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; AllianceGenome:HGNC:9644
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
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Genomic context

Location:: 12q24.13

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (112418947..112509918)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (112395849..112486820)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (112856751..112947722)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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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?

[Characteristic Analysis of Adult Acute Myeloid Leukemia Patients with PTPN11 Gene Mutation].
Title: [Characteristic Analysis of Adult Acute Myeloid Leukemia Patients with PTPN11 Gene Mutation].
MEST promotes immune escape in gastric cancer by downregulating MHCI expression via SHP2.
Title: MEST promotes immune escape in gastric cancer by downregulating MHCI expression via SHP2.
SHP2 as a primordial epigenetic enzyme expunges histone H3 pTyr-54 to amend androgen receptor homeostasis.
Title: SHP2 as a primordial epigenetic enzyme expunges histone H3 pTyr-54 to amend androgen receptor homeostasis.
MEK-SHP2 inhibition prevents tibial pseudarthrosis caused by NF1 loss in Schwann cells and skeletal stem/progenitor cells.
Title: MEK-SHP2 inhibition prevents tibial pseudarthrosis caused by NF1 loss in Schwann cells and skeletal stem/progenitor cells.
Macrophage SHP2 Deficiency Alleviates Diabetic Nephropathy via Suppression of MAPK/NF-kappaB- Dependent Inflammation.
Title: Macrophage SHP2 Deficiency Alleviates Diabetic Nephropathy via Suppression of MAPK/NF-κB- Dependent Inflammation.
SHP2 regulates GluA2 tyrosine phosphorylation required for AMPA receptor endocytosis and mGluR-LTD.
Title: SHP2 regulates GluA2 tyrosine phosphorylation required for AMPA receptor endocytosis and mGluR-LTD.
Spectrum of Mutations in PTPN11 in Russian Cohort.
Title: Spectrum of Mutations in PTPN11 in Russian Cohort.
Clinical Variability in a Family with Noonan Syndrome with a Homozygous PTPN11 Gene Variant in Two Individuals.
Title: Clinical Variability in a Family with Noonan Syndrome with a Homozygous PTPN11 Gene Variant in Two Individuals.
Mutations in PTPN11 could lead to a congenital myasthenic syndrome phenotype: a Noonan syndrome case series.
Title: Mutations in PTPN11 could lead to a congenital myasthenic syndrome phenotype: a Noonan syndrome case series.
Plasma-derived exosomal protein SHP2 deficiency induces neutrophil hyperactivation in Behcet's uveitis.
Title: Plasma-derived exosomal protein SHP2 deficiency induces neutrophil hyperactivation in Behcet's uveitis.

Submit: New GeneRIF Correction See all GeneRIFs (511)

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 2020-09-08) ClinGen Genome Curation PagePubMed Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2020-09-08) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

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

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cadherin binding	IPI Inferred from Physical Interaction more info	PubMed
enables cell adhesion molecule binding	IBA Inferred from Biological aspect of Ancestor more info
enables cell adhesion molecule binding	IPI Inferred from Physical Interaction more info	PubMed
enables histone H2AXY142 phosphatase activity	IEA Inferred from Electronic Annotation more info
enables insulin receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables molecular adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables non-membrane spanning protein tyrosine phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables non-membrane spanning protein tyrosine phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables non-membrane spanning protein tyrosine phosphatase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables non-membrane spanning protein tyrosine phosphatase activity	TAS Traceable Author Statement more info
enables peptide hormone receptor binding	IEA Inferred from Electronic Annotation more info
enables phosphoprotein phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables phosphotyrosine residue binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein tyrosine kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein tyrosine phosphatase activity	EXP Inferred from Experiment more info	PubMed
enables protein tyrosine phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein tyrosine phosphatase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein tyrosine phosphatase activity	TAS Traceable Author Statement more info
enables protein tyrosine phosphatase activity, metal-dependent	IEA Inferred from Electronic Annotation more info
enables receptor tyrosine kinase binding	IBA Inferred from Biological aspect of Ancestor more info
enables signaling receptor complex adaptor activity	IPI Inferred from Physical Interaction more info	PubMed

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

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cytoplasm	IC Inferred by Curator more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in mitochondrion	HTP more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of 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: SH2 domain-containing protein tyrosine phosphatase 2; 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

XP_054228694.1

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/TrEMBL

A0A3G1LBG2

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

cd14605
Location:272 → 528

PTPc-N11; catalytic domain of tyrosine-protein phosphatase non-receptor type 11
NM_001374625.1 → NP_001361554.1 tyrosine-protein phosphatase non-receptor type 11 isoform 4

Status: REVIEWED

Source sequence(s)

AC004086, AC004216

UniProtKB/TrEMBL

A0A3G1LBG2

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

cd14605
Location:271 → 523

PTPc-N11; catalytic domain of tyrosine-protein phosphatase non-receptor type 11
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

A8K1D9, Q06124, Q96HD7

UniProtKB/TrEMBL

A0A3G1LBG2

Related

ENSP00000340944.3, ENST00000351677.7

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

cd14605
Location:272 → 524

PTPc-N11; catalytic domain of tyrosine-protein phosphatase non-receptor type 11
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/TrEMBL

A0A8I5KVS6

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: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

112418947..112509918

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011538613.3 → XP_011536915.1 tyrosine-protein phosphatase non-receptor type 11 isoform X1

UniProtKB/TrEMBL

A0A3G1LBG2

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

cd14605
Location:271 → 527

PTPc-N11; catalytic domain of tyrosine-protein phosphatase non-receptor type 11

Alternate T2T-CHM13v2.0

Genomic

NC_060936.1 Alternate T2T-CHM13v2.0

Range

112395849..112486820

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054372719.1 → XP_054228694.1 tyrosine-protein phosphatase non-receptor type 11 isoform X1

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_018508.1: Suppressed sequence

Description

NM_018508.1: This RefSeq record was removed by NCBI staff. Contact [email protected] for further information.