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Q13882 (PTK6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 155. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein-tyrosine kinase 6

EC=2.7.10.2
Alternative name(s):
Breast tumor kinase
Tyrosine-protein kinase BRK
Gene names
Name:PTK6
Synonyms:BRK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length451 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.9 Ref.13 Ref.14 Ref.16 Ref.18 Ref.21 Ref.23 Ref.24 Ref.31

Isoform 2 inhibits PTK6 phosphorylation and PTK6 association with other tyrosine-phosphorylated proteins. Ref.9 Ref.13 Ref.14 Ref.16 Ref.18 Ref.21 Ref.23 Ref.24 Ref.31

Catalytic activity

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

Enzyme regulation

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. Ref.11 Ref.17 Ref.19 Ref.21 Ref.22

Subunit structure

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. Ref.7 Ref.9 Ref.10 Ref.14 Ref.16 Ref.19 Ref.25 Ref.27 Ref.28 Ref.30 Ref.31

Subcellular location

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. Ref.10 Ref.12 Ref.13 Ref.14 Ref.15 Ref.20

Tissue specificity

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. Ref.8 Ref.12 Ref.15 Ref.20

Domain

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.

Post-translational modification

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. Ref.11 Ref.13 Ref.30

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. BRK/PTK6/SIK subfamily.

Contains 1 protein kinase domain.

Contains 1 SH2 domain.

Contains 1 SH3 domain.

Biophysicochemical properties

Kinetic parameters:

KM=83 µM for ATP Ref.11

Vmax=37 nmol/min/mg enzyme

Sequence caution

The sequence BAG62908.1 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.

Ontologies

Keywords
   Cellular componentCell projection
Cytoplasm
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSH2 domain
SH3 domain
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell migration

Inferred from direct assay Ref.14. Source: UniProtKB

cellular response to retinoic acid

Inferred from mutant phenotype PubMed 17910947. Source: BHF-UCL

intestinal epithelial cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of growth

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein tyrosine kinase activity

Inferred from direct assay Ref.16. Source: UniProtKB

positive regulation of neuron projection development

Inferred from mutant phenotype PubMed 17910947. Source: BHF-UCL

protein autophosphorylation

Inferred from mutant phenotype Ref.11. Source: UniProtKB

protein phosphorylation

Traceable author statement Ref.1. Source: ProtInc

tyrosine phosphorylation of Stat3 protein

Inferred from direct assay Ref.21. Source: UniProtKB

tyrosine phosphorylation of Stat5 protein

Inferred from direct assay Ref.23. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay Ref.14. Source: UniProtKB

membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay Ref.10. Source: UniProtKB

ruffle

Inferred from direct assay Ref.14. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

identical protein binding

Inferred from physical interaction Ref.32PubMed 19401189. Source: IntAct

non-membrane spanning protein tyrosine kinase activity

Inferred from direct assay Ref.10. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.10Ref.16Ref.14Ref.21. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q13882-1)

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.
Isoform 2 (identifier: Q13882-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 451451Protein-tyrosine kinase 6
PRO_0000088133

Regions

Domain11 – 7262SH3
Domain78 – 17093SH2
Domain191 – 445255Protein kinase
Nucleotide binding197 – 2059ATP By similarity
Region171 – 19020Linker

Sites

Active site3121Proton acceptor By similarity
Binding site2191ATP By similarity

Amino acid modifications

Modified residue131Phosphotyrosine; by autocatalysis
Modified residue611Phosphotyrosine; by autocatalysis
Modified residue661Phosphotyrosine; by autocatalysis
Modified residue1141Phosphotyrosine; by autocatalysis Ref.26
Modified residue3421Phosphotyrosine; by autocatalysis Ref.11
Modified residue3511Phosphotyrosine; by autocatalysis Ref.11
Modified residue4471Phosphotyrosine Ref.11

Natural variations

Alternative sequence78 – 13457WFFGC…WRRAG → AGHAGCAALQDLAACRGPAA PERGGVLPQPARACELPQGP EPVPRPAAGRALPEARA in isoform 2.
VSP_042066
Alternative sequence135 – 451317Missing in isoform 2.
VSP_042067
Natural variant161L → F in a renal papillary sample; somatic mutation. Ref.33
VAR_041760
Natural variant4361A → T. Ref.33
Corresponds to variant rs56145017 [ dbSNP | Ensembl ].
VAR_041761

Experimental info

Mutagenesis441W → A: Strong decrease in STAP2 phosphorylation. Markedly decreased interaction between SH3 domain the linker region. Ref.9 Ref.22
Mutagenesis661Y → A: Decrease in STAP2 phosphorylation. Ref.9
Mutagenesis1051R → L: Decrease in STAP2 phosphorylation. Ref.9
Mutagenesis1841W → A: Abrogates interaction between PTK6-domain kinase and PTK6-linker. Abrogates autophosphorylation and phosphorylation of KHDRBS1. Ref.17
Mutagenesis2191K → M: Abolishes kinase activity and cell transformation, and phosphorylation of STAP2. Ref.7 Ref.9 Ref.13
Mutagenesis3421Y → A: 3-fold lower specific kinase activity. Decrease, but still significant, autophosphorylation. Decrease, but still significant, autophosphorylation; when associated to A-447. Ref.11
Mutagenesis4471Y → F: Decrease in transforming potential and increase in the kinase activity level. Decrease, but still significant, autophosphorylation; when associated to A-342. Ref.7 Ref.11 Ref.13

Secondary structure

............................... 451
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: CDCAC0EE242E1BD7

FASTA45151,834
        10         20         30         40         50         60 
MVSRDQAHLG PKYVGLWDFK SRTDEELSFR AGDVFHVARK EEQWWWATLL DEAGGAVAQG 

        70         80         90        100        110        120 
YVPHNYLAER ETVESEPWFF GCISRSEAVR RLQAEGNATG AFLIRVSEKP SADYVLSVRD 

       130        140        150        160        170        180 
TQAVRHYKIW RRAGGRLHLN EAVSFLSLPE LVNYHRAQSL SHGLRLAAPC RKHEPEPLPH 

       190        200        210        220        230        240 
WDDWERPREE FTLCRKLGSG YFGEVFEGLW KDRVQVAIKV ISRDNLLHQQ MLQSEIQAMK 

       250        260        270        280        290        300 
KLRHKHILAL YAVVSVGDPV YIITELMAKG SLLELLRDSD EKVLPVSELL DIAWQVAEGM 

       310        320        330        340        350        360 
CYLESQNYIH RDLAARNILV GENTLCKVGD FGLARLIKED VYLSHDHNIP YKWTAPEALS 

       370        380        390        400        410        420 
RGHYSTKSDV WSFGILLHEM FSRGQVPYPG MSNHEAFLRV DAGYRMPCPL ECPPSVHKLM 

       430        440        450 
LTCWCRDPEQ RPCFKALRER LSSFTSYENP T 

« Hide

Isoform 2 (ALT-PTK6) (deltam5) [UniParc].

Checksum: 7F350D1F4D13EBE9
Show »

FASTA13414,465

References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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]"Brk is coamplified with ErbB2 to promote proliferation in breast cancer."
Xiang B., Chatti K., Qiu H., Lakshmi B., Krasnitz A., Hicks J., Yu M., Miller W.T., Muthuswamy S.K.
Proc. Natl. Acad. Sci. U.S.A. 105:12463-12468(2008) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X78549 mRNA. Translation: CAA55295.1.
U61412 expand/collapse EMBL AC list , 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.
CCDSCCDS13524.1. [Q13882-1]
PIRS49016.
RefSeqNP_001243287.1. NM_001256358.1. [Q13882-2]
NP_005966.1. NM_005975.3. [Q13882-1]
UniGeneHs.51133.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1RJANMR-A75-174[»]
2KGTNMR-A1-72[»]
ProteinModelPortalQ13882.
SMRQ13882. Positions 1-450.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111720. 13 interactions.
DIPDIP-39785N.
IntActQ13882. 10 interactions.
MINTMINT-1494499.
STRING9606.ENSP00000217185.

Chemistry

BindingDBQ13882.
ChEMBLCHEMBL4601.
GuidetoPHARMACOLOGY2182.

PTM databases

PhosphoSiteQ13882.

Polymorphism databases

DMDM8928302.

Proteomic databases

MaxQBQ13882.
PaxDbQ13882.
PRIDEQ13882.

Protocols and materials databases

DNASU5753.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000217185; ENSP00000217185; ENSG00000101213. [Q13882-1]
ENST00000542869; ENSP00000442460; ENSG00000101213.
GeneID5753.
KEGGhsa:5753.
UCSCuc002yfg.4. human. [Q13882-1]
uc011aay.3. human. [Q13882-2]

Organism-specific databases

CTD5753.
GeneCardsGC20M062159.
HGNCHGNC:9617. PTK6.
HPACAB032952.
HPA036070.
HPA036071.
MIM602004. gene.
neXtProtNX_Q13882.
PharmGKBPA33960.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233858.
HOVERGENHBG008761.
InParanoidQ13882.
KOK08894.
OMAVRHYKIW.
OrthoDBEOG73BVCD.
PhylomeDBQ13882.
TreeFamTF351634.

Enzyme and pathway databases

BRENDA2.7.10.2. 2681.
SignaLinkQ13882.

Gene expression databases

BgeeQ13882.
CleanExHS_PTK6.
GenevestigatorQ13882.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR011009. 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]
PfamPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF14604. SH3_9. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00107. 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]
ProtoNetSearch...

Other

EvolutionaryTraceQ13882.
GeneWikiPTK6.
GenomeRNAi5753.
NextBio22386.
PROQ13882.
SOURCESearch...

Entry information

Entry namePTK6_HUMAN
AccessionPrimary (citable) accession number: Q13882
Secondary accession number(s): B2RCR3, B4DW46, Q58F01
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 155 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM