SII-SWORD/CoKE huggingface dataset:
UBAC1, ubiquitin-like domain (UBL_UBAC1)
Type: Domain

This domain is found in human UBAC1 (Ubiquitin-associated domain-containing protein 1) and related animal proteins. This domain shares significant sequence similarity with ubiquitin-like domains, and it is predicted to adopt a similar structure with ubiquitin fold topology.

Ubiquitin-associated domain-containing protein 1 (UBAC1) proteins include non-catalytic components of the KPC complex, a specific type of E3 ubiquitin-protein ligase complex. Members of this group function as adaptors within the KPC complex, facilitating the transfer of polyubiquitinated target proteins to the 26S proteasome for degradation. These proteins are involved in the polyubiquitination of key regulatory proteins such as CDKN1B, which plays a role in cell cycle control, and NFKB1, a component of the NF-kappa-B signalling pathway. The ubiquitin-associated (UBA) domains present in these proteins are responsible for recognising and binding polyubiquitinated substrates, indicating a role in targeting proteins for proteasomal degradation, which is essential for various cellular processes, including cell cycle progression and signal transduction .
TPPC8, C-terminal Ig-like domain (Ig_TPPC8_C)
Type: Domain

This entry represents an Ig-like domain found at the C-terminal of TPPC8.

TPPC8 plays a role in endoplasmic reticulum to Golgi apparatus trafficking at a very early stage . Together with TBC1D14, it maintains the cycling pool of ATG9 required for initiation of autophagy . It is one of the TRAPPIII complex specific subunits.
RDM1, DSRM domain (DSRM_RDM1)
Type: Domain

This entry represents a domain found in the human RDM1 (RAD52 Motif Containing 1) and related proteins. RDM1 is a protein involved in cellular responses to DNA damage and stress. It can bind to RNA, single-stranded DNA (ssDNA), and double-stranded DNA (dsDNA) . RDM1 plays a role in the cellular response to cisplatin, a chemotherapy drug that causes DNA damage . RDM1 is also involved in the heat-shock response and proteotoxic stress . This protein plays an oncogenic role in human lung adenocarcinoma cells. Its expression is significantly increased in lung tumors, and correlates with the clinical outcomes . RDM1 is a multidomain protein containing an N-terminal RRM domain and a C-terminal (this entry) DSRM domain.
YeeW-like domain (YeeW-like_dom)
Type: Domain

This domain is found covering the whole length of Protein YeeW from Escherichia coli and at the N-terminal end of sequences that also have

. It likely forms a homodimeric structure composed of three β-strands provided by each monomer, with one strand swapped with the other monomer. Members of this group are proteobacterial proteins likely to be phage derived.
Tandem CCCH zinc finger domains (Znf-CCCH_tandem)
Type: Domain

This pair of CCCH zinc finger domains is found in uncharacterised fungal proteins.
STIL, coiled coil region (STIL_CC)
Type: Domain

This coiled-coil region is found in the human SCL/TAL1 interrupting locus (STIL) protein and homologues. This region interacts with the Polo-like kinase 4 (PLK4) and binds to its Polo-box 3 (PB3) domain. It also uses a secondary interaction site in the PLK4 L1 region . This CC_STIL/PLK4 interaction mediates PLK4 activation as well as stabilization of centriolar PLK4 and plays a key role in centriole duplication.

SIL (also called STIL/TAL1 interrupting locus) is an immediate-early gene that is essential for embryonic development and is implicated in T-cell leukemia-associated translocations . Sil protein is necessary for proper mitotic spindle organisation in zebrafish and human cells and localizes to the mitotic spindle poles only during metaphase . Mouse Sil was suggested to play a role as a positive regulator of the sonic hedgehog pathway, acting downstream of PTCH1 . In human, cell cycle-dependent phosphorylation of Sil is required for its interaction with Pin1, a regulator of mitosis .

Primary microcephaly (MCPH) is an autosomal-recessive congenital disorder characterised by smaller-than-normal brain size and mental retardation. Three different homozygous mutations in SIL were identified in patients from three of the five families linked to the MCPH7 locus; all are predicted to truncate the Sil protein .
CEP63/Deup1, CEP152 binding coiled coil (CEP63/Deup1_CC)
Type: Domain

This coiled-coil domain is found in the human centrosomal protein 63 kDa (CEP63), its paralogue Deuterosome assembly protein 1 (Deup1) and homologues. In CEP63 this coiled-coil region interacts with the coiled-coil region of the centrosomal protein 152 kDa (CEP152) . Both proteins cooperatively form a heterotetrameric α-helical bundle. This complex functions in conjunction with its neighbouring hydrophobic motifs and self-assemble into a higher-order cylindrical architecture capable of recruiting downstream components, including Plk4, a key regulator for centriole duplication .

CEP63 and Deup1 are both involved in centriole amplification. While CEP63 mediates mother-centriole-dependent centriole duplication, Deup1 mediates de novo centriole amplification in multiciliated cells .
MAT1, C-terminal CAK anchor (MAT1_CAK-anch)
Type: Domain

This entry represents a region, known as CAK anchor, located toward the C-terminal of the human CDK-activating kinase assembly factor MAT1 and related proteins. The CAK anchor region of MAT1 binds between the C-terminal lobes of CDK7 and cyclin H, enhancing CDK7 kinase activity by positioning its activation loop in a catalytically competent conformation . Through these interactions, MAT1 acts as a stabilising factor, tightening the CDK7-cyclin H binary complex.

MAT1 (menage a trois 1) is a RING finger protein with a characteristic C3HC4 motif in its N-terminal domain that plays a crucial role in stabilizing the cyclin H-CDK7 complex, forming the functional CDK-activating kinase (CAK) enzymatic complex responsible for activating many CDK enzymes involved in cell cycle regulation . In vivo, CDK7 forms a stable complex with cyclin H and MAT1 only when phosphorylated at either Ser164 or Thr170 in its T-loop; this phosphorylation can bypass the requirement for MAT1 in CAK activation. While MAT1 addition and T-loop phosphorylation can independently stabilize and activate the CDK7 complex in vitro, under physiological conditions these mechanisms cooperate to maintain complex integrity. Notably, if CDK7 becomes dephosphorylated, even the presence of MAT1 cannot prevent dissociation of the complex into monomeric subunits, especially under prolonged elevated temperatures .
CEP250, coiled coil (CEP250_CC)
Type: Domain

This domain is found in the human Centrosomal protein 250 kDa (CEP250) and its homologues mainly from vertebrates. CEP250 plays an important role in centrosome cohesion during interphase by recruiting CCDC102B to the proximal ends of centriole . This domain interacts with FKBP12 and this interaction is mediated by small molecules such as WDB002 .
CEP152, CEP63 binding coiled coil (CEP152_CC)
Type: Domain

This coiled-coil domain is found in the human centrosomal protein 152 kDa (CEP152) and homologues. It interacts with the coiled-coil region of the centrosomal protein 63 kDa (CEP63) . Both proteins cooperatively form a heterotetrameric α-helical bundle. This complex functions in conjunction with its neighbouring hydrophobic motifs and self-assemble into a higher-order cylindrical architecture capable of recruiting downstream components, including Plk4, a key regulator for centriole duplication .
RsdA/BaiN/AoA(So)-like, Rossmann fold-like domain (RsdA/BaiN/AoA(So)_Rossmann)
Type: Domain

This entry represents a Rossmann fold-like domain surrounding two structural (β-barrel and H2TH α-helical) domains

.

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 .
CEP192, Aurora A binding region (CEP192_Aurora-A_bind)
Type: Binding_site

This region is found in human Centrosomal protein 192 kDa (CEP192) and homologues. CEP192 modulate both the Aurora A kinase activity and localisation. This region of CEP192 wraps around Aurora A and occupies the binding sites for the mitotic spindle-associated partners, TACC3 and TPX2, thus competing with them . This region binds the F-pocket/C-helix region of the N-lobe in a way that inhibits Aurora A, whereas TPX2 binding to the same region activates the kinase . The centrosomal CEP192-Aurora-A complex is the primary driver of Aurora-A auto-phosphorylation during mitosis.
TACC3, Aurora-A binding region (TACC3_Aurora-A_bind)
Type: Binding_site

This region is found in the human Transforming acidic coiled-coil-containing protein 3 (TACC3) and homologues. Phosphorylation of human TACC3 on S558 (located within this region) drives an interaction with the ankle region of the clathrin heavy chain (CHC) to form a complex that binds the microtubule lattice through the coiled-coil region of TACC3 and the β-propeller domain of CHC . TACC3 is also an Aurora-A activator and binds Aurora-A through a region N-terminal to the Ser558 phosphorylation site . Phosphorylation of Ser558 switches the local conformation of TACC3 from disordered to helical .
CEP152, PLK4 binding region (CEP152_PLK4_bind)
Type: Binding_site

This region is found in human Centrosomal protein 152 kDa (CEP152) and homologues. This region bind the cryptic polo box (CPB) of Polo-like kinase 4 (Plk4) in opposite orientations and in a mutually exclusive manner to Centrosomal protein 152 kDa (152) . Plk4 is a key regulator of centriole duplication, an event critical for the maintenance of genomic integrity. Its localization at subcentrosomal structures is regulated by CEP152 and CEP192.
CEP192, PLK4 binding region (CEP192_PLK4_bind)
Type: Binding_site

This region is found in human Centrosomal protein 192 kDa (CEP192) and homologues. This region bind the cryptic polo box (CPB) of Polo-like kinase 4 (Plk4) in opposite orientations and in a mutually exclusive manner to Centrosomal protein 152 kDa (152) . Plk4 is a key regulator of centriole duplication, an event critical for the maintenance of genomic integrity. Its localization at subcentrosomal structures is regulated by CEP152 and CEP192.
Smf/DprA, SLOG domain (DrpA_SLOG)
Type: Domain

This entry describes the SLOG domain in prokaryotic proteins. This domain adopts a three-layered α/β sandwich Rossmann fold with a characteristic substrate-binding loop rich in glycine and small residues in the standard location between strand-1 and helix-1. This domain is found in DNA processing protein A (DprA) from Streptococcus pneumoniae and Smf, the Bacillus subtilis orthologue, as well as putative DprA proteins in eukaryotes.

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 .
Sleeping Beauty transposase, HTH domain (HTH_SB)
Type: Domain

This entry represents the helix-turn-helix (HTH) domain, also known as PAI subdomain, found in Sleeping Beauty transposase and homologues. This domain improves the enzyme structural stability and transposon DNA-binding.
Non-canonical E2 ubiquitin-conjugating enzyme, C-terminal (E2_Ub-conjug_enz_C)
Type: Domain

This entry describes a domain found at the C-terminal end in a novel group of non-canonical E2 ubiquitin-conjugating proteins that lack the typical HPN motif found in conventional E2 enzymes, including

from Plasmodium falciparum and similar proteins mainly from in Apicomplexan parasites, fungi and some amoeba species. It possesses a highly conserved catalytic cysteine residue, which forms a thioester bond with ubiquitin . The N-terminal region of the members of this group is involved in protein-protein interactions with other components of the ubiquitin pathway, such as Rbx1. It is predicted to adopt an all-helical structure. This domain was previously known as DUF2009.
P3, C-terminal domain (P3_C)
Type: Domain

This entry represents the C-terminal domain of the Major capsid protein P3.

The P3 major capsid protein adopts a 'double-sandwich' structure comprising two eight-stranded viral β-sandwich domains with a jellyroll fold, each of which contains a 12-residue α-helix. This protein trimerises through a 'trimerisation loop' sequence, and is incorporated within the viral capsid .
Retroviral polymerase, SH3-like domain (SH3_retrovirus)
Type: Domain

This entry represents an SH3-like fold domain found in a variety of eukaryotic retroviral proteins.
BRINP, C-terminal domain (BRINP_C)
Type: Domain

This entry represents the C-terminal domain of BMP/retinoic acid-inducible neural-specific protein (BRINP) 1, 2 and 3.

BRINP proteins are involved in neurogenesis and brain development. These proteins play a role in inhibiting neuronal cell proliferation by negatively regulating cell cycle progression, particularly by suppressing the G1/S transition in postmitotic neurons. This regulation is essential for proper brain development and the functioning of GABAergic neurons. Additionally, certain BRINP proteins have been implicated in promoting the proliferation, migration, and invasion of pituitary gonadotrope cells when overexpressed, suggesting a potential role in pituitary tumour development. BRINP proteins are also characterised by their responsiveness to BMP and retinoic acid, which are key signalling molecules in neural-specific pathways .
IPO4/5-like, TPR repeats domain (TPR_IPO4/5)
Type: Domain

This region of tetratricopeptide (TPR)-like repeats is found towards the N-terminal end of human Importin-4/5 (IPO4/5) and similar eukaryotic proteins. IPO4 serves as receptor for nuclear localisation signals in cargo substrates .
RBM22, CCCH zinc finger domain (Znf-CCCH_RBM22)
Type: Domain

This CCCH-type zinc finger domain is found in human Pre-mRNA-splicing factor RBM22 and similar animal proteins. RBM22 is required for pre-mRNA splicing as component of the activated spliceosome . It is involved in the first step of pre-mRNA splicing. RBM22 binds directly to the internal stem-loop (ISL) domain of the U6 snRNA and to the pre-mRNA intron near the 5' splice site during the activation and catalytic phases of the spliceosome cycle.
STK11-interacting protein, C-terminal PH domain (PH_S11IP_C)
Type: Domain

This entry represents a pleckstrin homology (PH) domain found in human STK11-interacting protein (S11IP) and related proteins. STK11IP interacts with the serine/threonine kinase 11 (STK11), also known as liver kinase B1 (LKB1). This interaction is important for several cellular processes, including protein localisation and kinase activity regulation .
EndoE-GH18L, 2nd helical domain (EndoE-GH18L_3HB-2)
Type: Domain

This domain is the second helical domain (3HB-2) found in EndoE. It forms specific inter-domain interactions with 3HB-1 through hydrogen bonds and provides the architectural framework necessary for cooperative substrate processing in the full-length enzyme. The 3HB-2 domain is essential for positioning the GH18 and GH20 domains optimally, enabling the unique two-step mechanism where the C-terminal GH20 domain first trims terminal GlcNAc residues from complex-type N-glycans, followed by GH18-mediated core processing. This domain architecture represents an evolutionary adaptation unique to EndoE that facilitates both immune evasion through IgG antibody deglycosylation and nutrient acquisition in E. faecalis.
found in Endo-beta-N-acetylglucosaminidase and related bacterial proteins. It is predicted to adopt a three α-helical bundle topology .

The EndoE-GH18L domain represents a unique multi-modular architecture from the Endoglycosidase EndoE, comprising three structurally distinct domains: a GH18 catalytic domain (

) with (β/α)8-barrel topology that functions as an endo-β-1,4-N-acetylglucosaminidase, followed by two consecutive three α-helical bundle domains, 3HB-1 and 3HB-2 (

). The GH18 domain specifically processes the central core of complex-type and high-mannose-type N-glycans through substrate-assisted catalysis mediated by active site residues D184 and E186, while forming extensive contacts with the first helical bundle domain through hydrophobic interactions and salt bridges .
Domain of unknown function DUF7918 (DUF7918)
Type: Domain

This domain is found in uncharacterised fungal proteins. It is predicted to fold into a β-sandwich structure.
Domain of unknown function DUF7919 (DUF7919)
Type: Domain

This entry represents a family of uncharacterised bacterial proteins. This domain likely contains a zinc binding site.
Domain of unknown function DUF7920 (DUF7920)
Type: Domain

This entry represents a domain of unknown function found mostly in Trypanosoma. According to structure predictions it could adopt an ATP-grasp fold which is characterised by two α-β subdomains that grasp the ATP molecules between them .
Domain of unknown function DUF7921 (DUF7921)
Type: Domain

This entry represent the domain of unknown function found in Drosophila. According to structure predictions, it may adopt fybronectin type I module (FN1) fold.
Domain of unknown function DUF7922 (DUF7922)
Type: Domain

This domain is found in uncharacterised bacterial proteins. It is found sometimes in combination with (DUF6128)

. This domains is predicted to adopt a β-sandwich with an Ig-like topology.
Domain of unknown function DUF7923 (DUF7923)
Type: Domain

This domain is found in uncharacterised fungal proteins. It has detectable similarity to known PIN domains, in particular to NYN domain, and it is predicted to adopt a similar structure.
Domain of unknown function DUF7924 (DUF7924)
Type: Domain

This entry represents a domain found in uncharacterised fungal proteins. It has a remote similarity to members of the PD-(D/E)XK nuclease superfamily and it is likely to adopt similar structure with a conserved active site architecture.
Domain of unknown function DUF7925 (DUF7925)
Type: Domain

This domain is found in uncharacterised proteins predominantly from cyanobacteria. It is predicted to fold into a β-sandwich. Some members are likely to contain an isopeptide bond.
Domain of unknown function DUF7926 (DUF7926)
Type: Domain

This domain is found in uncharacterised bacterial proteins mainly from Actinomycetes. It is predicted to fold into a β-sandwich with topological similarity to domains members of the adhesin superfamily. Most members contain conserved lysine aspartate and asparagine residues that are likely to form an isopeptide bond. This domain is frequently found in combination with DUF5979.
Domain of unknown function DUF7927 (DUF7927)
Type: Domain

This domain of unknown function is found in multiple copies in a number of bacterial proteins. It is closely related to domains represented by DUF11 (

). Similarly to DUF11, this domain contains a conserved N-terminal lysine and a C-terminal asparagine with central aspartate/glutamate residues suggesting that it may contain an isopeptide bond.
Domain of unknown function DUF7928 (DUF7928)
Type: Domain

This domain is found in uncharacterised proteins mainly from fungi. It is predicted to fold into an α/β structure with topological similarity to AraD-like domains.
Domain of unknown function DUF7929 (DUF7929)
Type: Domain

This domain is found in a very small group of proteins mainly from Phyllobacteriaceae. It is predicted to fold into a β-sandwich with topological similarity to domains members of the adhesin superfamily. Members contain conserved lysine, aspartate and asparagine residues that are likely to form an isopeptide bond.
Domain of unknown function DUF7930 (DUF7930)
Type: Domain

This entry represents a C-terminal OB-fold domain found in nematode proteins that generally contain 3 OB-like domains.
Domain of unknown function DUF7931 (DUF7931)
Type: Domain

This entry represents a domain of unknown function mostly found in bacteria. According to structure predictions it might adopt a phospholipase D/nuclease fold. Whilst the typical phospholipase D motif HxK(x)4D(x)6GSxN is not strictly conserved the overall fold suggests a potential distant evolutionary relationship to the PLD superfamily. The PLD nucleases can have endonuclease or exonuclease activity. These enzymes use the imidazole group of histidine as a nucleophile in their catalytic mechanism .
Domain of unknown function DUF7932 (DUF7932)
Type: Domain

This entry describes a domain of unknown function located at the N-terminal of proteins mostly found in fungi. According to structure predictions it might adopt an immunoglobulin, fibronectin type III fold. It is formed of two antiparallel β-sheets stacked against each other, forming a β-sandwich .
Domain of unknown function DUF7933 (DUF7933)
Type: Domain

This domain of unknown function is found in multiple copies in a number of bacterial proteins. It is closely related to domains represented by DUF11 (

). Some members, similarly to DUF11, contains a conserved N-terminal lysine and a C-terminal asparagine with central aspartate/glutamate residues suggesting that they may contain an isopeptide bond.
Protein of unknown function DUF7934 (DUF7934)
Type: Family

This entry represents a family of uncharacterised proteins found in Bacillota species. From genomic context it is likely to be a phage derived protein. It contains a helical domain composed of segments from the N terminus and C terminus connected by a coiled coil region.
Protein of unknown function DUF7935 (DUF7935)
Type: Family

This entry represents an uncharacterised protein family. Structure prediction suggests that these proteins form a membrane bound octameric complex. The N terminus of the protein contains an transmembrane α helix and the rest of the protein adopts a four helical bundle domain. This family is often found associated with gliding motility proteins in STRING networks.
Domain of unknown function DUF7936 (DUF7936)
Type: Domain

This entry represents a small family of uncharacterised phage proteins. Structure prediction shows a compact domain composed of a three stranded β-sheet followed by two α-helices packed on one side of the sheet.
Domain of unknown function DUF7937 (DUF7937)
Type: Domain

This entry represents a family of uncharacterised membrane proteins found in Actinomycetes. These proteins contain 12 putative transmembrane helices.
Phage family of unknown function (DUF7938) (DUF7938)
Type: Family

This entry found in a small number of phage is uncharacterised. There is some evidence form AlphaFold 3 prediction that these proteins may form homodimers.