Q06124

※ Protein Information

Tag	Content
UniProt Accession	PTN11_HUMAN; Q06124;
Entrez ID	5781
GenBank Protein ID	NM_001330437.1; NM_002834.4; NM_080601.2;
GenBank Nucleotide ID	NP_001317366.1; NP_002825.3; NP_542168.1;
Protein Name	Tyrosine-protein phosphatase non-receptor type 11 (EC 3.1.3.48) (Protein-tyrosine phosphatase 1D) (PTP-1D) (Protein-tyrosine phosphatase 2C) (PTP-2C) (SH-PTP2) (SHP-2) (Shp2) (SH-PTP3)
Gene Name	PTPN11; PTP2C; SHPTP2
Organism	Homo sapiens
NCBI Taxa ID	9606
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. Positively regulates MAPK signal transduction pathway (PubMed:28074573). Dephosphorylates GAB1, ARHGAP35 and EGFR (PubMed:28074573). Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulatation of its RhoA binding activity. Dephosphorylates CDC73 (PubMed:26742426). 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. Positively regulates MAPK signal transduction pathway (PubMed:28074573). Dephosphorylates GAB1, ARHGAP35 and EGFR (PubMed:28074573). Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulatation of its RhoA binding activity. Dephosphorylates CDC73 (PubMed:26742426).
Sequence (Fasta)	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 598 Fasta Sequence >Q06124\|PTPN11; PTP2C; SHPTP2\|Homo sapiens (Human) MTSRRWFHPNITGVEAENLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLYGGEKFATLAELVQYYMEHHGQLKEKNGDVIELKYPLNCADPTSERWFHGHLSGKEAEKLLTEKGKHGSFLVRESQSHPGDFVLSVRTGDDKGESNDGKSKVTHVMIRCQELKYDVGGGERFDSLTDLVEHYKKNPMVETLGTVLQLKQPLNTTRINAAEIESRVRELSKLAETTDKVKQGFWEEFETLQQQECKLLYSRKEGQRQENKNKNRYKNILPFDHTRVVLHDGDPNEPVSDYINANIIMPEFETKCNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEYALKEYGVMRVRNVKESAAHDYTLRELKLSKVGQALLQGNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQESIMDAGPVVVHCSAGIGRTGTFIVIDILIDIIREKGVDCDIDVPKTIQMVRSQRSGMVQTEAQYRFIYMAVQHYIETLQRRIEEEQKSKRKGHEYTNIKYSLADQTSGDQSPLPPCTPTPPCAEMREDSARVYENVGLMQQQKSFR

※ PTM-Disease Association

Num	PTM	Disease	Cell Type	Type	PTM Site	PMID
1	Threonine Phosphorylation	Heart failure	HEK293T cells	P	T73	25802336
1	[Reference]: Overexpression of Shp2 T73A/S189A Inhibits Isoproterenol-induced Cardiac Hypertrophy
2	Serine Phosphorylation	Heart failure		P	S189	25802336
2	[Reference]: We demonstrate that phosphorylation of these residues disrupts Shp2 interaction with tyrosine-phosphorylated ligands and inhibits its protein-tyrosine phosphatase activity.?
3	Tyrosine Phosphorylation	Lymphoma		U	Y584	17483340
3	[Reference]: The tyrosine phosphatase Shp2 interacts with NPM-ALK and regulates anaplastic lymphoma cell growth and migration.
4	Tyrosine Phosphorylation	Prostate cancer/carcinoma/adenocarcinoma	tumor tissue	U	Y584	22307624
4	[Reference]: Tyrosine Phosphorylation Is Increased in Clinical Castration-Resistant Prostate Cancer Samples

