Q0VBZ0

SS
Gene name
CSK
Protein name
Tyrosine-protein kinase CSK
Names
EC 2.7.10.2 , C-Src kinase
Species
Bos taurus (Bovine)
KEGG Pathway
bta:509246
EC number
2.7.10.2: Protein-tyrosine kinases
Protein Class

Descriptions

The kinase Csk is the primary negative regulator of the Src‐family kinases (SFKs, e.g., Lck, Fyn, Lyn, Hck, Fgr, Blk, Yes). Csk phosphorylates a tyrosine on the SFK C‐terminal tail that mediates autoinhibition. Csk is recruited to membrane-anchored SFKs and activated allosterically via its SH2 domain, which binds SFK- phosphorylated motifs in CBP/PAG1 (Csk binding protein/phosphoprotein associated with glycosphingolipid- enriched microdomains), Paxillin, Fak, the Dok family, and other tyrosine-phosphorylated proteins. Csk also binds phosphatases, including PTPN12 (PTP‐PEST) and immune‐cell PTPN22 (LYP/Pep), which dephosphorylate SFK activation loop to promote autoinhibition. <br> Purified Csk homodimerizes in competition with PTPN22 binding through an interface that is mediated by symmetrical SH3-SH3 interactions and that overlaps the phosphatase binding footprint. Mutation in SH3 impairing homodimerization enhances PTPN22 binding.

Autoinhibitory domains (AIDs)

9-70 (SH3 domain) SS

Target domain

9-70 (SH3 domain)

Relief mechanism

Partner binding

Assay

80-171 (SH2 domain) SS

Target domain

195-444 (Protein kinase domain)

Relief mechanism

Ligand binding

Assay

Accessory elements

331-351 (Activation loop from InterPro)

Target domain

195-449 (Protein kinase domain)

Relief mechanism

Assay

References

Autoinhibited structure

Activated structure

1 structures for Q0VBZ0

Entry ID Method Resolution Chain Position Source
AF-Q0VBZ0-F1 Predicted AlphaFoldDB

