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P81718

- PTN6_RAT

UniProt

P81718 - PTN6_RAT

Protein

Tyrosine-protein phosphatase non-receptor type 6

Gene

Ptpn6

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 108 (01 Oct 2014)
      Sequence version 1 (01 May 1999)
      Previous versions | rss
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    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.By similarityPROSITE-ProRule annotation

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei421 – 4211SubstrateBy similarity
    Active sitei455 – 4551Phosphocysteine intermediatePROSITE-ProRule annotation
    Binding sitei502 – 5021SubstrateBy similarity

    GO - Molecular functioni

    1. natural killer cell lectin-like receptor binding Source: RGD
    2. protein tyrosine phosphatase activity Source: RGD
    3. transmembrane receptor protein tyrosine phosphatase activity Source: UniProtKB

    GO - Biological processi

    1. cell differentiation Source: UniProtKB
    2. cell proliferation Source: UniProtKB
    3. peptidyl-tyrosine dephosphorylation Source: GOC
    4. protein dephosphorylation Source: UniProtKB
    5. regulation of ERK1 and ERK2 cascade Source: UniProtKB
    6. response to wounding Source: RGD

    Keywords - Molecular functioni

    Hydrolase, Protein phosphatase

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tyrosine-protein phosphatase non-receptor type 6 (EC:3.1.3.48)
    Alternative name(s):
    Protein-tyrosine phosphatase SHP-1
    Gene namesi
    Name:Ptpn6
    Synonyms:Ptph6
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi620660. Ptpn6.

    Subcellular locationi

    Cytoplasm 1 Publication. Nucleus 1 Publication
    Note: In neurons, translocates into the nucleus after treatment with angiotensin II. Shuttles between the cytoplasm and nucleus via its association with PDPK By similarity.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 613613Tyrosine-protein phosphatase non-receptor type 6PRO_0000094760Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei66 – 661PhosphotyrosineBy similarity
    Modified residuei379 – 3791PhosphotyrosineBy similarity
    Modified residuei538 – 5381PhosphotyrosineBy similarity
    Modified residuei566 – 5661Phosphotyrosine; by LYNBy similarity

    Post-translational modificationi

    Phosphorylated on tyrosine residues. Binding of KITLG/SCF to KIT increases tyrosine phosphorylation By similarity. Phosphorylation at Tyr-566 enhances phosphatase activity By similarity.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiP81718.
    PRIDEiP81718.

    PTM databases

    PhosphoSiteiP81718.

    Expressioni

    Developmental stagei

    Highly expressed in embryonic cerebral cortex between day 18 and up to birth. Expression levels decrease after birth (at protein level).1 Publication

    Gene expression databases

    GenevestigatoriP81718.

    Interactioni

    Subunit structurei

    Monomer. Binds PTPNS1. Interacts with CDK2, FCRL2, FCRL3, FCRL4, CD300LF and CD84. Interacts with MILR1 (tyrosine-phosphorylated). Interacts with KIT. Interacts with KIR2DL1; the interaction is enhanced by ARRB2. Interacts (via SH2 1 domain) with ROS1; the interaction is direct and promotes ROS1 dephosphorylation. Interacts with EGFR; inhibits EGFR-dependent activation of MAPK/ERK. Interacts with LYN By similarity. Interacts with MTUS1. Interacts with the tyrosine phosphorylated form of PDPK1 By similarity.By similarity

    Protein-protein interaction databases

    BioGridi250571. 2 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliP81718.
    SMRiP81718. Positions 6-528.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini6 – 10297SH2 1CuratedPROSITE-ProRule annotationAdd
    BLAST
    Domaini112 – 215104SH2 2CuratedPROSITE-ProRule annotationAdd
    BLAST
    Domaini246 – 517272Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni455 – 4617Substrate bindingBy similarity

    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

    Contains 2 SH2 domains.CuratedPROSITE-ProRule annotation
    Contains 1 tyrosine-protein phosphatase domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, SH2 domain

    Phylogenomic databases

    eggNOGiCOG5599.
    HOGENOMiHOG000273907.
    HOVERGENiHBG000223.
    InParanoidiP81718.
    KOiK05697.
    PhylomeDBiP81718.

