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Q13882

- PTK6_HUMAN

UniProt

Q13882 - PTK6_HUMAN

Protein

Protein-tyrosine kinase 6

Gene

PTK6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 156 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    Functioni

    Non-receptor tyrosine-protein kinase implicated in the regulation of a variety of signaling pathways that control the differentiation and maintenance of normal epithelia, as well as tumor growth. Function seems to be context dependent and differ depending on cell type, as well as its intracellular localization. A number of potential nuclear and cytoplasmic substrates have been identified. These include the RNA-binding proteins: KHDRBS1/SAM68, KHDRBS2/SLM1, KHDRBS3/SLM2 and SFPQ/PSF; transcription factors: STAT3 and STAT5A/B and a variety of signaling molecules: ARHGAP35/p190RhoGAP, PXN/paxillin, BTK/ATK, STAP2/BKS. Associates also with a variety of proteins that are likely upstream of PTK6 in various signaling pathways, or for which PTK6 may play an adapter-like role. These proteins include ADAM15, EGFR, ERBB2, ERBB3 and IRS4. In normal or non-tumorigenic tissues, PTK6 promotes cellular differentiation and apoptosis. In tumors PTK6 contributes to cancer progression by sensitizing cells to mitogenic signals and enhancing proliferation, anchorage-independent survival and migration/invasion. Association with EGFR, ERBB2, ERBB3 may contribute to mammary tumor development and growth through enhancement of EGF-induced signaling via BTK/AKT and PI3 kinase. Contributes to migration and proliferation by contributing to EGF-mediated phosphorylation of ARHGAP35/p190RhoGAP, which promotes association with RASA1/p120RasGAP, inactivating RhoA while activating RAS. EGF stimulation resulted in phosphorylation of PNX/Paxillin by PTK6 and activation of RAC1 via CRK/CrKII, thereby promoting migration and invasion. PTK6 activates STAT3 and STAT5B to promote proliferation. Nuclear PTK6 may be important for regulating growth in normal epithelia, while cytoplasmic PTK6 might activate oncogenic signaling pathways.
    Isoform 2 inhibits PTK6 phosphorylation and PTK6 association with other tyrosine-phosphorylated proteins.

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

    Enzyme regulationi

    Activated by EGF, NRG1 and IGF1. Inhibited by SOCS3 to phosphorylate STAT3. Stabilized in the inactive form by an association between the SH3 domain and the SH2-TK linker region. Interaction between Trp-184 within SH2-TK linker region and the catalytic domain appears essential for positive regulation of kinase activity.5 Publications

    Kineticsi

    1. KM=83 µM for ATP1 Publication

    Vmax=37 nmol/min/mg enzyme1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei219 – 2191ATPPROSITE-ProRule annotation
    Active sitei312 – 3121Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi197 – 2059ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. identical protein binding Source: IntAct
    3. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB
    4. protein binding Source: UniProtKB
    5. protein serine/threonine kinase activity Source: Ensembl

    GO - Biological processi

    1. cell migration Source: UniProtKB
    2. cellular response to retinoic acid Source: BHF-UCL
    3. intestinal epithelial cell differentiation Source: Ensembl
    4. negative regulation of growth Source: Ensembl
    5. negative regulation of protein tyrosine kinase activity Source: UniProtKB
    6. positive regulation of neuron projection development Source: BHF-UCL
    7. protein autophosphorylation Source: UniProtKB
    8. protein phosphorylation Source: ProtInc
    9. tyrosine phosphorylation of Stat3 protein Source: UniProtKB
    10. tyrosine phosphorylation of Stat5 protein Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Transferase, Tyrosine-protein kinase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.10.2. 2681.
    SignaLinkiQ13882.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Protein-tyrosine kinase 6 (EC:2.7.10.2)
    Alternative name(s):
    Breast tumor kinase
    Tyrosine-protein kinase BRK
    Gene namesi
    Name:PTK6
    Synonyms:BRK
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 20

    Organism-specific databases

    HGNCiHGNC:9617. PTK6.

    Subcellular locationi

    Cytoplasm. Nucleus. Cell projectionruffle. Membrane By similarity
    Note: Colocalizes with KHDRBS1, KHDRBS2 or KHDRBS3, within the nucleus. Nuclear localization in epithelial cells of normal prostate but cytoplasmic localization in cancer prostate.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. membrane Source: UniProtKB-SubCell
    3. nucleus Source: UniProtKB
    4. ruffle Source: UniProtKB

    Keywords - Cellular componenti

    Cell projection, Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi44 – 441W → A: Strong decrease in STAP2 phosphorylation. Markedly decreased interaction between SH3 domain the linker region. 2 Publications
    Mutagenesisi66 – 661Y → A: Decrease in STAP2 phosphorylation. 1 Publication
    Mutagenesisi105 – 1051R → L: Decrease in STAP2 phosphorylation. 1 Publication
    Mutagenesisi184 – 1841W → A: Abrogates interaction between PTK6-domain kinase and PTK6-linker. Abrogates autophosphorylation and phosphorylation of KHDRBS1. 1 Publication
    Mutagenesisi219 – 2191K → M: Abolishes kinase activity and cell transformation, and phosphorylation of STAP2. 3 Publications
    Mutagenesisi342 – 3421Y → A: 3-fold lower specific kinase activity. Decrease, but still significant, autophosphorylation. Decrease, but still significant, autophosphorylation; when associated to A-447. 1 Publication
    Mutagenesisi447 – 4471Y → F: Decrease in transforming potential and increase in the kinase activity level. Decrease, but still significant, autophosphorylation; when associated to A-342. 3 Publications

    Organism-specific databases

    PharmGKBiPA33960.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 451451Protein-tyrosine kinase 6PRO_0000088133Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei13 – 131Phosphotyrosine; by autocatalysis
    Modified residuei61 – 611Phosphotyrosine; by autocatalysis
    Modified residuei66 – 661Phosphotyrosine; by autocatalysis
    Modified residuei114 – 1141Phosphotyrosine; by autocatalysis1 Publication
    Modified residuei342 – 3421Phosphotyrosine; by autocatalysis1 Publication
    Modified residuei351 – 3511Phosphotyrosine; by autocatalysis1 Publication
    Modified residuei447 – 4471Phosphotyrosine1 Publication

    Post-translational modificationi

    Autophosphorylated. Autophosphorylation of Tyr-342 leads to an increase of kinase activity. Tyr-447 binds to the SH2 domain when phosphorylated and negatively regulates kinase activity.4 Publications

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ13882.
    PaxDbiQ13882.
    PRIDEiQ13882.

    PTM databases

    PhosphoSiteiQ13882.

    Expressioni

    Tissue specificityi

    Epithelia-specific. Very high level in colon and high levels in small intestine and prostate, and low levels in some fetal tissues. Not expressed in breast or ovarian tissue but expressed in high percentage of breast and ovarian cancers. Also overexpressed in some metastatic melanomas, lymphomas, colon cancers, squamous cell carcinomas and prostate cancers. Also found in melanocytes. Not expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Isoform 2 is present in prostate epithelial cell lines derived from normal prostate and prostate adenocarcinomas, as well as in a variety of cell lines.4 Publications

    Gene expression databases

    BgeeiQ13882.
    CleanExiHS_PTK6.
    GenevestigatoriQ13882.

    Organism-specific databases

    HPAiCAB032952.
    HPA036070.
    HPA036071.

