CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-011358
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Tyrosine-protein phosphatase non-receptor type 11 
Protein Synonyms/Alias
 Protein-tyrosine phosphatase 1D; PTP-1D; Protein-tyrosine phosphatase 2C; PTP-2C; SH-PTP2; SHP-2; Shp2; SH-PTP3 
Gene Name
 PTPN11 
Gene Synonyms/Alias
 PTP2C; SHPTP2 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
198TDLVEHYKKNPMVETacetylation[1]
198TDLVEHYKKNPMVETubiquitination[2, 3]
280NKNKNRYKNILPFDHacetylation[1]
486LIDIIREKGVDCDIDacetylation[4]
594VGLMQQQKSFR****ubiquitination[5, 6]
Reference
 [1] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [4] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [5] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [6] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 
Functional Description
 Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. Dephosphorylates ROCK2 at Tyr-722 resulting in stimulatation of its RhoA binding activity. 
Sequence Annotation
 DOMAIN 6 102 SH2 1.
 DOMAIN 112 216 SH2 2.
 DOMAIN 247 521 Tyrosine-protein phosphatase.
 REGION 463 469 Substrate binding (By similarity).
 ACT_SITE 463 463 Phosphocysteine intermediate.
 BINDING 429 429 Substrate (By similarity).
 BINDING 510 510 Substrate (By similarity).
 MOD_RES 2 2 N-acetylthreonine.
 MOD_RES 62 62 Phosphotyrosine.
 MOD_RES 63 63 Phosphotyrosine.
 MOD_RES 66 66 Phosphotyrosine (By similarity).
 MOD_RES 280 280 N6-acetyllysine.
 MOD_RES 546 546 Phosphotyrosine; by PDGFR.
 MOD_RES 562 562 Phosphoserine.
 MOD_RES 584 584 Phosphotyrosine; by PDGFR.
 MOD_RES 595 595 Phosphoserine.  
Keyword
 3D-structure; Acetylation; Alternative splicing; Complete proteome; Cytoplasm; Deafness; Disease mutation; Hydrolase; Phosphoprotein; Protein phosphatase; Reference proteome; Repeat; SH2 domain. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 597 AA 
Protein Sequence
MTSRRWFHPN ITGVEAENLL LTRGVDGSFL ARPSKSNPGD FTLSVRRNGA VTHIKIQNTG 60
DYYDLYGGEK FATLAELVQY YMEHHGQLKE KNGDVIELKY PLNCADPTSE RWFHGHLSGK 120
EAEKLLTEKG KHGSFLVRES QSHPGDFVLS VRTGDDKGES NDGKSKVTHV MIRCQELKYD 180
VGGGERFDSL TDLVEHYKKN PMVETLGTVL QLKQPLNTTR INAAEIESRV RELSKLAETT 240
DKVKQGFWEE FETLQQQECK LLYSRKEGQR QENKNKNRYK NILPFDHTRV VLHDGDPNEP 300
VSDYINANII MPEFETKCNN SKPKKSYIAT QGCLQNTVND FWRMVFQENS RVIVMTTKEV 360
ERGKSKCVKY WPDEYALKEY GVMRVRNVKE SAAHDYTLRE LKLSKVGQAL LQGNTERTVW 420
QYHFRTWPDH GVPSDPGGVL DFLEEVHHKQ ESIMDAGPVV VHCSAGIGRT GTFIVIDILI 480
DIIREKGVDC DIDVPKTIQM VRSQRSGMVQ TEAQYRFIYM AVQHYIETLQ RRIEEEQKSK 540
RKGHEYTNIK YSLADQTSGD QSPLPPCTPT PPCAEMREDS ARVYENVGLM QQQKSFR 597 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005739; C:mitochondrion; IEA:Compara.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0043234; C:protein complex; IEA:Compara.
 GO:0004726; F:non-membrane spanning protein tyrosine phosphatase activity; IMP:UniProtKB.
 GO:0005070; F:SH3/SH2 adaptor activity; IDA:BHF-UCL.
 GO:0000187; P:activation of MAPK activity; IEA:Compara.
 GO:0036302; P:atrioventricular canal development; IMP:BHF-UCL.
 GO:0007411; P:axon guidance; TAS:Reactome.
 GO:0007596; P:blood coagulation; TAS:Reactome.
 GO:0007420; P:brain development; IMP:BHF-UCL.
 GO:0000077; P:DNA damage checkpoint; IEA:Compara.
 GO:0048013; P:ephrin receptor signaling pathway; IDA:UniProtKB.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0060325; P:face morphogenesis; IMP:BHF-UCL.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0048806; P:genitalia development; IMP:BHF-UCL.
 GO:0042593; P:glucose homeostasis; IEA:Compara.
 GO:0042445; P:hormone metabolic process; IEA:Compara.
 GO:0009755; P:hormone-mediated signaling pathway; IEA:Compara.
 GO:0048839; P:inner ear development; IMP:BHF-UCL.
 GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
 GO:0060333; P:interferon-gamma-mediated signaling pathway; TAS:Reactome.
 GO:0050900; P:leukocyte migration; TAS:Reactome.
 GO:0048609; P:multicellular organismal reproductive process; IEA:Compara.
 GO:0051463; P:negative regulation of cortisol secretion; IEA:Compara.
 GO:0060125; P:negative regulation of growth hormone secretion; IEA:Compara.
 GO:0046676; P:negative regulation of insulin secretion; IEA:Compara.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0035265; P:organ growth; IEA:Compara.
 GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
 GO:2001275; P:positive regulation of glucose import in response to insulin stimulus; IDA:BHF-UCL.
 GO:0046887; P:positive regulation of hormone secretion; IEA:Compara.
 GO:0033628; P:regulation of cell adhesion mediated by integrin; IMP:UniProtKB.
 GO:0060334; P:regulation of interferon-gamma-mediated signaling pathway; TAS:Reactome.
 GO:0040014; P:regulation of multicellular organism growth; IEA:Compara.
 GO:0046825; P:regulation of protein export from nucleus; IEA:Compara.
 GO:0060338; P:regulation of type I interferon-mediated signaling pathway; TAS:Reactome.
 GO:0031295; P:T cell costimulation; TAS:Reactome.
 GO:0006641; P:triglyceride metabolic process; IEA:Compara.
 GO:0060337; P:type I interferon-mediated signaling pathway; TAS:Reactome. 
Interpro
 IPR000980; SH2.
 IPR000387; Tyr/Dual-sp_Pase.
 IPR016130; Tyr_Pase_AS.
 IPR012152; Tyr_Pase_non-rcpt_typ-6/11.
 IPR000242; Tyr_Pase_rcpt/non-rcpt. 
Pfam
 PF00017; SH2
 PF00102; Y_phosphatase 
SMART
 SM00194; PTPc
 SM00252; SH2 
PROSITE
 PS50001; SH2
 PS00383; TYR_PHOSPHATASE_1
 PS50056; TYR_PHOSPHATASE_2
 PS50055; TYR_PHOSPHATASE_PTP 
PRINTS
 PR00700; PRTYPHPHTASE.
 PR00401; SH2DOMAIN.