat B (Reelin_subrepeat-B)
Type: Repeat

Reelin is an extracellular matrix serine protease that plays a role in layering of neurons in the cerebral cortex and cerebellum. It regulates microtubule function in neurons and neuronal migration. It binds to the extracellular domains of lipoprotein receptors VLDLR and LRP8/APOER2 which induces tyrosine phosphorylation of DAB1 and modulation of TAU phosphorylation. Reelin contains 8 tandemly repeated units, each of which is composed of two highly similar subrepeats of 150-190 amino acids (subrepeats A and B) that flank a central EGF domain .

This entry represents subrepeat B (also referred to R3B) which adopts a β-jelly roll fold similar to bacterial xylanase. They contain the signature Asp-box motif .
EPCAM/Trop-2, C-terminal (EPCAM-Trop-2_C)
Type: Domain

EpCAM (epithelial cell adhesion molecule, also known as Trop-1) and Trop-2 (also known as tumor-associated calcium signal transducer 2, TACSTD2) are transmembrane glycoproteins that belong to the tumour-associated calcium signal transducer (TACSTD) family. They are evolutionarily related and both are implicated in signalling triggered by proteolytic cleavage within the ectodomain . They share an overall similar structure but differ in their dimers formation. They consist of an ectodomain with an N-terminal, thyroglobulin type-1 (TY,

) and C-terminal domains. This entry represents the C-terminal domain of EpCAM and Trop-2, which has an α/β fold .
Inner capsid protein VP1, small protrusion domain (VP1_protrusion)
Type: Domain

This domain is found in Inner capsid protein VP1 from Cytoplasmic polyhedrosis virus (CPV). VP1, one of the three major capsid proteins of CPV, has an overall thin-plate-like shape similar to its counterparts in other reoviruses except for a protrusion domain on the outer capsid surface, which is unique in single-layered cypoviruses .
Capsid protein VP1/VP3, C-terminal (VP1/VP3_C)
Type: Domain

This entry represents the C-terminal domain of capsid proteins from reovirales that form the icosahedral capsid through self-assembly (they are also known as inner layer core proteins). The capsid encapsulates and protects the genomic RNA. These viruses encode VP1, VP3 and VP5 as major capsid proteins, encoded by RNA segment 1 and 3 in the case of VP1 and VP3, respectively, whereas RNA segment encoding VP5 is still unclear .
Viral structural protein 5 (VP5)
Type: Family

Viral structural protein 5 (VP5,

) is one of the three major capsid proteins found in Cytoplasmic polyhedrosis virus (CPV) . This family is found in Reovirales.
Vacuolar protein sorting-associated protein 27, GAT-like domain (Vps27_GAT-like)
Type: Domain

This domain is found in Vacuolar protein sorting-associated protein 27 from Saccharomyces cerevisiae (Vps27,

) and similar sequences predominantly found in yeast. Vps27 binds to ubiquitinated transmembrane proteins and recruits both ubiquitin ligases and deubiquitinating enzymes. Besides the GAT domain (this entry), Vps27 contains VHS (

) and FYVE domains (

). This domain forms a three α-helical bundle that resembles closely the structure of a GAT domain .
Acyl-CoA dehydrogenase-like, C-terminal domain (Acyl-CoA-dh-like_C)
Type: Domain

This is an all-α up-and-down bundle found in acyl-CoA dehydrogenases, such as

from Bacillus subtilis.
Acyl-ACP thioesterase-like, C-terminal domain (Acyl-ACP_TE_C)
Type: Domain

This entry represents a domain found in various acyl-acyl carrier protein (ACP) thioesterases (TE) and similar proteins. These proteins terminate fatty acyl group extension via hydrolysing an acyl group on a fatty acid . Members of this entry are usually composed of a pair of tandem HotDog domains. This entry represents the C-terminal one of the pair .
RecA-like, N-terminal (RecA-like_N)
Type: Domain

This entry represents the N-terminal region of RecA.

The recA gene product is a multifunctional enzyme that plays a role in homologous recombination, DNA repair and induction of the SOS response . In homologous recombination, the protein functions as a DNA-dependent ATPase, promoting synapsis, heteroduplex formation and strand exchange between homologous DNAs . RecA also acts as a protease cofactor that promotes autodigestion of the lexA product and phage repressors. The proteolytic inactivation of the lexA repressor by an activated form of recA may cause a derepression of the 20 or so genes involved in the SOS response, which regulates DNA repair, induced mutagenesis, delayed cell division and prophage induction in response to DNA damage .

RecA is a protein of about 350 amino-acid residues. Its sequence is very well conserved among eubacterial species. It is also found in the chloroplast of plants . RecA-like proteins are found in archaea and diverse eukaryotic organisms, like fission yeast, mouse or human. In the filament visualised by X-ray crystallography, β-strand 3, the loop C-terminal to β-strand 2, and α-helix D of the core domain form one surface that packs against α-helix A and β-strand 0 (the N-terminal domain) of an adjacent monomer during polymerisation . The core ATP-binding site domain is well conserved, with 14 invariant residues. It contains the nucleotide binding loop between β-strand 1 and α-helix C. The Escherichia coli sequence GPESSGKT matches the consensus sequence of amino acids (G/A)XXXXGK(T/S) for the Walker A box (also referred to as the P-loop) found in a number of nucleoside triphosphate (NTP)-binding proteins. Another nucleotide binding motif, the Walker B box is found at β-strand 4 in the RecA structure. The Walker B box is characterised by four hydrophobic amino acids followed by an acidic residue (usually aspartate). Nucleotide specificity and additional ATP binding interactions are contributed by the amino acid residues at β-strand 2 and the loop C-terminal to that strand, all of which are greater than 90% conserved among bacterial RecA proteins.
AF2093-like (AF2093-like)
Type: Family

This family represents the uncharacterised protein AF2093 (

), which has no known function. The three-dimensional fold (

) of this protein family resembles that of PDDEXK nucleases, but it lacks the typical catalytic site .