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Protein

Mast/stem cell growth factor receptor Kit

Gene

KIT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein 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 SHC1.10 Publications

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.

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation4 Publications

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. Inhibited by imatinib/STI-571 (Gleevec) and sunitinib; these compounds maintain the kinase in an inactive conformation.5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi568Magnesium1
Binding sitei623ATP1
Active sitei792Proton acceptorPROSITE-ProRule annotation1
Binding sitei796ATP1
Metal bindingi797Magnesium1
Metal bindingi810Magnesium1
Sitei936Important for interaction with phosphotyrosine-binding proteins1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi596 – 603ATP8
Nucleotide bindingi671 – 677ATP7

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • cytokine binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • phosphatidylinositol-4,5-bisphosphate 3-kinase activity Source: Reactome
  • protease binding Source: Ensembl
  • protein homodimerization activity Source: UniProtKB
  • protein tyrosine kinase activity Source: ProtInc
  • Ras guanyl-nucleotide exchange factor activity Source: Reactome
  • stem cell factor receptor activity Source: Ensembl
  • transmembrane receptor protein tyrosine kinase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionKinase, Receptor, Transferase, Tyrosine-protein kinase
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1 2681
ReactomeiR-HSA-1257604 PIP3 activates AKT signaling
R-HSA-1433557 Signaling by SCF-KIT
R-HSA-1433559 Regulation of KIT signaling
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8866910 TFAP2 (AP-2) family regulates transcription of growth factors and their receptors
SignaLinkiP10721
SIGNORiP10721

Names & Taxonomyi

Protein namesi
Recommended name:
Mast/stem cell growth factor receptor Kit (EC:2.7.10.1)
Short name:
SCFR
Alternative name(s):
Piebald trait protein
Short name:
PBT
Proto-oncogene c-Kit
Tyrosine-protein kinase Kit
p145 c-kit
v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog
CD_antigen: CD117
Gene namesi
Name:KIT
Synonyms:SCFR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000157404.15
HGNCiHGNC:6342 KIT
MIMi164920 gene
neXtProtiNX_P10721

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini26 – 524ExtracellularSequence analysisAdd BLAST499
Transmembranei525 – 545HelicalSequence analysisAdd BLAST21
Topological domaini546 – 976CytoplasmicSequence analysisAdd BLAST431

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Piebald trait (PBT)8 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAutosomal dominant genetic developmental abnormality of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes.
See also OMIM:172800
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_004104583E → K in PBT. 1 PublicationCorresponds to variant dbSNP:rs121913680EnsemblClinVar.1
Natural variantiVAR_033129584F → C in PBT. 1 PublicationCorresponds to variant dbSNP:rs28933371EnsemblClinVar.1
Natural variantiVAR_004105584F → L in PBT. 1 PublicationCorresponds to variant dbSNP:rs794726671EnsemblClinVar.1
Natural variantiVAR_033130601G → R in PBT. 1 Publication1
Natural variantiVAR_033131656L → P in PBT. 1 Publication1
Natural variantiVAR_004106664G → R in PBT. 1 PublicationCorresponds to variant dbSNP:rs121913679EnsemblClinVar.1
Natural variantiVAR_004107791R → G in PBT. 1 Publication1
Natural variantiVAR_033132796R → G in PBT; with sensorineural deafness. 1 PublicationCorresponds to variant dbSNP:rs121913684EnsemblClinVar.1
Natural variantiVAR_004108812G → V in PBT. 1 Publication1
Natural variantiVAR_033137847T → P in PBT. 1 PublicationCorresponds to variant dbSNP:rs121913687EnsemblClinVar.1
Natural variantiVAR_004110893 – 896Missing in PBT; severe. 1 Publication4
Gastrointestinal stromal tumor (GIST)4 Publications
The gene represented in this entry is involved in disease pathogenesis.
Disease descriptionCommon mesenchymal neoplasms arising in the gastrointestinal tract, most often in the stomach. They are histologically, immunohistochemically, and genetically different from typical leiomyomas, leiomyosarcomas, and schwannomas. Most GISTs are composed of a fairly uniform population of spindle-shaped cells. Some tumors are dominated by epithelioid cells or contain a mixture of spindle and epithelioid morphologies. Primary GISTs in the gastrointestinal tract commonly metastasize in the omentum and mesenteries, often as multiple nodules. However, primary tumors may also occur outside of the gastrointestinal tract, in other intra-abdominal locations, especially in the omentum and mesentery.
See also OMIM:606764
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_033124550 – 558Missing in GIST; somatic mutation. 2 Publications9
Natural variantiVAR_033123550K → I in GIST; somatic mutation. 1 Publication1
Natural variantiVAR_033125551 – 555Missing in GIST; somatic mutation. 1 Publication5
Natural variantiVAR_033128559 – 560Missing in GIST; somatic mutation. 1 Publication2
Natural variantiVAR_033126559V → A in GIST. 1 PublicationCorresponds to variant dbSNP:rs121913517EnsemblClinVar.1
Natural variantiVAR_033127559V → D in GIST; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs121913517EnsemblClinVar.1
Natural variantiVAR_007965559Missing in GIST. 1 Publication1
Testicular germ cell tumor (TGCT)
The gene represented in this entry may be involved in disease pathogenesis.
Disease descriptionA common malignancy in males representing 95% of all testicular neoplasms. TGCTs have various pathologic subtypes including: unclassified intratubular germ cell neoplasia, seminoma (including cases with syncytiotrophoblastic cells), spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma.
See also OMIM:273300
Leukemia, acute myelogenous (AML)
The gene represented in this entry is involved in disease pathogenesis. Somatic mutations that lead to constitutive activation of KIT are detected in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the kinase domain can result in a constitutively activated kinase.
Disease descriptionA subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes.
See also OMIM:601626

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi381R → A: Reduces autophosphorylation in response to KITLG/SCF. 1 Publication1
Mutagenesisi386E → A: Reduces autophosphorylation in response to KITLG/SCF. 1 Publication1
Mutagenesisi571I → A: Reduction in SH2B2/APS binding. Abolishes SH2B2/APS binding; when associated with A-939. 1 Publication1
Mutagenesisi623K → M: Stronger interaction with MPDZ. 1 Publication1
Mutagenesisi741S → A: Abolishes down-regulation of kinase activity by PKC/PRKCA-mediated phosphorylation; when associated with A-746. 1 Publication1
Mutagenesisi746S → A: Abolishes down-regulation of kinase activity by PKC/PRKCA-mediated phosphorylation; when associated with A-741. 1 Publication1
Mutagenesisi823Y → F: No decrease in activity. Leads to autophosphorylation at Tyr-900. 1 Publication1
Mutagenesisi939L → A: Reduction in SH2B2/APS binding. Abolishes SH2B2/APS binding; when associated with A-571. 1 Publication1

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

DisGeNETi3815
MalaCardsiKIT
MIMi172800 phenotype
273300 phenotype
601626 phenotype
606764 phenotype
OpenTargetsiENSG00000157404
Orphaneti98829 'Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22)'
102724 'Acute myeloid leukemia with t(8;21)(q22;q22) translocation'
98834 Acute myeloblastic leukemia with maturation
158799 Aleukemic mast cell leukemia
280785 Bullous diffuse cutaneous mastocytosis
158796 Classic mast cell leukemia
79455 Cutaneous mastocytoma
44890 Gastrointestinal stromal tumor
158778 Isolated bone marrow mastocytosis
158793 Lymphoadenopathic mastocytosis with eosinophilia
158772 Nodular urticaria pigmentosa
2884 Piebaldism
158769 Plaque-form urticaria pigmentosa
280794 Pseudoxanthomatous diffuse cutaneous mastocytosis
158775 Smouldering systemic mastocytosis
98849 Systemic mastocytosis with an associated clonal hematologic non-mast cell lineage disease
90389 Telangiectasia macularis eruptiva perstans
158766 Typical urticaria pigmentosa
PharmGKBiPA30128

