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P29350

- PTN6_HUMAN

UniProt

P29350 - PTN6_HUMAN

Protein

Tyrosine-protein phosphatase non-receptor type 6

Gene

PTPN6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 176 (01 Oct 2014)
      Sequence version 1 (01 Dec 1992)
      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.PROSITE-ProRule annotation

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei419 – 4191SubstrateBy similarity
    Active sitei453 – 4531Phosphocysteine intermediate
    Binding sitei500 – 5001SubstrateBy similarity

    GO - Molecular functioni

    1. protein binding Source: UniProtKB
    2. protein kinase binding Source: UniProtKB
    3. protein tyrosine phosphatase activity Source: Reactome
    4. transmembrane receptor protein tyrosine phosphatase activity Source: UniProtKB

    GO - Biological processi

    1. apoptotic process Source: ProtInc
    2. B cell receptor signaling pathway Source: Ensembl
    3. blood coagulation Source: Reactome
    4. cell differentiation Source: UniProtKB
    5. cell proliferation Source: UniProtKB
    6. cytokine-mediated signaling pathway Source: Reactome
    7. G-protein coupled receptor signaling pathway Source: ProtInc
    8. interferon-gamma-mediated signaling pathway Source: Reactome
    9. JAK-STAT cascade involved in growth hormone signaling pathway Source: Reactome
    10. leukocyte migration Source: Reactome
    11. natural killer cell mediated cytotoxicity Source: Ensembl
    12. negative regulation of cell proliferation Source: UniProtKB
    13. negative regulation of humoral immune response mediated by circulating immunoglobulin Source: Ensembl
    14. negative regulation of MAP kinase activity Source: Ensembl
    15. negative regulation of peptidyl-tyrosine phosphorylation Source: BHF-UCL
    16. negative regulation of T cell proliferation Source: Ensembl
    17. negative regulation of T cell receptor signaling pathway Source: Ensembl
    18. peptidyl-tyrosine phosphorylation Source: UniProtKB
    19. positive regulation of cell proliferation Source: BHF-UCL
    20. positive regulation of phosphatidylinositol 3-kinase signaling Source: BHF-UCL
    21. protein dephosphorylation Source: UniProtKB
    22. regulation of B cell differentiation Source: Ensembl
    23. regulation of ERK1 and ERK2 cascade Source: UniProtKB
    24. regulation of G1/S transition of mitotic cell cycle Source: BHF-UCL
    25. regulation of interferon-gamma-mediated signaling pathway Source: Reactome
    26. regulation of type I interferon-mediated signaling pathway Source: Reactome
    27. T cell costimulation Source: Reactome
    28. type I interferon signaling pathway Source: Reactome

    Keywords - Molecular functioni

    Hydrolase, Protein phosphatase

    Enzyme and pathway databases

    ReactomeiREACT_111133. Growth hormone receptor signaling.
    REACT_111225. Regulation of KIT signaling.
    REACT_12519. PECAM1 interactions.
    REACT_19324. PD-1 signaling.
    REACT_19344. Costimulation by the CD28 family.
    REACT_23837. Interleukin-3, 5 and GM-CSF signaling.
    REACT_23879. Platelet sensitization by LDL.
    REACT_23891. Interleukin receptor SHC signaling.
    REACT_23916. Signal regulatory protein (SIRP) family interactions.
    REACT_24980. Regulation of IFNG signaling.
    REACT_25078. Interferon gamma signaling.
    REACT_25162. Interferon alpha/beta signaling.
    REACT_25216. Regulation of IFNA signaling.
    SignaLinkiP29350.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tyrosine-protein phosphatase non-receptor type 6 (EC:3.1.3.48)
    Alternative name(s):
    Hematopoietic cell protein-tyrosine phosphatase
    Protein-tyrosine phosphatase 1C
    Short name:
    PTP-1C
    Protein-tyrosine phosphatase SHP-1
    SH-PTP1
    Gene namesi
    Name:PTPN6
    Synonyms:HCP, PTP1C
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:9658. PTPN6.

    Subcellular locationi

    Cytoplasm. Nucleus
    Note: In neurons, translocates into the nucleus after treatment with angiotensin II By similarity. Shuttles between the cytoplasm and nucleus via its association with PDPK1.By similarity

    GO - Cellular componenti

    1. alpha-beta T cell receptor complex Source: Ensembl
    2. cytoplasm Source: UniProtKB
    3. cytosol Source: Reactome
    4. extracellular vesicular exosome Source: UniProt
    5. membrane Source: ProtInc
    6. nucleolus Source: HPA
    7. nucleus Source: BHF-UCL

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA34002.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 595595Tyrosine-protein phosphatase non-receptor type 6PRO_0000094758Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei64 – 641Phosphotyrosine2 Publications
    Modified residuei377 – 3771PhosphotyrosineBy similarity
    Modified residuei536 – 5361PhosphotyrosineBy similarity
    Modified residuei564 – 5641Phosphotyrosine; by LYN2 Publications

    Post-translational modificationi

    Phosphorylated on tyrosine residues. Binding of KITLG/SCF to KIT increases tyrosine phosphorylation By similarity. Phosphorylation at Tyr-564 enhances phosphatase activity.By similarity3 Publications

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiP29350.
    PaxDbiP29350.
    PRIDEiP29350.

    2D gel databases

    OGPiP29350.

    PTM databases

    PhosphoSiteiP29350.

    Miscellaneous databases

    PMAP-CutDBP29350.

    Expressioni

    Tissue specificityi

    Isoform 1 is expressed in hematopoietic cells. Isoform 2 is expressed in non-hematopoietic cells.

    Gene expression databases

    ArrayExpressiP29350.
    BgeeiP29350.
    CleanExiHS_PTPN6.
    GenevestigatoriP29350.

    Organism-specific databases

    HPAiCAB004572.
    HPA001466.

    Interactioni

    Subunit structurei

    Monomer. Interacts with MTUS1 By similarity. Interacts with MILR1 (tyrosine-phosphorylated). Interacts with KIT By similarity. Binds PTPNS1, LILRB1 and LILRB2. Interacts with FCRL2, FCRL3, FCRL4, CD300LF, CDK2 and CD84. 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. Interacts with the tyrosine phosphorylated form of PDPK1.By similarity12 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CASP8Q147903EBI-78260,EBI-78060
    CD22P202734EBI-78260,EBI-78277
    CD33P201388EBI-78260,EBI-3906571
    CD37P110494EBI-78260,EBI-6139068
    EPORP1923511EBI-78260,EBI-617321
    FCGR2BP319943EBI-78260,EBI-724784
    KIR2DL1P436264EBI-78260,EBI-8684277
    KIR2DL3P4362813EBI-78260,EBI-8632435
    LAIR1Q6GTX85EBI-78260,EBI-965864
    LCKP062395EBI-78260,EBI-1348
    PECAM1P162844EBI-78260,EBI-716404
    PILRAQ9UKJ15EBI-78260,EBI-965833
    ROS1P089222EBI-78260,EBI-7371065
    tirB7UM994EBI-78260,EBI-2504426From a different organism.
    tirQ7DB772EBI-78260,EBI-6480811From a different organism.

    Protein-protein interaction databases

    BioGridi111742. 58 interactions.
    DIPiDIP-31002N.
    IntActiP29350. 43 interactions.
    MINTiMINT-134053.
    STRINGi9606.ENSP00000391592.

