PTPN6 protein tyrosine phosphatase non-receptor type 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PTPN6provided by HGNC
Official Full Name: protein tyrosine phosphatase non-receptor type 6provided by HGNC
Primary source: HGNC:HGNC:9658
See related: Ensembl:ENSG00000111679 MIM:176883; AllianceGenome:HGNC:9658
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: HCP; HCPH; SHP1; SHP-1; HPTP1C; PTP-1C; SHP-1L; SH-PTP1
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. N-terminal part of this PTP contains two tandem Src homolog (SH2) domains, which act as protein phospho-tyrosine binding domains, and mediate the interaction of this PTP with its substrates. This PTP is expressed primarily in hematopoietic cells, and functions as an important regulator of multiple signaling pathways in hematopoietic cells. This PTP has been shown to interact with, and dephosphorylate a wide spectrum of phospho-proteins involved in hematopoietic cell signaling. Multiple alternatively spliced variants of this gene, which encode distinct isoforms, have been reported. [provided by RefSeq, Jul 2008]
Expression: Broad expression in spleen (RPKM 76.2), lymph node (RPKM 74.9) and 19 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12p13.31

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (6946577..6961316)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (6957743..6974790)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (7055740..7070479)

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?

Association of Long Non-coding RNA C1RL-AS1 and PTPN6 Gene Polymorphisms with Ocular Behcet's Disease in Han Chinese.
Title: Association of Long Non-coding RNA C1RL-AS1 and PTPN6 Gene Polymorphisms with Ocular Behcet's Disease in Han Chinese.
Global and promoter specific hypermethylation of tumor suppressor genes P16, SOCS1, and SHP1 in oral squamous cell carcinoma and oral submucous fibrosis.
Title: Global and promoter specific hypermethylation of tumor suppressor genes P16, SOCS1, and SHP1 in oral squamous cell carcinoma and oral submucous fibrosis.
Single-cell and bulk sequencing analyses reveal the immune suppressive role of PTPN6 in glioblastoma.
Title: Single-cell and bulk sequencing analyses reveal the immune suppressive role of PTPN6 in glioblastoma.
Enhanced SHP-1 Expression in Podocyturia Is Associated with Kidney Dysfunction in Patients with Diabetes.
Title: Enhanced SHP-1 Expression in Podocyturia Is Associated with Kidney Dysfunction in Patients with Diabetes.
SHP-1 knockdown suppresses mitochondrial biogenesis and aggravates mitochondria-dependent apoptosis induced by all trans retinal through the STING/AMPK pathways.
Title: SHP-1 knockdown suppresses mitochondrial biogenesis and aggravates mitochondria-dependent apoptosis induced by all trans retinal through the STING/AMPK pathways.
A LILRB1 variant with a decreased ability to phosphorylate SHP-1 leads to autoimmune diseases.
Title: A LILRB1 variant with a decreased ability to phosphorylate SHP-1 leads to autoimmune diseases.
The regulatory effects of PTPN6 on inflammatory process: Reports from mice to men.
Title: The regulatory effects of PTPN6 on inflammatory process: Reports from mice to men.
Vitamin D3-VDR-PTPN6 axis mediated autophagy contributes to the inhibition of macrophage foam cell formation.
Title: Vitamin D3-VDR-PTPN6 axis mediated autophagy contributes to the inhibition of macrophage foam cell formation.
METTL14 benefits the mesenchymal stem cells in patients with steroid-associated osteonecrosis of the femoral head by regulating the m6A level of PTPN6.
Title: METTL14 benefits the mesenchymal stem cells in patients with steroid-associated osteonecrosis of the femoral head by regulating the m6A level of PTPN6.
The phosphatase Shp1 interacts with and dephosphorylates cortactin to inhibit invadopodia function.
Title: The phosphatase Shp1 interacts with and dephosphorylates cortactin to inhibit invadopodia function.

Submit: New GeneRIF Correction See all GeneRIFs (207)

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

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
Monocyte derived dendritic cells from HIV-infected clinical samples upregulate PTPN6 (SHP-1) expression	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-31976 (e-PCR)
- UniSTS:56850

RH80060 (e-PCR)
- UniSTS:90394

RH79905 (e-PCR)
- UniSTS:84041

RH46958 (e-PCR)
- UniSTS:4816

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables SH2 domain binding	IEA Inferred from Electronic Annotation more info
enables SH3 domain binding	IEA Inferred from Electronic Annotation more info
enables cell adhesion molecule binding	IEA Inferred from Electronic Annotation more info
enables non-membrane spanning protein tyrosine phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables phosphorylation-dependent protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables phosphotyrosine residue binding	IBA Inferred from Biological aspect of Ancestor more info
enables phosphotyrosine residue binding	IMP Inferred from Mutant Phenotype 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	IPI Inferred from Physical Interaction 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 transmembrane receptor protein tyrosine phosphatase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in B cell receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in G protein-coupled receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in MAPK cascade	IEA Inferred from Electronic Annotation more info
involved_in T cell costimulation	TAS Traceable Author Statement more info
involved_in T cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in T cell receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in cell differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in cytokine-mediated signaling pathway	TAS Traceable Author Statement more info
involved_in epididymis development	IEA Inferred from Electronic Annotation more info
involved_in hematopoietic progenitor cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in intracellular signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in megakaryocyte development	IEA Inferred from Electronic Annotation more info
involved_in mitotic cell cycle	IBA Inferred from Biological aspect of Ancestor more info
involved_in natural killer cell mediated cytotoxicity	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of MAPK cascade	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of T cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of T cell receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell population proliferation	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of humoral immune response mediated by circulating immunoglobulin	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of inflammatory response to wounding	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of interleukin-6 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of mast cell activation involved in immune response	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of peptidyl-tyrosine phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of tumor necrosis factor production	ISS Inferred from Sequence or Structural Similarity more info
involved_in peptidyl-tyrosine dephosphorylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in peptidyl-tyrosine dephosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in platelet aggregation	IEA Inferred from Electronic Annotation more info
involved_in platelet formation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell adhesion mediated by integrin	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of B cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in regulation of ERK1 and ERK2 cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of G1/S transition of mitotic cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of apoptotic process	TAS Traceable Author Statement more info	PubMed
involved_in regulation of release of sequestered calcium ion into cytosol	IEA Inferred from Electronic Annotation more info
involved_in regulation of type I interferon-mediated signaling pathway	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
part_of alpha-beta T cell receptor complex	IEA Inferred from Electronic Annotation more info
located_in cell-cell junction	IEA Inferred from Electronic Annotation more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in membrane	TAS Traceable Author Statement more info	PubMed
located_in nucleolus	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
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
located_in specific granule lumen	TAS Traceable Author Statement more info
located_in tertiary granule lumen	TAS Traceable Author Statement more info

General protein information

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Preferred Names: tyrosine-protein phosphatase non-receptor type 6

Names: hematopoietic cell phosphatase; hematopoietic cell protein-tyrosine phosphatase; protein-tyrosine phosphatase 1C; protein-tyrosine phosphatase SHP-1

NP_002822.2

EC 3.1.3.48

NP_536858.1

EC 3.1.3.48

NP_536859.1

EC 3.1.3.48

XP_011519290.1

EC 3.1.3.48

XP_024304874.1

EC 3.1.3.48

XP_047285187.1

EC 3.1.3.48

XP_047285188.1

EC 3.1.3.48

XP_054228689.1

EC 3.1.3.48

XP_054228690.1

EC 3.1.3.48

XP_054228691.1

EC 3.1.3.48

XP_054228692.1

EC 3.1.3.48

XP_054228693.1

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.

mRNA and Protein(s)

NM_002831.6 → NP_002822.2 tyrosine-protein phosphatase non-receptor type 6 isoform 1

See identical proteins and their annotated locations for NP_002822.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the predominant transcript and encodes the shortest isoform (1, also known as SHP-1).

Source sequence(s)

U47924

Consensus CDS

CCDS44820.1

UniProtKB/Swiss-Prot

A8K306, G3V0F8, P29350, Q969V8, Q9UK67

UniProtKB/TrEMBL

Q53EL0

Related

ENSP00000326010.9, ENST00000318974.14

Conserved Domains (3) summary

cd09931
Location:109 → 215

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

cd10340
Location:3 → 101

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

cd14606
Location:253 → 518

PTPc-N6; catalytic domain of tyrosine-protein phosphatase non-receptor type 6
NM_080548.5 → NP_536858.1 tyrosine-protein phosphatase non-receptor type 6 isoform 2

See identical proteins and their annotated locations for NP_536858.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate 5' terminal exon compared to transcript variant 1, resulting in an isoform (2) with a distinct and longer (by 2 aa) N-terminus, compared to isoform 1.

Source sequence(s)

U47924

Consensus CDS

CCDS41744.1

UniProtKB/TrEMBL

Q53EL0, Q53XS4

Related

ENSP00000382376.1, ENST00000399448.5

Conserved Domains (3) summary

cd09931
Location:111 → 217

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

cd10340
Location:6 → 103

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

cd00047
Location:274 → 516

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_080549.4 → NP_536859.1 tyrosine-protein phosphatase non-receptor type 6 isoform 3

See identical proteins and their annotated locations for NP_536859.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate 5' terminal exon, and an alternate acceptor splice site at the penultimate exon, compared to transcript variant 1, resulting in a longer isoform (3, also known as 70 kDa SHP-1L protein) with distinct N_ and C_ termini, compared to isoform 1.

Source sequence(s)

U47924

Consensus CDS

CCDS44821.1

UniProtKB/TrEMBL

Q53EL0

Related

ENSP00000391592.1, ENST00000456013.5

Conserved Domains (4) summary

cd09931
Location:109 → 215

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

cd10340
Location:3 → 101

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

smart00194
Location:243 → 514

PTPc; Protein tyrosine phosphatase, catalytic domain

cd00047
Location:272 → 514

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 ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

6946577..6961316

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011520988.2 → XP_011519290.1 tyrosine-protein phosphatase non-receptor type 6 isoform X1

See identical proteins and their annotated locations for XP_011519290.1

UniProtKB/TrEMBL

Q53EL0, Q53XS4

Conserved Domains (3) summary

cd09931
Location:111 → 217

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

cd10340
Location:6 → 103

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

cd00047
Location:274 → 516

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 ...
XM_047429231.1 → XP_047285187.1 tyrosine-protein phosphatase non-receptor type 6 isoform X3
XM_024449106.1 → XP_024304874.1 tyrosine-protein phosphatase non-receptor type 6 isoform X2

UniProtKB/Swiss-Prot

A8K306, G3V0F8, P29350, Q969V8, Q9UK67

UniProtKB/TrEMBL

Q53EL0

Conserved Domains (3) summary

cd09931
Location:109 → 215

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

cd10340
Location:3 → 101

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

cd14606
Location:253 → 518

PTPc-N6; catalytic domain of tyrosine-protein phosphatase non-receptor type 6
XM_047429232.1 → XP_047285188.1 tyrosine-protein phosphatase non-receptor type 6 isoform X4

Alternate T2T-CHM13v2.0

Genomic

NC_060936.1 Alternate T2T-CHM13v2.0

Range

6957743..6974790

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054372714.1 → XP_054228689.1 tyrosine-protein phosphatase non-receptor type 6 isoform X1

UniProtKB/TrEMBL

Q53XS4
XM_054372716.1 → XP_054228691.1 tyrosine-protein phosphatase non-receptor type 6 isoform X3
XM_054372715.1 → XP_054228690.1 tyrosine-protein phosphatase non-receptor type 6 isoform X2

UniProtKB/Swiss-Prot

A8K306, G3V0F8, P29350, Q969V8, Q9UK67
XM_054372717.1 → XP_054228692.1 tyrosine-protein phosphatase non-receptor type 6 isoform X4
XM_054372718.1 → XP_054228693.1 tyrosine-protein phosphatase non-receptor type 6 isoform X5