Chemistry databases

ChEMBLiCHEMBL1936
DrugBankiDB06080 ABT-869
DB01254 Dasatinib
DB00619 Imatinib
DB09078 Lenvatinib
DB05216 MP470
DB04868 Nilotinib
DB05913 OSI-930
DB06589 Pazopanib
DB01962 Phosphonotyrosine
DB08901 Ponatinib
DB08896 Regorafenib
DB00398 Sorafenib
DB01268 Sunitinib
DB05153 XL184
DB05146 XL820
GuidetoPHARMACOLOGYi1805

Polymorphism and mutation databases

BioMutaiKIT
DMDMi125472

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
ChainiPRO_000001675426 – 976Mast/stem cell growth factor receptor KitAdd BLAST951

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi58 ↔ 97PROSITE-ProRule annotation1 Publication
Glycosylationi130N-linked (GlcNAc...) asparagine2 Publications1
Disulfide bondi136 ↔ 186PROSITE-ProRule annotation1 Publication
Glycosylationi145N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi151 ↔ 183PROSITE-ProRule annotation1 Publication
Disulfide bondi233 ↔ 290PROSITE-ProRule annotation1 Publication
Glycosylationi283N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi293N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi300N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi320N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi352N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi367N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi428 ↔ 491PROSITE-ProRule annotation1 Publication
Glycosylationi463N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi486N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei547Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei553Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei568Phosphotyrosine; by autocatalysis4 Publications1
Modified residuei570Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei703Phosphotyrosine; by autocatalysis3 Publications1
Modified residuei721Phosphotyrosine; by autocatalysis3 Publications1
Modified residuei730Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei741Phosphoserine; by PKC/PRKCA1 Publication1
Modified residuei746Phosphoserine; by PKC/PRKCA1 Publication1
Modified residuei821Phosphoserine1 Publication1
Modified residuei823Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei891Phosphoserine1 Publication1
Modified residuei900Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei936Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei959PhosphoserineCombined sources1 Publication1

Post-translational modificationi

Ubiquitinated by SOCS6. KIT is rapidly ubiquitinated after autophosphorylation induced by KITLG/SCF binding, leading to internalization and degradation.2 Publications
Autophosphorylated on tyrosine residues. KITLG/SCF binding enhances autophosphorylation. Isoform 1 shows low levels of tyrosine phosphorylation in the absence of added KITLG/SCF (in vitro). Kinase activity is down-regulated by phosphorylation on serine residues by protein kinase C family members. Phosphorylation at Tyr-568 is required for interaction with PTPN11/SHP-2, CRK (isoform Crk-II) and members of the SRC tyrosine-protein kinase family. Phosphorylation at Tyr-570 is required for interaction with PTPN6/SHP-1. Phosphorylation at Tyr-703, Tyr-823 and Tyr-936 is important for interaction with GRB2. Phosphorylation at Tyr-721 is important for interaction with PIK3R1. Phosphorylation at Tyr-823 and Tyr-936 is important for interaction with GRB7.6 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP10721
MaxQBiP10721
PaxDbiP10721
PeptideAtlasiP10721
PRIDEiP10721
ProteomicsDBi52640
52641 [P10721-2]
52642 [P10721-3]

PTM databases

CarbonylDBiP10721
iPTMnetiP10721
PhosphoSitePlusiP10721

Expressioni

Tissue specificityi

Isoform 1 and isoform 2 are detected in spermatogonia and Leydig cells. Isoform 3 is detected in round spermatids, elongating spermatids and spermatozoa (at protein level). Widely expressed. Detected in the hematopoietic system, the gastrointestinal system, in melanocytes and in germ cells.2 Publications

Inductioni

Up-regulated by cis-retinoic acid in neuroblastoma cell lines.1 Publication

Gene expression databases

BgeeiENSG00000157404
CleanExiHS_KIT
ExpressionAtlasiP10721 baseline and differential
GenevisibleiP10721 HS

Organism-specific databases

HPAiCAB003288
CAB068253
CAB072867
HPA004471
HPA073252

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 (KITLG/SCF-bound) with IL1RL1. 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 similarity17 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • cytokine binding Source: UniProtKB
  • protease binding Source: Ensembl
  • protein homodimerization activity Source: UniProtKB
  • Ras guanyl-nucleotide exchange factor activity Source: Reactome

Protein-protein interaction databases

BioGridi110015, 53 interactors
DIPiDIP-1055N
IntActiP10721, 66 interactors
MINTiP10721
STRINGi9606.ENSP00000288135

Chemistry databases

BindingDBiP10721

Structurei

Secondary structure

1976
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi38 – 41Combined sources4
Beta strandi44 – 47Combined sources4
Beta strandi54 – 59Combined sources6
Beta strandi63 – 72Combined sources10
Beta strandi75 – 77Combined sources3
Beta strandi79 – 86Combined sources8
Helixi89 – 91Combined sources3
Beta strandi93 – 99Combined sources7
Beta strandi104 – 110Combined sources7
Beta strandi125 – 130Combined sources6
Beta strandi132 – 134Combined sources3
Beta strandi146 – 149Combined sources4
Beta strandi151 – 153Combined sources3
Beta strandi161 – 165Combined sources5
Turni166 – 168Combined sources3
Beta strandi169 – 174Combined sources6
Helixi177 – 179Combined sources3
Beta strandi183 – 188Combined sources6
Beta strandi193 – 200Combined sources8
Beta strandi203 – 205Combined sources3
Beta strandi213 – 215Combined sources3
Beta strandi219 – 224Combined sources6
Beta strandi229 – 239Combined sources11
Beta strandi243 – 248Combined sources6
Beta strandi258 – 263Combined sources6
Beta strandi265 – 267Combined sources3
Beta strandi269 – 279Combined sources11
Turni282 – 284Combined sources3
Beta strandi286 – 293Combined sources8
Beta strandi298 – 310Combined sources13
Beta strandi312 – 319Combined sources8
Beta strandi321 – 325Combined sources5
Beta strandi331 – 341Combined sources11
Beta strandi344 – 350Combined sources7
Beta strandi356 – 364Combined sources9
Beta strandi367 – 369Combined sources3
Beta strandi372 – 379Combined sources8
Helixi384 – 386Combined sources3
Beta strandi388 – 395Combined sources8
Beta strandi400 – 409Combined sources10
Beta strandi411 – 420Combined sources10
Helixi422 – 424Combined sources3
Beta strandi425 – 434Combined sources10
Beta strandi437 – 444Combined sources8
Beta strandi445 – 449Combined sources5
Beta strandi452 – 454Combined sources3
Beta strandi458 – 462Combined sources5
Beta strandi465 – 468Combined sources4
Beta strandi472 – 479Combined sources8
Helixi481 – 483Combined sources3
Beta strandi485 – 494Combined sources10
Beta strandi499 – 506Combined sources8
Beta strandi558 – 564Combined sources7
Beta strandi567 – 570Combined sources4
Turni573 – 575Combined sources3
Helixi580 – 582Combined sources3
Helixi586 – 588Combined sources3
Beta strandi589 – 597Combined sources9
Beta strandi599 – 613Combined sources15
Beta strandi617 – 625Combined sources9
Helixi631 – 647Combined sources17
Beta strandi656 – 660Combined sources5
Beta strandi662 – 665Combined sources4
Beta strandi667 – 671Combined sources5
Helixi678 – 684Combined sources7
Turni685 – 688Combined sources4
Beta strandi719 – 721Combined sources3
Helixi754 – 756Combined sources3
Beta strandi757 – 759Combined sources3
Helixi760 – 762Combined sources3
Helixi766 – 785Combined sources20
Beta strandi788 – 790Combined sources3
Helixi795 – 797Combined sources3
Beta strandi798 – 801Combined sources4
Turni802 – 804Combined sources3
Beta strandi805 – 808Combined sources4
Helixi812 – 814Combined sources3
Helixi817 – 819Combined sources3
Beta strandi823 – 825Combined sources3
Beta strandi827 – 831Combined sources5
Helixi833 – 835Combined sources3
Helixi838 – 843Combined sources6
Helixi848 – 863Combined sources16
Turni864 – 866Combined sources3
Helixi877 – 885Combined sources9
Helixi897 – 906Combined sources10
Helixi911 – 913Combined sources3
Helixi917 – 930Combined sources14
Turni931 – 933Combined sources3

