PTPN2 protein tyrosine phosphatase non-receptor type 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PTPN2provided by HGNC
Official Full Name: protein tyrosine phosphatase non-receptor type 2provided by HGNC
Primary source: HGNC:HGNC:9650
See related: Ensembl:ENSG00000175354 MIM:176887
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: PTN2; PTPT; TCPTP; TC-PTP; TCELLPTP
Summary: The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. Members of the PTP family share a highly conserved catalytic motif, which is essential for the catalytic activity. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. Epidermal growth factor receptor and the adaptor protein Shc were reported to be substrates of this PTP, which suggested the roles in growth factor mediated cell signaling. Multiple alternatively spliced transcript variants encoding different isoforms have been found. Two highly related but distinctly processed pseudogenes that localize to chromosomes 1 and 13, respectively, have been reported. [provided by RefSeq, May 2011]
Expression: Ubiquitous expression in appendix (RPKM 7.7), lymph node (RPKM 7.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 18p11.21

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
109.20210514	current	GRCh38.p13 (GCF_000001405.39)	18	NC_000018.10 (12785478..12884351, complement)
105.20201022	previous assembly	GRCh37.p13 (GCF_000001405.25)	18	NC_000018.9 (12785477..12884236, complement)

Chromosome 18 - NC_000018.10 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?

Proteasome regulation by reversible tyrosine phosphorylation at the membrane.
Title: Proteasome regulation by reversible tyrosine phosphorylation at the membrane.
Protein tyrosine phosphatase nonreceptor type 2 controls colorectal cancer development.
Title: Protein tyrosine phosphatase nonreceptor type 2 controls colorectal cancer development.
Protein tyrosine phosphatome metabolic screen identifies TC-PTP as a positive regulator of cancer cell bioenergetics and mitochondrial dynamics.
Title: Protein tyrosine phosphatome metabolic screen identifies TC-PTP as a positive regulator of cancer cell bioenergetics and mitochondrial dynamics.
Increased Plasma Soluble Interleukin-2 Receptor Alpha Levels in Patients With Long-Term Type 1 Diabetes With Vascular Complications Associated With IL2RA and PTPN2 Gene Polymorphisms.
Title: Increased Plasma Soluble Interleukin-2 Receptor Alpha Levels in Patients With Long-Term Type 1 Diabetes With Vascular Complications Associated With <i>IL2RA</i> and <i>PTPN2</i> Gene Polymorphisms.
PTPN2 negatively regulates macrophage inflammation in atherosclerosis.
Title: PTPN2 negatively regulates macrophage inflammation in atherosclerosis.
Optogenetic Analysis of Allosteric Control in Protein Tyrosine Phosphatases.
Title: Optogenetic Analysis of Allosteric Control in Protein Tyrosine Phosphatases.
PTPN2 Regulates Interactions Between Macrophages and Intestinal Epithelial Cells to Promote Intestinal Barrier Function.
Title: PTPN2 Regulates Interactions Between Macrophages and Intestinal Epithelial Cells to Promote Intestinal Barrier Function.
Inflammatory response or oxidative stress induces upregulation of PTPN2 and thus promotes the progression of laryngocarcinoma.
Title: Inflammatory response or oxidative stress induces upregulation of PTPN2 and thus promotes the progression of laryngocarcinoma.
PTPN2 regulates the activation of KRAS and plays a critical role in proliferation and survival of KRAS-driven cancer cells.
Title: PTPN2 regulates the activation of KRAS and plays a critical role in proliferation and survival of KRAS-driven cancer cells.
Overexpression of TC-PTP in murine epidermis attenuates skin tumor formation.
Title: Overexpression of TC-PTP in murine epidermis attenuates skin tumor formation.

Submit: New GeneRIF Correction See all GeneRIFs (111)

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
Genetics of rheumatoid arthritis contributes to biology and drug discovery. GeneReviews: Not available
Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions. GeneReviews: Not available
Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases. GeneReviews: Not available
Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. GeneReviews: Not available
Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. GeneReviews: Not available
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. GeneReviews: Not available
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. GeneReviews: Not available
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. GeneReviews: Not available
Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population. GeneReviews: Not available
Meta-analysis of genome-wide association studies in &gt;80 000 subjects identifies multiple loci for C-reactive protein levels. GeneReviews: Not available
Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci. GeneReviews: Not available
Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci. GeneReviews: Not available
Multiple common variants for celiac disease influencing immune gene expression. GeneReviews: Not available
Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. GeneReviews: Not available
Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. GeneReviews: Not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SGC31554 (e-PCR)
- UniSTS:76564