※ Disease Cross-ref Annotation

Database	Annotation
Cancer Gene Census	JMML, AML, MDS
CTD (Curated) (count: 16) (view all)	MESH:D000230 ; Adenocarcinoma MESH:D001254 ; Astrocytoma MESH:D002294 ; Carcinoma, Squamous Cell MESH:C535579 ; Cardiofaciocutaneous syndrome MESH:D056685 ; Costello Syndrome MESH:D004687 ; Enchondromatosis MESH:D005097 ; Exostoses, Multiple Hereditary MESH:D044542 ; LEOPARD Syndrome MESH:D007938 ; Leukemia MESH:D015470 ; Leukemia, Myeloid, Acute MESH:D054429 ; Leukemia, Myelomonocytic, Juvenile MESH:C562938 ; Metachondromatosis MESH:D009447 ; Neuroblastoma MESH:D065886 ; Neurodevelopmental Disorders MESH:D009634 ; Noonan Syndrome MESH:D015831 ; Osteochondroma
HGMD (count: 75) (view all)	CD041931; Noonan syndrome; Small deletions CD055729; Noonan syndrome; Small deletions CX060726; Noonan syndrome; Small indels CM032348; Noonan syndrome; Missense/nonsense CM021125; Noonan syndrome; Missense/nonsense CM052357; Atrioventricular septal defect; Missense/nonsense CM030492; Noonan syndrome; Missense/nonsense CM060441; Noonan syndrome; Missense/nonsense CM044250; Noonan syndrome; Missense/nonsense CM086895; Noonan syndrome; Missense/nonsense CM021126; Noonan syndrome; Missense/nonsense CM060445; Noonan syndrome; Missense/nonsense CM013415; Noonan syndrome; Missense/nonsense CM021127; Noonan syndrome; Missense/nonsense CM060446; Noonan syndrome; Missense/nonsense CM021128; Noonan syndrome; Missense/nonsense CM013416; Noonan syndrome; Missense/nonsense CM092721; Noonan syndrome ?; Missense/nonsense CM030493; Noonan syndrome; Missense/nonsense CM056378; Noonan syndrome; Missense/nonsense CM030494; Noonan syndrome; Missense/nonsense CM013417; Noonan syndrome; Missense/nonsense CM090463; Noonan syndrome; Missense/nonsense CM013418; Noonan syndrome; Missense/nonsense CM021129; Noonan syndrome; Missense/nonsense CM013419; Noonan syndrome; Missense/nonsense CM060442; Noonan syndrome; Missense/nonsense CM032349; Noonan syndrome; Missense/nonsense CM013420; Noonan syndrome; Missense/nonsense CM021130; Noonan syndrome; Missense/nonsense CM044251; Noonan syndrome; Missense/nonsense CM021132; Noonan syndrome; Missense/nonsense CM021131; Noonan syndrome; Missense/nonsense CM053388; Noonan syndrome; Missense/nonsense CM030495; Noonan syndrome; Missense/nonsense CM060443; Noonan syndrome; Missense/nonsense CM060444; Noonan syndrome; Missense/nonsense CM041069; ML / LEOPARD syndrome; Missense/nonsense CM021133; Noonan syndrome; Missense/nonsense CM013421; Noonan syndrome; Missense/nonsense CM086896; Noonan syndrome; Missense/nonsense CM024733; Noonan syndrome; Missense/nonsense CM021134; Noonan