P16277

SS
Gene name
Blk
Protein name
Tyrosine-protein kinase Blk
Names
EC 2.7.10.2 , B lymphocyte kinase , p55-Blk
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:12143
EC number
2.7.10.2: Protein-tyrosine kinases
Protein Class

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)

118-214 (SH2 domain) SS

Target domain

235-488 (Protein kinase domain)

Relief mechanism

PTM

Assay

215-234 (SH2-kinase linker) SS

Target domain

235-488 (Protein kinase domain)

Relief mechanism

Ligand binding

Assay

489-499 (C-terminal regulatory tail) SS

Target domain

235-488 (Protein kinase domain)

Relief mechanism

PTM

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

3 structures for P16277

Entry ID Method Resolution Chain Position Source
1BLJ NMR - A 107-218 PDB
1BLK NMR - A 107-218 PDB
AF-P16277-F1 Predicted AlphaFoldDB

27 variants for P16277

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3389308443 6 S>R No EVA
rs3389308440 49 D>N No EVA
rs3389335788 51 D>Y No EVA
rs3389348308 58 V>M No EVA
rs253480266 83 R>K No EVA
rs3389333752 114 E>D No EVA
rs3389332114 130 R>M No EVA
rs3389337830 140 G>D No EVA
rs3389308498 145 R>I No EVA
rs3389335812 151 K>R No EVA
rs256188337 161 I>V No EVA
rs3389352431 204 D>E No EVA
rs3389333805 215 V>M No EVA
rs3389336184 224 A>G No EVA
rs3389318159 226 D>N No EVA
rs3389343180 249 V>A No EVA
rs3389352432 280 N>Y No EVA
rs3389326362 291 V>I No EVA
rs3389335813 301 P>T No EVA
rs3389336220 305 V>A No EVA
rs3389333811 317 F>V No EVA
rs3389318165 413 W>* No EVA
rs3389332125 433 M>T No EVA
rs258202701 462 I>V No EVA
rs3389318111 464 T>A No EVA
rs3389337837 479 F>Y No EVA
rs3389333761 491 T>K No EVA

No associated diseases with P16277

10 regional properties for P16277

Type Name Position InterPro Accession
domain C2 domain 609 - 737 IPR000008
domain Phosphatidylinositol-specific phospholipase C, X domain 296 - 441 IPR000909
domain Phospholipase C, phosphatidylinositol-specific, Y domain 492 - 609 IPR001711
domain Pleckstrin homology domain 19 - 132 IPR001849
domain EF-hand domain 140 - 175 IPR002048
domain Phosphoinositide-specific phospholipase C, EF-hand-like domain 204 - 288 IPR015359
binding_site EF-Hand 1, calcium-binding site 153 - 165 IPR018247-1
binding_site EF-Hand 1, calcium-binding site 189 - 201 IPR018247-2
domain 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1, catalytic domain 295 - 596 IPR028391
domain 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1, EF-hand domain 144 - 283 IPR046975

Functions

Description
EC Number 2.7.10.2 Protein-tyrosine kinases
Subcellular Localization
  • Cell membrane ; Lipid-anchor
  • Present and active in lipid rafts (By similarity)
  • Membrane location is required for the phosphorylation of CD79A and CD79B
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

2 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.

4 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
non-membrane spanning protein tyrosine kinase activity Catalysis of the reaction
protein tyrosine kinase activity Catalysis of 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.

6 GO annotations of biological process

Name Definition
B cell receptor signaling pathway The series of molecular signals initiated by the cross-linking of an antigen receptor on a B cell.
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.
innate immune response Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens.
peptidyl-tyrosine phosphorylation The phosphorylation of peptidyl-tyrosine to form peptidyl-O4'-phospho-L-tyrosine.
positive regulation of insulin secretion Any process that activates or increases the frequency, rate or extent of the regulated release of insulin.
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.

