SCF_RAT
ID SCF_RAT Reviewed; 273 AA.
AC P21581; Q9QWZ4; Q9Z2E7;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2002, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Kit ligand;
DE AltName: Full=Hematopoietic growth factor KL;
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=Kitl, Mgf;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RA Teramoto T., Nagashima M., Thorgeirsson S.S.;
RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-201, AND PARTIAL PROTEIN SEQUENCE.
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 [3]
RP PROTEIN SEQUENCE OF 26-190, PYROGLUTAMATE FORMATION AT GLN-26,
RP GLYCOSYLATION AT ASN-90; ASN-145; SER-167; THR-168; THR-180 AND ASN-195,
RP LACK OF GLYCOSYLATION AT ASN-97, AND DISULFIDE BONDS.
RC STRAIN=Buffalo; TISSUE=Liver;
RX PubMed=1708771; DOI=10.1016/s0021-9258(18)92947-9;
RA Lu H.S., Clogston C.L., Wypych J., Fausset P.R., Lauren S., Mendiaz E.A.,
RA Zsebo K.M., Langley K.E.;
RT "Amino acid sequence and post-translational modification of stem cell
RT factor isolated from buffalo rat liver cell-conditioned medium.";
RL J. Biol. Chem. 266:8102-8107(1991).
RN [4]
RP PROTEIN SEQUENCE OF 26-39.
RX PubMed=2208278; DOI=10.1016/0092-8674(90)90300-4;
RA Zsebo K.M., Wypych J., McNiece I.K., Lu H.S., Smith K.A., Karkare S.B.,
RA Sachdev R.K., Yuschenkoff V.N., Birkett N.C., Williams L.R., Satyagal V.N.,
RA Tung W., Bosselman R.A., Mendiaz E.A., Langley K.E.;
RT "Identification, purification, and biological characterization of
RT hematopoietic stem cell factor from buffalo rat liver-conditioned medium.";
RL Cell 63:195-201(1990).
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. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000250}; Single-
CC pass type I membrane protein {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000250|UniProtKB:P21583}. Cytoplasm, cytoskeleton {ECO:0000250}.
CC Cell membrane {ECO:0000250|UniProtKB:P21583}; Single-pass type I
CC membrane protein {ECO:0000250}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:P21583}. Cell projection, filopodium
CC {ECO:0000250|UniProtKB:P21583}.
CC -!- SUBCELLULAR LOCATION: [Soluble KIT ligand]: Secreted {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=KL-1;
CC IsoId=P21581-1; Sequence=Displayed;
CC Name=2; Synonyms=KL-2;
CC IsoId=P21581-2; Sequence=VSP_006025;
CC -!- DEVELOPMENTAL STAGE: Acts in the early stages of hematopoiesis.
CC -!- PTM: A soluble form is produced by proteolytic processing of isoform 1
CC in the extracellular domain.
CC -!- PTM: The identity of N- and O-linked saccharides are not reported in
CC PubMed:1708771. The O-linked polysaccharides are probably the mucin
CC type linked to GalNAc. {ECO:0000269|PubMed:1708771}.
CC -!- SIMILARITY: Belongs to the SCF family. {ECO:0000305}.
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DR EMBL; AF071204; AAD02827.1; -; mRNA.
DR EMBL; AF071205; AAD02828.1; -; mRNA.
DR EMBL; M59966; AAA42117.1; -; mRNA.
DR PIR; B35974; B35974.
DR RefSeq; NP_068615.1; NM_021843.4. [P21581-1]
DR AlphaFoldDB; P21581; -.
DR SMR; P21581; -.
DR BioGRID; 248828; 2.
DR STRING; 10116.ENSRNOP00000008471; -.
DR GlyGen; P21581; 6 sites.
DR iPTMnet; P21581; -.
DR PhosphoSitePlus; P21581; -.
DR PaxDb; P21581; -.
DR Ensembl; ENSRNOT00000008471; ENSRNOP00000008471; ENSRNOG00000005386. [P21581-1]
DR GeneID; 60427; -.
DR KEGG; rno:60427; -.
DR CTD; 4254; -.
DR RGD; 3086; Kitlg.
DR eggNOG; ENOG502QTGT; Eukaryota.
DR GeneTree; ENSGT00390000018272; -.
DR HOGENOM; CLU_090207_0_0_1; -.
DR InParanoid; P21581; -.
DR OMA; CWISVMV; -.
DR OrthoDB; 1083457at2759; -.
DR PhylomeDB; P21581; -.
DR TreeFam; TF330811; -.
DR Reactome; R-RNO-1257604; PIP3 activates AKT signaling.
DR Reactome; R-RNO-1433557; Signaling by SCF-KIT.
DR Reactome; R-RNO-1433559; Regulation of KIT signaling.
DR Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
DR Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR PRO; PR:P21581; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000005386; Expressed in lung and 20 other tissues.
DR ExpressionAtlas; P21581; baseline and differential.
DR Genevisible; P21581; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0030175; C:filopodium; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; ISO:RGD.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005125; F:cytokine activity; ISO:RGD.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0005173; F:stem cell factor receptor binding; ISO:RGD.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0035234; P:ectopic germ cell programmed cell death; ISO:RGD.
DR GO; GO:0035162; P:embryonic hemopoiesis; ISO:RGD.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; ISO:RGD.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl.
DR GO; GO:0008584; P:male gonad development; ISO:RGD.
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:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0033026; P:negative regulation of mast cell apoptotic process; ISO:RGD.
DR GO; GO:0001755; P:neural crest cell migration; ISO:RGD.
DR GO; GO:0001541; P:ovarian follicle development; IDA:RGD.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:RGD.
DR GO; GO:1901534; P:positive regulation of hematopoietic progenitor cell differentiation; IEA:Ensembl.
DR GO; GO:1902035; P:positive regulation of hematopoietic stem cell proliferation; ISO:RGD.
DR GO; GO:0002687; P:positive regulation of leukocyte migration; ISO:RGD.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISO:RGD.
DR GO; GO:0070668; P:positive regulation of mast cell proliferation; ISO:RGD.
DR GO; GO:0045636; P:positive regulation of melanocyte differentiation; ISO:RGD.
DR GO; GO:0002763; P:positive regulation of myeloid leukocyte differentiation; ISO:RGD.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; ISO:RGD.
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 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 Alternative splicing; Cell adhesion; Cell membrane; Cell projection;
KW Cytoplasm; Cytoskeleton; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Growth factor; Membrane; Pyrrolidone carboxylic acid;
KW Reference proteome; Secreted; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000269|PubMed:1708771,
FT ECO:0000269|PubMed:2208278"
FT CHAIN 26..273
FT /note="Kit ligand"
FT /id="PRO_0000031917"
FT CHAIN 26..190
FT /note="Soluble KIT ligand"
FT /evidence="ECO:0000250"
FT /id="PRO_0000403393"
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 REGION 190..211
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 191..205
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 97
FT /note="Not glycosylated"
FT /evidence="ECO:0000269|PubMed:1708771"
FT MOD_RES 26
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:1708771"
FT CARBOHYD 90
FT /note="N-linked (GlcNAc...) asparagine; partial"
FT /evidence="ECO:0000269|PubMed:1708771"
FT CARBOHYD 145
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:1708771"
FT CARBOHYD 167
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000305|PubMed:1708771"
FT CARBOHYD 168
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000305|PubMed:1708771"
FT CARBOHYD 180
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000305|PubMed:1708771"
FT CARBOHYD 195
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 29..114
FT /evidence="ECO:0000269|PubMed:1708771"
FT DISULFID 68..163
FT /evidence="ECO:0000269|PubMed:1708771"
FT VAR_SEQ 174..202
FT /note="DSRVSVTKPFMLPPVAASSLRNDSSSSNR -> G (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_006025"
FT CONFLICT 207
FT /note="S -> P (in Ref. 1; AAD02828)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 273 AA; 30712 MW; C0F56527DC93FD27 CRC64;
MKKTQTWIIT CIYLQLLLFN PLVKTQEICR NPVTDNVKDI TKLVANLPND YMITLNYVAG
MDVLPSHCWL RDMVTHLSVS LTTLLDKFSN ISEGLSNYSI IDKLGKIVDD LVACMEENAP
KNVKESLKKP ETRNFTPEEF FSIFNRSIDA FKDFMVASDT SDCVLSSTLG PEKDSRVSVT
KPFMLPPVAA SSLRNDSSSS NRKAAKSPED PGLQWTAMAL PALISLVIGF AFGALYWKKK
QSSLTRAVEN IQINEEDNEI SMLQQKEREF QEV
