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P41499 (PTN11_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | 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 11

EC=3.1.3.48
Alternative name(s):
Protein-tyrosine phosphatase 1D
Short name=PTP-1D
Protein-tyrosine phosphatase SYP
SH-PTP2
Short name=SHP-2
Short name=Shp2
Gene names
Name:Ptpn11
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length597 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. Dephosphorylates ROCK2 at Tyr-722 resulting in stimulatation of its RhoA binding activity By similarity.

Catalytic activity

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

Enzyme regulation

Inhibited by orthovanadate, molybdate and spermidine. Ref.2

Subunit structure

Interacts with phosphorylated SIT1, LIME1, BCAR3 and MZPL1. Interacts with FCRL3, FCRL4, FCRL6, ANKHD1, SHB, INPP5D/SHIP1 and CD84 By similarity. Interacts with MILR1 (tyrosine-phosphorylated). Interacts with FLT1 (tyrosine-phosphorylated), FLT3 (tyrosine-phosphorylated), FLT4 (tyrosine-phosphorylated), KIT and GRB2 By similarity. Interacts with PTPNS1. Interacts with KIR2DL1; the interaction is enhanced by ARRB2. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) By similarity. Interacts with GAB2 By similarity. Interacts with TERT; the interaction retains TERT in the nucleus. Interacts with PECAM1 and FER. Interacts with EPHA2 (activated); participates in PTK2/FAK1 dephosphorylation in EPHA2 downstream signaling. Interacts with PDGFRA (tyrosine phosphorylated). Interacts with PDGFRB (tyrosine phosphorylated); this interaction increases the PTPN11 phosphatase activity By similarity. Interacts with ROS1; this mediates PTPN11 phosphorylation. Ref.4 Ref.5 Ref.6

Subcellular location

Cytoplasm By similarity.

Tissue specificity

Expressed in brain, muscle and lung. Ref.2

Domain

The SH2 domains repress phosphatase activity. Binding of these domains to phosphotyrosine-containing proteins relieves this auto-inhibition, possibly by inducing a conformational change in the enzyme.

Post-translational modification

Phosphorylated on Tyr-546 and Tyr-584 upon receptor protein tyrosine kinase activation; which creates a binding site for GRB2 and other SH2-containing proteins. Phosphorylated upon activation of the receptor-type kinase FLT3. Phosphorylated upon activation of the receptor-type kinase PDGFRA. Phosphorylated by activated PDGFRB By similarity.

Sequence similarities

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

Contains 2 SH2 domains.

Contains 1 tyrosine-protein phosphatase domain.

Biophysicochemical properties

Kinetic parameters:

KM=15 mM for pNPP Ref.2

KM=13 µM for nAChR

KM=67 nM for MBP

Vmax=16 µmol/min/mg enzyme toward pNPP

Vmax=98 nmol/min/mg enzyme toward nAChR

Vmax=15 µmol/min/mg enzyme toward MBP

pH dependence:

Optimum pH is 8.5.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   DomainRepeat
SH2 domain
   Molecular functionHydrolase
Protein phosphatase
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage checkpoint

Inferred from electronic annotation. Source: Ensembl

ERBB signaling pathway

Inferred from electronic annotation. Source: Ensembl

activation of MAPK activity

Inferred from electronic annotation. Source: Ensembl

atrioventricular canal development

Inferred from electronic annotation. Source: Ensembl

axonogenesis

Inferred from electronic annotation. Source: Ensembl

brain development

Inferred from electronic annotation. Source: Ensembl

ephrin receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

face morphogenesis

Inferred from electronic annotation. Source: Ensembl

genitalia development

Inferred from electronic annotation. Source: Ensembl

glucose homeostasis

Inferred from electronic annotation. Source: Ensembl

hormone metabolic process

Inferred from electronic annotation. Source: Ensembl

hormone-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

inner ear development

Inferred from electronic annotation. Source: Ensembl

multicellular organismal reproductive process

Inferred from electronic annotation. Source: Ensembl

negative regulation of cortisol secretion

Inferred from electronic annotation. Source: Ensembl

negative regulation of growth hormone secretion

Inferred from electronic annotation. Source: Ensembl

negative regulation of insulin secretion

Inferred from electronic annotation. Source: Ensembl

neurotrophin TRK receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

organ growth

Inferred from electronic annotation. Source: Ensembl

peptidyl-tyrosine dephosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of glucose import in response to insulin stimulus

Inferred from electronic annotation. Source: Ensembl

positive regulation of hormone secretion

Inferred from electronic annotation. Source: Ensembl

protein dephosphorylation

Inferred from direct assay PubMed 15272025PubMed 7711057. Source: RGD

regulation of cell adhesion mediated by integrin

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of multicellular organism growth

Inferred from electronic annotation. Source: Ensembl

regulation of protein export from nucleus

Inferred from electronic annotation. Source: Ensembl

triglyceride metabolic process

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytosol

Inferred from direct assay PubMed 7711057. Source: RGD

mitochondrion

Inferred from direct assay PubMed 15378208. Source: RGD

nucleus

Inferred from electronic annotation. Source: Ensembl

protein complex

Inferred from direct assay PubMed 10973965. Source: RGD

   Molecular_functionD1 dopamine receptor binding

Inferred from physical interaction PubMed 23328768. Source: RGD

insulin receptor binding

Inferred from direct assay PubMed 7711057. Source: RGD

insulin receptor substrate binding

Inferred from physical interaction PubMed 12891559. Source: RGD

non-membrane spanning protein tyrosine phosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

phospholipase binding

Inferred from direct assay PubMed 16814162. Source: RGD

protein domain specific binding

Inferred from physical interaction PubMed 10973965. Source: RGD

protein tyrosine phosphatase activity

Inferred from direct assay PubMed 15272025PubMed 15378208Ref.2PubMed 7711057. Source: RGD

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P41499-1)

Also known as: PTP1Di;

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: P41499-2)

Also known as: PTP1D;

The sequence of this isoform differs from the canonical sequence as follows:
     409-412: Missing.
Note: Much higher phosphatase activity than isoform 1, optimum pH is 7.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 597596Tyrosine-protein phosphatase non-receptor type 11
PRO_0000094769

Regions

Domain6 – 10297SH2 1
Domain112 – 216105SH2 2
Domain247 – 521275Tyrosine-protein phosphatase
Region463 – 4697Substrate binding By similarity

Sites

Active site4631Phosphocysteine intermediate By similarity
Binding site4291Substrate By similarity
Binding site5101Substrate By similarity

Amino acid modifications

Modified residue21N-acetylthreonine By similarity
Modified residue621Phosphotyrosine By similarity
Modified residue631Phosphotyrosine By similarity
Modified residue661Phosphotyrosine By similarity
Modified residue2801N6-acetyllysine By similarity
Modified residue5461Phosphotyrosine; by PDGFR By similarity
Modified residue5621Phosphoserine By similarity
Modified residue5841Phosphotyrosine; by PDGFR By similarity
Modified residue5951Phosphoserine By similarity

Natural variations

Alternative sequence409 – 4124Missing in isoform 2.
VSP_016676

Experimental info

Sequence conflict751A → P in AAA20543. Ref.1
Sequence conflict5511Y → S in AAA19133. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (PTP1Di) [UniParc].

Last modified December 20, 2005. Version 4.
Checksum: 7155D1E99161F5C2

FASTA59768,458
        10         20         30         40         50         60 
MTSRRWFHPN ITGVEAENLL LTRGVDGSFL ARPSKSNPGD FTLSVRRNGA VTHIKIQNTG 

        70         80         90        100        110        120 
DYYDLYGGEK FATLAELVQY YMEHHGQLKE KNGDVIELKY PLNCADPTSE RWFHGHLSGK 

       130        140        150        160        170        180 
EAEKLLTEKG KHGSFLVRES QSHPGDFVLS VRTGDDKGES NDSKSKVTHV MIRCQELKYD 

       190        200        210        220        230        240 
VGGGERFDSL TDLVEHYKKN PMVETLGTVL QLKQPLNTTR INAAEIESRV RELSKLAETT 

       250        260        270        280        290        300 
DKVKQGFWEE FETLQQQECK LLYSRKEGQR QENKNKNRYK NILPFDHTRV VLHDGDPNEP 

       310        320        330        340        350        360 
VSDYINANII MPEFETKCNN SKPKKSYIAT QGCLQNTVND FWRMVFQENS RVIVMTTKEV 

       370        380        390        400        410        420 
ERGKSKCVKY WPDECALKEY GVMRVRNVRE SAAHDYTLRE LKLSKVGQAL LQGNTERTVW 

