Tyr418

Site Information
RLIEDNEyTARQGAK SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 448234

In vivo Characterization
Methods used to characterize site in vivo:	immunoassay ( 3 , 11 , 16 , 17 ) , immunoprecipitation ( 36 ) , mass spectrometry ( 32 , 33 , 35 ) , mutation of modification site ( 28 , 34 ) , phospho-antibody ( 2 , 3 , 4 , 5 , 6 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 26 , 27 , 28 , 29 , 30 , 31 , 34 , 36 ) , western blotting ( 2 , 4 , 5 , 6 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 26 , 27 , 28 , 29 , 30 , 31 , 34 , 36 )
Disease tissue studied:	breast cancer ( 16 ) , breast ductal carcinoma ( 16 ) , colorectal cancer ( 30 ) , colorectal carcinoma ( 30 ) , leukemia ( 22 ) , lung cancer ( 31 ) , testicular cancer ( 36 ) , diabetes mellitus ( 27 ) , type 2 diabetes ( 27 )
Relevant cell line - cell type - tissue:	'brain, cerebral cortex' ( 15 , 17 ) , 'brain, hippocampus' ( 12 ) , 'muscle, skeletal' ( 5 ) , 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] ( 34 ) , 3T3 (fibroblast) [Src (human)] ( 31 ) , B lymphocyte ( 13 ) , BaF3 ('B lymphocyte, precursor') [EGFR (human)] ( 31 ) , BaF3 ('B lymphocyte, precursor') ( 33 , 35 ) , BALB/3T3 A31-1-1 ( 9 ) , bone marrow ( 14 ) , epithelial-prostate ( 3 ) , H630 ( 30 ) , HaCaT (keratinocyte) ( 11 ) , heart ( 4 ) , HEK293T (epithelial) ( 34 ) , HT-22 (neuron) ( 21 ) , HT-29 (intestinal) ( 30 ) , HUVEC (endothelial) ( 20 ) , JIMT-1 (breast cell) ( 16 ) , kidney ( 27 ) , lymph node ( 13 ) , M1 (myeloid) ( 22 ) , macrophage-peritoneum ( 18 ) , mammary gland ( 16 ) , MCF-7 (breast cell) ( 16 ) , MCT cells (epithelial) ( 27 ) , MDA-MB-231 (breast cell) ( 16 ) , MEF (fibroblast) ( 12 , 26 , 28 ) , microvessel endothelial ( 4 ) , mononuclear ( 30 ) , muscle ( 23 ) , myocyte-heart ( 29 ) , neuron-'brain, hippocampus' ( 2 ) , neuron:synaptosome ( 12 ) , neutrophil ( 14 ) , P19 (testicular) ( 36 ) , pericytes ( 19 ) , R22 ('muscle, smooth') ( 28 ) , RAW 264.7 (macrophage) ( 18 , 24 ) , skin ( 11 ) , ST2 (stromal) ( 6 ) , SW620 (intestinal) ( 30 ) , Swiss 3T3 (fibroblast) ( 34 ) , SYF (fibroblast) ( 28 , 30 ) , T47D (breast cell) ( 16 ) , thymocyte ( 13 ) , vascular smooth muscle cell ('muscle, smooth') ( 28 ) , WiDr (epithelial) ( 30 ) , ZR-75-1 (breast cell) ( 16 )

Upstream Regulation
Regulatory protein:	ADAMTSL3 (human) ( 2 ) , AGTRAP (human) ( 22 ) , beclin 1 (human) ( 18 ) , BVR (human) ( 12 ) , CASK (human) ( 4 ) , caveolin-1 (mouse) ( 29 ) , CFD (human) ( 4 ) , FAK (mouse) ( 19 ) , MTSS1 (human) ( 6 ) , PAG (rat) ( 26 ) , PGK1 (human) ( 18 ) , PIK3C3 (human) ( 18 ) , PLA2G5 (human) ( 18 ) , PSTPIP2 (human) ( 14 ) , PTPRD (human) ( 6 ) , THY1 (human) ( 11 )
Putative upstream phosphatases:	CD45 (human) ( 14 )
Phosphatases, in vitro:	PTPRA (human) ( 36 )
Treatments:	angiotensin_2 ( 22 ) , antibody ( 11 , 13 , 23 ) , atorvastatin ( 20 ) , CCL4 ( 7 ) , cholesterol ( 26 ) , dasatinib ( 16 , 17 , 30 ) , eCF506 ( 16 ) , ethanol ( 17 ) , exercise training ( 5 ) , high_glucose ( 4 ) , hypoxia ( 7 ) , ischemia/reperfusion ( 29 ) , isoflurane ( 29 ) , long-term_potentiation ( 2 ) , MCAO/R ( 1 ) , naloxone ( 29 ) , palmitate ( 4 ) , phorbol_ester ( 12 , 20 ) , PP1 ( 1 , 7 , 13 ) , PP2 ( 13 , 29 ) , pyrintegrin ( 12 ) , restraint stress ( 15 ) , saracatinib ( 16 ) , SB 366791 ( 21 ) , sevoflurane ( 21 ) , SKI-606 ( 16 ) , SNAP ( 24 ) , SU6656 ( 31 ) , TGF-beta ( 28 ) , thapsigargin ( 34 )

Downstream Regulation
Effects of modification on Src:	activity, induced ( 16 ) , enzymatic activity, induced ( 6 , 13 ) , phosphorylation ( 20 , 21 ) , protein degradation ( 13 ) , receptor internalization, induced ( 22 ) , ubiquitination ( 13 )
Effects of modification on biological processes:	autophagy, induced ( 1 ) , autophagy, inhibited ( 5 ) , cell adhesion, induced ( 11 , 12 ) , cell differentiation, induced ( 6 ) , cell growth, induced ( 16 ) , endocytosis, induced ( 22 ) , neural plasticity ( 2 , 12 , 21 ) , signaling pathway regulation ( 21 ) , transcription, induced ( 24 )

References
1	Tang T, et al. (2023) Src inhibition rescues FUNDC1-mediated neuronal mitophagy in ischaemic stroke. Stroke Vasc Neurol 37793899 Curated Info
2	Cramer TML, et al. (2023) Adamtsl3 mediates DCC signaling to selectively promote GABAergic synapse function. Cell Rep 42, 112947 37572323 Curated Info
3	Vlajic K, et al. (2023) Appearance of tuft cells during prostate cancer progression. Oncogene 42, 2374-2385 37386128 Curated Info
4	Zhang X, et al. (2023) Adipsin alleviates cardiac microvascular injury in diabetic cardiomyopathy through Csk-dependent signaling mechanism. BMC Med 21, 197 37237266 Curated Info
5	Yamauchi N, et al. (2023) High-intensity interval training in the form of isometric contraction improves fatigue resistance in dystrophin-deficient muscle. J Physiol 37184335 Curated Info
6	Chen M, et al. (2023) Metastasis suppressor 1 interacts with protein tyrosine phosphatase receptor-δ to regulate adipogenesis. FASEB J 37, e22857 36906292 Curated Info
7	Cheng Z, et al. (2023) Sarcoma protein kinase inhibition alleviates liver fibrosis by promoting hepatic stellate cells ferroptosis. Open Life Sci 18, 20220781 38077794 Curated Info
8	Ding H, et al. (2022) Curaxin CBL0137 inhibits endothelial inflammation and atherogenesis via suppression of the Src-YAP signalling axis. Br J Pharmacol 36495259 Curated Info
9	Adan H, et al. (2022) Activated Src requires Cadherin-11, Rac, and gp130 for Stat3 activation and survival of mouse Balb/c3T3 fibroblasts. Cancer Gene Ther 29, 1502-1513 35411090 Curated Info
10	Mizuta K, et al. (2022) Plectin promotes tumor formation by B16 mouse melanoma cells via regulation of Rous sarcoma oncogene activity. BMC Cancer 22, 936 36038818 Curated Info
11	Sedov E, et al. (2022) THY1-mediated mechanisms converge to drive YAP activation in skin homeostasis and repair. Nat Cell Biol 24, 1049-1063 35798842 Curated Info
12	Vasavda C, et al. (2022) Biliverdin reductase bridges focal adhesion kinase to Src to modulate synaptic signaling. Sci Signal 15, eabh3066 35536885 Curated Info
13	Lu W, Skrzypczynska KM, Weiss A (2021) Acute Csk inhibition hinders B cell activation by constraining the PI3 kinase pathway. Proc Natl Acad Sci U S A 118 34675079 Curated Info
14	Kralova J, et al. (2021) The receptor-type protein tyrosine phosphatase CD45 promotes onset and severity of IL-1β-mediated autoinflammatory osteomyelitis. J Biol Chem 297, 101131 34461100 Curated Info
15	Shi X, et al. (2021) Disrupting phosphorylation of Tyr-1070 at GluN2B selectively produces resilience to depression-like behaviors. Cell Rep 36, 109612 34433031 Curated Info
16	Temps C, et al. (2021) A novel mode of inhibiting SRC improves drug efficacy and tolerability. Cancer Res 81 34417202 Curated Info
17	Wang D, Howell BW, Olson EC (2021) Maternal Ethanol Exposure Acutely Elevates Src Family Kinase Activity in the Fetal Cortex. Mol Neurobiol 58 34272687 Curated Info
18	Fujioka D, et al. (2021) Group V Secretory Phospholipase A Regulates Endocytosis of Acetylated LDL by Transcriptional Activation of PGK1 in RAW264.7 Macrophage Cell Line. J Atheroscler Thromb 29 33775979 Curated Info
