SII-SWORD/CoKE huggingface dataset:
Shavenoid isoform B-like, N-terminal domain (Sha_B-like_N)
Type: Domain

This entry represents a small β-strand domain that contains six conserved cysteines that likely form three disulphide bridges. This domain is found in an extracellular context in a variety of proteins. This includes a small number of putative odorant receptors as well as proteins annotated as shavenoid proteins, including shavenoid isoform B from Drosophila

, where it is found at the N terminus.
SHC SH2 domain-binding protein 1-like, N-terminal domain (SHCBP-like_N)
Type: Domain

This entry represents the N-terminal domain of SHC SH2 domain-binding protein 1 (SHCBP) and related sequences from animals such as SHCBA-B, SHP1L and NESD. SHCBP is involved in the regulation of multiple signalling pathways, such as FGF, NF-kB, MAPK/ERK, PI3K/AKT, TGF-beta/Smad and beta-catenin signalling. SHCBP participates in T-cell development, the regulation of downstream signal transduction pathways, and cytokinesis during mitosis and meiosis. SHCBP has been demonstrated to correlate with different forms of cancer and other diseases, and may play an important role in tumourigenesis and progression . The N-terminal domain of SHCBP was shown to be pivotal for its binding with RACGAP1, a component of the central spindlin complex in the nucleus with a significant role in oncogenic development and tumour recurrence . This domain might be found in association with a C-terminal β-helix.
Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1/2-like, second C2 domain (C2_SHIP1-2_2nd)
Type: Domain

This entry represents the second C2 domain of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatases 1/2 and similar proteins from vertebrates. The C2 domains of these proteins modulate the activity of the phosphatase domain.

Human Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (SHIP) specifically hydrolyses the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the phosphoinositide 3-kinase pathways . It also functions as a negative regulator of B-cell antigen receptor signalling, myeloid cell proliferation/survival and chemotaxis, mast cell degranulation, immune cells homeostasis, integrin alpha-IIb/beta-3 signalling in platelets and JNK signalling in B-cells. This protein regulates proliferation of osteoclast precursors, macrophage programming, phagocytosis and activation and neutrophil migration and is required for endotoxin tolerance .
Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1/2-like, first C2 domain (C2_SHIP1-2_first)
Type: Domain

This entry represents the first C2 domain of Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatases 1/2 and similar proteins from vertebrates. The C2 domains of these proteins modulate the activity of the phosphatase domain.

Human Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (SHIP) specifically hydrolyses the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the phosphoinositide 3-kinase pathways . It also functions as a negative regulator of B-cell antigen receptor signalling, myeloid cell proliferation/survival and chemotaxis, mast cell degranulation, immune cells homeostasis, integrin alpha-IIb/beta-3 signalling in platelets and JNK signalling in B-cells. This protein regulates proliferation of osteoclast precursors, macrophage programming, phagocytosis and activation and neutrophil migration and is required for endotoxin tolerance .
GDS1, winged helix domain (WH_GDS1)
Type: Domain

This entry represents a winged helix DNA-binding domain in GDS1 and related fungal proteins. Winged helix domains are a subclass of the helix-turn-helix domains that include additional β-strand "wings". These domains are commonly involved in sequence-specific DNA recognition and binding.

The GDS1 proteins are involved in the regulation of mitochondrial function through nuclear control mechanisms. This suggests a role in the communication between the nucleus and mitochondria, potentially impacting mitochondrial biogenesis, energy production, or other mitochondrial processes. The specific mechanisms by which the GDS1 proteins influence mitochondrial function remain unknown, but their involvement in such critical cellular processes highlights their importance in cellular homeostasis and energy metabolism .
RTG2, C-terminal domain (RTG2_C)
Type: Domain

This domain is found C-terminal in the yeast Retrograde regulation protein 2 (RTG2) and related proteins. This domain shares significant similarity with known HD/PDEase domains and it is predicted to adopt similar structure.

RTG2 is required for controlling the interorganelle communication between mitochondria, peroxisomes, and the nucleus .
Rv1893-like (Rv1893)
Type: Family

This protein family includes a group of short sequences from actinomycetes, including Rv1893 from Mycobacterium tuberculosis (

) .
SigF-like, NTF2-like domain (NTF2_SigF)
Type: Domain

This domain is found in the SrfA-induced gene F protein (SigF) from Dictyostelium discoideum and related proteins mainly found in fungi. SigF was identified amongst genes whose expression is dependent on the MADS box transcription factor SrfA and are induced late in development . This domain has a detectable similarity to NTF2 domains and it is predicted to adopt a similar structure.
Signal transducer and activator of transcription b, N-terminal (STATB_N)
Type: Domain

This entry represents the N-terminal domain of Signal transducer and activator of transcription b (STATB) from C.elegans and similar proteins from nematodes. STATB can have a dual function, signal transduction and activation of transcription. It is required, together with with transcription factor elt-3, for up-regulation of the vacuolar H+-ATPase and acceleration of lysosome maturation at molt . It plays a role in the innate immune response to molting and injury of the adult epidermis where it positively regulates the expression of epidermal antimicrobial peptides .
Single-strand DNA deaminase toxin A-like, C-terminal (SsdA-like_C)
Type: Domain

This domain is found at the C-terminal end of Single-strand DNA deaminase toxin A from Pseudomonas syringae (SsdA,

) and similar uncharacterised bacterial and fungal sequences. SsdA shows a typical α-β deaminase configuration .
GRPD, C-terminal domain (GRDP_C)
Type: Domain

This entry represents the C-terminal domain in GRDP1 and GRDP2 proteins. It has a Tubby C-terminal domain-like fold, with a β-barrel packed around a central α-helix. The β-barrels contain 10 or 12 strands.

Glycine-rich domain-containing proteins (GRDPs) plays a regulatory role in abscisic acid (ABA) signalling and tolerance to abiotic stress during germination. It may be involved in the regulation of the ABI transcriptional factors and in the development of stress responses .
GRHL1/CP2, C-terminal domain (GRHL1/CP2_C)
Type: Domain

This domain is found at the C-terminal end of human Grainyhead-like protein 1 homolog (GRHL1), Transcription factor CP2-like protein 1 and similar animal and fungal proteins. This domain is normally found associated with

.

Grainyhead/CP2 are highly conserved transcription factors in metazoa that function as key regulators of epithelial differentiation and organ development. The family comprises two distinct groups, CP2 (CCAAT box-binding protein 2) and Grh (grainyhead). All family members share a common domain architecture . Grainyhead/Elf1 was first identified in Drosophila . Three grainyhead-like (Grhl) homologues constitute the Grh subfamily in mammals . Grhl proteins are predominantly expressed in epithelial tissues and are essential regulators of epithelial development and extracellular barrier repair after tissue damage . TFCP2 (LSF, CP2 transcription factor) is a critical regulator of erythroid gene expression . It also regulates the expression of the male-dominant sex-determining gene SRY . TFCP2 can interact with NF-E4 proteins, forming a heteromeric stage selector protein complex (SSP); this complex can bind stage selector element (SSE) and regulate embryonic globin expression in fetal-erythroid cells .
DNA utilization protein HofO, C-terminal domain (HofO_C)
Type: Domain

This entry represents the C-terminal domain in HofO and related proteins found in Enterobacteriaceae. It shows structural similarity to the Type II secretion system protein EspM (

).

The HofO proteins are involved in the utilisation of extracellular DNA as a nutrient source. Proteins in this group play a crucial role in the uptake and processing of DNA from the environment, allowing organisms such as Escherichia coli to use it as a source of carbon and energy. This function is particularly important in environments where other nutrients may be limited, providing a competitive advantage to organisms capable of utilising DNA in this manner .
HTH three-helical bundle domain (HTH_74)
Type: Domain

This HTH (helix-turn-helix) three-helical bundle domain is found in uncharacterised plant proteins. It has a very weak but detectable similarity to known HTH domains. It is predicted to fold into a three-helical bundle with an up-and-down anticlockwise topology and right-handed twist. This domain contains semi-conserved TSKALR sequence motif, predicted to be located on the C-terminal helix, which could potentially be involved in DNA interaction.
U3 small nucleolar RNA-associated protein 20, C-terminal (UTP20_C)
Type: Domain

This region of tetratricopeptide-like (TPR) repeats is found at the C-terminal end of eukaryotic proteins including U3 small nucleolar RNA-associated protein 20 from yeast and the human homologue, also known as Small subunit processome component 20 homolog or DRIM (Down-Regulated In Metastasis) (

). DRIM is differentially expressed in metastatic and non-metastatic human breast carcinoma cells . Proteins of this entry are involved in processing of non-coding RNA as components of the small-subunit (SSU) processome; SSU processome is involved in the biogenesis of the 18S rRNA . UTP20 is a huge α-solenoid that functions as a scaffold . This domain is often found C-terminal to

.
HVO_A0261-like, N-terminal domain (HVO_A0261-like_N)
Type: Domain

This entry represents the N-terminal HTH domain of a group of sequences mostly from archaea, such as HVO_A0261 (

) from H. volcanii. This domain is associated to

. This entry also includes some bacterial sequences.
Protein-tyrosine-phosphatase MKP1, C-terminal domain (MPK1_C)
Type: Domain

This domain represents the unique C-terminal extension found in plant Mitogen-activated protein kinase phosphatases (MPKs). The domain shows homology to members of the actin-binding gelsolin family, with highest similarity to villin. The domain is found across diverse plant species including Arabidopsis, maize, tomato and Medicago, suggesting it represents a plant-specific feature of MKPs. The function of this domain is currently unknown but may link stress response signalling to cytoskeleton dynamics. This domain is not found in MKPs from other organisms, making it a defining feature of the plant MPK family .

MKP1 from Arabidopsis thaliana acts as a negative regulator of MPK6 and MPK3 signalling, modulates defence response by repressing salicylic acid (SA) production, camalexin biosynthesis and SNC1-mediated responses and acts as a negative regulator of MPK6-mediated pathogen-associated molecular pattern (PAMP) responses, including MPK6 and MPK3 activation, accumulation of extracellular reactive oxygen species and inhibition of seedling growth. It is also involved in UV-B stress tolerance .
MRCK/ROCK kinase, PH domain (MRCK/ROCK_PH)
Type: Domain

This entry represents a pleckstrin homology (PH) domain found in Serine/threonine-protein kinase MRCK alpha/beta/gamma, in Rho-associated protein kinase 1/2 (ROCK1/2) and similar sequences mainly found in animals. MRCK (myotonic dystrophy kinase-related Cdc42-binding kinase) forms part of a tripartite C1-PH-CNH regulatory module. The PH domain is distinguished by a loop insertion between strands β6 and β7 that packs against the CNH domain. The domain contains conserved basic residues in the β1-β2 loop that may be involved in membrane binding. This PH domain shows weak binding to phosphoinositides with a preference for di-phosphorylated PIPs. The domain architecture of MRCK proteins includes an N-terminal kinase domain, a coiled-coil region, and C-terminal C1, PH and CNH domains arranged in a tripartite module that helps localise the protein to membranes.

Human Serine/threonine-protein kinase MRCK alpha/gamma are important downstream effectors of CDC42 and play a role in the regulation of cytoskeleton reorganisation and cell migration . Rho-associated protein kinase 1/2 are key regulator of the actin cytoskeleton and cell polarity .
MTC6, partial TIM-barrel domain (TIM-barrel_MTC6)
Type: Domain

This domain is found in the Maintenance of telomere capping protein 6 (MTC6) from Saccharomyces cerevisiae and related fungal proteins. MTC6 may be involved in telomere capping. The domain represented by this entry is predicted to fold into a partial TIM-barrel. It shares detectable similarity with the Phosphatidylinositol-specific phospholipase C.
PUMA/OVT1, coiled-coil region (PUMA/OVT1_CC)
Type: Domain

This entry represents a coiled-coil region found in PUMA from Parascaris univalens, Major antigen from Onchocerca volvulus (OVT1) and similar sequences mainly found in animals and some plant species. PUMA may play a role in the organisation of the spindle apparatus and its interaction with the centromeres . OVT1 may be a myofibrillar protein .
Plexin-B, PSI domain (PSI_Plexin-B)
Type: Domain

This entry represents a PSI domain found in Plexin B proteins. These are SEMA4 and SEMA5 receptors that play a role in axon guidance, invasive growth and cell migration . They play important roles in cell-cell signalling, glutamatergic (Plexin-B2) and GABAergic (Plexin-B1) synapse development and RHOA activation and subsequent changes of the actin cytoskeleton .
Matrix-remodeling-associated protein 7, helical domain (MXRA7_helical)
Type: Domain

This domain is found in the human Matrix-remodeling-associated protein 7 (MXRA7) and related animal proteins. In human, MXRA7 gene is located on chromosome 17. The precise function of MXRA7 is unknown but it was found that MXRA7 altered the expression of genes involved in leukaemic cell differentiation and growth . MXRA7 inhibits the proliferation and affects the differentiation of THP-1 human monocytic cells possibly through NF-kB signalling pathways . The domain represented by this entry is predicted to adopt non-compact α-helical structure. It contains a stretch of highly conserved glutamate residues defined by the semi-conserved EExEEE sequence motif.
Myosin-1-3, N-terminal SH3 domain (MYO1-3_N_SH3)
Type: Domain

This SH3 domain is found at the N-terminal end of Myosin-1-3 from Arabidopsis thaliana (MYO1-3) and similar plant proteins. MYO1 is the myosin heavy chain that is required for the cell cycle-regulated transport of various organelles and proteins for their segregation. It is involved in endocytosis via its action in endosomal trafficking .
APX 1, N-terminal C2 domain (C2_N_APX)
Type: Domain

This entry represents the N-terminal C2 domain found in anterior pharynx excess (APX) proteins. C2 domains typically function as calcium-dependent membrane-targeting modules. This specific C2 domain is found at the N-terminal of APX1 from Caenorhabditis elegans, a protein involved in the mediation of Notch signalling and in establishing left-right asymmetry during intestinal organogenesis . The domain is specific to nematodes.
C2CD3, N-terminal C2 domain (C2_C2CD3_N)
Type: Domain

This entry represents the N-terminal C2 domain found in C2 domain-containing protein 3 (C2CD3), which contain multiple C2 domains. C2CD3 is a component of the centrioles that acts as a positive regulator of centriole elongation and is required for primary cilium formation . It promotes assembly of centriolar distal appendage C2 domains typically function as calcium-dependent membrane-targeting modules.
RXYLT1, C-terminal domain (RXYLT1_C)
Type: Domain

This domain is found in human Ribitol-5-phosphate xylosyltransferase 1 (RXYLT1) and related proteins. It has a detectable similarity to domains members of Glycosyl transferase clan GT-B and it is predicted to adopt similar structure.

RXYLT1 acts as a UDP-D-xylose:ribitol-5-phosphate beta1,4-xylosyltransferase, which catalyses the transfer of UDP-D-xylose to ribitol 5-phosphate (Rbo5P) to form the Xylbeta1-4Rbo5P linkage on O-mannosyl glycan .
RXYLT1, N-terminal domain (RXYLT1_N)
Type: Domain

This domain is found in human Ribitol-5-phosphate xylosyltransferase 1 (RXYLT1) and related proteins. It has a detectable similarity to domains members of P-loop_NTPase clan and it is predicted to adopt similar structure.

RXYLT1 acts as a UDP-D-xylose:ribitol-5-phosphate beta1,4-xylosyltransferase, which catalyses the transfer of UDP-D-xylose to ribitol 5-phosphate (Rbo5P) to form the Xylbeta1-4Rbo5P linkage on O-mannosyl glycan .
Polycomb protein SUZ12-like, zinc finger domain (Znf_SUZ12)
Type: Domain

This entry represents the C2H2-type zinc finger domain found in several Polycomb group (PcG) proteins mainly from metazoa and plants, including human Polycomb protein SUZ12. SUZ12 is a component of the PRC2 complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene . This domain mediates stable binding of the TR domain of Jarid2, another component of the PRC2 complex, and the C-terminal domain of EPOP (C17orf96, a scaffold protein that bridges with the elongin BC complex) . The domain represented by this entry is often found associated with

.
Phosphofurin acidic cluster sorting protein 1/2, N-terminal C2 domain (PACS1/2_N)
Type: Domain

This entry represents the N-terminal C2 domain found in phosphofurin acidic cluster sorting (PACS) proteins. C2 domains typically function as calcium-dependent membrane-targeting modules.

PACS1 is a cytosolic sorting protein that directs the localisation of membrane proteins in the trans-Golgi network (TGN)/endosomal system. PACS1 connects the clathrin adaptor AP-1 to acidic cluster sorting motifs contained in the cytoplasmic domain of cargo proteins such as furin, the cation-independent mannose-6-phosphate receptor and in viral proteins such as human immunodeficiency virus type 1 Nef .

