SCF_HUMAN
ID SCF_HUMAN Reviewed; 273 AA.
AC P21583; A0AV09; A8K2Q4; B7ZLM4; Q16487; Q68DZ2; Q7M4N8; Q9UQK7;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 1.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Kit ligand;
DE AltName: Full=Mast cell growth factor;
DE Short=MGF;
DE AltName: Full=Stem cell factor;
DE Short=SCF;
DE AltName: Full=c-Kit ligand;
DE Contains:
DE RecName: Full=Soluble KIT ligand;
DE Short=sKITLG;
DE Flags: Precursor;
GN Name=KITLG; Synonyms=MGF, SCF;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2208279; DOI=10.1016/0092-8674(90)90301-t;
RA Martin F.H., Suggs S.V., Langley K.E., Lu H.S., Ting J., Okino K.H.,
RA Morris C.F., McNiece I.K., Jacobsen F.W., Mendiaz E.A., Birkett N.C.,
RA Smith K.A., Johnson M.J., Parker V.P., Flores J.C., Patel A.C.,
RA Fisher E.F., Erjavec H.O., Herrera C.J., Wypych J., Sachdev R.K.,
RA Pope J.A., Leslie I., Wen D., Lin C.-H., Cupples R.L., Zsebo K.M.;
RT "Primary structure and functional expression of rat and human stem cell
RT factor DNAs.";
RL Cell 63:203-211(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=1724381;
RA Anderson D.M., Williams D.E., Tushinski R., Gimpel S., Eisenman J.,
RA Cannizzaro L.A., Aronson M., Croce C.M., Huebner K., Cosman D.;
RT "Alternate splicing of mRNAs encoding human mast cell growth factor and
RT localization of the gene to chromosome 12q22-q24.";
RL Cell Growth Differ. 2:373-378(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=10049787; DOI=10.1006/bbrc.1999.0260;
RA Blair H.C., Julian B.A., Cao X., Jordan S.E., Dong S.S.;
RT "Parathyroid hormone-regulated production of stem cell factor in human
RT osteoblasts and osteoblast-like cells.";
RL Biochem. Biophys. Res. Commun. 255:778-784(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RA Han C., Peng X., Yuan J., Qiang B.;
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Tongue, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 26-40; 64-79; 87-102; 110-149 AND 154-190 (ISOFORM 1),
RP DISULFIDE BONDS, SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, AND
RP GLYCOSYLATION AT ASN-90; ASN-118; ASN-145; SER-167; THR-168 AND THR-180.
RX PubMed=1381905; DOI=10.1016/0003-9861(92)90106-7;
RA Lu H.S., Clogston C.L., Wypych J., Parker V.P., Lee T.D., Swiderek K.,
RA Baltera R.F. Jr., Patel A.C., Chang D.C., Brankow D.W., Liu X.-D.,
RA Ogden S.G., Karkare S.B., Hu S.S., Zsebo K.M., Langley K.E.;
RT "Post-translational processing of membrane-associated recombinant human
RT stem cell factor expressed in Chinese hamster ovary cells.";
RL Arch. Biochem. Biophys. 298:150-158(1992).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 167-248 (ISOFORM 2).
RX PubMed=1379846;
RA Toyota M., Hinoda Y., Itoh F., Tsujisaki M., Imai K., Yachi A.;
RT "Expression of two types of kit ligand mRNAs in human tumor cells.";
RL Int. J. Hematol. 55:301-304(1992).
RN [11]
RP REVIEW.
RX PubMed=10582791; DOI=10.1093/humupd/5.5.535;
RA Mauduit C., Hamamah S., Benahmed M.;
RT "Stem cell factor/c-kit system in spermatogenesis.";
RL Hum. Reprod. Update 5:535-545(1999).
RN [12]
RP REVIEW.
RX PubMed=15526160; DOI=10.1007/s00018-004-4189-6;
RA Ronnstrand L.;
RT "Signal transduction via the stem cell factor receptor/c-Kit.";
RL Cell. Mol. Life Sci. 61:2535-2548(2004).
