SII-SWORD/CoKE huggingface dataset:
ASAP1-like, SH3 domain (ASAP1-like_SH3)
Type: Domain

ASAP1 is an Arf GAP that associates with and regulates actin-based structures. It is also involved in actin remodeling affecting cell spreading and cell migration . ASAP1 contains BAR, PH, Arf GAP, Ank repeats, Proline-rich, E/DLPPKP repeat, and SH3 domains. It binds to focal adhesion kinase (FAK) via its SH3 domain . The BAR domain of ASAP1 is also critical for its cellular function in regulation of actin-based structures .

This entry includes the SH3 domain of ASAP1.
Tyrosine-protein kinase ABL, SH2 domain (ABL_SH2)
Type: Domain

ABL-family proteins are highly conserved tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. Several types of posttranslational modifications control ABL catalytic activity, subcellular localization, and stability, with consequences for both cytoplasmic and nuclear ABL functions. Binding partners provide additional regulation of ABL catalytic activity, substrate specificity, and downstream signaling. By combining this cassette with actin-binding and -bundling domains, ABL proteins are capable of connecting phosphoregulation with actin-filament reorganization .
SYK/ZAP-70, N-terminal SH2 domain (SYK/ZAP-70_N_SH2)
Type: Domain

ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells . They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function .
SH2D4B, SH2 domain (SH2D4B_SH2)
Type: Domain

SH2D4B contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites .
Chimaerin, SH2 domain (Chimaerin_SH2)
Type: Domain

Chimaerin is a family of GTPase activating proteins for the small G-protein Rac. Chimaerin family members have been implicated in development, neuritogenesis and cancer .

This entry represents the SH2 domain of alpha2-chimerin and beta2-chimerin.
Ras GTPase-activating protein 1, N-terminal SH2 domain (RasGAP_N_SH2)
Type: Domain

Ras GTPase-activating protein 1 (also known as p120-RasGAP) is an inhibitory regulator of the Ras-cyclic AMP pathway . Its C-terminal catalytic domain promotes GTP hydrolysis and plays a key role in the regulation of Ras-GTP bound . Its N-terminal part contains two SH2, SH3, PH (pleckstrin homology) and CaLB/C2 (calcium-dependent phospholipid-binding domain) domains, which allow various functions such as anti-/pro-apoptosis, proliferation and cell migration .

Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general the longer isoform contains two SH2 domains, an SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras .

This entry represents the N-terminal SH2 domain.
Ras GTPase-activating protein 1, C-terminal SH2 domain (RasGAP_C_SH2)
Type: Domain

Ras GTPase-activating protein 1 (also known as p120-RasGAP) is an inhibitory regulator of the Ras-cyclic AMP pathway . Its C-terminal catalytic domain promotes GTP hydrolysis and plays a key role in the regulation of Ras-GTP bound . Its N-terminal part contains two SH2, SH3, PH (pleckstrin homology) and CaLB/C2 (calcium-dependent phospholipid-binding domain) domains, which allow various functions such as anti-/pro-apoptosis, proliferation and cell migration .

Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general the longer isoform contains two SH2 domains, an SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras .

This entry represents the C-terminal SH2 domain.
DAPP1, SH2 domain (DAPP1_SH2)
Type: Domain

DAPP1/Bam32 is an adaptor protein that plays important roles in B cell receptor signalling, T cell receptor signalling and antibody affinity maturation in germinal centres . It contains a putative myristoylation site at its N terminus, followed by a SH2 domain, and a pleckstrin homology (PH) domain at its C terminus. It translocates to the plasma membrane of B-lymphoma cells upon BCR (B-cell receptor) cross-linking; this translocation is PI3K (phosphoinositide 3-kinase)-dependent and PH domain-mediated .

This entry represents the SH2 domain of DAPP1/Bam32. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites .
ShkA/ShkC, SH2 domain (ShkA/ShkC_SH2)
Type: Domain

This entry represents the SH2 domain found in shkA (also known as SHK1) and shkC from Dictyostelium discoideum. ShkA is a dual-specificity kinase is required for proper chemotaxis. Its SH2 domain is required for its plasma membrane/cortex localization and the proper function of SHK1 .

