P20826 (SCF_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Kit ligand

Alternative name(s):
Hematopoietic growth factor KL
Mast cell growth factor
Short name=MGF
Steel factor
Stem cell factor
Short name=SCF
c-Kit ligand

Cleaved into the following chain:

1. Soluble KIT ligand
   Short name=sKITLG

Gene names

Name:	Kitlg
Synonyms:	Kitl, Mgf, Sl, Slf

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	273 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Ref.14
Subcellular location	Isoform 1: Cell membrane; Single-pass type I membrane protein By similarity. Isoform 2: Cell membrane; Single-pass type I membrane protein By similarity. Cytoplasm › cytoskeleton By similarity. Soluble KIT ligand: Secreted By similarity.
Developmental stage	Acts in the early stages of hematopoiesis.
Post-translational modification	A soluble form is produced by proteolytic processing of isoform 1 in the extracellular domain.
Sequence similarities	Belongs to the SCF family.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell membrane Cytoplasm Cytoskeleton Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Growth factor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW embryonic hemopoiesis Inferred from electronic annotation. Source: Compara germ cell development Traceable author statement PubMed 12140361. Source: MGI germ cell programmed cell death Inferred from mutant phenotype PubMed 17107997. Source: MGI male gonad development Inferred from electronic annotation. Source: Compara negative regulation of mast cell apoptotic process Inferred from direct assay PubMed 12714518. Source: MGI neural crest cell migration Inferred from direct assay PubMed 11401406. Source: MGI positive regulation of DNA replication Inferred from electronic annotation. Source: Compara positive regulation of MAP kinase activity Inferred from genetic interaction PubMed 10620616. Source: MGI positive regulation of Ras protein signal transduction Inferred from direct assay PubMed 11435472. Source: MGI positive regulation of mast cell proliferation Inferred from direct assay PubMed 15947484. Source: MGI positive regulation of melanocyte differentiation Inferred from direct assay PubMed 16427619. Source: MGI positive regulation of myeloid leukocyte differentiation Inferred from genetic interaction PubMed 1375116PubMed 7690439. Source: MGI positive regulation of peptidyl-tyrosine phosphorylation Inferred from direct assay PubMed 10872802. Source: MGI
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular space Inferred from direct assay PubMed 14525951PubMed 7690439. Source: MGI integral to membrane Inferred from direct assay PubMed 12140361. Source: MGI plasma membrane Inferred from direct assay PubMed 14525951. Source: MGI
Molecular_function	cytokine activity Inferred from direct assay PubMed 12714518. Source: MGI stem cell factor receptor binding Inferred from direct assay PubMed 10872802. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P20826-1)

Also known as: KL-1;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P20826-2)

Also known as: KL-2;

The sequence of this isoform differs from the canonical sequence as follows:
     174-202: DSRVSVTKPFMLPPVAASSLRNDSSSSNR → G

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 25

25

Ref.10 Ref.12 Ref.13

Chain

26 – 273

248

Kit ligand

PRO_0000031914

Chain

26 – 190

165

Soluble KIT ligand By similarity

PRO_0000403392

Regions

Topological domain

26 – 214

189

Extracellular Potential

Transmembrane

215 – 237

23

Helical; Potential

Topological domain

238 – 273

36

Cytoplasmic Potential

Amino acid modifications

Glycosylation

90

1

N-linked (GlcNAc...) Potential

Glycosylation

97

1

N-linked (GlcNAc...) Potential

Glycosylation

145

1

N-linked (GlcNAc...) Potential

Glycosylation

195

1

N-linked (GlcNAc...) Potential

Disulfide bond

29 ↔ 114

Ref.14

Disulfide bond

68 ↔ 163

Ref.14

Natural variations

Alternative sequence

174 – 202

29

DSRVS…SSSNR → G in isoform 2.

VSP_006023

Natural variant

122

1

N → S in MGFSL-3NEU. Ref.7

Natural variant

193

1

L → P. Ref.6 Ref.7

Natural variant

207

1

A → S. Ref.6 Ref.7 Ref.9

Experimental info

Sequence conflict

215

1

W → L in AAB22555. Ref.2

Sequence conflict

215

1

W → L in AAB22554. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

273

Helix Strand Turn

Details...

Helix

35 – 39

5

Helix

40 – 45

6

Beta strand

53 – 57

5

Turn

59 – 63

5

Helix

66 – 68

3

Helix

70 – 85

16

Helix

97 – 118

22

Beta strand

131 – 135

5

Helix

137 – 151

15

Turn

153 – 156

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (KL-1) [UniParc]. Last modified February 1, 1991. Version 1. Checksum: A7FC899B592A7967	FASTA	273	30,645
	10 20 30 40 50 60 MKKTQTWIIT CIYLQLLLFN PLVKTKEICG NPVTDNVKDI TKLVANLPND YMITLNYVAG 70 80 90 100 110 120 MDVLPSHCWL RDMVIQLSLS LTTLLDKFSN ISEGLSNYSI IDKLGKIVDD LVLCMEENAP 130 140 150 160 170 180 KNIKESPKRP ETRSFTPEEF FSIFNRSIDA FKDFMVASDT SDCVLSSTLG PEKDSRVSVT 190 200 210 220 230 240 KPFMLPPVAA SSLRNDSSSS NRKAAKAPED SGLQWTAMAL PALISLVIGF AFGALYWKKK 250 260 270 QSSLTRAVEN IQINEEDNEI SMLQQKEREF QEV
	Isoform 2 (KL-2) [UniParc]. Checksum: 78160A204FABF93B	FASTA	245	27,614
	10 20 30 40 50 60 MKKTQTWIIT CIYLQLLLFN PLVKTKEICG NPVTDNVKDI TKLVANLPND YMITLNYVAG 70 80 90 100 110 120 MDVLPSHCWL RDMVIQLSLS LTTLLDKFSN ISEGLSNYSI IDKLGKIVDD LVLCMEENAP 130 140 150 160 170 180 KNIKESPKRP ETRSFTPEEF FSIFNRSIDA FKDFMVASDT SDCVLSSTLG PEKGKAAKAP 190 200 210 220 230 240 EDSGLQWTAM ALPALISLVI GFAFGALYWK KKQSSLTRAV ENIQINEEDN EISMLQQKER EFQEV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of mast cell growth factor, a hematopoietin that is active in both membrane bound and soluble forms." Anderson D.M., Lyman S.D., Baird A., Wignall J.M., Eisenman J., Rauch C., March C.J., Boswell H.S., Gimpel S.D., Cosman D., Williams D.E. Cell 63:235-243(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Strain: WCB6F1.
[2]	"Differential expression and processing of two cell associated forms of the kit-ligand: KL-1 and KL-2." Huang E.J., Nocka K.H., Buck J., Besmer P. Mol. Biol. Cell 3:349-362(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ISOFORMS 1 AND 2).
[3]	"Transmembrane form of the kit ligand growth factor is determined by alternative splicing and is missing in the Sld mutant." Flanagan J.G., Chan D.C., Leder P. Cell 64:1025-1035(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ISOFORMS 1 AND 2). Strain: WCB6F1.
[4]	"Developmental abnormalities in Steel17H mice result from a splicing defect in the steel factor cytoplasmic tail." Brannan C.I., Bedell M.A., Resnick J.L., Eppig J.J., Handel M.A., Williams D.E., Lyman S.D., Donovan P.J., Jenkins N.A., Copeland N.G. Genes Dev. 6:1832-1842(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1).
[5]	"Multiple pathways for Steel regulation suggested by genomic and sequence analysis of the murine Steel gene." Bedell M.A., Copeland N.G., Jenkins N.A. Genetics 142:927-934(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1). Strain: C57BL/6J.
[6]	"Molecular analysis of two new Steel mutations in mice shows a transversion or an insertion." Graw J., Loester J., Neuhaeuser-Klaus A., Pretsch W., Schmitt-John T. Mamm. Genome 7:843-846(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS PRO-193 AND SER-207. Strain: C3H/E1. Tissue: Brain.
[7]	"Detection of a point mutation (A to G) in exon 5 of the murine Mgf gene defines a novel allele at the Steel locus with a weak phenotype." Graw J., Neuhauser-Klaus A., Pretsch W. Mutat. Res. 382:75-78(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS SER-122; PRO-193 AND SER-207. Strain: 102/E1 X C3H/E1.
[8]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6J. Tissue: Cerebellum and Testis.
[9]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT SER-207.
[10]	"The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus." Huang E., Nocka K., Beier D.R., Chu T.Y., Buck J., Lahm H.W., Wellner D., Leder P., Besmer P. Cell 63:225-233(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 1-270 (ISOFORM 1), PROTEIN SEQUENCE OF 26-65.
[11]	"Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor." Zsebo K.M., Williams D.A., Geissler E.N., Broudy V.C., Martin F.H., Atkins H.L., Hsu R.-Y., Birkett N.C., Okino K.H., Murdock D.C., Jacobsen F.W., Langley K.E., Smith K.A., Takeishi T., Cattanach B.M., Galli S.J., Suggs S.V. Cell 63:213-224(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-201.
[12]	"Mast cell growth factor maps near the steel locus on mouse chromosome 10 and is deleted in a number of steel alleles." Copeland N.G., Gilbert D.J., Cho B.C., Donovan P.J., Jenkins N.A., Cosman D., Anderson D., Lyman S.D., Williams D.E. Cell 63:175-183(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 26-53.
[13]	"Identification of a ligand for the c-kit proto-oncogene." Williams D.E., Eisenman J., Baird A., Rauch C., van Ness K., March C.J., Park L.S., Martin U., Mochizuki D.Y., Boswell H.S., Burgess G.S., Cosman D., Lyman S.D. Cell 63:167-174(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 26-78.
[14]	"Structural basis for stem cell factor-KIT signaling and activation of class III receptor tyrosine kinases." Liu H., Chen X., Focia P.J., He X. EMBO J. 26:891-901(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 28-166 ALONE AND IN COMPLEX WITH KIT, SUBUNIT, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M59915 mRNA. Translation: AAA40095.1.
M57647 mRNA. Translation: AAA39538.1.
S40534 mRNA. Translation: AAB22555.2.
X68989 mRNA. Translation: CAA48778.1.
U44724 Genomic DNA. No translation available.
U44725 mRNA. Translation: AAC52447.1.
X95381 mRNA. Translation: CAA64667.1.
X99322 mRNA. Translation: CAA67698.1.
Y10287 mRNA. Translation: CAA71329.1.
AK018777 mRNA. Translation: BAB31402.1.
AK134301 mRNA. Translation: BAE22091.1.
AK165233 mRNA. Translation: BAE38091.1.
BC011322 mRNA. Translation: AAH11322.1.
S40364 mRNA. Translation: AAB22554.2.
M59912 mRNA. Translation: AAA39539.1.

IPI

IPI00123822.
IPI00229389.

PIR

A35971.
A37934.
B35971.
S65801.

RefSeq

NP_038626.1. NM_013598.2.

UniGene

Mm.45124.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2O26	X-ray	2.50	A/B/E/F	28-166	[»]
2O27	X-ray	2.20	A/B	28-166	[»]

ProteinModelPortal

P20826.

SMR

P20826. Positions 28-166.

ModBase

Search...

PTM databases

PhosphoSite

P20826.

Proteomic databases

PRIDE

P20826.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000020129; ENSMUSP00000020129; ENSMUSG00000019966.
ENSMUST00000105283; ENSMUSP00000100920; ENSMUSG00000019966.

GeneID

17311.

KEGG

mmu:17311.

UCSC

uc007gxp.1. mouse.
uc007gxq.1. mouse.

Organism-specific databases

CTD

17311.

MGI

MGI:96974. Kitl.

Phylogenomic databases

eggNOG

NOG39386.

GeneTree

ENSGT00390000018272.

HOGENOM

HOG000082493.

HOVERGEN

HBG036146.

InParanoid

P20826.

KO

K05461.

OMA

VKTKGIC.

OrthoDB

EOG41G34W.

Enzyme and pathway databases

Reactome

REACT_115202. Signal Transduction.

Gene expression databases

ArrayExpress

P20826.

Bgee

P20826.

CleanEx

MM_KITL.

Genevestigator

P20826.

GermOnline

ENSMUSG00000019966. Mus musculus.

Family and domain databases

Gene3D

1.20.1250.10. 1 hit.

InterPro

IPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR003452. SCF.
[Graphical view]

PANTHER

PTHR11574. PTHR11574. 1 hit.

Pfam

PF02404. SCF. 1 hit.
[Graphical view]

PIRSF

PIRSF015599. SCF. 1 hit.

SUPFAM

SSF47266. 4_helix_cytokine. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

P20826.

NextBio

291864.

PMAP-CutDB

P20826.

SOURCE

Search...

Entry information

Entry name

SCF_MOUSE

Accession

Primary (citable) accession number: P20826
Secondary accession number(s): P97332 , Q3TNJ7, Q62524, Q64222, Q921N5

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	February 1, 1991
Last modified:	April 3, 2013
This is version 138 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program