syndrome; Missense/nonsense CM060447; Noonan syndrome; Missense/nonsense CM073286; Noonan syndrome; Missense/nonsense CM013422; Noonan syndrome; Missense/nonsense CM044252; Noonan syndrome; Missense/nonsense CM021135; Noonan syndrome; Missense/nonsense CM021136; Noonan syndrome; Missense/nonsense CM070248; Noonan syndrome; Missense/nonsense CM043334; Noonan syndrome; Missense/nonsense CM043335; ML / LEOPARD syndrome; Missense/nonsense CM041070; ML / LEOPARD syndrome; Missense/nonsense CM021672; ML / LEOPARD syndrome; Missense/nonsense CM074987; ML / LEOPARD syndrome; Missense/nonsense CM067454; Noonan syndrome; Missense/nonsense CM053389; Noonan syndrome; Missense/nonsense CM044253; Noonan syndrome; Missense/nonsense CM041071; ML / LEOPARD syndrome; Missense/nonsense CM041072; ML / LEOPARD syndrome; Missense/nonsense CM021137; Noonan syndrome; Missense/nonsense CM022450; Noonan syndrome; Missense/nonsense CM055504; Noonan syndrome; Missense/nonsense CM044932; Noonan syndrome; Missense/nonsense CM060440; Noonan syndrome; Missense/nonsense CM032350; Noonan syndrome; Missense/nonsense CM086897; Noonan syndrome; Missense/nonsense CM013423; Noonan syndrome; Missense/nonsense CM031338; ML / LEOPARD syndrome; Missense/nonsense CM090464; Noonan syndrome; Missense/nonsense CM055503; Noonan syndrome; Missense/nonsense CM043070; ML / LEOPARD syndrome; Missense/nonsense CM052358; Noonan syndrome; Missense/nonsense CM090465; Noonan syndrome; Missense/nonsense CM032351; Noonan syndrome; Missense/nonsense
GWASdb (count: 16) (view all)	rs11066301; Hematological parameters; hematopoietic system disease\|coronary artery disease rs11066301; Other erythrocyte phenotypes; hematopoietic system disease rs11066301; Mean platelet volume; myocardial infarction\|hematopoietic system disease rs11066301; Red blood cell traits; hematopoietic system disease rs11066308; Response to alcohol consumption (flushing response); alcohol abuse\|alcohol dependence rs7976467; Blood pressure; hypertension rs7976467; Type 2 diabetes; type 2 diabetes mellitus rs11066320; Other erythrocyte phenotypes; hematopoietic system disease rs11066320; Soluble ICAM-1; fatty liver disease\|myocardial infarction rs11066320; Hypothyroidism; hypothyroidism rs11066320; Red blood cell traits; hematopoietic system disease rs11066320; Tetralogy of Fallot; tetralogy of Fallot rs12423190; Response to alcohol consumption (flushing response); alcohol abuse\|alcohol dependence rs7132778; Response to alcohol consumption (flushing response); alcohol abuse\|alcohol dependence rs7953150; Multiple complex diseases; Null rs7953150; Urinary metabolites; kidney disease

※ PTM Sites

PTM	Modification Sites
Phosphorylation (count: 35) (view all)	140 GSFLVRESQSHPGDF dbPAF 142 FLVRESQSHPGDFVL dbPAF 153 DFVLSVRTGDDKGES dbPAF 165 GESNDGKSKVTHVMI dbPAF 179 IRCQELKYDVGGGER dbPAF 189 GGGERFDSLTDLVEH dbPAF 263 QQECKLLYSRKEGQR dbPAF 264 QECKLLYSRKEGQRQ dbPAF 279 ENKNKNRYKNILPFD dbPAF 28 LTRGVDGSFLARPSK dbPAF 302 GDPNEPVSDYINANI dbPAF 304 PNEPVSDYINANIIM dbPAF 34 GSFLARPSKSNPGDF dbPAF 36 FLARPSKSNPGDFTL dbPAF 415 QALLQGNTERTVWQY dbPAF 515 MVQTEAQYRFIYMAV dbPAF 519 EAQYRFIYMAVQHYI dbPAF 546 SKRKGHEYTNIKYSL dbPAF 547 KRKGHEYTNIKYSLA dbPAF 551 HEYTNIKYSLADQTS dbPAF 552 EYTNIKYSLADQTSG dbPAF 557 KYSLADQTSGDQSPL dbPAF 558 YSLADQTSGDQSPLP dbPAF 562 DQTSGDQSPLPPCTP dbPAF 568 QSPLPPCTPTPPCAE dbPAF 570 PLPPCTPTPPCAEMR dbPAF 580 CAEMREDSARVYENV dbPAF 584 REDSARVYENVGLMQ dbPAF 59 THIKIQNTGDYYDLY dbPAF 595 GLMQQQKSFR***** dbPAF 62 KIQNTGDYYDLYGGE dbPAF 63 IQNTGDYYDLYGGEK dbPAF 66 TGDYYDLYGGEKFAT dbPAF 73 YGGEKFATLAELVQY dbPAF 80 TLAELVQYYMEHHGQ dbPAF
Acetylation (count: 13) (view all)	131 KLLTEKGKHGSFLVR PLMD 178 MIRCQELKYDVGGGE PLMD 198 TDLVEHYKKNPMVET PLMD 213 LGTVLQLKQPLNTTR PLMD 242 KLAETTDKVKQGFWE PLMD 280 NKNKNRYKNILPFDH PLMD 358 RVIVMTTKEVERGKS PLMD 486 LIDIIREKGVDCDID PLMD 496 DCDIDVPKTIQMVRS PLMD 55 NGAVTHIKIQNTGDY PLMD 594 VGLMQQQKSFR**** PLMD 91 HHGQLKEKNGDVIEL PLMD 99 NGDVIELKYPLNCAD PLMD
Ubiquitination (count: 5)	157 SVRTGDDKGESNDGK PLMD 198 TDLVEHYKKNPMVET PLMD 358 RVIVMTTKEVERGKS PLMD 540 IEEEQKSKRKGHEYT PLMD 594 VGLMQQQKSFR**** PLMD
Malonylation (count: 6)	131 KLLTEKGKHGSFLVR PLMD 280 NKNKNRYKNILPFDH PLMD 35 SFLARPSKSNPGDFT PLMD 486 LIDIIREKGVDCDID PLMD 496 DCDIDVPKTIQMVRS PLMD 91 HHGQLKEKNGDVIEL PLMD

※ Protein-Protein Interaction

Network

Interaction

Source

O00459	Q06124	IntAct
O14543	Q06124	HPRD
O15111	Q06124	HPRD
O60674	Q06124	HPRD
O95297	Q06124	IntAct
P00533	Q06124	MINT;HPRD
P04040	Q06124	MINT
P04626	Q06124	MINT;HPRD
P06213	Q06124	MINT
P08069	Q06124	HPRD
P08581	Q06124	MINT
P09619	Q06124	MINT
P10721	Q06124	HPRD
P12931	Q06124	MINT;HPRD
P17252	Q06124	HPRD
P19174	Q06124	MINT
P22681	Q06124	HPRD
P23458	Q06124	HPRD
P27361	Q06124	HPRD
P27986	Q06124	HPRD
P29317	Q06124	IntAct;HPRD
P31260	Q06124	MINT
P32239	Q06124	MINT
P32927	Q06124	HPRD
P33151	Q06124	HPRD
P35568	Q06124	MINT;HPRD
P35968	Q06124	HPRD
P40763	Q06124	HPRD
P42224	Q06124	HPRD
P42229	Q06124	HPRD
P42702	Q06124	HPRD
P46109	Q06124	HPRD
P49023	Q06124	MINT
P51692	Q06124	HPRD
P62993	Q06124	IntAct; MINT
P68104	Q06124	MINT
Q03135	Q06124	MINT;HPRD
Q05639	Q06124	MINT
Q06124	Q08345	MINT
Q06124	Q13480	IntAct; MINT
Q06124	Q14289	HPRD
Q06124	Q15051	IntAct
Q06124	Q15303	MINT
Q06124	Q8IZP0	MINT
Q06124	Q9H9S4	MINT
Q06124	Q9UQC2	IntAct; MINT;HPRD
Q06124	Q9Y4H2	HPRD

PTMD Annotation Information

※ Protein Information

Functional Description

Fasta Sequence

※ PTM-Disease Association

※ Disease Cross-ref Annotation

※ PTM Sites

※ Protein-Protein Interaction