P32577

SS
Gene name
Csk
Protein name
Tyrosine-protein kinase CSK
Names
EC 2.7.10.2 , C-Src kinase
Species
Rattus norvegicus (Rat)
KEGG Pathway
rno:315707
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

195-445 (Protein kinase domain)

Relief mechanism

Assay

References

Autoinhibited structure

Activated structure

3 structures for P32577

Entry ID Method Resolution Chain Position Source
1K9A X-ray 250 A A/B/C/D/E/F 1-450 PDB
2RSY NMR - A 80-173 PDB
AF-P32577-F1 Predicted AlphaFoldDB

No variants for P32577

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for P32577

No associated diseases with P32577

8 regional properties for P32577

Type Name Position InterPro Accession
domain Protein kinase domain 195 - 445 IPR000719
domain SH2 domain 80 - 171 IPR000980
domain Serine-threonine/tyrosine-protein kinase, catalytic domain 195 - 440 IPR001245
domain SH3 domain 9 - 70 IPR001452
active_site Tyrosine-protein kinase, active site 310 - 322 IPR008266
binding_site Protein kinase, ATP binding site 201 - 222 IPR017441
domain Tyrosine-protein kinase, catalytic domain 195 - 440 IPR020635
domain CSK-like, SH2 domain 78 - 175 IPR035027

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

3 GO annotations of cellular component

Name Definition
cell-cell junction A cell junction that forms a connection between two or more cells of an organism; excludes direct cytoplasmic intercellular bridges, such as ring canals in insects.
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.

9 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
identical protein binding Binding to an identical protein or proteins.
metal ion binding Binding to a metal ion.
non-membrane spanning protein tyrosine kinase activity Catalysis of the reaction
proline-rich region binding Binding to a proline-rich region, i.e. a region that contains a high proportion of proline residues, in a protein.
protein kinase A catalytic subunit binding Binding to one or both of the catalytic subunits of protein kinase A.
protein phosphatase binding Binding to a protein phosphatase.
protein tyrosine kinase activity Catalysis of the reaction
protein tyrosine kinase binding Binding to protein tyrosine kinase.

13 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.
cellular response to peptide hormone stimulus Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a peptide hormone stimulus. A peptide hormone is any of a class of peptides that are secreted into the blood stream and have endocrine functions in living animals.
negative regulation of bone resorption Any process that stops, prevents, or reduces the frequency, rate or extent of bone resorption.
negative regulation of cell population proliferation Any process that stops, prevents or reduces the rate or extent of cell proliferation.
negative regulation of ERK1 and ERK2 cascade Any process that stops, prevents, or reduces the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade.
negative regulation of Golgi to plasma membrane protein transport Any process that stops, prevents, or reduces the frequency, rate or extent of the transport of proteins from the Golgi to the plasma membrane.
negative regulation of interleukin-6 production Any process that stops, prevents, or reduces the frequency, rate, or extent of interleukin-6 production.
negative regulation of low-density lipoprotein particle clearance Any process that decreases the rate, frequency or extent of low-density lipoprotein particle clearance. Low-density lipoprotein particle clearance is the process in which a low-density lipoprotein particle is removed from the blood via receptor-mediated endocytosis and its constituent parts degraded.
negative regulation of phagocytosis Any process that stops, prevents, or reduces the frequency, rate or extent of phagocytosis.
oligodendrocyte differentiation The process in which a relatively unspecialized cell acquires the specialized features of an oligodendrocyte. An oligodendrocyte is a type of glial cell involved in myelinating the axons of neurons in the central nervous system.
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..

86 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
Q0VBZ0 CSK Tyrosine-protein kinase CSK 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
Q62689 Jak2 Tyrosine-protein kinase JAK2 Rattus norvegicus (Rat) SS
Q63272 Jak3 Tyrosine-protein kinase JAK3 Rattus norvegicus (Rat) SS
F1LM93 Yes1 Tyrosine-protein kinase Yes Rattus norvegicus (Rat) SS
P41243 Matk Megakaryocyte-associated tyrosine-protein kinase Rattus norvegicus (Rat) SS
Q62662 Frk Tyrosine-protein kinase FRK Rattus norvegicus (Rat) SS
Q62844 Fyn Tyrosine-protein kinase Fyn Rattus norvegicus (Rat) SS
Q6P6U0 Fgr Tyrosine-protein kinase Fgr Rattus norvegicus (Rat) SS
Q64725 Syk Tyrosine-protein kinase SYK Rattus norvegicus (Rat) SS
Q07014 Lyn Tyrosine-protein kinase Lyn Rattus norvegicus (Rat) SS
Q9WUD9 Src Proto-oncogene tyrosine-protein kinase Src Rattus norvegicus (Rat) SS
P50545 Hck Tyrosine-protein kinase HCK Rattus norvegicus (Rat) SS
P70600 Ptk2b Protein-tyrosine kinase 2-beta Rattus norvegicus (Rat) PR
O35346 Ptk2 Focal adhesion kinase 1 Rattus norvegicus (Rat) SS
Q5U2X5 Tnk2 Activated CDC42 kinase 1 Rattus norvegicus (Rat) SS
Q01621 Lck Proto-oncogene tyrosine-protein kinase LCK Rattus norvegicus (Rat) SS
P09760 Fer Tyrosine-protein kinase Fer Rattus norvegicus (Rat) PR
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
Q9FPR3 EDR1 Serine/threonine-protein kinase EDR1 Arabidopsis thaliana (Mouse-ear cress) PR
Q2MHE4 HT1 Serine/threonine/tyrosine-protein kinase HT1 Arabidopsis thaliana (Mouse-ear cress) PR
Q05609 CTR1 Serine/threonine-protein kinase CTR1 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
MSAIQASWPS GTECIAKYNF HGTAEQDLPF CKGDVLTIVA VTKDPNWYKA KNKVGREGII
70 80 90 100 110 120
PANYVQKREG VKAGTKLSLM PWFHGKITRE QAERLLYPPE TGLFLVREST NYPGDYTLCV
130 140 150 160 170 180
SCEGKVEHYR IMYHASKLSI DEEVYFENLM QLVEHYTTDA DGLCTRLIKP KVMEGTVAAQ
190 200 210 220 230 240
DEFYRSGWAL NMKELKLLQT IGKGEFGDVM LGDYRGNKVA VKCIKNDATA QAFLAEASVM
250 260 270 280 290 300
TQLRHSNLVQ LLGVIVEEKG 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 CPPAVYDVMK
430 440
NCWHLDAATR PTFLQLREQL EHIRTHELHL