SII-SWORD/CoKE huggingface dataset:
ATP-dependent DNA helicase uvsW, N-terminal domain superfamily (UvsW_N_sf)
Type: Homologous_superfamily

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.
UV-stimulated scaffold protein A, C-terminal domain (UVSSA_C)
Type: Domain

This entry represents a domain found at the C-terminal end of UVSSA and similar eukaryotic proteins.

UV-stimulated scaffold protein A (UVSSA) is part of a UV-induced ubiquitinated protein complex involved in transcription-coupled nucleotide excision repair (TC-NER) in response to UV damage. It stabilise the TC-NER master organising protein ERCC6 (also known as CSB) by delivering the deubiquitinating enzyme USP7 to TC-NER complexes .
Virion DNA-directed RNA polymerase domain (vRNAP_dom)
Type: Domain

This domain is found in Virion DNA-directed RNA polymerase from Bacteriophage N4 (vRNAP,

), responsible for the transcription of the early region of the double-stranded linear DNA genome of the lytic coliphage. This domain adopts a mostly α-helical structure .
Virion DNA-directed RNA polymerase, plug insertion domain (vRNAP_plug)
Type: Domain

This domain is found in Virion DNA-directed RNA polymerase from Bacteriophage N4 (vRNAP,

), responsible for the transcription of the early region of the double-stranded linear DNA genome of the lytic coliphage. This entry represents a short insertion that forms a globular module named plug, which blocks the activity of the protein .
VPg (VPg)
Type: Domain

This entry represents the viral genome-linked protein (VPg) from Caliciviruses, such as Feline calicivirus (FCV). VPg plays a key role in translation initiation from genomic and subgenomic RNAs and is thought to function as a cap substitute for ribosomal recruitment. It interacts with the initiation factor eIF4E. This protein shows a compact helical structure flanked by flexible N- and C-terminal ends .
CRISPR associated protein Cas6, C-terminal domain (Cas_Cas6_C)
Type: Domain

This group of proteins is one of several protein families that are always found associated with prokaryotic CRISPRs, themselves a family of clustered regularly interspaced short palindromic repeats, DNA repeats found in nearly half of all bacterial and archaeal genomes. These DNA repeat regions have a remarkably regular structure: unique sequences of constant size, called spacers, sit between each pair of repeats . It has been shown that the CRISPRs are virus-derived sequences acquired by the host to enable them to resist viral infection. The Cas proteins from the host use the CRISPRs to mediate an antiviral response. After transcription of the CRISPR, a complex of Cas proteins termed Cascade cleaves a CRISPR RNA precursor in each repeat and retains the cleavage products containing the virus-derived sequence. Assisted by the helicase Cas3, these mature CRISPR RNAs then serve as small guide RNAs that enable Cascade to interfere with virus proliferation . Cas5 contains an endonuclease motif, whose inactivation leads to loss of resistance, even in the presence of phage-derived spacers . In Type I and III CRISPR/Cas systems, the Cas6 family of endoribonucleases generates functional CRISPR-derived RNAs by site-specific cleavage of repeat sequences in precursor transcripts .

The structure of Cas6 showed it adopts a tandem ferredoxin/RRM fold . This entry represents the C-terminal domain.
tRNA synthetases class I (E and Q), anti-codon binding domain (tRNA-synt_1c_C2)
Type: Domain

This entry represents the second ribosomal L25-like domain of tRNA synthetases class I, which is part of the anticodon binding domain. Other tRNA synthetase sub-families are too dissimilar to be included. This entry includes only glutamyl and glutaminyl tRNA synthetases. In some organisms, a single glutamyl-tRNA synthetase aminoacylates both tRNA(Glu) and tRNA(Gln).
Trehalose synthase, N-terminal domain (TreT_GT1)
Type: Domain

This domain is found at the N-terminal end of Trehalose synthase from Pyrococcus horikoshii (TreT,

) and similar proteins from bacteria and fungi. TreT synthesises an α,α-trehalose from nucleoside diphosphate glucose and glucose. This protein has a typical GT-B glycosyltransferase structure with dual α/β Rossmann-folds. The N-terminal domain shows a core of six β-strands and seven associated α-helices . This domain is found in the middle region of trehalose phosphorylase TREPH (also known as trehalose synthase) from Pleurotus pulmonarius and related fungal sequences.
TRAFD1/XAF1, zinc finger (TRAFD1-XIAF1_Znf)
Type: Domain