PACS2 controls the endoplasmic reticulum (ER)-mitochondria communication, including the apposition of mitochondria with the ER and ER homeostasis. In response to apoptotic inducer, it translocates the proapoptotic member Bid to mitochondria .
U1 small nuclear ribonucleoprotein component SNU71, RNA binding domain (SNU71_RBD)
Type: Domain

This entry represents the RNA binding domain (RBD, also known as RNA recognition motif, RRM) found in U1 small nuclear ribonucleoprotein component SNU71 from yeast, which is a component of the U1 snRNP particle that recognises and binds the 5'-splice site of pre-mRNA .
U1 small nuclear ribonucleoprotein component SNU71, N-terminal (SNU71_N)
Type: Domain

This entry represents the N-terminal domain of U1 small nuclear ribonucleoprotein component SNU71 from yeast, which is a component of the U1 snRNP particle that recognises and binds the 5'-splice site of pre-mRNA . This domain is involved in protein cross-linking and binds between Prp42 N-terminal and the Snu56 KH-like fold .
Transcription factor spt8, beta-propeller (Beta-prop_SPT8)
Type: Domain

This entry represents the β-propeller found in Transcription factor SPT8 (SPT8) from fungi. SPT8 is a member of the transcription regulatory histone acetylation (HAT) complex SAGA. SPT8 interacts with TATA-binding protein (TBP) acting as a suppressor of transcription initiation defects caused by promoter insertions of the transposable element Ty .
Protein-arginine N-acetylglucosaminyltransferase SseK/NleB (SseK_NleB)
Type: Family

This entry represents the proteobacterial effector proteins SseK and NleB and their homologues. SseK and NleB are bona fide protein-arginine N-acetylglucosaminyltransferases that glycosylate host proteins on arginine residues, leading to reduced NF-kappaB-dependent responses to infection . These proteins have different substrate specificity. They have a detectable sequence similarity and share similar structural core with glucosyltransferases family 88 (

) . A conserved HEN motif (His-Glu-Asn) in their active site is important for enzyme catalysis and bacterial virulence .
Stalled ribosome sensor GCN1-like, HEAT repeats region (HEAT_GCN1)
Type: Domain

This region of HEAT repeats is found in human Stalled ribosome sensor GCN1 and similar eukaryotic proteins. GCN1 is a ribosome collision sensor that plays a key role in the RNF14 -RNF25 translation quality control pathway, which occurs when a ribosome has stalled during translation, promoting ubiquitination and degradation of translation factors on stalled ribosomes . The structure of this protein is predicted to be entirely formed by HEAT repeats.
Terminal repeat-encoded protein TreK-like, staphylococcus phage (Phage_TreK-like)
Type: Family

This entry represents terminal repeat-encoded proteins (TreK) found in Twort-like Staphylococcus phages. Twort-like viruses are members of the Myoviridae family and are characterised by large genomes (>125 kb) with a low G+C content (30-31%) and terminally redundant ends. These terminal repeats are several thousand base pairs long and may influence the host range. The TreK protein is encoded within these terminal repeat regions. Twort-like phages are known for their broad host range and strictly lytic life cycle, making them suitable candidates for phage therapy against Staphylococcus aureus infections. This domain is often found in various Staphylococcus phages, particularly those belonging to the Herelleviridae family. The protein is typically around 90-95 amino acids in length. While its exact function remains unknown, its conservation among Twort-like phages suggests it plays an important role in phage biology, possibly related to host range determination or genome packaging. Structure prediction shows these proteins form a globular domain that includes a five-stranded highly curved β-sheet with a C-terminal helix.
S-Adenosylmethionine lyase-like (S-AdoMet_lyase-like)
Type: Family

This entry represents S-Adenosylmethionine lyases (

) and related proteins. S-Adenosylmethionine lyase catalyses the hydrolysis of S-adenosyl-L-methionine, cleaving it to form L-homoserine and methylthioadenosine. This enzyme is produced by Bacteriophage T3, which infects Escherichia coli cells. SAM hydrolase can remove S-adenosylmethionine from the E. coli cell, thereby inhibiting a variety of SAM-related activities, such as dam and dcm methylase-directed DNA modifications and the synthesis of spermidine from putrescine . It inhibits the host S-adenosylmethionine synthase METK/MAT which prevents methylation of the viral genome . This activity facilitates the transition of the virus from a lytic to a lysogenic infection under certain stress conditions, such as glucose starvation, by blocking viral expression. Expression of SAM hydrolase in T3-transformed E. coli induces the met regulon by cleaving the SAM co-repressor to form 5'-methylthioadenosine, which is then cleaved to produce 5-methylthioribose . Additionally, S-Adenosylmethionine lyase induces the polymerisation of the host's S-adenosylmethionine synthase into inactive filaments, which contributes to the unmethylated state of the viral genome, although it does not confer immunity against host restriction-modification systems. This family shows structural similarity to

.