108 variants for Q0VBZ0

Variant ID(s) Position Change Description Diseaes Association Provenance
rs449556149 8 W>G No EVA
rs876411981 18 Y>D No EVA
rs3423493126 22 G>S No EVA
rs135375252 41 V>G No EVA
rs471027001 89 R>L No EVA
rs876557356 101 T>A No EVA
rs475346281 104 F>V No EVA
rs455028697 106 V>G No EVA
rs876356682 148 N>T No EVA
rs457765406 157 T>P No EVA
rs444022301 158 S>P No EVA
rs475368891 159 D>H No EVA
rs462068779 160 A>P No EVA
rs441837038 160 A>V No EVA
rs473085716 162 G>V No EVA
rs471962608 176 T>P No EVA
rs451660879 183 F>S No EVA
rs437997130 184 F>S No EVA
rs469327586 185 R>H No EVA
rs439570821 191 N>D No EVA
rs471316086 194 D>V No EVA
rs457592228 195 L>R No EVA
rs437391975 198 L>V No EVA
rs468569697 205 E>G No EVA
rs468569697 205 E>V No EVA
rs454498580 208 D>Y No EVA
rs441378056 249 V>G No EVA
rs472806707 260 S>G No EVA
rs452137299 265 V>F No EVA
rs476293208 266 T>P No EVA
rs456167744 268 Y>S No EVA
rs435970709 269 M>R No EVA
rs453981329 271 K>R No EVA
rs477998764 273 S>R No EVA
rs464263680 275 V>G No EVA
rs450403043 278 L>V No EVA
rs481581030 279 R>P No EVA
rs461890368 280 S>P No EVA
rs441837076 281 R>P No EVA
rs459512624 286 L>H No EVA
rs471924065 291 L>R No EVA
rs444462039 293 K>N No EVA
rs466034560 298 V>G No EVA
rs445894130 300 E>D No EVA
rs477324535 301 A>V No EVA
rs463586715 306 E>* No EVA
rs482364507 329 K>Q No EVA
rs462198190 340 S>P No EVA
rs442007042 342 T>P No EVA
rs473398013 344 D>A No EVA
rs460017398 350 V>I No EVA
rs439908265 352 W>R No EVA
rs471090624 353 T>A No EVA
rs452127625 383 G>A No EVA
rs472266159 383 G>W No EVA
rs431909778 387 Y>H No EVA
rs459111670 393 K>E No EVA
rs445446822 397 P>T No EVA
rs482759572 398 R>W No EVA
rs442451489 399 V>A No EVA
rs442451489 399 V>E No EVA
rs442451489 399 V>G No EVA
rs473766995 401 K>M No EVA
rs460476255 402 G>R No EVA
rs440323286 404 K>E No EVA
rs471700222 405 M>L No EVA
rs437709853 406 D>E No EVA
rs451444469 406 D>V No EVA
rs476519902 407 A>T No EVA
rs467769587 408 P>L No EVA
rs436412011 408 P>T No EVA
rs434322558 409 D>A No EVA
rs465663636 409 D>E No EVA
rs434322558 409 D>G No EVA
rs445464946 410 G>S No EVA
rs483180071 413 P>T No EVA
rs469087741 418 V>G No EVA
rs480327171 422 C>G No EVA
rs460134000 423 W>G No EVA
rs439985551 424 H>L No EVA
rs439985551 424 H>P No EVA
rs478156402 425 L>V No EVA
rs457837938 426 D>N No EVA
rs444211889 426 D>V No EVA
rs455349369 427 A>G No EVA
rs475377989 427 A>P No EVA
rs442928457 428 A>P No EVA
rs474319184 429 T>P No EVA
rs433925309 432 S>P No EVA
rs465675877 434 L>R No EVA
rs451990642 435 Q>K No EVA
rs438232304 435 Q>R No EVA
rs469606168 436 L>P No EVA
rs480421452 439 Q>E No EVA
rs466637068 441 E>A No EVA
rs446414913 443 I>L No EVA
rs477570657 443 I>S No EVA
rs477570657 443 I>T No EVA
rs457899542 445 T>P No EVA
rs444324256 446 H>R No EVA
rs481906013 447 E>* No EVA
rs461814682 447 E>D No EVA
rs481906013 447 E>K No EVA
rs441805950 448 L>P No EVA
rs454165366 449 H>D No EVA
rs876030187 449 H>P No EVA
rs471766628 450 L>P No EVA
rs451702425 451 L>S No EVA

No associated diseases with Q0VBZ0

13 regional properties for Q0VBZ0

Type Name Position InterPro Accession
domain C2 domain 1 - 117 IPR000008
domain Protein kinase domain 408 - 668 IPR000719
domain AGC-kinase, C-terminal 669 - 737 IPR000961
domain Protein kinase C-like, phorbol ester/diacylglycerol-binding domain 169 - 221 IPR002219-1
domain Protein kinase C-like, phorbol ester/diacylglycerol-binding domain 242 - 294 IPR002219-2
active_site Serine/threonine-protein kinase, active site 528 - 540 IPR008271
binding_site Protein kinase, ATP binding site 414 - 437 IPR017441
domain Protein kinase, C-terminal 689 - 730 IPR017892
domain Diacylglycerol/phorbol-ester binding 167 - 181 IPR020454-1
domain Diacylglycerol/phorbol-ester binding 183 - 192 IPR020454-2
domain Diacylglycerol/phorbol-ester binding 197 - 208 IPR020454-3
domain Diacylglycerol/phorbol-ester binding 281 - 293 IPR020454-4
domain Novel protein kinase C epsilon, catalytic domain 412 - 732 IPR034669

Functions

Description
EC Number 2.7.10.2 Protein-tyrosine kinases
Subcellular Localization
  • Cytoplasm
  • Cell membrane
  • Mainly cytoplasmic, also present in lipid rafts
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

2 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

3 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

4 GO annotations of biological process

Name Definition
adaptive immune response An immune response mediated by cells expressing specific receptors for antigens produced through a somatic diversification process, and allowing for an enhanced secondary response to subsequent exposures to the same antigen (immunological memory).
adherens junction organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly 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.
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 Fc receptor mediated stimulatory signaling pathway Any process that modulates the rate, frequency or extent of the Fc receptor mediated stimulatory signaling pathway..

79 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
A0JNB0 FYN Tyrosine-protein kinase Fyn Bos taurus (Bovine) SS
Q3ZC95 BTK Tyrosine-protein kinase Bos taurus (Bovine) EV SS
Q17R13 TNK2 Activated CDC42 kinase 1 Bos taurus (Bovine) SS
P42683 LCK Proto-oncogene tyrosine-protein kinase LCK 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
P41239 CSK Tyrosine-protein kinase CSK Gallus gallus (Chicken) SS
Q24592 hop Tyrosine-protein kinase hopscotch Drosophila melanogaster (Fruit fly) PR
Q9V9J3 Src42A Tyrosine-protein kinase Src42A Drosophila melanogaster (Fruit fly) SS
P00528 Src64B Tyrosine-protein kinase Src64B Drosophila melanogaster (Fruit fly) SS
P08630 Btk Tyrosine-protein kinase Btk Drosophila melanogaster (Fruit fly) 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
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
P41240 CSK Tyrosine-protein kinase CSK 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
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
P39688 Fyn Tyrosine-protein kinase Fyn 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
P41241 Csk Tyrosine-protein kinase CSK Mus musculus (Mouse) EV
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
P41243 Matk Megakaryocyte-associated tyrosine-protein kinase Rattus norvegicus (Rat) SS
F1LM93 Yes1 Tyrosine-protein kinase Yes Rattus norvegicus (Rat) SS
P32577 Csk Tyrosine-protein kinase CSK Rattus norvegicus (Rat) SS
O45539 src-2 Tyrosine protein-kinase src-2 Caenorhabditis elegans SS
G5EE56 src-1 Tyrosine protein-kinase src-1 Caenorhabditis elegans SS
Q8I7I5 rol-3 Protein roller-3 Caenorhabditis elegans PR
O16262 nipi-4 Protein nipi-4 Caenorhabditis elegans PR
G5ECJ6 csk-1 Tyrosine-protein kinase csk-1 Caenorhabditis elegans SS
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
MSAIQAAWPS GTECIAKYNF HGTAEQDLPF CKGDVLTIVA VTKDPNWYKA KNKVGREGII
70 80 90 100 110 120
PANYVQKREG VKAGTKLSLM PWFHGKITRE QAERLLCPPE TGLFLVREST NYPGDYTLCV
130 140 150 160 170 180
SCDGKVEHYR IMYHASKLSI DEEVYFENLM QLVEHYTSDA DGLCTRLIKP KVMEGTVAAQ
190 200 210 220 230 240
DEFFRSGWAL NMKDLKLLQT IGKGEFGDVM LGDYRGNKVA VKCIKNDATA QAFLAEASVM
250 260 270 280 290 300
TQLRHSNLVQ LLGVIVEEKS GLYIVTEYMA KGSLVDYLRS RGRSVLGGDC LLKFSLDVCE
310 320 330 340 350 360
AMEYLEGNNF VHRDLAARNV LVSEDNVAKV SDFGLTKEAS STQDTGKLPV KWTAPEALRE
370 380 390 400 410 420
KKFSTKSDVW SFGILLWEIY SFGRVPYPRI PLKDVVPRVE KGYKMDAPDG CPPAVYEVMK
430 440
NCWHLDAATR PSFLQLREQL ERIKTHELHL