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P10721 (KIT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 177. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (8) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·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):
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 names
Name:KIT
Synonyms:SCFR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length976 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein 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. Ref.11 Ref.15 Ref.17 Ref.20 Ref.21 Ref.22 Ref.25 Ref.26 Ref.30 Ref.31

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.1 Ref.30 Ref.39 Ref.40

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. Inhibited by imatinib/STI-571 (Gleevec) and sunitinib; these compounds maintain the kinase in an inactive conformation. Ref.11 Ref.12 Ref.30 Ref.38 Ref.40

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. Ref.11 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.24 Ref.25 Ref.30 Ref.37 Ref.39

Subcellular location

Isoform 1: Cell membrane; Single-pass type I membrane protein Ref.1 Ref.5 Ref.26 Ref.28.

Isoform 2: Cell membrane; Single-pass type I membrane protein Ref.1 Ref.5 Ref.26 Ref.28.

Isoform 3: Cytoplasm. Note: Detected in the cytoplasm of spermatozoa, especially in the equatorial and subacrosomal region of the sperm head. Ref.1 Ref.5 Ref.26 Ref.28

Tissue specificity

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. Ref.1 Ref.28

Induction

Up-regulated by cis-retinoic acid in neuroblastoma cell lines. Ref.5 Ref.11 Ref.12 Ref.30 Ref.38 Ref.40

Post-translational modification

Ubiquitinated by SOCS6. KIT is rapidly ubiquitinated after autophosphorylation induced by KITLG/SCF binding, leading to internalization and degradation. Ref.25 Ref.26

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. Ref.1 Ref.11 Ref.12 Ref.13 Ref.15 Ref.16 Ref.21 Ref.26 Ref.29 Ref.30 Ref.37 Ref.39 Ref.40 Ref.41

Involvement in disease

Piebald trait (PBT) [MIM:172800]: Autosomal dominant genetic developmental abnormality of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.42 Ref.43 Ref.44 Ref.46 Ref.47 Ref.48 Ref.49 Ref.51 Ref.56

Gastrointestinal stromal tumor (GIST) [MIM:606764]: Common 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.
Note: The gene represented in this entry is involved in disease pathogenesis. Ref.48 Ref.52 Ref.53 Ref.57 Ref.58

Testicular germ cell tumor (TGCT) [MIM:273300]: A 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.
Note: The gene represented in this entry may be involved in disease pathogenesis. Ref.48

Leukemia, acute myelogenous (AML) [MIM:601626]: A 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.
Note: 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. Ref.48

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.

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
Cytoplasm
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Proto-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 term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processFc receptor signaling pathway

Inferred from direct assay PubMed 20100931. Source: UniProtKB

Fc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

Kit signaling pathway

Inferred from direct assay Ref.39. Source: UniProtKB

T cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

actin cytoskeleton reorganization

Inferred from direct assay PubMed 1721869. Source: UniProtKB

activation of MAPK activity

Inferred from direct assay Ref.30. Source: UniProtKB

cell chemotaxis

Inferred from direct assay PubMed 1721869. Source: UniProtKB

cellular response to thyroid hormone stimulus

Inferred from electronic annotation. Source: Ensembl

cytokine-mediated signaling pathway

Inferred from direct assay Ref.30. 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

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

epithelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

erythrocyte differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

erythropoietin-mediated signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

germ cell migration

Inferred from electronic annotation. Source: Ensembl

glycosphingolipid metabolic process

Inferred from electronic annotation. Source: Ensembl

hemopoiesis

Traceable author statement Ref.33. Source: UniProtKB

immature B cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

inflammatory response

Inferred from sequence or structural similarity. Source: UniProtKB

innate immune response

Traceable author statement. Source: Reactome

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 expression pattern PubMed 17848411. Source: UniProtKB

mast cell chemotaxis

Inferred from direct assay PubMed 20100931. Source: UniProtKB

mast cell cytokine production

Inferred from direct assay PubMed 20100931. Source: UniProtKB

mast cell degranulation

Inferred from mutant phenotype PubMed 20100931. Source: UniProtKB

mast cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

mast cell proliferation

Traceable author statement Ref.36. 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

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

ovarian follicle development

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-tyrosine phosphorylation

Inferred from direct assay Ref.30. Source: UniProtKB

phosphatidylinositol-mediated signaling

Traceable author statement. Source: Reactome

pigmentation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of JAK-STAT cascade

Inferred from mutant phenotype Ref.31. Source: UniProtKB

positive regulation of MAPK cascade

Inferred from mutant phenotype Ref.30. Source: UniProtKB

positive regulation of Notch signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell migration

Inferred from electronic annotation. Source: Ensembl

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 long-term neuronal synaptic plasticity