In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites .
ShkD/ShkE, SH2 domain (ShkD/ShkE_SH2)
Type: Domain

SH2-bearing genes cloned from Dictyostelium include two transcription factors, STATa and STATc, and a signaling factor, SHK1 (shkA). A database search of the Dictyostelium discoideum genome revealed two additional putative STAT sequences, dd-STATb and dd-STATd, and four additional putative SHK genes, dd-SHK2 (shkB), dd-SHK3 (shkC), dd-SHK4 (shkD), and dd-SHK5 (shkE). This entry contains SH2 domains of shkD and shkE. All of the SHK members are most closely related to the protein kinases found in plants. However these kinases in plants are not conjugated to any SH2 or SH2-like sequences. Alignment data indicates that the SHK SH2 domains carry some features of the STAT SH2 domains in Dictyostelium. When STATc's linker domain was used for a BLAST search, the sequence between the protein kinase domain and the SH2 domain (the linker) of SHK was recovered, suggesting a close relationship among these molecules within this region. SHK's linker domain is predicted to contain an α-helix which is indeed homologous to that of STAT. Based on the phylogenetic alignment, SH2 domains can be grouped into two categories, STAT-type and Src-type. SHK family members are in between, but are closer to the STAT-type which indicates a close relationship between SHK and STAT families in their SH2 domains and further supports the notion that SHKs linker-SH2 domain evolved from STAT or STATL (STAT-like Linker-SH2) domain found in plants. In SHK, STAT, and SPT6, the linker-SH2 domains all reside exclusively in the C-terminal regions. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites .
PTK6, SH2 domain (PTK6_SH2)
Type: Domain

Human protein-tyrosine kinase-6 (PTK6, also known as breast tumor kinase (Brk)) is a member of the non-receptor protein-tyrosine kinase family and is expressed in two-thirds of all breast tumours . PTK6 contains an SH3 domain, an SH2 domain, and catalytic domains. For the case of the non-receptor protein-tyrosine kinases, the SH2 domain is typically involved in negative regulation of kinase activity by binding to a phosphorylated tyrosine residue near to the C terminus. The C-terminal sequence of PTK6 (PTSpYENPT where pY is phosphotyrosine) is thought to be a self-ligand for the SH2 domain .
SH3BP2, SH2 domain (SH3BP2_SH2)
Type: Domain

The adaptor protein 3BP2/SH3BP2 is a cytoplasmic adaptor that contributes to the regulation of immune responses . The protein-tyrosine kinase Syk phosphorylates 3BP2 which results in the activation of Rac1 through the interaction with the SH2 domain of Vav1 and induces the binding to the SH2 domain of the upstream protein-tyrosine kinase Lyn and enhances its kinase activity . 3BP2 has a positive regulatory role in IgE-mediated mast cell activation . In lymphocytes, engagement of T cell or B cell receptors triggers tyrosine phosphorylation of 3BP2 . 3BP2 is required for the proliferation of B cells and B cell receptor signaling. Mutations in the 3BP2 gene are responsible for cherubism resulting in excessive bone resorption in the jaw .

This entry represents the SH2 domain of SH3BP2.
SH3 domain-binding protein 2 (SH3BP2)
Type: Family

The adaptor protein 3BP2/SH3BP2 is a cytoplasmic adaptor that contributes to the regulation of immune responses . The protein-tyrosine kinase Syk phosphorylates 3BP2 which results in the activation of Rac1 through the interaction with the SH2 domain of Vav1 and induces the binding to the SH2 domain of the upstream protein-tyrosine kinase Lyn and enhances its kinase activity . 3BP2 has a positive regulatory role in IgE-mediated mast cell activation . In lymphocytes, engagement of T cell or B cell receptors triggers tyrosine phosphorylation of 3BP2 . 3BP2 is required for the proliferation of B cells and B cell receptor signaling. Mutations in the 3BP2 gene are responsible for cherubism resulting in excessive bone resorption in the jaw .
Fes/Fps/Fer, SH2 domain (Fes/Fps/Fer_SH2)
Type: Domain

The Fps family consists of members Fps/Fes and Fer/Flk/Tyk3. They are cytoplasmic protein-tyrosine kinases implicated in signaling downstream from cytokines, growth factors and immune receptors . Fes/Fps/Fer contains three coiled-coil regions, an SH2 (Src-homology-2) and a TK (tyrosine kinase catalytic) domain signature . This entry represents the SH2 domain.

In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites .
Tyrosine-protein kinase Lck, SH2 domain (Lck_SH2)
Type: Domain

Lck is a member of the Src non-receptor type tyrosine kinase family of proteins. CD4 and CD8 directly couple with Lck, and cross-linking of these receptors leads to Lck activation .

The Src non-receptor type tyrosine kinase (SFK) family members have an unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail. The SH2 domain of SFKs is involved in kinase autoinhibition and T-cell receptor signaling. The binding SH2 domains to phosphotyrosine (pY) sites is critical for the autoinhibition and substrate recognition of the SFKs .
Tyrosine-protein kinase HCK, SH2 domain (HCK_SH2)
Type: Domain

HCK is a member of the Src non-receptor type tyrosine kinase (SFK) family. HCK is expressed as two isoforms, p59Hck and p61Hck, in phagocytes. It plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration . Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail .

The Src non-receptor type tyrosine kinase (SFK) family members have an unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail. The SH2 domain of SFKs is involved in kinase autoinhibition and T-cell receptor signaling. The binding SH2 domains to phosphotyrosine (pY) sites is critical for the autoinhibition and substrate recognition of the SFKs .
Tyrosine-protein kinase Lyn, SH2 domain (Lyn_SH2)
Type: Domain

Lyn is a member of the Src non-receptor type tyrosine kinase family. It plays an important role in the regulation of B-cell differentiation, proliferation, survival and apoptosis, and is important for immune self-tolerance . It also mediates the responses to cytokines and growth factors in hematopoietic progenitors, platelets, erythrocytes, and in mature myeloid cells, such as dendritic cells, neutrophils and eosinophils . Lyn plays an essential role in the transmission of signals through phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based inhibitory motifs (ITIM) in regulatory proteins .

This entry represents the SH2 domain of Lyn.

The Src non-receptor type tyrosine kinase (SFK) family members have an unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail. The SH2 domain of SFKs is involved in kinase autoinhibition and T-cell receptor signaling. The binding SH2 domains to phosphotyrosine (pY) sites is critical for the autoinhibition and substrate recognition of the SFKs .
Tyrosine-protein kinase Blk, SH2 domain (Blk_SH2)
Type: Domain

Blk is a member of the Src non-receptor type tyrosine kinase family of proteins. Blk is involved in B-cell receptor signaling and B-cell development . Unlike most other Src members Blk lacks cysteine residues in the SH4 domain that undergo palmitylation. Blk is required for the development of IL-17-producing gamma-delta T cells .

The Src non-receptor type tyrosine kinase (SFK) family members have an unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail. The SH2 domain of SFKs is involved in kinase autoinhibition and T-cell receptor signaling. The binding SH2 domains to phosphotyrosine (pY) sites is critical for the autoinhibition and substrate recognition of the SFKs .
STAT2, SH2 domain (STAT2_SH2)
Type: Domain

STAT2 is a member of the STAT protein family. In response to interferon, STAT2 forms a complex with STAT1 and IFN regulatory factor family protein p48 (ISGF3G), in which this protein acts as a transactivator, but lacks the ability to bind DNA directly . Transcription adaptor P300/CBP (EP300/CREBBP) has been shown to interact specifically with STAT2, which is thought to be involved in the process of blocking IFN-alpha response by adenovirus .

STAT proteins have a dual function: signal transduction and activation of transcription. When cytokines are bound to cell surface receptors, the associated Janus kinases (JAKs) are activated, leading to tyrosine phosphorylation of the given STAT proteins . Phosphorylated STATs form dimers, translocate to the nucleus, and bind specific response elements to activate transcription of target genes . STAT proteins contain an N-terminal domain (NTD), a coiled-coil domain (CCD), a DNA-binding domain (DBD), an α-helical linker domain (LD), an SH2 domain, and a transactivation domain (TAD). The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6 .
STAT3, SH2 domain (STAT3_SH2)
Type: Domain

STAT3 is a member of the STAT protein family. STAT3 mediates the expression of a variety of genes in response to cell stimuli, and plays a key role in many cellular processes such as cell growth and apoptosis. STAT3 has been shown to interact with Rho GTPases Three alternatively spliced transcript variants encoding distinct isoforms have been described. STAT3 activation is required for self-renewal of embryonic stem cells (ESCs) and is essential for the differentiation of the TH17 helper T cells . Mutations in the STAT3 gene result in hyperimmunoglobulin E syndrome and human cancers .

STAT proteins have a dual function: signal transduction and activation of transcription. When cytokines are bound to cell surface receptors, the associated Janus kinases (JAKs) are activated, leading to tyrosine phosphorylation of the given STAT proteins . Phosphorylated STATs form dimers, translocate to the nucleus, and bind specific response elements to activate transcription of target genes . STAT proteins contain an N-terminal domain (NTD), a coiled-coil domain (CCD), a DNA-binding domain (DBD), an α-helical linker domain (LD), an SH2 domain, and a transactivation domain (TAD). The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6 .
STAT4, SH2 domain (STAT4_SH2)
Type: Domain

Signal transducer and activator of transcription 4 (STAT4) transduces interleukin-12, interleukin-23, and type I interferon cytokine signals in T cells and monocytes . It plays an important role in CD4+ Th1 lineage differentiation and IFN-gamma protein expression by CD4+ T cells . It is crucial for both innate and adaptive immune responses to viral infection . Variations of the STAT4 gene affect the susceptibility to autoimmune diseases , such as systemic lupus erythematosus 11 (SLEB11) and rheumatoid arthritis (RA) .