19	Lees DM, et al. (2021) Phosphorylation of pericyte FAK-Y861 affects tumour cell apoptosis and tumour blood vessel regression. Angiogenesis 24 33730293 Curated Info
20	Baganha F, et al. (2021) Atorvastatin pleiotropically decreases intraplaque angiogenesis and intraplaque haemorrhage by inhibiting ANGPT2 release and VE-Cadherin internalization. Angiogenesis 24 33550461 Curated Info
21	Liu Y, et al. (2021) TRPV1 Antagonist Prevents Neonatal Sevoflurane-Induced Synaptic Abnormality and Cognitive Impairment in Mice Through Regulating the Src/Cofilin Signaling Pathway. Front Cell Dev Biol 9, 684516 34307363 Curated Info
22	Polidoro JZ, Rebouças NA, Girardi ACC (2021) The Angiotensin II Type 1 Receptor-Associated Protein Attenuates Angiotensin II-Mediated Inhibition of the Renal Outer Medullary Potassium Channel in Collecting Duct Cells. Front Physiol 12, 642409 34054566 Curated Info
23	Ghazanfari N, et al. (2015) Forced expression of muscle specific kinase slows postsynaptic acetylcholine receptor loss in a mouse model of MuSK myasthenia gravis. Physiol Rep 3 26702075 Curated Info
24	Hsieh MY, et al. (2014) The Inducible Nitric-oxide Synthase (iNOS)/Src Axis Mediates Toll-like Receptor 3 Tyrosine 759 Phosphorylation and Enhances Its Signal Transduction, Leading to Interferon-β Synthesis in Macrophages. J Biol Chem 289, 9208-20 24526685 Curated Info
25	Pan Q, et al. (2011) Cdk5 targets active Src for ubiquitin-dependent degradation by phosphorylating Src(S75). Cell Mol Life Sci 68, 3425-36 21442427 Curated Info
26	Oneyama C, et al. (2008) The lipid raft-anchored adaptor protein Cbp controls the oncogenic potential of c-Src. Mol Cell 30, 426-36 18498747 Curated Info
27	Sataranatarajan K, Lee MJ, Mariappan MM, Feliers D (2008) PKCdelta regulates the stimulation of vascular endothelial factor mRNA translation by angiotensin II through hnRNP K. Cell Signal 20, 969-77 18295448 Curated Info
28	Samarakoon R, Higgins SP, Higgins CE, Higgins PJ (2008) TGF-beta1-induced plasminogen activator inhibitor-1 expression in vascular smooth muscle cells requires pp60(c-src)/EGFR(Y845) and Rho/ROCK signaling. J Mol Cell Cardiol 44, 527-38 18255094 Curated Info
29	Patel HH, et al. (2007) Mechanisms of cardiac protection from ischemia/reperfusion injury: a role for caveolae and caveolin-1. FASEB J 21, 1565-74 17272740 Curated Info
30	Serrels A, et al. (2006) Identification of potential biomarkers for measuring inhibition of Src kinase activity in colon cancer cells following treatment with dasatinib. Mol Cancer Ther 5, 3014-22 17148760 Curated Info
31	Sharma SV, et al. (2006) A common signaling cascade may underlie "addiction" to the Src, BCR-ABL, and EGF receptor oncogenes. Cancer Cell 10, 425-35 17097564 Curated Info
32	Zhou J (2006) CST Curation Set: 1969; Year: 2006; Biosample1/Treatment/Isotope: tissue, brain/untreated/L, Biosample2/Treatment/Isotope: tissue, brain/untreated/H; Disease: -; SILAC: Y; Specificities of Antibodies Used to Purify Peptides prior to LCMS: YXp[ST] Curated Info
33	Goss V (2006) CST Curation Set: 1403; Year: 2006; Biosample/Treatment: cell line, BaF3/-; Disease: chronic myelogenous leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
34	Hong M, et al. (2005) Transcriptional regulation of the Grp78 promoter by endoplasmic reticulum stress: role of TFII-I and its tyrosine phosphorylation. J Biol Chem 280, 16821-8 15664986 Curated Info
35	Gu T (2005) CST Curation Set: 700; Year: 2005; Biosample/Treatment: cell line, BaF3/-; Disease: chronic myelogenous leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
36	den Hertog J, et al. (1993) Receptor protein tyrosine phosphatase alpha activates pp60c-src and is involved in neuronal differentiation. EMBO J 12, 3789-98 7691597 Curated Info