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P29351 (PTN6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 156. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Ptpn6
Synonyms:Hcp, Hcph, Ptp1C
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length595 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.10

Catalytic activity

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

Subunit structure

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. Ref.5 Ref.9 Ref.10 Ref.11 Ref.14

Subcellular location

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.

Tissue specificity

Expressed predominantly in hematopoietic cells. Ref.8

Domain

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

Post-translational modification

Phosphorylated on tyrosine residues. Phosphorylation at Tyr-564 enhances phosphatase activity By similarity. Binding of KITLG/SCF to KIT increases tyrosine phosphorylation. Ref.7 Ref.10

Involvement in disease

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.

Sequence similarities

Belongs to the protein-tyrosine phosphatase family. Non-receptor class 2 subfamily.

Contains 2 SH2 domains.

Contains 1 tyrosine-protein phosphatase domain.

Ontologies

Keywords
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   DomainRepeat
SH2 domain
   Molecular functionHydrolase
Protein phosphatase
   PTMPhosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processB cell receptor signaling pathway

Inferred from mutant phenotype PubMed 9254656. Source: MGI

abortive mitotic cell cycle

Inferred from mutant phenotype PubMed 23509158. Source: MGI

cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

cytokine-mediated signaling pathway

Traceable author statement PubMed 8943354. Source: MGI

hematopoietic progenitor cell differentiation

Inferred from mutant phenotype PubMed 24029230. Source: MGI

intracellular signal transduction

Inferred from direct assay PubMed 10229828. Source: MGI

megakaryocyte development

Inferred from mutant phenotype PubMed 23509158. Source: MGI

natural killer cell mediated cytotoxicity

Inferred from mutant phenotype PubMed 6971254. Source: MGI

negative regulation of B cell receptor signaling pathway

Inferred from genetic interaction PubMed 23509253. Source: MGI

negative regulation of MAP kinase activity

Inferred from mutant phenotype PubMed 9064344PubMed 9254656. Source: MGI

negative regulation of MAPK cascade

Inferred from mutant phenotype PubMed 9064344PubMed 9254656. Source: MGI

negative regulation of T cell proliferation

Inferred from mutant phenotype PubMed 9064344. Source: MGI

negative regulation of T cell receptor signaling pathway

Inferred from mutant phenotype PubMed 9064344. Source: MGI

negative regulation of humoral immune response mediated by circulating immunoglobulin

Inferred from mutant phenotype PubMed 9254656. Source: MGI

negative regulation of peptidyl-tyrosine phosphorylation

Inferred from mutant phenotype PubMed 9254656. Source: MGI

peptidyl-tyrosine dephosphorylation

Inferred from direct assay PubMed 8632004PubMed 8943354PubMed 9064344. Source: GOC

peptidyl-tyrosine phosphorylation

Inferred from electronic annotation. Source: Ensembl

platelet aggregation

Inferred from mutant phenotype PubMed 23509158. Source: MGI

platelet formation

Inferred from genetic interaction PubMed 23509158. Source: MGI

positive regulation of cell adhesion mediated by integrin

Inferred from mutant phenotype PubMed 23509158. Source: MGI

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of phosphatidylinositol 3-kinase signaling

Inferred from electronic annotation. Source: Ensembl

protein dephosphorylation

Inferred from direct assay PubMed 8632004PubMed 9064344. Source: MGI

regulation of B cell differentiation

Inferred from mutant phenotype PubMed 9254656. Source: MGI

regulation of ERK1 and ERK2 cascade

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of G1/S transition of mitotic cell cycle

Inferred from electronic annotation. Source: Ensembl

regulation of release of sequestered calcium ion into cytosol

Inferred from genetic interaction PubMed 23509253. Source: MGI

   Cellular_componentalpha-beta T cell receptor complex

Inferred from direct assay PubMed 9064344. Source: MGI

cell-cell junction

Inferred from direct assay PubMed 23793062. Source: MGI

cytoplasm

Traceable author statement PubMed 8943354. Source: MGI

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionSH2 domain binding

Inferred from direct assay PubMed 8632004. Source: MGI

SH3 domain binding

Inferred from direct assay PubMed 8632004. Source: MGI

phosphotyrosine binding

Inferred from physical interaction PubMed 10229828. Source: MGI

protein binding

Inferred from physical interaction Ref.14. Source: UniProtKB

protein tyrosine phosphatase activity

Inferred from direct assay PubMed 8632004PubMed 8943354PubMed 9064344. Source: MGI

transmembrane receptor protein tyrosine phosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Cd22P353295EBI-2620699,EBI-300059
Stat1P422252EBI-2620699,EBI-647118
tirB7UM992EBI-2620699,EBI-2504426From a different organism.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P29351-1)

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.
Isoform 2 (identifier: P29351-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-3: MVR → MLSRG
Isoform 3 (identifier: P29351-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 595595Tyrosine-protein phosphatase non-receptor type 6
PRO_0000094759

Regions

Domain4 – 10097SH2 1
Domain110 – 213104SH2 2
Domain244 – 515272Tyrosine-protein phosphatase
Region453 – 4597Substrate binding By similarity

Sites

Active site4531Phosphocysteine intermediate By similarity
Binding site4191Substrate By similarity
Binding site5001Substrate By similarity

Amino acid modifications

Modified residue641Phosphotyrosine By similarity
Modified residue3771Phosphotyrosine Ref.12
Modified residue5361Phosphotyrosine Ref.12
Modified residue5641Phosphotyrosine; by LYN By similarity

Natural variations

Alternative sequence1 – 3939Missing in isoform 3.
VSP_005132
Alternative sequence1 – 33MVR → MLSRG in isoform 2.
VSP_005131
Alternative sequence40 – 445SLSVR → MLSRG in isoform 3.
VSP_005133
Natural variant77 – 9923EYYTQ…HLKYP → VPRPHIWRAGGVTAAGQGRA LD in motheaten (me).
Natural variant100 – 595496Missing in motheaten (me).

Experimental info

Sequence conflict2401A → R in AAA37796. Ref.1
Sequence conflict5721K → Q in AAA37796. Ref.1
Sequence conflict5861E → D in AAH12660. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 11, 2002. Version 2.
Checksum: CF17300D032638D2

FASTA59567,559
        10         20         30         40         50         60 
MVRWFHRDLS GPDAETLLKG RGVPGSFLAR PSRKNQGDFS LSVRVDDQVT HIRIQNSGDF 

        70         80         90        100        110        120 
YDLYGGEKFA TLTELVEYYT QQQGILQDRD GTIIHLKYPL NCSDPTSERW YHGHISGGQA 

       130        140        150        160        170        180 
ESLLQAKGEP WTFLVRESLS QPGDFVLSVL NDQPKAGPGS PLRVTHIKVM CEGGRYTVGG 

       190        200        210        220        230        240 
SETFDSLTDL VEHFKKTGIE EASGAFVYLR QPYYATRVNA ADIENRVLEL NKKQESEDTA 

       250        260        270        280        290        300 
KAGFWEEFES LQKQEVKNLH QRLEGQRPEN KSKNRYKNIL PFDHSRVILQ GRDSNIPGSD 

       310        320        330        340        350        360 
YINANYVKNQ LLGPDENSKT YIASQGCLDA TVNDFWQMAW QENTRVIVMT TREVEKGRNK 

       370        380        390        400        410        420 
CVPYWPEVGT QRVYGLYSVT NSREHDTAEY KLRTLQISPL DNGDLVREIW HYQYLSWPDH 

       430        440        450        460        470        480 
GVPSEPGGVL SFLDQINQRQ ESLPHAGPII VHCSAGIGRT GTIIVIDMLM ESISTKGLDC 

       490        500        510        520        530        540 
DIDIQKTIQM VRAQRSGMVQ TEAQYKFIYV AIAQFIETTK KKLEIIQSQK GQESEYGNIT 

       550        560        570        580        590 
YPPAVRSAHA KASRTSSKHK EEVYENVHSK SKKEEKVKKQ RSADKEKNKG SLKRK 

« Hide

Isoform 2 [UniParc].

