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O97799 (KIT_CANFA) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismCanis familiaris (Dog) (Canis lupus familiaris) [Reference proteome]
Taxonomic identifier9615 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis

Protein attributes

Sequence length979 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
   DiseaseProto-oncogene
   DomainImmunoglobulin domain
Repeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processFc 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: Ensembl

cytokine-mediated signaling pathway

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

ectopic germ cell programmed cell death

Inferred from electronic annotation. Source: Ensembl

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

glycosphingolipid metabolic process

Inferred from electronic annotation. Source: Ensembl

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

lymphoid progenitor cell differentiation

Inferred from electronic annotation. Source: Ensembl

male gonad development

Inferred from electronic annotation. Source: Ensembl

mast cell chemotaxis

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

negative regulation of programmed cell death

Inferred from electronic annotation. Source: Ensembl

ovarian follicle development

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

pigmentation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of tyrosine phosphorylation of Stat1 protein

Inferred from electronic annotation. Source: Ensembl

positive regulation of tyrosine phosphorylation of Stat3 protein

Inferred from electronic annotation. Source: Ensembl

positive regulation of tyrosine phosphorylation of Stat5 protein

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Inferred from electronic annotation. Source: Ensembl

regulation of cell shape

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of developmental pigmentation

Inferred from electronic annotation. Source: Ensembl

response to radiation

Inferred from electronic annotation. Source: Ensembl

spermatid development

Inferred from electronic annotation. Source: Ensembl

spermatogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

stem cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentexternal side of plasma membrane

Inferred from electronic annotation. Source: Ensembl

extracellular space

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

mast cell granule

Inferred from sequence or structural similarity. Source: GOC

nucleus

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP 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: Ensembl

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2727 Potential
Chain28 – 979952Mast/stem cell growth factor receptor Kit
PRO_0000016751

Regions

Topological domain28 – 527500Extracellular Potential
Transmembrane528 – 54821Helical; Potential
Topological domain549 – 979431Cytoplasmic Potential
Domain29 – 11486Ig-like C2-type 1
Domain123 – 20785Ig-like C2-type 2
Domain214 – 31198Ig-like C2-type 3
Domain320 – 41394Ig-like C2-type 4
Domain416 – 51095Ig-like C2-type 5
Domain592 – 940349Protein kinase
Nucleotide binding599 – 6068ATP By similarity
Nucleotide binding674 – 6807ATP By similarity
Region571 – 5733Important for interaction with phosphotyrosine-binding proteins By similarity

Sites

Active site7951Proton acceptor By similarity
Metal binding5711Magnesium By similarity
Metal binding8001Magnesium By similarity
Metal binding8131Magnesium By similarity
Binding site6261ATP By similarity
Binding site7991ATP By similarity
Site5711Interaction with SH2B2/APS By similarity
Site9391Important for interaction with phosphotyrosine-binding proteins By similarity
Site9391Interaction with SH2B2/APS By similarity

Amino acid modifications

Modified residue5501Phosphotyrosine; by autocatalysis By similarity
Modified residue5561Phosphotyrosine; by autocatalysis By similarity
Modified residue5711Phosphotyrosine; by autocatalysis By similarity
Modified residue5731Phosphotyrosine; by autocatalysis By similarity
Modified residue7061Phosphotyrosine; by autocatalysis By similarity
Modified residue7241Phosphotyrosine; by autocatalysis By similarity
Modified residue7331Phosphotyrosine; by autocatalysis By similarity
Modified residue7441Phosphoserine; by PKC/PRKCA By similarity
Modified residue7491Phosphoserine; by PKC/PRKCA By similarity
Modified residue8241Phosphoserine By similarity
Modified residue8261Phosphotyrosine; by autocatalysis By similarity
Modified residue8941Phosphoserine By similarity
Modified residue9031Phosphotyrosine; by autocatalysis By similarity
Modified residue9391Phosphotyrosine; by autocatalysis By similarity
Modified residue9621Phosphoserine By similarity
Glycosylation961N-linked (GlcNAc...) Potential
Glycosylation1321N-linked (GlcNAc...) Potential
Glycosylation1471N-linked (GlcNAc...) Potential
Glycosylation2861N-linked (GlcNAc...) Potential
Glycosylation2961N-linked (GlcNAc...) Potential
Glycosylation3031N-linked (GlcNAc...) Potential
Glycosylation3551N-linked (GlcNAc...) Potential
Glycosylation3701N-linked (GlcNAc...) Potential
Glycosylation4031N-linked (GlcNAc...) Potential
Glycosylation4661N-linked (GlcNAc...) Potential
Glycosylation4891N-linked (GlcNAc...) Potential
Disulfide bond60 ↔ 99 By similarity
Disulfide bond138 ↔ 188 By similarity
Disulfide bond153 ↔ 185 By similarity
Disulfide bond235 ↔ 293 By similarity
Disulfide bond431 ↔ 494 By similarity

Natural variations

Alternative sequence512 – 5154Missing in isoform 2.
VSP_020224

Experimental info

Sequence conflict231Q → R in AAD02327. Ref.1
Sequence conflict3321E → Q in AAD02327. Ref.1
Sequence conflict4421D → G in AAD02327. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified September 5, 2006. Version 2.
Checksum: 46C30D5DEB8E33D3

FASTA979109,753
        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 

« Hide

Isoform 2 [UniParc].

Checksum: D845FADB06231FD9
Show »

FASTA975109,367

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.
RefSeqNP_001003181.1. NM_001003181.1.
XP_005628025.1. XM_005627968.1.
UniGeneCfa.184.

3D structure databases

ProteinModelPortalO97799.
SMRO97799. Positions 35-510, 550-930.
ModBaseSearch...
MobiDBSearch...

Protein family/group databases

MEROPSI43.001.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSCAFT00000049830; ENSCAFP00000039467; ENSCAFG00000002065. [O97799-2]
GeneID403811.
KEGGcfa:403811.

Organism-specific databases

CTD3815.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00720000108490.
HOGENOMHOG000112008.
HOVERGENHBG004335.
InParanoidO97799.
KOK05091.
OMAYFCPGTE.
OrthoDBEOG7S7SCZ.
TreeFamTF325768.

Enzyme and pathway databases

BRENDA2.7.10.1. 1154.

Family and domain databases

Gene3D2.60.40.10. 5 hits.
InterProIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_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]
PfamPF07679. I-set. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFPIRSF500951. SCGF_recepter. 1 hit.
PIRSF000615. TyrPK_CSF1-R. 1 hit.
SMARTSM00409. IG. 3 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 2 hits.
PROSITEPS50835. 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]
ProtoNetSearch...

Other

NextBio20817307.

Entry information

Entry nameKIT_CANFA
AccessionPrimary (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: April 16, 2014
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families