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Protein

Tyrosine-protein phosphatase non-receptor type 6

Gene

Ptpn6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Modulates signaling by tyrosine phosphorylated cell surface receptors such as KIT and the EGF receptor/EGFR. The SH2 regions may interact with other cellular components to modulate its own phosphatase activity against interacting substrates. Together with MTUS1, induces UBE2V2 expression upon angiotensin II stimulation. Plays a key role in hematopoiesis.1 Publication

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei419SubstrateBy similarity1
Active sitei453Phosphocysteine intermediatePROSITE-ProRule annotation1
Binding sitei500SubstrateBy similarity1

GO - Molecular functioni

  • cell adhesion molecule binding Source: UniProtKB
  • phosphotyrosine binding Source: MGI
  • protein kinase binding Source: MGI
  • protein tyrosine phosphatase activity Source: MGI
  • SH2 domain binding Source: MGI
  • SH3 domain binding Source: MGI
  • transmembrane receptor protein tyrosine phosphatase activity Source: UniProtKB

GO - Biological processi

  • abortive mitotic cell cycle Source: MGI
  • B cell receptor signaling pathway Source: MGI
  • cell differentiation Source: UniProtKB
  • cell proliferation Source: UniProtKB
  • cytokine-mediated signaling pathway Source: MGI
  • hematopoietic progenitor cell differentiation Source: MGI
  • intracellular signal transduction Source: MGI
  • JAK-STAT cascade involved in growth hormone signaling pathway Source: Reactome
  • megakaryocyte development Source: MGI
  • natural killer cell mediated cytotoxicity Source: MGI
  • negative regulation of B cell receptor signaling pathway Source: MGI
  • negative regulation of humoral immune response mediated by circulating immunoglobulin Source: MGI
  • negative regulation of MAPK cascade Source: MGI
  • negative regulation of MAP kinase activity Source: MGI
  • negative regulation of peptidyl-tyrosine phosphorylation Source: MGI
  • negative regulation of T cell proliferation Source: MGI
  • negative regulation of T cell receptor signaling pathway Source: MGI
  • peptidyl-tyrosine phosphorylation Source: MGI
  • platelet aggregation Source: MGI
  • platelet formation Source: MGI
  • positive regulation of cell adhesion mediated by integrin Source: MGI
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of phosphatidylinositol 3-kinase signaling Source: MGI
  • protein dephosphorylation Source: MGI
  • regulation of B cell differentiation Source: MGI
  • regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • regulation of G1/S transition of mitotic cell cycle Source: MGI
  • regulation of interferon-gamma-mediated signaling pathway Source: Reactome
  • regulation of release of sequestered calcium ion into cytosol Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Enzyme and pathway databases

ReactomeiR-MMU-114604. GPVI-mediated activation cascade.
R-MMU-1433559. Regulation of KIT signaling.
R-MMU-388841. Costimulation by the CD28 family.
R-MMU-389948. PD-1 signaling.
R-MMU-391160. Signal regulatory protein (SIRP) family interactions.
R-MMU-512988. Interleukin-3, 5 and GM-CSF signaling.
R-MMU-6798695. Neutrophil degranulation.
R-MMU-877300. Interferon gamma signaling.
R-MMU-877312. Regulation of IFNG signaling.
R-MMU-909733. Interferon alpha/beta signaling.
R-MMU-912526. Interleukin receptor SHC signaling.
R-MMU-912694. Regulation of IFNA signaling.
R-MMU-982772. Growth hormone receptor signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein phosphatase non-receptor type 6 (EC:3.1.3.48)
Alternative name(s):
70Z-SHP
Hematopoietic cell protein-tyrosine phosphatase
PTPTY-42
Protein-tyrosine phosphatase 1C
Short name:
PTP-1C
SH-PTP1
Short name:
SHP-1
Gene namesi
Name:Ptpn6
Synonyms:Hcp, Hcph, Ptp1C
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:96055. Ptpn6.

Subcellular locationi

  • Cytoplasm
  • Nucleus By similarity

  • Note: In neurons, translocates into the nucleus after treatment with angiotensin II. Shuttles between the cytoplasm and nucleus via its association with PDPK1 (By similarity).By similarity

GO - Cellular componenti

  • alpha-beta T cell receptor complex Source: MGI
  • cell-cell junction Source: MGI
  • cytoplasm Source: MGI
  • cytosol Source: Reactome
  • extracellular exosome Source: MGI
  • nucleolus Source: MGI
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Defects in Ptpn6 are the cause of the motheaten (me) or viable motheaten (mev) phenotypes. Mice homozygous for the recessive allelic mutations develop severe defects in hematopoiesis.

Keywords - Diseasei

Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000947591 – 595Tyrosine-protein phosphatase non-receptor type 6Add BLAST595

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei10PhosphoserineBy similarity1
Modified residuei57PhosphoserineCombined sources1
Modified residuei64PhosphotyrosineBy similarity1
Modified residuei377PhosphotyrosineCombined sources1
Modified residuei536PhosphotyrosineCombined sources1
Modified residuei564Phosphotyrosine; by LYNBy similarity1

Post-translational modificationi

Phosphorylated on tyrosine residues. Phosphorylation at Tyr-564 enhances phosphatase activity (By similarity). Binding of KITLG/SCF to KIT increases tyrosine phosphorylation.By similarity2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP29351.
MaxQBiP29351.
PaxDbiP29351.
PeptideAtlasiP29351.
PRIDEiP29351.

PTM databases

iPTMnetiP29351.
PhosphoSitePlusiP29351.

Expressioni

Tissue specificityi

Expressed predominantly in hematopoietic cells.1 Publication

Gene expression databases

BgeeiENSMUSG00000004266.
CleanExiMM_PTPN6.
ExpressionAtlasiP29351. baseline and differential.
GenevisibleiP29351. MM.

Interactioni

Subunit structurei

Monomer. Interacts with FCRL2, FCRL3, FCRL4, CD84 and MTUS1 (By similarity). Binds PTPNS1. Interacts with CD300LF and CDK2. Interacts with MILR1 (tyrosine-phosphorylated). Interacts with KIR2DL1; the interaction is enhanced by ARRB2 (By similarity). Interacts (via SH2 1 domain) with ROS1; the interaction is direct and promotes ROS1 dephosphorylation (By similarity). Interacts with EGFR; inhibits EGFR-dependent activation of MAPK/ERK. Interacts with LYN (By similarity). Interacts with KIT. Interacts with the tyrosine phosphorylated form of PDPK1 (By similarity). Interacts with CEACAM1 (via cytoplasmic domain); this interaction depends on the monomer/dimer equilibrium and is phosphorylation-dependent (PubMed:19948503, PubMed:9867848).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Cd22P353295EBI-2620699,EBI-300059
Stat1P422252EBI-2620699,EBI-647118
tirB7UM992EBI-2620699,EBI-2504426From a different organism.

GO - Molecular functioni

  • cell adhesion molecule binding Source: UniProtKB
  • phosphotyrosine binding Source: MGI
  • protein kinase binding Source: MGI
  • SH2 domain binding Source: MGI
  • SH3 domain binding Source: MGI

Protein-protein interaction databases

BioGridi200256. 9 interactors.
DIPiDIP-41455N.
IntActiP29351. 8 interactors.
MINTiMINT-192591.
STRINGi10090.ENSMUSP00000004377.

Structurei

3D structure databases

ProteinModelPortaliP29351.
SMRiP29351.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 100SH2 1PROSITE-ProRule annotationAdd BLAST97
Domaini110 – 213SH2 2PROSITE-ProRule annotationAdd BLAST104
Domaini244 – 515Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd BLAST272

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni453 – 459Substrate bindingBy similarity7

Domaini

The N-terminal SH2 domain functions as an auto-inhibitory domain, blocking the catalytic domain in the ligand-free close conformation.By similarity

Sequence similaritiesi

Contains 2 SH2 domains.PROSITE-ProRule annotation
Contains 1 tyrosine-protein phosphatase domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, SH2 domain

Phylogenomic databases

eggNOGiKOG0790. Eukaryota.
COG5599. LUCA.
GeneTreeiENSGT00770000120452.
HOVERGENiHBG000223.
InParanoidiP29351.
KOiK05697.
OMAiQAKGEPW.
PhylomeDBiP29351.
TreeFamiTF351632.

Family and domain databases

Gene3Di3.30.505.10. 2 hits.
3.90.190.10. 1 hit.
InterProiIPR029021. Prot-tyrosine_phosphatase-like.
IPR000242. PTPase_domain.
IPR000980. SH2.
IPR016130. Tyr_Pase_AS.
IPR003595. Tyr_Pase_cat.
IPR012152. Tyr_Pase_non-rcpt_typ-6/11.
IPR000387. TYR_PHOSPHATASE_dom.
[Graphical view]
PfamiPF00017. SH2. 2 hits.
PF00102. Y_phosphatase. 1 hit.
[Graphical view]
PIRSFiPIRSF000929. Tyr-Ptase_nr_6. 1 hit.
PRINTSiPR00700. PRTYPHPHTASE.
PR00401. SH2DOMAIN.
SMARTiSM00194. PTPc. 1 hit.
SM00404. PTPc_motif. 1 hit.
SM00252. SH2. 2 hits.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 1 hit.
SSF55550. SSF55550. 2 hits.
PROSITEiPS50001. SH2. 2 hits.
PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P29351-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MVRWFHRDLS GPDAETLLKG RGVPGSFLAR PSRKNQGDFS LSVRVDDQVT
60 70 80 90 100
HIRIQNSGDF YDLYGGEKFA TLTELVEYYT QQQGILQDRD GTIIHLKYPL
110 120 130 140 150
NCSDPTSERW YHGHISGGQA ESLLQAKGEP WTFLVRESLS QPGDFVLSVL
160 170 180 190 200
NDQPKAGPGS PLRVTHIKVM CEGGRYTVGG SETFDSLTDL VEHFKKTGIE
210 220 230 240 250
EASGAFVYLR QPYYATRVNA ADIENRVLEL NKKQESEDTA KAGFWEEFES
260 270 280 290 300
LQKQEVKNLH QRLEGQRPEN KSKNRYKNIL PFDHSRVILQ GRDSNIPGSD
310 320 330 340 350
YINANYVKNQ LLGPDENSKT YIASQGCLDA TVNDFWQMAW QENTRVIVMT
360 370 380 390 400
TREVEKGRNK CVPYWPEVGT QRVYGLYSVT NSREHDTAEY KLRTLQISPL
410 420 430 440 450
DNGDLVREIW HYQYLSWPDH GVPSEPGGVL SFLDQINQRQ ESLPHAGPII
460 470 480 490 500
VHCSAGIGRT GTIIVIDMLM ESISTKGLDC DIDIQKTIQM VRAQRSGMVQ
510 520 530 540 550
TEAQYKFIYV AIAQFIETTK KKLEIIQSQK GQESEYGNIT YPPAVRSAHA
560 570 580 590
KASRTSSKHK EEVYENVHSK SKKEEKVKKQ RSADKEKNKG SLKRK
Length:595
Mass (Da):67,559
Last modified:July 11, 2002 - v2
Checksum:iCF17300D032638D2
GO
Isoform 2 (identifier: P29351-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-3: MVR → MLSRG

Show »
Length:597
Mass (Da):67,717
Checksum:iE8491CE77E06E989
GO
Isoform 3 (identifier: P29351-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-39: Missing.
     40-44: SLSVR → MLSRG

Show »
Length:556
Mass (Da):63,179
Checksum:iCACF025DF9D7BC2D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti240A → R in AAA37796 (PubMed:1732748).Curated1
Sequence conflicti572K → Q in AAA37796 (PubMed:1732748).Curated1
Sequence conflicti586E → D in AAH12660 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti77 – 99EYYTQ…HLKYP → VPRPHIWRAGGVTAAGQGRA LD in motheaten (me). Add BLAST23
Natural varianti100 – 595Missing in motheaten (me). Add BLAST496

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0051321 – 39Missing in isoform 3. CuratedAdd BLAST39
Alternative sequenceiVSP_0051311 – 3MVR → MLSRG in isoform 2. Curated3
Alternative sequenceiVSP_00513340 – 44SLSVR → MLSRG in isoform 3. Curated5

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M68902 mRNA. Translation: AAA37796.1.
M90389 mRNA. Translation: AAA40007.1.
S63763 mRNA. No translation available.
S63764 mRNA. No translation available.
S63803 mRNA. No translation available.
AC002397 Genomic DNA. Translation: AAC36009.1.
AC002397 Genomic DNA. Translation: AAC36008.1.
U65955
, U65952, U65953, U65954 Genomic DNA. Translation: AAD00152.1.
U65955
, U65951, U65952, U65953, U65954 Genomic DNA. Translation: AAD00151.1.
BC012660 mRNA. Translation: AAH12660.1.
CCDSiCCDS39628.1. [P29351-1]
CCDS51908.1. [P29351-2]
PIRiA44390.
RefSeqiNP_001071173.1. NM_001077705.2. [P29351-2]
NP_038573.2. NM_013545.3. [P29351-1]
UniGeneiMm.271799.

Genome annotation databases

EnsembliENSMUST00000004377; ENSMUSP00000004377; ENSMUSG00000004266. [P29351-2]
ENSMUST00000112484; ENSMUSP00000108103; ENSMUSG00000004266. [P29351-1]
ENSMUST00000171549; ENSMUSP00000129124; ENSMUSG00000004266. [P29351-2]
ENSMUST00000174265; ENSMUSP00000133991; ENSMUSG00000004266. [P29351-3]
GeneIDi15170.
KEGGimmu:15170.
UCSCiuc009drk.2. mouse. [P29351-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M68902 mRNA. Translation: AAA37796.1.
M90389 mRNA. Translation: AAA40007.1.
S63763 mRNA. No translation available.
S63764 mRNA. No translation available.
S63803 mRNA. No translation available.
AC002397 Genomic DNA. Translation: AAC36009.1.
AC002397 Genomic DNA. Translation: AAC36008.1.
U65955
, U65952, U65953, U65954 Genomic DNA. Translation: AAD00152.1.
U65955
, U65951, U65952, U65953, U65954 Genomic DNA. Translation: AAD00151.1.
BC012660 mRNA. Translation: AAH12660.1.
CCDSiCCDS39628.1. [P29351-1]
CCDS51908.1. [P29351-2]
PIRiA44390.
RefSeqiNP_001071173.1. NM_001077705.2. [P29351-2]
NP_038573.2. NM_013545.3. [P29351-1]
UniGeneiMm.271799.

3D structure databases

ProteinModelPortaliP29351.
SMRiP29351.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200256. 9 interactors.
DIPiDIP-41455N.
IntActiP29351. 8 interactors.
MINTiMINT-192591.
STRINGi10090.ENSMUSP00000004377.

PTM databases

iPTMnetiP29351.
PhosphoSitePlusiP29351.

Proteomic databases

EPDiP29351.
MaxQBiP29351.
PaxDbiP29351.
PeptideAtlasiP29351.
PRIDEiP29351.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000004377; ENSMUSP00000004377; ENSMUSG00000004266. [P29351-2]
ENSMUST00000112484; ENSMUSP00000108103; ENSMUSG00000004266. [P29351-1]
ENSMUST00000171549; ENSMUSP00000129124; ENSMUSG00000004266. [P29351-2]
ENSMUST00000174265; ENSMUSP00000133991; ENSMUSG00000004266. [P29351-3]
GeneIDi15170.
KEGGimmu:15170.
UCSCiuc009drk.2. mouse. [P29351-1]

Organism-specific databases

CTDi5777.
MGIiMGI:96055. Ptpn6.

Phylogenomic databases

eggNOGiKOG0790. Eukaryota.
COG5599. LUCA.
GeneTreeiENSGT00770000120452.
HOVERGENiHBG000223.
InParanoidiP29351.
KOiK05697.
OMAiQAKGEPW.
PhylomeDBiP29351.
TreeFamiTF351632.

Enzyme and pathway databases

ReactomeiR-MMU-114604. GPVI-mediated activation cascade.
R-MMU-1433559. Regulation of KIT signaling.
R-MMU-388841. Costimulation by the CD28 family.
R-MMU-389948. PD-1 signaling.
R-MMU-391160. Signal regulatory protein (SIRP) family interactions.
R-MMU-512988. Interleukin-3, 5 and GM-CSF signaling.
R-MMU-6798695. Neutrophil degranulation.
R-MMU-877300. Interferon gamma signaling.
R-MMU-877312. Regulation of IFNG signaling.
R-MMU-909733. Interferon alpha/beta signaling.
R-MMU-912526. Interleukin receptor SHC signaling.
R-MMU-912694. Regulation of IFNA signaling.
R-MMU-982772. Growth hormone receptor signaling.

Miscellaneous databases

ChiTaRSiPtpn6. mouse.
PROiP29351.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000004266.
CleanExiMM_PTPN6.
ExpressionAtlasiP29351. baseline and differential.
GenevisibleiP29351. MM.

Family and domain databases

Gene3Di3.30.505.10. 2 hits.
3.90.190.10. 1 hit.
InterProiIPR029021. Prot-tyrosine_phosphatase-like.
IPR000242. PTPase_domain.
IPR000980. SH2.
IPR016130. Tyr_Pase_AS.
IPR003595. Tyr_Pase_cat.
IPR012152. Tyr_Pase_non-rcpt_typ-6/11.
IPR000387. TYR_PHOSPHATASE_dom.
[Graphical view]
PfamiPF00017. SH2. 2 hits.
PF00102. Y_phosphatase. 1 hit.
[Graphical view]
PIRSFiPIRSF000929. Tyr-Ptase_nr_6. 1 hit.
PRINTSiPR00700. PRTYPHPHTASE.
PR00401. SH2DOMAIN.
SMARTiSM00194. PTPc. 1 hit.
SM00404. PTPc_motif. 1 hit.
SM00252. SH2. 2 hits.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 1 hit.
SSF55550. SSF55550. 2 hits.
PROSITEiPS50001. SH2. 2 hits.
PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPTN6_MOUSE
AccessioniPrimary (citable) accession number: P29351
Secondary accession number(s): O35128
, Q63872, Q63873, Q63874, Q921G3, Q9QVA6, Q9QVA7, Q9QVA8, Q9R0V6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: July 11, 2002
Last modified: November 30, 2016
This is version 182 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.