    Structurei

    Secondary structure

    1
    595
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi11 – 2111
    Beta strandi26 – 316
    Beta strandi33 – 4513
    Beta strandi48 – 558
    Beta strandi57 – 593
    Beta strandi61 – 633
    Beta strandi68 – 703
    Helixi72 – 809
    Beta strandi89 – 913
    Helixi105 – 1073
    Beta strandi111 – 1144
    Helixi117 – 12711
    Beta strandi132 – 1376
    Beta strandi139 – 1413
    Beta strandi145 – 15410
    Beta strandi155 – 1573
    Beta strandi162 – 1709
    Helixi172 – 1743
    Beta strandi175 – 1817
    Beta strandi184 – 1863
    Helixi187 – 19711
    Beta strandi199 – 2013
    Beta strandi202 – 2043
    Beta strandi205 – 2073
    Helixi221 – 2233
    Beta strandi236 – 2383
    Helixi244 – 25613
    Turni257 – 2593
    Helixi263 – 2664
    Helixi268 – 2736
    Beta strandi275 – 2784
    Turni283 – 2853
    Beta strandi286 – 2883
    Beta strandi290 – 2923
    Beta strandi294 – 2963
    Turni297 – 3004
    Beta strandi301 – 3077
    Beta strandi309 – 3124
    Helixi314 – 3163
    Beta strandi321 – 3244
    Helixi329 – 3313
    Helixi332 – 34110
    Beta strandi346 – 3494
    Beta strandi353 – 3553
    Beta strandi356 – 3583
    Beta strandi371 – 3744
    Beta strandi377 – 38610
    Beta strandi388 – 39912
    Helixi400 – 4023
    Beta strandi403 – 4053
    Beta strandi407 – 4148
    Beta strandi419 – 4213
    Beta strandi424 – 4263
    Helixi427 – 44216
    Beta strandi443 – 4453
    Beta strandi449 – 4524
    Beta strandi454 – 4574
    Helixi458 – 47619
    Helixi484 – 4929
    Helixi502 – 52322

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1FPRX-ray2.50A243-526[»]
    1GWZX-ray2.50A243-541[»]
    1X6CNMR-A110-214[»]
    2B3OX-ray2.80A1-532[»]
    2RMXNMR-A110-214[»]
    2YU7NMR-A110-214[»]
    3PS5X-ray3.10A1-595[»]
    4GRYX-ray1.70A243-528[»]
    4GRZX-ray1.37A243-528[»]
    4GS0X-ray1.80A/B243-528[»]
    4HJPX-ray1.40A243-528[»]
    4HJQX-ray1.80A/B243-528[»]
    ProteinModelPortaliP29350.
    SMRiP29350. Positions 1-529.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP29350.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini4 – 10097SH2 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini110 – 213104SH2 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini244 – 515272Tyrosine-protein phosphatasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni453 – 4597Substrate bindingBy similarity

    Domaini

    The N-terminal SH2 domain functions as an auto-inhibitory domain, blocking the catalytic domain in the ligand-free close conformation.2 Publications

    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.
    HOGENOMiHOG000273907.
    HOVERGENiHBG000223.
    InParanoidiP29350.
    KOiK05697.
    OMAiQAKGEPW.
    PhylomeDBiP29350.
    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 (4)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P29350-1) [UniParc]FASTAAdd to Basket

    Also known as: Long

    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

    MVRWFHRDLS GLDAETLLKG RGVHGSFLAR PSRKNQGDFS LSVRVGDQVT    50
    HIRIQNSGDF YDLYGGEKFA TLTELVEYYT QQQGVLQDRD GTIIHLKYPL 100
    NCSDPTSERW YHGHMSGGQA ETLLQAKGEP WTFLVRESLS QPGDFVLSVL 150
    SDQPKAGPGS PLRVTHIKVM CEGGRYTVGG LETFDSLTDL VEHFKKTGIE 200
    EASGAFVYLR QPYYATRVNA ADIENRVLEL NKKQESEDTA KAGFWEEFES 250
    LQKQEVKNLH QRLEGQRPEN KGKNRYKNIL PFDHSRVILQ GRDSNIPGSD 300
    YINANYIKNQ LLGPDENAKT YIASQGCLEA TVNDFWQMAW QENSRVIVMT 350
    TREVEKGRNK CVPYWPEVGM QRAYGPYSVT NCGEHDTTEY KLRTLQVSPL 400
    DNGDLIREIW HYQYLSWPDH GVPSEPGGVL SFLDQINQRQ ESLPHAGPII 450
    VHCSAGIGRT GTIIVIDMLM ENISTKGLDC DIDIQKTIQM VRAQRSGMVQ 500
    TEAQYKFIYV AIAQFIETTK KKLEVLQSQK GQESEYGNIT YPPAMKNAHA 550
    KASRTSSKHK EDVYENLHTK NKREEKVKKQ RSADKEKSKG SLKRK 595
    Length:595
    Mass (Da):67,561
    Last modified:December 1, 1992 - v1
    Checksum:i4D7736C21D3542D2
    GO
    Isoform 2 (identifier: P29350-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-3: MVR → MLSRG

    Show »
    Length:597
    Mass (Da):67,719
    Checksum:i6A291A2860159389
    GO
    Isoform 3 (identifier: P29350-2) [UniParc]FASTAAdd to Basket

    Also known as: Short

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

    Show »
    Length:556
    Mass (Da):63,125
    Checksum:iE903558D44643643
    GO
    Isoform 4 (identifier: P29350-4) [UniParc]FASTAAdd to Basket

    Also known as: 70-kDa, SHP-1L

    The sequence of this isoform differs from the canonical sequence as follows:
         559-595: HKEDVYENLH...EKSKGSLKRK → SLESSAGTVA...CTLRTRGRRK

    Show »
    Length:624
    Mass (Da):70,131
    Checksum:iCB73D33EA910A7A0
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti6 – 61H → L in AAA82880. (PubMed:7665165)Curated
    Sequence conflicti86 – 861L → V in AAA36610. (PubMed:1736296)Curated
    Sequence conflicti86 – 861L → V in AAD53317. (PubMed:10497187)Curated
    Sequence conflicti146 – 1461V → E in AAA82880. (PubMed:7665165)Curated
    Sequence conflicti146 – 1461V → E in AAA82879. (PubMed:7665165)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 3939Missing in isoform 3. 1 PublicationVSP_005129Add
    BLAST
    Alternative sequencei1 – 33MVR → MLSRG in isoform 2. 1 PublicationVSP_007775
    Alternative sequencei40 – 445SLSVR → MLSRG in isoform 3. 1 PublicationVSP_005130
    Alternative sequencei559 – 59537HKEDV…SLKRK → SLESSAGTVAASPVRRGGQR GLPVPGPPVLSPDLHQLPVL APLHPAADTRRMCMRTCTLR TRGRRK in isoform 4. 1 PublicationVSP_044447Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M74903 mRNA. Translation: AAA35963.1.
    X62055 mRNA. Translation: CAA43982.1.
    M77273 mRNA. Translation: AAA36610.1.
    U15528
    , U15536, U15535, U15534, U15533, U15532, U15531, U15530, U15529 Genomic DNA. Translation: AAA82880.1.
    U15528
    , U15537, U15535, U15534, U15533, U15532, U15531, U15530, U15529 Genomic DNA. Translation: AAA82879.1.
    U47924 Genomic DNA. Translation: AAB51322.1.
    U47924 Genomic DNA. Translation: AAB51323.1.
    AF178946 mRNA. Translation: AAD53317.1.
    AB079851 Genomic DNA. Translation: BAC81774.1.
    AB079851 Genomic DNA. Translation: BAC81775.1.
    AK290421 mRNA. Translation: BAF83110.1.
    CH471116 Genomic DNA. Translation: EAW88703.1.
    CH471116 Genomic DNA. Translation: EAW88704.1.
    BC002523 mRNA. Translation: AAH02523.1.
    BC007667 mRNA. Translation: AAH07667.1.
    CCDSiCCDS41744.1. [P29350-3]
    CCDS44820.1. [P29350-1]
    CCDS44821.1. [P29350-4]
    PIRiB42031. S20825.
    RefSeqiNP_002822.2. NM_002831.5. [P29350-1]
    NP_536858.1. NM_080548.4. [P29350-3]
    NP_536859.1. NM_080549.3. [P29350-4]
    UniGeneiHs.63489.

    Genome annotation databases

    EnsembliENST00000318974; ENSP00000326010; ENSG00000111679. [P29350-1]
    ENST00000399448; ENSP00000382376; ENSG00000111679. [P29350-3]
    ENST00000456013; ENSP00000391592; ENSG00000111679. [P29350-4]
    GeneIDi5777.
    KEGGihsa:5777.
    UCSCiuc001qsb.2. human. [P29350-1]
    uc009zfl.1. human. [P29350-4]
    uc010sfr.1. human. [P29350-2]

    Polymorphism databases

    DMDMi131469.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M74903 mRNA. Translation: AAA35963.1 .
    X62055 mRNA. Translation: CAA43982.1 .
    M77273 mRNA. Translation: AAA36610.1 .
    U15528
    , U15536 , U15535 , U15534 , U15533 , U15532 , U15531 , U15530 , U15529 Genomic DNA. Translation: AAA82880.1 .
    U15528
    , U15537 , U15535 , U15534 , U15533 , U15532 , U15531 , U15530 , U15529 Genomic DNA. Translation: AAA82879.1 .
    U47924 Genomic DNA. Translation: AAB51322.1 .
    U47924 Genomic DNA. Translation: AAB51323.1 .
    AF178946 mRNA. Translation: AAD53317.1 .
    AB079851 Genomic DNA. Translation: BAC81774.1 .
    AB079851 Genomic DNA. Translation: BAC81775.1 .
    AK290421 mRNA. Translation: BAF83110.1 .
    CH471116 Genomic DNA. Translation: EAW88703.1 .
    CH471116 Genomic DNA. Translation: EAW88704.1 .
    BC002523 mRNA. Translation: AAH02523.1 .
    BC007667 mRNA. Translation: AAH07667.1 .
    CCDSi CCDS41744.1. [P29350-3 ]
    CCDS44820.1. [P29350-1 ]
    CCDS44821.1. [P29350-4 ]
    PIRi B42031. S20825.
    RefSeqi NP_002822.2. NM_002831.5. [P29350-1 ]
    NP_536858.1. NM_080548.4. [P29350-3 ]
    NP_536859.1. NM_080549.3. [P29350-4 ]
    UniGenei Hs.63489.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1FPR X-ray 2.50 A 243-526 [» ]
    1GWZ X-ray 2.50 A 243-541 [» ]
    1X6C NMR - A 110-214 [» ]
    2B3O X-ray 2.80 A 1-532 [» ]
    2RMX NMR - A 110-214 [» ]
    2YU7 NMR - A 110-214 [» ]
    3PS5 X-ray 3.10 A 1-595 [» ]
    4GRY X-ray 1.70 A 243-528 [» ]
    4GRZ X-ray 1.37 A 243-528 [» ]
    4GS0 X-ray 1.80 A/B 243-528 [» ]
    4HJP X-ray 1.40 A 243-528 [» ]
    4HJQ X-ray 1.80 A/B 243-528 [» ]
    ProteinModelPortali P29350.
    SMRi P29350. Positions 1-529.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111742. 58 interactions.
    DIPi DIP-31002N.
    IntActi P29350. 43 interactions.
    MINTi MINT-134053.
    STRINGi 9606.ENSP00000391592.

    Chemistry

    BindingDBi P29350.
    ChEMBLi CHEMBL3166.

    PTM databases

    PhosphoSitei P29350.

    Polymorphism databases

    DMDMi 131469.

    2D gel databases

    OGPi P29350.

    Proteomic databases

    MaxQBi P29350.
    PaxDbi P29350.
    PRIDEi P29350.

    Protocols and materials databases

    DNASUi 5777.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000318974 ; ENSP00000326010 ; ENSG00000111679 . [P29350-1 ]
    ENST00000399448 ; ENSP00000382376 ; ENSG00000111679 . [P29350-3 ]
    ENST00000456013 ; ENSP00000391592 ; ENSG00000111679 . [P29350-4 ]
    GeneIDi 5777.
    KEGGi hsa:5777.
    UCSCi uc001qsb.2. human. [P29350-1 ]
    uc009zfl.1. human. [P29350-4 ]
    uc010sfr.1. human. [P29350-2 ]

    Organism-specific databases

    CTDi 5777.
    GeneCardsi GC12P007055.
    HGNCi HGNC:9658. PTPN6.
    HPAi CAB004572.
    HPA001466.
    MIMi 176883. gene.
    neXtProti NX_P29350.
    PharmGKBi PA34002.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5599.
    HOGENOMi HOG000273907.
    HOVERGENi HBG000223.
    InParanoidi P29350.
    KOi K05697.
    OMAi QAKGEPW.
    PhylomeDBi P29350.
    TreeFami TF351632.

    Enzyme and pathway databases

    Reactomei REACT_111133. Growth hormone receptor signaling.
    REACT_111225. Regulation of KIT signaling.
    REACT_12519. PECAM1 interactions.
    REACT_19324. PD-1 signaling.
    REACT_19344. Costimulation by the CD28 family.
    REACT_23837. Interleukin-3, 5 and GM-CSF signaling.
    REACT_23879. Platelet sensitization by LDL.
    REACT_23891. Interleukin receptor SHC signaling.
    REACT_23916. Signal regulatory protein (SIRP) family interactions.
    REACT_24980. Regulation of IFNG signaling.
    REACT_25078. Interferon gamma signaling.
    REACT_25162. Interferon alpha/beta signaling.
    REACT_25216. Regulation of IFNA signaling.
    SignaLinki P29350.

    Miscellaneous databases

    ChiTaRSi PTPN6. human.
    EvolutionaryTracei P29350.
    GeneWikii PTPN6.
    GenomeRNAii 5777.
    NextBioi 22466.
    PMAP-CutDB P29350.
    PROi P29350.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P29350.
    Bgeei P29350.
    CleanExi HS_PTPN6.
    Genevestigatori P29350.

    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. "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] (ISOFORM 1).
    2. "A protein-tyrosine phosphatase with sequence similarity to the SH2 domain of the protein-tyrosine kinases."
      Shen S.H., Bastien L., Posner B.I., Chretien P.
      Nature 352:736-739(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
      Tissue: Mammary gland.
    3. Erratum
      Shen S.H., Bastien L., Posner B.I., Chretien P.
      Nature 353:868-868(1991)
      Cited for: SEQUENCE REVISION.
    4. "Isolation of a src homology 2-containing tyrosine phosphatase."
      Plutzky J., Neel B.G., Rosenberg R.D.
      Proc. Natl. Acad. Sci. U.S.A. 89:1123-1127(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    5. "Human protein tyrosine phosphatase 1C (PTPN6) gene structure: alternate promoter usage and exon skipping generate multiple transcripts."
      Banville D., Stocco R., Shen S.H.
      Genomics 27:165-173(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1; 2 AND 3).
    6. "Large-scale sequencing in human chromosome 12p13: experimental and computational gene structure determination."
      Ansari-Lari M.A., Shen Y., Muzny D.M., Lee W., Gibbs R.A.
      Genome Res. 7:268-280(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    7. "Human 70-kDa SHP-1L differs from 68-kDa SHP-1 in its C-terminal structure and catalytic activity."
      Jin Y.J., Yu C.L., Burakoff S.J.
      J. Biol. Chem. 274:28301-28307(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
    8. "Gene silencing of SHP-1 gene in leukemias/lymphomas by aberrant methylation."
      Oka T., Ouchida M.
      Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2).
    9. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Umbilical cord blood.
    10. "The finished DNA sequence of human chromosome 12."
      Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.
      , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
      Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    11. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    12. "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] (ISOFORM 2).
      Tissue: Placenta.
    13. "Tyrosine phosphorylation of an SH2-containing protein tyrosine phosphatase is coupled to platelet thrombin receptor via a pertussis toxin-sensitive heterotrimeric G-protein."
      Li R.Y., Gaits F., Ragab A., Ragab-Thomas J.M.F., Chap H.
      EMBO J. 14:2519-2526(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION.
    14. "A novel immunoglobulin superfamily receptor for cellular and viral MHC class I molecules."
      Cosman D., Fanger N., Borges L., Kubin M., Chin W., Peterson L., Hsu M.-L.
      Immunity 7:273-282(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH LILRB1.
    15. "The MHC class I binding proteins LIR-1 and LIR-2 inhibit Fc receptor-mediated signaling in monocytes."
      Fanger N.A., Cosman D., Peterson L., Braddy S.C., Maliszewski C.R., Borges L.
      Eur. J. Immunol. 28:3423-3434(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH LILRB2.
    16. "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.
    17. "Functional interaction between SHPTP1 and the Lyn tyrosine kinase in the apoptotic response to DNA damage."
      Yoshida K., Kharbanda S., Kufe D.
      J. Biol. Chem. 274:34663-34668(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH LYN, PHOSPHORYLATION AT TYR-564.
    18. "Molecular cloning and characterization of SPAP1, an inhibitory receptor."
      Xu M.-J., Zhao R., Zhao Z.J.
      Biochem. Biophys. Res. Commun. 280:768-775(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FCRL2 AND FCRL3.
    19. "Distinct interactions of the X-linked lymphoproliferative syndrome gene product SAP with cytoplasmic domains of members of the CD2 receptor family."
      Lewis J., Eiben L.J., Nelson D.L., Cohen J.I., Nichols K.E., Ochs H.D., Notarangelo L.D., Duckett C.S.
      Clin. Immunol. 100:15-23(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CD84.
    20. "Negative regulation of Ros receptor tyrosine kinase signaling. An epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1."
      Keilhack H., Mueller M., Boehmer S.A., Frank C., Weidner K.M., Birchmeier W., Ligensa T., Berndt A., Kosmehl H., Guenther B., Mueller T., Birchmeier C., Boehmer F.D.
      J. Cell Biol. 152:325-334(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN ROS1 DEPHOSPHORYLATION, INTERACTION WITH ROS1.
    21. Cited for: INTERACTION WITH FCRL4.
    22. "IgSF13, a novel human inhibitory receptor of the immunoglobulin superfamily, is preferentially expressed in dendritic cells and monocytes."
      Sui L., Li N., Liu Q., Zhang W., Wan T., Wang B., Luo K., Sun H., Cao X.
      Biochem. Biophys. Res. Commun. 319:920-928(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CD300LF.
    23. "Signal transduction via the stem cell factor receptor/c-Kit."
      Ronnstrand L.
      Cell. Mol. Life Sci. 61:2535-2548(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON ROLE IN KIT SIGNALING.
    24. "Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor."
      Roskoski R. Jr.
      Biochem. Biophys. Res. Commun. 337:1-13(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON ROLE IN KIT SIGNALING.
    25. "An essential function for beta-arrestin 2 in the inhibitory signaling of natural killer cells."
      Yu M.-C., Su L.-L., Zou L., Liu Y., Wu N., Kong L., Zhuang Z.-H., Sun L., Liu H.P., Hu J.-H., Li D., Strominger J.L., Zang J.-W., Pei G., Ge B.-X.
      Nat. Immunol. 9:898-907(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH KIR2DL1.
    26. "The nuclear localization of 3'-phosphoinositide-dependent kinase-1 is dependent on its association with the protein tyrosine phosphatase SHP-1."
      Sephton C.F., Zhang D., Lehmann T.M., Pennington P.R., Scheid M.P., Mousseau D.D.
      Cell. Signal. 21:1634-1644(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PDPK1.
    27. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
      Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
      Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-64, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Leukemic T-cell.
    28. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    29. "Compartmentalized CDK2 is connected with SHP-1 and beta-catenin and regulates insulin internalization."
      Fiset A., Xu E., Bergeron S., Marette A., Pelletier G., Siminovitch K.A., Olivier M., Beauchemin N., Faure R.L.
      Cell. Signal. 23:911-919(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, INTERACTION WITH CDK2.
    30. "Crystal structure of the catalytic domain of protein-tyrosine phosphatase SHP-1."
      Yang J., Liang X., Niu T., Meng W., Zhao Z., Zhou G.W.
      J. Biol. Chem. 273:28199-28207(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 248-399.
    31. "Crystal structure of human protein-tyrosine phosphatase SHP-1."
      Yang J., Liu L., He D., Song X., Liang X., Zhao Z.J., Zhou G.W.
      J. Biol. Chem. 278:6516-6520(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-532, DOMAIN SH2.
    32. "Solution structures of the SH2 domain of human protein-tyrosine phosphatase SHP-1."
      RIKEN structural genomics initiative (RSGI)
      Submitted (NOV-2005) to the PDB data bank
      Cited for: STRUCTURE BY NMR OF 110-214.
    33. "Crystal structure of human protein tyrosine phosphatase SHP-1 in the open conformation."
      Wang W., Liu L., Song X., Mo Y., Komma C., Bellamy H.D., Zhao Z.J., Zhou G.W.
      J. Cell. Biochem. 112:2062-2071(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS), DOMAIN SH2.

    Entry informationi

    Entry nameiPTN6_HUMAN
    AccessioniPrimary (citable) accession number: P29350
    Secondary accession number(s): A8K306
    , G3V0F8, Q969V8, Q9UK67
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 1992
    Last sequence update: December 1, 1992
    Last modified: October 1, 2014
    This is version 176 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3