SII-SWORD/CoKE huggingface dataset:
Janus kinase 2, catalytic domain (PTKc_Jak2_rpt2)
Type: Domain

Jak2 is widely expressed in many tissues. It is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors . Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities . It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis .

Jak2 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Despite this, the presumed pseudokinase (repeat 1) domain of Jak2 exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Inactivation of the repeat 1 domain increased Jak2 basal activity, suggesting that it modulates the kinase activity of the C-terminal catalytic (repeat 2) domain .

This entry represents the C-terminal catalytic domain.
CBY1-interacting BAR domain-containing protein 1/2, BAR domain (BAR_CBAR1/2)
Type: Domain

BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions . This group is composed of CBY1-interacting BAR domain-containing protein 1/2 (also known as the family with sequence similarity 92 (FAM92)), which were originally identified by the presence of the unknown domain DUF1208. This domain shows similarity to the BAR domains of sorting nexins. Mammals contain at least two member types, CBAR1 (FAM92A) and CBAR2 (FAM92B), which may exist in many variants. These may be involved in ciliogenesis regulation during limb morphogenesis . Human CBAR1 plays an important role in the mitochondrial function and is essential for maintaining mitochondrial morphology and inner membrane ultrastructure . The Xenopus homologue of CBAR1A (FAM92A1), xVAP019, is essential for embryo survival and cell differentiation. CBAR1A may be involved in regulating cell proliferation and apoptosis .
Phosphatidylinositol 3-kinase regulatory subunit alpha, SH3 domain (PI3K_p85alpha_SH3)
Type: Domain

This entry represents the SH3 domain of PI3K (phosphoinositide-3-kinase) subunit alpha (also known as subunit p85-alpha).
IRTKS, SH3 domain (IRTKS_SH3)
Type: Domain

IRTKS (insulin receptor tyrosine kinase substrate) or BAIAP2L1 (brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1, also knoiwn as BAR/IMD domain-containing adapter protein 2-like 1) is widely expressed, serves as a substrate for the insulin receptor, and binds the small GTPase Rac ]. It plays a role in regulating the actin cytoskeleton and colocalizes with F-actin, cortactin, VASP, and vinculin. BAIAP2L1 expression leads to the formation of short actin bundles, distinct from filopodia-like protrusions induced by the expression of the related protein IRSp53 . IRTKS mediates the recruitment of effector proteins Tir and EspFu, which regulate host cell actin reorganization, to bacterial attachment sites .

IRTKS contains an N-terminal IMD or Inverse-Bin/Amphiphysin/Rvs (I-BAR) domain, an SH3 domain, and a WASP homology 2 (WH2) actin-binding motif at the C terminus. The SH3 domain of IRTKS has been shown to bind the proline-rich C terminus of EspFu .
Pinkbar, SH3 (Pinkbar_SH3)
Type: Domain

This entry represents the SH3 domain of Pinkbar.

Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 2 (Baiap2l2), also known as BAR/IMD domain-containing adapter protein 2-like 2 and planar intestinal and kidney specific BAR domain protein (Pinkbar), is an I-BAR (Bin/amphipysin/Rvs) domain containing protein. BAR domain forms an anti-parallel all-helical dimer, with a curved (banana-like) shape, that promotes membrane tubulation. BAR domain proteins can be classified into three types: BAR, F-BAR and I-BAR. BAR and F-BAR proteins generate positive membrane curvature, while I-BAR proteins induce negative curvature .

In humans Baiap2l2 is specifically expressed in intestinal epithelial cells, where it localises to Rab13-positive vesicles and to the plasma membrane at intercellular junctions . The BAR domain of Baiap2l2 does not induce membrane protrusions or invaginations; instead, it promotes the formation of planar membrane sheets .
BAR/IMD domain-containing adapter protein 2, SH3 domain (BAIP2_SH3)
Type: Domain

This entry represents the SH3 domain of BAIP2 which has been shown to bind the proline-rich C terminus of EspFu (E. coli secreted protein F-like from prophage U) .