    Interactioni

    Subunit structurei

    Interacts with GAP-A.p65 By similarity. Interacts (via SH3 and SH2 domains) with KHDRBS1. Interacts (via SH3 and SH2 domains) with phosphorylated IRS4. Interacts with ADAM15. Interacts (via SH3 domain) with SFPQ. Interacts with EGFR and ERBB2. Interacts with STAP2. Interacts with PNX. Interacts with SFPQ. Interacts with PTK/ATK. Interacts with CTNNB1.By similarity10 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself2EBI-1383632,EBI-1383632
    ERBB2P046262EBI-1383632,EBI-641062
    GAB1Q134806EBI-1383632,EBI-517684
    KITP107214EBI-1383632,EBI-1379503
    SFPQP232465EBI-1383632,EBI-355453

    Protein-protein interaction databases

    BioGridi111720. 13 interactions.
    DIPiDIP-39785N.
    IntActiQ13882. 10 interactions.
    MINTiMINT-1494499.
    STRINGi9606.ENSP00000217185.

    Structurei

    Secondary structure

    1
    451
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi12 – 143
    Beta strandi35 – 406
    Beta strandi45 – 506
    Beta strandi56 – 627
    Turni64 – 663
    Beta strandi67 – 704
    Helixi85 – 928
    Beta strandi102 – 1065
    Beta strandi108 – 1125
    Beta strandi114 – 1185
    Beta strandi125 – 1317
    Beta strandi133 – 1353
    Beta strandi137 – 1404
    Beta strandi143 – 1475
    Helixi148 – 15710
    Beta strandi162 – 1643

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1RJANMR-A75-174[»]
    2KGTNMR-A1-72[»]
    ProteinModelPortaliQ13882.
    SMRiQ13882. Positions 1-450.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ13882.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini11 – 7262SH3PROSITE-ProRule annotationAdd
    BLAST
    Domaini78 – 17093SH2PROSITE-ProRule annotationAdd
    BLAST
    Domaini191 – 445255Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni171 – 19020LinkerAdd
    BLAST

    Domaini

    The SH3 domain plays a major role in substrate interactions. The SH2 domain of PTK6 plays a role in protein-protein interactions, but is likely more important for the regulation of catalytic activity.

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Tyr protein kinase family. BRK/PTK6/SIK subfamily.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation
    Contains 1 SH2 domain.PROSITE-ProRule annotation
    Contains 1 SH3 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    SH2 domain, SH3 domain

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000233858.
    HOVERGENiHBG008761.
    InParanoidiQ13882.
    KOiK08894.
    OMAiVRHYKIW.
    OrthoDBiEOG73BVCD.
    PhylomeDBiQ13882.
    TreeFamiTF351634.

    Family and domain databases

    Gene3Di3.30.505.10. 1 hit.
    InterProiIPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR000980. SH2.
    IPR001452. SH3_domain.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    [Graphical view]
    PfamiPF07714. Pkinase_Tyr. 1 hit.
    PF00017. SH2. 1 hit.
    PF14604. SH3_9. 1 hit.
    [Graphical view]
    PRINTSiPR00401. SH2DOMAIN.
    PR00452. SH3DOMAIN.
    PR00109. TYRKINASE.
    SMARTiSM00252. SH2. 1 hit.
    SM00326. SH3. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF50044. SSF50044. 1 hit.
    SSF55550. SSF55550. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    PS50001. SH2. 1 hit.
    PS50002. SH3. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q13882-1) [UniParc]FASTAAdd to Basket

    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

    MVSRDQAHLG PKYVGLWDFK SRTDEELSFR AGDVFHVARK EEQWWWATLL    50
    DEAGGAVAQG YVPHNYLAER ETVESEPWFF GCISRSEAVR RLQAEGNATG 100
    AFLIRVSEKP SADYVLSVRD TQAVRHYKIW RRAGGRLHLN EAVSFLSLPE 150
    LVNYHRAQSL SHGLRLAAPC RKHEPEPLPH WDDWERPREE FTLCRKLGSG 200
    YFGEVFEGLW KDRVQVAIKV ISRDNLLHQQ MLQSEIQAMK KLRHKHILAL 250
    YAVVSVGDPV YIITELMAKG SLLELLRDSD EKVLPVSELL DIAWQVAEGM 300
    CYLESQNYIH RDLAARNILV GENTLCKVGD FGLARLIKED VYLSHDHNIP 350
    YKWTAPEALS RGHYSTKSDV WSFGILLHEM FSRGQVPYPG MSNHEAFLRV 400
    DAGYRMPCPL ECPPSVHKLM LTCWCRDPEQ RPCFKALRER LSSFTSYENP 450
    T 451
    Length:451
    Mass (Da):51,834
    Last modified:November 1, 1996 - v1
    Checksum:iCDCAC0EE242E1BD7
    GO
    Isoform 2 (identifier: Q13882-2) [UniParc]FASTAAdd to Basket

    Also known as: ALT-PTK6, deltam5

    The sequence of this isoform differs from the canonical sequence as follows:
         78-134: WFFGCISRSE...RHYKIWRRAG → AGHAGCAALQ...AGRALPEARA
         135-451: Missing.

    Show »
    Length:134
    Mass (Da):14,465
    Checksum:i7F350D1F4D13EBE9
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti16 – 161L → F in a renal papillary sample; somatic mutation. 1 Publication
    VAR_041760
    Natural varianti436 – 4361A → T.1 Publication
    Corresponds to variant rs56145017 [ dbSNP | Ensembl ].
    VAR_041761

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei78 – 13457WFFGC…WRRAG → AGHAGCAALQDLAACRGPAA PERGGVLPQPARACELPQGP EPVPRPAAGRALPEARA in isoform 2. 2 PublicationsVSP_042066Add
    BLAST
    Alternative sequencei135 – 451317Missing in isoform 2. 2 PublicationsVSP_042067Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X78549 mRNA. Translation: CAA55295.1.
    U61412
    , U61406, U61407, U61408, U61409, U61410, U61411 Genomic DNA. Translation: AAC34935.1.
    AK315232 mRNA. Translation: BAG37660.1.
    AK301364 mRNA. Translation: BAG62908.1. Sequence problems.
    AL121829 Genomic DNA. Translation: CAC15525.1.
    BC035843 mRNA. Translation: AAH35843.1.
    CCDSiCCDS13524.1. [Q13882-1]
    PIRiS49016.
    RefSeqiNP_001243287.1. NM_001256358.1. [Q13882-2]
    NP_005966.1. NM_005975.3. [Q13882-1]
    UniGeneiHs.51133.

    Genome annotation databases

    EnsembliENST00000217185; ENSP00000217185; ENSG00000101213. [Q13882-1]
    ENST00000542869; ENSP00000442460; ENSG00000101213.
    GeneIDi5753.
    KEGGihsa:5753.
    UCSCiuc002yfg.4. human. [Q13882-1]
    uc011aay.3. human. [Q13882-2]

    Polymorphism databases

    DMDMi8928302.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X78549 mRNA. Translation: CAA55295.1 .
    U61412
    , U61406 , U61407 , U61408 , U61409 , U61410 , U61411 Genomic DNA. Translation: AAC34935.1 .
    AK315232 mRNA. Translation: BAG37660.1 .
    AK301364 mRNA. Translation: BAG62908.1 . Sequence problems.
    AL121829 Genomic DNA. Translation: CAC15525.1 .
    BC035843 mRNA. Translation: AAH35843.1 .
    CCDSi CCDS13524.1. [Q13882-1 ]
    PIRi S49016.
    RefSeqi NP_001243287.1. NM_001256358.1. [Q13882-2 ]
    NP_005966.1. NM_005975.3. [Q13882-1 ]
    UniGenei Hs.51133.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1RJA NMR - A 75-174 [» ]
    2KGT NMR - A 1-72 [» ]
    ProteinModelPortali Q13882.
    SMRi Q13882. Positions 1-450.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111720. 13 interactions.
    DIPi DIP-39785N.
    IntActi Q13882. 10 interactions.
    MINTi MINT-1494499.
    STRINGi 9606.ENSP00000217185.

    Chemistry

    BindingDBi Q13882.
    ChEMBLi CHEMBL4601.
    GuidetoPHARMACOLOGYi 2182.

    PTM databases

    PhosphoSitei Q13882.

    Polymorphism databases

    DMDMi 8928302.

    Proteomic databases

    MaxQBi Q13882.
    PaxDbi Q13882.
    PRIDEi Q13882.

    Protocols and materials databases

    DNASUi 5753.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000217185 ; ENSP00000217185 ; ENSG00000101213 . [Q13882-1 ]
    ENST00000542869 ; ENSP00000442460 ; ENSG00000101213 .
    GeneIDi 5753.
    KEGGi hsa:5753.
    UCSCi uc002yfg.4. human. [Q13882-1 ]
    uc011aay.3. human. [Q13882-2 ]

    Organism-specific databases

    CTDi 5753.
    GeneCardsi GC20M062159.
    HGNCi HGNC:9617. PTK6.
    HPAi CAB032952.
    HPA036070.
    HPA036071.
    MIMi 602004. gene.
    neXtProti NX_Q13882.
    PharmGKBi PA33960.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233858.
    HOVERGENi HBG008761.
    InParanoidi Q13882.
    KOi K08894.
    OMAi VRHYKIW.
    OrthoDBi EOG73BVCD.
    PhylomeDBi Q13882.
    TreeFami TF351634.

    Enzyme and pathway databases

    BRENDAi 2.7.10.2. 2681.
    SignaLinki Q13882.

    Miscellaneous databases

    EvolutionaryTracei Q13882.
    GeneWikii PTK6.
    GenomeRNAii 5753.
    NextBioi 22386.
    PROi Q13882.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q13882.
    CleanExi HS_PTK6.
    Genevestigatori Q13882.