       430        440        450        460        470        480 
QYHFRTWPDH GVPSDPGGVL DFLEEVHHKQ ESIVDAGPVV VHCSAGIGRT GTFIVIDILI 

       490        500        510        520        530        540 
DIIREKGVDC DIDVPKTIQM VRSQRSGMVQ TEAQYRFIYM AVQHYIETLQ RRIEEEQKSK 

       550        560        570        580        590 
RKGHEYTNIK YSLVDQTSGD QSPLPPCTPT PPCAEMREDS ARVYENVGLM QQQRSFR 

« Hide

Isoform 2 (PTP1D) [UniParc].

Checksum: 3329F10F0F60AF48
Show »

FASTA59368,033

References

[1]"Identification of protein-tyrosine phosphatases prevalent in adipocytes by molecular cloning."
Ding W., Zhang W.R., Sullivan K., Hashimoto N., Goldstein B.J.
Biochem. Biophys. Res. Commun. 202:902-907(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Strain: Sprague-Dawley.
[2]"RNA splicing regulates the activity of a SH2 domain-containing protein tyrosine phosphatase."
Mei L., Dorherty C.A., Huganir R.L.
J. Biol. Chem. 269:12254-12262(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
Strain: Sprague-Dawley.
Tissue: Brain.
[3]"Purification and characterization of a rat liver protein-tyrosine phosphatase with sequence similarity to src-homology region 2."
Hiraga A., Munakata H., Hata K., Suzuki Y., Tsuiki S.
Eur. J. Biochem. 209:195-206(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE.
[4]"Activation of protein-tyrosine phosphatase SH-PTP2 by a tyrosine-based activation motif of a novel brain molecule."
Ohnishi H., Kubota M., Ohtake A., Sato K., Sano S.
J. Biol. Chem. 271:25569-25574(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PTPNS1.
[5]"A family of proteins that inhibit signalling through tyrosine kinase receptors."
Kharitonenkov A., Chen Z., Sures I., Wang H., Schilling J., Ullrich A.
Nature 386:181-186(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PTPNS1.
[6]"ROS fusion tyrosine kinase activates a SH2 domain-containing phosphatase-2/phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling axis to form glioblastoma in mice."
Charest A., Wilker E.W., McLaughlin M.E., Lane K., Gowda R., Coven S., McMahon K., Kovach S., Feng Y., Yaffe M.B., Jacks T., Housman D.
Cancer Res. 66:7473-7481(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ROS1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U09307 mRNA. Translation: AAA20543.1.
U05963 mRNA. Translation: AAA19133.1.
PIRA53593.
RefSeqNP_001171064.1. NM_001177593.1.
NP_037220.2. NM_013088.2.
UniGeneRn.98209.

3D structure databases

ProteinModelPortalP41499.
SMRP41499. Positions 3-529.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid247651. 2 interactions.
IntActP41499. 8 interactions.
MINTMINT-4591731.
STRING10116.ENSRNOP00000041842.

PTM databases

PhosphoSiteP41499.

Proteomic databases

PaxDbP41499.
PRIDEP41499.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000046323; ENSRNOP00000041842; ENSRNOG00000030124. [P41499-2]
GeneID25622.
KEGGrno:25622.
UCSCRGD:3447. rat. [P41499-1]

Organism-specific databases

CTD5781.
RGD3447. Ptpn11.

Phylogenomic databases

eggNOGCOG5599.
GeneTreeENSGT00750000117233.
HOGENOMHOG000273907.
HOVERGENHBG000223.
InParanoidP41499.
KOK07293.
OMAKEYGAMR.
OrthoDBEOG7NPFST.
PhylomeDBP41499.
TreeFamTF351632.

Enzyme and pathway databases

ReactomeREACT_197471. Cell-Cell communication.

Gene expression databases

GenevestigatorP41499.

Family and domain databases

Gene3D3.30.505.10. 2 hits.
InterProIPR000980. 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]
SUPFAMSSF55550. 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

NextBio607397.
PROP41499.

Entry information

Entry namePTN11_RAT
AccessionPrimary (citable) accession number: P41499
Secondary accession number(s): Q62626
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: December 20, 2005
Last modified: April 16, 2014
This is version 133 of the entry and version 4 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