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KITLG (KIT ligand)

Identity

Other namesMGF (Mast Cell Growth Factor)
SCF (Stem Cell factor)
HGNC (Hugo) KITLG
LocusID (NCBI) 4254
Location 12q21.32
Location_base_pair Starts at 88886570 and ends at 88974250 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

 
Description Genomic sequence not known; 9 exons
Transcription 1,4 Kb mRNA; alternative splicing gives rise to different transcripts, mainly represented by those for a membrane and a soluble form.

Protein

Description the membrane bound form is a surface molecule of 248 aa, that includes 23 aa of the highly hydrophobic transmembrane domain; the second form corresponds to a soluble protein constituted by the first 165 aa of the extracellular domain released by a posttranslational processing, consisting in a proteolytic cleavage of the mature SCF in the extracellular juxtamembrane region; the full length transcripts encode for a transmembrane precursor of the soluble protein; an alternative splicing that involves the region corresponding to exon 6 of the SCF cDNA, which contains the proteolytic cleavage site, encodes for a surface molecule.
Expression SCF transcripts have been found in the cells surrounding kit-positive cells, such as granulosa and Sertoli cells, bone marrow stromal cells and in fibroblasts, keratinocytes and mature granulocytes; SCF expression of peripheral lymphocytes and monocytes is still controversial.
Localisation plasma membrane or interstitial space
Function SCF/MGF binding of receptor KIT, with tyrosine kinase activity, induces receptor dimerization, autophosphorylation and signal transduction via molecules containing SH2-domains; the soluble and the transmembrane protein have a different biological activity; the soluble form mainly stimulates cellular proliferation; the membrane-bound isoform induces an activation of the receptor more prolonged than the soluble one
Homology with PDGFRb, PDGFRa, and CSF-1.

Mutations

Germinal human mutations are yet unknown in human MGF/SCF gene; mouse mutations at the murine steel (Sl) locus that encodes MGF are known and give rise to deficiencies in pigment cells, germ cells, and blood cells; in particular the steel-Dickie (Sld) mouse has a 4.0-kb intragenic deletion that truncates the Sl coding sequence; Sld mice are only capable of encoding a soluble truncated growth factor that lacks both transmembrane and cytoplasmic domains.

Implicated in

Entity Mastocytosis
Disease In skin from patients with mastocytosis, MGF was found prevalently free in the dermis and in extracellular spaces between keratinocytes suggesting the presence of a soluble form of the protein; altered distribution of mast cell growth factor in the skin of patients with cutaneous mastocytosis is consistent with abnormal production of the soluble form of the factor, resulting by an increased cleavage of SCF with excessive release of a soluble form from the normally membrane bound form; no sequence abnormalities were detected in MGF mRNA.
  
Entity Gynecological tumors
Disease findings obtained on three cervical carcinomas (ovarian serous adenocarcinoma, small cell carcinoma and ovarian immature teratoma) and two gynecological cancer cell lines (ME180 and HGCM) demonstrate coexpression of c-Kit receptor and SCF; these observations are consistent with the possibility that an autocrine activation of SCF/KIT system might be involved in gynecological malignancies.
  
Entity Small-cell lung cancer
Disease SCF is expressed in small-cell lung cancer (SCLC); abundant expression of SCF and c-Kit mRNA was seen in 32% of SCLC cell lines and 66% of SCLC tumors; an autocrine mechanism in the pathogenesis of SCLC is strongly suggested.
  

