SII-SWORD/CoKE huggingface dataset:
EDR1/CTR1/ARMC3-like, peptidase-like domain (EDR1/CTR1/ARMC3-like_pept-like)
Type: Domain

This entry represents a peptidase-like domain mainly found in plant proteins, including serine/threonine-protein kinases EDR1 and CTR1 from Arabidopsis thaliana. EDR1 regulates disease resistance and ethylene-induced senescence, and is also involved in stress response signaling and cell death regulation . CTR1 acts as a negative regulator in the ethylene response pathway . It phosphorylates the cytosolic C-terminal domain of EIN2, preventing the signaling in the absence of ethylene .

This entry also includes proteins from animals, such as ARMC3, which is essential for male fertility and sperm motility. During spermatogenesis, promotes the autophagic degradation of excessive ribosomes, providing energy resources for mitochondria and thus ensuring sperm flagellar motility .
Flagellar protein FlgA, HotDog domain-like (FlgA_HD-like)
Type: Domain

This domain is found in the flagellar protein FlgA from Thermotoga maritima (

) and similar sequences from Thermotogales. Its structure has been characterised (

).
Transcriptional regulator SarA/SarZ/Rot-like, helix-turn-helix domain (Transc_reg_Sar_Rot_HTH)
Type: Domain

This entry represents a helix-turn-helix (HTH) domain found in bacterial transcriptional regulatory proteins, including SarA, SarZ and Rot from Staphylococcus aureus . Sar is a global regulator with both positive and negative effects that controls expression of several virulence factors and biofilm formation process in a cell density-dependent manner. Rot plays a key role in regulating S. aureus virulence through activation or repression of promoters that control expression of a large number of critical virulence factors .
Rootletin-like, coiled-coil (Rootletin-like_CC)
Type: Domain

This is a coiled-coil domain found in rootletin (also known as Ciliary rootlet coiled-coil protein, CROCC), CROCC2, the centrosome-associated protein CEP250 and related sequences, involved in centrosome cohesion .

Rootletin is the major structural component of the ciliary rootlet, a cytoskeletal-like structure in ciliated cells which originates from the basal body at the proximal end of a cilium and extends proximally toward the cell nucleus. It is required for the correct positioning of the cilium basal body relative to the cell nucleus, to allow for ciliogenesis and contributes to centrosome cohesion before mitosis .

CEP250 (also known as C-Nap1) is a Nek2-interacting protein localised at centrosomes during interphase and has been implicated in the cell-cycle regulated cohesion of microtubule-organizing centers . It recruits CCDC102B to the proximal ends of centrioles .
Pyruvate-ferredoxin oxidoreductase, insertion domain (Pyruv_OxRed_insertion)
Type: Domain

This entry represents the insertion domain of Pyruvate-flavodoxin oxidoreductase from Desulfocurvibacter africanus (Por) and similar bacterial sequences. Por catalyses the ferredoxin-dependent oxidative decarboxylation of pyruvate required for the transfer of electrons from pyruvate to ferredoxin . This domain adopts a four helical bundle fold.
Adenylosuccinate lyase, C-terminal domain (ASLyase_C)
Type: Domain

This entry represents the C-terminal helical domain present in the adenylosuccinate lyase from Pyrobaculum aerophilum and similar archaeal proteins. This domain is remotely related to

(Adenylosuccinate lyase C terminus).
GFO/IDH/MocA-like oxidoreductase domain (GFO_IDH_MocA-like_dom)
Type: Domain

This entry includes a domain found in a set of oxidorecuctases from GFO/IDH/MocA family, including Inositol 2-dehydrogenase from Streptomyces coelicolor, human Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase, 1,5-anhydro-D-fructose reductase from Rhizobium meliloti and Levoglucosan dehydrogenase from Pseudarthrobacter phenanthrenivorans .
GT-D fold-like domain (GT-D-like)
Type: Domain

This domain is related to the GT-D fold glycosyltransferase domain (

). These protein domains share a common sequence motif R[VIL]GDGE, significant structural similarity based on the predicted AF2 model, but low sequence similarity. This domain is found standalone and in combination with other domains in a number of proteins from bacteria.
RsaL-like, HTH domain (HTH_RsaL-like)
Type: Domain

This is a helix-turn-helix (HTH) domain found in quorum-sensing regulator RsaL (

) from Pseudomonas aeruginosa and related proteins . RsaL is a QS repressor that reduces QS signal production and ensures homeostasis by functioning in opposition to LasR .
Transcriptional repressor NrdR-like, N-terminal domain (NrdR-like_N)
Type: Domain

This entry represents the N-terminal domain of the Transcriptional repressor NrdR and similar sequences, which is a zinc β-ribbon domain, followed by an ATP-cone domain (

) . These proteins negatively regulates transcription of bacterial ribonucleotide reductase nrd genes and operons by binding to NrdR-boxes. This domain harbors two conserved CxxC motifs that coordinate a zinc ion, and binds to the highly conserved NrdR boxes (

) .
Pus10, THUMP domain, archaeal (Pus10_THUMP_arc)
Type: Domain

This entry represents the THUMP domain found in Pus10 proteins from archaea. Pus10 is a tRNA pseudouridine synthase responsible for the synthesis of pseudouridine from uracil-54 and uracil-55 in the psi GC loop of transfer RNAs .
ACK/TNK-like, SAM domain (ACK/TNK-like_SAM)
Type: Domain

This entry represents the SAM (sterile alpha motif) domain of ACK/TNK-like subfamily of non-receptor tyrosine-protein kinases. It is usually located at the N terminus and is followed by the catalytic domain and a number of other domains. This is a putative protein-protein interaction domain .
UBP24/USP9X/USP9Y, ubiquitin-like domain (UBP24/USP9X/USP9Y_UBL)
Type: Domain

This entry represents a Ubiquitin-like domain found in a ubiquitin carboxyl-terminal hydrolases, such as UBP24, USP9X and USP9Y from human and its orthologue from Drosophila, the probable ubiquitin carboxyl-terminal hydrolase FAF. UCHs are thiol proteases that recognise and hydrolyse the peptide bond at the C-terminal glycine of ubiquitin .

UBP24 regulates cell survival in various contexts through modulating the protein stability of some of its substrates including DDB2, MCL1 or TP53 . It plays a positive role on ferritinophagy where ferritin is degraded in lysosomes and releases free iron . USP9X and USP9Y are involved in deubiquitination of target proteins . USP9X is also involved in the processing of ubiquitin precursors and therefore, it may play an important regulatory role at the level of protein turnover by preventing degradation of proteins.
UPF0425 pyridoxal phosphate-dependent protein MJ0158-like, C-terminal domain (UPF0425_MJ0158-like_C)
Type: Domain

This entry represents the C-terminal domain of UPF0425 pyridoxal phosphate-dependent protein MJ0158 from Methanocaldococcus jannaschii and similar sequences mainly found in archaea.
RsdA/BaiN/AoA(So)-like, insert domain (RsdA/BaiN/AoA(So)-like_dom)
Type: Domain

This entry represents two structural (β-barrel and H2TH α-helical) domains that are found inserted within a Rossmann fold-like domain

.

This domain is found in 3-dehydro-bile acid delta(4,6)-reductase from Clostridium scindens (BaiN), Ribosomal RNA dihydrouridine synthase (rdsA) from Escherichia coli and Aminoacetone oxidase (aao(So)) from Streptococcus cristatus.

BaiN is involved in the secondary bile acid metabolism. It catalyses two subsequent reductions of the double bonds within the bile acid A/B rings of 3-oxochol-4,6-dien-24-oyl-CoA and 12alpha-hydroxy-3-oxochol-4,6-dien-24-oyl-CoA to yield 3-oxocholan-24-oyl-CoA and 12alpha-hydroxy-3-oxocholan-24-oyl-CoA, respectively .

RdsA catalyses the synthesis of 5,6-dihydrouridine (D) at position 2449 in 23S rRNA. It can use NADH as a source of reducing equivalents but not NADPH .

Aao(So) is a flavoprotein thought to catalyse the condensation of two aminoacetone molecules to form 3,6-dimethyl-2,5-dihydropyrazine, which is then oxidised to 2,5-dimethylpyrazine, suggesting a role in a microbial defence pathway that avoids toxic methylglyoxal production. It has low aminoacetone oxidase activity and can generate hydrogen peroxide from aminoacetone, peptone, and several L-amino acids, indicating a potential function in oxidative metabolism and antimicrobial defence. However, it shows little to no activity toward substrates like L-malate, oxaloacetate, or alpha-aminobutyrate. Overall, it contributes to antioxidant defence mechanisms .
Tex-like, central region (Tex-like_central_region)
Type: Domain

This domain is found in the transcriptional accessory protein Tex protein from Bordetella pertussis, in the human and yeast transcription elongation factor SPT6 and in similar sequences maily from bacteria and eukaryotes. Tex belongs to a family of prokaryotic transcriptional accessory factors that likely function in a variety of transcriptional processes . SPT6 binds histone H3 and plays a key role in the regulation of transcription elongation and mRNA processing . It enhances the transcription elongation by RNA polymerase II (RNAPII) and is also required for the efficient activation of transcriptional elongation by the HIV-1 nuclear transcriptional activator, Tat . This domain is mainly α-helical, showing a number of small helices that wrap around a long central helix. It is often found immediately N-terminal to

.
Restriction endonuclease, type I, HsdR, second RecA-like helicase domain (HsdR_RecA-like_helicase_dom_2)
Type: Domain

This entry represents the second RecA-like helicase domain (the third domain) found in a restriction (R) subunit (HsdR) of a number of type I restriction enzymes, including the Type I restriction enzyme EcoR124I/EcoR124II endonuclease subunit from Escherichia coli . Subunit R is required for both nuclease and ATPase activities, but not for modification . This domain folds into an α/β structure consisting of a central β-sheet and α-helices packed on both sides of it .
FGAR-AT, PurM N-terminal-like domain (FGAR-AT_PurM_N-like)
Type: Domain

This entry represents the PurM_N-like domain of Phosphoribosylformylglycinamidine synthase from Schizosaccharomyces pombe (FGAR-AT) and related proteins from eukaryotes and bacteria. FGAR-AT catalyses the ATP-dependent conversion of formylglycinamide ribonucleotide (FGAR) to formylglycinamidine ribonucleotide (FGAM) in the fourth step of the purine biosynthetic pathway. This domain consists of an antiparallel β-sheet with two α-helices packed on one side .
PTEN2A/B, C2 domain (PTEN2A/B_C2)
Type: Domain

This entry represents a C2 domain found in PTEN2A (Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and protein-tyrosine-phosphatase) and PTEN2B from plants. These proteins are tyrosine phosphatases that exhibit also a weak lipid phosphatase activity towards PtdIns3P .
COMMD8, helical N-terminal domain (COMMD8_HN)
Type: Domain

This entry represents the α-helical N-terminal domain (HN) of COMMD8, one of the subunits of the CCC complex (Commander complex), which regulates the Retromer-independent retrieval and recycling of hundreds of proteins including integrins and lipoprotein receptors .
BIRD-IDD transcription factor, fourth C2HC zinc finger (C2CH-4th_BIRD-IDD)
Type: Domain

This C2HC zinc finger domain is found in the plant BIRD/INDETERMINATE DOMAIN (IDD) transcription factor family. Members of this BIRD/IDD family such as JACKDAW (JKD)/IDD10, BALDIBIS (BIB), MAGPIE (MGP)/IDD3 are required for asymmetric cell division of ground tissue and QC specification by direct protein-protein interaction with SHR and/or SCR to control ground tissue patterning during root growth . SHR-SCR functions as a transcription cofactor by binding to the zinc finger domains of these transcription factors. Members of the BIRD/IDD family contain 4 zinc finger domains, two classical C2H2 followed by two C2HC zinc finger domains. This entry represents the fourth C2HC zinc finger domain that is involved in interaction with SHR-SCR .
BIRD-IDD transcription factor, second C2H2 zinc finger (C2H2-2nd_BIRD-IDD)
Type: Domain

This C2H2 zinc finger domain is found in the plant BIRD/INDETERMINATE DOMAIN (IDD) transcription factor family. Members of this BIRD/IDD family such as JACKDAW (JKD)/IDD10, BALDIBIS (BIB), MAGPIE (MGP)/IDD3 are required for asymmetric cell division of ground tissue and QC specification by direct protein-protein interaction with SHR and/or SCR to control ground tissue patterning during root growth . SHR-SCR functions as a transcription cofactor by binding to the zinc finger domains of these transcription factors. Members of the BIRD/IDD family contain 4 zinc finger domains, two classical C2H2 followed by two C2HC zinc finger domains. This entry represents the second C2H2 zinc finger domain that is involved in DNA binding .
BIRD-IDD transcription factor, third C2HC zinc finger (C2CH-3rd_BIRD-IDD)
Type: Domain

This C2HC zinc finger domain is found in the plant BIRD/INDETERMINATE DOMAIN (IDD) transcription factor family. Members of this BIRD/IDD family such as JACKDAW (JKD)/IDD10, BALDIBIS (BIB), MAGPIE (MGP)/IDD3 are required for asymmetric cell division of ground tissue and QC specification by direct protein-protein interaction with SHR and/or SCR to control ground tissue patterning during root growth . SHR-SCR functions as a transcription cofactor by binding to the zinc finger domains of these transcription factors. Members of the BIRD/IDD family contain 4 zinc finger domains, two classical C2H2 followed by two C2HC zinc finger domains. This entry represents the third C2HC zinc finger domain that is involved in interaction with SHR-SCR and in DNA binding .
Choice-of-anchor I domain (Choice_anch_I)
Type: Domain

This entry represents the choice-of-anchor I domain, found in the alkaline phosphatase PhoA of Synechocystis sp. PCC 6803 (

), upstream of the region presumed to have phosphatase activity. It is also found in Mesenchyme-specific cell surface glycoprotein from Strongylocentrotus purpuratus that is likely involved in in mesenchyme cell migration, adhesion, fusion, or spicule formation . Proteins with this domain include a number with the PEP-CTERM protein-sorting domain, but also a number with the LPXTG protein-sorting domain, making this a choice-of-anchor domain, found in proteins targeted for covalent attachment at the cell surface by at least two different protein-sorting systems.
Large ribosomal subunit protein mL44, endonuclease domain (RM44_endonuclase)
Type: Domain

Large ribosomal subunit protein mL44 (RM44) is a component of the 39S subunit of mitochondrial ribosome. It may play a role in the assembly/stability of nascent mitochondrial polypeptides exiting the ribosome. This entry represents the endonuclease (RNase III-like) domain of RM44 .
ATP synthase A/B type, C-terminal domain (ATP-synt_VA_C)
Type: Domain

This entry represents a small α-helical domain found at the C-terminal end of a variety of ATP synthases e.g. mitochondrial F1-ATPase

.
DNA polymerase epsilon ,catalytic subunit A, thumb domain (POL2_thumb)
Type: Domain

This entry represents the thumb domain of DNA polymerase epsilon catalytic subunit A from Saccharomyces cerevisiae (POL2) and its homologues from eukaryotes. The catalytic component of the DNA polymerase epsilon complex is involved in chromosomal DNA replication where it has been shown to participate in leading-strand synthesis . This domain, which makes contacts in the DNA minor groove, shows a mainly α-helical structure .
Proline-rich AKT1 substrate 1, N-terminal domain (PRAS_NT)
Type: Domain

This entry represents a domain found in the N-terminal of the PRAS (Proline-rich AKT1 substrate 1) family .

PRAS is a proline-rich protein that can be phosphorylated by AKT, and in the phosphorylated state binds to 14-3-3. The AKT signalling pathway contributes to regulation of apoptosis after a variety of cell death stimuli, and PRAS is found to be a substrate . PRAS plays an important role in regulating cell survival downstream of the PI3-K/Akt pathway after reperfusion injury after transient focal cerebral ischemia. Copper/zinc-SOD (SOD1), a cytosolic isoenzyme of superoxide dismutase, SOD, is highly protective against ischemia and re-perfusion injury after transient focal cerebral ischemia, and SOD1 thus contributes to the inhibition of direct oxidation of PRAS and the activation of its signalling pathway . PRAS is also an mTOR binding partner, and PRAS phosphorylation by AKT and its association with 14-3-3, a cytosolic anchor protein, are crucial for insulin to stimulate mTOR (mammalian target of rapamycin) .
Sulfocyanin, N-terminal (SoxE_N)
Type: Domain

This entry represents an α-helix found at the N-terminal of Sulfocyanin from Sulfolobus acidocaldarius (SoxE) and similar archaeal sequences. SoxE is a blue copper protein involved in in electron transfer reactions .
E3 ubiquitin-protein ligase UBR1-like, winged-helix domain (UBR1-like_winged-helix)
Type: Domain

This entry represents the winged-helix domain of E3 ubiquitin-protein ligase UBR1/2/3 and the plant homologue PRT6. These E3 ubiquitin-protein ligases recognise and bind to proteins bearing specific N-terminal residues that are destabilising according to the N-end rule, leading to their ubiquitination and subsequent degradation . This domain participates in the protein-protein interactions, e.g interaction with the donor ubiquitin .
Integrator complex subunit 7-like, C-terminal domain, plant (INTS7_C_plant)
Type: Domain

This entry represents a C-terminal domain found in the putative Integrator complex subunit 7 (INTS7) from plants. INTS7 is a component of the integrator complex, a complex that is recruited to the U1 and U2 snRNA genes and mediates the snRNAs' 3' end processing. The integrator complex interacts with the C-terminal tail of the largest subunit of RNA-polymerase II to promote 3'-snRNA processing .
Pyridoxamine 5'-phosphate oxidase-like (Putative_PNPOx_2)
Type: Domain

This domain is found in bacterial Pyridoxamine 5'-phosphate oxidase-like proteins. It folds into a β-barrel capped at the top and bottom with α-helices.
Histone-lysine N-methyltransferase NSD-like, variant PHD zinc finger (PHDvar_NSD)
Type: Domain

This domain is found in the NSD (nuclear receptor SET domain- containing) family of histone-lysine N-methyltransferase such as NSD1, NSD2, NSD3 and other related proteins . It is a variant of the classical PHD zinc finger containing a C4HC2H zinc finger-like motif which is distinct from the typical C4HC3 motif.
Histone-lysine N-methyltransferase NSD-like, PHD zinc finger (NSD_PHD)
Type: Domain

This domain is found in the NSD (nuclear receptor SET domain- containing) family of histone-lysine N-methyltransferase such as NSD1, NSD2, NSD3 and other related proteins . It adopts a classical PHD finger fold and is frequently found in tandem with an atypical (C5HCH) plant homeodomain (PHD) finger. Both domains form an integral unit that plays an important role by engaging in multiple protein-protein interactions. This domain determines the differences in the histone binding specificity of the NSD family members.
Hda, lid domain (Hda_lid)
Type: Domain

This entry represents the lid domain found at the C-terminal of the Regulatory inactivation of DnaA Hda protein from Shewanella amazonensis, the essential component of RIDA (regulatory inactivation of DnaA), and related proteins predominantly from proteobacteria. This domain is a short four-helical bundle that contains the sensor II motif .
Integration host factor-like, helix-two turn-helix domain (IHF-like_H2TH)
Type: Domain

This entry represents helix-two turn-helix (H2TH) domains found in Integration host factor from Streptomyces coelicolor (IHF) and similar proteins mainly found in actinomycetes. IHF is a nucleoid-associated protein (NAP) that probably plays a role in chromosome compactation. It contributes to development and secondary metabolism, but is dispensable for growth and viability . This domain is also found at the N-terminal of guanylate kinases.
Heterogeneous nuclear ribonucleoprotein L, RRM domain (HNRNPL_RRM)
Type: Domain

This entry represents the fourth RRM domain found at the C-terminal of human Heterogeneous nuclear ribonucleoprotein L (HNRNPL) , an splicing factor binding to exonic or intronic sites and acting as either an activator or repressor of exon inclusion .
5,10-methenyltetrahydromethanopterin hydrogenase, N-terminal domain (HMD_N)
Type: Domain

This entry represents the N-terminal domain of 5,10-methenyltetrahydromethanopterin hydrogenase (HMD) and related proteins, an enzyme of the methanogenic energy metabolism. HMD is an iron-sulphur-cluster-free enzyme that contains an intrinsic CO ligand bound to iron. This domain has a Rossmann fold-like structure that contains a mononucleotide-binding site, which could harbour the GMP moiety of the cofactor .
ATP-dependent RNA helicase SUV3, DEXQ-box helicase domain (DEXQc_SUV3)
Type: Domain

This entry represents the DEXQ-box helicase domain found in ATP-dependent RNA helicase SUPV3L1 (Suv3) and similar sequences from eukaryotes and bacteria. SUV3 is a major helicase player in mitochondrial RNA metabolism. It is a component of the mitochondrial degradosome (mtEXO) complex, that degrades 3' overhang double-stranded RNA with a 3'-to-5' directionality in an ATP-dependent manner. It is also involved in the degradation of non-coding mitochondrial transcripts and tRNA-like molecules .
DNA-directed RNA polymerase III subunit RPC3, winged-helix domain (POLR3C_WHD)
Type: Domain

This entry represents the WH-like domain (WH4) found at the C-terminal of the DNA-directed RNA polymerase III subunit RPC3 (POLR3C) from humans (also known as hRPC62) . POLR3C exhibits helicase activity . Helicases are enzymes responsible for unwinding DNA or RNA helices, facilitating essential processes such as transcription and DNA replication. RNA polymerase (pol) III is responsible for transcribing tRNAs, 5S RNA, and U6 RNA in eukaryotes. The human Pol III complex consists of a total of 17 subunits.
DNA polymerase II, insertion domain (PolB_insertion)
Type: Domain

This is the insertion domain found in DNA polymerase II from E. coli (PolB), a member of family B of DNA polymerases . Members of this family are found in proteobacteria.
RsiG-like domain (RsiG-like_dom)
Type: Domain

This entry represents a domain found in the anti-sigma factor RsiG from Streptomyces and its homologues. RsiG binds and sequesters the sporulation-specific sigma factor WhiG in a fashion dependent on 3',5'-cyclic diguanylic acid (c-di-GMP). This domain adopts an α-helix and in Streptomyces self associates to form a dimer . This dimer binds c-di-GMP via two E(X)3-S(X)2-R(X)3-Q(X)-D repeat motifs, one on each helix. The complex RsiG-(c-di-GMP) binds to the sporulation-specific sigma factor, WhiG. Some homologues of RsiG contain a second helix and hence two c-di-GMP binding motifs .
Activating protease CtpA/B, N-terminal domain (CtpA/B_N)
Type: Domain

This domain is found N-terminal of Carboxy-terminal processing protease CtpA, CtpB and related proteins. CtpB is involved in signal transduction pathway leading to the proteolytic activation of the mother cell transcription factor pro-sigma-K during sporulation. This domain contains auto-cleavage site at which it is proteolytically cleaved. The remaining part in the mature enzyme is involved in dimerisation .
PNO1, second type I KH domain (KH_PNO1_2nd)
Type: Domain

PNO1 is an RNA-binding protein that acts as a ribosome assembly factor and plays an important role in ribosome biogenesis. It positively regulates dimethylation of two adjacent adenosines in the loop of a conserved hairpin near the 3'-end of 18S rRNA. PNO1 contains two K-homology (KH) RNA-binding domains; the second one is represented in this entry .
PNO1, first type I KH domain (KH-I_PNO1_first)
Type: Domain

PNO1 is an RNA-binding protein that acts as a ribosome assembly factor and plays an important role in ribosome biogenesis. It positively regulates dimethylation of two adjacent adenosines in the loop of a conserved hairpin near the 3'-end of 18S rRNA. PNO1 contains two K-homology (KH) RNA-binding domains, the first one is represented in this entry. The KH1 domain is a divergent KH domain that lacks the RNA-binding GXXG motif .