RN [13]
RP REVIEW.
RX PubMed=15625120; DOI=10.1634/stemcells.2004-0117;
RA Lennartsson J., Jelacic T., Linnekin D., Shivakrupa R.;
RT "Normal and oncogenic forms of the receptor tyrosine kinase kit.";
RL Stem Cells 23:16-43(2005).
RN [14]
RP INVOLVEMENT IN SHEP7.
RX PubMed=17952075; DOI=10.1038/ng.2007.13;
RA Sulem P., Gudbjartsson D.F., Stacey S.N., Helgason A., Rafnar T.,
RA Magnusson K.P., Manolescu A., Karason A., Palsson A., Thorleifsson G.,
RA Jakobsdottir M., Steinberg S., Palsson S., Jonasson F., Sigurgeirsson B.,
RA Thorisdottir K., Ragnarsson R., Benediktsdottir K.R., Aben K.K.,
RA Kiemeney L.A., Olafsson J.H., Gulcher J., Kong A., Thorsteinsdottir U.,
RA Stefansson K.;
RT "Genetic determinants of hair, eye and skin pigmentation in Europeans.";
RL Nat. Genet. 39:1443-1452(2007).
RN [15]
RP POLYMORPHISM LINKED TO BLOND HAIR COLOR.
RX PubMed=24880339; DOI=10.1038/ng.2991;
RA Guenther C.A., Tasic B., Luo L., Bedell M.A., Kingsley D.M.;
RT "A molecular basis for classic blond hair color in Europeans.";
RL Nat. Genet. 46:748-752(2014).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS), AND DISULFIDE BONDS.
RX PubMed=10880433; DOI=10.1093/emboj/19.13.3192;
RA Jiang X., Gurel O., Mendiaz E.A., Stearns G.W., Clogston C.L., Lu H.S.,
RA Osslund T.D., Syed R.S., Langley K.E., Hendrickson W.A.;
RT "Structure of the active core of human stem cell factor and analysis of
RT binding to its receptor kit.";
RL EMBO J. 19:3192-3203(2000).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 26-166, AND DISULFIDE BONDS.
RX PubMed=10884405; DOI=10.1073/pnas.97.14.7732;
RA Zhang Z., Zhang R., Joachimiak A., Schlessinger J., Kong X.P.;
RT "Crystal structure of human stem cell factor: implication for stem cell
RT factor receptor dimerization and activation.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:7732-7737(2000).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 26-166 IN COMPLEX WITH KIT, AND
RP DISULFIDE BONDS.
RX PubMed=17662946; DOI=10.1016/j.cell.2007.05.055;
RA Yuzawa S., Opatowsky Y., Zhang Z., Mandiyan V., Lax I., Schlessinger J.;
RT "Structural basis for activation of the receptor tyrosine kinase KIT by
RT stem cell factor.";
RL Cell 130:323-334(2007).
RN [19]
RP VARIANT FPHH SER-36, AND CHARACTERIZATION OF VARIANT FPHH SER-36.
RX PubMed=19375057; DOI=10.1016/j.ajhg.2009.03.019;
RA Wang Z.-Q., Si L., Tang Q., Lin D., Fu Z., Zhang J., Cui B., Zhu Y.,
RA Kong X., Deng M., Xia Y., Xu H., Le W., Hu L., Kong X.;
RT "Gain-of-function mutation of KIT ligand on melanin synthesis causes
RT familial progressive hyperpigmentation.";
RL Am. J. Hum. Genet. 84:672-677(2009).
RN [20]
RP VARIANT DCUA 67-HIS-CYS-68 DELINS ARG, CHARACTERIZATION OF VARIANT DCUA
RP 67-HIS-CYS-68 DELINS ARG, INVOLVEMENT IN DCUA, VARIANT VAL-104,
RP CHARACTERIZATION OF VARIANT VAL-104, AND SUBCELLULAR LOCATION (ISOFORM 2).