    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]

    Sequencei

    Sequence statusi: Complete.

    P81718-1 [UniParc]FASTAAdd to Basket

    « Hide

    MLSRGWFHRD LSGPDAETLL KGRGVPGSFL ARPSRKNQGD FSLSVRVDDQ    50
    VTHIRIQNSG DFYDLYGGEK FATSTELVEY YTQQQGILQD RDGTIIHLKY 100
    PLNCSDPTSE RWYHGHMSGG QAESLLQAKG EPWTFLVRES LSQPGDFVLS 150
    VLNDQPKAAP GSPLRVTHIK VMCEGGRYTV GGSETFDSLT DLVEHFKKTG 200
    IEEASGAFVY LRQPYYATRV NAADIENRVL ELNKKQESED TAKAGFWEEF 250
    ESLQKQEAKN LHQRLEGQRP ENKSKNRYKN ILPFDHSRVI LQGRDSNIPG 300
    SDYINANYVK NQLLGPDENS KTYIASQGCL DATVNDFWQM AWQENTRVIV 350
    MTTREVEKGR NKCVPYWPEV GTQRVYGLYS VTNCKEHDTA EYKLRTLQIS 400
    PLDNGDLVRE IWHYQYLSWP DHGVPSEPGG VLSFLDQINQ RQESLPHAGP 450
    IIVHCSAGIG RTGTIIVIDM LMESVSTKGL DCDIDIQKTI QMVRAQRSGM 500
    VQTEAQYKFI YVAIAQFIET TKKKLEIIQS QRGQESEYGN ITYPPALRSA 550
    HAKASRTSSK HKEEVYENVH SKNKKEEKVK KQRSADKEKN KGSLKRNISL 600
    TPCRGLRWAD RDL 613
    Length:613
    Mass (Da):69,578
    Last modified:May 1, 1999 - v1
    Checksum:i29364B22E8F45C87
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U77038 mRNA. Translation: AAD00262.1.
    RefSeqiNP_446360.1. NM_053908.1.
    UniGeneiRn.18985.

    Genome annotation databases

    GeneIDi116689.
    KEGGirno:116689.
    UCSCiRGD:620660. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U77038 mRNA. Translation: AAD00262.1 .
    RefSeqi NP_446360.1. NM_053908.1.
    UniGenei Rn.18985.

    3D structure databases

    ProteinModelPortali P81718.
    SMRi P81718. Positions 6-528.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 250571. 2 interactions.

    PTM databases

    PhosphoSitei P81718.

    Proteomic databases

    PaxDbi P81718.
    PRIDEi P81718.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 116689.
    KEGGi rno:116689.
    UCSCi RGD:620660. rat.

    Organism-specific databases

    CTDi 5777.
    RGDi 620660. Ptpn6.

    Phylogenomic databases

    eggNOGi COG5599.
    HOGENOMi HOG000273907.
    HOVERGENi HBG000223.
    InParanoidi P81718.
    KOi K05697.
    PhylomeDBi P81718.

    Miscellaneous databases

    NextBioi 619552.
    PROi P81718.

    Gene expression databases

    Genevestigatori P81718.

    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. "The rat SH2-containing protein-tyrosine phosphatase SHP-1 is a positive regulator of NGF-induced neuronal differentiation of PC12 cells."
      Aoki N., Yamaguchi-Aoki Y., Ullrich A.
      Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Angiotensin II-induced neural differentiation via angiotensin II type 2 (AT2) receptor-MMS2 cascade involving interaction between AT2 receptor-interacting protein and Src homology 2 domain-containing protein-tyrosine phosphatase 1."
      Li J.-M., Mogi M., Tsukuda K., Tomochika H., Iwanami J., Min L.-J., Nahmias C., Iwai M., Horiuchi M.
      Mol. Endocrinol. 21:499-511(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, INTERACTION WITH MTUS1.

    Entry informationi

    Entry nameiPTN6_RAT
    AccessioniPrimary (citable) accession number: P81718
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 19, 2003
    Last sequence update: May 1, 1999
    Last modified: October 1, 2014
    This is version 108 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3