External links

Nomenclature
HGNC (Hugo)KITLG   6343
Cards
AtlasMGFID142
Entrez_Gene (NCBI)KITLG  4254  KIT ligand
GeneCards (Weizmann)KITLG
Ensembl (Hinxton) [Gene_View]  chr12:88886570-88974250 [Contig_View]  KITLG [Vega]
cBioPortalKITLG
AceView (NCBI)KITLG
Genatlas (Paris)KITLG
WikiGenes4254
SOURCE (Princeton)NM_000899 NM_003994
Genomic and cartography
GoldenPath (UCSC)KITLG  -  12q21.32   chr12:88886570-88974250 -  12q22   [Description]    (hg19-Feb_2009)
EnsemblKITLG - 12q22 [CytoView]
Mapping of homologs : NCBIKITLG [Mapview]
OMIM145250   184745   611664   
Gene and transcription
Genbank (Entrez)AF119835 AF400436 AF400437 AK025245 AK055903
RefSeq transcript (Entrez)NM_000899 NM_003994
RefSeq genomic (Entrez)AC_000144 NC_000012 NC_018923 NG_012098 NT_029419 NW_001838061 NW_004929384
Consensus coding sequences : CCDS (NCBI)KITLG
Cluster EST : UnigeneHs.1048 [ NCBI ]
CGAP (NCI)Hs.1048
Alternative Splicing : Fast-db (Paris)GSHG0007665
Gene ExpressionKITLG [ NCBI-GEO ]     KITLG [ SEEK ]   KITLG [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP21583 (Uniprot)
NextProtP21583  [Medical]
With graphics : InterProP21583
Splice isoforms : SwissVarP21583 (Swissvar)
Domains : Interpro (EBI)4_helix_cytokine-like_core [organisation]   4_helix_cytokine_core [organisation]   SCF [organisation]  
Related proteins : CluSTrP21583
Domain families : Pfam (Sanger)SCF (PF02404)   
Domain families : Pfam (NCBI)pfam02404   
DMDM Disease mutations4254
Blocks (Seattle)P21583
PDB (SRS)1EXZ    1SCF    2E9W   
PDB (PDBSum)1EXZ    1SCF    2E9W   
PDB (IMB)1EXZ    1SCF    2E9W   
PDB (RSDB)1EXZ    1SCF    2E9W   
Peptide AtlasP21583
HPRD01698
IPIIPI00009450   IPI00220142   IPI00479376   IPI01010816   
Protein Interaction databases
DIP (DOE-UCLA)P21583
IntAct (EBI)P21583
BioGRIDKITLG
InParanoidP21583
Interologous Interaction database P21583
IntegromeDBKITLG
STRING (EMBL)KITLG
Ontologies - Pathways
Ontology : AmiGOneural crest cell migration  positive regulation of myeloid leukocyte differentiation  cytokine activity  stem cell factor receptor binding  protein binding  extracellular region  extracellular space  cytoplasm  cytoskeleton  plasma membrane  plasma membrane  cell adhesion  signal transduction  epidermal growth factor receptor signaling pathway  growth factor activity  cell proliferation  fibroblast growth factor receptor signaling pathway  male gonad development  integral component of membrane  negative regulation of mast cell apoptotic process  embryonic hemopoiesis  ectopic germ cell programmed cell death  Fc-epsilon receptor signaling pathway  positive regulation of MAP kinase activity  innate immune response  positive regulation of melanocyte differentiation  positive regulation of DNA replication  positive regulation of Ras protein signal transduction  neurotrophin TRK receptor signaling pathway  phosphatidylinositol-mediated signaling  positive regulation of peptidyl-tyrosine phosphorylation  positive regulation of mast cell proliferation  extrinsic apoptotic signaling pathway in absence of ligand  
Ontology : EGO-EBIneural crest cell migration  positive regulation of myeloid leukocyte differentiation  cytokine activity  stem cell factor receptor binding  protein binding  extracellular region  extracellular space  cytoplasm  cytoskeleton  plasma membrane  plasma membrane  cell adhesion  signal transduction  epidermal growth factor receptor signaling pathway  growth factor activity  cell proliferation  fibroblast growth factor receptor signaling pathway  male gonad development  integral component of membrane  negative regulation of mast cell apoptotic process  embryonic hemopoiesis  ectopic germ cell programmed cell death  Fc-epsilon receptor signaling pathway  positive regulation of MAP kinase activity  innate immune response  positive regulation of melanocyte differentiation  positive regulation of DNA replication  positive regulation of Ras protein signal transduction  neurotrophin TRK receptor signaling pathway  phosphatidylinositol-mediated signaling  positive regulation of peptidyl-tyrosine phosphorylation  positive regulation of mast cell proliferation  extrinsic apoptotic signaling pathway in absence of ligand  
Pathways : BIOCARTAErythrocyte Differentiation Pathway [Genes]    Regulation of BAD phosphorylation [Genes]    IL 17 Signaling Pathway [Genes]    Melanocyte Development and Pigmentation [Genes]    CDK Regulation of DNA Replication [Genes]   
Pathways : KEGGRas signaling pathway    Rap1 signaling pathway    Cytokine-cytokine receptor interaction    PI3K-Akt signaling pathway    Hematopoietic cell lineage    Melanogenesis    Pathways in cancer   
Protein Interaction DatabaseKITLG
Wikipedia pathwaysKITLG
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)KITLG
snp3D : Map Gene to Disease4254
SNP (GeneSNP Utah)KITLG
SNP : HGBaseKITLG
Genetic variants : HAPMAPKITLG
Exome VariantKITLG
1000_GenomesKITLG 
Somatic Mutations in Cancer : COSMICKITLG 
CONAN: Copy Number AnalysisKITLG 
Mutations and Diseases : HGMDKITLG
Mutations and Diseases : intOGenKITLG
Genomic VariantsKITLG  KITLG [DGVbeta]
dbVarKITLG
ClinVarKITLG
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM145250    184745    611664   
MedgenKITLG
GENETestsKITLG
Disease Genetic AssociationKITLG
Huge Navigator KITLG [HugePedia]  KITLG [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneKITLG
Homology/Alignments : Family Browser (UCSC)KITLG
Phylogenetic Trees/Animal Genes : TreeFamKITLG
Chemical/Protein Interactions : CTD4254
Chemical/Pharm GKB GenePA30129
Clinical trialKITLG
Other databases
Probes
Litterature
PubMed177 Pubmed reference(s) in Entrez
CoreMineKITLG
iHOPKITLG
OncoSearchKITLG

Bibliography

Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor.
Zsebo KM, Williams DA, Geissler EN, Broudy VC, Martin FH, Atkins HL, Hsu RY, Birkett NC, Okino KH, Murdock DC
Cell. 1990 ; 63 (1) : 213-224.
PMID 1698556
 
Primary structure and functional expression of rat and human stem cell factor DNAs.
Martin FH, Suggs SV, Langley KE, Lu HS, Ting J, Okino KH, Morris CF, McNiece IK, Jacobsen FW, Mendiaz EA
Cell. 1990 ; 63 (1) : 203-211.
PMID 2208279
 
[Some data on the state of the hematoencephalic barrier in cerebral cysticercosis.]
ANTONOV IP, SIZONENKO TP
Zhurnal nevropatologii i psikhiatrii imeni S.S. Korsakova (Moscow, Russia : 1952). 1963 ; 63 : 213-216.
PMID 14013385
 
Coexpression of the stem cell factor and the c-kit genes in small-cell lung cancer.
Hibi K, Takahashi T, Sekido Y, Ueda R, Hida T, Ariyoshi Y, Takagi H, Takahashi T
Oncogene. 1991 ; 6 (12) : 2291-2296.
PMID 1722571
 
Altered metabolism of mast-cell growth factor (c-kit ligand) in cutaneous mastocytosis.
Longley BJ Jr, Morganroth GS, Tyrrell L, Ding TG, Anderson DM, Williams DE, Halaban R
The New England journal of medicine. 1993 ; 328 (18) : 1302-1307.
PMID 7682288
 
Expression of interleukins 1, 3, 6, stem cell factor and their receptors in acute leukemia blast cells and in normal peripheral lymphocytes and monocytes.
Ferrari S, Grande A, Manfredini R, Tagliafico E, Zucchini P, Torelli G, Torelli U
European journal of haematology. 1993 ; 50 (3) : 141-148.
PMID 7682516
 
Human peripheral blood granulocytes and myeloid leukemic cell lines express both transcripts encoding for stem cell factor.
Ramenghi U, Ruggieri L, Dianzani I, Rosso C, Brizzi MF, Camaschella C, Pietsch T, Saglio G
Stem cells (Dayton, Ohio). 1994 ; 12 (5) : 521-526.
PMID 7528592
 
Coexpression of the c-kit receptor and the stem cell factor in gynecological tumors.
Inoue M, Kyo S, Fujita M, Enomoto T, Kondoh G
Cancer research. 1994 ; 54 (11) : 3049-3053.
PMID 7514496
 
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Last year publicationsautomatic search in PubMed

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Contributor(s)

Written10-1998Alessandro Beghini
Updated06-2000Lidia Larizza and Alessandro Beghini

Citation

This paper should be referenced as such :
Larizza, L ; Beghini, A
KITLG (KIT ligand)
Atlas Genet Cytogenet Oncol Haematol. 2000;4(3):99-100.
Free online version   Free pdf version   [Bibliographic record ]
History of this paper:
Larizza, L ; Beghini, A. KITLG (KIT ligand). Atlas Genet Cytogenet Oncol Haematol. 2000;4(3):99-100.
http://documents.irevues.inist.fr/bitstream/2042/37633/1/06-2000-MGFID142.pdf
URL : http://AtlasGeneticsOncology.org/Genes/MGFID142.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Tue Aug 26 15:28:50 CEST 2014

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