SII-SWORD/CoKE huggingface dataset:
Domain of unknown function DUF7939 (DUF7939)
Type: Domain

This entry is a small α-helical domain found at the C terminus of proteins a family of uncharacterised bacterial proteins that have a set of β-sandwich domains towards the N terminus including

.
Protein of unknown function DUF7940 (DUF7940)
Type: Family

This family contains a set of uncharacterised bacterial and phage proteins that are annotated as putative holins.
Protein of unknown function DUF7941 (DUF7941)
Type: Family

This entry represents an uncharacterised family of phage proteins from Uroviricota. These proteins are about 300 amino acids in length. They may represent phage structural proteins.
Protein of unknown function DUF7942 (DUF7942)
Type: Family

This family of uncharacterised bacterial proteins is found mainly in Actinomycetes. Members of this family are predicted to contain three transmembrane helices. A member of this family, SCO4225, is a putative integral membrane protein found in Streptomyces coelicolor,

. The gene encoding SCO4225 is part of a cluster of genes (phoU to sco4225) that are involved in phosphate regulation and metabolism. This gene cluster is regulated by the two-component system PhoR-PhoP, which responds to phosphate availability in the environment . The expression of SCO4225 is directly regulated by MacR, a response regulator that binds to a specific sequence in the promoter region of SCO4225. This regulation links SCO4225 to other genes in the MacR regulon, many of which are also membrane proteins .
Domain of unknown function DUF7943 (DUF7943)
Type: Domain

This domain is found in uncharacterised bacterial proteins. It is predicted to fold into an alpha- helical bundle. This domain is found in the hypothetical protein ESA_00282 from Cronobacter sakazakii that plays a significant role in biofilm formation and bacterial adhesion. This protein contributes to the adhesion of C. sakazakii to biotic surfaces, such as intestinal epithelial cells and play a role in the pathogenesis .
Domain of unknown function DUF7944 (DUF7944)
Type: Domain

This domain is found in uncharacterised bacterial proteins mainly from Moraxellales. It is predicted to fold into an array of α-helices. It contains two invariant cysteine residues which are predicted to form a disulfide bond.
Protein of unknown function DUF7945 (DUF7945)
Type: Family

This domain is found in uncharacterised bacterial proteins predominantly from Actinomycetes. It is predicted to fold into an array of α-helices. Members of this entry include REIS_1423, which was suggested to be the antitoxin for REIS_1424-like toxins.
Domain of unknown function DUF7946 (DUF7946)
Type: Domain

This entry represents a domain of unknown function found that covers the whole length of Protein 40A from Enterobacteria phage phi80 and at the N-terminal of the small β-barrel domain

in a group of uncharacterised proteobacterial and phage proteins. Its function is unknown.
Domain of unknown function DUF7947 (DUF7947)
Type: Domain

This entry represents a domain of unknown function found at the C terminus of a set of bacterial and phage proteins. It forms small five stranded β-barrel domain.
Domain of unknown function DUF7948 (DUF7948)
Type: Domain

This entry represents a potential adhesive domain found at the N terminus of a variety of bacterial cell surface proteins. The structure shows a large β-sandwich fold.
Domain of unknown function DUF7949 (DUF7949)
Type: Domain

This entry describes a domain of unknown function in putative EGF-like domain-containing proteins found in eukaryotes, mainly ameobas. According to structure predictions it adopts an EGF-like fold which contain six conserved cysteine residues. The EGF-like fold has two-stranded β-sheets followed by a loop to a short C-termini. It usually occurs in tandem repeats . The domain described by this entry has the 6 conserved cysteine residues. It also acquires a similar structure to the EGF-like fold and it is 40 amino acids long.
Domain of unknown function DUF7950 (DUF7950)
Type: Domain

This entry represents a domain of unknown function in a group of uncharacterised proteins mainly from plants and prokaryotes. According to structure predictions it adopts a sensor-like fold, consisting of 7 β-strands arranged in a β-barrel like fold, surrounded by a small α-helix.
Repeat of unknown function DUF7951 (DUF7951)
Type: Repeat

This entry describes a repeat of unknown function found at the C-terminal of uncharacterised proteins mainly from animals. It displays a TPR fold.
Domain of unknown function DUF7952 (DUF7952)
Type: Domain

