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PTPN11 (protein tyrosine phosphatase non-receptor type 11)

Gene

5781

Protein tyrosine phosphatase non-receptor type 11

PTPN11

BPTP3, CFC, JMML, METCDS, NS1, PTP-1D, PTP2C, SH-PTP2, SH-PTP3, SHP2

12q24.13

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains two tandem Src homology-2 domains, which function as phospho-tyrosine binding domains and mediate the interaction of this PTP with its substrates. This PTP is widely expressed in most tissues and plays a regulatory role in various cell signaling events that are important for a diversity of cell functions, such as mitogenic activation, metabolic control, transcription regulation, and cell migration. Mutations in this gene are a cause of Noonan syndrome as well as acute myeloid leukemia. [provided by RefSeq, Aug 2016]

Show/Hide all(107)

SNP ID	Visualize variation	Clinical significance	Consequence
rs28933386	A>G	Pathogenic	Missense variant, coding sequence variant
rs80338836	GTG>-	Pathogenic	Coding sequence variant, inframe deletion
rs121918453	G>A,C,T	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs121918454	C>A,G,T	Conflicting-interpretations-of-pathogenicity, likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs121918455	A>C,G	Pathogenic	Coding sequence variant, missense variant
rs121918456	A>C,G	Pathogenic-likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs121918457	C>T	Pathogenic-likely-pathogenic, pathogenic	Coding sequence variant, genic downstream transcript variant, missense variant
rs121918458	T>A,G	Pathogenic	Coding sequence variant, genic downstream transcript variant, missense variant
rs121918459	A>G	Pathogenic	Coding sequence variant, missense variant
rs121918460	T>A,G	Pathogenic	Coding sequence variant, missense variant
rs121918461	A>C,G,T	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs121918462	C>T	Pathogenic	Coding sequence variant, missense variant
rs121918463	T>A,C,G	Pathogenic	Coding sequence variant, missense variant
rs121918464	G>A,C	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs121918465	A>C,G,T	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs121918466	A>G	Pathogenic	Coding sequence variant, missense variant
rs121918467	C>A,T	Pathogenic	Coding sequence variant, missense variant
rs121918468	G>A,T	Pathogenic	Coding sequence variant, genic downstream transcript variant, missense variant
rs121918469	G>C	Pathogenic	Coding sequence variant, genic downstream transcript variant, missense variant
rs121918470	A>C,G	Pathogenic, likely-pathogenic	Coding sequence variant, genic downstream transcript variant, missense variant
rs139188627	T>C	Conflicting-interpretations-of-pathogenicity	Synonymous variant, genic downstream transcript variant, coding sequence variant
rs141140214	C>T	Conflicting-interpretations-of-pathogenicity, likely-benign, uncertain-significance	Missense variant, genic downstream transcript variant, coding sequence variant
rs143433437	C>T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Missense variant, coding sequence variant
rs146749153	T>A,C	Conflicting-interpretations-of-pathogenicity, likely-benign	Intron variant
rs267606989	C>T	Pathogenic	Stop gained, coding sequence variant
rs369155025	G>A,C,T	Likely-pathogenic	Missense variant, coding sequence variant
rs372736227	A>G	Conflicting-interpretations-of-pathogenicity, uncertain-significance, likely-benign	Coding sequence variant, synonymous variant
rs376607329	G>A,T	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs387907157	C>T	Pathogenic	Genic downstream transcript variant, coding sequence variant, stop gained
rs387907158	A>T	Pathogenic	Stop gained, coding sequence variant
rs397507501	A>G	Pathogenic	Missense variant, coding sequence variant
rs397507502	C>A,T	Conflicting-interpretations-of-pathogenicity, benign	Coding sequence variant, synonymous variant
rs397507503	C>T	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs397507504	A>G	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs397507505	A>C,G,T	Pathogenic	Missense variant, coding sequence variant
rs397507506	C>A,G	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs397507507	G>A,C,T	Pathogenic	Missense variant, coding sequence variant
rs397507508	GTGA>T	Pathogenic	Inframe indel, coding sequence variant
rs397507509	G>C,T	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs397507510	G>A,C,T	Pathogenic	Missense variant, coding sequence variant
rs397507511	G>A,C	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs397507512	T>C,G	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs397507513	A>C	Pathogenic	Missense variant, coding sequence variant
rs397507514	G>C,T	Pathogenic	Missense variant, coding sequence variant
rs397507517	A>C	Pathogenic	Missense variant, coding sequence variant
rs397507518	G>A	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs397507519	A>C	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs397507520	G>C,T	Pathogenic	Missense variant, coding sequence variant
rs397507523	A>G	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs397507524	ACA>-,ACAACA	Likely-pathogenic, uncertain-significance, pathogenic	Inframe insertion, coding sequence variant, inframe deletion
rs397507525	C>T	Pathogenic	Missense variant, coding sequence variant
rs397507526	T>A,G	Not-provided, pathogenic	Missense variant, coding sequence variant
rs397507527	G>A,T	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs397507529	A>G	Pathogenic	Missense variant, coding sequence variant
rs397507530	C>G	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs397507531	T>A,C,G	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs397507534	G>A,T	Conflicting-interpretations-of-pathogenicity, benign	Missense variant, coding sequence variant
rs397507537	A>C	Pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant
rs397507539	C>A,G,T	Likely-pathogenic, pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant
rs397507540	C>A,T	Pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant
rs397507541	C>T	Pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant
rs397507542	G>T	Pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant
rs397507543	G>A	Pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant
rs397507544	C>T	Pathogenic, pathogenic-likely-pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant
rs397507545	G>A,C	Pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant
rs397507546	G>A,C,T	Likely-pathogenic, other, pathogenic, pathogenic-likely-pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant
rs397507547	A>G	Pathogenic, pathogenic-likely-pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant
rs397507548	A>C	Pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant
rs397507549	C>A,G	Pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant
rs397507550	G>A,C,T	Pathogenic, pathogenic-likely-pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant, synonymous variant
rs397509345	AG>CC	Pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant
rs397516801	A>G	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs397516802	AC>CT	Pathogenic	Missense variant, coding sequence variant
rs397516803	C>A	Likely-pathogenic	Missense variant, coding sequence variant
rs397516806	A>G,T	Uncertain-significance, pathogenic	Missense variant, coding sequence variant
rs397516807	A>-	Pathogenic	Stop gained, coding sequence variant
rs397516809	G>A,T	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant, synonymous variant
rs397516810	T>G	Pathogenic	Missense variant, coding sequence variant
rs398122857	GTACG>-	Pathogenic	Frameshift variant, coding sequence variant
rs398122858	CTGGTG>AAGAACACAGGGGAGAGCA	Pathogenic	Frameshift variant, coding sequence variant
rs398122859	CT>-	Pathogenic	Frameshift variant, coding sequence variant
rs398122860	C>-	Pathogenic	Frameshift variant, coding sequence variant
rs398122861	A>C	Pathogenic	Splice acceptor variant
rs398122862	G>T	Pathogenic	Splice acceptor variant
rs727503380	A>T	Likely-pathogenic	Coding sequence variant, missense variant
rs727503381	A>T	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs730880994	A>G	Likely-pathogenic	Coding sequence variant, missense variant, genic downstream transcript variant
rs765642157	T>A,G	Uncertain-significance, pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs777603059	A>G	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs869025574	GAT>-	Pathogenic	Coding sequence variant, inframe deletion
rs886039463	C>A	Pathogenic	Coding sequence variant, genic downstream transcript variant, missense variant
rs886039711	AC>GA	Pathogenic	Coding sequence variant, genic downstream transcript variant, missense variant
rs886041495	T>C	Pathogenic	Coding sequence variant, missense variant
rs923052172	C>T	Pathogenic	Coding sequence variant, stop gained
rs1052382672	T>C	Uncertain-significance, likely-pathogenic	Missense variant, coding sequence variant
rs1057517917	AT>GC	Pathogenic	Missense variant, coding sequence variant
rs1057517935	TG>AA	Pathogenic	Missense variant, coding sequence variant
rs1391791847	C>A,G	Likely-pathogenic	Coding sequence variant, missense variant
rs1398859175	A>G	Likely-pathogenic	Coding sequence variant, missense variant
rs1555267558	T>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1555270113	G>A	Pathogenic	Stop gained, coding sequence variant
rs1566164987	C>T	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs1566168783	C>-	Pathogenic	Frameshift variant, coding sequence variant
rs1566186833	AG>CC	Pathogenic	Genic downstream transcript variant, missense variant, coding sequence variant
rs1592847299	G>C	Likely-pathogenic	Splice acceptor variant
rs1592852902	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs1592852978	G>-	Pathogenic	Coding sequence variant, frameshift variant

Show/Hide all(26)

miRTarBase ID	miRNA	Experiments	Reference
MIRT003549	hsa-miR-489-3p	Luciferase reporter assay, Western blot	20700123
MIRT003549	hsa-miR-489-3p	Luciferase reporter assay	26918448
MIRT006482	hsa-miR-181a-5p	Luciferase reporter assay, Western blot	17382377
MIRT007150	hsa-miR-23a-3p	Luciferase reporter assay	23420868
MIRT022573	hsa-miR-124-3p	Microarray	18668037
MIRT024234	hsa-miR-218-5p	Sequencing	20371350
MIRT038301	hsa-miR-130b-5p	CLASH	23622248
MIRT041308	hsa-miR-193b-3p	CLASH	23622248
MIRT044548	hsa-miR-320a	CLASH	23622248
MIRT047153	hsa-miR-183-5p	CLASH	23622248
MIRT616220	hsa-miR-6826-5p	HITS-CLIP	23824327
MIRT616221	hsa-miR-548t-3p	HITS-CLIP	23824327
MIRT616222	hsa-miR-548ap-3p	HITS-CLIP	23824327
MIRT616223	hsa-miR-548aa	HITS-CLIP	23824327
MIRT616224	hsa-miR-548z	HITS-CLIP	23824327
MIRT616225	hsa-miR-548h-3p	HITS-CLIP	23824327
MIRT616226	hsa-miR-548d-3p	HITS-CLIP	23824327
MIRT616227	hsa-miR-548bb-3p	HITS-CLIP	23824327
MIRT616228	hsa-miR-548ac	HITS-CLIP	23824327
MIRT722993	hsa-miR-4659b-3p	HITS-CLIP	19536157
MIRT722994	hsa-miR-4659a-3p	HITS-CLIP	19536157
MIRT722995	hsa-miR-6875-3p	HITS-CLIP	19536157
MIRT722996	hsa-miR-942-5p	HITS-CLIP	19536157
MIRT722997	hsa-miR-6870-3p	HITS-CLIP	19536157
MIRT722998	hsa-miR-6793-3p	HITS-CLIP	19536157
MIRT722999	hsa-miR-6729-3p	HITS-CLIP	19536157

Show/Hide all(91)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000077	Process	DNA damage checkpoint	IEA
GO:0000187	Process	Activation of MAPK activity	IEA
GO:0001784	Function	Phosphotyrosine residue binding	IMP	12051764
GO:0001784	Function	Phosphotyrosine residue binding	IPI	11986327, 12051764
GO:0004721	Function	Phosphoprotein phosphatase activity	IDA	15133037
GO:0004725	Function	Protein tyrosine phosphatase activity	EXP	22759635
GO:0004725	Function	Protein tyrosine phosphatase activity	IDA	15133037, 23029125, 26742426, 28074573
GO:0004725	Function	Protein tyrosine phosphatase activity	IMP	10206955, 17562706
GO:0004725	Function	Protein tyrosine phosphatase activity	TAS
GO:0004726	Function	Non-membrane spanning protein tyrosine phosphatase activity	IDA	16481357
GO:0004726	Function	Non-membrane spanning protein tyrosine phosphatase activity	IMP	10655584
GO:0004726	Function	Non-membrane spanning protein tyrosine phosphatase activity	TAS
GO:0005158	Function	Insulin receptor binding	IPI	7493946
GO:0005515	Function	Protein binding	IPI	7493946, 7504175, 7513703, 7523381, 7530043, 7642582, 7688466, 8119896, 8183548, 8538796, 8648092, 8810330, 8895367, 9312087, 9535915, 9593725, 9632781, 9658397, 9774457, 9792637, 10206955, 10540326, 10655584, 10660596, 10681522, 10704309, 10887109, 11323411, 11453982, 12577067, 12614
GO:0005634	Component	Nucleus	IDA	15133037, 26742426
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IDA	10940933, 15133037, 26742426
GO:0005739	Component	Mitochondrion	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006641	Process	Triglyceride metabolic process	IEA
GO:0007173	Process	Epidermal growth factor receptor signaling pathway	TAS
GO:0007229	Process	Integrin-mediated signaling pathway	IEA
GO:0007411	Process	Axon guidance	TAS
GO:0007420	Process	Brain development	IMP	11704759
GO:0007507	Process	Heart development	IMP	12058348
GO:0008543	Process	Fibroblast growth factor receptor signaling pathway	IMP	16481357
GO:0008543	Process	Fibroblast growth factor receptor signaling pathway	TAS
GO:0009755	Process	Hormone-mediated signaling pathway	IEA
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0019901	Function	Protein kinase binding	ISS
GO:0019904	Function	Protein domain specific binding	IEA
GO:0021697	Process	Cerebellar cortex formation	IEA
GO:0030159	Function	Signaling receptor complex adaptor activity	IPI	7493946
GO:0030168	Process	Platelet activation	TAS
GO:0030220	Process	Platelet formation	IEA
GO:0030971	Function	Receptor tyrosine kinase binding	IEA
GO:0031295	Process	T cell costimulation	TAS
GO:0031748	Function	D1 dopamine receptor binding	IEA
GO:0032331	Process	Negative regulation of chondrocyte differentiation	ISS
GO:0032528	Process	Microvillus organization	IEA
GO:0032728	Process	Positive regulation of interferon-beta production	ISS
GO:0032755	Process	Positive regulation of interleukin-6 production	ISS
GO:0032760	Process	Positive regulation of tumor necrosis factor production	ISS
GO:0032991	Component	Protein-containing complex	IMP	17562706
GO:0033277	Process	Abortive mitotic cell cycle	IEA
GO:0033628	Process	Regulation of cell adhesion mediated by integrin	IMP	10655584
GO:0033629	Process	Negative regulation of cell adhesion mediated by integrin	IEA
GO:0035264	Process	Multicellular organism growth	IEA
GO:0035265	Process	Organ growth	IEA
GO:0035335	Process	Peptidyl-tyrosine dephosphorylation	IDA	15133037
GO:0035335	Process	Peptidyl-tyrosine dephosphorylation	IMP	10655584, 17562706
GO:0035855	Process	Megakaryocyte development	IEA
GO:0036302	Process	Atrioventricular canal development	IMP	12058348
GO:0038127	Process	ERBB signaling pathway	IDA	15133037
GO:0042445	Process	Hormone metabolic process	IEA
GO:0042593	Process	Glucose homeostasis	IEA
GO:0043254	Process	Regulation of protein-containing complex assembly	IDA	7493946
GO:0043274	Function	Phospholipase binding	IEA
GO:0043560	Function	Insulin receptor substrate binding	IEA
GO:0045296	Function	Cadherin binding	IPI	15985432
GO:0045778	Process	Positive regulation of ossification	ISS
GO:0045931	Process	Positive regulation of mitotic cell cycle	IEA
GO:0046326	Process	Positive regulation of glucose import	IDA	7493946
GO:0046628	Process	Positive regulation of insulin receptor signaling pathway	IDA	7493946
GO:0046676	Process	Negative regulation of insulin secretion	IEA
GO:0046825	Process	Regulation of protein export from nucleus	IEA
GO:0046887	Process	Positive regulation of hormone secretion	IEA
GO:0048008	Process	Platelet-derived growth factor receptor signaling pathway	IEA
GO:0048011	Process	Neurotrophin TRK receptor signaling pathway	IEA
GO:0048013	Process	Ephrin receptor signaling pathway	IDA	10655584
GO:0048609	Process	Multicellular organismal reproductive process	IEA
GO:0048806	Process	Genitalia development	IMP	12058348
GO:0048839	Process	Inner ear development	IMP	12058348
GO:0048873	Process	Homeostasis of number of cells within a tissue	IEA
GO:0050731	Process	Positive regulation of peptidyl-tyrosine phosphorylation	IMP	26706435
GO:0050839	Function	Cell adhesion molecule binding	IPI	15985432
GO:0050900	Process	Leukocyte migration	TAS
GO:0051428	Function	Peptide hormone receptor binding	IEA
GO:0051463	Process	Negative regulation of cortisol secretion	IEA
GO:0051897	Process	Positive regulation of protein kinase B signaling	TAS
GO:0060020	Process	Bergmann glial cell differentiation	IEA
GO:0060125	Process	Negative regulation of growth hormone secretion	IEA
GO:0060325	Process	Face morphogenesis	IMP	11704759
GO:0060338	Process	Regulation of type I interferon-mediated signaling pathway	TAS
GO:0061582	Process	Intestinal epithelial cell migration	IEA
GO:0070102	Process	Interleukin-6-mediated signaling pathway	TAS
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	IMP	28074573
GO:0071260	Process	Cellular response to mechanical stimulus	IEA
GO:0071345	Process	Cellular response to cytokine stimulus	TAS
GO:0071364	Process	Cellular response to epidermal growth factor stimulus	IMP	28074573
GO:1990782	Function	Protein tyrosine kinase binding	IPI	15985432

MIM	HGNC	e!Ensembl
176876	9644	ENSG00000179295

Protein

UniProt ID

Q06124

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)

Protein function

Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus (PubMed:10655584, PubMed:18559669, PubMed:18829466, PubMed:26742426, PubMed:28074573). Positively regulates MAPK signal transduction pathway (PubMed:28074573). Dephosphorylates GAB1, ARHGAP35 and EGFR (PubMed:28074573). Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulation of its RhoA binding activity (PubMed:18559669). Dephosphorylates CDC73 (PubMed:26742426). Dephosphorylates SOX9 on tyrosine residues, leading to inactivate SOX9 and promote ossification (By similarity).

PDB

2SHP , 3B7O , 3MOW , 3O5X , 3TKZ , 3TL0 , 3ZM0 , 3ZM1 , 3ZM2 , 3ZM3 , 4DGP , 4DGX , 4GWF , 4H1O , 4H34 , 4JE4 , 4JEG , 4JMG , 4NWF , 4NWG , 4OHD , 4OHE , 4OHH , 4OHI , 4OHL , 4PVG , 4QSY , 4RDD , 5BK8 , 5DF6 , 5EHP , 5EHR , 5I6V , 5IBM , 5IBS , 5X7B , 5X94 , 5XZR , 6ATD , 6BMR , 6BMU , 6BMV , 6BMW , 6BMX , 6BMY , 6BN5 , 6CMP , 6CMQ , 6CMR , 6CMS , 6CRF

Family and domains

Pfam

Accession	ID	Position in sequence	Description	Type
PF00017	SH2	6 → 81	SH2 domain	Domain
PF00017	SH2	112 → 197	SH2 domain	Domain
PF00102	Y_phosphatase	273 → 524	Protein-tyrosine phosphatase	Domain

Sequence

MTSRRWFHPNITGVEAENLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTG
DYYDLYGGEKFATLAELVQYYMEHHGQLKEKNGDVIELKYPLNCADPTSERWFHGHLSGK
EAEKLLTEKGKHGSFLVRESQSHPGDFVLSVRTGDDKGESNDGKSKVTHVMIRCQELKYD
VGGGERFDSLTDLVEHYKKNPMVETLGTVLQLKQPLNTTRINAAEIESRVRELSKLAETT
DKVKQGFWEEFETLQQQECKLLYSRKEGQRQENKNKNRYKNILPFDHTRVVLHDGDPNEP
VSDYINANIIMPEFETKCNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEV
ERGKSKCVKYWPDEYALKEYGVMRVRNVKESAAHDYTLRELKLSKVGQGNTERTVWQYHF
RTWPDHGVPSDPGGVLDFLEEVHHKQESIMDAGPVVVHCSAGIGRTGTFIVIDILIDIIR
EKGVDCDIDVPKTIQMVRSQRSGMVQTEAQYRFIYMAVQHYIETLQRRIEEEQKSKRKGH
EYTNIKYSLADQTSGDQSPLPPCTPTPPCAEMREDSARVYENVGLMQQQKSFR

Sequence length

593

Interactions

View interactions

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