PTK6
entrez
5753
canonical
uniprot
Q13882
canonical
ensembl
ENSG00000101213
resolver
ensp
ENSP00000217185
resolver
ensp
ENSP00000442460
resolver
genesymbol
PTK6
resolver
genesymbol_syn
BRK
resolver
hgnc
HGNC:9617
resolver
uniprot
B2RCR3
resolver
uniprot
B4DW46
resolver
uniprot
Q58F01
resolver
uniprot_entry
PTK6_HUMAN
resolver
uniprot_sec
B2RCR3
resolver
uniprot_sec
B4DW46
resolver
uniprot_sec
Q58F01
resolver
activity_regulation
ACTIVITY 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. {ECO:0000269|PubMed:12121988, ECO:0000269|PubMed:15870689, ECO:0000269|PubMed:15961400, ECO:0000269|PubMed:16568091, ECO:0000269|PubMed:17822667}.
uniprot
proteins
amino_acid_sequence
MVSRDQAHLGPKYVGLWDFKSRTDEELSFRAGDVFHVARKEEQWWWATLLDEAGGAVAQGYVPHNYLAERETVESEPWFFGCISRSEAVRRLQAEGNATGAFLIRVSEKPSADYVLSVRDTQAVRHYKIWRRAGGRLHLNEAVSFLSLPELVNYHRAQSLSHGLRLAAPCRKHEPEPLPHWDDWERPREEFTLCRKLGSGYFGEVFEGLWKDRVQVAIKVISRDNLLHQQMLQSEIQAMKKLRHKHILALYAVVSVGDPVYIITELMAKGSLLELLRDSDEKVLPVSELLDIAWQVAEGMCYLESQNYIHRDLAARNILVGENTLCKVGDFGLARLIKEDVYLSHDHNIPYKWTAPEALSRGHYSTKSDVWSFGILLHEMFSRGQVPYPGMSNHEAFLRVDAGYRMPCPLECPPSVHKLMLTCWCRDPEQRPCFKALRERLSSFTSYENPT
uniprot
proteins
ec_number
2.7.10.2
uniprot
proteins
function
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. Phosphorylates the GTPase-activating protein ARAP1 following EGF stimulation which enhances EGFR signaling by delaying EGFR down-regulation (PubMed:20554524). Also associates 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. {ECO:0000269|PubMed:20554524}.; FUNCTION: [Isoform 2]: Inhibits PTK6 phosphorylation and PTK6 association with other tyrosine-phosphorylated proteins.
uniprot
proteins
mass_dalton
51834
uniprot
proteins
mutagenesis
MUTAGEN 44; /note="W->A: Strong decrease in STAP2 phosphorylation. Markedly decreased interaction between SH3 domain the linker region."; /evidence="ECO:0000269|PubMed:10980601, ECO:0000269|PubMed:17822667"; MUTAGEN 66; /note="Y->A: Decrease in STAP2 phosphorylation."; /evidence="ECO:0000269|PubMed:10980601"; MUTAGEN 105; /note="R->A: Abolishes interaction with ARAP1."; /evidence="ECO:0000269|PubMed:20554524"; MUTAGEN 105; /note="R->L: Decrease in STAP2 phosphorylation."; /evidence="ECO:0000269|PubMed:10980601"; MUTAGEN 184; /note="W->A: Abrogates interaction between PTK6-domain kinase and PTK6-linker. Abrogates autophosphorylation and phosphorylation of KHDRBS1."; /evidence="ECO:0000269|PubMed:15961400"; MUTAGEN 219; /note="K->M: Abolishes kinase activity and cell transformation, and phosphorylation of STAP2. Reduces interaction with ARAP1."; /evidence="ECO:0000269|PubMed:10980601, ECO:0000269|PubMed:15471878, ECO:0000269|PubMed:20554524, ECO:0000269|PubMed:8940083"; MUTAGEN 219; /note="K->R: Abolishes kinase activity."; /evidence="ECO:0000269|PubMed:27480927"; MUTAGEN 342; /note="Y->A: 3-fold lower specific kinase activity. Decreased, but still significant, autophosphorylation. Decreased, but still significant, autophosphorylation; when associated with A-447."; /evidence="ECO:0000269|PubMed:12121988"; MUTAGEN 447; /note="Y->F: Decrease in transforming potential and increase in the kinase activity level. Decreased, but still significant, autophosphorylation; when associated with A-342."; /evidence="ECO:0000269|PubMed:12121988, ECO:0000269|PubMed:15471878, ECO:0000269|PubMed:8940083
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000269|PubMed:10913193, ECO:0000269|PubMed:12121988, ECO:0000269|PubMed:15471878, ECO:0000269|PubMed:20026641}.
uniprot
proteins
protein_family
BRK/PTK6/SIK subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
10913193
uniprot
proteins
pubmed
10980601
uniprot
proteins
pubmed
11780052
uniprot
proteins
pubmed
12121988
uniprot
proteins
pubmed
12833144
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15056653
uniprot
proteins
pubmed
15471878
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15509496
uniprot
proteins
pubmed
15539407
uniprot
proteins
pubmed
15572663
uniprot
proteins
pubmed
15870689
uniprot
proteins
pubmed
15961400
uniprot
proteins
pubmed
16179349
uniprot
proteins
pubmed
16568091
uniprot
proteins
pubmed
16651629
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17822667
uniprot
proteins
pubmed
17997837
uniprot
proteins
pubmed
18296648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18719096
uniprot
proteins
pubmed
18829532
uniprot
proteins
pubmed
19439179
uniprot
proteins
pubmed
20026641
uniprot
proteins
pubmed
20193745
uniprot
proteins
pubmed
20554524
uniprot
proteins
pubmed
21479203
uniprot
proteins
pubmed
27480927
uniprot
proteins
pubmed
27993680
uniprot
proteins
pubmed
8036022
uniprot
proteins
pubmed
8940083
uniprot
proteins
pubmed
9185712
uniprot
proteins
pubmed
9333026
uniprot
proteins
pubmed
9749526
uniprot
proteins
sequence_length
451
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell projection, ruffle. Membrane {ECO:0000250}. Note=Colocalizes with KHDRBS1, KHDRBS2 or KHDRBS3, within the nucleus. Nuclear localization in epithelial cells of normal prostate but cytoplasmic localization in cancer prostate.
uniprot
proteins