PTK6_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: PTK6_HUMAN
• UniProt AC: Q13882
• Protein Name: Protein-tyrosine kinase 6
• Gene Name: PTK6
• Organism: Homo sapiens (Human).
• Sequence Length: 451
• Subcellular Localization: Cytoplasm. Nucleus. Cell projection, ruffle. Membrane. Colocalizes with KHDRBS1, KHDRBS2 or KHDRBS3, within the nucleus. Nuclear localization in epithelial cells of normal prostate but cytoplasmic localization in cancer prostate.
• Protein Description: 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..
• Protein Sequence: MVSRDQAHLGPKYVGLWDFKSRTDEELSFRAGDVFHVARKEEQWWWATLLDEAGGAVAQGYVPHNYLAERETVESEPWFFGCISRSEAVRRLQAEGNATGAFLIRVSEKPSADYVLSVRDTQAVRHYKIWRRAGGRLHLNEAVSFLSLPELVNYHRAQSLSHGLRLAAPCRKHEPEPLPHWDDWERPREEFTLCRKLGSGYFGEVFEGLWKDRVQVAIKVISRDNLLHQQMLQSEIQAMKKLRHKHILALYAVVSVGDPVYIITELMAKGSLLELLRDSDEKVLPVSELLDIAWQVAEGMCYLESQNYIHRDLAARNILVGENTLCKVGDFGLARLIKEDVYLSHDHNIPYKWTAPEALSRGHYSTKSDVWSFGILLHEMFSRGQVPYPGMSNHEAFLRVDAGYRMPCPLECPPSVHKLMLTCWCRDPEQRPCFKALRERLSSFTSYENPT

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
13	Phosphorylation	QAHLGPKYVGLWDFK HCCCCCCCEEEEECC	11.68	19060867
61	Phosphorylation	GGAVAQGYVPHNYLA CCCCCCCCCCHHHEE	9.95	12121988
66	Phosphorylation	QGYVPHNYLAERETV CCCCCHHHEEECEEC	12.31	12121988
111	Phosphorylation	IRVSEKPSADYVLSV EEECCCCCCCEEEEE	44.85	28152594
114	Phosphorylation	SEKPSADYVLSVRDT CCCCCCCEEEEECCC	11.73	21082442
117	Phosphorylation	PSADYVLSVRDTQAV CCCCEEEEECCCHHH	12.69	28152594
127	Phosphorylation	DTQAVRHYKIWRRAG CCHHHHHHHHHHHCC	8.13	-
159	Phosphorylation	VNYHRAQSLSHGLRL HCHHHHHHHHHHHHH	30.75	17192257
161	Phosphorylation	YHRAQSLSHGLRLAA HHHHHHHHHHHHHCC	22.28	23312004
222	Phosphorylation	QVAIKVISRDNLLHQ HHHHHHHCCCCHHHH	36.25	30206219
271	Phosphorylation	TELMAKGSLLELLRD HHHHHCCCHHHHHCC	29.13	29457462
279	Phosphorylation	LLELLRDSDEKVLPV HHHHHCCCCCCEECH	41.03	-
342	Phosphorylation	RLIKEDVYLSHDHNI HHHHCCEECCCCCCC	18.14	25159151
344	Phosphorylation	IKEDVYLSHDHNIPY HHCCEECCCCCCCCC	14.80	26356563
351	Phosphorylation	SHDHNIPYKWTAPEA CCCCCCCCEECCCHH	18.50	27259358
352	Ubiquitination	HDHNIPYKWTAPEAL CCCCCCCEECCCHHH	32.49	29967540
442	Phosphorylation	KALRERLSSFTSYEN HHHHHHHHHCCCCCC	29.62	28152594
443	Phosphorylation	ALRERLSSFTSYENP HHHHHHHHCCCCCCC	36.82	28152594
445	Phosphorylation	RERLSSFTSYENPT- HHHHHHCCCCCCCC-	32.14	28152594
446	Phosphorylation	ERLSSFTSYENPT-- HHHHHCCCCCCCC--	28.56	22617229
447	Phosphorylation	RLSSFTSYENPT--- HHHHCCCCCCCC---	19.37	17822667
451	Phosphorylation	FTSYENPT------- CCCCCCCC-------	63.93	26356563

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
13	Y	Phosphorylation	Kinase	PTK6	Q13882	GPS
61	Y	Phosphorylation	Kinase	PTK6	Q13882	GPS
66	Y	Phosphorylation	Kinase	PTK6	Q13882	GPS
114	Y	Phosphorylation	Kinase	PTK6	Q13882	GPS
342	Y	Phosphorylation	Kinase	PTK6	Q13882	PhosphoELM
351	Y	Phosphorylation	Kinase	PTK6	Q13882	GPS
447	Y	Phosphorylation	Kinase	PTK6	Q13882	PhosphoELM
447	Y	Phosphorylation	Kinase	SRMS	Q9H3Y6	PSP

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of PTK6_HUMAN !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of PTK6_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
KHDR1_HUMAN	KHDRBS1	physical	10913193
A4_HUMAN	APP	physical	21832049
ERBB2_HUMAN	ERBB2	physical	18719096
PTK6_HUMAN	PTK6	physical	18719096
REL_HUMAN	REL	physical	25416956
WASL_HUMAN	WASL	physical	25416956
EXOC5_HUMAN	EXOC5	physical	25416956
FCHO1_HUMAN	FCHO1	physical	25416956
CCD33_HUMAN	CCDC33	physical	25416956
EFHC2_HUMAN	EFHC2	physical	25416956
KHDR2_HUMAN	KHDRBS2	physical	25416956
SOCS3_HUMAN	SOCS3	physical	22547065
TCPG_HUMAN	CCT3	physical	25852190
TCPD_HUMAN	CCT4	physical	25852190
TCPQ_HUMAN	CCT8	physical	25852190
TCPA_HUMAN	TCP1	physical	25852190
PTK6_HUMAN	PTK6	physical	26751287
HIF1A_HUMAN	HIF1A	physical	26751287

Drug and Disease Associations

• Kegg Disease
• There are no disease associations of PTM sites.
• OMIM Disease
• There are no disease associations of PTM sites.
• Kegg Drug
• There are no disease associations of PTM sites.
• DrugBank
• DB05294: Vandetanib

Related Literatures of Post-Translational Modification

Phosphorylation

"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe 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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-114 AND SER-159, ANDMASS SPECTROMETRY.
PubMed: 18691976

"An extensive survey of tyrosine phosphorylation revealing new sitesin human mammary epithelial cells.";
Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A.,Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D.,Wiley H.S., Qian W.-J.;
J. Proteome Res. 8:3852-3861(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-447, AND MASSSPECTROMETRY.
PubMed: 19534553

"Multiple reaction monitoring for robust quantitative proteomicanalysis of cellular signaling networks.";
Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M.;
Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-447, AND MASSSPECTROMETRY.
PubMed: 17389395

"Global survey of phosphotyrosine signaling identifies oncogenickinases in lung cancer.";
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.;
Cell 131:1190-1203(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-447, AND MASSSPECTROMETRY.
PubMed: 18083107

"Time-resolved mass spectrometry of tyrosine phosphorylation sites inthe epidermal growth factor receptor signaling network reveals dynamicmodules.";
Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J.,Lauffenburger D.A., White F.M.;
Mol. Cell. Proteomics 4:1240-1250(2005).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-447, AND MASSSPECTROMETRY.
PubMed: 15951569