This entry represents a domain of unknown function found in putative SANT domain-containing proteins and uncharacterised proteins found in plants. This domain is predicted to adopt an EF-hand-like fold. The EF-hand fold is a helix-loop-helix motif that can bind calcium atoms. The EF-hand fold is usually tandemly repeated, and the number of repeats ranges from two to eight .
Domain of unknown function DUF7953 (DUF7953)
Type: Domain

The domain described by this entry is located towards the N-terminal in putative transmembrane and uncharacterised proteins found in plants. It is predicted to adopt a C2 fold. C2 domains are membrane-binding modules that share a common overall fold: a single compact greek-key motif organised as an eight-stranded anti-parallel β-sandwich consisting of a pair of four-stranded β-sheets .
Nischarin, C-terminal PH domain (PH_NISCH_C)
Type: Domain

This domain is found at the C-terminal end of human Nischarin and related animal proteins. Nischarin functions as a molecular scaffold, interacting with various protein partners and playing important roles in cell migration, cytoskeletal organisation, and tumour suppression . Nischarin expression is often reduced in various human cancers, including breast, ovarian, and lung cancers . Its downregulation has been associated with increased tumour growth and metastasis.
Membrane protein YohP-like (YohP-like)
Type: Family

This family represents the membrane protein YohP from E. coli and related sequences from proteobacteria. YohP is a 27-amino-acid-long protein located in the inner membrane of E. coli . YohP is recognised by the signal recognition particle (SRP). In contrast to the canonical cotranslational recognition by SRP, SRP was found to bind to YohP post-translationally . The exact function of YohP is unknown but it was found that compresses the nucleoid upon overexpression .
BBH37-like, helical domain (BBH37-like_helical)
Type: Domain

This domain is found in Borrelia burgdorferi outer surface protein BBH37 (

) and related proteins from Spirochaetales. Many members posses a lipid attachment site. This domain folds into a helical bundle (

).
YTH1-like, RRM domain (RRM_YTH1)
Type: Domain

This RRM domain is found in the YTH domain-containing family protein 1 (YTH1) from Cryphonectria parasitica and similar fungal proteins. YTH1 specifically recognises and binds N6-methyladenosine (m6A)-containing mRNAs, and regulates their stability and processing .
BCD1, alpha/beta domain (BCD1_alpha/beta)
Type: Domain

This domain is found in Box C/D snoRNA protein 1 from Saccharomyces cerevisiae (BCD1), which is required for box C/D snoRNAs accumulation involved in snoRNA processing, snoRNA transport to the nucleolus and ribosome biogenesis . This domain shows an α-β configuration and is often found associated with

.
AsqO/PenF-like, C-terminal domain (AsqO/PenF-like_C)
Type: Domain

This domain is found at the C-terminal end of Quinolone epoxide rearrangement protein asqO from Emericella nidulans and similar fungal proteins, including Quinolone epoxide rearrangement protein penF from Penicillium thymicola. Proteins in this family are predicted to consist of two similar β-barrel domains:

and this entry.

AsqO is part of the gene cluster that mediates the biosynthesis of the aspoquinolone mycotoxins . Within the pathway, AsqO catalyses an enzymatic 3-exo-tet cyclisation to yield the cyclopropyl-THF ring system in aspoquinolone .

Quinolone epoxide rearrangement protein PenF is a part of the gene cluster that mediates the biosynthesis of penigequinolones, potent insecticidal alkaloids that contain a highly modified 10-carbon prenyl group . PenF catalyses the cationic rearrangement of the epoxide formed by penE (before ring opening to produce yaequinolone C) into yaequinolone D .
Densovirus VP1 protein (AdSDV_VP1)
Type: Family

This entry represents the structural protein VP1 of the Acheta domesticus segmented densovirus (AdSDV), the first parvovirus discovered with a bipartite genome. This structural protein forms the viral capsid, which displays T=1 icosahedral symmetry. Unlike other parvoviruses, AdSDV packages its NS and VP cassettes on separate genome segments. VP1 is encoded by vpORF1 on the vp segment, and forms the eight-stranded jelly roll fold that is characteristic of parvoviral capsid proteins. The capsid formed by this protein shows a unique DNA-packaging mechanism involving the elongated C-terminal tail, which "pins" the ssDNA genome to the capsid interior at the twofold symmetry axis . AdSDV VP1 is phylogenetically related to the VP proteins of mosquito-infecting brevihamaparvoviruses, but unlike other members of the Hamaparvovirinae, it infects the common house cricket and causes paralysis followed by death.
Tectonic-1-3, N-terminal domain (TCTN1-3_N)
Type: Domain

This is domain is found N-terminal in tectonic proteins (TCTN1-3) It contains a number of conserved cysteine residues predicted to form disulfide bonds. Although function of this domain is currently unknown, studies on TCTN2 suggest that it is indispensable for its functions .