Checksum: E8491CE77E06E989
Show »

FASTA59767,717
Isoform 3 [UniParc].

Checksum: CACF025DF9D7BC2D
Show »

FASTA55663,179

References

« Hide 'large scale' references
[1]"Protein tyrosine phosphatase containing SH2 domains: characterization, preferential expression in hematopoietic cells, and localization to human chromosome 12p12-p13."
Yi T., Cleveland J.L., Ihle J.N.
Mol. Cell. Biol. 12:836-846(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: DBA/2.
[2]"Characterization of hematopoietic intracellular protein tyrosine phosphatases: description of a phosphatase containing an SH2 domain and another enriched in proline-, glutamic acid-, serine-, and threonine-rich sequences."
Matthews R.J., Bowne D.B., Flores E., Thomas M.L.
Mol. Cell. Biol. 12:2396-2405(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Mutations at the murine motheaten locus are within the hematopoietic cell protein-tyrosine phosphatase (Hcph) gene."
Schultz L.D., Schweitzer P.A., Rajan T.V., Yi T., Ihle J.N., Matthews R.J., Thomas M.L., Beier D.R.
Cell 73:1445-1454(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS MOTHEATEN AND VIABLE MOTHEATEN.
Strain: C57BL/6J.
Tissue: Bone marrow.
[4]"Comparative sequence analysis of a gene-rich cluster at human chromosome 12p13 and its syntenic region in mouse chromosome 6."
Ansari-Lari M.A., Oeltjen J.C., Schwartz S., Zhang Z., Muzny D.M., Lu J., Gorrell J.H., Chinault A.C., Belmont J.W., Miller W., Gibbs R.A.
Genome Res. 8:29-40(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 3).
[5]"Murine SHP-1 splice variants with altered Src homology 2 (SH2) domains. Implications for the SH2-mediated intramolecular regulation of SHP-1."
Martin A., Tsui H.W., Shulman M.J., Isenman D., Tsui F.W.
J. Biol. Chem. 274:21725-21734(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), SUBUNIT.
Strain: C3H.
Tissue: Adrenal gland.
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]"Protein tyrosine phosphatase-1C is rapidly phosphorylated in tyrosine in macrophages in response to colony stimulating factor-1."
Yeung Y.-G., Berg K.L., Pixley F.J., Angeletti R.H., Stanley E.R.
J. Biol. Chem. 267:23447-23450(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 54-68; 128-135; 137-151; 242-252; 278-285; 293-308 AND 373-382, PHOSPHORYLATION.
[8]"Identification of novel protein tyrosine phosphatases of hematopoietic cells by polymerase chain reaction amplification."
Yi T., Cleveland J.L., Ihle J.N.
Blood 78:2222-2228(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 342-451, TISSUE SPECIFICITY.
Strain: BALB/c.
Tissue: Myeloid leukemia cell.
[9]"High expression of inhibitory receptor SHPS-1 and its association with protein tyrosine phosphatase SHP-1 in macrophages."
Veillette A., Thibaudeau E., Latour S.
J. Biol. Chem. 273:22719-22728(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PTPNS1.
[10]"SHP-1 binds and negatively modulates the c-Kit receptor by interaction with tyrosine 569 in the c-Kit juxtamembrane domain."
Kozlowski M., Larose L., Lee F., Le D.M., Rottapel R., Siminovitch K.A.
Mol. Cell. Biol. 18:2089-2099(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH KIT, FUNCTION IN MODULATING KIT SIGNALING, PHOSPHORYLATION.
[11]"CMRF-35-like molecule-1, a novel mouse myeloid receptor, can inhibit osteoclast formation."
Chung D.-H., Humphrey M.B., Nakamura M.C., Ginzinger D.G., Seaman W.E., Daws M.R.
J. Immunol. 171:6541-6548(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CD300LF.
Strain: C57BL/6.
[12]"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling."
Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R.
J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-377 AND TYR-536, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Mast cell.
[13]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"An immunoglobulin-like receptor, Allergin-1, inhibits immunoglobulin E-mediated immediate hypersensitivity reactions."
Hitomi K., Tahara-Hanaoka S., Someya S., Fujiki A., Tada H., Sugiyama T., Shibayama S., Shibuya K., Shibuya A.
Nat. Immunol. 11:601-607(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MILR1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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 expand/collapse EMBL AC list , U65952, U65953, U65954 Genomic DNA. Translation: AAD00152.1.
U65955 expand/collapse EMBL AC list , U65951, U65952, U65953, U65954 Genomic DNA. Translation: AAD00151.1.
BC012660 mRNA. Translation: AAH12660.1.
CCDSCCDS39628.1. [P29351-1]
CCDS51908.1. [P29351-2]
PIRA44390.
RefSeqNP_001071173.1. NM_001077705.2. [P29351-2]
NP_038573.2. NM_013545.3. [P29351-1]
UniGeneMm.271799.

3D structure databases

ProteinModelPortalP29351.
SMRP29351. Positions 1-529.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid200256. 6 interactions.
DIPDIP-41455N.
IntActP29351. 8 interactions.
MINTMINT-192591.

PTM databases

PhosphoSiteP29351.

Proteomic databases

MaxQBP29351.
PaxDbP29351.
PRIDEP29351.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000004377; ENSMUSP00000004377; ENSMUSG00000004266. [P29351-2]
ENSMUST00000112484; ENSMUSP00000108103; ENSMUSG00000004266. [P29351-1]
ENSMUST00000171549; ENSMUSP00000129124; ENSMUSG00000004266. [P29351-2]
ENSMUST00000174265; ENSMUSP00000133991; ENSMUSG00000004266. [P29351-3]
GeneID15170.
KEGGmmu:15170.
UCSCuc009drk.1. mouse. [P29351-1]

Organism-specific databases

CTD5777.
MGIMGI:96055. Ptpn6.

Phylogenomic databases

eggNOGCOG5599.
GeneTreeENSGT00750000117233.
HOVERGENHBG000223.
KOK05697.
OMAQAKGEPW.
OrthoDBEOG7NPFST.
PhylomeDBP29351.
TreeFamTF351632.

Enzyme and pathway databases

ReactomeREACT_223082. Cell-Cell communication.

Gene expression databases

ArrayExpressP29351.
BgeeP29351.
CleanExMM_PTPN6.
GenevestigatorP29351.

Family and domain databases

Gene3D3.30.505.10. 2 hits.
3.90.190.10. 1 hit.
InterProIPR029021. Prot-tyrosine_phosphatase-like.
IPR000980. SH2.
IPR000387. Tyr/Dual-sp_Pase.
IPR016130. Tyr_Pase_AS.
IPR012152. Tyr_Pase_non-rcpt_typ-6/11.
IPR000242. Tyr_Pase_rcpt/non-rcpt.
[Graphical view]
PfamPF00017. SH2. 2 hits.
PF00102. Y_phosphatase. 1 hit.
[Graphical view]
PIRSFPIRSF000929. Tyr-Ptase_nr_6. 1 hit.
PRINTSPR00700. PRTYPHPHTASE.
PR00401. SH2DOMAIN.
SMARTSM00194. PTPc. 1 hit.
SM00252. SH2. 2 hits.
[Graphical view]
SUPFAMSSF52799. SSF52799. 1 hit.
SSF55550. SSF55550. 2 hits.
PROSITEPS50001. SH2. 2 hits.
PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPTPN6. mouse.
NextBio287680.
PROP29351.
SOURCESearch...

Entry information

Entry namePTN6_MOUSE
AccessionPrimary (citable) accession number: P29351
Secondary accession number(s): O35128 expand/collapse secondary AC list , Q63872, Q63873, Q63874, Q921G3, Q9QVA6, Q9QVA7, Q9QVA8, Q9R0V6
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: July 11, 2002
Last modified: July 9, 2014
This is version 156 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot