Descriptions

Human PTK6 (also known as breast tumor kinase (Brk)) is a non-receptor protein-tyrosine kinase. 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. PTK6 is composed of SH3, SH2, and catalytic domains. The SH3 domain binds the proline-rich linker region between the SH2 domain and the catalytic domain. The disruption of the interaction enhances the oncogenic property of PTK6. In addition, mutation at SH2 domain of PTK6 resulted in higher catalytic activity. The site plays an important role in its negative regulation of the enzyme activity. Tyr(P) peptide derived from the C-terminal region of PTK6 including Tyr(P)-447 successfully bound to the SH2 domain, supporting the autoinhibitory role of PTK6 protein.

Autoinhibitory domains (AIDs)

Target domain

271-524 (Protein kinase domain)

Relief mechanism

Ligand binding

Assay

Target domain

271-524 (Protein kinase domain)

Relief mechanism

Ligand binding

Assay

Target domain

271-524 (Protein kinase domain)

Relief mechanism

Assay

Target domain

271-524 (Protein kinase domain)

Relief mechanism

PTM

Assay

Accessory elements

407-431 (Activation loop from InterPro)

Target domain

271-520 (Tyrosine-protein kinase, catalytic domain)

Relief mechanism

Assay

References

Autoinhibited structure

Activated structure

1 structures for Q6EWH2

Entry ID Method Resolution Chain Position Source
AF-Q6EWH2-F1 Predicted AlphaFoldDB

No variants for Q6EWH2

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q6EWH2

No associated diseases with Q6EWH2

5 regional properties for Q6EWH2

Type Name Position InterPro Accession
domain 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain 526 - 850 IPR002073
domain GAF domain 154 - 314 IPR003018-1
domain GAF domain 336 - 503 IPR003018-2
domain HD/PDEase domain 600 - 777 IPR003607
conserved_site 3'5'-cyclic nucleotide phosphodiesterase, conserved site 643 - 654 IPR023174

Functions

Description
EC Number 2.7.10.- Protein-tyrosine kinases
Subcellular Localization
  • Cytoplasm
  • Nucleus
  • Transiently expressed in the nucleus at mid-blastula stage (3
  • 3 hpf) in a large subset of cells
  • Nuclear localization is not observed from late blastula stage onward
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

3 GO annotations of cellular component

Name Definition
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
extrinsic component of cytoplasmic side of plasma membrane The component of a plasma membrane consisting of gene products and protein complexes that are loosely bound to its cytoplasmic surface, but not integrated into the hydrophobic region.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.

5 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
metal ion binding Binding to a metal ion.
non-membrane spanning protein tyrosine kinase activity Catalysis of the reaction
protein kinase activity Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction
signaling receptor binding Binding to one or more specific sites on a receptor molecule, a macromolecule that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function.

10 GO annotations of biological process

Name Definition
adherens junction maintenance The maintenance of an adherens junction. An adherens junction is a cell-cell junction composed of the epithelial cadherin-catenin complex at which the cytoplasmic face of the plasma membrane is attached to actin filaments.
cell differentiation The cellular developmental process in which a relatively unspecialized cell, e.g. embryonic or regenerative cell, acquires specialized structural and/or functional features that characterize a specific cell. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state.
convergent extension involved in gastrulation The morphogenetic process in which an epithelium narrows along one axis and lengthens in a perpendicular axis usually resulting in the formation of the three primary germ layers, ectoderm, mesoderm and endoderm.
gastrulation with mouth forming second A gastrulation process in which the initial invagination becomes the anus and the mouth forms second.
innate immune response Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens.
myelination The process in which myelin sheaths are formed and maintained around neurons. Oligodendrocytes in the brain and spinal cord and Schwann cells in the peripheral nervous system wrap axons with compact layers of their plasma membrane. Adjacent myelin segments are separated by a non-myelinated stretch of axon called a node of Ranvier.
phosphorylation The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide.
regulation of cytosolic calcium ion concentration Any process involved in the maintenance of an internal steady state of calcium ions within the cytosol of a cell or between the cytosol and its surroundings.
T cell receptor signaling pathway The series of molecular signals initiated by the cross-linking of an antigen receptor on a T cell.
transmembrane receptor protein tyrosine kinase signaling pathway The series of molecular signals initiated by an extracellular ligand binding to a receptor on the surface of the target cell where the receptor possesses tyrosine kinase activity, and ending with the regulation of a downstream cellular process, e.g. transcription.

77 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q0VBZ0 CSK Tyrosine-protein kinase CSK Bos taurus (Bovine) SS
Q3ZC95 BTK Tyrosine-protein kinase Bos taurus (Bovine) EV SS
A0JNB0 FYN Tyrosine-protein kinase Fyn Bos taurus (Bovine) SS
P42683 LCK Proto-oncogene tyrosine-protein kinase LCK Gallus gallus (Chicken) SS
P41239 CSK Tyrosine-protein kinase CSK Gallus gallus (Chicken) SS
P00523 SRC Proto-oncogene tyrosine-protein kinase Src Gallus gallus (Chicken) EV
Q02977 YRK Proto-oncogene tyrosine-protein kinase Yrk Gallus gallus (Chicken) SS
Q8JH64 BTK Tyrosine-protein kinase BTK Gallus gallus (Chicken) SS
P09324 YES1 Tyrosine-protein kinase Yes Gallus gallus (Chicken) SS
Q75R65 JAK2 Tyrosine-protein kinase JAK2 Gallus gallus (Chicken) SS
Q05876 FYN Tyrosine-protein kinase Fyn Gallus gallus (Chicken) SS
Q24592 hop Tyrosine-protein kinase hopscotch Drosophila melanogaster (Fruit fly) PR
P08630 Btk Tyrosine-protein kinase Btk Drosophila melanogaster (Fruit fly) SS
Q9V9J3 Src42A Tyrosine-protein kinase Src42A Drosophila melanogaster (Fruit fly) SS
P00528 Src64B Tyrosine-protein kinase Src64B Drosophila melanogaster (Fruit fly) SS
P41240 CSK Tyrosine-protein kinase CSK Homo sapiens (Human) SS
P51451 BLK Tyrosine-protein kinase Blk Homo sapiens (Human) SS
P06239 LCK Tyrosine-protein kinase Lck Homo sapiens (Human) EV
P23458 JAK1 Tyrosine-protein kinase JAK1 Homo sapiens (Human) SS
P51813 BMX Cytoplasmic tyrosine-protein kinase BMX Homo sapiens (Human) SS
P12931 SRC Proto-oncogene tyrosine-protein kinase Src Homo sapiens (Human) EV
P09769 FGR Tyrosine-protein kinase Fgr Homo sapiens (Human) SS
P42680 TEC Tyrosine-protein kinase Tec Homo sapiens (Human) SS
O60674 JAK2 Tyrosine-protein kinase JAK2 Homo sapiens (Human) EV
P42679 MATK Megakaryocyte-associated tyrosine-protein kinase Homo sapiens (Human) SS
P52333 JAK3 Tyrosine-protein kinase JAK3 Homo sapiens (Human) SS
Q08881 ITK Tyrosine-protein kinase ITK/TSK Homo sapiens (Human) EV
P07948 LYN Tyrosine-protein kinase Lyn Homo sapiens (Human) SS
P29597 TYK2 Non-receptor tyrosine-protein kinase TYK2 Homo sapiens (Human) EV
Q13882 PTK6 Protein-tyrosine kinase 6 Homo sapiens (Human) EV
P08631 HCK Tyrosine-protein kinase HCK Homo sapiens (Human) EV
P07947 YES1 Tyrosine-protein kinase Yes Homo sapiens (Human) SS
P42685 FRK Tyrosine-protein kinase FRK Homo sapiens (Human) EV
Q06187 BTK Tyrosine-protein kinase BTK Homo sapiens (Human) EV
P06241 FYN Tyrosine-protein kinase Fyn Homo sapiens (Human) SS
Q9R117 Tyk2 Non-receptor tyrosine-protein kinase TYK2 Mus musculus (Mouse) SS
P08103 Hck Tyrosine-protein kinase HCK Mus musculus (Mouse) SS
P16277 Blk Tyrosine-protein kinase Blk Mus musculus (Mouse) SS
Q62270 Srms Tyrosine-protein kinase Srms Mus musculus (Mouse) SS
Q64434 Ptk6 Protein-tyrosine kinase 6 Mus musculus (Mouse) SS
P05480 Src Proto-oncogene tyrosine-protein kinase Src Mus musculus (Mouse) EV
P14234 Fgr Tyrosine-protein kinase Fgr Mus musculus (Mouse) SS
P35991 Btk Tyrosine-protein kinase BTK Mus musculus (Mouse) EV
P41241 Csk Tyrosine-protein kinase CSK Mus musculus (Mouse) EV
P25911 Lyn Tyrosine-protein kinase Lyn Mus musculus (Mouse) EV
Q62137 Jak3 Tyrosine-protein kinase JAK3 Mus musculus (Mouse) SS
Q62120 Jak2 Tyrosine-protein kinase JAK2 Mus musculus (Mouse) EV
P06240 Lck Proto-oncogene tyrosine-protein kinase LCK Mus musculus (Mouse) SS
P24604 Tec Tyrosine-protein kinase Tec Mus musculus (Mouse) SS
Q04736 Yes1 Tyrosine-protein kinase Yes Mus musculus (Mouse) SS
P52332 Jak1 Tyrosine-protein kinase JAK1 Mus musculus (Mouse) SS
Q03526 Itk Tyrosine-protein kinase ITK/TSK Mus musculus (Mouse) SS
P41242 Matk Megakaryocyte-associated tyrosine-protein kinase Mus musculus (Mouse) SS
Q922K9 Frk Tyrosine-protein kinase FRK Mus musculus (Mouse) SS
P39688 Fyn Tyrosine-protein kinase Fyn Mus musculus (Mouse) SS
O19064 JAK2 Tyrosine-protein kinase JAK2 Sus scrofa (Pig) SS
A1Y2K1 FYN Tyrosine-protein kinase Fyn Sus scrofa (Pig) SS
Q62662 Frk Tyrosine-protein kinase FRK Rattus norvegicus (Rat) SS
Q07014 Lyn Tyrosine-protein kinase Lyn Rattus norvegicus (Rat) SS
P50545 Hck Tyrosine-protein kinase HCK Rattus norvegicus (Rat) SS
Q9WUD9 Src Proto-oncogene tyrosine-protein kinase Src Rattus norvegicus (Rat) SS
Q01621 Lck Proto-oncogene tyrosine-protein kinase LCK Rattus norvegicus (Rat) SS
Q6P6U0 Fgr Tyrosine-protein kinase Fgr Rattus norvegicus (Rat) SS
Q62689 Jak2 Tyrosine-protein kinase JAK2 Rattus norvegicus (Rat) SS
Q63272 Jak3 Tyrosine-protein kinase JAK3 Rattus norvegicus (Rat) SS
P32577 Csk Tyrosine-protein kinase CSK Rattus norvegicus (Rat) SS
P41243 Matk Megakaryocyte-associated tyrosine-protein kinase Rattus norvegicus (Rat) SS
F1LM93 Yes1 Tyrosine-protein kinase Yes Rattus norvegicus (Rat) SS
Q62844 Fyn Tyrosine-protein kinase Fyn Rattus norvegicus (Rat) SS
G5ECJ6 csk-1 Tyrosine-protein kinase csk-1 Caenorhabditis elegans SS
O45539 src-2 Tyrosine protein-kinase src-2 Caenorhabditis elegans SS
G5EE56 src-1 Tyrosine protein-kinase src-1 Caenorhabditis elegans SS
Q2MHE4 HT1 Serine/threonine/tyrosine-protein kinase HT1 Arabidopsis thaliana (Mouse-ear cress) PR
O12990 jak1 Tyrosine-protein kinase JAK1 Danio rerio (Zebrafish) (Brachydanio rerio) PR
F1RDG9 fynb Tyrosine-protein kinase fynb Danio rerio (Zebrafish) (Brachydanio rerio) SS
Q1JPZ3 src Proto-oncogene tyrosine-protein kinase Src Danio rerio (Zebrafish) (Brachydanio rerio) SS
A1A5H8 yes1 Tyrosine-protein kinase yes Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MGCVQCKDKE ATKLTDERET SVSQHAGYRY GSDPTPQHYP SFGVTAIPNY NNFHAPVSQG
70 80 90 100 110 120
VTVFGGVNSS SHSGTLRSRG GTGVTLFVAL YDYEARSEDD LSFRKGEKFQ ILNSTEGDWW
130 140 150 160 170 180
EARSLTTGGT GYIPSNYVAP VDSIQAEDWY FGKLGRKDAE RQLLSNGNPR GTFLIRESET
190 200 210 220 230 240
TKGAYSLSIQ DWDETKGDHV KHYKIRKLDN GGYYITTRAQ FETLQQLVHH YSARAAGLCC
250 260 270 280 290 300
RLIVPCHKGM PRLADLSVKT KDVWEIPRES LQLIKRLGNG QFGEVWMGTW NGNTKVAVKT
310 320 330 340 350 360
LKPGTMSPES FLEEAQIMKK LRHDKLVQLY AVVSEEPIYI VTEYMSKGSL LDFLKDGEGR
370 380 390 400 410 420
GLKLPNLVDM AAQVAAGMAY IERMNYIHRD LRSANILVGD SLVCKIADFG LARLIEDNEY
430 440 450 460 470 480
TARQGAKFPI KWTAPEAALY GRFTIKSDVW SFGILLTELV TKGRVPYPGM NNREVLEQVE
490 500 510 520 530
RGYRMPCPQD CPSSLHELML QCWKRDPEER PTFEYLQAFL EDYFTATEPQ YQPGDNL