RH65175 (e-PCR)
- UniSTS:89633

sY3084 (e-PCR)
- UniSTS:515126

GDB:217060 (e-PCR)
- UniSTS:156225

STS-N53696 (e-PCR)
- UniSTS:76658

D1S1425 (e-PCR)
- UniSTS:149621

RH36905 (e-PCR)
- UniSTS:87932

RH12560 (e-PCR)
- UniSTS:84170

GDB:196599 (e-PCR)
- UniSTS:155871

ECD04345 (e-PCR)
- UniSTS:285422

STS-M78585 (e-PCR)
- UniSTS:42996

Homology

Homologs of the PTPN2 gene: The PTPN2 gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, and frog.
Orthologs from Annotation Pipeline: 418 organisms have orthologs with human gene PTPN2
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables STAT family protein binding	IEA Inferred from Electronic Annotation more info
enables integrin binding	IPI Inferred from Physical Interaction more info	PubMed
enables non-membrane spanning protein tyrosine phosphatase activity	IEA Inferred from Electronic Annotation more info
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	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 receptor tyrosine kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables syntaxin binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in B cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in T cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in erythrocyte differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in glucose homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in insulin receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of ERK1 and ERK2 cascade	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of T cell receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of chemotaxis	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of epidermal growth factor receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of inflammatory response	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of insulin receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of interferon-gamma-mediated signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of interleukin-2-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of interleukin-4-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of interleukin-6-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of lipid storage	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of macrophage colony-stimulating factor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of macrophage differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of platelet-derived growth factor receptor-beta signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of positive thymic T cell selection	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of tumor necrosis factor-mediated signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of type I interferon-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of tyrosine phosphorylation of STAT protein	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peptidyl-tyrosine dephosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of PERK-mediated unfolded protein response	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of gluconeogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of hepatocyte growth factor receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of interferon-gamma-mediated signaling pathway	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum-Golgi intermediate compartment	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
colocalizes_with plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: tyrosine-protein phosphatase non-receptor type 2

Names: T-cell protein tyrosine phosphatase

NP_001193942.1

EC 3.1.3.48

NP_001295216.1

EC 3.1.3.48

NP_002819.2

EC 3.1.3.48

NP_536347.1

EC 3.1.3.48

NP_536348.1

EC 3.1.3.48

XP_005258181.1

EC 3.1.3.48

XP_005258182.1

EC 3.1.3.48

XP_011524007.1

EC 3.1.3.48

XP_011524008.1

EC 3.1.3.48

XP_011524009.1

EC 3.1.3.48

XP_016881373.1

EC 3.1.3.48

XP_016881374.1

EC 3.1.3.48

XP_016881375.1

EC 3.1.3.48

XP_016881376.1

EC 3.1.3.48

XP_016881377.1

EC 3.1.3.48

XP_024306996.1

EC 3.1.3.48

XP_024306997.1

EC 3.1.3.48

XP_024306998.1

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_029116.1 RefSeqGene

Range

5001..103858

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001207013.2 → NP_001193942.1 tyrosine-protein phosphatase non-receptor type 2 isoform 4

See identical proteins and their annotated locations for NP_001193942.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) contains an additional in-frame exon in the middle coding region and an alternate 3' region, which includes a part of the C-terminal coding region, when compared to variant 1. The resulting isoform (4) has an additional internal segment and a shorter and distinct C-terminus, as compared to isoform 1.

Source sequence(s)

AK225706, BG699440, BQ010946

Consensus CDS

CCDS59306.1

UniProtKB/Swiss-Prot

P17706

Related

ENSP00000466936.1, ENST00000591115.5

Conserved Domains (1) summary

cl28904
Location:19 → 295

PTP_DSP_cys; cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily
NM_001308287.1 → NP_001295216.1 tyrosine-protein phosphatase non-receptor type 2 isoform 5

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation from an alternate start codon compared to variant 1. The resulting isoform (5) has a shorter and distinct N-terminus, as compared to isoform 1.

Source sequence(s)

AB209569, AP001077

Consensus CDS

CCDS77155.1

UniProtKB/TrEMBL

K7EQG9, Q59F91

Related

ENSP00000467823.1, ENST00000591497.5

Conserved Domains (2) summary

cd00047
Location:26 → 245

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 ...

pfam00102
Location:26 → 245

Y_phosphatase; Protein-tyrosine phosphatase
NM_002828.4 → NP_002819.2 tyrosine-protein phosphatase non-receptor type 2 isoform 1

See identical proteins and their annotated locations for NP_002819.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AB209569, AK292570, AP001077, BG699440, DB350067

Consensus CDS

CCDS11865.1

UniProtKB/Swiss-Prot

P17706

UniProtKB/TrEMBL

Q59F91

Related

ENSP00000311857.3, ENST00000309660.10

Conserved Domains (1) summary

cd14607
Location:19 → 272

PTPc-N2; catalytic domain of tyrosine-protein phosphatase non-receptor type 2
NM_080422.3 → NP_536347.1 tyrosine-protein phosphatase non-receptor type 2 isoform 2

See identical proteins and their annotated locations for NP_536347.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate 3' region, which includes a part of the C-terminal coding region, when compared to variant 1. The resulting isoform (2) has a shorter and distinct C-terminus, as compared to isoform 1.