3D structure databases

ProteinModelPortaliP10721
SMRiP10721
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10721

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 112Ig-like C2-type 1Add BLAST86
Domaini121 – 205Ig-like C2-type 2Add BLAST85
Domaini212 – 308Ig-like C2-type 3Add BLAST97
Domaini317 – 410Ig-like C2-type 4Add BLAST94
Domaini413 – 507Ig-like C2-type 5Add BLAST95
Domaini589 – 937Protein kinasePROSITE-ProRule annotationAdd BLAST349

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni568 – 570Important for interaction with phosphotyrosine-binding proteins3

Sequence similaritiesi

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

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0200 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118923
HOGENOMiHOG000112008
HOVERGENiHBG104348
InParanoidiP10721
KOiK05091
OMAiPTFKQIV
OrthoDBiEOG091G01TL
PhylomeDBiP10721
TreeFamiTF325768

Family and domain databases

Gene3Di2.60.40.10, 5 hits
InterProiView protein in InterPro
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003599 Ig_sub
IPR003598 Ig_sub2
IPR013151 Immunoglobulin
IPR011009 Kinase-like_dom_sf
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
IPR001824 Tyr_kinase_rcpt_3_CS
PfamiView protein in Pfam
PF00047 ig, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PIRSFiPIRSF500951 SCGF_recepter, 1 hit
SMARTiView protein in SMART
SM00409 IG, 3 hits
SM00408 IGc2, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF48726 SSF48726, 3 hits
SSF56112 SSF56112, 2 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 1 hit
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

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P10721-1) [UniParc]FASTAAdd to basket
Also known as: GNNK(+), KitA(+)

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 LCVLLLLLRV QTGSSQPSVS PGEPSPPSIH PGKSDLIVRV
60 70 80 90 100
GDEIRLLCTD PGFVKWTFEI LDETNENKQN EWITEKAEAT NTGKYTCTNK
110 120 130 140 150
HGLSNSIYVF VRDPAKLFLV DRSLYGKEDN DTLVRCPLTD PEVTNYSLKG
160 170 180 190 200
CQGKPLPKDL RFIPDPKAGI MIKSVKRAYH RLCLHCSVDQ EGKSVLSEKF
210 220 230 240 250
ILKVRPAFKA VPVVSVSKAS YLLREGEEFT VTCTIKDVSS SVYSTWKREN
260 270 280 290 300
SQTKLQEKYN SWHHGDFNYE RQATLTISSA RVNDSGVFMC YANNTFGSAN
310 320 330 340 350
VTTTLEVVDK GFINIFPMIN TTVFVNDGEN VDLIVEYEAF PKPEHQQWIY
360 370 380 390 400
MNRTFTDKWE DYPKSENESN IRYVSELHLT RLKGTEGGTY TFLVSNSDVN
410 420 430 440 450
AAIAFNVYVN TKPEILTYDR LVNGMLQCVA AGFPEPTIDW YFCPGTEQRC
460 470 480 490 500
SASVLPVDVQ TLNSSGPPFG KLVVQSSIDS SAFKHNGTVE CKAYNDVGKT
510 520 530 540 550
SAYFNFAFKG NNKEQIHPHT LFTPLLIGFV IVAGMMCIIV MILTYKYLQK
560 570 580 590 600
PMYEVQWKVV EEINGNNYVY IDPTQLPYDH KWEFPRNRLS FGKTLGAGAF
610 620 630 640 650
GKVVEATAYG LIKSDAAMTV AVKMLKPSAH LTEREALMSE LKVLSYLGNH
660 670 680 690 700
MNIVNLLGAC TIGGPTLVIT EYCCYGDLLN FLRRKRDSFI CSKQEDHAEA
710 720 730 740 750
ALYKNLLHSK ESSCSDSTNE YMDMKPGVSY VVPTKADKRR SVRIGSYIER
760 770 780 790 800
DVTPAIMEDD ELALDLEDLL SFSYQVAKGM AFLASKNCIH RDLAARNILL
810 820 830 840 850
THGRITKICD FGLARDIKND SNYVVKGNAR LPVKWMAPES IFNCVYTFES
860 870 880 890 900
DVWSYGIFLW ELFSLGSSPY PGMPVDSKFY KMIKEGFRML SPEHAPAEMY
910 920 930 940 950
DIMKTCWDAD PLKRPTFKQI VQLIEKQISE STNHIYSNLA NCSPNRQKPV
960 970
VDHSVRINSV GSTASSSQPL LVHDDV
Length:976
Mass (Da):109,865
Last modified:July 1, 1989 - v1
Checksum:i81B0CD76817F3454
GO
Isoform 2 (identifier: P10721-2) [UniParc]FASTAAdd to basket
Also known as: GNNK(-), Kit(+)