TCTN1, TCTN2, and TCTN3 are members of the tectonic protein family that play crucial roles in ciliogenesis and ciliary function. While they share some common functions, each protein also has specific roles in the process of cilia formation and maintenance. These proteins interact with several other ciliopathy proteins, forming a complex known as the Tectonic ciliopathy complex. This complex is required for hedgehog signalling transduction and regulation of ciliary membrane composition .
Ams2/SPT21, N-terminal domain (Ams2-SPT21_N)
Type: Domain

This entry describes the N-terminal domain found in CENP-A multicopy suppressor protein 2 (Ams2) and SPT21 proteins found in Schizosaccharomyces pombe and Saccharomyces cerevisiae respectively. Ams2 is required for proper chromosome segregation via regulation of CENP-A localisation to the centromere . SPT21 is required for transcriptional silencing . The N-terminal of Ams2 physically interacts with other Ams2 proteins . This domain is predicted to fold into an unique topology resembling a hybrid structure composed a five-stranded β-barrel capped with α-helix and which two strands protrude to complete a five stranded curved β-sheet that grasp the α-helix.
Tsg, C-terminal domain (Tsg_C)
Type: Domain

This entry represents the C-terminal domain of Tsg. This domain contains a mixed α/β fold. It is stabilised by disulfide bonds. It directly binds the C-terminal region of Chordin, a BMP antagonist, to stabilise the inhibitory complex that blocks BMP-receptor interactions .

Twisted gastrulation (Tsg) was identified in Drosophila melanogaster as being required to specify the dorsal-most structures in the embryo, for example, the amnioserosa. Biochemical experiments have revealed three key properties of Tsg:

It can synergistically inhibit Dpp/BMP action in both D. melanogaster and vertebrates by forming a tripartite complex between itself, SOG/chordin and a BMP ligand;

Tsg seems to enhance the Tld/BMP-1-mediated cleavage rate of SOG/chordin and may change the preference of site utilisation;

Tsg can promote the dissociation of chordin cysteine-rich-containing fragments from the ligand to inhibit BMP signalling .
WCX domain (WCX_dom)
Type: Domain

This domain is found in the PafB and PafC heteromeric regulators that act as transcriptional activators and belong to the large bacterial family of WYL domain- containing proteins . In these proteins, WCX domain (WYL C-terminal extension) is found next to the WYL domain. WCX domain is involved in heterodimer formation. It folds into an α/β structure composed of four-stranded β-sheet with α-helices packed on it with topology similar to ferredoxin-like domains .
Anti-CRISPR protein AcrF2 (AcrF2)
Type: Family

AcrF2 is involved in helping bacteriophages evade the CRISPR/Cas type I-F immune system in bacteria. This function allows the phage to bypass the bacterial defence mechanism, which typically targets and degrades foreign genetic material. By inhibiting the CRISPR/Cas system, the Anti-CRISPR protein 30 family plays a crucial role in the survival and propagation of phages within bacterial hosts .
Anti-CRISPR protein F31 (AcrF31)
Type: Family

This entry represents anti-CRISPR protein AcrF31, a fusion of AcrIE4 and AcrIF7 domains that inhibits both type I-E and type I-F CRISPR-Cas systems . The N-terminal domain adopts a novel α-helical fold and targets the PAM (protospacer adjacent motif) interaction site of the type I-E Cas8e subunit. The C-terminal domain exhibits an α-β fold like native AcrIF7, which disables target DNA recognition by the PAM interaction site in the type I-F Cas8f subunit. The two domains are connected by a flexible linker that allows prompt docking onto their cognate Cas8 targets . Conserved negative charges in each Acr domain are required for interaction with their Cas8 targets. This protein was first identified in Pseudomonas citronellolis.
Anti-CRISPR protein AcrF8 (AcrF8)
Type: Family

This entry represents AcrF8, an anti-CRISPR protein that inhibits the type I-F CRISPR-Cas system. AcrF8 is a 92-residue protein that occupies the cavity surrounded by Cas5f, Cas7.4-7.6f, and Cas8f subunits in the Csy complex. AcrF8 forms unique interactions with crRNA, making it distinct from other anti-CRISPR proteins against the Csy complex . Specifically, AcrF8 interacts with nucleobases of three nucleotides of crRNA (U[+21], U[+22], G[+23]) that are located just after the kink caused by the thumb of Cas7.5f. This interaction forms a continuous 4-nt region that interferes with DNA-crRNA hybridisation. AcrF8 thus prevents target DNA hybridisation to crRNA and subsequent DNA degradation by Cas3 .
STIL, N-terminal domain (STIL_N)
Type: Domain

This entry represents the N-terminal domain in human SCL/TAL1 interrupting locus (STIL) protein and homologues.

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 .
UBE2O, N-terminal SH3-A domain (SH3-A_UBE2O)
Type: Domain

This domain is found at the N-terminal in the human E3-independent E2 ubiquitin-conjugating enzyme (UBE2O) and related proteins. The domain represented by this entry folds into an open β-barrel with a typical SH3-like topology. This domain contains a large unstructured region with a high content of glycine residues.

UBE2O is involved in the monoubiquitination of diverse targets to mediate important processes such as targeting proteins for quality control, regulation of nuclear trafficking of chromatin-associated proteins and clearing ribosomes during erythropoiesis . UBE2O is a multidomain protein composed of several SH3-like domains (

,

,

,

), UBC domain (

) and a CR3 helix. The CR3 helix is a conserved region that is part of a non-canonical extension to the typical E2 fold. It forms the curved edge of the hook, together with the UBC domain, which is critical for UBE20 function .
UBE2O-like, SH3-B domain (UBE2O-like_SH3-B)
Type: Domain

This domain is found in the human E3-independent E2 ubiquitin-conjugating enzyme (UBE2O) and related eukaryotic proteins. The domain represented by this entry folds into an open β-barrel with typical SH3 topology. It precedes the ubiquitin-binding SH3-C domain (

).

UBE2O is involved in the monoubiquitination of diverse targets to mediate important processes such as targeting proteins for quality control, regulation of nuclear trafficking of chromatin-associated proteins and clearing ribosomes during erythropoiesis . UBE2O is a multidomain protein composed of several SH3-like domains (

,

,

,

), UBC domain (

) and a CR3 helix. The CR3 helix is a conserved region that is part of a non-canonical extension to the typical E2 fold. It forms the curved edge of the hook, together with the UBC domain, which is critical for UBE20 function .

This entry also includes the probable ubiquitin-conjugating enzyme E2 23/24 from Arabidopsis thaliana (UBC23/24) and similar plant proteins. UBC23 accepts the ubiquitin from the E1 complex and catalyses its covalent attachment to other proteins. UBC24 is a E2 ubiquitin-protein ligase that mediates E1-dependent protein ubiquitination .
UBE2O-like, SH3-C domain (UBE2O-like_SH3-C)
Type: Domain

This domain is found in the human E3-independent E2 ubiquitin-conjugating enzyme UBE2O and related proteins. The domain represented by this entry folds into an open β-barrel with typical SH3 topology. It binds ubiquitin via a unique, distinct interface and plays a key role in the UBE2O target selection .

UBE2O is involved in the monoubiquitination of diverse targets to mediate important processes such as targeting proteins for quality control, regulation of nuclear trafficking of chromatin-associated proteins and clearing ribosomes during erythropoiesis . UBE2O is a multidomain protein composed of several SH3-like domains (

,

,

,

), UBC domain (

) and a CR3 helix. The CR3 helix is a conserved region that is part of a non-canonical extension to the typical E2 fold. It forms the curved edge of the hook, together with the UBC domain, which is critical for UBE20 function .

This entry also includes the probable ubiquitin-conjugating enzyme E2 23/24 from Arabidopsis thaliana (UBC23/24) and similar plant proteins. UBC23 accepts the ubiquitin from the E1 complex and catalyses its covalent attachment to other proteins. UBC24 is a E2 ubiquitin-protein ligase that mediates E1-dependent protein ubiquitination .
UBE2O-like, tandem tSH3-B domain (UBE2O-like_tSH3-B)
Type: Domain

This domain is found in the human E3-independent E2 ubiquitin-conjugating enzyme UBE2O and related proteins. The domain represented by this entry folds into two tandem, intertwined β-barrels, each of which has a typical SH3 topology . This tandem SH3-like domain is involved in binding to NAP1L1, one of the major regulators of the UBE2O target selection .

UBE2O is involved in the monoubiquitination of diverse targets to mediate important processes such as targeting proteins for quality control, regulation of nuclear trafficking of chromatin-associated proteins and clearing ribosomes during erythropoiesis . UBE2O is a multidomain protein composed of several SH3-like domains (

,

,

,

), UBC domain (

) and a CR3 helix. The CR3 helix is a conserved region that is part of a non-canonical extension to the typical E2 fold. It forms the curved edge of the hook, together with the UBC domain, which is critical for UBE20 function .

This entry also includes the probable ubiquitin-conjugating enzyme E2 23/24 from Arabidopsis thaliana (UBC23/24) and similar plant proteins. UBC23 accepts the ubiquitin from the E1 complex and catalyses its covalent attachment to other proteins. UBC24 is a E2 ubiquitin-protein ligase that mediates E1-dependent protein ubiquitination .
PseI/NeuA/NeuB, SAF domain (SAF_PseI/NeuA/NeuB)
Type: Domain

This entry represents the SAF domain at the C-terminal in acid synthases such as PseI, NeuA, NeuB and related proteins.

NeuB is the prokaryotic N-acetylneuraminic acid synthase. It catalyses the direct formation of N-acetylneuraminic acid (Neu5Ac), the most common sialic acid, by condensation of phosphoenolpyruvate (PEP) and N-acetylmannosamine (ManNAc). Mammals synthesise the 9-phosphate form, Neu5Ac-9-P, and utilise ManNAc-6-P instead of ManNAc . The bacterial and mammalian enzymes share 30%-40% sequence identity and are composed of two distinct domains. The N-terminal domain (NeuB domain,

) consists of ~250 amino acid residues, and is considered to bind the sugar substrates. The C-terminal domain consists of ~75 amino acid residues, and is called the antifreeze-like (AFL) domain, since it is similar to those observed in a variety of functional type III antifreeze proteins (AFPs) .

Also included in this group are spore coat polysaccharide biosynthesis proteins (SpsE), while AFPs are not included.
Phenyloxazoline synthase MbtB-like, condensation domain (Condensation_MtbB-like)
Type: Domain

This entry represents the condesantion domain found in Phenyloxazoline synthase MbtB, Pyochelin synthetase PchF/E and similar bacterial proteins. This domain is a pseudo-dimer of two lobes, the N-terminal lobe (N-lobe) and the C-terminal lobe (C-lobe), each of them consisting of one large central β-sheet, flanked by predominantly α-helices. The active site motif, HHxxxDG, is located in a loop that connects the central strand of the N-lobe and one of its long α-helices.

Phenyloxazoline synthase MbtB and pyochelin synthetases PchF and PchE are non-ribosomal peptide synthetases (NRPSs) involved in siderophore biosynthesis. MbtB catalyses the condensation of salicylate with serine/threonine to form phenyloxazoline rings during mycobactin synthesis in Mycobacterium tuberculosis, containing adenylation, condensation, and cyclisation domains essential for substrate recognition and bond formation . PchF and PchE function sequentially in Pseudomonas aeruginosa, where PchE adenylates and incorporates cysteine while PchF adds a second cysteine and performs crucial thiazoline reduction and N-methylation, producing the mature pyochelin molecule .
Glycoside hydrolase family 29, N-terminal (Glyco_hydro_29_N)
Type: Domain

This entry represents the N-terminal domain of O-Glycosyl hydrolases family 29 proteins.

O-Glycosyl hydrolases family 29 (

) encompasses alpha-L-fucosidases (

) , which is a lysosomal enzyme responsible for hydrolysing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins. Alpha-L-fucosidase is responsible for hydrolysing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins.

Fucosylated glycoconjugates are involved in numerous biological events, making alpha-l-fucosidases, the enzymes responsible for their processing, critically important. Deficiency in alpha-l-fucosidase activity is associated with fucosidosis, a lysosomal storage disorder characterised by rapid neurodegeneration, resulting in severe mental and motor deterioration . The enzyme is a hexamer and displays a two-domain fold, composed of a catalytic (β/α)(8)-like domain and a C-terminal β-sandwich domain .

Drosophila melanogaster spermatozoa contains an alpha-l-fucosidase that might be involved in fertilisation by interacting with alpha-l-fucose residues on the micropyle of the eggshell . In human sperm, membrane-associated alpha-l-fucosidase is stable for extended periods of time, which is made possible by membrane domains and compartmentalisation. These help preserve protein integrity .

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.