Source sequence(s)

AK290649, BG699440, BQ010946

Consensus CDS

CCDS11863.1

UniProtKB/Swiss-Prot

P17706

UniProtKB/TrEMBL

A8K3N4

Related

ENSP00000320298.3, ENST00000327283.7

Conserved Domains (1) summary

cd14607
Location:19 → 272

PTPc-N2; catalytic domain of tyrosine-protein phosphatase non-receptor type 2
NM_080423.3 → NP_536348.1 tyrosine-protein phosphatase non-receptor type 2 isoform 3

See identical proteins and their annotated locations for NP_536348.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an alternate 3' region, which includes a part of the C-terminal coding region, when compared to variant 1. The resulting isoform (3) has a shorter and distinct C-terminus, as compared to isoform 1.

Source sequence(s)

BC016727, BQ010946

Consensus CDS

CCDS11864.1

UniProtKB/Swiss-Prot

P17706

Related

ENSP00000320546.3, ENST00000353319.8

Conserved Domains (2) summary

smart00194
Location:5 → 274

PTPc; Protein tyrosine phosphatase, catalytic domain

cd00047
Location:45 → 274

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: Homo sapiens Updated Annotation Release 109.20210514

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000018.10 Reference GRCh38.p13 Primary Assembly

Range

12785478..12884351 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005258125.4 → XP_005258182.1 tyrosine-protein phosphatase non-receptor type 2 isoform X2

Conserved Domains (1) summary

cl28904
Location:19 → 295

PTP_DSP_cys; cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily
XM_017025888.2 → XP_016881377.1 tyrosine-protein phosphatase non-receptor type 2 isoform X10

Conserved Domains (2) summary

cd00047
Location:1 → 175

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 ...

pfam00102
Location:1 → 175

Y_phosphatase; Protein-tyrosine phosphatase
XM_024451228.1 → XP_024306996.1 tyrosine-protein phosphatase non-receptor type 2 isoform X7

Conserved Domains (1) summary

pfam00102
Location:42 → 229

Y_phosphatase; Protein-tyrosine phosphatase
XM_017025884.1 → XP_016881373.1 tyrosine-protein phosphatase non-receptor type 2 isoform X4
XM_017025887.2 → XP_016881376.1 tyrosine-protein phosphatase non-receptor type 2 isoform X9
XM_005258124.4 → XP_005258181.1 tyrosine-protein phosphatase non-receptor type 2 isoform X1

Conserved Domains (1) summary

cl28904
Location:19 → 295

PTP_DSP_cys; cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily
XM_017025886.1 → XP_016881375.1 tyrosine-protein phosphatase non-receptor type 2 isoform X8

UniProtKB/TrEMBL

D3DUJ3

Conserved Domains (1) summary

cd00047
Location:1 → 175

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_011525706.2 → XP_011524008.1 tyrosine-protein phosphatase non-receptor type 2 isoform X6

Conserved Domains (1) summary

cl28904
Location:19 → 227

PTP_DSP_cys; cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily
XM_011525705.3 → XP_011524007.1 tyrosine-protein phosphatase non-receptor type 2 isoform X3

Conserved Domains (1) summary

cl28904
Location:26 → 266

PTP_DSP_cys; cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily
XM_017025885.2 → XP_016881374.1 tyrosine-protein phosphatase non-receptor type 2 isoform X5

UniProtKB/TrEMBL

K7EQG9

Conserved Domains (2) summary

cd00047
Location:26 → 245

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 ...

pfam00102
Location:26 → 245

Y_phosphatase; Protein-tyrosine phosphatase
XM_024451229.1 → XP_024306997.1 tyrosine-protein phosphatase non-receptor type 2 isoform X8

Related

ENSP00000493693.1, ENST00000645191.1

Conserved Domains (1) summary

cd00047
Location:1 → 175

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_024451230.1 → XP_024306998.1 tyrosine-protein phosphatase non-receptor type 2 isoform X8

Related

ENSP00000496181.1, ENST00000646492.1

Conserved Domains (1) summary

cd00047
Location:1 → 175

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_011525707.2 → XP_011524009.1 tyrosine-protein phosphatase non-receptor type 2 isoform X11

Conserved Domains (2) summary

cd00047
Location:8 → 118

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 ...

pfam00102
Location:9 → 118

Y_phosphatase; Protein-tyrosine phosphatase