PTPN11 protein tyrosine phosphatase non-receptor type 11 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PTPN11provided by HGNC
Official Full Name: protein tyrosine phosphatase non-receptor type 11provided by HGNC
Primary source: HGNC:HGNC:9644
See related: Ensembl:ENSG00000179295 MIM:176876
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CFC; NS1; JMML; SHP2; BPTP3; PTP2C; METCDS; PTP-1D; SH-PTP2; SH-PTP3
Summary: 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]
Expression: Ubiquitous expression in brain (RPKM 42.2), fat (RPKM 37.5) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 12q24.13

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
109.20191205	current	GRCh38.p13 (GCF_000001405.39)	12	NC_000012.12 (112418915..112509918)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (112856536..112947717)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Pathogenic somatic variants of PTPN11 associated with hypothalamic hamartoma were found.
Title: Pathogenic variants of DYNC2H1, KIAA0556, and PTPN11 associated with hypothalamic hamartoma.
The effect of E76K gain-of-function mutation (found in juvenile myelomonocytic leukemia) on SHP2 was studied using molecular dynamics.
Title: Exploring the effect of E76K mutation on SHP2 cause gain-of-function activity by a molecular dynamics study.
PTPN11 germline mutations are associated with high-grade glioma in Noonan syndrome.
Title: Occurrence of high-grade glioma in Noonan syndrome: Report of two cases.
Mechanism of Folding and Binding of the N-Terminal SH2 Domain from SHP2
Title: Mechanism of Folding and Binding of the N-Terminal SH2 Domain from SHP2.
SHP2 may be a favorable indicator of prognosis in thyroid carcinoma.
Title: Clinicopathological and prognostic significance of SHP2 and Hook1 expression in patients with thyroid carcinoma.
Our data show that SHP-2 inactivation by ROS in sepsis releases a protective break, resulting in endothelial activation.
Title: Inactivation of the tyrosine phosphatase SHP-2 drives vascular dysfunction in Sepsis.
Our study uncovered an important role of SHP2 in bone development and cartilage homeostasis by influencing the osteogenic differentiation of hypertrophic chondrocytes and provided insight into the pathogenesis and potential treatment of skeletal diseases, such as osteopenia and osteoporosis
Title: SHP2 Regulates the Osteogenic Fate of Growth Plate Hypertrophic Chondrocytes.
SHP2 associates with nuclear localization of STAT3: significance in progression and prognosis of colorectal cancer
Title: SHP2 associates with nuclear localization of STAT3: significance in progression and prognosis of colorectal cancer.
These data demonstrate that the formation of this MPZL1-PTPN11-GRB2 complex is triggered by the attachment of HER2+ breast cancer cells to fibronectin.
Title: MPZL1 forms a signalling complex with GRB2 adaptor and PTPN11 phosphatase in HER2-positive breast cancer cells.
we suggest that the prognostic value of SHP2 could reflect the nuclear localization of SHP2 and its interaction with nuclear YAP1
Title: Association of nuclear localization of SHP2 and YAP1 with unfavorable prognosis in non-small cell lung cancer.

Submit: New GeneRIF Correction See all GeneRIFs (391)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Juvenile myelomonocytic leukemia MedGen: C0349639 OMIM: 607785 GeneReviews: Not available	Compare labs
LEOPARD syndrome 1 MedGen: C4551484 OMIM: 151100 GeneReviews: Noonan Syndrome with Multiple Lentigines	Compare labs
Metachondromatosis MedGen: C0410530 OMIM: 156250 GeneReviews: Not available	Compare labs
Noonan syndrome MedGen: C0028326 GeneReviews: Noonan Syndrome	Compare labs
Noonan syndrome 1 MedGen: C4551602 OMIM: 163950 GeneReviews: Noonan Syndrome	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated (2012-03-22) ClinGen Genome Curation PagePubMed Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated (2012-03-22) ClinGen Genome Curation PagePubMed

NHGRI GWAS Catalog

Description
A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genetics of rheumatoid arthritis contributes to biology and drug discovery. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association study identifies loci on 12q24 and 13q32 associated with tetralogy of Fallot. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
New gene functions in megakaryopoiesis and platelet formation. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Novel associations for hypothyroidism include known autoimmune risk loci. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Progressive HIV-1 infection is linked to upregulated CXCL8 (IL8), CXCR1, and PTPN11 (SHP2) expression in PBMC samples from HIV-1 infected children	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HCV-E2 and HIV-gp120 act collaboratively to trigger a specific set of downstream signaling pathways that include activation of p38 mitogen-activated protein (MAP) kinase and the tyrosine phosphatase, SHP2, in hepatocytes	PubMed
Tat	tat	HIV-1 Tat C treated human brain microvascular endothelial cells result in downregulation and dissociation of VE-PTP and SHP2 from VE-cadherin	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-30316 (e-PCR)
- UniSTS:35867

WI-7628 (e-PCR)
- UniSTS:57652

WI-18740 (e-PCR)
- UniSTS:66916

D12S1863 (e-PCR)
- UniSTS:32111

PTPN11_1308 (e-PCR)
- UniSTS:277622

PTPN11_v403 (e-PCR)
- UniSTS:277622

RH78116 (e-PCR)
- UniSTS:23159

D12S84 (e-PCR), detects polymorphism
- UniSTS:50589

G34953 (e-PCR)
- UniSTS:117663

RH67010 (e-PCR)
- UniSTS:86484

D12S1920 (e-PCR)
- UniSTS:12794

Homology

Homologs of the PTPN11 gene: The PTPN11 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, and mosquito.
Orthologs from Annotation Pipeline: 291 organisms have orthologs with human gene PTPN11
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
D1 dopamine receptor binding	IEA Inferred from Electronic Annotation more info
SH3/SH2 adaptor activity	IPI Inferred from Physical Interaction more info	PubMed
cadherin binding	IPI Inferred from Physical Interaction more info	PubMed
cell adhesion molecule binding	IPI Inferred from Physical Interaction more info	PubMed
insulin receptor binding	IPI Inferred from Physical Interaction more info	PubMed
insulin receptor substrate binding	IEA Inferred from Electronic Annotation more info
non-membrane spanning protein tyrosine phosphatase activity	IMP Inferred from Mutant Phenotype more info	PubMed
non-membrane spanning protein tyrosine phosphatase activity	TAS Traceable Author Statement more info
peptide hormone receptor binding	IEA Inferred from Electronic Annotation more info
phospholipase binding	IEA Inferred from Electronic Annotation more info
phosphoprotein phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
phosphotyrosine residue binding	IMP Inferred from Mutant Phenotype more info	PubMed
phosphotyrosine residue binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein domain specific binding	IEA Inferred from Electronic Annotation more info
protein kinase binding	ISS Inferred from Sequence or Structural Similarity more info
protein tyrosine kinase binding	IPI Inferred from Physical Interaction more info	PubMed
protein tyrosine phosphatase activity	EXP Inferred from Experiment more info	PubMed
protein tyrosine phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
protein tyrosine phosphatase activity	IMP Inferred from Mutant Phenotype more info	PubMed
protein tyrosine phosphatase activity	TAS Traceable Author Statement more info
receptor tyrosine kinase binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
Bergmann glial cell differentiation	IEA Inferred from Electronic Annotation more info
DNA damage checkpoint	IEA Inferred from Electronic Annotation more info
ERBB signaling pathway	IDA Inferred from Direct Assay more info	PubMed
T cell costimulation	TAS Traceable Author Statement more info
abortive mitotic cell cycle	IEA Inferred from Electronic Annotation more info
activation of MAPK activity	IEA Inferred from Electronic Annotation more info
atrioventricular canal development	IMP Inferred from Mutant Phenotype more info	PubMed
axon guidance	TAS Traceable Author Statement more info
brain development	IMP Inferred from Mutant Phenotype more info	PubMed
cellular response to cytokine stimulus	TAS Traceable Author Statement more info
cellular response to epidermal growth factor stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
cellular response to mechanical stimulus	IEA Inferred from Electronic Annotation more info
cerebellar cortex formation	IEA Inferred from Electronic Annotation more info
cytokine-mediated signaling pathway	TAS Traceable Author Statement more info
ephrin receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
epidermal growth factor receptor signaling pathway	TAS Traceable Author Statement more info
face morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
fibroblast growth factor receptor signaling pathway	TAS Traceable Author Statement more info
genitalia development	IMP Inferred from Mutant Phenotype more info	PubMed
glucose homeostasis	IEA Inferred from Electronic Annotation more info
heart development	IMP Inferred from Mutant Phenotype more info	PubMed
homeostasis of number of cells within a tissue	IEA Inferred from Electronic Annotation more info
hormone metabolic process	IEA Inferred from Electronic Annotation more info
hormone-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
inner ear development	IMP Inferred from Mutant Phenotype more info	PubMed
integrin-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
interleukin-6-mediated signaling pathway	TAS Traceable Author Statement more info
intestinal epithelial cell migration	IEA Inferred from Electronic Annotation more info
leukocyte migration	TAS Traceable Author Statement more info
megakaryocyte development	IEA Inferred from Electronic Annotation more info
microvillus organization	IEA Inferred from Electronic Annotation more info
multicellular organism growth	IEA Inferred from Electronic Annotation more info
multicellular organismal reproductive process	IEA Inferred from Electronic Annotation more info
negative regulation of cell adhesion mediated by integrin	IEA Inferred from Electronic Annotation more info
negative regulation of cortisol secretion	IEA Inferred from Electronic Annotation more info
negative regulation of growth hormone secretion	IEA Inferred from Electronic Annotation more info
negative regulation of insulin secretion	IEA Inferred from Electronic Annotation more info
neurotrophin TRK receptor signaling pathway	IEA Inferred from Electronic Annotation more info
organ growth	IEA Inferred from Electronic Annotation more info
peptidyl-tyrosine dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
peptidyl-tyrosine dephosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
platelet activation	TAS Traceable Author Statement more info
platelet formation	IEA Inferred from Electronic Annotation more info
platelet-derived growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
positive regulation of ERK1 and ERK2 cascade	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of glucose import	IDA Inferred from Direct Assay more info	PubMed
positive regulation of hormone secretion	IEA Inferred from Electronic Annotation more info
positive regulation of insulin receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
positive regulation of interferon-beta production	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of interleukin-6 production	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of mitotic cell cycle	IEA Inferred from Electronic Annotation more info
positive regulation of peptidyl-tyrosine phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of protein kinase B signaling	TAS Traceable Author Statement more info
positive regulation of tumor necrosis factor production	ISS Inferred from Sequence or Structural Similarity more info
regulation of cell adhesion mediated by integrin	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of protein complex assembly	IDA Inferred from Direct Assay more info	PubMed
regulation of protein export from nucleus	IEA Inferred from Electronic Annotation more info
regulation of type I interferon-mediated signaling pathway	TAS Traceable Author Statement more info
triglyceride metabolic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytosol	TAS Traceable Author Statement more info
mitochondrion	IEA Inferred from Electronic Annotation more info
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IDA Inferred from Direct Assay more info	PubMed
protein-containing complex	IMP Inferred from Mutant Phenotype more info	PubMed