    Family and domain databases

    Gene3Di 3.30.505.10. 1 hit.
    InterProi IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR000980. SH2.
    IPR001452. SH3_domain.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    [Graphical view ]
    Pfami PF07714. Pkinase_Tyr. 1 hit.
    PF00017. SH2. 1 hit.
    PF14604. SH3_9. 1 hit.
    [Graphical view ]
    PRINTSi PR00401. SH2DOMAIN.
    PR00452. SH3DOMAIN.
    PR00109. TYRKINASE.
    SMARTi SM00252. SH2. 1 hit.
    SM00326. SH3. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF50044. SSF50044. 1 hit.
    SSF55550. SSF55550. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    PS50001. SH2. 1 hit.
    PS50002. SH3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning and characterisation of cDNAs encoding a novel non-receptor tyrosine kinase, brk, expressed in human breast tumours."
      Mitchell P.J., Barker K.T., Martindale J.E., Kamalati T., Lowe P.N., Page M.J., Gusterson B.A., Crompton M.R.
      Oncogene 9:2383-2390(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Mammary tumor.
    2. "Characterisation and chromosome mapping of the human non receptor tyrosine kinase gene, brk."
      Mitchell P.J., Barker K.T., Shipley J., Crompton M.R.
      Oncogene 15:1497-1502(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
    3. "Exon-intron structure of the human PTK6 gene demonstrates that PTK6 constitutes a distinct family of non-receptor tyrosine kinase."
      Lee H.-Y., Kim M., Lee K.-H., Kang K.-N., Lee S.-T.
      Mol. Cells 8:401-407(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Melanocyte.
    4. "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] (ISOFORMS 1 AND 2).
      Tissue: Urinary bladder.
    5. "The DNA sequence and comparative analysis of human chromosome 20."
      Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E.
      , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
      Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "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 1).
      Tissue: Blood.
    7. "Brk, a breast tumor-derived non-receptor protein-tyrosine kinase, sensitizes mammary epithelial cells to epidermal growth factor."
      Kamalati T., Jolin H.E., Mitchell P.J., Barker K.T., Jackson L.E., Dean C.J., Page M.J., Gusterson B.A., Crompton M.R.
      J. Biol. Chem. 271:30956-30963(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION, INTERACTION WITH EGFR, MUTAGENESIS OF LYS-219 AND TYR-447.
    8. "Loss of expression of receptor tyrosine kinase family genes PTK7 and SEK in metastatic melanoma."
      Easty D.J., Mitchell P.J., Patel K., Florenes V.A., Spritz R.A., Bennett D.C.
      Int. J. Cancer 71:1061-1065(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    9. "A novel adaptor-like protein which is a substrate for the non-receptor tyrosine kinase, BRK."
      Mitchell P.J., Sara E.A., Crompton M.R.
      Oncogene 19:4273-4282(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH STAP2, MUTAGENESIS OF TRP-44; TYR-66; ARG-105 AND LYS-219.
    10. "Sik (BRK) phosphorylates Sam68 in the nucleus and negatively regulates its RNA binding ability."
      Derry J.J., Richard S., Valderrama Carvajal H., Ye X., Vasioukhin V., Cochrane A.W., Chen T., Tyner A.L.
      Mol. Cell. Biol. 20:6114-6126(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, INTERACTION WITH KHDRBS1.
    11. "Regulation of the nonreceptor tyrosine kinase Brk by autophosphorylation and by autoinhibition."
      Qiu H., Miller W.T.
      J. Biol. Chem. 277:34634-34641(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT TYR-342; TYR-351 AND TYR-447, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF TYR-342 AND TYR-447, ENZYME REGULATION, IDENTIFICATION BY MASS SPECTROMETRY.
    12. "Altered localization and activity of the intracellular tyrosine kinase BRK/Sik in prostate tumor cells."
      Derry J.J., Prins G.S., Ray V., Tyner A.L.
      Oncogene 22:4212-4220(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    13. "The nuclear tyrosine kinase BRK/Sik phosphorylates and inhibits the RNA-binding activities of the Sam68-like mammalian proteins SLM-1 and SLM-2."
      Haegebarth A., Heap D., Bie W., Derry J.J., Richard S., Tyner A.L.
      J. Biol. Chem. 279:54398-54404(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-219 AND TYR-447, PHOSPHORYLATION.
    14. "Brk activates rac1 and promotes cell migration and invasion by phosphorylating paxillin."
      Chen H.Y., Shen C.H., Tsai Y.T., Lin F.C., Huang Y.P., Chen R.H.
      Mol. Cell. Biol. 24:10558-10572(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CELL MIGRATION, FUNCTION IN PHOSPHORYLATION OF PXN, SUBCELLULAR LOCATION, INTERACTION WITH PXN.
    15. "Differential expression of the non-receptor tyrosine kinase BRK in oral squamous cell carcinoma and normal oral epithelium."
      Petro B.J., Tan R.C., Tyner A.L., Lingen M.W., Watanabe K.
      Oral Oncol. 40:1040-1047(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
    16. "Regulated association of protein kinase B/Akt with breast tumor kinase."
      Zhang P., Ostrander J.H., Faivre E.J., Olsen A., Fitzsimmons D., Lange C.A.
      J. Biol. Chem. 280:1982-1991(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF BTK, INTERACTION WITH BTK.
    17. "An intramolecular interaction between SH2-kinase linker and kinase domain is essential for the catalytic activity of protein-tyrosine kinase-6."
      Kim H.I.E., Lee S.T.
      J. Biol. Chem. 280:28973-28980(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF TRP-184, ENZYME REGULATION.
    18. "Tyrosine phosphorylation of sam68 by breast tumor kinase regulates intranuclear localization and cell cycle progression."
      Lukong K.E., Larocque D., Tyner A.L., Richard S.
      J. Biol. Chem. 280:38639-38647(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF KHDRBS1.
    19. "Interaction between Brk kinase and insulin receptor substrate-4."
      Qiu H., Zappacosta F., Su W., Annan R.S., Miller W.T.
      Oncogene 24:5656-5664(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH IRS4, ENZYME REGULATION.
    20. "Expression and oncogenic role of Brk (PTK6/Sik) protein tyrosine kinase in lymphocytes."
      Kasprzycka M., Majewski M., Wang Z.J., Ptasznik A., Wysocka M., Zhang Q., Marzec M., Gimotty P., Crompton M.R., Wasik M.A.
      Am. J. Pathol. 168:1631-1641(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
    21. "Identification of STAT3 as a specific substrate of breast tumor kinase."
      Liu L., Gao Y., Qiu H., Miller W.T., Poli V., Reich N.C.
      Oncogene 25:4904-4912(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF STAT3, ENZYME REGULATION.
    22. "Molecular dissection of the interaction between the SH3 domain and the SH2-Kinase Linker region in PTK6."
      Kim H.I.E., Jung J., Lee E.S., Kim Y.C., Lee W., Lee S.T.
      Biochem. Biophys. Res. Commun. 362:829-834(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION, MUTAGENESIS OF TRP-44.
    23. "Signal transducer and activator of transcription 5b: a new target of breast tumor kinase/protein tyrosine kinase 6."
      Weaver A.M., Silva C.M.
      Breast Cancer Res. 9:R79-R79(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF STAT5B.
    24. "Breast tumor kinase phosphorylates p190RhoGAP to regulate rho and ras and promote breast carcinoma growth, migration, and invasion."
      Shen C.H., Chen H.Y., Lin M.S., Li F.Y., Chang C.C., Kuo M.L., Settleman J., Chen R.H.
      Cancer Res. 68:7779-7787(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF ARHGAP35.
    25. "Distinct functions of natural ADAM-15 cytoplasmic domain variants in human mammary carcinoma."
      Zhong J.L., Poghosyan Z., Pennington C.J., Scott X., Handsley M.M., Warn A., Gavrilovic J., Honert K., Kruger A., Span P.N., Sweep F.C., Edwards D.R.
      Mol. Cancer Res. 6:383-394(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ADAM15.
    26. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
      Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
      Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-114, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    27. Cited for: INTERACTION WITH ERBB2.
    28. "BRK phosphorylates PSF promoting its cytoplasmic localization and cell cycle arrest."
      Lukong K.E., Huot M.E., Richard S.
      Cell. Signal. 21:1415-1422(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SFPQ.
    29. "Building a better understanding of the intracellular tyrosine kinase PTK6 - BRK by BRK."
      Brauer P.M., Tyner A.L.
      Biochim. Biophys. Acta 1806:66-73(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION.
    30. "Identification of beta-catenin as a target of the intracellular tyrosine kinase PTK6."
      Palka-Hamblin H.L., Gierut J.J., Bie W., Brauer P.M., Zheng Y., Asara J.M., Tyner A.L.
      J. Cell Sci. 123:236-245(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION OF CTNNB1, INTERACTION WITH CTNNB1.
    31. "The alternative splice variant of protein tyrosine kinase 6 negatively regulates growth and enhances PTK6-mediated inhibition of beta-catenin."
      Brauer P.M., Zheng Y., Evans M.D., Dominguez-Brauer C., Peehl D.M., Tyner A.L.
      PLoS ONE 6:E14789-E14789(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION (ISOFORM 2), INTERACTION (ISOFORM 2) WITH KHDRBS1 AND CTNNB1.
    32. "Solution structure and backbone dynamics of the non-receptor protein-tyrosine kinase-6 Src homology 2 domain."
      Hong E., Shin J., Kim H.I., Lee S.T., Lee W.
      J. Biol. Chem. 279:29700-29708(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 75-174.
    33. "Patterns of somatic mutation in human cancer genomes."
      Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
      , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
      Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS [LARGE SCALE ANALYSIS] PHE-16 AND THR-436.

    Entry informationi

    Entry nameiPTK6_HUMAN
    AccessioniPrimary (citable) accession number: Q13882
    Secondary accession number(s): B2RCR3, B4DW46, Q58F01
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: November 1, 1996
    Last modified: October 1, 2014
    This is version 156 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 20
      Human chromosome 20: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3