This entry represents a TRAF (C2H2)-type zinc finger found in human TRAD1 (TRAF-type zinc finger domain-containing protein 1), XIAF1 (XIAP-associated factor 1) and similar eukaryotic proteins. TRAFD1 is a negative feedback regulator that controls excessive innate immune responses . XIAF1 seems to function as a negative regulator of members of the IAP (inhibitor of apoptosis protein) family . These proteins share amino acid identity with zinc fingers of TRAF6 .
TNF receptor-associated factor 3/5, RING domain (TRAF3/5_RING)
Type: Domain

This is the RING domain of TNF receptor-associated factors 3 and 5 (TRAF3/5). The RING domain is common among ubiquitin E3 ligases and it is found at the N-terminal of TRAFs, followed by a series of zinc fingers and a C-terminal MATH/TRAF domain. This domain, together with the zinc fingers, is required for ligase activity .
TRAF2, second zinc finger (TRAF2_Znf)
Type: Domain

TRAF2 regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis . It has E3-ubiquitin protein ligase activity and promotes K63-linked ubiquitination of target proteins. It consists of an N-terminal domain with RING (

) and several zinc fingers, and a C-terminal TRAF domain that comprises a coiled-coil (

) and a TRAF-C domain . This entry represents the second β-β-α zinc finger.
Thiamin pyrophosphokinase-like, substrate-binding domain (Thi_PPkinase-like_C)
Type: Domain

This domain is found at the C-terminal end of a group of poorly characterised proteins predominantly found in bacteroidetes and campylobacteria, including Thiamin pyrophosphokinase from Bacteroides thetaiotaomicron. This protein consists of a N-terminal catalytic domain (

) and a C- terminal domain which shows an structure mainly composed of β-strands.
Tetracyclin repressor YgfC-like, C-terminal domain (TetR_YgfC-like_C)
Type: Domain

This domain is found at the C-terminal end of Transcriptional regulator from Lactococcus lactis (YgfC, also known as heme-regulated transporter regulator, HrtR

) and similar proteins predominantly from firmicutes. YgfC senses and binds a heme molecule to regulate the expression of the heme-efflux system responsible for heme homeostasis in this bacteria. This member of the TetR family of transcriptional regulators shows two helical domains and adopts a dimeric configuration .

This entry represents the heme-sensing (heme-binding) domain, which contains the α-helices that form the four-helix bundle that constitutes a dimer interface.
TetR/AcrR transcriptional repressor, C-terminal domain (TetR_C_44)
Type: Domain

TetR/AcrR family transcriptional repressors regulate a wide range of cellular activities, including multidrug resistance, virulence and pathogenicity of bacteria. Members of this family are two domain proteins consisting of N-terminal HTH DNA-binding domain and C-terminal ligand recognition domain.

This entry represents the C-terminal domain that besides the ligand recognition, is involved in dimerisation. In contrast to the N-terminal domain, this domain is more diverse allowing different regulators in the TetR/AcrR family to accommodate specific sets of inducing ligands.
Transcriptional regulator SbtR-like, C-terminal domain (TetR_SbtR-like_C)
Type: Domain

This domain is found at the C-terminal end of Transcriptional regulator SbtR from Thermus thermophilus (

) , SCO0520 from Streptomyces coelicolor (

) and similar sequences predominantly found in actinobacteria. This domain is found associated with

.
Tetracyclin repressor AcrR1-like, C-terminal domain (TetR_AcrR1-like_C)
Type: Domain

This domain is found at the C-terminal end of a small group of bacterial transcriptional regulators, including AcrR1 from Aquifex aeolicus (

). It adopts an all-α structure (

).
A9CJY8-like, N-terminal domain (A9CJY8-like_N)
Type: Domain

This domain is found in a group of prokaryotic uncharacterised proteins, including

from Agrobacterium fabrum. Members of this entry consist of two ACT-like domains, an N-terminal one, represented in this entry and a C-terminal one represented in

.
ACAD9/ACADV-like, C-terminal domain (ACAD9/ACADV-like_C)
Type: Domain

This entry represents the second C-terminal domain from human Complex I assembly factor ACAD9 and Very long-chain specific acyl-CoA dehydrogenase (ACADV) and similar sequences predominantly found in animal and bacteria.

Acyl-CoA dehydrogenases catalyse the alpha,beta-dehydrogenation of acyl-CoA thioesters to the corresponding trans 2,3-enoyl CoA-products with reduction of enzyme-bound FAD. They consist of an N-terminal all-α domain, a middle open (5,8) barrel domain and a four-helical bundle C-terminal domain. Members of the acyl-CoA dehydrogenase family differ in the number of C-terminal domains.

