ID:CSK_HUMAN DESCRIPTION: RecName: Full=Tyrosine-protein kinase CSK; EC=2.7.10.2; AltName: Full=C-Src kinase; AltName: Full=Protein-tyrosine kinase CYL; FUNCTION: Non-receptor tyrosine-protein kinase that plays an important role in the regulation of cell growth, differentiation, migration and immune response. Phosphorylates tyrosine residues located in the C-terminal tails of Src-family kinases (SFKs) including LCK, SRC, HCK, FYN, LYN or YES1. Upon tail phosphorylation, Src-family members engage in intramolecular interactions between the phosphotyrosine tail and the SH2 domain that result in an inactive conformation. To inhibit SFKs, CSK is recruited to the plasma membrane via binding to transmembrane proteins or adapter proteins located near the plasma membrane. Suppresses signaling by various surface receptors, including T- cell receptor (TCR) and B-cell receptor (BCR) by phosphorylating and maintaining inactive several positive effectors such as FYN or LCK. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. SUBUNIT: Homodimer (via SH3-domain). Interacts with PTPN8 (By similarity). Interacts with phosphorylated SIT1, PAG1, LIME1 and TGFB1I1; these interactions serve to recruit CSK to the membrane where it can phosphorylate and inhibit Src-family kinases. Interacts with SRCIN1. Interacts with RHOH. Interacts (via SH2 domain) with SCIMP. INTERACTION: P00523:SRC (xeno); NbExp=6; IntAct=EBI-1380630, EBI-848039; SUBCELLULAR LOCATION: Cytoplasm (By similarity). Cell membrane (By similarity). Note=Mainly cytoplasmic, also present in lipid rafts (By similarity). TISSUE SPECIFICITY: Expressed in lung and macrophages. DOMAIN: The architecture of this protein is similar to that of Src-family kinases (SFKs) with one N-terminal SH3 domain, one SH2 domain, and a C-terminal kinase domain. PTM: Phosphorylated at Ser-364 by PKA, leading to increased activity. Autophosphorylated. SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. CSK subfamily. SIMILARITY: Contains 1 protein kinase domain. SIMILARITY: Contains 1 SH2 domain. SIMILARITY: Contains 1 SH3 domain. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/csk/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P41240
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0001817 regulation of cytokine production GO:0002250 adaptive immune response GO:0002376 immune system process GO:0006468 protein phosphorylation GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway GO:0007417 central nervous system development GO:0007420 brain development GO:0008285 negative regulation of cell proliferation GO:0010989 negative regulation of low-density lipoprotein particle clearance GO:0016310 phosphorylation GO:0030154 cell differentiation GO:0031295 T cell costimulation GO:0032715 negative regulation of interleukin-6 production GO:0033673 negative regulation of kinase activity GO:0034332 adherens junction organization GO:0038083 peptidyl-tyrosine autophosphorylation GO:0042127 regulation of cell proliferation GO:0042997 negative regulation of Golgi to plasma membrane protein transport GO:0043406 positive regulation of MAP kinase activity GO:0045087 innate immune response GO:0045779 negative regulation of bone resorption GO:0046777 protein autophosphorylation GO:0048709 oligodendrocyte differentiation GO:0050765 negative regulation of phagocytosis GO:0050852 T cell receptor signaling pathway GO:0060368 regulation of Fc receptor mediated stimulatory signaling pathway GO:0070373 negative regulation of ERK1 and ERK2 cascade GO:0071375 cellular response to peptide hormone stimulus
BC106073 - Homo sapiens c-src tyrosine kinase, mRNA (cDNA clone MGC:117393 IMAGE:6526810), complete cds. AK290531 - Homo sapiens cDNA FLJ78579 complete cds, highly similar to Homo sapiens c-src tyrosine kinase (CSK), mRNA. X60114 - H.sapiens cyl mRNA for cytoplasmic tryrosine kinase. JD389321 - Sequence 370345 from Patent EP1572962. AK298245 - Homo sapiens cDNA FLJ51496 complete cds, highly similar to Tyrosine-protein kinase CSK (EC 2.7.10.2). AK223626 - Homo sapiens mRNA for c-src tyrosine kinase variant, clone: FCC134G03. AK310136 - Homo sapiens cDNA, FLJ17178. JD396504 - Sequence 377528 from Patent EP1572962. JD159602 - Sequence 140626 from Patent EP1572962. JD132762 - Sequence 113786 from Patent EP1572962. AK312669 - Homo sapiens cDNA, FLJ93062, Homo sapiens c-src tyrosine kinase (CSK), mRNA. BC104847 - Homo sapiens c-src tyrosine kinase, mRNA (cDNA clone MGC:132507 IMAGE:8143850), complete cds. BC104875 - Homo sapiens c-src tyrosine kinase, mRNA (cDNA clone MGC:132535 IMAGE:8143878), complete cds. X59932 - Human mRNA for C-SRC-kinase. JD139139 - Sequence 120163 from Patent EP1572962. AK127672 - Homo sapiens cDNA FLJ45770 fis, clone NETRP2002197, highly similar to Tyrosine-protein kinase CSK (EC 2.7.10.2). JD257183 - Sequence 238207 from Patent EP1572962. AB451420 - Homo sapiens CSK mRNA for c-src tyrosine kinase, partial cds, clone: FLJ08127AAAF. AB527572 - Synthetic construct DNA, clone: pF1KB6656, Homo sapiens CSK gene for c-src tyrosine kinase, without stop codon, in Flexi system. CR541960 - Homo sapiens full open reading frame cDNA clone RZPDo834E0634D for gene CSK, c-src tyrosine kinase; complete cds, without stopcodon. AB451288 - Homo sapiens CSK mRNA for c-src tyrosine kinase, complete cds, clone: FLJ08127AAAN. KJ890982 - Synthetic construct Homo sapiens clone ccsbBroadEn_00376 CSK gene, encodes complete protein. AK297694 - Homo sapiens cDNA FLJ55227 complete cds, highly similar to Tyrosine-protein kinase CSK (EC 2.7.10.2). AY007162 - Homo sapiens clone CDABP0138 mRNA sequence. AK309344 - Homo sapiens cDNA, FLJ99385. JD020870 - Sequence 1894 from Patent EP1572962. JD032819 - Sequence 13843 from Patent EP1572962. JD023027 - Sequence 4051 from Patent EP1572962. JD035032 - Sequence 16056 from Patent EP1572962. JD230864 - Sequence 211888 from Patent EP1572962. JD173135 - Sequence 154159 from Patent EP1572962. DL491863 - Novel nucleic acids. JD191642 - Sequence 172666 from Patent EP1572962. DL490430 - Novel nucleic acids. JD054857 - Sequence 35881 from Patent EP1572962. JD261961 - Sequence 242985 from Patent EP1572962. JD477506 - Sequence 458530 from Patent EP1572962. JD442826 - Sequence 423850 from Patent EP1572962. JD533551 - Sequence 514575 from Patent EP1572962. JD445920 - Sequence 426944 from Patent EP1572962. JD471205 - Sequence 452229 from Patent EP1572962. JD417910 - Sequence 398934 from Patent EP1572962. JD123692 - Sequence 104716 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_integrinPathway - Integrin Signaling Pathway h_srcRPTPPathway - Activation of Src by Protein-tyrosine phosphatase alpha h_CSKPathway - Activation of Csk by cAMP-dependent Protein Kinase Inhibits Signaling through the T Cell Receptor h_cell2cellPathway - Cell to Cell Adhesion Signaling
Reactome (by CSHL, EBI, and GO)
Protein P41240 (Reactome details) participates in the following event(s):
R-HSA-177923 Sustained activation of SRC kinase by SHP2 R-HSA-203774 Interaction of Csk with PAG R-HSA-377644 Release of CSK from SRC R-HSA-8855375 PTPN22 dissociates from CSK R-HSA-389762 Phosphorylation of PD-1 R-HSA-202233 Inactivation of Lck by Csk R-HSA-354077 Integrin alphaIIb beta3 activation R-HSA-377641 Clustering of Integrin alphaIIb beta3 complexes R-HSA-389759 Interaction of SHP-1 or SHP-2 with phospho PD-1 R-HSA-354149 Interaction of integrin alphaIIb beta3 with Fibrinogen R-HSA-432096 Activated integrin alphaIIb beta3 binds SHC1 R-HSA-389758 Dephosphorylation of CD3-zeta by PD-1 bound phosphatases R-HSA-5672972 MAP2Ks and MAPKs bind to the activated RAF complex R-HSA-6802912 High kinase activity BRAF mutants bind MAP2Ks and MAPKs R-HSA-6802914 RAS:GTP:moderate kinase activity p-RAF complexes bind MAP2Ks and MAPKs R-HSA-6802925 Mutant RAS:p-RAF complexes bind MAP2Ks and MAPKs R-HSA-6802934 p-BRAF and RAF fusion dimers bind MAP2Ks and MAPKs R-HSA-6802942 RAS:GTP:p-RAF complexes paradoxically bind MAP2Ks and MAPKs R-HSA-5672980 Dissociation of RAS:RAF complex R-HSA-6802932 Dissociation of BRAF/RAF fusion complex R-HSA-6803227 Dissociation of high activity BRAF complexes R-HSA-6803230 Dissociation of moderate activity BRAF complexes R-HSA-6803233 Dissociation of oncogenic RAS:RAF complex R-HSA-6803234 Dissociation of paradoxically activated RAS:BRAF complexes R-HSA-5672978 RAF phosphorylates MAP2K dimer R-HSA-5672973 MAP2Ks phosphorylate MAPKs R-HSA-6802918 Activated MAP2Ks phosphorylate MAPKs downstream of inactive BRAF mutants R-HSA-6802943 RAS:GTP:inactive p-RAF complexes phosphorylate MAP2Ks R-HSA-6802919 RAS:GTP:moderate kinase activity p-RAF complexes phosphorylate MAP2Ks R-HSA-6802921 Activated MAP2Ks phosphorylate MAPKs downstream of moderate kinase activity BRAF mutants R-HSA-6802911 High kinase activity BRAF complexes phosphorylate MAP2Ks R-HSA-6802910 Activated MAP2Ks phosphorylate MAPKs downstream of high kinase activity BRAF mutants R-HSA-6802926 Mutant RAS:p-RAF complexes phosphorylate MAP2Ks R-HSA-6802922 Activated MAP2Ks phosphorylate MAPKs downstream of oncogenic RAS R-HSA-6802933 p-BRAF and RAF fusion dimers phosphorylate MAP2Ks R-HSA-6802935 MAPKs are phosphorylated downstream of BRAF and RAF fusion dimers R-HSA-180292 GAB1 signalosome R-HSA-202427 Phosphorylation of CD3 and TCR zeta chains R-HSA-354192 Integrin alphaIIb beta3 signaling R-HSA-177929 Signaling by EGFR R-HSA-389948 PD-1 signaling R-HSA-202403 TCR signaling R-HSA-76009 Platelet Aggregation (Plug Formation) R-HSA-9006921 Integrin signaling R-HSA-9006934 Signaling by Receptor Tyrosine Kinases R-HSA-388841 Costimulation by the CD28 family R-HSA-1280218 Adaptive Immune System R-HSA-76002 Platelet activation, signaling and aggregation R-HSA-162582 Signal Transduction R-HSA-168256 Immune System R-HSA-109582 Hemostasis R-HSA-5674135 MAP2K and MAPK activation R-HSA-6802948 Signaling by high-kinase activity BRAF mutants R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants R-HSA-6802949 Signaling by RAS mutants R-HSA-6802952 Signaling by BRAF and RAF fusions R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF R-HSA-5673001 RAF/MAP kinase cascade R-HSA-6802957 Oncogenic MAPK signaling R-HSA-5684996 MAPK1/MAPK3 signaling R-HSA-5663202 Diseases of signal transduction R-HSA-5683057 MAPK family signaling cascades R-HSA-1643685 Disease
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
