Q28317 (KIT_CAPHI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mast/stem cell growth factor receptor Kit
Short name=SCFR
EC=2.7.10.1

Alternative name(s):
Proto-oncogene c-Kit
Tyrosine-protein kinase Kit
CD_antigen=CD117

Gene names

Name:

KIT

Organism

Capra hircus (Goat)

Taxonomic identifier

9925 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Caprinae › Capra

Protein attributes

Sequence length	978 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and 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. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1 By similarity.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Enzyme regulation	Present in an inactive conformation in the absence of bound ligand. KITLG/SCF binding leads to dimerization and activation by autophosphorylation on tyrosine residues. Activity is down-regulated by PRKCA-mediated phosphorylation on serine residues By similarity.
Subunit structure	Monomer in the absence of bound KITLG/SCF. Homodimer in the presence of bound KITLG/SCF, forming a heterotetramer with two KITLG/SCF molecules. Interacts (via phosphorylated tyrosine residues) with the adapter proteins GRB2 and GRB7 (via SH2 domain), and SH2B2/APS. Interacts (via C-terminus) with MPDZ (via the tenth PDZ domain). Interacts (via phosphorylated tyrosine residues) with PIK3R1 and PIK3CD. Interacts (via phosphorylated tyrosine) with CRK (isoform Crk-II), FYN, SHC1 and MATK/CHK (via SH2 domain). Interacts with LYN and FES/FPS. Interacts (via phosphorylated tyrosine residues) with the protein phosphatases PTPN6/SHP-1 (via SH2 domain), PTPN11/SHP-2 (via SH2 domain) and PTPRU. Interacts with PLCG1. Interacts with DOK1 and TEC By similarity.
Subcellular location	Cell membrane; Single-pass type I membrane protein.
Post-translational modification	Ubiquitinated by SOCS6 By similarity. KIT is rapidly ubiquitinated after autophosphorylation induced by KITLG/SCF binding, leading to internalization and degradation By similarity. Autophosphorylated on tyrosine residues. KITLG/SCF binding promotes autophosphorylation. Phosphorylated tyrosine residues are important for interaction with specific binding partners By similarity.
Miscellaneous	Numerous proteins are phosphorylated in response to KIT signaling, but it is not evident to determine which are directly phosphorylated by KIT under in vivo conditions By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily. Contains 5 Ig-like C2-type (immunoglobulin-like) domains. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Disease	Proto-oncogene
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological_process	Fc receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB Kit signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB T cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB actin cytoskeleton reorganization Inferred from sequence or structural similarity. Source: UniProtKB activation of MAPK activity Inferred from sequence or structural similarity. Source: UniProtKB cell chemotaxis Inferred from sequence or structural similarity. Source: UniProtKB dendritic cell cytokine production Inferred from sequence or structural similarity. Source: UniProtKB detection of mechanical stimulus involved in sensory perception of sound Inferred from sequence or structural similarity. Source: UniProtKB digestive tract development Inferred from sequence or structural similarity. Source: UniProtKB embryonic hemopoiesis Inferred from sequence or structural similarity. Source: UniProtKB erythrocyte differentiation Inferred from sequence or structural similarity. Source: UniProtKB erythropoietin-mediated signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB immature B cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB inflammatory response Inferred from sequence or structural similarity. Source: UniProtKB lamellipodium assembly Inferred from sequence or structural similarity. Source: UniProtKB mast cell cytokine production Inferred from sequence or structural similarity. Source: UniProtKB mast cell degranulation Inferred from sequence or structural similarity. Source: UniProtKB mast cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB megakaryocyte development Inferred from sequence or structural similarity. Source: UniProtKB melanocyte adhesion Inferred from sequence or structural similarity. Source: UniProtKB melanocyte differentiation Inferred from sequence or structural similarity. Source: UniProtKB melanocyte migration Inferred from sequence or structural similarity. Source: UniProtKB ovarian follicle development Inferred from sequence or structural similarity. Source: UniProtKB peptidyl-tyrosine phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of cell shape Inferred from sequence or structural similarity. Source: UniProtKB signal transduction by phosphorylation Inferred from electronic annotation. Source: GOC spermatogenesis Inferred from sequence or structural similarity. Source: UniProtKB stem cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW cytokine binding Inferred from sequence or structural similarity. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW receptor signaling protein tyrosine kinase activity Inferred from electronic annotation. Source: InterPro transmembrane receptor protein tyrosine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25	Potential
	Chain	26 – 978	953	Mast/stem cell growth factor receptor Kit		PRO_0000016752
Regions
	Topological domain	26 – 525	500	Extracellular Potential
	Transmembrane	526 – 546	21	Helical; Potential
	Topological domain	547 – 978	432	Cytoplasmic Potential
	Domain	27 – 112	86	Ig-like C2-type 1
	Domain	121 – 205	85	Ig-like C2-type 2
	Domain	212 – 309	98	Ig-like C2-type 3
	Domain	318 – 411	94	Ig-like C2-type 4
	Domain	414 – 508	95	Ig-like C2-type 5
	Domain	590 – 939	350	Protein kinase
	Nucleotide binding	597 – 604	8	ATP By similarity
	Nucleotide binding	672 – 678	7	ATP By similarity
	Region	569 – 571	3	Important for interaction with phosphotyrosine-binding proteins By similarity
Sites
	Active site	794	1	Proton acceptor By similarity
	Metal binding	569	1	Magnesium By similarity
	Metal binding	799	1	Magnesium By similarity
	Metal binding	812	1	Magnesium By similarity
	Binding site	624	1	ATP By similarity
	Binding site	798	1	ATP By similarity
	Site	569	1	Interaction with SH2B2/APS By similarity
	Site	938	1	Important for interaction with phosphotyrosine-binding proteins By similarity
	Site	938	1	Interaction with SH2B2/APS By similarity
Amino acid modifications
	Modified residue	569	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	571	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	704	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	722	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	743	1	Phosphoserine; by PKC/PRKCA By similarity
	Modified residue	748	1	Phosphoserine; by PKC/PRKCA By similarity
	Modified residue	823	1	Phosphoserine By similarity
	Modified residue	825	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	893	1	Phosphoserine By similarity
	Modified residue	902	1	Phosphotyrosine By similarity
	Modified residue	938	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	961	1	Phosphoserine By similarity
	Glycosylation	94	1	N-linked (GlcNAc...) Potential
	Glycosylation	130	1	N-linked (GlcNAc...) Potential
	Glycosylation	145	1	N-linked (GlcNAc...) Potential
	Glycosylation	284	1	N-linked (GlcNAc...) Potential
	Glycosylation	294	1	N-linked (GlcNAc...) Potential
	Glycosylation	301	1	N-linked (GlcNAc...) Potential
	Glycosylation	321	1	N-linked (GlcNAc...) Potential
	Glycosylation	353	1	N-linked (GlcNAc...) Potential
	Glycosylation	368	1	N-linked (GlcNAc...) Potential
	Glycosylation	401	1	N-linked (GlcNAc...) Potential
	Glycosylation	464	1	N-linked (GlcNAc...) Potential
	Glycosylation	487	1	N-linked (GlcNAc...) Potential
	Disulfide bond	58 ↔ 97		By similarity
	Disulfide bond	136 ↔ 186		By similarity
	Disulfide bond	151 ↔ 183		By similarity
	Disulfide bond	233 ↔ 291		By similarity
	Disulfide bond	429 ↔ 492		By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q28317 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: CA4D663F98205CA9	FASTA	978	109,722
	10 20 30 40 50 60 MRGARGAWDF LFVLLLLLLV QTGSSQPSVS PGELSLPSIH PAKSELIVSV GDEIRLLCTD 70 80 90 100 110 120 PGFVKWTFEI LGQLSEKTNP EWITEKAEAT NTGNYTCTNK GGLSSSIYVF VRDPEKLFLI 130 140 150 160 170 180 DLPLYGKEEN DTLVRCPLTD PEVTNYSLTG CEGKPLPKDL TFVADPKAGI TIRNVKREYH 190 200 210 220 230 240 RLCLHCSANQ KGKSMLSKKF TLKVRAAIKA VPVVSVSKTS YLLREGEEFA VTCLIKDVSS 250 260 270 280 290 300 SVDSMWIKEN SQQSKAQTKK NSWHQGDFSY LRQERLTISS ARVNDSGVFM CYANNTFGSA 310 320 330 340 350 360 NVTTTLEVVD KGFINIFPMM NTTVFVNDGE NVDLVVEYEA YPKPEHRQWI YMNRTSTDKW 370 380 390 400 410 420 DDYPKSENES NIRYVNELHL TRLKGTEGGT YTFHVSNSDV NSSVTFNVNV NTKPEILTHD 430 440 450 460 470 480 RLVNGMLQCV AAGFPEPTID WYFCPGTEQR CSVPVGPVDV QIQNSSVSPF GKLVVYSTID 490 500 510 520 530 540 DSTFKHNGTV ECRAYNDVGK SSASFNFAFK GNNKEQIHAH TLFTPLLIGF VIAAGLMCIF 550 560 570 580 590 600 VMILTYKYLQ KPMYEVQWKV VEEINGNNYV YIDPTQLPYD HKWEFPRNRL SFGKTLGAGA 610 620 630 640 650 660 FGKVVEATAY GLIKSDAAMT VAVKMLKPSA HLTEREALMS ELKVLSYLGN HMNIVNLLGA 670 680 690 700 710 720 CTIGGPTLVI TEYCCYGDLL NFLRRKRDSF ICSKQEDHAE VALYKNLLHS KESSCNDSTN 730 740 750 760 770 780 EYMDMKPGVS YVVPTKAADK RRSARIGSYI ERDVTPAIME DDELALDLED LLSFSYQVAK 790 800 810 820 830 840 GMAFLASKNC IHRDLAARNI LLTHGRITKI CDFGLARDIK NDSNYVVKGN ARLPVKWMAP 850 860 870 880 890 900 ESIFNCVYTF ESDVWSYGIF LWELFSLGSS PYPGMPVDSK FYKMIKEGFR MLSPEHAPAE 910 920 930 940 950 960 MYDIMKTCWD ADPLKRPTFK QIVQLIEKQI SESTNHIYSN LANCSPHREN PAVDHSVRIN 970 SVGSSASSTQ PLLVHEDV

References

[1]

"Molecular cloning of cDNA encoding the c-kit receptor of Shiba goats and a novel alanine insertion specific to goats and sheep in the kinase insert region." Tanaka S., Yanagisawa N., Tojo H., Kim Y.-J., Tsujimura T., Kitamura Y., Sawasaki T., Tachi C. Biochim. Biophys. Acta 1352:151-155(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Shiba. Tissue: Cerebellum.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D45168 mRNA. Translation: BAA08116.1.
UniGene	Chi.23505.
3D structure databases
ProteinModelPortal	Q28317.
SMR	Q28317. Positions 33-508, 548-929.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Phylogenomic databases
HOVERGEN	HBG004335.
Enzyme and pathway databases
BRENDA	2.7.10.1. 1166.
Family and domain databases
Gene3D	2.60.40.10. 5 hits.
InterPro	IPR007110. Ig-like_dom. IPR013783. Ig-like_fold. IPR013098. Ig_I-set. IPR003599. Ig_sub. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR027263. SCGF_receptor. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. IPR008266. Tyr_kinase_AS. IPR020635. Tyr_kinase_cat_dom. IPR016243. Tyr_kinase_CSF1/PDGF_rcpt. IPR001824. Tyr_kinase_rcpt_3_CS. [Graphical view]
Pfam	PF07679. I-set. 1 hit. PF07714. Pkinase_Tyr. 1 hit. [Graphical view]
PIRSF	PIRSF500951. SCGF_recepter. 1 hit. PIRSF000615. TyrPK_CSF1-R. 1 hit.
SMART	SM00409. IG. 3 hits. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS50835. IG_LIKE. 2 hits. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. 1 hit. PS00240. RECEPTOR_TYR_KIN_III. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

KIT_CAPHI

Accession

Primary (citable) accession number: Q28317

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 109 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program