ACAD9 primarily participates in the assembly of the mitochondrial complex I and therefore plays a role in oxidative phosphorylation [

,

, . It does not seem to play a primary role in fatty acid oxidation in vivo .
Acyl-CoA thioesterase-like, N-terminal HotDog domain (TesB_ACOT8-like_N)
Type: Domain

This entry contains a wide variety of enzymes, principally acyl-CoA thioesterases, including Acyl-CoA thioesterase 2 from Escherichia coli (TesB, ) and human Acyl-coenzyme A thioesterase 8 (ACOT8, ). These enzymes are part of the Hotdog fold superfamily . This is the N-terminal of a pair of HotDog domains. In some instances, such as in in acyl-CoA hydrolase 2 from Arabidopsis thaliana, this domain is found in the central region.
Acyl-CoA thioesterase-like, C-terminal domain (ACOT8-like_C)
Type: Domain

This entry contains a wide variety of enzymes, principally thioesterases, including Acyl-coenzyme A thioesterase 8 from Mus musculus (ACOT8). These enzymes are part of the Hotdog fold superfamily . This domain represents the C-terminal domain in a pair of HotDog domains, usually found with

.
Adhesin AWP2-like, C-terminal YTTT repeat (AWP2-like_YTTT_rpt)
Type: Repeat

This entry represents a short sequence repeat found at the C terminus of Adhesin AWP2 from the yeast Candida glabrata. AlphaFold predicts this repeat to adopt a beta hairpin structure. This repeat is found in multiple copies in a range of fungal species .
Anoctamin, transmembrane domain (Anoctamin_TM)
Type: Domain

This entry represents the transmembrane domain from the anoctamin family of proteins, which includes anoctamin1-10 (Ano1-10 or TMEM16A-J) . Seven members could be divided into two subfamilies; Ca2-dependent Cl(-) channels (TMEM16A and 16B) and Ca2-dependent lipid scramblases (TMEM16C, 16D, 16F, 16G, and 16J) . This entry also includes anoctamin-like protein At1g73020 from Arabidopsis and increased sodium tolerance protein 2 (Ist2) from budding yeasts.
Integral membrane bound transporter domain (Memb_transporter_dom)
Type: Domain

This entry represents a domain found in a group of probable integral membrane bound transporters mainly found in bacteria, including putative arylamide transporter from Mycobacterium tuberculosis (

) . It is predicted to adopt an all-α configuration,
Protelomerase TelK-like, stirrup domain (TelK_stirrup)
Type: Domain

This domain is found in Protelomerase from Klebsiella phage phiKO2 (TelK) and similar proteins from tailed bacteriophages and bacterial prophages mainly from Gammaproteobacteria.

TelK is a hairpin telomere resolvase with DNA cleavage-rejoining activity that resolves the catenated circular dimer produced from the bidirectional replication of a chromosome. The core of the TelK monomer consists of an N-terminal domain and a catalytic domain connected by a long α-helical linker. However, there are two extensions of the protein: a C-terminal DNA binding domain named the stirrup and an N-terminal core binding domain. This entry represents the stirrup domain, which shows α-helical and β-hairpin segments, that binds to DNA using the winged helix-turn-helix motif and contacts the DNA flanking the cleavage site, extending the DNA binding interface. It is essential for the orientation and extent of DNA bending and for the refolding of cleaved DNA strands into hairpins .
Set1/Ash2 histone methyltransferase complex subunit ASH2-like, PHD zinc finger (ASH2-like_PHD)
Type: Domain

This entry represents the PHD zinc finger domain of human ASH2 and similar animal sequences. This domain does not have histone tail-binding activity.

Set1/Ash2 histone methyltransferase complex subunit ASH2 from humans (ASH2L, named after 'Absent, small, homeotic disks-2-like') is a component of the Set1/Ash2 histone methyltransferase (HMT) complex and has an important role in regulating the methylation of histone H3 on lysine 4. It consists of an atypical PHD finger at the N-terminal, represented in this entry, followed by a winged-helix (

) and a C-terminal SPRY domain (

) .
Anoctamin, alpha-beta plait domain, fungal-type (Anoctamin_N_fung)
Type: Domain

This entry represents an α/β plait domain found at the N-terminal of a group of fungal TMEM16 family of proteins, also known as anoctamins, including

from Aspergillus fumigatus and ist2 from S.pombe. Proteins in this entry operate as Ca2-activated lipid scramblases . This domain may play a role in dimerisation, although the precise function of this domain is uncertain.
Emfourin (Emfourin)
Type: Family

This family represents a protealysin inhibitor called Emfourin, after M4 family inhibitor (M4in), as protealysin is a metallo-endopeptidase from MEROPS peptidase family M4 . Emfourin is a potent inhibitor that forms a 1:1 stoichiometry complex with protealysin.
Transmembrane protein EpsG-like (EpsG-like)
Type: Family

This entry represents a family of bacterial proteins are related to Transmembrane protein EpsG from Bacillus subtilis (

). EpsG (also known as YveQ) may be involved in the production of the exopolysaccharide (EPS) component of the extracellular matrix during biofilm formation .
Bleomycin resistance protein domain (Bleomycin_resist_prot_dom)
Type: Domain

This domain is found in Bleomycin resistance protein from Lachnoclostridium phytofermentans (Cphy_0674,

) and similar bacterial sequences. It is found usually associated with

. It shows an α-β structure.
Protelomerase TelK-like, muzzle domain (TelK_muzzle)
Type: Domain

This domain is found in protelomerase from Klebsiella phage phiKO2 (TelK) and similar proteins from tailed bacteriophages and bacterial prophages mainly from gammaproteobacteria.

TelK is a hairpin telomere resolvase with DNA cleavage-rejoining activity that resolves the catenated circular dimer produced from the bidirectional replication of a chromosome. The core of the TelK monomer consists of an N-terminal domain and a catalytic domain connected by a long α-helical linker. However, there are two extensions of the protein: a C-terminal DNA binding domain named the stirrup (

) and an N-terminal domain. The latter has an insertion termed the muzzle, represented in this entry, which folds into two long α-helices. This protruding element is packed against the DNA-binding catalytic and N-terminal domains of the opposite subunit in each dimer .
AAA+ ATPase, lid domain (AAA_lid)
Type: Domain

This entry represents the AAA lid domain from the DNA polymerase III, gamma subunit-related protein from Thermotoga maritima (

).
Haptoglobin-hemoglobin receptor (HpHbR)
Type: Family

Haptoglobin-hemoglobin receptor (HpHbR), a protein found within the variant surface glycoprotein (VSG) from trypanosomes, plays a key role in determining if humans can be infected by these parasites developing sleeping sickness. HpHbR is responsible for the acquisition of haem, an important growth factor for these organism that are deficient in its biosynthesis. This protein folds into an elongated three α-helical bundle with a small head structure containing the ligand-binding site that is distal to the C-terminal GPI-anchor attachment site. This structure appears to be conserved among trypanosome species .
Putative poly(A) polymerase, catalytic subunit, C-terminal, mimivirus (APMV_polyA_pol_cat_2nd)
Type: Domain

This domain is found at the C-terminal end of Putative poly(A) polymerase catalytic subunit from Acanthamoeba polyphaga mimivirus (APMV) and similar sequences from mimiviruses. This entry comprises domains D3 and D4. D3 is very similar to the D2 domain (part of

) and shows the typical topology of a nucleotidyltransferase (NT) domain made of a mixed five-stranded β-sheet and two connecting helices. D4 is an extension that the entrance of the central tunnel at the interface of the dimer .
Conjugal transfer protein-like, C-terminal domain (TcpM-like_C)
Type: Domain

This domain is found at the C-terminal end of the transfer protein TraM from Enterococcus faecalis (

) and similar proteins from bacilli. Its structure is similar to this of the conjugative type IV secretion systems (T4SS) VirB8 proteins from Agrobacterium tumefaciens and to the transfer protein TcpC from Clostridium perfringens. It shows two anti-parallel α-helices and an anti-parallel, highly curved β-sheet, made up of five β-strands .
CRISPR-associated endonuclease Cas9, alpha-helical lobe (Cas9_lobe)
Type: Domain

This entry represents the α-helical lobe of the Francisella novicida Cas9 protein (

,

). This domain is also found in similar bacterial sequences.
Complement component 3, CUB domain, first segment (C3_CUB1)
Type: Domain

Complement C3 is major component in the both the classical and alternative complement activation pathways. C3 is cleaved into two chains (alpha and beta) by C3 convertases. C3 is a multidomain protein. This entry represents the first segment of the CUB domain , which is completed by the second segment of the CUB domain, represented in [

]. The CUB domain is interrupted by the TE domain (

). The CUB, TE and MG8 domains form a massive, tightly packed super domain.

This domain is also found in venom factors, also known as Complement C3 homologues. These are complement-activating proteins with structural and functional similarities to complement component C3b, the activated form of C3 .
Ubiquitin-associated protein 1-like, UBA2 domain (UBAP-1-like_UBA2)
Type: Domain

This domain is found in Ubiquitin-associated protein 1 (UBAP-1) and similar proteins predominantly found in animals. UBAP-1 is involved in vesicular trafficking process, as it's a component of an endosome-specific endosomal sorting complex I (ESCRT-I). It is thought to play an important role in the ubiquitin pathway and cell progression. It co-localises with TDP-43 proteins in neuronal cytoplasmic inclusions and acts as a genetic risk factor for frontotemporal lobar degeneration (FTLD). This protein contains an N-terminal UBAP-1-MVB12-associated (UMA) domain, and several tandem ubiquitin- associated (UBA) domains that may be responsible for the binding of ubiquitin-conjugating enzymes. This entry corresponds to UBA2 domain .
Restriction endonuclease type II-like domain (Restrct_endonuc-II-like_dom)
Type: Domain

This entry represents a domain found in a group of prokaryotic proteins. This domain resembles the core structure found in most type II restriction endonucleases, which consists of a 3-layer α/β/α topology with mixed β-sheets .
Exosome complex component RRP40, type I KH domain (RRP40_KH-I)
Type: Domain

This entry represents the type I K homology (KH) RNA-binding domain from human Exosome complex component RRP40 and similar proteins from eukaryotes. It is a divergent KH domain that lacks the RNA-binding GXXG motif .

RRP40, also called exosome component 3 (EXOSC3), or ribosomal RNA-processing protein 40, is a non-catalytic component of the RNA exosome complex which has 3'-->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. Mutations of EXOSC3 gene are associated with neurological diseases .
tRNA (adenine(58)-N(1))-methyltransferase catalytic subunit TRM61, C-terminal (TRM61_C)
Type: Domain

This entry represents the C-terminal domain of yeast tRNA (adenine(58)-N(1))-methyltransferase catalytic subunit TRM61 and similar proteins widespread among all cellular organisms. TRM61, also known as GCD14, catalyses the formation of N1-methyladenine at position 58 (m1A58) in initiator methionyl-tRNA . It is also required for repression of GCN4 mRNA translation by the upstream open reading frames (uORFs) under conditions of amino acid sufficiency . This domain adopts a class I MTase fold that consists of a seven-stranded mixed β-sheet sandwiched by helices .
SPP1 phage GP23.1-like (SPP1_GP23.1-like)
Type: Family

Gp23.1 (

) from Bacillus subtilis SPP1 phage adopts a hexamer assembly and is likely to function as a chaperone . This family of highly conserved sequences is found in phages with long non-contractile tails and in bacterial prophages.
MRN complex-interacting protein, N-terminal domain (MRNIP_N)
Type: Domain

This domain is found at the N-terminal of human MRN complex-interacting protein (MRNIP) and similar proteins from eukaryotes. MRNIP plays a role in preventing the accumulation of damaged DNA in cells. It associates with the MRE11-RAD50-NBS1 (MRN) damage-sensing complex and is rapidly recruited to sites of DNA damage. Phosphorylation of a serine promotes nuclear localisation of MRNIP .
CRISPR-associated endonuclease Cas9, PI domain, C-terminal domain (Cas9_PI_C)
Type: Domain

This domain is found at the C-terminal end of CRISPR-associated endonuclease Cas9 from Staphylococcus aureus (Cas9) and similar sequences specific to Staphylococcus. Cas9 adopts a bilobed architecture consisting of a REC lobe and a NUC lobe connected by an arginine-rich bridge helix and a linker loop. The C-terminal region, known as the PI domain, can be divided into a Topoisomerase-homology (TOPO) domain (

) and a C- terminal domain (this entry). This domain forms a twisted six-stranded anti-parallel β-sheet .
Flagellar hook-associated protein 1, D3 domain (FlgK_D3)
Type: Domain

This entry includes Flagellar hook-associated protein 1 from Burkholderia pseudomallei (the causing agent of melioidosis) (

, known as FlgK or HAP1) and similar sequences predominantly found in betaproteobacteria. FlgK is one of three HAPs that form the hook-filament junction and has structural similarity to flagellin. This protein has a multidomain fold comprising an elongated α-helical scaffold core, and depending on the bacterial species, a variable number of smaller domains . FlgK has two β-sandwich domains protruding from the large α-helical core, referred to as D2 and D3 domains in , with the second one (D3) represented in this entry . FlgK has cytotoxic effects suggesting an important role in pathogenesis and is highly immunogenic. Domains D2 and D3 have been identified as epitopes with increased immunogenic potential for vaccine development .
Mannanase, galactose-binding domain-like (Mann_GBD_bact)
Type: Domain

This is a galactose-binding domain-like found at the C-terminal of alkaline mannanases, such as

from Bacillus sp. JAMB-602 and related bacterial sequences which belong to the Glycoside Hydrolase Family 5 (

).