Target name

P12931: Proto-oncogene tyrosine-protein kinase Src

  Protein function

Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1. Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal reorganization is also controlled through the phosphorylation of cortactin (CTTN). When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). Another type of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1. Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors. Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1. Plays a role in EGF-mediated calcium-activated chloride channel activation. Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) at 'Tyr-1477'. Involved in beta-arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and activation of ADRBK1, leading to beta-arrestin phosphorylation and internalization. Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor. Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus. Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. Both the formation of a SRC-PTK2B/PYK2 complex and SRC kinase activity are necessary for this function. Recruited to activated integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in turn induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function. Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase. Phosphorylates DDR2 on tyrosine residues, thereby promoting its subsequent autophosphorylation. Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-731'. Enhances DDX58/RIG-I-elicited antiviral signaling. Phosphorylates PDPK1 at 'Tyr-9', 'Tyr-373' and 'Tyr-376'. Phosphorylates BCAR1 at 'Tyr-128'. Phosphorylates CBLC at multiple tyrosine residues, phosphorylation at 'Tyr-341' activates CBLC E3 activity. Required for podosome formation (By similarity).

  Database links

Uniprot primary ID P12931
PDB ID 1A1C 1O44 1O45 1O46 1O47 1A1E 1O41 1O42 1O43 1SHD 1O48 1O49 1A07 4HXJ 1HCT 2H8H 1A08 1A09 4F5A 3VRO 4F5B 2SRC 1KSW 1O4B 1A1A 1HCS 4MXO 4F59 3ZMP 3ZMQ 4MXY 4MXX 4MXZ 1O4D 1O4E 1O4F 1O4G 1O4A 2BDJ 1O4C 1O4L 4K11 2BDF 1O4O 1O4H 1O4I 1O4J 1O4K 1O4M 1O4N 1FMK
DrugBank ID DB06616 DB01254 DB08901 DB09079
BioGrid ID 112592
PharmGKB ID PA36111
KEGG ID hsa:6714
STRING ID 9606.ENSP00000350941
IntAct ID P12931
DMDM 125711
Reactome R-HSA-418886 R-HSA-171007 R-HSA-5663220 R-HSA-389513 R-HSA-1295596 R-HSA-372708 R-HSA-191647 R-HSA-389356 R-HSA-418885 R-HSA-437239 R-HSA-418592 R-HSA-430116 R-HSA-1433559 R-HSA-186763 R-HSA-180292 R- R-HSA-4420097 R-HSA-391160 R-HSA-5673000 R-HSA-2029481
SignaLink P12931
BioCyc MetaCyc:HS02256-MONOMER
Entrez Gene (Gene ID) 6714
BindingDB P12931

  Model Performance Metrics

Fingerprint type Sensitivity SEN_std Specificity SPE_std Accuracy ACC_std F1-score F1-score_std AUC AUC_std MCC MCC_std Download model
FP2 fingerprints 0.800 0.000 0.860 0.000 0.830 0.000 0.830 0.000 0.900 0.000 0.665 0.005 Download
Estate fingerprints 0.766 0.005 0.774 0.000 0.770 0.000 0.770 0.000 0.850 0.000 0.541 0.003 Download
MACCS fingerprints 0.801 0.003 0.719 0.000 0.760 0.000 0.770 0.000 0.840 0.000 0.530 0.000 Download
Daylight fingerprints 0.830 0.000 0.770 0.000 0.800 0.000 0.810 0.000 0.840 0.000 0.600 0.000 Download
ECFP2 fingerprints 0.850 0.000 0.870 0.000 0.860 0.000 0.860 0.000 0.935 0.005 0.728 0.004 Download
ECFP4 fingerprints 0.826 0.005 0.952 0.000 0.889 0.003 0.880 0.000 0.950 0.000 0.779 0.003 Download
ECFP6 fingerprints 0.800 0.000 0.964 0.004 0.882 0.004 0.871 0.003 0.950 0.000 0.780 0.000 Download

  Download datasets

Positive dataset Negative dataset

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