CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-005766
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Tyrosine-protein phosphatase non-receptor type 6 
Protein Synonyms/Alias
 Hematopoietic cell protein-tyrosine phosphatase; Protein-tyrosine phosphatase 1C; PTP-1C; Protein-tyrosine phosphatase SHP-1; SH-PTP1 
Gene Name
 PTPN6 
Gene Synonyms/Alias
 HCP; PTP1C 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
19LDAETLLKGRGVHGSubiquitination[1, 2]
34FLARPSRKNQGDFSLubiquitination[2]
232NRVLELNKKQESEDTubiquitination[2]
233RVLELNKKQESEDTAubiquitination[2]
253EEFESLQKQEVKNLHubiquitination[2]
277NKGKNRYKNILPFDHacetylation[3]
277NKGKNRYKNILPFDHubiquitination[2, 4, 5]
360EVEKGRNKCVPYWPEubiquitination[2]
391EHDTTEYKLRTLQVSubiquitination[1, 2, 6]
522FIETTKKKLEVLQSQubiquitination[2]
Reference
 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] 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]
 [3] 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]
 [4] 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]
 [5] 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]
 [6] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724] 
Functional Description
 Modulates signaling by tyrosine phosphorylated cell surface receptors such as KIT and the EGF receptor/EGFR. The SH2 regions may interact with other cellular components to modulate its own phosphatase activity against interacting substrates. Together with MTUS1, induces UBE2V2 expression upon angiotensin II stimulation. Plays a key role in hematopoiesis. 
Sequence Annotation
 DOMAIN 4 100 SH2 1.
 DOMAIN 110 213 SH2 2.
 DOMAIN 244 515 Tyrosine-protein phosphatase.
 REGION 453 459 Substrate binding (By similarity).
 ACT_SITE 453 453 Phosphocysteine intermediate.
 BINDING 419 419 Substrate (By similarity).
 BINDING 500 500 Substrate (By similarity).
 MOD_RES 64 64 Phosphotyrosine.
 MOD_RES 377 377 Phosphotyrosine (By similarity).
 MOD_RES 536 536 Phosphotyrosine (By similarity).
 MOD_RES 564 564 Phosphotyrosine; by LYN.  
Keyword
 3D-structure; Alternative splicing; Complete proteome; Cytoplasm; Hydrolase; Nucleus; Phosphoprotein; Protein phosphatase; Reference proteome; Repeat; SH2 domain. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 595 AA 
Protein Sequence
MVRWFHRDLS GLDAETLLKG RGVHGSFLAR PSRKNQGDFS LSVRVGDQVT HIRIQNSGDF 60
YDLYGGEKFA TLTELVEYYT QQQGVLQDRD GTIIHLKYPL NCSDPTSERW YHGHMSGGQA 120
ETLLQAKGEP WTFLVRESLS QPGDFVLSVL SDQPKAGPGS PLRVTHIKVM CEGGRYTVGG 180
LETFDSLTDL VEHFKKTGIE EASGAFVYLR QPYYATRVNA ADIENRVLEL NKKQESEDTA 240
KAGFWEEFES LQKQEVKNLH QRLEGQRPEN KGKNRYKNIL PFDHSRVILQ GRDSNIPGSD 300
YINANYIKNQ LLGPDENAKT YIASQGCLEA TVNDFWQMAW QENSRVIVMT TREVEKGRNK 360
CVPYWPEVGM QRAYGPYSVT NCGEHDTTEY KLRTLQVSPL DNGDLIREIW HYQYLSWPDH 420
GVPSEPGGVL SFLDQINQRQ ESLPHAGPII VHCSAGIGRT GTIIVIDMLM ENISTKGLDC 480
DIDIQKTIQM VRAQRSGMVQ TEAQYKFIYV AIAQFIETTK KKLEVLQSQK GQESEYGNIT 540
YPPAMKNAHA KASRTSSKHK EDVYENLHTK NKREEKVKKQ RSADKEKSKG SLKRK 595 
Gene Ontology
 GO:0042105; C:alpha-beta T cell receptor complex; IEA:Compara.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0016020; C:membrane; TAS:ProtInc.
 GO:0005634; C:nucleus; IDA:BHF-UCL.
 GO:0005001; F:transmembrane receptor protein tyrosine phosphatase activity; IDA:UniProtKB.
 GO:0006915; P:apoptotic process; TAS:ProtInc.
 GO:0050853; P:B cell receptor signaling pathway; IEA:Compara.
 GO:0007596; P:blood coagulation; TAS:Reactome.
 GO:0030154; P:cell differentiation; IDA:UniProtKB.
 GO:0008283; P:cell proliferation; IDA:UniProtKB.
 GO:0007186; P:G-protein coupled receptor signaling pathway; TAS:ProtInc.
 GO:0060333; P:interferon-gamma-mediated signaling pathway; TAS:Reactome.
 GO:0060397; P:JAK-STAT cascade involved in growth hormone signaling pathway; TAS:Reactome.
 GO:0050900; P:leukocyte migration; TAS:Reactome.
 GO:0042267; P:natural killer cell mediated cytotoxicity; IEA:Compara.
 GO:0008285; P:negative regulation of cell proliferation; NAS:UniProtKB.
 GO:0002924; P:negative regulation of humoral immune response mediated by circulating immunoglobulin; IEA:Compara.
 GO:0043407; P:negative regulation of MAP kinase activity; IEA:Compara.
 GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; IMP:BHF-UCL.
 GO:0042130; P:negative regulation of T cell proliferation; IEA:Compara.
 GO:0050860; P:negative regulation of T cell receptor signaling pathway; IEA:Compara.
 GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
 GO:0008284; P:positive regulation of cell proliferation; IMP:BHF-UCL.
 GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase cascade; IMP:BHF-UCL.
 GO:0045577; P:regulation of B cell differentiation; IEA:Compara.
 GO:0070372; P:regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
 GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; IMP:BHF-UCL.
 GO:0060334; P:regulation of interferon-gamma-mediated signaling pathway; TAS:Reactome.
 GO:0060338; P:regulation of type I interferon-mediated signaling pathway; TAS:Reactome.
 GO:0031295; P:T cell costimulation; TAS:Reactome.
 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.