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stem cell factor; mast-cell growth factor; c-kit ligand; steel homolog (SCF, KITLG, MGF)
Function:
- ligand for c-kit receptor-type tyrosine kinase
- role in the regulation of
- cell survival & proliferation
- hematopoiesis
- stem cell maintenance
- gametogenesis
- mast cell development, migration & function
- enhances mast cell adhesion to fibronectin (PI-3-kinase dependent)
- melanogenesis
- can activate several signaling pathways
- promotes phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, & subsequent activation of the kinase AKT1
- transmits signals via GRB2 & activation of RAS, RAF1 & the MAP kinases MAPK1/ERK2 &/or MAPK3/ERK1
- KITLG/SCF & KIT promote activation of STAT family members STAT1, STAT3 & STAT5
- KITLG/SCF & KIT promote activation of PLCG1, leading to the production of the cellular signaling molecules diacylglycerol & inositol 1,4,5-trisphosphate
- KITLG/SCF acts synergistically with other cytokines, probably interleukins
- a soluble form (sKITLG) is produced by proteolytic processing of isoform 1 in the extracellular domain
- soluble form exists as a cleavage product of the extracellular domain
- heterotetramer with KIT, binding two KIT molecules; thereby mediates KIT dimerization & subsequent activation by autophosphorylation
Structure:
- found in two differentially glycosylated forms, LMW-SCF & HMW-SCF.
- LMW-SCF
- fully N-glycosylated at Asn-145
- partially N-glycosylated at Asn-90
- O-glycosylated at Ser-167, Thr-168 & Thr-180,
- not glycosylated at Asn-97 or Asn-118
- HMW-SCF
- N-glycosylated at Asn-118, Asn-90 & Asn-145
- O-glycosylated at Ser-167, Thr-168 & Thr-180
- not glycosylated at Asn-97 homodimer, non-covalently linked (probable)
- belongs to the SCF family
Compartment:
- isoform 1: cell membrane; single-pass type 1 membrane protein
- isoform 2:
- cell membrane; single-pass type 1 membrane protein
- cytoplasm, cytoskeleton
- soluble KIT ligand: secreted
Alternative splicing: named isoforms=3
Expression: acts in the early stages of hematopoiesis
Polymorphism:
- genetic variations in KITLG are associated with variation in skin/hair/eye pigmentation type 7
Pathology:
- defects in KITLG are the cause of familial progressive hyperpigmentation
Interactions
molecular events
Related
c-kit protein; mast/stem cell growth factor receptor; SCFR; proto-oncogene tyrosine-protein kinase Kit; c-kit; CD117 (KIT)
steel locus or SI locus gene
General
cytokine
Properties
SIZE: entity length = 273 aa
MW = 31 kD
COMPARTMENT: cytoplasm
MOTIF: signal sequence {1-25}
cysteine residue {C29}
MODIFICATION: cysteine residue {C114}
cysteine residue {C68}
MODIFICATION: cysteine residue {C163}
N-glycosylation site {N90}
asparagine residue {97}
cysteine residue {C114}
MODIFICATION: cysteine residue {C29}
N-glycosylation site {N118}
N-glycosylation site {N145}
cysteine residue {C163}
MODIFICATION: cysteine residue {C68}
Ser glycosylation site {S167}
Thr glycosylation site {T168}
Thr glycosylation site {T180}
N-glycosylation site {N195}
transmembrane domain {215-237}
Database Correlations
OMIM correlations
MORBIDMAP 184745
UniProt P21583
Pfam PF02404
Entrez Gene 4254
Kegg hsa:4254
References
- UniProt :accession P21583
- Atlas of Genetics & Cytogenetics in Oncology & Haematology
http://atlasgeneticsoncology.org/genes/MGFID142.html