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FLASH GENE
Symbol CSK contributors: mct/ - updated : 14-03-2012
HGNC name c-src tyrosine kinase
HGNC id 2444
Location 15q24.2      Physical location : 75.074.424 - 75.095.539
Synonym name protein-tyrosine kinase CYL
Synonym symbol(s) MGC117393, c-Src
EC.number 2.7.10.2
DNA
TYPE functioning gene
STRUCTURE 21.12 kb     14 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
14 - 2236 50.6 450 - 2005 15890649
13 - 2755 50.6 450 - 2005 15890649
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivesalivary gland   highly
Lymphoid/Immunespleen   highly
 tonsils   highly
Skin/Tegumentskin   highly
cells
SystemCellPubmedSpeciesStageRna symbol
Lymphoid/ImmuneT cell
Skeletonosteoclast Homo sapiens
cell lineage hematopoietic cells
cell lines
fluid/secretion blood, lymph
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal regulatory region containing SH3, SH2 and SRC homology domains, that may bind to different phosphoproteins, providing a basis for different cellular functions for CSK and MATK (Ayrapetov 2005)
  • a catalytic protein kinase domain
  • C-terminal specifically phosphorylates Src family kinases on a C-terminal Tyr residue, which down-regulates their activities, and SH2 domain contains a unique disulfide bond that is not present in other known SH2 domains
  • conjugated ubiquitinated
    mono polymer homomer , dimer
    HOMOLOGY
    Homologene
    FAMILY
  • Tyr protein kinase family, CSK subfamily
  • C-terminal Src kinase (Csk) family of protein tyrosine kinases
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    basic FUNCTION
  • specifically phosphorylating Tyr-504 on LCK, which acts as a negative regulatory site
  • additional player in the regulation of the immune system by ITIM-bearing receptors
  • suppression of its activity stimulates muscle differentiation by activating MAPK14 uni-directionally
  • essential regulator of podosome structure, dynamics and organization
  • serves to maintain the constancy of baseline excitatory synaptic transmission by inhibiting Src kinase-dependent synaptic plasticity in the hippocampus
  • potential role for PAG1 as a suppressor of CSK-mediated tumor progression
  • mediate the mitogenic response to PDGF in fibroblasts
  • plays an indispensable role in ruffled border formation and bone resorption and is constitutively active in osteoclasts
  • CSK and transcription factor NFKB are considered crucial components required for normal osteoclastogenesis
  • CELLULAR PROCESS cell cycle
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • part of a signaling complex with PTK2B, LPXN, and PTPN12 to regulate migration of prostate cancer cells
  • forms homodimers through interactions mediated by the SH3 domain in a manner that buries the recognition surface for SH3 ligands
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • tyrosine kinase, non receptor type PTPN8
  • interacting by its proline rich domain to the SH3 domain of CSK
  • interacts with phosphorylated SIT1, PAG1 and LIME1
  • phosphorylated LAIR1 bound CSK (interaction required the SH2 domain of CSK and phosphorylation of the tyrosine in the N-terminal ITIM of LAIR1)
  • interaction of CSK with LNX1 depends on the C-terminal PDZ ligand of CSK
  • PAG1 recruitment of CSK into lipid rafts is critical to c-Src kinase activity and bone resorption in osteoclasts
  • associates with TRAF6-p62 interacting with receptor activator of NFKB (RANK) distal region and the complex facilitate activation of RANK down stream signal transduction cascades including NFKB
  • IKBKG the regulatory subunit of the IKK complex, is crucial for osteoclastogenesis and interacts with CSK in osteoclast
  • SCIMP binds to the BLNK adaptor protein and also to the inhibitory kinase CSK
  • cooperative roles of C-terminal Src kinase (CSK) binding protein (PAG1) and Caveolin-1 (CAV1) in the mechanism of Src family tyrosine kinase (SFK) inhibition by CSK
  • F11R recruits CSK to the integrin-SRC complex in resting platelets
  • EEF2 is a substrate of CSK and could locate in the nucleus
  • cell & other
    REGULATION
    activated by the engagement of its Src homology (SH) 2 domain
    Other myristoylation and the pocket residues regulate CSK, but in a manner very different from that for ABL1
    ubiquitinated by LNX1, suggesting an interdependent regulation of CSK and LNX1
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in colorectal cancer (important early event in colorectal cancer pathogenesis)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS