SII-SWORD/CoKE huggingface dataset:
ZNF462, N-terminal C2H2 zinc finger (Znf_C2H2_ZNF462_N)
Type: Domain

This entry represents a C2H2 zinc finger at the N-terminal in the human ZNF462 and related proteins.

Zinc finger protein 462 (ZNF462) is involved in transcription by regulating chromatin structure and organisation . ZNF462 is a multidomain protein that contains a number of classical C2H2 zinc fingers.
ZNF462, C2H2 zinc finger 1 (Znf_C2H2_ZNF462_1st)
Type: Domain

This entry represents the first C2H2 zinc finger in the human ZNF462 and related proteins. This domain can be found in a different position in other ZNF462 proteins.

Zinc finger protein 462 (ZNF462) is involved in transcription by regulating chromatin structure and organisation . ZNF462 is a multidomain protein that contains a number of classical C2H2 zinc fingers.
ZNF462, C2H2 zinc finger 2 (Znf_C2H2_ZNF462_2nd)
Type: Domain

This entry represents the second C2H2 zinc finger in the human ZNF462 and related proteins. This domain can be found in a different position in other ZNF462 proteins.

Zinc finger protein 462 (ZNF462) is involved in transcription by regulating chromatin structure and organisation . ZNF462 is a multidomain protein that contains a number of classical C2H2 zinc fingers.
EBNA2, core domain (EBNA2_core)
Type: Domain

This entry represents the core transactivation domain in EBNA2. This region contains several functional elements, including a second dimerisation motif (Dim2), a CBF1/RBP-Jk adapter binding region, a poly-proline region, and a C-terminal acidic transactivation domain (C-TAD). EBNA2 does not bind directly to DNA but is recruited to promoters through interactions with cellular DNA-binding proteins such as RBP-Jk/CBF1 and PU.1. The C-TAD (aa 448-471) can recruit components of the basic transcriptional machinery and chromatin modifiers like p300/CBP and PCAF. Through these interactions, EBNA2 activates the expression of viral (LMP1, LMP2A/B) and cellular genes (CD21, CD23, c-myc) to drive B-cell proliferation. The C-TAD is intrinsically unstructured but forms an amphipathic α-helix when bound to interaction partners.

Epstein-Barr virus nuclear antigen 2 (EBNA2) is a key viral transcriptional regulator essential for B-cell transformation by EBV. EBNA2 plays a crucial role in activating resting B-cells in the host and stimulating their proliferation. It achieves this by upregulating the expression of viral genes, including EBNA1-6, LMP1, LMP2A, and LMP2B, as well as several host genes such as CD21, CD23, and MYC. EBNA2 functions as an adaptor molecule that activates transcription by binding to cellular sequence-specific DNA-binding proteins, including host factors CBF1, SMARCB1, and SPI1. When positioned near promoter regions, its acidic activation domain recruits core and associated transcription factors, such as TFIIB, TAF40, TFIIH components ERCC2 and ERCC3, and CBP, to initiate transcription. Additionally, EBNA2 can influence the activity of cell cycle regulators, slowing progression at the G2/M phase. It is also implicated in inducing chromosomal instability by disrupting mitotic checkpoints, causing multi-nucleation, and promoting the formation of micronuclei in infected cells .
EBNA2, N-terminal domain (EBNA2_N)
Type: Domain

This entry represents the N-terminal dimerisation domain in EBNA2. This domain (also known as END domain) forms a novel dimeric fold comprising four β-strands and a short exposed α-helix. The dimer is stabilised by anti-parallel interactions of β-strands, forming a strong hydrophobic interface. EBNA2 is a key regulator of viral and cellular gene expression that plays an essential role in B-cell transformation by EBV. In addition to its role in transcriptional regulation, the END domain has been shown to compromise the mitotic spindle checkpoint and cause chromosomal instability, which may contribute to EBV-mediated tumorigenesis.

Epstein-Barr virus nuclear antigen 2 (EBNA2) is a key viral transcriptional regulator essential for B-cell transformation by EBV. EBNA2 plays a crucial role in activating resting B-cells in the host and stimulating their proliferation. It achieves this by upregulating the expression of viral genes, including EBNA1-6, LMP1, LMP2A, and LMP2B, as well as several host genes such as CD21, CD23, and MYC. EBNA2 functions as an adaptor molecule that activates transcription by binding to cellular sequence-specific DNA-binding proteins, including host factors CBF1, SMARCB1, and SPI1. When positioned near promoter regions, its acidic activation domain recruits core and associated transcription factors, such as TFIIB, TAF40, TFIIH components ERCC2 and ERCC3, and CBP, to initiate transcription. Additionally, EBNA2 can influence the activity of cell cycle regulators, slowing progression at the G2/M phase. It is also implicated in inducing chromosomal instability by disrupting mitotic checkpoints, causing multi-nucleation, and promoting the formation of micronuclei in infected cells .
STIM1/2, EF-hand (EF-hand_STIM1/2)
Type: Domain

This EF-hand domain is found towards the N-terminal end of human STIM1, STIM2 and related STIM proteins.

STIM1 (Stromal Interaction Molecule 1) is a key Ca2+ sensor located in the membrane of the endoplasmic reticulum (ER). Upon depletion of ER Ca2+ stores, STIM1 undergoes a conformational change and oligomerises, migrating to ER-plasma membrane junctions to activate Orai1, a Ca2+-release-activated Ca2+ (CRAC) channel, in the plasma membrane. STIM1 contains a single SAM (sterile alpha motif) domain (

) and an unpaired EF-hand domain (

) in the conserved luminal region, which together serve as a Ca2+-sensing module. These domains form a stable intramolecular complex when Ca2+ is bound. During Ca2+ depletion, destabilisation of the EF-SAM interaction leads to partial unfolding and promotes homooligomerisation, an essential step for CRAC channel activation . The cytoplasmic region includes coiled-coil domains that are conserved in structure and position and are necessary for interaction with Orai1 . In human cells, STIM1 and its homologue STIM2 regulate store-operated calcium entry (SOCE) as well as basal cytoplasmic Ca2+ levels .
SWAP70, N-terminal EF-hand domain (EF-hand_SWAP70_N)
Type: Domain

This predicted EF-hand domain is found at the N-terminal end of SWAP70 and similar proteins mainly found in animals.

SWAP-70 (also called Differentially expressed in FDCP 6/DEF-6 or IRF4-binding protein) functions in cellular signal transduction pathways (in conjunction with Rac), regulates cell motility through actin rearrangement, and contributes to the transformation and invasion activity of mouse embryo fibroblasts. Metazoan SWAP-70 is found in B lymphocytes, mast cells, and in a variety of organs. Metazoan SWAP-70 contains an N-terminal EF-hand motif (

), a centrally located PH domain (

), and a C-terminal coiled-coil domain. The PH domain of Metazoan SWAP-70 contains a phosphoinositide-binding site and a nuclear localisation signal (NLS), which localises SWAP-70 to the plasma membrane and nucleus, respectively. The NLS is a sequence of four Lys residues located at the N-terminsl of the C-terminal a-helix; this is a unique characteristic of the Metazoan SWAP-70 PH domain. The SWAP-70 PH domain binds PtdIns(3,4,5)P3 and PtdIns(4,5)P2 embedded in lipid bilayer vesicles .
SWAP70, PH domain (PH_SWAP70)
Type: Domain

This entry represents the PH domain in SWAP-70 proteins and related eukaryotic proteins.

SWAP-70 (also called Differentially expressed in FDCP 6/DEF-6 or IRF4-binding protein) functions in cellular signal transduction pathways (in conjunction with Rac), regulates cell motility through actin rearrangement, and contributes to the transformation and invasion activity of mouse embryo fibroblasts. Metazoan SWAP-70 is found in B lymphocytes, mast cells, and in a variety of organs. Metazoan SWAP-70 contains an N-terminal EF-hand motif (

), a centrally located PH domain (

), and a C-terminal coiled-coil domain. The PH domain of Metazoan SWAP-70 contains a phosphoinositide-binding site and a nuclear localisation signal (NLS), which localises SWAP-70 to the plasma membrane and nucleus, respectively. The NLS is a sequence of four Lys residues located at the N-terminsl of the C-terminal a-helix; this is a unique characteristic of the Metazoan SWAP-70 PH domain. The SWAP-70 PH domain binds PtdIns(3,4,5)P3 and PtdIns(4,5)P2 embedded in lipid bilayer vesicles .
Fimovirus nucleocapsid protein (Fimo_NCAP)
Type: Family

The fimovirus nucleocapsid family is responsible for encapsidating the viral genome, thereby protecting it from degradation by nucleases. This encapsidation process results in the formation of a nucleocapsid (NC), which is a complex of the genomic RNA and the nucleoprotein. The nucleocapsid serves as a template for both viral transcription and replication, playing a crucial role in the viral life cycle by ensuring the stability and availability of the viral genome for these processes.
FimV, N-terminal domain (FimV_N)
Type: Domain

This entry represents the N-terminal domain of the motility hub protein FimV that is located N-terminal to the LysM domain (

). This domain adopts an immunoglobulin (Ig)-fold structure and is likely involved in interactions with other proteins and might contribute to the localisation of components of the type IV pilus and type II secretion machinery to the bacterial cell poles.

FimV is an inner membrane protein that plays a role in twitching motility, type IV pilus assembly, and type II secretion in bacteria like Pseudomonas aeruginosa. Disruption of FimV blocks twitching motility from type IV pili, which suggests a role in peptidoglycan layer remodelling required by type IV fimbrial systems . The C-terminal of FimV proteins is represented by

. In between is a highly variable, often repeat-filled region rich in the negatively charged amino acids Asp and Glu.
SORL1, Fn3 domain (FN3_SORL1)
Type: Domain

This Fn3 domain is found towards the C-terminal of human Sortilin-related receptor (SORL1).

SORL1 is a multifunctional sorting receptor involved in the intracellular trafficking and localisation of various protein cargoes. It cooperates with the AP-1 complex in Golgi-endosome sorting pathways and regulates the trafficking of amyloid precursor protein (APP), retaining it in the trans-Golgi network to prevent its processing into amyloidogenic peptides Abeta40 and Abeta42 in late endosomes . It may also facilitate lysosomal degradation of newly formed amyloid-beta peptides but does not influence APP transport between the endoplasmic reticulum and Golgi compartments . SORL1 acts as a sorting receptor for several other key proteins, including the BDNF receptor NTRK2/TRKB, promoting its intracellular redistribution and enhancing BDNF signalling ; GDNF and its receptor GFRA1, directing GDNF for lysosomal degradation while recycling GFRA1 and mediating RET endocytosis ; ERBB2/HER2, regulating its recycling to the plasma membrane to sustain PI3K-dependent signalling and support proliferation in ERBB2-driven cancers ; lipoprotein lipase (LPL), targeting it for lysosomal degradation ; APOA5, inducing its internalisation and sorting to both lysosomes and the trans-Golgi network ; and the insulin receptor (INSR), promoting its recycling to the cell surface and enhancing insulin responsiveness in adipose tissue without affecting its internalisation . SORL1 also plays roles in renal ion homeostasis through the intracellular sorting of STK39 and PPP3CB, and its N-terminal ectodomain promotes proliferation and migration of smooth muscle cells via uPAR/PLAUR, contributing to extracellular matrix remodelling and intimal thickening following vascular injury . It further supports monocyte adhesion and may enhance monocyte/macrophage proliferation and migration, contributing to foam cell formation and atherosclerosis. In haematopoietic stem and progenitor cells, SORL1 mediates hypoxia-enhanced adhesion to bone marrow stroma via PLAUR . Additionally, it functions as a metabolic regulator that limits adipose tissue energy expenditure by inhibiting the BMP/Smad pathway, and may modulate signalling of the CLCF1-CRLF1-CNTFR complex and IL6 by promoting lysosomal degradation and shifting the balance between cis and trans IL6 signalling .
SNRNP200 helicase-like, winged helix-turn-helix domain (SNRNP200_wHTH)
Type: Domain

This entry represents a winged Helix-Turn-Helix domain found in a variety of helicase enzymes, including U5 small nuclear ribonucleoprotein 200 kDa helicase (SNRNP200), Pre-mRNA-splicing helicase BRR2 and RQC trigger complex helicase SLH1.

SNRNP200 catalyses the ATP-dependent unwinding of U4/U6 RNA duplices, an essential step in the assembly of a catalytically active spliceosome . It plays a role in pre-mRNA splicing as a core component of precatalytic, catalytic and postcatalytic spliceosomal complexes .

BRR2 is an RNA helicase that plays an essential role in pre-mRNA splicing as component of the U5 snRNP and U4/U6-U5 tri-snRNP complexes. It is involved in spliceosome assembly, activation and disassembly. It catalyses the ATP-dependent unwinding of U4/U6 RNA duplices, an essential step in the assembly of a catalytically active spliceosome .

SLH1 is involved in activation of the ribosome quality control (RQC) pathway, a pathway that degrades nascent peptide chains during problematic translation . It drives the splitting of stalled ribosomes that are polyubiquitinated in a HEL2-dependent manner, as part of the ribosome quality control trigger (RQT) complex . It also represses the translation of non-poly(A) mRNAs together with SKI2 .
Fusellovirus capsid protein VP2 (Fusello_VP2)
Type: Family

The Fusellovirus capsid protein VP2 family is characterised by its role in binding to DNA, which is crucial for the function of the SSV1 virus. This protein is highly basic, suggesting a strong affinity for the negatively charged DNA. The interaction between the Capsid protein VP2 and the viral DNA is essential for the virus' lifecycle, potentially influencing the assembly or stability of the viral capsid. The precise mechanism by which this protein contributes to viral function is not fully detailed, but its essential nature indicates a critical role in the virus' ability to replicate or infect host cells.
Putative filamentous viruses peptidase (FV_peptidase)
Type: Family

This entry represents a family of uncharacterised proteins from archaeal filamentous viruses including HAV1, PFV1 and PFV2, and TTV1. Structure predictions show similarity to viral peptidase proteins, suggesting this is a virus-processing peptidase.
Gabija anti-defense 1 (Gad1)
Type: Family

This entry represents the Gabija anti-defense 1 (Gad1) protein family, which is encoded by bacteriophages to counteract the bacterial Gabija anti-phage defence system. Gad1 forms an octameric web that encases the Gabija GajAB complex, blocking its ability to bind and cleave phage DNA. The relatively large size of Gad1 (35 kDa) allows it to form multiple interaction interfaces with the host defence complex. Structural studies show that Gad1 contains distinctive fist, arm and shoulder domains that work together to inhibit GajA nuclease activity. The interaction between Gad1 and GajAB enables phages to overcome this widespread bacterial defence system .
Calcineurin domain containing, winged helix-turn-helix domain (wHTH-Calcineurin_assc)
Type: Domain

This entry represents a wHTH domain found at the C-terminal end of proteins containing Calcineurin-CE (covered by

), in antiviral immunity systems containing an ORC/CDC6 like AAA+ ATPase (

) .
ZMIZ1/ZMIZ2, GBD-like domain (ZMIZ1/ZMIZ2_GBD-like)
Type: Domain

This domain is found in the human Zinc finger MIZ domain-containing protein 1/2 (ZMIZ1 and ZMIZ2) and related proteins. This domain is predicted to fold into a β-sandwich with a topology typical for galactose-binding domains. It is closely related to

. It is frequently found in combination with

.

ZMIZ1 is a transcriptional regulator that functions as a direct cofactor of Notch1, modulating Notch target gene expression through interaction with the RAM1 domain via its N-terminal tetratricopeptide repeat (TPR) domain (

) . It has been shown that ZMIZ1 and Notch1 cooperatively recruit one another to chromatin through direct TPR-mediated interaction, leading to a modest increase in activating histone marks and a corresponding reduction in repressive marks . In addition to its role in Notch signalling, ZMIZ1 enhances ligand-dependent transcriptional activity of the androgen receptor (AR) and promotes AR sumoylation , . It also acts as a coactivator in the TGF-beta signalling pathway by potentiating the transcriptional activity of the SMAD3/SMAD4 complex .
WDR72-like, alpha-solenoid domain (WDR72_alpha-sol)
Type: Domain

This entry represents an α-solenoid domain found in WDR72. This entry also includes WDR7, whose function is currently unknown.

WD repeat-containing protein 72 (WDR72) plays a major role in the formation of tooth enamel, particularly during the maturation phase of amelogenesis, where it is essential for normal enamel matrix formation and the clearance of enamel proteins . WDR72 may also be involved in the localisation of the calcium transporter SLC24A4 to the ameloblast cell membrane. These proteins share a distinct domain architecture comprising one or two β-propellers followed by an α-solenoid domain

, an evolutionarily conserved structure common among proteins that form membrane coat complexes, dating back to the early eukaryotic endomembrane system .
Gp11, C-terminal domain (Gp11_C)
Type: Domain

This entry represents the C-terminal β-barrel domain found in the Phage Mu Gp11 protein. The function of this protein is not known. In some proteins, this domain covers the whole sequence.
ATXR3, GYF domain (ATXR3_GYF)
Type: Domain

This entry represents the presumed GYF domain in ATXR3 from Arabidopsis thaliana. This domain, which is usually associated with

and

, is predicted to adopt an α-β configuration.

Histone-lysine N-methyltransferase (ATXR3), also known as SET DOMAIN GROUP 2 (SDG2), is involved in the trimethylation of lysine 4 on histone H3 (H3K4me3), a critical post-translational modification that regulates chromatin structure and gene expression. It is essential for both sporophyte and gametophyte development , . Acting as a diurnal 'writer', it counteracts the nocturnal demethylase activity of JMJ14, thus orchestrating the circadian rhythm of histone modifications like H3K4me3 and modulating the rhythmic expression of target genes that follow a diurnal cycle. This process relies on the circadian clock oscillators CCA1 and LHY to maintain the proper timing of these modifications .
WDR11, first beta-propeller (Beta-prop_WDR11_1st)
Type: Domain

This entry represents the first β-propeller found at the N-terminal end of WD repeat-containing protein 11 (WDR11) from animals and similar eukaryotic proteins.

Members of the WDR11 family share a domain architecture consisting of two β-propellers followed by a TPR domain. WDR11 has been implicated in human developmental genetic disorders characterised by delayed puberty and infertility. WDR11 modulates the Hedgehog (Hh) signalling pathway and is essential for adequate ciliogenesis . The β-propellers in WDR11 are involved in protein-protein interaction. This are essential for proper interaction with EMX1, a homeodomain transcription factor involved in the development of olfactory neurons. Impaired pubertal development is suggested to result from a deficiency of productive WDR11 protein interaction . WDR11 is also involved in vesicle traffic as it binds TBC1D23, a vesicle-golgin adaptor required for endosome-to-Golgi trafficking . WDR11 is part of the WDR11 complex (consisting of WDR11, C17orf75 and FAM91A) that facilitates the tethering of AP-1-derived vesicles . Mutations of the WDR11 gene have been linked to congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS), human developmental genetic disorders defined by delayed puberty and infertility .
WDR11, second beta-propeller (Beta-prop_WDR11_2nd)
Type: Domain

This entry represents the second β-propeller found in WD repeat-containing protein 11 (WDR11) from animals and similar eukaryotic proteins.

Members of the WDR11 family share a domain architecture consisting of two β-propellers followed by a TPR domain. WDR11 has been implicated in human developmental genetic disorders characterised by delayed puberty and infertility. WDR11 modulates the Hedgehog (Hh) signalling pathway and is essential for adequate ciliogenesis . The β-propellers in WDR11 are involved in protein-protein interaction. This are essential for proper interaction with EMX1, a homeodomain transcription factor involved in the development of olfactory neurons. Impaired pubertal development is suggested to result from a deficiency of productive WDR11 protein interaction . WDR11 is also involved in vesicle traffic as it binds TBC1D23, a vesicle-golgin adaptor required for endosome-to-Golgi trafficking . WDR11 is part of the WDR11 complex (consisting of WDR11, C17orf75 and FAM91A) that facilitates the tethering of AP-1-derived vesicles . Mutations of the WDR11 gene have been linked to congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS), human developmental genetic disorders defined by delayed puberty and infertility .
WDR11, TPR domain (TPR_WDR11)
Type: Domain

This entry represents the TPR domain found at the C-terminal of WD repeat-containing protein 11 (WDR11) from animals and similar eukaryotic proteins.

Members of the WDR11 family share a domain architecture consisting of two β-propellers followed by a TPR domain. WDR11 has been implicated in human developmental genetic disorders characterised by delayed puberty and infertility. WDR11 modulates the Hedgehog (Hh) signalling pathway and is essential for adequate ciliogenesis . The β-propellers in WDR11 are involved in protein-protein interaction. This are essential for proper interaction with EMX1, a homeodomain transcription factor involved in the development of olfactory neurons. Impaired pubertal development is suggested to result from a deficiency of productive WDR11 protein interaction . WDR11 is also involved in vesicle traffic as it binds TBC1D23, a vesicle-golgin adaptor required for endosome-to-Golgi trafficking . WDR11 is part of the WDR11 complex (consisting of WDR11, C17orf75 and FAM91A) that facilitates the tethering of AP-1-derived vesicles . Mutations of the WDR11 gene have been linked to congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS), human developmental genetic disorders defined by delayed puberty and infertility .
WDR19, first beta-propeller (Beta-prop_WDR19_1st)
Type: Domain

This entry represents the first β-propeller of WRD19 (also known as IFT144) from animals and the orthologue from C.elegans DYF2. This domain is also found in the WD repeat-containing protein 39-A/B from Salmo salar.

WDR19 is a core component of the IFT complex A (IFT-A, together with IFT140 and IFT122), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), being involved in cilia function and/or assembly . IFT-A polymerises interacts with IFT-B, and uses an array of β-propeller and TPR domains to create 'carriages' of the IFT train that engage TULP adaptor proteins .
VWC2L, C-terminal domain (VWC2L_C)
Type: Domain

This domain is found at the C-terminal end of human von Willebrand factor C domain-containing protein 2-like (VWC2L), its paralogue von Willebrand factor C domain-containing protein 2 (Brorin), encoded by gene VWC2 and similar proteins predominantly found in vertebrates. VWC2L may play a role in neurogenesis, bone differentiation and matrix mineralisation . Brorin is a BMP antagonist, which may play a role in neural development. It also promotes cell adhesion . This domain is predicted to adopt an all-β configuration.