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Protein

Protein-tyrosine kinase 6

Gene

Ptk6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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.3 Publications

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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei219ATPPROSITE-ProRule annotation1
Active sitei312Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi197 – 205ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase, Tyrosine-protein kinase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2 3474
ReactomeiR-MMU-187577 SCF(Skp2)-mediated degradation of p27/p21
R-MMU-69231 Cyclin D associated events in G1
R-MMU-8847993 ERBB2 Activates PTK6 Signaling
R-MMU-8849468 PTK6 Regulates Proteins Involved in RNA Processing
R-MMU-8849469 PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1
R-MMU-8849470 PTK6 Regulates Cell Cycle
R-MMU-8849471 PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases
R-MMU-8849472 PTK6 Down-Regulation
R-MMU-8849474 PTK6 Activates STAT3
R-MMU-8857538 PTK6 promotes HIF1A stabilization

Names & Taxonomyi

Protein namesi
Recommended name:
Protein-tyrosine kinase 6 (EC:2.7.10.2)
Alternative name(s):
SRC-related intestinal kinase
Gene namesi
Name:Ptk6
Synonyms:Sik
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:99683 Ptk6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell projection, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Deficient mice have an increased cell turnover in the small intestine, which is accompanied by increased villus length and crypt depth and delayed enterocyte differentiation that is accompanied by increased PTK/AKT and WNT signaling.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi447Y → F: Increase in the kinase activation level. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000881341 – 451Protein-tyrosine kinase 6Add BLAST451

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei13PhosphotyrosineBy similarity1
Modified residuei61PhosphotyrosineBy similarity1
Modified residuei66PhosphotyrosineBy similarity1
Modified residuei114PhosphotyrosineBy similarity1
Modified residuei342Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei351PhosphotyrosineBy similarity1
Modified residuei447PhosphotyrosineBy similarityCurated1

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 (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ64434
PaxDbiQ64434
PRIDEiQ64434

PTM databases

iPTMnetiQ64434
PhosphoSitePlusiQ64434

Expressioni

Tissue specificityi

Expressed only in epithelial tissues, including the skin and lining of the alimentary canal. Restricted to the cell layers immediately above the proliferative cell zone in these epithelia.1 Publication

Developmental stagei

First detected at day 15.5 of gestation in the embryo, where it is expressed in the newly forming granular layer of the skin. Is found in stomach at day 17.5.1 Publication

Gene expression databases

BgeeiENSMUSG00000038751
CleanExiMM_PTK6
ExpressionAtlasiQ64434 baseline and differential
GenevisibleiQ64434 MM

Interactioni

Subunit structurei

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

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ64434, 1 interactor
MINTiQ64434
STRINGi10090.ENSMUSP00000016511

Structurei

3D structure databases

ProteinModelPortaliQ64434
SMRiQ64434
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini8 – 72SH3PROSITE-ProRule annotationAdd BLAST65
Domaini78 – 170SH2PROSITE-ProRule annotationAdd BLAST93
Domaini191 – 445Protein kinasePROSITE-ProRule annotationAdd BLAST255

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni171 – 190LinkerAdd BLAST20

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 (By similarity).By similarity

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. BRK/PTK6/SIK subfamily.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG0197 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118938
HOGENOMiHOG000233858
HOVERGENiHBG008761
InParanoidiQ64434
OMAiVRHYKIW
OrthoDBiEOG091G0596
PhylomeDBiQ64434
TreeFamiTF351634

Family and domain databases

CDDicd10358 SH2_PTK6_Brk, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR035846 PTK6_SH2
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PF00017 SH2, 1 hit
PF00018 SH3_1, 1 hit
PRINTSiPR00401 SH2DOMAIN
PR00452 SH3DOMAIN
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SM00326 SH3, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
SSF55550 SSF55550, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in 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

Sequencei

Sequence statusi: Complete.

Q64434-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVSWDKAHLG PKYVGLWDFK ARTDEELSFQ AGDLLHVTKK EELWWWATLL
60 70 80 90 100
DAEGKALAEG YVPHNYLAEK ETVESEPWFF GCISRSEAMH RLQAEDNSKG
110 120 130 140 150
AFLIRVSQKP GADYVLSVRD AQAVRHYRIW KNNEGRLHLN EAVSFSNLSE
160 170 180 190 200
LVDYHKTQSL SHGLQLSMPC WKHKTEPLPH WDDWERPREE FTLCKKLGAG
210 220 230 240 250
YFGEVFEALW KGQVHVAVKV ISRDNLLHQH TFQAEIQAMK KLRHKHILSL
260 270 280 290 300
YAVATAGDPV YIITELMPKG NLLQLLRDSD EKALPILELV DFASQVAEGM
310 320 330 340 350
CYLESQNYIH RDLAARNVLV TENNLCKVGD FGLARLVKED IYLSHEHNVP
360 370 380 390 400
YKWTAPEALS RGHYSIKSDV WSFGVLLHEI FSRGQMPYPG MSNHETFLRV
410 420 430 440 450
DAGYRMPCPL ECPPNIHKLM LSCWSRDPKQ RPCFKDLCEK LTGITRYENL

V
Length:451
Mass (Da):51,972
Last modified:November 1, 1996 - v1
Checksum:i8FBEC26025498DEC
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U16805 mRNA Translation: AAA67929.1
AF016545 Genomic DNA Translation: AAB94550.1
CCDSiCCDS17203.1
RefSeqiNP_033210.1, NM_009184.2
UniGeneiMm.4497

Genome annotation databases

EnsembliENSMUST00000016511; ENSMUSP00000016511; ENSMUSG00000038751
GeneIDi20459
UCSCiuc008olk.1 mouse

Similar proteinsi

Entry informationi

Entry nameiPTK6_MOUSE
AccessioniPrimary (citable) accession number: Q64434
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1996
Last modified: May 23, 2018
This is version 163 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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