Tyr564

Site Information
sKHKEEVyENVHsKS SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 448912

In vivo Characterization
Methods used to characterize site in vivo:	[32P] bio-synthetic labeling ( 36 ) , flow cytometry ( 2 ) , immunoassay ( 2 ) , immunoprecipitation ( 19 ) , mass spectrometry ( 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 20 , 21 , 22 , 23 , 24 , 25 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ) , mutation of modification site ( 19 , 36 ) , phospho-antibody ( 1 , 3 , 4 , 6 , 19 ) , phosphoamino acid analysis ( 36 ) , phosphopeptide mapping ( 36 ) , western blotting ( 1 , 3 , 4 , 6 , 19 )
Disease tissue studied:	leukemia ( 21 , 22 , 23 , 24 , 33 ) , chronic myelogenous leukemia ( 33 ) , lung cancer ( 27 , 28 , 29 , 30 , 31 , 32 ) , non-small cell lung cancer ( 27 , 28 , 29 , 30 , 31 , 32 )
Relevant cell line - cell type - tissue:	B lymphocyte ( 4 , 11 , 12 ) , BaF3 ('B lymphocyte, precursor') ( 20 , 33 ) , CD4+ (T lymphocyte) ( 3 ) , liver ( 34 , 35 ) , LSTRA (T lymphocyte) ( 36 ) , lung ( 27 , 28 , 29 ) , lymph node ( 4 ) , lymphocyte ( 2 ) , lymphocyte-spleen ( 6 ) , mast-bone marrow [LYN (mouse), homozygous knockout] ( 19 ) , mast-bone marrow [PLCB3 (mouse), homozygous knockout] ( 19 ) , RAW 264.7 (macrophage) ( 7 , 21 , 22 , 23 , 24 ) , T lymphocyte-thymus ( 36 ) , thymocyte ( 1 )

Upstream Regulation
Regulatory protein:	HLAA (human) ( 2 ) , THEMIS (human) ( 3 )
Putative in vivo kinases:	LYN (mouse) ( 19 )
Putative upstream phosphatases:	SHP-1 (human) ( 1 )
Treatments:	antibody ( 2 , 6 , 36 ) , H2O2 ( 1 ) , latrunculin_A ( 6 ) , NAC ( 1 ) , PP1 ( 4 ) , vanadate ( 1 )

Downstream Regulation
Effects of modification on SHP-1:	enzymatic activity, induced ( 19 ) , enzymatic activity, inhibited ( 1 )
Effects of modification on biological processes:	cell growth, altered ( 19 )

Disease / Diagnostics Relevance
Relevant diseases:	chronic myelogenous leukemia ( 19 )

References
1	Choi S, et al. (2023) THEMIS increases TCR signaling in CD4CD8 thymocytes by inhibiting the activity of the tyrosine phosphatase SHP1. Sci Signal 16, eade1274 37159521 Curated Info
2	Schmied L, et al. (2023) SHP-1 localization to the activating immune synapse promotes NK cell tolerance in MHC class I deficiency. Sci Signal 16, eabq0752 37040441 Curated Info
3	Yang C, et al. (2022) THEMIS enhances the magnitude of normal and neuroinflammatory type 1 immune responses by promoting TCR-independent signals. Sci Signal 15, eabl5343 35857631 Curated Info
4	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
5	Jondle CN, et al. (2020) B Cell-Intrinsic Expression of Interferon Regulatory Factor 1 Supports Chronic Murine Gammaherpesvirus 68 Infection. J Virol 32321819 Curated Info
6	Gasparrini F, et al. (2016) Nanoscale organization and dynamics of the siglec CD22 cooperate with the cytoskeleton in restraining BCR signalling. EMBO J 35, 258-80 26671981 Curated Info
7	Pinto SM, et al. (2015) Quantitative phosphoproteomic analysis of IL-33-mediated signaling. Proteomics 15, 532-44 25367039 Curated Info
8	Ren H (2011) CST Curation Set: 12902; Year: 2011; Biosample/Treatment: /untreated; Disease: -; 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
9	Ren H (2011) CST Curation Set: 12904; Year: 2011; Biosample/Treatment: /untreated; Disease: -; 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
10	Ren H (2011) CST Curation Set: 12906; Year: 2011; Biosample/Treatment: /untreated; Disease: -; 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
11	Ren H (2011) CST Curation Set: 12893; Year: 2011; Biosample/Treatment: primary cells, B lymphocyte/untreated; Disease: -; 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
12	Ren H (2011) CST Curation Set: 12894; Year: 2011; Biosample/Treatment: primary cells, B lymphocyte/untreated; Disease: -; 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
13	Ren H (2011) CST Curation Set: 12895; Year: 2011; Biosample/Treatment: /untreated; Disease: -; 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
14	Ren H (2011) CST Curation Set: 12896; Year: 2011; Biosample/Treatment: /untreated; Disease: -; 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
15	Ren H (2011) CST Curation Set: 12897; Year: 2011; Biosample/Treatment: /untreated; Disease: -; 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
16	Ren H (2011) CST Curation Set: 12898; Year: 2011; Biosample/Treatment: /untreated; Disease: -; 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
17	Ren H (2011) CST Curation Set: 12900; Year: 2011; Biosample/Treatment: /untreated; Disease: -; 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
18	Ren H (2011) CST Curation Set: 12901; Year: 2011; Biosample/Treatment: /untreated; Disease: -; 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
19	Xiao W, et al. (2010) Lyn- and PLC-beta3-dependent regulation of SHP-1 phosphorylation controls Stat5 activity and myelomonocytic leukemia-like disease. Blood 116, 6003-13 20858858 Curated Info
20	Moritz A (2009) CST Curation Set: 7223; Year: 2009; Biosample/Treatment: cell line, BaF3/serum starved; 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
21	Possemato A (2009) CST Curation Set: 7168; Year: 2009; Biosample/Treatment: cell line, RAW 264.7/LPS; Disease: 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
22	Possemato A (2009) CST Curation Set: 7169; Year: 2009; Biosample/Treatment: cell line, RAW 264.7/MG132; Disease: 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
23	Possemato A (2009) CST Curation Set: 7167; Year: 2009; Biosample/Treatment: cell line, RAW 264.7/LPS; Disease: 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
24	Possemato A (2009) CST Curation Set: 7166; Year: 2009; Biosample/Treatment: cell line, RAW 264.7/control; Disease: 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
25	Rikova K (2008) CST Curation Set: 4775; Year: 2008; Biosample/Treatment: cell line, Dana Farber-KTL(LN)-4/untreated; Disease: -; 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
26	Rikova K (2008) CST Curation Set: 4437; Year: 2008; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; 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
27	Rikova K (2008) CST Curation Set: 4438; Year: 2008; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; 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
28	Rikova K (2008) CST Curation Set: 4439; Year: 2008; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; 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
29	Rikova K (2008) CST Curation Set: 4440; Year: 2008; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; 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
30	Rikova K (2008) CST Curation Set: 4251; Year: 2008; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; 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
31	Rikova K (2008) CST Curation Set: 4252; Year: 2008; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; 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
32	Rikova K (2008) CST Curation Set: 4254; Year: 2008; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; 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
33	Gu T (2007) CST Curation Set: 3402; Year: 2007; Biosample/Treatment: cell line, Baf3(MSCV-NEO)/IL3 withdrawal; 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	Guo A (2007) CST Curation Set: 2985; Year: 2007; Biosample/Treatment: tissue, liver/Insulin; Disease: -; 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
35	Guo A (2007) CST Curation Set: 2986; Year: 2007; Biosample/Treatment: tissue, liver/Insulin; Disease: -; 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	Lorenz U, et al. (1994) Lck-dependent tyrosyl phosphorylation of the phosphotyrosine phosphatase SH-PTP1 in murine T cells. Mol Cell Biol 14, 1824-34 8114715 Curated Info