RX PubMed=26522471; DOI=10.1016/j.ajhg.2015.09.011;
RG Baylor-Hopkins Center for Mendelian Genomics;
RA Zazo Seco C., Serrao de Castro L., van Nierop J.W., Morin M., Jhangiani S.,
RA Verver E.J., Schraders M., Maiwald N., Wesdorp M., Venselaar H.,
RA Spruijt L., Oostrik J., Schoots J., van Reeuwijk J., Lelieveld S.H.,
RA Huygen P.L., Insenser M., Admiraal R.J., Pennings R.J., Hoefsloot L.H.,
RA Arias-Vasquez A., de Ligt J., Yntema H.G., Jansen J.H., Muzny D.M.,
RA Huls G., van Rossum M.M., Lupski J.R., Moreno-Pelayo M.A., Kunst H.P.,
RA Kremer H.;
RT "Allelic Mutations of KITLG, Encoding KIT Ligand, Cause Asymmetric and
RT Unilateral Hearing Loss and Waardenburg Syndrome Type 2.";
RL Am. J. Hum. Genet. 97:647-660(2015).
CC -!- FUNCTION: Ligand for the receptor-type protein-tyrosine kinase KIT.
CC Plays an essential role in the regulation of cell survival and
CC proliferation, hematopoiesis, stem cell maintenance, gametogenesis,
CC mast cell development, migration and function, and in melanogenesis.
CC KITLG/SCF binding can activate several signaling pathways. Promotes
CC phosphorylation of PIK3R1, the regulatory subunit of
CC phosphatidylinositol 3-kinase, and subsequent activation of the kinase
CC AKT1. KITLG/SCF and KIT also transmit signals via GRB2 and activation
CC of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1.
CC KITLG/SCF and KIT promote activation of STAT family members STAT1,
CC STAT3 and STAT5. KITLG/SCF and KIT promote activation of PLCG1, leading
CC to the production of the cellular signaling molecules diacylglycerol
CC and inositol 1,4,5-trisphosphate. KITLG/SCF acts synergistically with
CC other cytokines, probably interleukins.
CC -!- SUBUNIT: Homodimer, non-covalently linked (Probable). Heterotetramer
CC with KIT, binding two KIT molecules; thereby mediates KIT dimerization
CC and subsequent activation by autophosphorylation.
CC {ECO:0000269|PubMed:17662946, ECO:0000305}.
CC -!- INTERACTION:
CC P21583; P10721: KIT; NbExp=2; IntAct=EBI-1379527, EBI-1379503;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Single-pass type I
CC membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:26522471}. Cytoplasm, cytoskeleton {ECO:0000250}.
CC Cell membrane {ECO:0000269|PubMed:26522471}; Single-pass type I
CC membrane protein {ECO:0000250}. Cell projection, lamellipodium
CC {ECO:0000269|PubMed:26522471}. Cell projection, filopodium
CC {ECO:0000269|PubMed:26522471}.
CC -!- SUBCELLULAR LOCATION: [Soluble KIT ligand]: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=SCF248;
CC IsoId=P21583-1; Sequence=Displayed;
CC Name=2; Synonyms=SCF220;
CC IsoId=P21583-2; Sequence=VSP_006022;
CC Name=3;
CC IsoId=P21583-3; Sequence=VSP_032762, VSP_032763;
CC -!- DEVELOPMENTAL STAGE: Acts in the early stages of hematopoiesis.
CC -!- PTM: A soluble form (sKITLG) is produced by proteolytic processing of
CC isoform 1 in the extracellular domain. {ECO:0000269|PubMed:1381905}.
CC -!- PTM: Found in two differentially glycosylated forms, LMW-SCF and HMW-
CC SCF. LMW-SCF is fully N-glycosylated at Asn-145, partially N-
CC glycosylated at Asn-90, O-glycosylated at Ser-167, Thr-168 and Thr-180,
CC and not glycosylated at Asn-97 or Asn-118. HMW-SCF is N-glycosylated at
CC Asn-118, Asn-90 and Asn-145, O-glycosylated at Ser-167, Thr-168 and
CC Thr-180, and not glycosylated at Asn-97. {ECO:0000269|PubMed:1381905}.
CC -!- PTM: A soluble form exists as a cleavage product of the extracellular
CC domain. {ECO:0000269|PubMed:1381905}.
CC -!- POLYMORPHISM: Genetic variants in KITLG define the skin/hair/eye
CC pigmentation variation locus 7 (SHEP7) [MIM:611664]. Hair, eye and skin
CC pigmentation are among the most visible examples of human phenotypic
CC variation, with a broad normal range that is subject to substantial
CC geographic stratification. In the case of skin, individuals tend to
CC have lighter pigmentation with increasing distance from the equator. By
CC contrast, the majority of variation in human eye and hair color is
CC found among individuals of European ancestry, with most other human
CC populations fixed for brown eyes and black hair.
CC -!- POLYMORPHISM: A non-coding SNP (dbSNP:rs12821256) has been shown to be
CC associated with classic blond hair color in Europeans. This SNP is
CC located 350 kb upstream from KITLG, in an enhancer specifically active
CC in the hair follicle environment. It alters a LEF1 binding site,
CC reducing LEF1 responsiveness in cultured keratinocytes. This SNP is not
CC associated with eye pigmentation. It is most prevalent in Northern
CC Europe (PubMed:24880339). {ECO:0000269|PubMed:24880339}.
CC -!- DISEASE: Hyperpigmentation with or without hypopigmentation, familial
CC progressive (FPHH) [MIM:145250]: A disorder characterized by
CC hyperpigmented patches in the skin, present in early infancy and
CC increasing in size and number with age. Hyperpigmentation has variable
CC intensity, and sometimes is associated with cafe-au-lait macules and
CC larger hypopigmented ash-leaf macules. {ECO:0000269|PubMed:19375057}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Deafness, congenital, unilateral or asymmetric (DCUA)
CC [MIM:616697]: An autosomal dominant form of non-syndromic,
CC sensorineural deafness characterized by inability to hear affecting one
CC ear. Some patients suffers from asymmetric, bilateral hearing loss.
CC {ECO:0000269|PubMed:26522471}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the SCF family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MGFID142.html";
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=two's company - Issue 163 of
CC August 2014;
CC URL="https://web.expasy.org/spotlight/back_issues/163/";
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DR EMBL; M59964; AAA85450.1; -; mRNA.
DR EMBL; AF119835; AAD22048.1; -; mRNA.
DR EMBL; AF400436; AAK92485.1; -; mRNA.
DR EMBL; AF400437; AAK92486.1; -; mRNA.
DR EMBL; AK290319; BAF83008.1; -; mRNA.
DR EMBL; AK293002; BAF85691.1; -; mRNA.
DR EMBL; CR749222; CAH18078.1; -; mRNA.
DR EMBL; CH471054; EAW97417.1; -; Genomic_DNA.
DR EMBL; BC069733; AAH69733.1; -; mRNA.
DR EMBL; BC069783; AAH69783.1; -; mRNA.
DR EMBL; BC069797; AAH69797.1; -; mRNA.
DR EMBL; BC074725; AAH74725.1; -; mRNA.
DR EMBL; BC126166; AAI26167.1; -; mRNA.
DR EMBL; BC143899; AAI43900.1; -; mRNA.
DR EMBL; S42571; AAB22846.2; -; mRNA.
DR CCDS; CCDS31867.1; -. [P21583-2]
DR CCDS; CCDS31868.1; -. [P21583-1]
DR PIR; A35974; A35974.
DR PIR; B61190; B61190.
DR PIR; S29052; S29052.
DR RefSeq; NP_000890.1; NM_000899.4. [P21583-1]
DR RefSeq; NP_003985.2; NM_003994.5. [P21583-2]
DR PDB; 1EXZ; X-ray; 2.30 A; A/B/C/D=26-166.
DR PDB; 1SCF; X-ray; 2.20 A; A/B/C/D=1-273.
DR PDB; 2E9W; X-ray; 3.50 A; C/D=26-166.
DR PDBsum; 1EXZ; -.
DR PDBsum; 1SCF; -.
DR PDBsum; 2E9W; -.
DR AlphaFoldDB; P21583; -.
DR SMR; P21583; -.
DR BioGRID; 110410; 29.
DR IntAct; P21583; 6.
DR STRING; 9606.ENSP00000228280; -.
DR BindingDB; P21583; -.
DR ChEMBL; CHEMBL2346489; -.
DR GlyGen; P21583; 7 sites.
DR iPTMnet; P21583; -.
DR MetOSite; P21583; -.
DR PhosphoSitePlus; P21583; -.
DR BioMuta; KITLG; -.
DR DMDM; 134289; -.
DR jPOST; P21583; -.
DR MassIVE; P21583; -.
DR MaxQB; P21583; -.
DR PaxDb; P21583; -.
DR PeptideAtlas; P21583; -.
DR PRIDE; P21583; -.
DR ProteomicsDB; 53880; -. [P21583-1]
DR ProteomicsDB; 53881; -. [P21583-2]
DR ProteomicsDB; 53882; -. [P21583-3]
DR Antibodypedia; 3883; 890 antibodies from 46 providers.
DR DNASU; 4254; -.
DR Ensembl; ENST00000347404.10; ENSP00000054216.5; ENSG00000049130.16. [P21583-2]
DR Ensembl; ENST00000644744.1; ENSP00000495951.1; ENSG00000049130.16. [P21583-1]
DR GeneID; 4254; -.
DR KEGG; hsa:4254; -.
DR MANE-Select; ENST00000644744.1; ENSP00000495951.1; NM_000899.5; NP_000890.1.
DR UCSC; uc001tav.4; human. [P21583-1]
DR CTD; 4254; -.
DR DisGeNET; 4254; -.
DR GeneCards; KITLG; -.
DR HGNC; HGNC:6343; KITLG.
DR HPA; ENSG00000049130; Low tissue specificity.
DR MalaCards; KITLG; -.
DR MIM; 145250; phenotype.
DR MIM; 184745; gene.
DR MIM; 611664; phenotype.
DR MIM; 616697; phenotype.
DR neXtProt; NX_P21583; -.
DR OpenTargets; ENSG00000049130; -.
DR Orphanet; 90635; Autosomal dominant non-syndromic sensorineural deafness type DFNA.
DR Orphanet; 280628; Familial progressive hyper- and hypopigmentation.
DR Orphanet; 79146; Familial progressive hyperpigmentation.
DR Orphanet; 363494; Non-seminomatous germ cell tumor of testis.
DR Orphanet; 895; Waardenburg syndrome type 2.
DR PharmGKB; PA30129; -.
DR VEuPathDB; HostDB:ENSG00000049130; -.
DR eggNOG; ENOG502QTGT; Eukaryota.
DR GeneTree; ENSGT00390000018272; -.
DR HOGENOM; CLU_090207_0_0_1; -.
DR InParanoid; P21583; -.
DR OMA; CWISVMV; -.
DR PhylomeDB; P21583; -.
DR TreeFam; TF330811; -.
DR PathwayCommons; P21583; -.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. [P21583-1]
DR Reactome; R-HSA-1433557; Signaling by SCF-KIT. [P21583-1]
DR Reactome; R-HSA-1433559; Regulation of KIT signaling. [P21583-1]
DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer. [P21583-1]
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. [P21583-1]
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. [P21583-1]
DR SignaLink; P21583; -.
DR SIGNOR; P21583; -.
DR BioGRID-ORCS; 4254; 2 hits in 1072 CRISPR screens.
DR ChiTaRS; KITLG; human.
DR EvolutionaryTrace; P21583; -.
DR GeneWiki; Stem_cell_factor; -.
DR GenomeRNAi; 4254; -.
DR Pharos; P21583; Tbio.
DR PRO; PR:P21583; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P21583; protein.
DR Bgee; ENSG00000049130; Expressed in visceral pleura and 186 other tissues.
DR ExpressionAtlas; P21583; baseline and differential.
DR Genevisible; P21583; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR GO; GO:0030175; C:filopodium; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0005173; F:stem cell factor receptor binding; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0035234; P:ectopic germ cell programmed cell death; IEA:Ensembl.
DR GO; GO:0035162; P:embryonic hemopoiesis; IDA:DFLAT.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl.
DR GO; GO:0008584; P:male gonad development; IEP:UniProtKB.
DR GO; GO:0033024; P:mast cell apoptotic process; IEA:Ensembl.
DR GO; GO:0097531; P:mast cell migration; IEA:Ensembl.
DR GO; GO:0070662; P:mast cell proliferation; IEA:Ensembl.
DR GO; GO:0097324; P:melanocyte migration; IEA:Ensembl.
DR GO; GO:0002573; P:myeloid leukocyte differentiation; IEA:Ensembl.
DR GO; GO:0033026; P:negative regulation of mast cell apoptotic process; IEA:Ensembl.
DR GO; GO:0001755; P:neural crest cell migration; IEA:Ensembl.
DR GO; GO:0001541; P:ovarian follicle development; IEA:Ensembl.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL.
DR GO; GO:1901534; P:positive regulation of hematopoietic progenitor cell differentiation; TAS:GO_Central.
DR GO; GO:1902035; P:positive regulation of hematopoietic stem cell proliferation; IEA:Ensembl.
DR GO; GO:0002687; P:positive regulation of leukocyte migration; IEA:Ensembl.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IEA:Ensembl.
DR GO; GO:0070668; P:positive regulation of mast cell proliferation; IEA:Ensembl.
DR GO; GO:0045636; P:positive regulation of melanocyte differentiation; IEA:Ensembl.
DR GO; GO:0002763; P:positive regulation of myeloid leukocyte differentiation; IEA:Ensembl.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; IEA:Ensembl.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IEA:Ensembl.
DR GO; GO:0007265; P:Ras protein signal transduction; IEA:Ensembl.
DR GO; GO:0042098; P:T cell proliferation; IEA:Ensembl.
DR DisProt; DP00917; -.
DR Gene3D; 1.20.1250.10; -; 1.
DR InterPro; IPR009079; 4_helix_cytokine-like_core.
DR InterPro; IPR003452; SCF.
DR PANTHER; PTHR11574; PTHR11574; 1.
DR Pfam; PF02404; SCF; 1.
DR PIRSF; PIRSF015599; SCF; 1.
DR SUPFAM; SSF47266; SSF47266; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell adhesion; Cell membrane;
KW Cell projection; Cytoplasm; Cytoskeleton; Deafness;
KW Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein;
KW Growth factor; Membrane; Non-syndromic deafness; Reference proteome;
KW Secreted; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..25
FT CHAIN 26..273
FT /note="Kit ligand"
FT /id="PRO_0000031913"
FT CHAIN 26..190
FT /note="Soluble KIT ligand"
FT /id="PRO_0000403391"
FT TOPO_DOM 26..214
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 215..237
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 238..273
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT SITE 97
FT /note="Not glycosylated"
FT CARBOHYD 90
FT /note="N-linked (GlcNAc...) asparagine; partial"
FT /evidence="ECO:0000269|PubMed:1381905"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine; partial"
FT /evidence="ECO:0000269|PubMed:1381905"
FT CARBOHYD 145
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:1381905"
FT CARBOHYD 167
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|PubMed:1381905"
FT CARBOHYD 168
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:1381905"
FT CARBOHYD 180
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:1381905"
FT CARBOHYD 195
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 29..114
FT DISULFID 68..163
FT VAR_SEQ 1..35
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_032762"
FT VAR_SEQ 36..43
FT /note="NVKDVTKL -> MPSCLAAQ (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_032763"
FT VAR_SEQ 174..202
FT /note="DSRVSVTKPFMLPPVAASSLRNDSSSSNR -> G (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10049787,
FT ECO:0000303|PubMed:1379846, ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:1724381,
FT ECO:0000303|Ref.4"
FT /id="VSP_006022"
FT VARIANT 36
FT /note="N -> S (in FPHH; gain-of-function mutation; sKITLG
FT reveales that the mutant Ser-36 sKITLG increases the
FT content of the melanin by 109% compared with the wild-type
FT sKITLG; tyrosinase activity is significantly increased by
FT the mutant sKITLG compared to wild-type control;
FT dbSNP:rs121918653)"
FT /evidence="ECO:0000269|PubMed:19375057"
FT /id="VAR_063237"
FT VARIANT 54
FT /note="T -> A (in dbSNP:rs3741457)"
FT /id="VAR_042652"
FT VARIANT 67..68
FT /note="HC -> R (in DCUA; loss of cell membrane
FT association)"
FT /evidence="ECO:0000269|PubMed:26522471"
FT /id="VAR_076222"
FT VARIANT 104
FT /note="L -> V (found in a patient with Waardenburg syndrome
FT type 2 (WS2) and hearing loss; unknown pathological
FT significance; reduces secretion; dbSNP:rs864309655)"
FT /evidence="ECO:0000269|PubMed:26522471"
FT /id="VAR_076223"
FT VARIANT 210
FT /note="D -> Y (in dbSNP:rs41283112)"
FT /id="VAR_063238"
FT VARIANT 232
FT /note="F -> Y (in dbSNP:rs12721563)"
FT /id="VAR_042653"
FT CONFLICT 55
FT /note="L -> S (in Ref. 3; AAD22048 and 4; AAK92486)"
FT /evidence="ECO:0000305"
FT CONFLICT 128
FT /note="K -> R (in Ref. 3; AAD22048 and 4; AAK92486)"
FT /evidence="ECO:0000305"
FT CONFLICT 134
FT /note="L -> F (in Ref. 3; AAD22048 and 4; AAK92486)"
FT /evidence="ECO:0000305"
FT HELIX 30..32
FT /evidence="ECO:0007829|PDB:2E9W"
FT HELIX 37..46
FT /evidence="ECO:0007829|PDB:1SCF"
FT STRAND 53..56
FT /evidence="ECO:0007829|PDB:1SCF"
FT TURN 59..63
FT /evidence="ECO:0007829|PDB:1SCF"
FT HELIX 66..68
FT /evidence="ECO:0007829|PDB:1SCF"
FT HELIX 70..85
FT /evidence="ECO:0007829|PDB:1SCF"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:2E9W"
FT HELIX 97..114
FT /evidence="ECO:0007829|PDB:1SCF"
FT STRAND 120..122
FT /evidence="ECO:0007829|PDB:1EXZ"
FT STRAND 132..135
FT /evidence="ECO:0007829|PDB:1SCF"
FT HELIX 137..149
FT /evidence="ECO:0007829|PDB:1SCF"
FT TURN 150..152
FT /evidence="ECO:0007829|PDB:1SCF"
FT STRAND 157..160
FT /evidence="ECO:0007829|PDB:1SCF"
SQ SEQUENCE 273 AA; 30899 MW; 19FD362CB59C6607 CRC64;
MKKTQTWILT CIYLQLLLFN PLVKTEGICR NRVTNNVKDV TKLVANLPKD YMITLKYVPG
MDVLPSHCWI SEMVVQLSDS LTDLLDKFSN ISEGLSNYSI IDKLVNIVDD LVECVKENSS
KDLKKSFKSP EPRLFTPEEF FRIFNRSIDA FKDFVVASET SDCVVSSTLS PEKDSRVSVT
KPFMLPPVAA SSLRNDSSSS NRKAKNPPGD SSLHWAAMAL PALFSLIIGF AFGALYWKKR
QPSLTRAVEN IQINEEDNEI SMLQEKEREF QEV
