SII-SWORD/CoKE huggingface dataset:
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2, SH3 domain (PLCgamma2_SH3)
Type: Domain

PLCgamma2 (phospholipase C-gamma-2 or 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2) is primarily expressed in haematopoietic cells, specifically in B cells . It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells . PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC . PLCgamma2 contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by an SH3 domain and C2 domain.
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1, SH3 domain (PLCgamma1_SH3)
Type: Domain

PLCgamma1 (phospholipase C-II or 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1) is widely expressed and is essential in growth and development . It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation . PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC . PLCgamma contains a pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF) . It also interacts with Cbl, inhibiting its phosphorylation and activity.

This entry represents the SH3 domain of PLCgamma1.
Abl Interactor 1, SH3 domain (Abi1_SH3)
Type: Domain

Abi1, also called e3B1, is a central regulator of actin cytoskeletal reorganization through interactions with many protein complexes. It is part of WAVE, a nucleation-promoting factor complex, that links Rac 1 activation to actin polymerization causing lamellipodia protrusion at the plasma membrane . Abi1 is a target of alpha4 integrin, regulating membrane protrusions at sites of integrin engagement . Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration . Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain.

This entry represents the SH3 domain of Abi1.
Abl interactor 2, SH3 domain (Abi2_SH3)
Type: Domain

Abi2 is a component of the WAVE1 complex. It localises to sites of actin polymerisation at the tips of lamellipodia and filopodia . Mice deficient with Abi2 show defects in orientation and migration of lens fibres, neuronal migration, dendritic spine morphology, as well as deficiencies in learning and memory . Abi proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain . The SH3 domain of Abi binds to a PxxP motif in Abl .

This entry represents the SH3 domain of Abi2.
TRIM36, PRY/SPRY domain (SPRY/PRY_TRIM36)
Type: Domain

This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C terminus of TRIM36. TRIM36 (also known as Haprin or RNF98) has a ubiquitin ligase activity and interacts with centromere protein-H, one of the kinetochore proteins. It has been shown that TRIM36 is potentially associated with chromosome segregation and that an excess of TRIM36 may cause chromosomal instability . In Xenopus laevis, TRIM36 is expressed during early embryogenesis and plays an important role in the arrangement of somites during their formation .
Rho guanine nucleotide exchange factor 9, SH3 domain (ARHGEF9_SH3)
Type: Domain

ARHGEF9 (Rho guanine nucleotide exchange factor 9, also called PEM2 or collybistin) selectively activates Cdc42 by exchanging bound GDP for free GTP . It is highly expressed in the brain and it interacts with gephyrin, a postsynaptic protein associated with GABA and glycine receptors. Mutations in the ARHGEF9 gene cause X-linked mental retardation with associated features like seizures, hyper-anxiety, aggressive behavior, and sensory hyperarousal . ARHGEF9 contains a SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains .

This entry represents the SH3 domain of ARHGEF9.
VAV1 protein, second SH3 domain (VAV1_SH3_2)
Type: Domain

VAV1 (also known as proto-oncogene vav) is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells . It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization . It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others .

The VAV protein family members are multiple domain proteins, including Vav from flies and VAV1/2/3 from mammals. VAV1 predominates in hematopoietic cells, whereas VAV2 and VAV3 are more broadly expressed. They have a calponin homology (CH) domain, an acidic domain (AC), a Dbl homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich (CR) domain containing a zinc finger, and a complex region with SH2 and SH3 domains. Therefore they may participate in the activity of several pathways . They are signal transducer proteins that couple tyrosine kinase signals with the activation of the Rho/Rac GTPases, .

This entry represents the second SH3 domain of VAV1. This domain interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2 .
VAV1 protein, first SH3 domain (VAV1_SH3_1)
Type: Domain

VAV1 (also known as proto-oncogene vav) is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells . It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization . It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others .

The VAV protein family members are multiple domain proteins, including Vav from flies and VAV1/2/3 from mammals. VAV1 predominates in hematopoietic cells, whereas VAV2 and VAV3 are more broadly expressed. They have a calponin homology (CH) domain, an acidic domain (AC), a Dbl homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich (CR) domain containing a zinc finger, and a complex region with SH2 and SH3 domains. Therefore they may participate in the activity of several pathways . They are signal transducer proteins that couple tyrosine kinase signals with the activation of the Rho/Rac GTPases, .

This entry represents the first SH3 domain of VAV1.
TRIM46, PRY/SPRY domain (SPRY/PRY_TRIM46)
Type: Domain

TRIM46 is required for neuronal polarisation and axon formation. It localises to the newly specified axon and organises uniform microtubule orientation in axons . This entry represents the PRY/SPRY domain at C-terminal of TRIM46. It consists of the distinct N-terminal PRY subdomain followed by the SPRY subdomain

TRIM proteins are a family of E3 ubiquitin ligases defined by their N-terminal tripartite motif, also known as RBCC. This motif consists of a RING domain, which confers E3 ligase activity, one or two B-box domains that are zinc-binding motifs, and a coiled-coil region that facilitates protein dimerisation. These proteins play critical roles in various cellular processes, including innate immunity, transcriptional regulation, and protein degradation .

The B30.2 domain was first identified as a protein domain encoded by an exon (named B30-2) in the Homo sapiens class I major histocompatibility complex region , whereas the SPRY domain was first identified in a Dictyostelium discoideum kinase splA and mammalian calcium-release channels ryanodine receptors . B30.2 domain consists of PRY and SPRY subdomains. The SPRY domains (after SPla and the RYanodine Receptor) are shorter at the N terminus than the B30.2 domains. The ~200-residue B30.2/SPRY (for B30.2 and/or SPRY) domain is present in a large number of proteins with diverse individual functions in different biological processes. The B30.2/SPRY domain in these proteins is likely to function through protein-protein interaction .
The N-terminal ~60 residues of B30.2/SPRY domains are poorly conserved and, as a consequence, a new domain name PRY was coined for a group of similar sequence segments N-terminal to the SPRY domains . The B30.2/SPRY domain contains three highly conserved motifs (LDP, WEVE and LDYE) . The B30.2/SPRY domain adopts a highly distorted, compact β-sandwich fold with two additional short β-helices at the N terminus. The β-sandwich of the B30.2/SPRY domain consists of two layers of β-sheets: sheet A composed of eight strands and sheet B composed of seven strands. All the β-strands are in antiparallel arrangement . The 5th β-strand corresponding to WEVE motif . Both the N- and C-terminal ends of the B30.2/SPRY domains in general are close to each other .
VAV2 protein, second SH3 domain (VAV2_SH3_2)
Type: Domain

VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42 . It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others . It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins .

This entry represents the second SH3 domain of VAV2.
VAV2 protein, first SH3 domain (VAV2_SH3_1)
Type: Domain

VAV2 is widely expressed and functions as a guanine nucleotide exchange factor (GEF) for RhoA, RhoB and RhoG and also activates Rac1 and Cdc42 . It is implicated in many cellular and physiological functions including blood pressure control, eye development, neurite outgrowth and branching, EGFR endocytosis and degradation, and cell cluster morphology, among others . It has been reported to associate with Nek3. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins .

This entry represents the first SH3 domain of VAV2.
VAV3 protein, second SH3 domain (VAV3_SH3_2)
Type: Domain

VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1 . It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration . It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity . VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains.
Shank1, SH3 domain (Shank1_SH3)
Type: Domain

Shank1, also called SSTRIP (Somatostatin receptor-interacting protein), is a brain-specific protein that plays a role in the construction of postsynaptic density (PSD) and the maturation of dendritic spines . Mice deficient in Shank1 show altered PSD composition, thinner PSDs, smaller dendritic spines, and weaker basal synaptic transmission, although synaptic plasticity is normal. They show increased anxiety and impaired fear memory, but also show better spatial learning . A Shank protein carries scaffolding functions through multiple sites of protein-protein interaction in its domain architecture, including ankyrin (ANK) repeats, a long proline rich region, as well as SH3, PDZ, and SAM domains.

This entry represents the SH3 domain of Shank1 which binds GRIP, a scaffold protein that binds AMPA receptors and Eph receptors/ligands .
Stac3, first SH3 domain (Stac3_SH3_1)
Type: Domain

Stac (SH3 and cysteine-rich domain-containing) proteins are putative adaptor proteins that contain a cysteine-rich C1 domain and one or two SH3 domains at the C terminus. There are three mammalian members (Stac1, Stac2, and Stac3) of this family. Stac1 and Stac3 contain two SH3 domains while Stac2 contains a single SH3 domain at the C terminus. Stac3 is specific to skeletal muscle and is a component of the excitation-contraction coupling machinery. A mutation in the Stac3 gene has been linked to a severe muscle disease, Native American myopathy (NAM) .

This entry represents the first SH3 domain of Stac3.
Intersectin-2, first SH3 domain (Intersectin-2_SH3_1)
Type: Domain

Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction . It plays a role in clathrin-coated pit (CCP) formation . It binds to many proteins through its multidomain structure and facilitates the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation . It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains.

This entry represents the first SH3 domain of ITSN2.
Intersectin-2, second SH3 domain (Intersectin-2_SH3_2)
Type: Domain

Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction . It plays a role in clathrin-coated pit (CCP) formation . It binds to many proteins through its multidomain structure and facilitates the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation . It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains.

This entry represents the second SH3 domain of ITSN2.
Intersectin-2, third SH3 domain (Intersectin-2_SH3_3)
Type: Domain

Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction . It plays a role in clathrin-coated pit (CCP) formation . It binds to many proteins through its multidomain structure and facilitates the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation . It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains.

This entry represents the third SH3 domain of ITSN2.
Intersectin-2, fourth SH3 domain (Intersectin-2_SH3_4)
Type: Domain

Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction . It plays a role in clathrin-coated pit (CCP) formation . It binds to many proteins through its multidomain structure and facilitates the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation . It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains.

This entry represents the fourth SH3 domain of ITSN2.
Intersectin-2, fifth SH3 domain (Intersectin-2_SH3_5)
Type: Domain

Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction . It plays a role in clathrin-coated pit (CCP) formation . It binds to many proteins through its multidomain structure and facilitates the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation . It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains.

This entry represents the fifth SH3 domain of ITSN2.
Fibronectin type III and SPRY containing 1, PRY/SPRY domain (SPRY/PRY_FSD1)
Type: Domain

This domain is part of the fibronectin type III and SPRY domain-containing 1 (FSD1) and FSD1-like (FSD1L) proteins. These are centrosome-associated proteins that are characterised by an N-terminal coiled-coil region downstream of B-box (BBC) domain, a central fibronectin type III (FN3) domain, and a C-terminal PRY/SPRY domain . The FSD1 protein associates with a subset of microtubules and may be involved in the stability and organization of microtubules during cytokinesis .
PACSIN1/PACSIN2, SH3 domain (PACSIN1/PACSIN2_SH3)
Type: Domain

PACSIN1 and PACSIN2 belong to the PACSIN family that contains a N-terminal F-BAR (FCH-BAR) domain and a C-terminal SH3 domain . They are cytoplasmic phosphoproteins that play a role in vesicle formation and transport .

PACSIN1 (also known as Syndapin-1) is upregulated upon differentiation into neuronal cells . The SH3 domain of PACSIN1 mediates activation of neural WASP (N-WASP), which is required to regulate actin polymerisation and is essential for proper neuromorphogenesis and cellular motility . Two phosphorylation sites within the F-BAR domain of PACSIN1 are used for membrane tubulation regulation .
Cas scaffolding protein family member 4, SH3 domain (CASS4_SH3)
Type: Domain

CASS4, also called HEPL (HEF1-EFS-p130Cas-like), is a member of the CAS family. It localizes to focal adhesions and plays a role in regulating FAK activity, focal adhesion integrity, and cell spreading .

CAS (Crk-associated substrate) family members are adaptor proteins that contain a highly conserved N-terminal SH3 domain, an adjacent unstructured domain (substrate domain) containing multiple tyrosine phosphorylation sites that enable binding by SH2-domain containing proteins, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Most of these domains mediate protein-protein interactions. Through these interactions, they assemble larger signaling complexes that are essential for cell proliferation, survival, migration, and other processes . The CAS family consists of four members: BCAR1, HEF1, EFS, and CASS4 .
BCAR1, SH3 domain (BCAR1_SH3)
Type: Domain

Breast cancer anti-estrogen resistance protein 1 (BCAR1, also known as p130Cas)
is a member of the Cas (Crk-associated substrate) family of adaptor proteins, which function as key signalling nodes with important regulatory roles in normal and pathological cells . BCAR1 plays a central coordinating role for tyrosine kinase-based signalling through focal adhesion kinase (FAK) . It is readily phosphorylated by FAK and Src . Overexpression of BCAR1 confers anti-estrogen resistance on breast cancer cells . It regulates the tumour suppressor function of TGF-beta during breast cancer progression through regulation of Smad2/3 activity .

This entry represents the SH3 domain of BCAR1.
Enhancer of filamentation 1, SH3 domain (NEDD9_SH3)
Type: Domain

Enhancer of filamentation 1 (also known as NEDD9 or Cas-L) is a member of the CAS family. It is a scaffolding protein that assembles signaling complexes regulating multiple cellular processes, such as cell adhesion, migration, invasion, and metastasis. It is commonly dysregulated during cancer progression. It interacts with Aurora-A kinase to control ciliary resorption, and with Src and other partners to influence proliferative signaling pathways often activated in autosomal dominant polycystic kidney disease .

CAS (Crk-associated substrate) family members are adaptor proteins that contain a highly conserved N-terminal SH3 domain, an adjacent unstructured domain (substrate domain) containing multiple tyrosine phosphorylation sites that enable binding by SH2-domain containing proteins, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Most of these domains mediate protein-protein interactions. Through these interactions, they assemble larger signaling complexes that are essential for cell proliferation, survival, migration, and other processes . The CAS family consists of four members: BCAR1, HEF1, EFS, and CASS4 .
Embryonal Fyn-associated substrate, SH3 domain (EFS_SH3)
Type: Domain

EFS (also known as SIN) is a member of the CAS family. It is involved in T lymphocyte development and immune system maturation. It has also been linked to several disorders, such as cancers and Chediak-Higashi syndrome .

CAS (Crk-associated substrate) family members are adaptor proteins that contain a highly conserved N-terminal SH3 domain, an adjacent unstructured domain (substrate domain) containing multiple tyrosine phosphorylation sites that enable binding by SH2-domain containing proteins, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. Most of these domains mediate protein-protein interactions. Through these interactions, they assemble larger signaling complexes that are essential for cell proliferation, survival, migration, and other processes . The CAS family consists of four members: BCAR1, HEF1, EFS, and CASS4 .