90 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
A0JNB0 FYN Tyrosine-protein kinase Fyn Bos taurus (Bovine) SS
Q0VBZ0 CSK Tyrosine-protein kinase CSK Bos taurus (Bovine) SS
Q3ZC95 BTK Tyrosine-protein kinase Bos taurus (Bovine) EV 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
Q05876 FYN Tyrosine-protein kinase Fyn Gallus gallus (Chicken) SS
Q75R65 JAK2 Tyrosine-protein kinase JAK2 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
P00528 Src64B Tyrosine-protein kinase Src64B Drosophila melanogaster (Fruit fly) SS
Q9V9J3 Src42A Tyrosine-protein kinase Src42A Drosophila melanogaster (Fruit fly) SS
P41240 CSK Tyrosine-protein kinase CSK Homo sapiens (Human) SS
P06239 LCK Tyrosine-protein kinase Lck Homo sapiens (Human) EV
P23458 JAK1 Tyrosine-protein kinase JAK1 Homo sapiens (Human) SS
P06241 FYN Tyrosine-protein kinase Fyn 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
P51451 BLK Tyrosine-protein kinase Blk Homo sapiens (Human) SS
Q9R117 Tyk2 Non-receptor tyrosine-protein kinase TYK2 Mus musculus (Mouse) SS
Q62137 Jak3 Tyrosine-protein kinase JAK3 Mus musculus (Mouse) SS
Q62120 Jak2 Tyrosine-protein kinase JAK2 Mus musculus (Mouse) EV
P52332 Jak1 Tyrosine-protein kinase JAK1 Mus musculus (Mouse) SS
P05480 Src Proto-oncogene tyrosine-protein kinase Src Mus musculus (Mouse) EV
P06240 Lck Proto-oncogene tyrosine-protein kinase LCK Mus musculus (Mouse) SS
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
Q03526 Itk Tyrosine-protein kinase ITK/TSK Mus musculus (Mouse) SS
Q04736 Yes1 Tyrosine-protein kinase Yes Mus musculus (Mouse) SS
Q64434 Ptk6 Protein-tyrosine kinase 6 Mus musculus (Mouse) SS
Q922K9 Frk Tyrosine-protein kinase FRK Mus musculus (Mouse) SS
P48025 Syk Tyrosine-protein kinase SYK Mus musculus (Mouse) SS
P43404 Zap70 Tyrosine-protein kinase ZAP-70 Mus musculus (Mouse) SS
P25911 Lyn Tyrosine-protein kinase Lyn Mus musculus (Mouse) EV
P39688 Fyn Tyrosine-protein kinase Fyn Mus musculus (Mouse) SS
P08103 Hck Tyrosine-protein kinase HCK Mus musculus (Mouse) SS
P24604 Tec Tyrosine-protein kinase Tec Mus musculus (Mouse) SS
P41242 Matk Megakaryocyte-associated tyrosine-protein kinase Mus musculus (Mouse) SS
Q9QVP9 Ptk2b Protein-tyrosine kinase 2-beta Mus musculus (Mouse) PR
P34152 Ptk2 Focal adhesion kinase 1 Mus musculus (Mouse) SS
Q99ML2 Tnk1 Non-receptor tyrosine-protein kinase TNK1 Mus musculus (Mouse) PR
O54967 Tnk2 Activated CDC42 kinase 1 Mus musculus (Mouse) SS
P70451 Fer Tyrosine-protein kinase Fer Mus musculus (Mouse) PR
Q6J9G1 Styk1 Tyrosine-protein kinase STYK1 Mus musculus (Mouse) PR
P00520 Abl1 Tyrosine-protein kinase ABL1 Mus musculus (Mouse) EV
Q62270 Srms Tyrosine-protein kinase Srms Mus musculus (Mouse) SS
Q4JIM5 Abl2 Tyrosine-protein kinase ABL2 Mus musculus (Mouse) SS
A1Y2K1 FYN Tyrosine-protein kinase Fyn Sus scrofa (Pig) SS
O19064 JAK2 Tyrosine-protein kinase JAK2 Sus scrofa (Pig) SS
Q62662 Frk Tyrosine-protein kinase FRK Rattus norvegicus (Rat) SS
Q62844 Fyn Tyrosine-protein kinase Fyn 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
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
O22558 STY8 Serine/threonine-protein kinase STY8 Arabidopsis thaliana (Mouse-ear cress) PR
Q8RWL6 STY17 Serine/threonine-protein kinase STY17 Arabidopsis thaliana (Mouse-ear cress) PR
F4JTP5 STY46 Serine/threonine-protein kinase STY46 Arabidopsis thaliana (Mouse-ear cress) PR
A1A5H8 yes1 Tyrosine-protein kinase yes Danio rerio (Zebrafish) (Brachydanio rerio) SS
F1RDG9 fynb Tyrosine-protein kinase fynb Danio rerio (Zebrafish) (Brachydanio rerio) SS
O12990 jak1 Tyrosine-protein kinase JAK1 Danio rerio (Zebrafish) (Brachydanio rerio) PR
Q1JPZ3 src Proto-oncogene tyrosine-protein kinase Src Danio rerio (Zebrafish) (Brachydanio rerio) SS
Q6EWH2 fyna Tyrosine-protein kinase fyna Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MGLLSSKRQV SEKGKGWSPV KIRTQDKAPP PLPPLVVFNH LAPPSPNQDP DEEERFVVAL
70 80 90 100 110 120
FDYAAVNDRD LQVLKGEKLQ VLRSTGDWWL ARSLVTGREG YVPSNFVAPV ETLEVEKWFF
130 140 150 160 170 180
RTISRKDAER QLLAPMNKAG SFLIRESESN KGAFSLSVKD ITTQGEVVKH YKIRSLDNGG
190 200 210 220 230 240
YYISPRITFP TLQALVQHYS KKGDGLCQKL TLPCVNLAPK NLWAQDEWEI PRQSLKLVRK
250 260 270 280 290 300
LGSGQFGEVW MGYYKNNMKV AIKTLKEGTM SPEAFLGEAN VMKTLQHERL VRLYAVVTRE
310 320 330 340 350 360
PIYIVTEYMA RGCLLDFLKT DEGSRLSLPR LIDMSAQVAE GMAYIERMNS IHRDLRAANI
370 380 390 400 410 420
LVSETLCCKI ADFGLARIID SEYTAQEGAK FPIKWTAPEA IHFGVFTIKA DVWSFGVLLM
430 440 450 460 470 480
EIVTYGRVPY PGMSNPEVIR SLEHGYRMPC PETCPPELYN DIITECWRGR PEERPTFEFL
490
QSVLEDFYTA TEGQYELQP