SII-SWORD/CoKE huggingface dataset:
PEP5/VPS11 N-terminal (PEP5_VPS11_N)
Type: Domain

This entry represents the β-propeller domain found at the N-terminal of the Pep5-like zinc finger protein from Schizosaccharomyces pombe and its orthologues from human and mice known as vacuolar protein sorting protein 11.

Vacuolar protein sorting protein 11 (vps11) aggregates with other Vps proteins to form the homotypic fusion and protein sorting complex (HOPS), which promotes the fusion of late endosomes and autophagosomes with lysosomes . Pep5 (also known as Vps11) was initially isolated as a protease deficient mutant and shown to be involved in protein trafficking and vacuole biogenesis pathways .

WD-40 repeats (also known as WD or beta-transducin repeats) are short ~40 amino acid motifs, often terminating in a Trp-Asp (W-D) dipeptide. WD40 repeats usually assume a 7-8 bladed β-propeller fold, but proteins have been found with 4 to 16 repeated units, which also form a circularised β-propeller structure. WD-repeat proteins are a large family found in all eukaryotes and are implicated in a variety of functions ranging from signal transduction and transcription regulation to cell cycle control and apoptosis. Repeated WD40 motifs act as a site for protein-protein or protein-DNA interaction, and proteins containing WD40 repeats are known to serve as platforms for the assembly of protein complexes or mediators of transient interplay among other proteins . The specificity of the proteins is determined by the sequences outside the repeats themselves. Examples of such complexes are G proteins (beta subunit is a β-propeller), TAFII transcription factor, and E3 ubiquitin ligase . In Arabidopsis spp., several WD40-containing proteins act as key regulators of plant-specific developmental events.
PEP5/VPS11, clathrin heavy-chain repeat (CHCR_PEP5_VPS11)
Type: Repeat

This entry represents the clathrin heavy-chain repeat (CHCR) repeat found in Pep5-like zinc finger protein from Schizosaccharomyces pombe (also known as Vps11) and its ortologues from human, mouse and A. thaliana Vacuolar protein sorting-associated protein 11 (VPS11) .

Vacuolar protein sorting protein 11 (vps11) aggregates with other Vps proteins to form the homotypic fusion and protein sorting complex (HOPS), which promotes the fusion of late endosomes and autophagosomes with lysosomes . Pep5 (also known as Vps11) was initially isolated as a protease deficient mutant and shown to be involved in protein trafficking and vacuole biogenesis pathways .

Clathrin is a triskelion-shaped cytoplasmic protein that polymerises into a polyhedral lattice on intracellular membranes to form protein-coated membrane vesicles. Lattice formation induces the sorting of membrane proteins during endocytosis and organelle biogenesis by interacting with membrane-associated adaptor molecules. Clathrin functions as a trimer, and these trimers, or triskelions, are comprised of three legs joined by a central vertex. Each leg consists of one heavy chain and one light chain. The clathrin heavy-chain contains a 145-residue repeat that is present in seven copies . The clathrin heavy-chain repeat (CHCR) is also found in nonclathrin proteins such as Pep3, Pep5, Vam6, Vps41, Vps8 from Saccharomyces cerevisiae and their orthologues from other eukaryotes such as Vps11 in zebra fish . These proteins, like clathrins, are involved in vacuolar maintenance and protein sorting. The CHCR repeats in these proteins could mediate protein-protein interactions, or possibly represent clathrin-binding domains, or perform clathrin-like functions. CHCR repeats in the clathrin heavy chain, Saccharomyces cerevisiae Vamp2 and human Vamp6 have been implicated in homooligomerization, suggesting that this may be the primary function of this repeat.

The CHCR repeat folds into an elongated right-handed superhelix coil of short α-helices . Individual 'helix-turn-helix-loop' or helix hairpin units comprise the canonical repeat and stack along the superhelix axis to form a single extended domain. The canonical hairpin repeat of the clathrin superhelix resembles a tetratrico peptide repeat (TPR), but is shorter and lacks the characteristic spacing of the hydrophobic residues in TPRs.
Peptidoglycan hydrolase PcsB, coiled-coil domain (PcsB_CC)
Type: Domain

This coiled-coil (CC) domain is found at the N-terminal of Peptidoglycan hydrolase PcsB from Streptococcus pneumoniae

and similar bacterial proteins. PcsB forms a dimer, and the CC domain acts as a pair of molecular tweezers, locking the catalytic domain of each dimeric partner in an inactive configuration .

PcsB is required for the maintenance of normal growth and cellular morphology and is involved in the splitting of the septum during cell division . This protein is organised into three regions: an α-helical coiled coil (CC) domain, an alanine-rich linker region and a globular catalytic CHAP domain (

) with an α+β papain-like amidase fold .
Period circadian protein homolog PER 1-3, bHLH-like domain (PER1-3_bHLH)
Type: Domain

This domain is found in the family of Period circadian protein homologs (PER1, PER2, PER3) found in vertebrates, such as PER2

in human and PER2

in mouse. This domain is a bHLH domain which is known to interact with DNA. It is more closely related to Circadian locomoter output cycles protein kaput (Clock).

PER proteins (PER 1-3) are transcriptional repressors which form the core component of the circadian clock. They play a critical role in rhythm generation, whereas delays imposed by post-translational modifications are important for determining the period of the rhythms. The core clock genes: PER1/2/3 and CRY1/2 form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression .
GreAB-C-like domain (GrebAB-C-like)
Type: Domain

This is a GreAB-C-like domain found mostly in the N-terminal of uncharacterised bacterial proteins. This domain has been found in antiviral immunity systems, where it forms a circular permuted domain embedded in TPR repeats. In these proteins, the GreAB-C domain is located at the C-terminal followed, usually, by a PIN domain with a variable N-terminal domain often harbouring effector domains .

GreA and GreB are prokaryotic transcript cleavage factors that play a crucial role in regulating RNA polymerase (RNAP) transcript elongation. They have several key functions in preventing elongation arrest, improving transcription accuracy, and facilitating the transition from transcription initiation to elongation. They have a similar structural organisation and consist of two domains: a C-terminal globular and an extended N-terminal coiled-coil domain. Their structural features, particularly the coiled-coil domain, are essential for modifying the RNAP active site to perform these cleavage reactions .
Fatty acyl-CoA reductase Maqu_2507-like (Maqu_2507-like)
Type: Family

This protein family includes the fatty acyl-CoA reductase Maqu_2507 from Marinobacter aquaeolei (

) and similar bacterial sequences. Maqu_2507 catalyses the reduction of fatty acyl-CoA ranging from C8:0 to C20:4 by four electrons to the corresponding fatty alcohols .
PUB2-4-like, N-terminal domain (PUB2-4-like_N)
Type: Domain

This domain is found at the N-terminal end of U-box domain-containing protein 2, 3 and 4 from Arabidopsis thaliana (PUB2/3/4) and similar plant sequences. This domain is predicted to show an all-α configuration. It is often found associated with

and

.
PGAP2IP, C-terminal nuclease-like domain (Exo_endo_phos_PGAP2IP_C)
Type: Domain

This domain is found C-terminal in the human PGAP2-interacting protein and its homologues in yeast, including

. PGAP2IP is composed of three domains. Two of these domains are predicted to adopt a very similar structure consisting of six transmembrane helices, suggesting a possible duplication event in these proteins (

,

). Its yeast homologue CWH43 is involved in the remodelling of the lipid moiety of GPI anchors to ceramides . The domain represented by this entry has a significant sequence similarity to DNase I-like domains and endonuclease/exonuclease/phosphatase proteins

in prokaryotes; it is predicted to adopt a similar structure.
Rab11-FIP3/4 domain (Rab11-FIP3/4_dom)
Type: Domain

This domain is found in human Rab11 family-interacting protein 3 and 4 (Rab11-FIP3/4) and similar proteins mainly found in animals. Proteins in this family are involved in regulating endocytic trafficking, cytokinesis, and intracellular ciliogenesis by facilitating membrane delivery . This domain is predicted to adopt an α-helical configuration.
PH-like domain, trypanosoma (PH-like_tryp)
Type: Domain

This domain is found in uncharacterised proteins mainly from Trypanosomes. It has a weak sequence similarity to known PH-domains and it is predicted to adopt similar structure. It contains a conserved GTFKT sequence motif. This domain is also found in putative Glucosyltransferases, Rab-like GTPase activators and Myotubularins (GRAM) domain-containing proteins

, which are a group of uncharacterised proteins that have similar fold as PH-domains .
Renin receptor, N-terminal domain (RENR_N)
Type: Domain

This domain is found N-terminal in the human renin receptor and related proteins, including the Drosophila homologue, known as dPRR. The domain represented by this entry is predicted to adopt an α/β structure with topological similarity to alkaline phosphatase.

Renin receptor is a multifunctional protein which functions as a renin, prorenin cellular receptor and is involved in the assembly of the lysosomal proton-transporting V-type ATPase (V-ATPase) and the acidification of the endo-lysosomal system . Through its function in V-type ATPase (v-ATPase) assembly and acidification of the lysosome it regulates protein degradation and may control different signalling pathways important for proper brain development, synapse morphology and synaptic transmission .
RESC1/2, CYTH-like domain (RESC1_2_CYTH-like_dom)
Type: Domain

This domain is found in the RNA-editing substrate-binding complex protein 1 and 2 (RESC1,

, and RESC2,

) from Trypanosoma brucei and related proteins. In Trypanosoma, the editosome, composed of RNA-editing substrate-binding complex (RESC) and RNA-editing catalytic complex (RECC) is involved in guide RNA (gRNA)-programmed editing to recode cryptic mitochondrial transcripts into messenger RNAs. RESC1 and RESC2 are paralogs that are essential components of the RESC complex and the RESC1/2 dimer stabilises gRNAs and most other proteins bind mRNAs . This domain has detectable similarity to members of the CYTH-like phosphatase superfamily and adopts similar structure .
RFX1-4/6/8-like, BCD domain (RFX1-4/6/8-like_BCD)
Type: Domain

This domain is found in site specific DNA binding proteins that are members of the RFX family of transcription factors, including human RFX (1-4/6/8) . Members of this family are found in animals and fungi, and initially were identified as regulatory factors that bind to a conserved cis-regulatory element called the X-box motif. Members of the RFX family contain a highly conserved HTH DNA-binding domain (

) followed by another conserved domain (BCD) composed of the so-called B, C and D regions which are involved mainly in dimerisation. This entry represents the BCD domain which is predicted to fold into array of α-helices.
Rgr-1, C-terminal domain (Rgr-1_C)
Type: Domain

This domain is found at the C-terminal end of Mediator of RNA polymerase II transcription subunit 14 from Caenorhabditis elegans (Rgr-1) and similar nematode proteins. Rgr-1 is a component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. This domain is predicted to show an α-β configuration.
RHG40/28/18, C-terminal ubiquitin-like domain (RHG40/28/18_ubiquitin)
Type: Domain

This domain is found at the C-terminal end of human Rho GTPase-activating protein 40, 28 and 18 (RHG40/28/18) and similar GTPase activators for Rho-type GTPases. This activity plays a crucial role in regulating cellular processes such as actin polymerisation, cell shape, spreading, and migration . This domain is predicted to adopt an ubiquitin-like fold and is usually found associated to

.
Ribonuclease II, winged helix domain (WH_RNase_II)
Type: Domain

This entry represents a winged helix domain found in ribonuclease II (RNR1) from Arabidopsis thaliana and similar sequences from plants, cyanobacteria and some proteobacterial species. RNR1 is a 3'-5' exoribonuclease that catalyses 3' maturation of chloroplast and mitochondrion ribosomal RNAs. It degrades short nucleotidic extensions to generate the mature 3'-ends . It is involved in the maturation of 23S, 16S and 5S rRNAs.
RNA helicase DeaD, dimerization domain (DeaD_dimer)
Type: Domain

This entry represents the dimerisation domain found in the ATP-dependent RNA helicase DeaD (also known as CsdA) and related proteins. DeaD is involved in various cellular processes after cold shock, including ribosome biogenesis, mRNA degradation and translation initiation. It was found to unwind double-stranded RNA in the absence of ATP. In E.coli DeaD is associated with the pre50S particles and is involved in the biogenesis of the 50S subunit, and plays an essential role in the survival at low temperature. DeaD is a multidomain protein, composed of a conserved helicase core and a C-terminal domain that is probably involved in RNA recognition. The domain represented by this entry is indispensable for stabilising the DeaD dimeric structure . This domain consists of three α-helices, two of which entangle with the helices of another monomer and tightly pack to form the dimeric core .
Ketoreductase domain (KR_dom)
Type: Domain

The ketoreductase (KR) domain is a conserved catalytic domain that belongs to the short-chain dehydrogenase/reductase (SDR) superfamily and contains a Rossmann fold, which is crucial for binding the NADPH cofactor . Its primary function is to catalyse the NADPH-dependent reduction of beta-keto groups to beta-hydroxy groups during the biosynthesis of fatty acids, polyketides, and related compounds. The specific substrates and products can vary depending on the enzyme .

The ketoreductase (KR) domain is a conserved catalytic domain in various enzyme systems involved in fatty acid and polyketide biosynthesis. It is present in:

Mammalian fatty acid synthases (FAS)

Polyketide synthases (PKS)

Fungal 6-methylsalicylic acid synthase

Bacterial phthioceranic/hydroxyphthioceranic acid synthases

3-oxoacyl-[acyl-carrier-protein] reductase FabG

Diacetyl reductase [(S)-acetoin forming]

Acetoacetyl-CoA reductase

Hydroxynaphthalene reductase-like protein Arp2
RNA-binding protein vts1-like, alpha-helical domain (Vts1_dom)
Type: Domain

This domain is found in RNA-binding protein vts1 from Aspergillus fumigatus and related proteins from animals and fungi, including zinc finger CCHC domain-containing protein 2 (ZCCHC2), protein Smaug homolog 1 (SMAG1) from vertebrates and germline survival defective-1 from C. elegans. Vts1 is involved in post-transcriptional regulation through transcript degradation. This domain is predicted to adopt an all-α configuration.
RNase T2-like, C-terminal domain (RNaseT2L_C)
Type: Domain

This domain is found C-terminal in Ribonuclease T2-like from Emericella nidulans and related fungal proteins. Ribonuclease T2-like enzymes preferentially cleave single-stranded RNA between purine and uridine residues to generate two nucleotide fragments with 2'3'-cyclic phosphate adenosine/guanosine terminus and uridine residue . This domain is predicted to adopt a β-Trefoil fold.
Rol-3, five-bladed beta-propeller (Beta-prop_Rol-3)
Type: Domain

This domain is found in the Protein roller-3 (Rol-3) from Caenorhabditis elegans and related proteins. Rol-3 plays a crucial role in the development and locomotion in nematodes. Rol-3 has an essential function during early to mid-larval development . The domain represented by this entry is predicted to fold into a five bladed β-propeller.
Rv3818-like, SCP2-like domain (SCP2_Rv3818)
Type: Domain

This domain is found in the putative Rieske 2Fe-2S iron-sulfur protein Rv3818 from Mycobacterium tuberculosis and similar actinobacterial proteins. Rv3818 was identified as a high-confidence drug target. This domain is predicted to adopt an α-β configuration and is usually found associated with

and

.
Salactin (Salactin)
Type: Family

This protein family represents salactin (

) from Halobacterium salinarum and similar sequences. Salactin is an actin homologue found in halophilic archaea , which is involved in DNA segregation .
SBNO, alpha/beta domain (SBNO_a/b_dom)
Type: Domain

This domain is found in the family of Strawberry notch homologue (SBNO 1/2) proteins from animals and includes the plant homologue Protein FORGETTER 1. SBNO2 acts as a transcriptional coregulator exhibiting both coactivator and corepressor functions . It inhibits the DCSTAMP-repressive activity of TAL1 and enhances the access of the transcription factor MITF to the DC-STAMP promoter in osteoclast . Arabidopsis FORGETTER1 mediates stress-induced chromatin memory via nucleosome remodelling . The domain represented by this entry is located toward the C-terminal end. It is predicted to adopt α/β structure with a curved five-stranded antiparallel β-sheet. Towards the C terminus, this domain has three highly conserved cysteine residues and a histidine which may be involved in metal coordination.
Adhesion GPCR Gpr126, SEA domain (SEA_Gpr126)
Type: Domain

This entry represents the Sperm protein, Enterokinase and Agrin (SEA) domain found in the adhesion G protein-coupled receptor Gpr126/ADGRG6 from vertebrates. The domain adopts a ferredoxin-like α/β sandwich fold and is located between the PTX and HormR domains in the extracellular region. In human GPR126, this domain contains a furin cleavage site that is conserved in many mammals and birds . After cleavage, the domain remains intact until mechanical force causes separation, similar to SEA domains in other proteins like Mucins and Notch. The SEA domain plays a role in regulating receptor function through proteolytic processing and mechanical force sensing.

The mouse member is involved in many biological processes, such as myelination, sprouting angiogenesis, placenta, ear and cartilage development . It also acts as a regulator of body length and bone mass and as a regulator of blood-brain barrier formation in the central nervous system via its association with LRP1 and ITGB1 .
LRR-containing protein, second PH domain (PH_2nd_LRR)
Type: Domain

This entry represents the second of two N-terminal pleckstrin homology (PH) domains found in fungal proteins that also contain C-terminal leucine-rich repeats (LRRs).
Selenocysteine-specific elongation factor, beta-barrel domain (Beta-barrel_SelB)
Type: Domain

This domain is found in Selenocysteine-specific elongation factor from Escherichia coli (SelB) and similar bacterial proteins. SelB is a translation factor necessary for the incorporation of selenocysteine into proteins. It probably replaces EF-Tu for the insertion of selenocysteine directed by the UGA codon.
Spore germination protein, N-terminal domain (GerAC_N)
Type: Domain

This entry represents the N-terminal domain of spore germination proteins such as GERXC, GERLC, GERKC, GERAC, GERBC and others. In Bacillus cereus, GERLC contributes to the L-alanine germination response .
Sororin, C-terminal region (Sororin_C)
Type: Domain

This entry represents a conserved region found at the C-terminal of sororin from animals and plants (

from Arabidopsis thaliana). Sororin is an essential, cell cycle-dependent mediator of sister chromatid cohesion. The protein is nuclear in interphase cells, dispersed from the chromatin in mitosis, and interacts with the cohesin complex. This protein protects cohesin from WAPL, which otherwise releases cohesin from DNA.
Smf/DprA, SAM domain (DprA_SAM)
Type: Domain

This entry represents the N-terminal domain found in Smf and DprA proteins mainly from Enterobacterales. Smf (Smf homologue) and DprA (DNA processing chain A) proteins are involved in DNA processing and transformation. The domain adopts a SAM-like fold, similar to other domains involved in nucleic acid interactions.

DprA is a new member of the recombination-mediator protein family, dedicated to natural bacterial transformation . In Helicobacter pylori, DprA is required for natural chromosomal and plasmid transformation . It has now been shown that DprA binds cooperatively to single-stranded DNA (ssDNA) and interacts with RecA. In the process, DprA-RecA-ssDNA filaments are produced and these filaments catalyse the homology-dependent formation of joint molecules. While the Escherichia coli SSB protein limits access of RecA to ssDNA, DprA alleviates this barrier . DprA has a role not only in ensuring production of transformants via interaction with RecA, it is also involved in competence shut-off via interaction with ComE .
Target of rapamycin complex 2 subunit MAPKAP1-like, Ras-binding domain (RBD_SIN1)
Type: Domain

This entry represents the Ras-binding domain (RBD) found in human Target of rapamycin complex 2 subunit MAPKAP1 (SIN1) and similar proteins mainly found in vertebrates and nematodes. SIN1 is an essential component of mTOR complex 2 (mTORC2), which helps regulate cell survival and proliferation through phosphorylation of AGC kinase family members and transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output . The domain adopts a ubiquitin-like fold and is found between the CRIM and PH domains.
Single-strand DNA endonuclease 1, chromo domain (Chromo_SEND1)
Type: Domain

This domain is found in Single-strand DNA endonuclease 1 from Arabidopsis thaliana (SEND1) and similar plant proteins. SEND1 cleaves flap structures at the junction between single-stranded DNA and double-stranded DNA with a specific cleavage site in the 5' overhang strand exactly one nucleotide 3' of the branch point. It resolves holliday junctions (HJs) by symmetrically oriented incisions in two opposing strands near the junction point, thus leading to ligatable products. This domain is often found associated with

and

. It is predicted to fold into three-stranded curved β-sheet packed against an α-helix.
RapA, DEXH-box helicase domain (DEXDc_RapA)
Type: Domain

This entry describes the DEXH-box helicase domain found in prokaryotic RapA proteins. In prokaryotes, RapA's DEXH-box domain functions to remodel protein-nucleic acid complexes, particularly in the context of RNA polymerase recycling during transcription .

RapA, a prokaryotic Swi2/Snf2 ATPase associated with RNA polymerase (RNAP), functions primarily to stimulate RNAP recycling by binding to and remodeling post-termination complexes (PTCs) . This ATP-dependent process involves RapA binding to the RNAP at the RNA exit channel, triggering conformational changes that open the RNAP clamp and allow DNA dissociation, thereby facilitating the release of RNAP from DNA after transcription termination and enabling its participation in subsequent rounds of transcription .