General protein information

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Preferred Names: tyrosine-protein phosphatase non-receptor type 11

Names: protein-tyrosine phosphatase 1D; protein-tyrosine phosphatase 2C

NP_001317366.1

EC 3.1.3.48

NP_001361554.1

EC 3.1.3.48

NP_002825.3

EC 3.1.3.48

NP_542168.1

EC 3.1.3.48

XP_011536915.1

EC 3.1.3.48

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007459.1 RefSeqGene

Range

5001..96182

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_614

mRNA and Protein(s)

NM_001330437.2 → NP_001317366.1 tyrosine-protein phosphatase non-receptor type 11 isoform 3

Status: REVIEWED

Source sequence(s)

AC004086, AC004216

Consensus CDS

CCDS81741.1

UniProtKB/Swiss-Prot

Q06124

Related

ENSP00000489597.1, ENST00000635625.1

Conserved Domains (3) summary

cd09931
Location:111 → 218

SH2_C-SH2_SHP_like; C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins

cd10340
Location:5 → 103

SH2_N-SH2_SHP_like; N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins

cd00047
Location:276 → 523

PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...
NM_001374625.1 → NP_001361554.1 tyrosine-protein phosphatase non-receptor type 11 isoform 4

Status: REVIEWED

Source sequence(s)

AC004086, AC004216
NM_002834.5 → NP_002825.3 tyrosine-protein phosphatase non-receptor type 11 isoform 1

See identical proteins and their annotated locations for NP_002825.3

Status: REVIEWED

Source sequence(s)

AC004086, AC004216

Consensus CDS

CCDS9163.1

UniProtKB/Swiss-Prot

Q06124

Related

ENSP00000340944.2, ENST00000351677.6

Conserved Domains (3) summary

cd09931
Location:111 → 218

SH2_C-SH2_SHP_like; C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins

cd10340
Location:5 → 103

SH2_N-SH2_SHP_like; N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins

cd00047
Location:276 → 519

PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...
NM_080601.3 → NP_542168.1 tyrosine-protein phosphatase non-receptor type 11 isoform 2

See identical proteins and their annotated locations for NP_542168.1

Status: REVIEWED

Source sequence(s)

BC008692

Consensus CDS

CCDS58280.1

UniProtKB/Swiss-Prot

Q06124

Related

ENSP00000376376.1, ENST00000392597.5

Conserved Domains (3) summary

cd09931
Location:111 → 218

SH2_C-SH2_SHP_like; C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins

cd10340
Location:5 → 103

SH2_N-SH2_SHP_like; N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins

smart00194
Location:246 → 459

PTPc; Protein tyrosine phosphatase, catalytic domain

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20191205

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p13 Primary Assembly

Range

112418915..112509918

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011538613.2 → XP_011536915.1 tyrosine-protein phosphatase non-receptor type 11 isoform X1

Conserved Domains (3) summary

cd09931
Location:110 → 217

SH2_C-SH2_SHP_like; C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins

cd10340
Location:5 → 102

SH2_N-SH2_SHP_like; N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins

cd00047
Location:275 → 522

PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...