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Protein

Mast/stem cell growth factor receptor Kit

Gene

KIT

Organism
Canis lupus familiaris (Dog) (Canis familiaris)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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).By similarity

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Enzyme regulationi

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).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi571MagnesiumBy similarity1
Binding sitei626ATPPROSITE-ProRule annotation1
Active sitei795Proton acceptorPROSITE-ProRule annotation1
Binding sitei799ATPPROSITE-ProRule annotation1
Metal bindingi800MagnesiumBy similarity1
Metal bindingi813MagnesiumBy similarity1
Sitei939Important for interaction with phosphotyrosine-binding proteinsBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi599 – 606ATPPROSITE-ProRule annotation8
Nucleotide bindingi674 – 680ATPPROSITE-ProRule annotation7

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 1153.
ReactomeiR-CFA-1257604. PIP3 activates AKT signaling.
R-CFA-1433557. Signaling by SCF-KIT.
R-CFA-1433559. Regulation of KIT signaling.
R-CFA-5673001. RAF/MAP kinase cascade.
R-CFA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Mast/stem cell growth factor receptor Kit (EC:2.7.10.1)
Short name:
SCFR
Alternative name(s):
Proto-oncogene c-Kit
Tyrosine-protein kinase Kit
CD_antigen: CD117
Gene namesi
Name:KIT
OrganismiCanis lupus familiaris (Dog) (Canis familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
Proteomesi
  • UP000002254 Componenti: Chromosome 13

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini28 – 527ExtracellularSequence analysisAdd BLAST500
Transmembranei528 – 548HelicalSequence analysisAdd BLAST21
Topological domaini549 – 979CytoplasmicSequence analysisAdd BLAST431

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
ChainiPRO_000001675128 – 979Mast/stem cell growth factor receptor KitAdd BLAST952

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi60 ↔ 99PROSITE-ProRule annotation
Glycosylationi96N-linked (GlcNAc...)Sequence analysis1
Glycosylationi132N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi138 ↔ 188PROSITE-ProRule annotation
Glycosylationi147N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi153 ↔ 185PROSITE-ProRule annotation
Disulfide bondi235 ↔ 293PROSITE-ProRule annotation
Glycosylationi286N-linked (GlcNAc...)Sequence analysis1
Glycosylationi296N-linked (GlcNAc...)Sequence analysis1
Glycosylationi303N-linked (GlcNAc...)Sequence analysis1
Glycosylationi355N-linked (GlcNAc...)Sequence analysis1
Glycosylationi370N-linked (GlcNAc...)Sequence analysis1
Glycosylationi403N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi431 ↔ 494PROSITE-ProRule annotation
Glycosylationi466N-linked (GlcNAc...)Sequence analysis1
Glycosylationi489N-linked (GlcNAc...)Sequence analysis1
Modified residuei550Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei556Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei571Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei573Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei706Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei724Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei733Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei744Phosphoserine; by PKC/PRKCABy similarity1
Modified residuei749Phosphoserine; by PKC/PRKCABy similarity1
Modified residuei824PhosphoserineBy similarity1
Modified residuei826Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei894PhosphoserineBy similarity1
Modified residuei903Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei939Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei962PhosphoserineBy similarity1

Post-translational modificationi

Ubiquitinated by SOCS6. 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).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiO97799.

Interactioni

Subunit structurei

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. Interacts with IL1RAP (independent of stimulation with KITLG/SCF). A mast cell-specific KITLG/SCF-induced interleukin-33 signaling complex contains IL1RL1, IL1RAP, KIT and MYD88 (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei571Interaction with SH2B2/APSBy similarity1
Sitei939Interaction with SH2B2/APSBy similarity1

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000039467.

Structurei

3D structure databases

ProteinModelPortaliO97799.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini29 – 114Ig-like C2-type 1Add BLAST86
Domaini123 – 207Ig-like C2-type 2Add BLAST85
Domaini214 – 311Ig-like C2-type 3Add BLAST98
Domaini320 – 413Ig-like C2-type 4Add BLAST94
Domaini416 – 510Ig-like C2-type 5Add BLAST95
Domaini592 – 940Protein kinasePROSITE-ProRule annotationAdd BLAST349

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni571 – 573Important for interaction with phosphotyrosine-binding proteinsBy similarity3

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118923.
HOGENOMiHOG000112008.
HOVERGENiHBG004335.
InParanoidiO97799.
KOiK05091.
OMAiYFCPGTE.
OrthoDBiEOG091G01TL.
TreeFamiTF325768.

Family and domain databases

Gene3Di2.60.40.10. 5 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013151. Immunoglobulin.
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]
PfamiPF00047. ig. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF500951. SCGF_recepter. 1 hit.
PIRSF000615. TyrPK_CSF1-R. 1 hit.
SMARTiSM00409. IG. 4 hits.
SM00408. IGc2. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 3 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50835. 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]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O97799-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MRGARGAWDF LCVLLLLLLL GVQTGSSQPS VSPGEPSLPS IHPAKSELIV
60 70 80 90 100
SVGDELRLSC TDPGFVKWTF ETLGQLNENT HNEWITEKAE AGHTGNYTCT
110 120 130 140 150
NRDGLSRSIY VFVRDPAKLF LVDLPLYGKE GNDTLVRCPL TDPEVTNYSL
160 170 180 190 200
RGCEGKPLPK DLTFVADPKA GITIRNVKRE YHRLCLHCSA DQKGRTVLSK
210 220 230 240 250
KFTLKVRAAI RAVPVVSVSK TSSLLKEGEA FSVMCFIKDV SSFVDSMWIK
260 270 280 290 300
ENSQQTNAQT QSNSWHHGDF NFERQEKLII SSARVNDSGV FMCYANNTFG
310 320 330 340 350
SANVTTTLEV VDKGFINIFP MMSTTIFVND GENVDLIVEY EAYPKPEHQQ
360 370 380 390 400
WIYMNRTFTD KWEDYPKSDN ESNIRYVSEL HLTRLKGNEG GTYTFQVSNS
410 420 430 440 450
DVNSSVTFNV YVNTKPEILT HESLTNGMLQ CVVAGFPEPA VDWYFCPGAE
460 470 480 490 500
QRCSVPIGPM DVQMQNSSLS PSGKLVVQSS IDYSAFKHNG TVECRAYNNV
510 520 530 540 550
GRSSAFFNFA FKGNSKEQIH PHTLFTPLLI GFVIAAGMMC IIVMILTYKY
560 570 580 590 600
LQKPMYEVQW KVVEEINGNN YVYIDPTQLP YDHKWEFPRN RLSFGKTLGA
610 620 630 640 650
GAFGKVVEAT AYGLIKSDAA MTVAVKMLKP SAHLTEREAL MSELKVLSYL
660 670 680 690 700
GNHMNIVNLL GACTVGGPTL VITEYCCYGD LLNFLRRKRD SFICSKQEDH
710 720 730 740 750
GEVALYKNLL HSKESSCSDS TNEYMDMKPG VSYVVPTKAD KRRSARIGSY
760 770 780 790 800
IERDVTPAIM EDDELALDLE DLLSFSYQVA KGMAFLASKN CIHRDLAARN
810 820 830 840 850
ILLTHGRITK ICDFGLARDI KNDSNYVVKG NARLPVKWMA PESIFNCVYT
860 870 880 890 900
FESDVWSYGI FLWELFSLGS SPYPGMPVDS KFYKMIKEGF RMLSPEHAPA
910 920 930 940 950
EMYDIMKTCW DADPLKRPTF KQIVQLIEKQ ISDSTNHIYS NLANCSPNPE
960 970
RPVVDHSVRI NSVGSSASST QPLLVHEDV
Length:979
Mass (Da):109,753
Last modified:September 5, 2006 - v2
Checksum:i46C30D5DEB8E33D3
GO
Isoform 2 (identifier: O97799-2) [UniParc]FASTAAdd to basket

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

Show »
Length:975
Mass (Da):109,367
Checksum:iD845FADB06231FD9
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti23Q → R in AAD02327 (PubMed:9989791).Curated1
Sequence conflicti332E → Q in AAD02327 (PubMed:9989791).Curated1
Sequence conflicti442D → G in AAD02327 (PubMed:9989791).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_020224512 – 515Missing in isoform 2. 2 Publications4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF044249 mRNA. Translation: AAD02327.1.
AF448148 mRNA. Translation: AAL40833.1.
AY296484 mRNA. Translation: AAP51178.1.
AY313776 mRNA. Translation: AAP76390.1.
RefSeqiNP_001003181.1. NM_001003181.1.
XP_005628025.1. XM_005627968.2. [O97799-1]
UniGeneiCfa.184.

Genome annotation databases

EnsembliENSCAFT00000049830; ENSCAFP00000039467; ENSCAFG00000002065. [O97799-2]
GeneIDi403811.
KEGGicfa:403811.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF044249 mRNA. Translation: AAD02327.1.
AF448148 mRNA. Translation: AAL40833.1.
AY296484 mRNA. Translation: AAP51178.1.
AY313776 mRNA. Translation: AAP76390.1.
RefSeqiNP_001003181.1. NM_001003181.1.
XP_005628025.1. XM_005627968.2. [O97799-1]
UniGeneiCfa.184.

3D structure databases

ProteinModelPortaliO97799.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000039467.

Proteomic databases

PaxDbiO97799.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSCAFT00000049830; ENSCAFP00000039467; ENSCAFG00000002065. [O97799-2]
GeneIDi403811.
KEGGicfa:403811.

Organism-specific databases

CTDi3815.

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118923.
HOGENOMiHOG000112008.
HOVERGENiHBG004335.
InParanoidiO97799.
KOiK05091.
OMAiYFCPGTE.
OrthoDBiEOG091G01TL.
TreeFamiTF325768.

Enzyme and pathway databases

BRENDAi2.7.10.1. 1153.
ReactomeiR-CFA-1257604. PIP3 activates AKT signaling.
R-CFA-1433557. Signaling by SCF-KIT.
R-CFA-1433559. Regulation of KIT signaling.
R-CFA-5673001. RAF/MAP kinase cascade.
R-CFA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.

Family and domain databases

Gene3Di2.60.40.10. 5 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013151. Immunoglobulin.
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]
PfamiPF00047. ig. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF500951. SCGF_recepter. 1 hit.
PIRSF000615. TyrPK_CSF1-R. 1 hit.
SMARTiSM00409. IG. 4 hits.
SM00408. IGc2. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 3 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50835. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiKIT_CANLF
AccessioniPrimary (citable) accession number: O97799
Secondary accession number(s): Q7YRV7, Q8WN23
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: September 5, 2006
Last modified: November 2, 2016
This is version 149 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.