Q13882 (PTK6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	451 AA.
Sequence status	Complete.
Protein existence	Evidence 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 projection › ruffle. 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 component	Cell projection Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	SH2 domain SH3 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell 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_component	cytoplasm 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_function	ATP 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...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-1383632,EBI-1383632
ERBB2	P04626	2	EBI-1383632,EBI-641062
GAB1	Q13480	6	EBI-1383632,EBI-517684
KIT	P10721	4	EBI-1383632,EBI-1379503
SFPQ	P23246	5	EBI-1383632,EBI-355453

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 451

451

Protein-tyrosine kinase 6

PRO_0000088133

Regions

Domain

11 – 72

62

SH3

Domain

78 – 170

93

SH2

Domain

191 – 445

255

Protein kinase

Nucleotide binding

197 – 205

9

ATP By similarity

Region

171 – 190

20

Linker

Sites

Active site

312

1

Proton acceptor By similarity

Binding site

219

1

ATP By similarity

Amino acid modifications

Modified residue

13

1

Phosphotyrosine; by autocatalysis

Modified residue

61

1

Phosphotyrosine; by autocatalysis

Modified residue

66

1

Phosphotyrosine; by autocatalysis

Modified residue

114

1

Phosphotyrosine; by autocatalysis Ref.26

Modified residue

342

1

Phosphotyrosine; by autocatalysis Ref.11

Modified residue

351

1

Phosphotyrosine; by autocatalysis Ref.11

Modified residue

447

1

Phosphotyrosine Ref.11

Natural variations

Alternative sequence

78 – 134

57

WFFGC…WRRAG → AGHAGCAALQDLAACRGPAA PERGGVLPQPARACELPQGP EPVPRPAAGRALPEARA in isoform 2.

VSP_042066

Alternative sequence

135 – 451

317

Missing in isoform 2.

VSP_042067

Natural variant

16

1

L → F in a renal papillary sample; somatic mutation. Ref.33

VAR_041760

Natural variant

436

1

A → T. Ref.33
Corresponds to variant rs56145017 [ dbSNP | Ensembl ].

VAR_041761

Experimental info

Mutagenesis

44

1

W → A: Strong decrease in STAP2 phosphorylation. Markedly decreased interaction between SH3 domain the linker region. Ref.9 Ref.22

Mutagenesis

66

1

Y → A: Decrease in STAP2 phosphorylation. Ref.9

Mutagenesis

105

1

R → L: Decrease in STAP2 phosphorylation. Ref.9

Mutagenesis

184

1

W → A: Abrogates interaction between PTK6-domain kinase and PTK6-linker. Abrogates autophosphorylation and phosphorylation of KHDRBS1. Ref.17

Mutagenesis

219

1

K → M: Abolishes kinase activity and cell transformation, and phosphorylation of STAP2. Ref.7 Ref.9 Ref.13

Mutagenesis

342

1

Y → A: 3-fold lower specific kinase activity. Decrease, but still significant, autophosphorylation. Decrease, but still significant, autophosphorylation; when associated to A-447. Ref.11

Mutagenesis

447

1

Y → 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

1

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451

Helix Strand Turn

Details...

Beta strand

12 – 14

3

Beta strand

35 – 40

6

Beta strand

45 – 50

6

Beta strand

56 – 62

7

Turn

64 – 66

3

Beta strand

67 – 70

4

Helix

85 – 92

8

Beta strand

102 – 106

5

Beta strand

108 – 112

5

Beta strand

114 – 118

5

Beta strand

125 – 131

7

Beta strand

133 – 135

3

Beta strand

137 – 140

4

Beta strand

143 – 147

5

Helix

148 – 157

10

Beta strand

162 – 164

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: CDCAC0EE242E1BD7	FASTA	451	51,834
	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
	Isoform 2 (ALT-PTK6) (deltam5) [UniParc]. Checksum: 7F350D1F4D13EBE9	FASTA	134	14,465
	10 20 30 40 50 60 MVSRDQAHLG PKYVGLWDFK SRTDEELSFR AGDVFHVARK EEQWWWATLL DEAGGAVAQG 70 80 90 100 110 120 YVPHNYLAER ETVESEPAGH AGCAALQDLA ACRGPAAPER GGVLPQPARA CELPQGPEPV 130 PRPAAGRALP EARA

References

	« Hide 'large scale' referencesShow '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. , 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]	"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. , 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 , 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.

CCDS

CCDS13524.1. [Q13882-1]

PIR

S49016.

RefSeq

NP_001243287.1. NM_001256358.1. [Q13882-2]
NP_005966.1. NM_005975.3. [Q13882-1]

UniGene

Hs.51133.

3D structure databases

PDBe
RCSB-PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1RJA	NMR	-	A	75-174	[»]
2KGT	NMR	-	A	1-72	[»]

ProteinModelPortal

Q13882.

SMR

Q13882. Positions 1-450.

ModBase

Search...

MobiDB

Search...

Protein-protein interaction databases

BioGrid

111720. 13 interactions.

DIP

DIP-39785N.

IntAct

Q13882. 10 interactions.

MINT

MINT-1494499.

STRING

9606.ENSP00000217185.

Chemistry

BindingDB

Q13882.

ChEMBL

CHEMBL4601.

GuidetoPHARMACOLOGY

2182.

PTM databases

PhosphoSite

Q13882.

Polymorphism databases

DMDM

8928302.

Proteomic databases

MaxQB

Q13882.

PaxDb

Q13882.

PRIDE

Q13882.

Protocols and materials databases

DNASU

5753.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000217185; ENSP00000217185; ENSG00000101213. [Q13882-1]
ENST00000542869; ENSP00000442460; ENSG00000101213.

GeneID

5753.

KEGG

hsa:5753.

UCSC

uc002yfg.4. human. [Q13882-1]
uc011aay.3. human. [Q13882-2]

Organism-specific databases

CTD

5753.

GeneCards

GC20M062159.

HGNC

HGNC:9617. PTK6.

HPA

CAB032952.
HPA036070.
HPA036071.

MIM

602004. gene.

neXtProt

NX_Q13882.

PharmGKB

PA33960.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000233858.

HOVERGEN

HBG008761.

InParanoid

Q13882.

KO

K08894.

OMA

VRHYKIW.

OrthoDB

EOG73BVCD.

PhylomeDB

Q13882.

TreeFam

TF351634.

Enzyme and pathway databases

BRENDA

2.7.10.2. 2681.

SignaLink

Q13882.

Gene expression databases

Bgee

Q13882.

CleanEx

HS_PTK6.

Genevestigator

Q13882.

Family and domain databases

Gene3D

3.30.505.10. 1 hit.

InterPro

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]

Pfam

PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF14604. SH3_9. 1 hit.
[Graphical view]

PRINTS

PR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.

SMART

SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]

SUPFAM

SSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.

PROSITE

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]

ProtoNet

Search...

Other

EvolutionaryTrace

Q13882.

GeneWiki

PTK6.

GenomeRNAi

5753.

NextBio

22386.

PRO

Q13882.

SOURCE

Search...

Entry information

Entry name

PTK6_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.