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Protein

Tyrosine-protein phosphatase non-receptor type 6

Gene

Ptpn6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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
  • phosphorylation-dependent protein binding Source: MGI
  • phosphotyrosine residue 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
  • 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 dephosphorylation 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 release of sequestered calcium ion into cytosol Source: MGI

Keywordsi

Molecular functionHydrolase, 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-512988 Interleukin-3, 5 and GM-CSF signaling
R-MMU-5690714 CD22 mediated BCR regulation
R-MMU-6798695 Neutrophil degranulation
R-MMU-877300 Interferon gamma signaling
R-MMU-909733 Interferon alpha/beta signaling
R-MMU-912526 Interleukin receptor SHC signaling
R-MMU-912694 Regulation of IFNA signaling
R-MMU-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:96055 Ptpn6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

CarbonylDBiP29351
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 MTUS1 (By similarity). Interacts with MILR1 (tyrosine-phosphorylated) (PubMed:20526344). Interacts with KIT (PubMed:9528781). Interacts with SIRPA/PTPNS1 (PubMed:9712903). Interacts with FCRL2 and FCRL4 (By similarity). Interacts with CD84 (By similarity). Interacts with CD300LF (PubMed:14662855). Interacts with CDK2 (By similarity). 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 (By similarity). Interacts with LYN (By similarity). 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). Interacts with MPIG6B (via ITIM motif) (PubMed:23112346). Interacts with KLRI1 and KLRI2 (By similarity).By similarity6 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • cell adhesion molecule binding Source: UniProtKB
  • phosphorylation-dependent protein binding Source: MGI
  • phosphotyrosine residue binding Source: MGI
  • protein kinase binding Source: MGI
  • SH2 domain binding Source: MGI
  • SH3 domain binding Source: MGI

Protein-protein interaction databases

BioGridi200256, 10 interactors
DIPiDIP-41455N
ELMiP29351
IntActiP29351, 18 interactors
MINTiP29351
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

Keywords - Domaini

Repeat, SH2 domain

Phylogenomic databases

eggNOGiKOG0790 Eukaryota
COG5599 LUCA
GeneTreeiENSGT00910000144001
HOVERGENiHBG000223
InParanoidiP29351
KOiK05697
OMAiQAKGEPW
PhylomeDBiP29351
TreeFamiTF351632

Family and domain databases

Gene3Di3.30.505.10, 2 hits
3.90.190.10, 1 hit
InterProiView protein in InterPro
IPR029021 Prot-tyrosine_phosphatase-like
IPR000242 PTPase_domain
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR016130 Tyr_Pase_AS
IPR003595 Tyr_Pase_cat
IPR012152 Tyr_Pase_non-rcpt_typ-6/11
IPR000387 TYR_PHOSPHATASE_dom
PfamiView protein in Pfam
PF00017 SH2, 2 hits
PF00102 Y_phosphatase, 1 hit
PIRSFiPIRSF000929 Tyr-Ptase_nr_6, 1 hit
PRINTSiPR00700 PRTYPHPHTASE
PR00401 SH2DOMAIN
SMARTiView protein in SMART
SM00194 PTPc, 1 hit
SM00404 PTPc_motif, 1 hit
SM00252 SH2, 2 hits
SUPFAMiSSF52799 SSF52799, 1 hit
SSF55550 SSF55550, 2 hits
PROSITEiView protein in PROSITE
PS50001 SH2, 2 hits
PS00383 TYR_PHOSPHATASE_1, 1 hit
PS50056 TYR_PHOSPHATASE_2, 1 hit
PS50055 TYR_PHOSPHATASE_PTP, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiPTN6_MOUSE
AccessioniPrimary (citable) accession number: P29351
Secondary accession number(s): O35128
, Q63872, Q63873, Q63874, Q921G3, Q9QVA6, Q9QVA7, Q9QVA8, Q9R0V6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: July 11, 2002
Last modified: April 25, 2018
This is version 193 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome
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Main funding by: National Institutes of Health