The sequence of this isoform differs from the canonical sequence as follows:
     510-513: Missing.

Show »
Length:972
Mass (Da):109,451
Checksum:iD59DEFE9AF761FDA
GO
Isoform 3 (identifier: P10721-3) [UniParc]FASTAAdd to basket
Also known as: TR-KIT

The sequence of this isoform differs from the canonical sequence as follows:
     412-413: KP → SL
     414-976: Missing.

Show »
Length:413
Mass (Da):46,658
Checksum:i08B327362CEF1B7E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti764L → I in AAH71593 (PubMed:15489334).Curated1
Sequence conflicti838P → H in AAH71593 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_042021532V → I1 PublicationCorresponds to variant dbSNP:rs55792975EnsemblClinVar.1
Natural variantiVAR_042022541M → L1 PublicationCorresponds to variant dbSNP:rs3822214EnsemblClinVar.1
Natural variantiVAR_061289541M → V. Corresponds to variant dbSNP:rs3822214EnsemblClinVar.1
Natural variantiVAR_033124550 – 558Missing in GIST; somatic mutation. 2 Publications9
Natural variantiVAR_033123550K → I in GIST; somatic mutation. 1 Publication1
Natural variantiVAR_033125551 – 555Missing in GIST; somatic mutation. 1 Publication5
Natural variantiVAR_033128559 – 560Missing in GIST; somatic mutation. 1 Publication2
Natural variantiVAR_033126559V → A in GIST. 1 PublicationCorresponds to variant dbSNP:rs121913517EnsemblClinVar.1
Natural variantiVAR_033127559V → D in GIST; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs121913517EnsemblClinVar.1
Natural variantiVAR_007965559Missing in GIST. 1 Publication1
Natural variantiVAR_004104583E → K in PBT. 1 PublicationCorresponds to variant dbSNP:rs121913680EnsemblClinVar.1
Natural variantiVAR_033129584F → C in PBT. 1 PublicationCorresponds to variant dbSNP:rs28933371EnsemblClinVar.1
Natural variantiVAR_004105584F → L in PBT. 1 PublicationCorresponds to variant dbSNP:rs794726671EnsemblClinVar.1
Natural variantiVAR_033130601G → R in PBT. 1 Publication1
Natural variantiVAR_033131656L → P in PBT. 1 Publication1
Natural variantiVAR_004106664G → R in PBT. 1 PublicationCorresponds to variant dbSNP:rs121913679EnsemblClinVar.1
Natural variantiVAR_042023691C → S1 PublicationCorresponds to variant dbSNP:rs35200131Ensembl.1
Natural variantiVAR_042024715S → N1 PublicationCorresponds to variant dbSNP:rs56094246Ensembl.1
Natural variantiVAR_042025737D → N in a colorectal adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs751005114EnsemblClinVar.1
Natural variantiVAR_004107791R → G in PBT. 1 Publication1
Natural variantiVAR_033132796R → G in PBT; with sensorineural deafness. 1 PublicationCorresponds to variant dbSNP:rs121913684EnsemblClinVar.1
Natural variantiVAR_042026804R → W in a colorectal adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs145602440EnsemblClinVar.1
Natural variantiVAR_004108812G → V in PBT. 1 Publication1
Natural variantiVAR_033133816D → F in mastocytosis; requires 2 nucleotide substitutions; somatic mutation; constitutively activated and is much more rapidly autophosphorylated than wild type. 1 Publication1
Natural variantiVAR_033134816D → H in a testicular tumor; seminoma; somatic mutation; constitutively activated. 3 PublicationsCorresponds to variant dbSNP:rs121913506EnsemblClinVar.1
Natural variantiVAR_004109816D → V in mast cell leukemia and mastocytosis; somatic mutation; constitutively activated; loss of interaction with MPDZ. 7 PublicationsCorresponds to variant dbSNP:rs121913507EnsemblClinVar.1
Natural variantiVAR_023828816D → Y in acute myeloid leukemia, mastocytosis and a germ cell tumor of the testis; somatic mutation; constitutively activated. 4 PublicationsCorresponds to variant dbSNP:rs121913506EnsemblClinVar.1
Natural variantiVAR_033135820D → G in mast cell disease; systemic. 1 PublicationCorresponds to variant dbSNP:rs121913682EnsemblClinVar.1
Natural variantiVAR_023829822N → K in a germ cell tumor of the testis; somatic mutation. 2 PublicationsCorresponds to variant dbSNP:rs121913514EnsemblClinVar.1
Natural variantiVAR_023830829A → P in a germ cell tumor of the testis; somatic mutation. 2 PublicationsCorresponds to variant dbSNP:rs1057519713Ensembl.1
Natural variantiVAR_033136839E → K in mastocytosis; somatic mutation; dominant negative mutation; loss of autophosphorylation. 1 PublicationCorresponds to variant dbSNP:rs121913509EnsemblClinVar.1
Natural variantiVAR_033137847T → P in PBT. 1 PublicationCorresponds to variant dbSNP:rs121913687EnsemblClinVar.1
Natural variantiVAR_004110893 – 896Missing in PBT; severe. 1 Publication4

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_041866412 – 413KP → SL in isoform 3. 1 Publication2
Alternative sequenceiVSP_041867414 – 976Missing in isoform 3. 1 PublicationAdd BLAST563
Alternative sequenceiVSP_038385510 – 513Missing in isoform 2. 3 Publications4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X06182 mRNA Translation: CAA29548.1
X69301
, X69302, X69303, X69304, X69305, X69306, X69307, X69308, X69309, X69310, X69311, X69312, X69313, X69314, X69315, X69316 Genomic DNA Translation: CAA49159.1
U63834 Genomic DNA Translation: AAC50968.1
U63834 Genomic DNA Translation: AAC50969.1
EU826594 mRNA Translation: ACF47630.1
GU983671 mRNA Translation: ADF36702.1
HM015525 mRNA Translation: ADF50068.1
HM015526 mRNA Translation: ADF50069.1
AK304031 mRNA Translation: BAG64945.1
AC006552 Genomic DNA No translation available.
AC092545 Genomic DNA No translation available.
BC071593 mRNA Translation: AAH71593.1
S67773 Genomic DNA Translation: AAB29529.1
CCDSiCCDS3496.1 [P10721-1]
CCDS47058.1 [P10721-2]
PIRiS01426 TVHUKT
RefSeqiNP_000213.1, NM_000222.2 [P10721-1]
NP_001087241.1, NM_001093772.1 [P10721-2]
UniGeneiHs.479754

Genome annotation databases

EnsembliENST00000288135; ENSP00000288135; ENSG00000157404 [P10721-1]
ENST00000412167; ENSP00000390987; ENSG00000157404 [P10721-2]
GeneIDi3815
KEGGihsa:3815
UCSCiuc010igr.4 human [P10721-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiKIT_HUMAN
AccessioniPrimary (citable) accession number: P10721
Secondary accession number(s): B5A956
, D5LXN2, D5M931, F5H8F8, Q6IQ28, Q99662, Q9UM99
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: July 18, 2018
This is version 221 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  8. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  9. SIMILARITY comments
    Index of protein domains and families

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