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 24-JAN-2024, entry version 205. DE RecName: Full=Kit ligand; DE AltName: Full=Mast cell growth factor {ECO:0000305|PubMed:1724381}; DE Short=MGF {ECO:0000305|PubMed:1724381}; DE AltName: Full=Stem cell factor {ECO:0000305|PubMed:2208279}; DE Short=SCF {ECO:0000305|PubMed:2208279}; DE AltName: Full=c-Kit ligand; DE Contains: DE RecName: Full=Soluble KIT ligand; DE Short=sKITLG; DE Flags: Precursor; GN Name=KITLG {ECO:0000312|HGNC:HGNC:6343}; 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 WS2F 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). RN [21] RP VARIANT WS2F CYS-32, AND INVOLVEMENT IN WS2F. RX PubMed=28504826; DOI=10.1111/pcmr.12597; RA Ogawa Y., Kono M., Akiyama M.; RT "Pigmented macules in Waardenburg syndrome type 2 due to KITLG mutation."; RL Pigment Cell Melanoma Res. 30:501-504(2017). RN [22] RP VARIANTS WS2F CYS-32; THR-148 AND 215-TRP--VAL-273 DEL, AND INVOLVEMENT IN RP WS2F. RX PubMed=35543077; DOI=10.1111/jdv.18207; RA Vona B., Schwartzbaum D.A., Rodriguez A.A., Lewis S.S., Toosi M.B., RA Radhakrishnan P., Bozan N., Akin R., Doosti M., Manju R., Duman D., RA Sineni C.J., Nampoothiri S., Karimiani E.G., Houlden H., Bademci G., RA Tekin M., Girisha K.M., Maroofian R., Douzgou S.; RT "Biallelic KITLG variants lead to a distinct spectrum of hypomelanosis and RT sensorineural hearing loss."; RL J. Eur. Acad. Dermatol. Venereol. 36:1606-1611(2022). 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 -!- DISEASE: Waardenburg syndrome 2F (WS2F) [MIM:619947]: A form of CC Waardenburg syndrome, an auditory-pigmentary disorder characterized by CC sensorineural deafness, pigmentary disturbances of the hair, skin and CC eyes, and absence of dystopia canthorum which is the lateral CC displacement of the inner canthus of each eye. WS2F is an autosomal CC recessive form with variable expressivity, characterized by congenital CC or neonatal-onset sensorineural hearing loss. CC {ECO:0000269|PubMed:26522471, ECO:0000269|PubMed:28504826, CC ECO:0000269|PubMed:35543077}. Note=The disease may be caused by CC variants 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="https://atlasgeneticsoncology.org/gene/142/MGF"; 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/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 8DFM; EM; 3.45 A; C/D=26-166. DR PDB; 8DFP; EM; 3.17 A; C/D=28-155. DR PDB; 8DFQ; EM; 3.96 A; C/D=26-166. DR PDBsum; 1EXZ; -. DR PDBsum; 1SCF; -. DR PDBsum; 2E9W; -. DR PDBsum; 8DFM; -. DR PDBsum; 8DFP; -. DR PDBsum; 8DFQ; -. DR AlphaFoldDB; P21583; -. DR EMDB; EMD-2648; -. DR EMDB; EMD-27408; -. DR EMDB; EMD-27410; -. DR EMDB; EMD-27411; -. DR SMR; P21583; -. DR BioGRID; 110410; 29. DR IntAct; P21583; 6. DR STRING; 9606.ENSP00000495951; -. DR BindingDB; P21583; -. DR ChEMBL; CHEMBL2346489; -. DR GlyCosmos; P21583; 7 sites, No reported glycans. DR GlyGen; P21583; 10 sites, 1 O-linked glycan (5 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; 9606-ENSP00000228280; -. DR PeptideAtlas; P21583; -. DR ProteomicsDB; 53880; -. [P21583-1] DR ProteomicsDB; 53881; -. [P21583-2] DR ProteomicsDB; 53882; -. [P21583-3] DR Pumba; P21583; -. DR Antibodypedia; 3883; 997 antibodies from 47 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 AGR; HGNC:6343; -. 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 MIM; 619947; phenotype. DR neXtProt; NX_P21583; -. DR OpenTargets; ENSG00000049130; -. 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; 90635; Rare autosomal dominant non-syndromic sensorineural deafness type DFNA. 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; TKGICRN; -. DR OrthoDB; 3991511at2759; -. 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; 3 hits in 1155 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 187 other cell types or tissues. DR ExpressionAtlas; P21583; baseline and differential. 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: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: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: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:0014070; P:response to organic cyclic compound; 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; KIT LIGAND; 1. DR PANTHER; PTHR11574:SF0; KIT LIGAND; 1. DR Pfam; PF02404; SCF; 1. DR PIRSF; PIRSF015599; SCF; 1. DR SUPFAM; SSF47266; 4-helical cytokines; 1. DR Genevisible; P21583; HS. 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; Waardenburg syndrome. 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 32 FT /note="R -> C (in WS2F; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28504826, FT ECO:0000269|PubMed:35543077" FT /id="VAR_087496" 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 (in WS2F; uncertain significance; reduces FT secretion; dbSNP:rs864309655)" FT /evidence="ECO:0000269|PubMed:26522471" FT /id="VAR_076223" FT VARIANT 148 FT /note="I -> T (in WS2F; uncertain significance; FT dbSNP:rs751013211)" FT /evidence="ECO:0000269|PubMed:35543077" FT /id="VAR_087497" FT VARIANT 210 FT /note="D -> Y (in dbSNP:rs41283112)" FT /id="VAR_063238" FT VARIANT 215..273 FT /note="Missing (in WS2F; uncertain significance)" FT /evidence="ECO:0000269|PubMed:35543077" FT /id="VAR_087498" 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 TURN 30..32 FT /evidence="ECO:0007829|PDB:8DFP" 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:8DFP" 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 //