STAT proteins have a dual function: signal transduction and activation of transcription. When cytokines are bound to cell surface receptors, the associated Janus kinases (JAKs) are activated, leading to tyrosine phosphorylation of the given STAT proteins . Phosphorylated STATs form dimers, translocate to the nucleus, and bind specific response elements to activate transcription of target genes . STAT proteins contain an N-terminal domain (NTD), a coiled-coil domain (CCD), a DNA-binding domain (DBD), an α-helical linker domain (LD), an SH2 domain, and a transactivation domain (TAD). The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6 .

This entry represents the SH2 domain of STAT4.
STAT6, SH2 domain (STAT6_SH2)
Type: Domain

STAT6 mediate signals from the IL-4 receptor. Unlike the other STAT proteins which bind an IFNgamma Activating Sequence (GAS), STAT6 stands out as having a unique binding site preference. This site consists of a palindromic sequence separated by a 3 bp spacer (TTCNNNG-AA)(N3 site). STAT6 is able to bind the GAS site but only at a low affinity upon IL-4-induced activation . There is speculation that the inappropriate activation of STAT6 is involved in uncontrolled cell growth in an oncogenic state . IL-4 signaling via STAT6 initially occurs unopposed, but is then dampened by a negative feedback mechanism through the IL-4/Stat6 dependent induction of SOCS1 expression. The IL-4 dependent aspect of Th2 differentiation requires the activation of STAT6. IL-4 signaling and STAT6 appear to play an important role in the immune response. It was shown that large scale chromatin remodeling of the IL-4 gene occurs as cells differentiate into Th2 effectors is STAT6 dependent .

STAT proteins have a dual function: signal transduction and activation of transcription. When cytokines are bound to cell surface receptors, the associated Janus kinases (JAKs) are activated, leading to tyrosine phosphorylation of the given STAT proteins . Phosphorylated STATs form dimers, translocate to the nucleus, and bind specific response elements to activate transcription of target genes . STAT proteins contain an N-terminal domain (NTD), a coiled-coil domain (CCD), a DNA-binding domain (DBD), an α-helical linker domain (LD), an SH2 domain, and a transactivation domain (TAD). The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6 .
STAT5a/5b, DNA-binding domain (STAT5a/5b_DBD)
Type: Domain

STAT proteins have a dual function: signal transduction and activation of transcription. When cytokines are bound to cell surface receptors, the associated Janus kinases (JAKs) are activated, leading to tyrosine phosphorylation of the given STAT proteins . Phosphorylated STATs form dimers, translocate to the nucleus, and bind specific response elements to activate transcription of target genes . STAT proteins contain an N-terminal domain (NTD), a coiled-coil domain (CCD), a DNA-binding domain (DBD), an α-helical linker domain (LD), an SH2 domain, and a transactivation domain (TAD). The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6 .

STAT5 is a member of the STAT family of transcription factors. Two highly related proteins, STAT5a and STAT5b are encoded by separate genes, but are 90% identical at the amino acid level. Both STAT5a and STAT5b are ubiquitously expressed and functionally interchangeable. They regulate B and T cell development . These proteins are central signalling molecules in leukaemias driven by Abelson fusion tyrosine kinases, having a key role in resistance of leukaemic cells against treatment with tyrosine kinase inhibitors (TKI) . They differentially regulate cellular behaviour in human mammary carcinoma .

This entry represents the DNA-binding domain (DBD) of STAT5, which has an Ig-like fold.
STAT1, SH2 domain (STAT1_SH2)
Type: Domain

STAT1 is a member of the STAT family of transcription factors. STAT1 is involved in upregulating genes due to a signal by interferons . STAT1 forms a heterodimer with STAT2 that can bind Interferon Stimulated Response Element (ISRE) promoter element in response to either IFN-alpha or IFN-beta stimulation .

STAT proteins have a dual function: signal transduction and activation of transcription. When cytokines are bound to cell surface receptors, the associated Janus kinases (JAKs) are activated, leading to tyrosine phosphorylation of the given STAT proteins . Phosphorylated STATs form dimers, translocate to the nucleus, and bind specific response elements to activate transcription of target genes . STAT proteins contain an N-terminal domain (NTD), a coiled-coil domain (CCD), a DNA-binding domain (DBD), an α-helical linker domain (LD), an SH2 domain, and a transactivation domain (TAD). The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6 .
Tyrosine-protein kinase JAK2, SH2 domain (JAK2_SH2)
Type: Domain

Jak2 is a protein tyrosine kinase involved in a specific subset of cytokine receptor signaling pathways. It has been found to be constitutively associated with the prolactin receptor and is required for responses to gamma interferon . Mice that do not express an active protein for this gene exhibit embryonic lethality associated with the absence of definitive erythropoiesis .

In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites .