Reviewed, UniProtKB/Swiss-Prot P21583 (SCF_HUMAN)

Names and origin

Protein names

Recommended name:
    Kit ligand
Alternative name(s):
    C-kit ligand
    Stem cell factor
      Short name=SCF
    Mast cell growth factor
      Short name=MGF

Gene names

Name:	KITLG
Synonyms:	MGF, SCF

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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	Stimulates the proliferation of mast cells. Able to augment the proliferation of both myeloid and lymphoid hematopoietic progenitors in bone marrow culture. Mediates also cell-cell adhesion. Acts synergistically with other cytokines, probably interleukins.
Subunit structure	Homodimer, non-covalently linked Probable.
Subcellular location	Isoform 1: Cell membrane; Single-pass type I membrane protein By similarity. Secreted By similarity. Note: Also exists as a secreted soluble form (isoform 1 only) By similarity. Isoform 2: Cell membrane; Single-pass type I membrane protein By similarity. Cytoplasm › cytoskeleton 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. Found in two differentially glycosylated forms, LMW-SCF and HMW-SCF. LMW-SCF is fully N-glycosylated at Asn-145, partially N-glycosylated at Asn-90, O-glycosylated at Ser-167, Thr-168 and Thr-180, and not glycosylated at Asn-97 or Asn-118. HMW-SCF is N-glycosylated at Asn-118, Asn-90 and Asn-145, O-glycosylated at Ser-167, Thr-168 and Thr-180, and not glycosylated at Asn-97. Ref.9
Polymorphism	Genetic variations in KITLG are associated with variation in skin/hair/eye pigmentation type 7 (SHEP7) [MIM:611664]. Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair.
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
Molecular function	Growth factor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW cell proliferation Ref.1 Traceable author statement. Source: ProtInc hemopoiesis Non-traceable author statement. Source: UniProtKB positive regulation of DNA replication Inferred from direct assay. Source: UniProtKB signal transduction Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Ref.3 Non-traceable author statement. Source: UniProtKB
Molecular function	growth factor activity Inferred from electronic annotation. Source: UniProtKB-KW identical protein binding Ref.13 Inferred from physical interaction. Source: IntAct stem cell factor receptor binding Ref.1 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-1379527,EBI-1379527
KIT	P10721	1	EBI-1379527,EBI-1379503

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P21583-1)

Also known as: SCF248;

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.

Note: Also exists as a secreted soluble form (isoform 1 only) (By similarity).

Isoform 2 (identifier: P21583-2)

Also known as: SCF220;

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

Isoform 3 (identifier: P21583-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-35: Missing.
     36-43: NVKDVTKL → MPSCLAAQ

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 25

25

Ref.9

Chain

26 – 273

248

Kit ligand

PRO_0000031913

Regions

Topological domain

26 – 214

189

Extracellular Potential

Transmembrane

215 – 237

23

Potential

Topological domain

238 – 273

36

Cytoplasmic Potential

Sites

Site

97

1

Not glycosylated

Amino acid modifications

Glycosylation

90

1

N-linked (GlcNAc...); partial Ref.9

Glycosylation

118

1

N-linked (GlcNAc...); partial Ref.9

Glycosylation

145

1

N-linked (GlcNAc...) Ref.9

Glycosylation

167

1

O-linked (GalNAc...) Ref.9

Glycosylation

168

1

O-linked (GalNAc...) Ref.9

Glycosylation

180

1

O-linked (GalNAc...) Ref.9

Glycosylation

195

1

N-linked (GlcNAc...) Potential

Disulfide bond

29 ↔ 114

Ref.9 Ref.12 Ref.13 Ref.14

Disulfide bond

68 ↔ 163

Ref.9 Ref.12 Ref.13 Ref.14

Natural variations

Alternative sequence

1 – 35

35

Missing in isoform 3.

VSP_032762

Alternative sequence

36 – 43

8

NVKDVTKL → MPSCLAAQ in isoform 3.

VSP_032763

Alternative sequence

174 – 202

29

DSRVS…SSSNR → G in isoform 2.

VSP_006022

Natural variant

54

1

T → A: dbSNP rs3741457.

VAR_042652

Natural variant

232

1

F → Y: dbSNP rs12721563.

VAR_042653

Experimental info

Sequence conflict

55

1

L → S in AAD22048. Ref.3

Sequence conflict

55

1

L → S in AAK92486. Ref.4

Sequence conflict

128

1

K → R in AAD22048. Ref.3

Sequence conflict

128

1

K → R in AAK92486. Ref.4

Sequence conflict

134

1

L → F in AAD22048. Ref.3

Sequence conflict

134

1

L → F in AAK92486. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

273

Helix Strand Turn

Details...

Helix

37 – 45

9

Beta strand

53 – 57

5

Turn

59 – 63

5

Helix

66 – 68

3

Helix

70 – 85

16

Helix

97 – 117

21

Beta strand

120 – 122

3

Beta strand

131 – 135

5

Helix

137 – 152

16

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (SCF248) [UniParc]. Last modified May 1, 1991. Version 1. Checksum: 19FD362CB59C6607	FASTA	273	30,899
	10 20 30 40 50 60 MKKTQTWILT CIYLQLLLFN PLVKTEGICR NRVTNNVKDV TKLVANLPKD YMITLKYVPG 70 80 90 100 110 120 MDVLPSHCWI SEMVVQLSDS LTDLLDKFSN ISEGLSNYSI IDKLVNIVDD LVECVKENSS 130 140 150 160 170 180 KDLKKSFKSP EPRLFTPEEF FRIFNRSIDA FKDFVVASET SDCVVSSTLS PEKDSRVSVT 190 200 210 220 230 240 KPFMLPPVAA SSLRNDSSSS NRKAKNPPGD SSLHWAAMAL PALFSLIIGF AFGALYWKKR 250 260 270 QPSLTRAVEN IQINEEDNEI SMLQEKEREF QEV
	Isoform 2 (SCF220). Checksum: 937AEA64456DF4FA	FASTA	245	27,867
	10 20 30 40 50 60 MKKTQTWILT CIYLQLLLFN PLVKTEGICR NRVTNNVKDV TKLVANLPKD YMITLKYVPG 70 80 90 100 110 120 MDVLPSHCWI SEMVVQLSDS LTDLLDKFSN ISEGLSNYSI IDKLVNIVDD LVECVKENSS 130 140 150 160 170 180 KDLKKSFKSP EPRLFTPEEF FRIFNRSIDA FKDFVVASET SDCVVSSTLS PEKGKAKNPP 190 200 210 220 230 240 GDSSLHWAAM ALPALFSLII GFAFGALYWK KRQPSLTRAV ENIQINEEDN EISMLQEKER EFQEV
	Isoform 3. Checksum: 7D6B1E487BE3709B	FASTA	238	26,667
	10 20 30 40 50 60 MPSCLAAQVA NLPKDYMITL KYVPGMDVLP SHCWISEMVV QLSDSLTDLL DKFSNISEGL 70 80 90 100 110 120 SNYSIIDKLV NIVDDLVECV KENSSKDLKK SFKSPEPRLF TPEEFFRIFN RSIDAFKDFV 130 140 150 160 170 180 VASETSDCVV SSTLSPEKDS RVSVTKPFML PPVAASSLRN DSSSSNRKAK NPPGDSSLHW 190 200 210 220 230 AAMALPALFS LIIGFAFGAL YWKKRQPSLT RAVENIQINE EDNEISMLQE KEREFQEV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure and functional expression of rat and human stem cell factor DNAs." Martin F.H., Suggs S.V., Langley K.E., Lu H.S., Ting J., Okino K.H., Morris C.F., McNiece I.K., Jacobsen F.W., Mendiaz E.A., Birkett N.C., Smith K.A., Johnson M.J., Parker V.P., Flores J.C., Patel A.C., Fisher E.F., Erjavec H.O. , Herrera C.J., Wypych J., Sachdev R.K., Pope J.A., Leslie I., Wen D., Lin C.-H., Cupples R.L., Zsebo K.M. Cell 63:203-211(1990) [PubMed: 2208279] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Alternate splicing of mRNAs encoding human mast cell growth factor and localization of the gene to chromosome 12q22-q24." Anderson D.M., Williams D.E., Tushinski R., Gimpel S., Eisenman J., Cannizzaro L.A., Aronson M., Croce C.M., Huebner K., Cosman D. Cell Growth Differ. 2:373-378(1991) [PubMed: 1724381] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]	"Parathyroid hormone-regulated production of stem cell factor in human osteoblasts and osteoblast-like cells." Blair H.C., Julian B.A., Cao X., Jordan S.E., Dong S.S. Biochem. Biophys. Res. Commun. 255:778-784(1999) [PubMed: 10049787] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]	Han C., Peng X., Yuan J., Qiang B. Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Tongue and Trachea.
[6]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Amygdala.
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Brain and Colon.
[9]	"Post-translational processing of membrane-associated recombinant human stem cell factor expressed in Chinese hamster ovary cells." Lu H.S., Clogston C.L., Wypych J., Parker V.P., Lee T.D., Swiderek K., Baltera R.F. Jr., Patel A.C., Chang D.C., Brankow D.W., Liu X.-D., Ogden S.G., Karkare S.B., Hu S.S., Zsebo K.M., Langley K.E. Arch. Biochem. Biophys. 298:150-158(1992) [PubMed: 1381905] [Abstract] Cited for: PROTEIN SEQUENCE OF 26-40; 64-79; 87-102; 110-149 AND 154-190 (ISOFORM 1), DISULFIDE BONDS, GLYCOSYLATION AT ASN-90; ASN-118; ASN-145; SER-167; THR-168 AND THR-180.
[10]	"Expression of two types of kit ligand mRNAs in human tumor cells." Toyota M., Hinoda Y., Itoh F., Tsujisaki M., Imai K., Yachi A. Int. J. Hematol. 55:301-304(1992) [PubMed: 1379846] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 167-248 (ISOFORM 2).
[11]	"Genetic determinants of hair, eye and skin pigmentation in Europeans." Sulem P., Gudbjartsson D.F., Stacey S.N., Helgason A., Rafnar T., Magnusson K.P., Manolescu A., Karason A., Palsson A., Thorleifsson G., Jakobsdottir M., Steinberg S., Palsson S., Jonasson F., Sigurgeirsson B., Thorisdottir K., Ragnarsson R., Benediktsdottir K.R. , Aben K.K., Kiemeney L.A., Olafsson J.H., Gulcher J., Kong A., Thorsteinsdottir U., Stefansson K. Nat. Genet. 39:1443-1452(2007) [PubMed: 17952075] [Abstract] Cited for: INVOLVEMENT IN SHEP7.
[12]	"Structure of the active core of human stem cell factor and analysis of binding to its receptor kit." Jiang X., Gurel O., Mendiaz E.A., Stearns G.W., Clogston C.L., Lu H.S., Osslund T.D., Syed R.S., Langley K.E., Hendrickson W.A. EMBO J. 19:3192-3203(2000) [PubMed: 10880433] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS), DISULFIDE BONDS.
[13]	"Crystal structure of human stem cell factor: implication for stem cell factor receptor dimerization and activation." Zhang Z., Zhang R., Joachimiak A., Schlessinger J., Kong X.P. Proc. Natl. Acad. Sci. U.S.A. 97:7732-7737(2000) [PubMed: 10884405] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 26-166, DISULFIDE BONDS.
[14]	"Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor." Yuzawa S., Opatowsky Y., Zhang Z., Mandiyan V., Lax I., Schlessinger J. Cell 130:323-334(2007) [PubMed: 17662946] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 26-166 IN COMPLEX WITH KIT, DISULFIDE BONDS.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M59964 mRNA. Translation: AAA85450.1.
AF119835 mRNA. Translation: AAD22048.1.
AF400436 mRNA. Translation: AAK92485.1.
AF400437 mRNA. Translation: AAK92486.1.
AK290319 mRNA. Translation: BAF83008.1.
AK293002 mRNA. Translation: BAF85691.1.
CR749222 mRNA. Translation: CAH18078.1.
CH471054 Genomic DNA. Translation: EAW97417.1.
BC069733 mRNA. Translation: AAH69733.1.
BC069783 mRNA. Translation: AAH69783.1.
BC069797 mRNA. Translation: AAH69797.1.
BC074725 mRNA. Translation: AAH74725.1.
BC126166 mRNA. Translation: AAI26167.1.
BC143899 mRNA. Translation: AAI43900.1.
S42571 mRNA. Translation: AAB22846.2.

IPI

IPI00009450.
IPI00220142.
IPI00479376.

PIR

A35974.
B61190.
S29052.

RefSeq

NP_000890.1.
NP_003985.2.

UniGene

Hs.1048

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EXZ	X-ray	2.30	A/B/C/D	26-166	[»]
1SCF	X-ray	2.20	A/B/C/D	1-273	[»]
2E9W	X-ray	3.50	C/D	26-166	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P21583. 1 interaction.

STRING

P21583.

Proteomic databases

PRIDE

P21583.

Genome annotation databases

Ensembl

ENST00000228280; ENSP00000228280; ENSG00000049130; Homo sapiens. [Genome view]
ENST00000347404; ENSP00000054216; ENSG00000049130; Homo sapiens. [Genome view]

GeneID

4254.

KEGG

hsa:4254.

UCSC

uc001tav.1. human.
uc001taw.1. human.

Organism-specific databases

CTD

4254.

GeneCards

GC12M087393.

H-InvDB

HIX0026342.

HGNC

HGNC:6343. KITLG.

HPA

CAB004569.

MIM

184745. gene.
611664. phenotype.

Orphanet

79146. Hyperpigmentation progressive, familial.

PharmGKB

PA30129.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG19660.

HOVERGEN

P21583.

OrthoDB

EOG95B40W.

PhylomeDB

P21583.

Enzyme and pathway databases

Pathway_Interaction_DB

kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).

Gene expression databases

ArrayExpress

P21583.

Bgee

P21583.

CleanEx

HS_KITLG.

Genevestigator

P21583.

GermOnline

ENSG00000049130. Homo sapiens.

Family and domain databases

InterPro

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

PANTHER

PTHR11574. SCF. 1 hit.

Pfam

PF02404. SCF. 1 hit.
[Graphical view]

PIRSF

PIRSF015599. SCF. 1 hit.

ProtoNet

Search...

Other Resources

NextBio

16773.

PMAP-CutDB

P21583.

SOURCE

Search...

Entry information

Entry name

SCF_HUMAN

Accession

Primary (citable) accession number: P21583
Secondary accession number(s): A0AV09 , A8K2Q4, B7ZLM4, Q16487, Q68DZ2, Q7M4N8, Q9UQK7

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1991
Last sequence update:	May 1, 1991
Last modified:	January 19, 2010
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.