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P41499

- PTN11_RAT

UniProt

P41499 - PTN11_RAT

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Protein

Tyrosine-protein phosphatase non-receptor type 11

Gene

Ptpn11

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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).By similarity

Catalytic activityi

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

Enzyme regulationi

Inhibited by orthovanadate, molybdate and spermidine.1 Publication

Kineticsi

  1. KM=15 mM for pNPP1 Publication
  2. KM=13 µM for nAChR1 Publication
  3. KM=67 nM for MBP1 Publication

Vmax=16 µmol/min/mg enzyme toward pNPP1 Publication

Vmax=98 nmol/min/mg enzyme toward nAChR1 Publication

Vmax=15 µmol/min/mg enzyme toward MBP1 Publication

pH dependencei

Optimum pH is 8.5.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei429 – 4291SubstrateBy similarity
Active sitei463 – 4631Phosphocysteine intermediatePROSITE-ProRule annotation
Binding sitei510 – 5101SubstrateBy similarity

GO - Molecular functioni

  1. D1 dopamine receptor binding Source: RGD
  2. insulin receptor binding Source: RGD
  3. insulin receptor substrate binding Source: RGD
  4. non-membrane spanning protein tyrosine phosphatase activity Source: UniProtKB
  5. phospholipase binding Source: RGD
  6. protein domain specific binding Source: RGD
  7. protein tyrosine phosphatase activity Source: RGD

GO - Biological processi

  1. abortive mitotic cell cycle Source: Ensembl
  2. activation of MAPK activity Source: Ensembl
  3. atrioventricular canal development Source: Ensembl
  4. axonogenesis Source: Ensembl
  5. brain development Source: Ensembl
  6. DNA damage checkpoint Source: Ensembl
  7. ephrin receptor signaling pathway Source: UniProtKB
  8. ERBB signaling pathway Source: Ensembl
  9. face morphogenesis Source: Ensembl
  10. genitalia development Source: Ensembl
  11. glucose homeostasis Source: Ensembl
  12. hormone-mediated signaling pathway Source: Ensembl
  13. hormone metabolic process Source: Ensembl
  14. inner ear development Source: Ensembl
  15. integrin-mediated signaling pathway Source: Ensembl
  16. megakaryocyte development Source: Ensembl
  17. multicellular organismal reproductive process Source: Ensembl
  18. negative regulation of cell adhesion mediated by integrin Source: Ensembl
  19. negative regulation of cortisol secretion Source: Ensembl
  20. negative regulation of growth hormone secretion Source: Ensembl
  21. negative regulation of insulin secretion Source: Ensembl
  22. neurotrophin TRK receptor signaling pathway Source: Ensembl
  23. organ growth Source: Ensembl
  24. peptidyl-tyrosine dephosphorylation Source: UniProtKB
  25. platelet formation Source: Ensembl
  26. positive regulation of glucose import in response to insulin stimulus Source: Ensembl
  27. positive regulation of hormone secretion Source: Ensembl
  28. protein dephosphorylation Source: RGD
  29. regulation of cell adhesion mediated by integrin Source: UniProtKB
  30. regulation of multicellular organism growth Source: Ensembl
  31. regulation of protein export from nucleus Source: Ensembl
  32. triglyceride metabolic process Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Enzyme and pathway databases

ReactomeiREACT_195025. Signaling by SCF-KIT.
REACT_195204. Signaling by Leptin.
REACT_196235. Interferon alpha/beta signaling.
REACT_196236. Regulation of IFNA signaling.
REACT_196448. Regulation of IFNG signaling.
REACT_198729. Constitutive PI3K/AKT Signaling in Cancer.
REACT_198995. Negative regulation of FGFR signaling.
REACT_199007. Spry regulation of FGF signaling.
REACT_199232. Prolactin receptor signaling.
REACT_199244. Interleukin-6 signaling.
REACT_206819. Downstream signal transduction.
REACT_231872. Netrin mediated repulsion signals.
REACT_233219. Costimulation by the CD28 family.
REACT_239061. Tie2 Signaling.
REACT_239501. Signal regulatory protein (SIRP) family interactions.
REACT_240421. FRS2-mediated cascade.
REACT_240952. ERK2 activation.
REACT_244383. CTLA4 inhibitory signaling.
REACT_244635. Interleukin-3, 5 and GM-CSF signaling.
REACT_245188. GAB1 signalosome.
REACT_255658. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
REACT_256279. PI3K Cascade.
REACT_256376. PI-3K cascade.
REACT_257653. PIP3 activates AKT signaling.
REACT_260327. PD-1 signaling.
REACT_260564. ERK1 activation.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Ptpn11
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 12

Organism-specific databases

RGDi3447. Ptpn11.

Subcellular locationi

Cytoplasm By similarity

GO - Cellular componenti

  1. cytosol Source: RGD
  2. mitochondrion Source: RGD
  3. nucleus Source: Ensembl
  4. protein complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 597596Tyrosine-protein phosphatase non-receptor type 11PRO_0000094769Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylthreonineBy similarity
Modified residuei62 – 621PhosphotyrosineBy similarity
Modified residuei63 – 631PhosphotyrosineBy similarity
Modified residuei66 – 661PhosphotyrosineBy similarity
Modified residuei546 – 5461Phosphotyrosine; by PDGFRBy similarity
Modified residuei562 – 5621PhosphoserineBy similarity
Modified residuei584 – 5841Phosphotyrosine; by PDGFRBy similarity
Modified residuei595 – 5951PhosphoserineBy similarity

Post-translational modificationi

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).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiP41499.
PRIDEiP41499.

PTM databases

PhosphoSiteiP41499.

Expressioni

Tissue specificityi

Expressed in brain, muscle and lung.1 Publication

Gene expression databases

GenevestigatoriP41499.

Interactioni

Subunit structurei

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.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Jak2Q626893EBI-7180604,EBI-8656708
SirpaP977103EBI-7180604,EBI-7945080

Protein-protein interaction databases

BioGridi247651. 2 interactions.
DIPiDIP-47397N.
IntActiP41499. 8 interactions.
MINTiMINT-4591731.
STRINGi10116.ENSRNOP00000041842.

Structurei

3D structure databases

ProteinModelPortaliP41499.
SMRiP41499. Positions 3-529.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini6 – 10297SH2 1PROSITE-ProRule annotationAdd
BLAST
Domaini112 – 216105SH2 2PROSITE-ProRule annotationAdd
BLAST
Domaini247 – 521275Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni463 – 4697Substrate bindingBy similarity

Domaini

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.

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

eggNOGiCOG5599.
GeneTreeiENSGT00770000120452.
HOGENOMiHOG000273907.
HOVERGENiHBG000223.
InParanoidiP41499.
KOiK07293.
OMAiKEYGAMR.
OrthoDBiEOG7NPFST.
PhylomeDBiP41499.
TreeFamiTF351632.

Family and domain databases

Gene3Di3.30.505.10. 2 hits.
3.90.190.10. 1 hit.
InterProiIPR029021. 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]
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.
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 (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P41499-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MTSRRWFHPN ITGVEAENLL LTRGVDGSFL ARPSKSNPGD FTLSVRRNGA
60 70 80 90 100
VTHIKIQNTG DYYDLYGGEK FATLAELVQY YMEHHGQLKE KNGDVIELKY
110 120 130 140 150
PLNCADPTSE RWFHGHLSGK EAEKLLTEKG KHGSFLVRES QSHPGDFVLS
160 170 180 190 200
VRTGDDKGES NDSKSKVTHV MIRCQELKYD VGGGERFDSL TDLVEHYKKN
210 220 230 240 250
PMVETLGTVL QLKQPLNTTR INAAEIESRV RELSKLAETT DKVKQGFWEE
260 270 280 290 300
FETLQQQECK LLYSRKEGQR QENKNKNRYK NILPFDHTRV VLHDGDPNEP
310 320 330 340 350
VSDYINANII MPEFETKCNN SKPKKSYIAT QGCLQNTVND FWRMVFQENS
360 370 380 390 400
RVIVMTTKEV ERGKSKCVKY WPDECALKEY GVMRVRNVRE SAAHDYTLRE
410 420 430 440 450
LKLSKVGQAL LQGNTERTVW QYHFRTWPDH GVPSDPGGVL DFLEEVHHKQ
460 470 480 490 500
ESIVDAGPVV VHCSAGIGRT GTFIVIDILI DIIREKGVDC DIDVPKTIQM
510 520 530 540 550
VRSQRSGMVQ TEAQYRFIYM AVQHYIETLQ RRIEEEQKSK RKGHEYTNIK
560 570 580 590
YSLVDQTSGD QSPLPPCTPT PPCAEMREDS ARVYENVGLM QQQRSFR
Length:597
Mass (Da):68,458
Last modified:December 20, 2005 - v4
Checksum:i7155D1E99161F5C2
GO
Isoform 2 (identifier: P41499-2) [UniParc]FASTAAdd to Basket

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.

Show »
Length:593
Mass (Da):68,033
Checksum:i3329F10F0F60AF48
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti75 – 751A → P in AAA20543. (PubMed:8048963)Curated
Sequence conflicti551 – 5511Y → S in AAA19133. (PubMed:7512964)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei409 – 4124Missing in isoform 2. 2 PublicationsVSP_016676

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U09307 mRNA. Translation: AAA20543.1.
U05963 mRNA. Translation: AAA19133.1.
PIRiA53593.
RefSeqiNP_001171064.1. NM_001177593.1. [P41499-1]
NP_037220.2. NM_013088.2. [P41499-2]
UniGeneiRn.98209.

Genome annotation databases

EnsembliENSRNOT00000046323; ENSRNOP00000041842; ENSRNOG00000030124. [P41499-2]
GeneIDi25622.
KEGGirno:25622.
UCSCiRGD:3447. rat. [P41499-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U09307 mRNA. Translation: AAA20543.1 .
U05963 mRNA. Translation: AAA19133.1 .
PIRi A53593.
RefSeqi NP_001171064.1. NM_001177593.1. [P41499-1 ]
NP_037220.2. NM_013088.2. [P41499-2 ]
UniGenei Rn.98209.

3D structure databases

ProteinModelPortali P41499.
SMRi P41499. Positions 3-529.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 247651. 2 interactions.
DIPi DIP-47397N.
IntActi P41499. 8 interactions.
MINTi MINT-4591731.
STRINGi 10116.ENSRNOP00000041842.

PTM databases

PhosphoSitei P41499.

Proteomic databases

PaxDbi P41499.
PRIDEi P41499.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000046323 ; ENSRNOP00000041842 ; ENSRNOG00000030124 . [P41499-2 ]
GeneIDi 25622.
KEGGi rno:25622.
UCSCi RGD:3447. rat. [P41499-1 ]

Organism-specific databases

CTDi 5781.
RGDi 3447. Ptpn11.

Phylogenomic databases

eggNOGi COG5599.
GeneTreei ENSGT00770000120452.
HOGENOMi HOG000273907.
HOVERGENi HBG000223.
InParanoidi P41499.
KOi K07293.
OMAi KEYGAMR.
OrthoDBi EOG7NPFST.
PhylomeDBi P41499.
TreeFami TF351632.

Enzyme and pathway databases

Reactomei REACT_195025. Signaling by SCF-KIT.
REACT_195204. Signaling by Leptin.
REACT_196235. Interferon alpha/beta signaling.
REACT_196236. Regulation of IFNA signaling.
REACT_196448. Regulation of IFNG signaling.
REACT_198729. Constitutive PI3K/AKT Signaling in Cancer.
REACT_198995. Negative regulation of FGFR signaling.
REACT_199007. Spry regulation of FGF signaling.
REACT_199232. Prolactin receptor signaling.
REACT_199244. Interleukin-6 signaling.
REACT_206819. Downstream signal transduction.
REACT_231872. Netrin mediated repulsion signals.
REACT_233219. Costimulation by the CD28 family.
REACT_239061. Tie2 Signaling.
REACT_239501. Signal regulatory protein (SIRP) family interactions.
REACT_240421. FRS2-mediated cascade.
REACT_240952. ERK2 activation.
REACT_244383. CTLA4 inhibitory signaling.
REACT_244635. Interleukin-3, 5 and GM-CSF signaling.
REACT_245188. GAB1 signalosome.
REACT_255658. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
REACT_256279. PI3K Cascade.
REACT_256376. PI-3K cascade.
REACT_257653. PIP3 activates AKT signaling.
REACT_260327. PD-1 signaling.
REACT_260564. ERK1 activation.

Miscellaneous databases

NextBioi 607397.
PROi P41499.

Gene expression databases

Genevestigatori P41499.

Family and domain databases

Gene3Di 3.30.505.10. 2 hits.
3.90.190.10. 1 hit.
InterProi IPR029021. 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 ]
Pfami PF00017. SH2. 2 hits.
PF00102. Y_phosphatase. 1 hit.
[Graphical view ]
PIRSFi PIRSF000929. Tyr-Ptase_nr_6. 1 hit.
PRINTSi PR00700. PRTYPHPHTASE.
PR00401. SH2DOMAIN.
SMARTi SM00194. PTPc. 1 hit.
SM00252. SH2. 2 hits.
[Graphical view ]
SUPFAMi SSF52799. SSF52799. 1 hit.
SSF55550. SSF55550. 2 hits.
PROSITEi PS50001. SH2. 2 hits.
PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50055. TYR_PHOSPHATASE_PTP. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiPTN11_RAT
AccessioniPrimary (citable) accession number: P41499
Secondary accession number(s): Q62626
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: December 20, 2005
Last modified: November 26, 2014
This is version 140 of the entry and version 4 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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3