Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P41499

- PTN11_RAT

UniProt

P41499 - PTN11_RAT

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
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 138 (01 Oct 2014)
      Sequence version 4 (20 Dec 2005)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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 binding Source: UniProtKB
    7. protein domain specific binding Source: RGD
    8. protein tyrosine phosphatase activity Source: RGD

    GO - Biological processi

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

    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.

    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

    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.
    GeneTreeiENSGT00750000117233.
    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

    MTSRRWFHPN ITGVEAENLL LTRGVDGSFL ARPSKSNPGD FTLSVRRNGA    50
    VTHIKIQNTG DYYDLYGGEK FATLAELVQY YMEHHGQLKE KNGDVIELKY 100
    PLNCADPTSE RWFHGHLSGK EAEKLLTEKG KHGSFLVRES QSHPGDFVLS 150
    VRTGDDKGES NDSKSKVTHV MIRCQELKYD VGGGERFDSL TDLVEHYKKN 200
    PMVETLGTVL QLKQPLNTTR INAAEIESRV RELSKLAETT DKVKQGFWEE 250
    FETLQQQECK LLYSRKEGQR QENKNKNRYK NILPFDHTRV VLHDGDPNEP 300
    VSDYINANII MPEFETKCNN SKPKKSYIAT QGCLQNTVND FWRMVFQENS 350
    RVIVMTTKEV ERGKSKCVKY WPDECALKEY GVMRVRNVRE SAAHDYTLRE 400
    LKLSKVGQAL LQGNTERTVW QYHFRTWPDH GVPSDPGGVL DFLEEVHHKQ 450
    ESIVDAGPVV VHCSAGIGRT GTFIVIDILI DIIREKGVDC DIDVPKTIQM 500
    VRSQRSGMVQ TEAQYRFIYM AVQHYIETLQ RRIEEEQKSK RKGHEYTNIK 550
    YSLVDQTSGD QSPLPPCTPT PPCAEMREDS ARVYENVGLM QQQRSFR 597
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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 ENSGT00750000117233.
    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.

    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: October 1, 2014
    This is version 138 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