O97799 (KIT_CANFA) 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

Canis familiaris (Dog) (Canis lupus familiaris) [Reference proteome]

Taxonomic identifier

9615 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Carnivora › Caniformia › Canidae › Canis › Canis lupus

Protein attributes

Sequence length	979 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 PIK3 catalytic subunit. 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
Coding sequence diversity	Alternative splicing
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
Technical term	Complete proteome Reference proteome
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 cellular response to thyroid hormone stimulus Inferred from electronic annotation. Source: Compara 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 germ cell programmed cell death Inferred from electronic annotation. Source: Compara glycosphingolipid metabolic process Inferred from electronic annotation. Source: Compara immature B cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB inflammatory response Inferred from sequence or structural similarity. Source: UniProtKB intracellular protein kinase cascade Inferred from electronic annotation. Source: Compara lamellipodium assembly Inferred from sequence or structural similarity. Source: UniProtKB lymphoid progenitor cell differentiation Inferred from electronic annotation. Source: Compara male gonad development Inferred from electronic annotation. Source: Compara mast cell chemotaxis Inferred from electronic annotation. Source: Compara 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 myeloid progenitor cell differentiation Inferred from electronic annotation. Source: Compara negative regulation of programmed cell death Inferred from electronic annotation. Source: Compara ovarian follicle development Inferred from sequence or structural similarity. Source: UniProtKB peptidyl-tyrosine phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of gene expression Inferred from electronic annotation. Source: Compara positive regulation of sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara positive regulation of tyrosine phosphorylation of Stat1 protein Inferred from electronic annotation. Source: Compara positive regulation of tyrosine phosphorylation of Stat3 protein Inferred from electronic annotation. Source: Compara positive regulation of tyrosine phosphorylation of Stat5 protein Inferred from electronic annotation. Source: Compara protein autophosphorylation Inferred from electronic annotation. Source: Compara regulation of cell shape Inferred from sequence or structural similarity. Source: UniProtKB regulation of developmental pigmentation Inferred from electronic annotation. Source: Compara response to radiation Inferred from electronic annotation. Source: Compara signal transduction by phosphorylation Inferred from electronic annotation. Source: GOC spermatid development Inferred from electronic annotation. Source: Compara spermatogenesis Inferred from sequence or structural similarity. Source: UniProtKB stem cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: Compara external side of plasma membrane Inferred from electronic annotation. Source: Compara extracellular space Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from electronic annotation. Source: Compara
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 stem cell factor receptor activity Inferred from electronic annotation. Source: Compara transmembrane receptor protein tyrosine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: O97799-1)

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: O97799-2)

The sequence of this isoform differs from the canonical sequence as follows:
     512-515: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27	Potential
	Chain	28 – 979	952	Mast/stem cell growth factor receptor Kit		PRO_0000016751
Regions
	Topological domain	28 – 527	500	Extracellular Potential
	Transmembrane	528 – 548	21	Helical; Potential
	Topological domain	549 – 979	431	Cytoplasmic Potential
	Domain	29 – 114	86	Ig-like C2-type 1
	Domain	123 – 207	85	Ig-like C2-type 2
	Domain	214 – 311	98	Ig-like C2-type 3
	Domain	320 – 413	94	Ig-like C2-type 4
	Domain	416 – 510	95	Ig-like C2-type 5
	Domain	592 – 940	349	Protein kinase
	Nucleotide binding	599 – 606	8	ATP By similarity
	Nucleotide binding	674 – 680	7	ATP By similarity
	Region	571 – 573	3	Important for interaction with phosphotyrosine-binding proteins By similarity
Sites
	Active site	795	1	Proton acceptor By similarity
	Metal binding	571	1	Magnesium By similarity
	Metal binding	800	1	Magnesium By similarity
	Metal binding	813	1	Magnesium By similarity
	Binding site	626	1	ATP By similarity
	Binding site	799	1	ATP By similarity
	Site	571	1	Interaction with SH2B2/APS By similarity
	Site	939	1	Important for interaction with phosphotyrosine-binding proteins By similarity
	Site	939	1	Interaction with SH2B2/APS By similarity
Amino acid modifications
	Modified residue	550	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	556	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	571	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	573	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	706	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	724	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	733	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	744	1	Phosphoserine; by PKC/PRKCA By similarity
	Modified residue	749	1	Phosphoserine; by PKC/PRKCA By similarity
	Modified residue	824	1	Phosphoserine By similarity
	Modified residue	826	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	894	1	Phosphoserine By similarity
	Modified residue	903	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	939	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	962	1	Phosphoserine By similarity
	Glycosylation	96	1	N-linked (GlcNAc...) Potential
	Glycosylation	132	1	N-linked (GlcNAc...) Potential
	Glycosylation	147	1	N-linked (GlcNAc...) Potential
	Glycosylation	286	1	N-linked (GlcNAc...) Potential
	Glycosylation	296	1	N-linked (GlcNAc...) Potential
	Glycosylation	303	1	N-linked (GlcNAc...) Potential
	Glycosylation	355	1	N-linked (GlcNAc...) Potential
	Glycosylation	370	1	N-linked (GlcNAc...) Potential
	Glycosylation	403	1	N-linked (GlcNAc...) Potential
	Glycosylation	466	1	N-linked (GlcNAc...) Potential
	Glycosylation	489	1	N-linked (GlcNAc...) Potential
	Disulfide bond	60 ↔ 99		By similarity
	Disulfide bond	138 ↔ 188		By similarity
	Disulfide bond	153 ↔ 185		By similarity
	Disulfide bond	235 ↔ 293		By similarity
	Disulfide bond	431 ↔ 494		By similarity
Natural variations
	Alternative sequence	512 – 515	4	Missing in isoform 2.		VSP_020224
Experimental info
	Sequence conflict	23	1	Q → R in AAD02327. Ref.1
	Sequence conflict	332	1	E → Q in AAD02327. Ref.1
	Sequence conflict	442	1	D → G in AAD02327. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 5, 2006. Version 2. Checksum: 46C30D5DEB8E33D3	FASTA	979	109,753
	10 20 30 40 50 60 MRGARGAWDF LCVLLLLLLL GVQTGSSQPS VSPGEPSLPS IHPAKSELIV SVGDELRLSC 70 80 90 100 110 120 TDPGFVKWTF ETLGQLNENT HNEWITEKAE AGHTGNYTCT NRDGLSRSIY VFVRDPAKLF 130 140 150 160 170 180 LVDLPLYGKE GNDTLVRCPL TDPEVTNYSL RGCEGKPLPK DLTFVADPKA GITIRNVKRE 190 200 210 220 230 240 YHRLCLHCSA DQKGRTVLSK KFTLKVRAAI RAVPVVSVSK TSSLLKEGEA FSVMCFIKDV 250 260 270 280 290 300 SSFVDSMWIK ENSQQTNAQT QSNSWHHGDF NFERQEKLII SSARVNDSGV FMCYANNTFG 310 320 330 340 350 360 SANVTTTLEV VDKGFINIFP MMSTTIFVND GENVDLIVEY EAYPKPEHQQ WIYMNRTFTD 370 380 390 400 410 420 KWEDYPKSDN ESNIRYVSEL HLTRLKGNEG GTYTFQVSNS DVNSSVTFNV YVNTKPEILT 430 440 450 460 470 480 HESLTNGMLQ CVVAGFPEPA VDWYFCPGAE QRCSVPIGPM DVQMQNSSLS PSGKLVVQSS 490 500 510 520 530 540 IDYSAFKHNG TVECRAYNNV GRSSAFFNFA FKGNSKEQIH PHTLFTPLLI GFVIAAGMMC 550 560 570 580 590 600 IIVMILTYKY LQKPMYEVQW KVVEEINGNN YVYIDPTQLP YDHKWEFPRN RLSFGKTLGA 610 620 630 640 650 660 GAFGKVVEAT AYGLIKSDAA MTVAVKMLKP SAHLTEREAL MSELKVLSYL GNHMNIVNLL 670 680 690 700 710 720 GACTVGGPTL VITEYCCYGD LLNFLRRKRD SFICSKQEDH GEVALYKNLL HSKESSCSDS 730 740 750 760 770 780 TNEYMDMKPG VSYVVPTKAD KRRSARIGSY IERDVTPAIM EDDELALDLE DLLSFSYQVA 790 800 810 820 830 840 KGMAFLASKN CIHRDLAARN ILLTHGRITK ICDFGLARDI KNDSNYVVKG NARLPVKWMA 850 860 870 880 890 900 PESIFNCVYT FESDVWSYGI FLWELFSLGS SPYPGMPVDS KFYKMIKEGF RMLSPEHAPA 910 920 930 940 950 960 EMYDIMKTCW DADPLKRPTF KQIVQLIEKQ ISDSTNHIYS NLANCSPNPE RPVVDHSVRI 970 NSVGSSASST QPLLVHEDV
	Isoform 2 [UniParc]. Checksum: D845FADB06231FD9	FASTA	975	109,367
	10 20 30 40 50 60 MRGARGAWDF LCVLLLLLLL GVQTGSSQPS VSPGEPSLPS IHPAKSELIV SVGDELRLSC 70 80 90 100 110 120 TDPGFVKWTF ETLGQLNENT HNEWITEKAE AGHTGNYTCT NRDGLSRSIY VFVRDPAKLF 130 140 150 160 170 180 LVDLPLYGKE GNDTLVRCPL TDPEVTNYSL RGCEGKPLPK DLTFVADPKA GITIRNVKRE 190 200 210 220 230 240 YHRLCLHCSA DQKGRTVLSK KFTLKVRAAI RAVPVVSVSK TSSLLKEGEA FSVMCFIKDV 250 260 270 280 290 300 SSFVDSMWIK ENSQQTNAQT QSNSWHHGDF NFERQEKLII SSARVNDSGV FMCYANNTFG 310 320 330 340 350 360 SANVTTTLEV VDKGFINIFP MMSTTIFVND GENVDLIVEY EAYPKPEHQQ WIYMNRTFTD 370 380 390 400 410 420 KWEDYPKSDN ESNIRYVSEL HLTRLKGNEG GTYTFQVSNS DVNSSVTFNV YVNTKPEILT 430 440 450 460 470 480 HESLTNGMLQ CVVAGFPEPA VDWYFCPGAE QRCSVPIGPM DVQMQNSSLS PSGKLVVQSS 490 500 510 520 530 540 IDYSAFKHNG TVECRAYNNV GRSSAFFNFA FKEQIHPHTL FTPLLIGFVI AAGMMCIIVM 550 560 570 580 590 600 ILTYKYLQKP MYEVQWKVVE EINGNNYVYI DPTQLPYDHK WEFPRNRLSF GKTLGAGAFG 610 620 630 640 650 660 KVVEATAYGL IKSDAAMTVA VKMLKPSAHL TEREALMSEL KVLSYLGNHM NIVNLLGACT 670 680 690 700 710 720 VGGPTLVITE YCCYGDLLNF LRRKRDSFIC SKQEDHGEVA LYKNLLHSKE SSCSDSTNEY 730 740 750 760 770 780 MDMKPGVSYV VPTKADKRRS ARIGSYIERD VTPAIMEDDE LALDLEDLLS FSYQVAKGMA 790 800 810 820 830 840 FLASKNCIHR DLAARNILLT HGRITKICDF GLARDIKNDS NYVVKGNARL PVKWMAPESI 850 860 870 880 890 900 FNCVYTFESD VWSYGIFLWE LFSLGSSPYP GMPVDSKFYK MIKEGFRMLS PEHAPAEMYD 910 920 930 940 950 960 IMKTCWDADP LKRPTFKQIV QLIEKQISDS TNHIYSNLAN CSPNPERPVV DHSVRINSVG 970 SSASSTQPLL VHEDV

References

[1]	"Clustering of activating mutations in c-KIT's juxtamembrane coding region in canine mast cell neoplasms." Ma Y., Longley B.J., Wang X., Blount J.L., Langley K., Caughey G.H. J. Invest. Dermatol. 112:165-170(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]	Zemke D., Yuzbasiyan-Gurkan V. Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Characterization of an isoform and RH mapping of canine c-kit." Tsai K.L., Guyon R., Murphy K.E. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF044249 mRNA. Translation: AAD02327.1. AF448148 mRNA. Translation: AAL40833.1. AY296484 mRNA. Translation: AAP51178.1. AY313776 mRNA. Translation: AAP76390.1.
RefSeq	NP_001003181.1. NM_001003181.1.
UniGene	Cfa.184.
3D structure databases
ProteinModelPortal	O97799.
SMR	O97799. Positions 35-510, 550-930.
ModBase	Search...
Protein family/group databases
MEROPS	I43.001.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSCAFT00000049830; ENSCAFP00000039467; ENSCAFG00000002065.
GeneID	403811.
KEGG	cfa:403811.
Organism-specific databases
CTD	3815.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00660000095142.
HOGENOM	HOG000112008.
HOVERGEN	HBG004335.
InParanoid	O97799.
KO	K05091.
OMA	DSGVFMC.
OrthoDB	EOG4W0XCD.
Enzyme and pathway databases
BRENDA	2.7.10.1. 1154.
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...
Other
NextBio	20817307.

Entry information

Entry name

KIT_CANFA

Accession

Primary (citable) accession number: O97799
Secondary accession number(s): Q7YRV7, Q8WN23

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	September 5, 2006
Last modified:	May 1, 2013
This is version 117 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program