IRSp53, also known as IRS-58 or BAR/IMD domain-containing adapter protein 2 (BAIP2 or BAIAP2 for brain-specific angiogenesis inhibitor 1-associated protein 2), is an I-BAR (Bin/amphipysin/Rvs) domain containing protein. BAR domain forms an anti-parallel all-helical dimer, with a curved (banana-like) shape, that promotes membrane tubulation. BAR domain proteins can be classified into three types: BAR, F-BAR and I-BAR. BAR and F-BAR proteins generate positive membrane curvature, while I-BAR proteins induce negative curvature .

IRSp53 is an adaptor protein that acts at the membrane-actin interface, coupling membrane deformation with F-actin polymerisation . It is involved in the formation of filopodia and lamellipodia in cultured mesenchymal cells and contributes to assembly/maintenance of tight junctions in cultured epithelial cells . IRSp53 contains an N-terminal I-BAR domain, followed by a partial CRIB domain and a SH3 domain. It binds to small GTPase Cdc42, Rac1 and WAVE1 . IRSp53 binds Rac through its I-BAR domain and to WAVE through its SH3 domain, and thus contributes to membrane ruffling . Its SH3 domain also interacts with other regulators of actin dynamics, such as WAVE2, Mena, mDia1, Dynamin1, Eps8 and N-WASP .

This protein has been associated with human breast cancer and Gilles de la Tourette syndrome .
UDP-glycosyltransferase family, conserved site (UDP_glycos_trans_CS)
Type: Conserved_site

This entry represents the conserved domain of about 50 amino acid residues located in their C-terminal section of these enzymes.

UDP glycosyltransferases (UGT) are a superfamily of enzymes that catalyzes the addition of the glycosyl group from a UTP-sugar to a small hydrophobic molecule. Members of this family include:

Mammalian UDP-glucuronosyl transferases (

) (UDPGT) . A large family of membrane-bound microsomal enzymes which catalyze the transfer of glucuronic acid to a wide variety of exogenous and endogenous lipophilic substrates. These enzymes are of major importance in the detoxification and subsequent elimination of xenobiotics such as drugs and carcinogens.

A large number of putative UDPGT from Caenorhabditis elegans.

Mammalian 2-hydroxyacylsphingosine 1-beta-galactosyltransferase (

) (also known as UDP-galactose-ceramide galactosyltransferase). This enzyme catalyzes the transfer of galactose to ceramide, a key enzymatic step in the biosynthesis of galactocerebrosides, which are abundant sphingolipids of the myelin membrane of the central nervous system and peripheral nervous system.

Plants flavonol O(3)-glucosyltransferase (

). An enzyme that catalyzes the transfer of glucose from UDP-glucose to a flavanol. This reaction is essential and one of the last steps in anthocyanin pigment biosynthesis.

Baculoviruses ecdysteroid UDP-glucosyltransferase (

) (egt). This enzyme catalyzes the transfer of glucose from UDP-glucose to ectysteroids which are insect molting hormones. The expression of egt in the insect host interferes with the normal insect development by blocking the molting process.

Prokaryotic zeaxanthin glucosyltransferase (

) (gene crtX), an enzyme involved in carotenoid biosynthesis and that catalyses the glycosylation reaction which converts zeaxanthin to zeaxanthin-beta-diglucoside.

Streptomyces macrolide glycosyltransferases (

) . These enzymes specifically inactivates macrolide anitibiotics via 2'-O-glycosylation using UDP-glucose.
Src-like-adapter, SH3 domain (SLAP_SH3)
Type: Domain

This entry represents the SH3 domain of SLAP.

Src-like adapter proteins (SLAP and SLAP2) are involved in the regulation of immune cell surface expression and signaling. They negatively regulate T cell receptor signaling and act as critical inhibitors of platelet (hem)ITAM signaling in the setting of arterial thrombosis and ischemic stroke . They contain adjacent Src homology 3 (SH3) and Src homology 2 (SH2) domains. SLAP has been shown to regulate receptor tyrosine kinase (RTK) signaling . It also binds to the receptor tyrosine kinase Flt3 and plays a role in signal transduction downstream of Flt3 . SLAP2 acts as a negative regulator of FLT3 signaling .
ZO-1, SH3 domain (ZO-1_SH3)
Type: Domain

This entry represents the SH3 domain of ZO-1.

The zona occuldens proteins (ZO-1, ZO-2 and ZO-3) are a family of tight junction associated proteins that function as cross-linkers, anchoring the TJ strand proteins to the actin-based cytoskeleton . Each protein contains three PDZ (postsynaptic density, disc-large, ZO-1) domains, a single SH3 (Src Homology-3) domain and a catalytically inactive GK (guanylate kinase) domain, the presence of which identifies them as members of the membrane-associated guanylate kinase (MAGUK) protein family. The signature PDZ-SH3-GuK tandem of MAGUKs may form a structural supramodule with three domains interacting with each other to assemble into an integral structural unit .
ZO-2, SH3 domain (ZO-2_SH3)
Type: Domain

This entry represents the SH3 domain of ZO-2.

The zona occuldens proteins (ZO-1, ZO-2 and ZO-3) are a family of tight junction associated proteins that function as cross-linkers, anchoring the TJ strand proteins to the actin-based cytoskeleton . Each protein contains three PDZ (postsynaptic density, disc-large, ZO-1) domains, a single SH3 (Src Homology-3) domain and a catalytically inactive GK (guanylate kinase) domain, the presence of which identifies them as members of the membrane-associated guanylate kinase (MAGUK) protein family. The signature PDZ-SH3-GuK tandem of MAGUKs may form a structural supramodule with three domains interacting with each other to assemble into an integral structural unit .
MPP7, SH3 domain (MPP7_SH3)
Type: Domain

MPP7 is a scaffolding protein that binds to DLG1 and promotes tight junction formation and epithelial cell polarity . Mutations in the MPP7 gene may be associated with the pathogenesis of diabetes and extreme bone mineral density . It is one of seven vertebrate homologues of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK) . The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain.
MPP4, SH3 domain (MPP4_SH3)
Type: Domain

This entry represents the SH3 domain of MPP4.

The membrane-associated guanylate kinase (MAGUK) p55 subfamily (also known as MPP subfamily) members include the Drosophila Stardust protein and its vertebrate homologues, MPP1-7. They contain the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, they also contain the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains . MPP2-7 have two additional L27 domains at their N terminus. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain .
MPP5, SH3 domain (MPP5_SH3)
Type: Domain

MPP5, also called PALS1 (protein associated with Lin7) or Nagie oko protein in zebrafish or Stardust in Drosophila , is a scaffolding protein which associates with Crumbs homologue 1 (CRB1), CRB2, or CRB3 through its PDZ domain and with PALS1-associated tight junction protein (PATJ) or multi-PDZ domain protein 1 (MUPP1) through its L27 domain . The resulting tri-protein complexes are core proteins of the Crumb complex, which localizes at tight junctions or subapical regions, and is involved in the maintenance of apical-basal polarity in epithelial cells and the morphogenesis and function of photoreceptor cells . MPP5 is critical for the proper stratification of the retina and is also expressed in T lymphocytes where it is important for TCR-mediated activation of NFkB . Drosophila Stardust exists in several isoforms, some of which show opposing functions in photoreceptor cells, which suggests that the relative ratio of different Crumbs complexes regulates photoreceptor homeostasis . MPP5 belongs to the membrane-associated guanylate kinase (MAGUK) p55 subfamily.

The membrane-associated guanylate kinase (MAGUK) p55 subfamily (also known as MPP subfamily) members include the Drosophila Stardust protein and its vertebrate homologues, MPP1-7. They contain the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, they also contain the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains . MPP2-7 have two additional L27 domains at their N terminus. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain .
MPP2, SH3 domain (MPP2_SH3)
Type: Domain

This entry represents the SH3 domain of MPP2.

The membrane-associated guanylate kinase (MAGUK) p55 subfamily (also known as MPP subfamily) members include the Drosophila Stardust protein and its vertebrate homologues, MPP1-7. They contain the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, they also contain the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains . MPP2-7 have two additional L27 domains at their N terminus. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain .
MPP6, SH3 domain (MPP6_SH3)
Type: Domain

This entry represents the SH3 domain of MPP6 (also known as VAM-1), which is a scaffolding protein that binds to Veli-1, a homologue of Caenorhabditis Lin-7 . MPP6 belongs to the membrane-associated guanylate kinase (MAGUK) p55 subfamily.

The membrane-associated guanylate kinase (MAGUK) p55 subfamily (also known as MPP subfamily) members include the Drosophila Stardust protein and its vertebrate homologues, MPP1-7. They contain the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, they also contain the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains . MPP2-7 have two additional L27 domains at their N terminus. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain .
MPP3, SH3 domain (MPP3_SH3)
Type: Domain

This entry represents the SH3 domain of MPP3, which is a scaffolding protein that colocalizes with MPP5 and CRB1 at the subapical region adjacent to adherens junctions and may function in photoreceptor polarity. It interacts with some nectins and regulates their trafficking and processing. Nectins are cell-cell adhesion proteins involved in the establishment apical-basal polarity at cell adhesion sites . MPP3 belongs to the membrane-associated guanylate kinase (MAGUK) p55 subfamily.

The membrane-associated guanylate kinase (MAGUK) p55 subfamily (also known as MPP subfamily) members include the Drosophila Stardust protein and its vertebrate homologues, MPP1-7. They contain the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, they also contain the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains . MPP2-7 have two additional L27 domains at their N terminus. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain .
CACNB2, SH3 domain (CACNB2_SH3)
Type: Domain

Ca2+ ions are unique in that they not only carry charge but they are also the most widely used of diffusible second messengers. Voltage-dependent Ca2+ channels (VDCC) are a family of molecules that allow cells to couple electrical activity to intracellular Ca2+ signalling. The opening and closing of these channels by depolarizing stimuli, such as action potentials, allows Ca2+ ions to enter neurons down a steep electrochemical gradient, producing transient intracellular Ca2+ signals. Many of the processes that occur in neurons, including transmitter release, gene transcription and metabolism are controlled by Ca2+ influx occurring simultaneously at different cellular locales. The pore is formed by the alpha-1 subunit which incorporates the conduction pore, the voltage sensor and gating apparatus, and the known sites of channel regulation by second messengers, drugs, and toxins . The activity of this pore is modulated by four tightly-coupled subunits: an intracellular beta subunit; a transmembrane gamma subunit; and a disulphide-linked complex of alpha-2 and delta subunits, which are proteolytically cleaved from the same gene product. Properties of the protein including gating voltage-dependence, G protein modulation and kinase susceptibility can be influenced by these subunits.

Voltage-gated calcium channels are classified as T, L, N, P, Q and R, and are distinguished by their sensitivity to pharmacological blocks, single-channel conductance kinetics, and voltage-dependence. On the basis of their voltage activation properties, the voltage-gated calcium classes can be further divided into two broad groups: the low (T-type) and high (L, N, P, Q and R-type) threshold-activated channels.

The beta subunit is a soluble and intracellular protein that interacts with the transmembrane alpha1 subunit. It facilitates the trafficking and proper localization of the alpha1 subunit to the cellular plasma membrane. Vertebrates contain four different beta subunits from distinct genes (beta1-4); each exists as multiple splice variants . All are expressed in the brain while other tissues show more specific expression patterns. The beta subunits show similarity to MAGUK (membrane-associated guanylate kinase) proteins in that they contain SH3 and inactive guanylate kinase (GuK) domains; however, they do not appear to contain a PDZ domain .
Sorbin and SH3 domain-containing protein 1, third SH3 domain (SORBS1_SH3)
Type: Domain

This entry represents the third SH3 domain of Sorbin and SH3 domain-containing protein 1.

Sorbin and SH3 domain-containing protein 1 (also known as c-Cbl associated protein CAP or ponsin) belongs to a family of adaptor protein containing two other members, ArgBP2 and vinexin . It has an N-terminal sorbin homology (SoHo) domain and three C-terminal SH3 domain (Src homology domain 3) . It has been implicated in insulin signalling and is required for insulin-stimulated glucose transport . CAP binds to the major endocytic factor dynamin and affects the actin cytoskeleton organisation .
Vinexin, SH3 domain 3 (Vinexin_SH3_3)
Type: Domain

This entry represents the third SH3 domain of vinexin.

Vinexin belongs to a family of adaptor protein containing two other members, ArgBP2 and CAP (c-Cbl associated protein)/ponsin .
It has an N-terminal sorbin homology (SoHo) domain and three C-terminal SH3 domain (Src homology domain 3) . There are two vinexin isoforms in humans - vinexin alpha, which contains a SoHo domain and three SH3 domains , and vinexin beta, which contains only three SH3 domains . Its SH3 domains are associated with vinculin, WAVE2, DLG5/lp-dlg, Abl, and Cbl, while the SoHo domain is associated with flotillin and the estrogen receptor . The interaction between vinexin and vinculin is essential for recruiting vinexins to focal adhesions . Its interaction with vinculin can enhance actin cytoskeletal organisation and cell spreading .
Vinexin, SH3 domain 2 (Vinexin_SH3_2)
Type: Domain

This entry represents the second SH3 domain of vinexin.

Vinexin belongs to a family of adaptor protein containing two other members, ArgBP2 and CAP (c-Cbl associated protein)/ponsin .
It has an N-terminal sorbin homology (SoHo) domain and three C-terminal SH3 domain (Src homology domain 3) . There are two vinexin isoforms in humans - vinexin alpha, which contains a SoHo domain and three SH3 domains , and vinexin beta, which contains only three SH3 domains . Its SH3 domains are associated with vinculin, WAVE2, DLG5/lp-dlg, Abl, and Cbl, while the SoHo domain is associated with flotillin and the estrogen receptor . The interaction between vinexin and vinculin is essential for recruiting vinexins to focal adhesions . Its interaction with vinculin can enhance actin cytoskeletal organisation and cell spreading .
Vinexin, SH3 domain 1 (Vinexin_SH3_1)
Type: Domain

This entry represents the first SH3 domain of vinexin.

Vinexin belongs to a family of adaptor protein containing two other members, ArgBP2 and CAP (c-Cbl associated protein)/ponsin .
It has an N-terminal sorbin homology (SoHo) domain and three C-terminal SH3 domain (Src homology domain 3) . There are two vinexin isoforms in humans - vinexin alpha, which contains a SoHo domain and three SH3 domains , and vinexin beta, which contains only three SH3 domains . Its SH3 domains are associated with vinculin, WAVE2, DLG5/lp-dlg, Abl, and Cbl, while the SoHo domain is associated with flotillin and the estrogen receptor . The interaction between vinexin and vinculin is essential for recruiting vinexins to focal adhesions . Its interaction with vinculin can enhance actin cytoskeletal organisation and cell spreading .
Sorbin and SH3 domain-containing protein 1, first SH3 domain (SORBS1_SH3_1)
Type: Domain

This entry represents the first SH3 domain of Sorbin and SH3 domain-containing protein 1.

Sorbin and SH3 domain-containing protein 1 (also known as c-Cbl associated protein CAP or ponsin) belongs to a family of adaptor protein containing two other members, ArgBP2 and vinexin . It has an N-terminal sorbin homology (SoHo) domain and three C-terminal SH3 domain (Src homology domain 3) . It has been implicated in insulin signalling and is required for insulin-stimulated glucose transport . CAP binds to the major endocytic factor dynamin and affects the actin cytoskeleton organisation .
Sorbin and SH3 domain-containing protein 1, second SH3 domain (SORBS1_SH3_2)
Type: Domain

This entry represents the second SH3 domain of Sorbin and SH3 domain-containing protein 1.

Sorbin and SH3 domain-containing protein 1 (also known as c-Cbl associated protein CAP or ponsin) belongs to a family of adaptor protein containing two other members, ArgBP2 and vinexin . It has an N-terminal sorbin homology (SoHo) domain and three C-terminal SH3 domain (Src homology domain 3) . It has been implicated in insulin signalling and is required for insulin-stimulated glucose transport . CAP binds to the major endocytic factor dynamin and affects the actin cytoskeleton organisation .