SCF Human Active Protein

This gene encodes the ligand of the tyrosine-kinase receptor encoded by the KIT locus. This ligand is a pleiotropic factor that acts in utero in germ cell and neural cell development, and hematopoiesis, all believed to reflect a role in cell migration. In adults, it functions pleiotropically, while mostly noted for its continued requirement in hematopoiesis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Function: Ligand for the receptor-type protein-tyrosine kinase KIT. Plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. KITLG/SCF binding can activate several signaling pathways. Promotes phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and subsequent activation of the kinase AKT1. KITLG/SCF and KIT also transmit signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. KITLG/SCF and KIT promote activation of STAT family members STAT1, STAT3 and STAT5. KITLG/SCF and KIT promote activation of PLCG1, leading to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KITLG/SCF acts synergistically with other cytokines, probably interleukins.

Subunit structure: Homodimer, non-covalently linked

Probable. Heterotetramer with KIT, binding two KIT molecules; thereby mediates KIT dimerization and subsequent activation by autophosphorylation.

Subcellular location: Isoform 1: Cell membrane; Single-pass type I membrane protein Ref.9. Isoform 2: Cell membrane; Single-pass type I membrane protein

By similarity. Cytoplasm › cytoskeleton

By similarity Ref.9. Soluble KIT ligand: Secreted Ref.9.

Developmental stage: Acts in the early stages of hematopoiesis.

Post-translational modification: A soluble form (sKITLG) is produced by proteolytic processing of isoform 1 in the extracellular domain.Found in two differentially glycosylated forms, LMW-SCF and HMW-SCF. LMW-SCF is fully N-glycosylated at Asn-145, partially N-glycosylated at Asn-90, O-glycosylated at Ser-167, Thr-168 and Thr-180, and not glycosylated at Asn-97 or Asn-118. HMW-SCF is N-glycosylated at Asn-118, Asn-90 and Asn-145, O-glycosylated at Ser-167, Thr-168 and Thr-180, and not glycosylated at Asn-97. Ref.9A soluble form exists as a cleavage product of the extracellular domain.

Polymorphism: Genetic variants in KITLG define the skin/hair/eye pigmentation variation locus 7 (SHEP7) [

MIM:611664]. Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair.

Involvement in disease: Familial progressive hyperpigmentation (FPH) [MIM:145250]: A disorder characterized by hyperpigmented patches in the skin, present in early infancy and increasing in size and number with age.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.18

Sequence similarities: Belongs to the SCF family.