Inferred from electronic annotation. Source: Ensembl

positive regulation of phosphatidylinositol 3-kinase activity

Traceable author statement Ref.33. Source: UniProtKB

positive regulation of phosphatidylinositol 3-kinase signaling

Traceable author statement Ref.33. Source: UniProtKB

positive regulation of phospholipase C activity

Traceable author statement Ref.33. Source: UniProtKB

positive regulation of pseudopodium assembly

Inferred from electronic annotation. Source: Ensembl

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from mutant phenotype Ref.31. Source: UniProtKB

positive regulation of tyrosine phosphorylation of Stat1 protein

Inferred from mutant phenotype Ref.31. Source: UniProtKB

positive regulation of tyrosine phosphorylation of Stat3 protein

Inferred from mutant phenotype Ref.31. Source: UniProtKB

positive regulation of tyrosine phosphorylation of Stat5 protein

Inferred from mutant phenotype Ref.31. Source: UniProtKB

protein autophosphorylation

Inferred from direct assay Ref.30. Source: UniProtKB

regulation of cell proliferation

Traceable author statement Ref.33Ref.36. Source: UniProtKB

regulation of cell shape

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of developmental pigmentation

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement Ref.55. Source: ProtInc

signal transduction by phosphorylation

Traceable author statement Ref.53. Source: GOC

somatic stem cell division

Inferred from electronic annotation. Source: Ensembl

somatic stem cell maintenance

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

stem cell maintenance

Traceable author statement Ref.36. Source: UniProtKB

visual learning

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentacrosomal vesicle

Inferred from electronic annotation. Source: Ensembl

cytoplasmic side of plasma membrane

Inferred from electronic annotation. Source: Ensembl

external side of plasma membrane

Inferred from electronic annotation. Source: Ensembl

extracellular space

Inferred from direct assay PubMed 14625290. Source: BHF-UCL

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

mast cell granule

Inferred from mutant phenotype PubMed 20100931. Source: GOC

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

cytokine binding

Inferred from direct assay Ref.30. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein homodimerization activity

Inferred from physical interaction Ref.30. Source: UniProtKB

protein tyrosine kinase activity

Traceable author statement Ref.44. Source: ProtInc

receptor signaling protein tyrosine kinase activity

Traceable author statement Ref.53. Source: ProtInc

stem cell factor receptor activity

Inferred from electronic annotation. Source: Ensembl

transmembrane receptor protein tyrosine kinase activity

Inferred from direct assay Ref.30. Source: UniProtKB

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P10721-1)

Also known as: GNNK(+); Kit(+);

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: P10721-2)

Also known as: GNNK(-); KitA(+);

The sequence of this isoform differs from the canonical sequence as follows:
     510-513: Missing.
Isoform 3 (identifier: P10721-3)

Also known as: TR-KIT;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Potential
Chain26 – 976951Mast/stem cell growth factor receptor Kit
PRO_0000016754

Regions

Topological domain26 – 524499Extracellular Potential
Transmembrane525 – 54521Helical; Potential
Topological domain546 – 976431Cytoplasmic Potential
Domain27 – 11286Ig-like C2-type 1
Domain121 – 20585Ig-like C2-type 2
Domain212 – 30897Ig-like C2-type 3
Domain317 – 41094Ig-like C2-type 4
Domain413 – 50795Ig-like C2-type 5
Domain589 – 937349Protein kinase
Nucleotide binding596 – 6038ATP
Nucleotide binding671 – 6777ATP
Region568 – 5703Important for interaction with phosphotyrosine-binding proteins

Sites

Active site7921Proton acceptor By similarity
Metal binding5681Magnesium
Metal binding7971Magnesium
Metal binding8101Magnesium
Binding site6231ATP
Binding site7961ATP
Site9361Important for interaction with phosphotyrosine-binding proteins

Amino acid modifications

Modified residue5471Phosphotyrosine; by autocatalysis Probable
Modified residue5531Phosphotyrosine; by autocatalysis Probable
Modified residue5681Phosphotyrosine; by autocatalysis Ref.13 Ref.26 Ref.37 Ref.41
Modified residue5701Phosphotyrosine; by autocatalysis Ref.13 Ref.37
Modified residue7031Phosphotyrosine; by autocatalysis Ref.16 Ref.26 Ref.29
Modified residue7211Phosphotyrosine; by autocatalysis Ref.13 Ref.26 Ref.29
Modified residue7301Phosphotyrosine; by autocatalysis Probable
Modified residue7411Phosphoserine; by PKC/PRKCA Ref.12
Modified residue7461Phosphoserine; by PKC/PRKCA Ref.12
Modified residue8211Phosphoserine Ref.12
Modified residue8231Phosphotyrosine; by autocatalysis Ref.29
Modified residue8911Phosphoserine Ref.21
Modified residue9001Phosphotyrosine; by autocatalysis Ref.21 Ref.29
Modified residue9361Phosphotyrosine; by autocatalysis Ref.16 Ref.26
Modified residue9591Phosphoserine Ref.12 Ref.27
Glycosylation1301N-linked (GlcNAc...) Ref.23 Ref.39
Glycosylation1451N-linked (GlcNAc...) Potential
Glycosylation2831N-linked (GlcNAc...) Ref.39
Glycosylation2931N-linked (GlcNAc...) Ref.39
Glycosylation3001N-linked (GlcNAc...) Ref.39
Glycosylation3201N-linked (GlcNAc...) Ref.39
Glycosylation3521N-linked (GlcNAc...) Ref.39
Glycosylation3671N-linked (GlcNAc...) Ref.39
Glycosylation4631N-linked (GlcNAc...) Potential
Glycosylation4861N-linked (GlcNAc...) Potential
Disulfide bond58 ↔ 97 Ref.39
Disulfide bond136 ↔ 186 Ref.39
Disulfide bond151 ↔ 183 Ref.39
Disulfide bond233 ↔ 290 Ref.39
Disulfide bond428 ↔ 491 Ref.39

Natural variations

Alternative sequence412 – 4132KP → SL in isoform 3.
VSP_041866
Alternative sequence414 – 976563Missing in isoform 3.
VSP_041867
Alternative sequence510 – 5134Missing in isoform 2.
VSP_038385
Natural variant5321V → I. Ref.60
Corresponds to variant rs55792975 [ dbSNP | Ensembl ].
VAR_042021
Natural variant5411M → L. Ref.60
Corresponds to variant rs3822214 [ dbSNP | Ensembl ].
VAR_042022
Natural variant5411M → V.
Corresponds to variant rs3822214 [ dbSNP | Ensembl ].
VAR_061289
Natural variant550 – 5589Missing in GIST; somatic mutation.
VAR_033124
Natural variant5501K → I in GIST; somatic mutation. Ref.53
Corresponds to variant rs28933968 [ dbSNP | Ensembl ].
VAR_033123
Natural variant551 – 5555Missing in GIST; somatic mutation.
VAR_033125
Natural variant559 – 5602Missing in GIST; somatic mutation. Ref.52
VAR_033128
Natural variant5591V → A in GIST. Ref.57
VAR_033126
Natural variant5591V → D in GIST; somatic mutation. Ref.53
VAR_033127
Natural variant5591Missing in GIST. Ref.52
VAR_007965
Natural variant5831E → K in PBT. Ref.42
VAR_004104
Natural variant5841F → C in PBT. Ref.56
Corresponds to variant rs28933371 [ dbSNP | Ensembl ].
VAR_033129
Natural variant5841F → L in PBT. Ref.43
VAR_004105
Natural variant6011G → R in PBT. Ref.56
VAR_033130
Natural variant6561L → P in PBT. Ref.56
VAR_033131
Natural variant6641G → R in PBT. Ref.44
VAR_004106
Natural variant6911C → S. Ref.60
Corresponds to variant rs35200131 [ dbSNP | Ensembl ].
VAR_042023
Natural variant7151S → N. Ref.60
Corresponds to variant rs56094246 [ dbSNP | Ensembl ].
VAR_042024
Natural variant7371D → N in a colorectal adenocarcinoma sample; somatic mutation. Ref.60
VAR_042025
Natural variant7911R → G in PBT. Ref.46
VAR_004107
Natural variant7961R → G in PBT; with sensorineural deafness. Ref.49
VAR_033132
Natural variant8041R → W in a colorectal adenocarcinoma sample; somatic mutation. Ref.60
VAR_042026
Natural variant8121G → V in PBT. Ref.46
VAR_004108
Natural variant8161D → F in mastocytosis; requires 2 nucleotide substitutions; somatic mutation; constitutively activated and is much more rapidly autophosphorylated than wild type. Ref.55
VAR_033133
Natural variant8161D → H in a testicular tumor; seminoma; somatic mutation; constitutively activated. Ref.29 Ref.40 Ref.54
Corresponds to variant rs28933969 [ dbSNP | Ensembl ].
VAR_033134
Natural variant8161D → V in mast cell leukemia and mastocytosis; somatic mutation; constitutively activated; loss of interaction with MPDZ. Ref.18 Ref.24 Ref.26 Ref.30 Ref.40 Ref.45 Ref.55
VAR_004109
Natural variant8161D → Y in acute myeloid leukemia, mastocytosis and a germ cell tumor of the testis; somatic mutation; constitutively activated. Ref.50 Ref.55 Ref.59 Ref.60
VAR_023828
Natural variant8201D → G in mast cell disease; systemic. Ref.48
VAR_033135
Natural variant8221N → K in a germ cell tumor of the testis; somatic mutation. Ref.59 Ref.60
VAR_023829
Natural variant8291A → P in a germ cell tumor of the testis; somatic mutation. Ref.59 Ref.60
VAR_023830
Natural variant8391E → K in mastocytosis; somatic mutation; dominant negative mutation; loss of autophosphorylation. Ref.55
VAR_033136
Natural variant8471T → P in PBT. Ref.51
VAR_033137
Natural variant893 – 8964Missing in PBT; severe.
VAR_004110

Experimental info

Mutagenesis3811R → A: Reduces autophosphorylation in response to KITLG/SCF. Ref.39
Mutagenesis3861E → A: Reduces autophosphorylation in response to KITLG/SCF. Ref.39
Mutagenesis5711I → A: Reduction in SH2B2/APS binding. Abolishes SH2B2/APS binding; when associated with A-939. Ref.20
Mutagenesis6231K → M: Stronger interaction with MPDZ. Ref.18
Mutagenesis7411S → A: Abolishes down-regulation of kinase activity by PKC/PRKCA-mediated phosphorylation; when associated with A-746. Ref.12
Mutagenesis7461S → A: Abolishes down-regulation of kinase activity by PKC/PRKCA-mediated phosphorylation; when associated with A-741. Ref.12
Mutagenesis8231Y → F: No decrease in activity. Leads to autophosphorylation at Tyr-900. Ref.29
Mutagenesis9391L → A: Reduction in SH2B2/APS binding. Abolishes SH2B2/APS binding; when associated with A-571. Ref.20
Sequence conflict7641L → I in AAH71593. Ref.9
Sequence conflict8381P → H in AAH71593. Ref.9

Secondary structure

............................................................................................................................................................. 976
Helix Strand Turn

Details...

Sequences

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

Last modified July 1, 1989. Version 1.
Checksum: 81B0CD76817F3454

FASTA976109,865
        10         20         30         40         50         60 
MRGARGAWDF LCVLLLLLRV QTGSSQPSVS PGEPSPPSIH PGKSDLIVRV GDEIRLLCTD 

        70         80         90        100        110        120 
PGFVKWTFEI LDETNENKQN EWITEKAEAT NTGKYTCTNK HGLSNSIYVF VRDPAKLFLV 

       130        140        150        160        170        180 
DRSLYGKEDN DTLVRCPLTD PEVTNYSLKG CQGKPLPKDL RFIPDPKAGI MIKSVKRAYH 

       190        200        210        220        230        240 
RLCLHCSVDQ EGKSVLSEKF ILKVRPAFKA VPVVSVSKAS YLLREGEEFT VTCTIKDVSS 

       250        260        270        280        290        300 
SVYSTWKREN SQTKLQEKYN SWHHGDFNYE RQATLTISSA RVNDSGVFMC YANNTFGSAN 

       310        320        330        340        350        360 
VTTTLEVVDK GFINIFPMIN TTVFVNDGEN VDLIVEYEAF PKPEHQQWIY MNRTFTDKWE 

       370        380        390        400        410        420 
DYPKSENESN IRYVSELHLT RLKGTEGGTY TFLVSNSDVN AAIAFNVYVN TKPEILTYDR 

       430        440        450        460        470        480 
LVNGMLQCVA AGFPEPTIDW YFCPGTEQRC SASVLPVDVQ TLNSSGPPFG KLVVQSSIDS 

       490        500        510        520        530        540 
SAFKHNGTVE CKAYNDVGKT SAYFNFAFKG NNKEQIHPHT LFTPLLIGFV IVAGMMCIIV 

       550        560        570        580        590        600 
MILTYKYLQK PMYEVQWKVV EEINGNNYVY IDPTQLPYDH KWEFPRNRLS FGKTLGAGAF 

       610        620        630        640        650        660 
GKVVEATAYG LIKSDAAMTV AVKMLKPSAH LTEREALMSE LKVLSYLGNH MNIVNLLGAC 

       670        680        690        700        710        720 
TIGGPTLVIT EYCCYGDLLN FLRRKRDSFI CSKQEDHAEA ALYKNLLHSK ESSCSDSTNE 

       730        740        750        760        770        780 
YMDMKPGVSY VVPTKADKRR SVRIGSYIER DVTPAIMEDD ELALDLEDLL SFSYQVAKGM 

       790        800        810        820        830        840 
AFLASKNCIH RDLAARNILL THGRITKICD FGLARDIKND SNYVVKGNAR LPVKWMAPES 

       850        860        870        880        890        900 
IFNCVYTFES DVWSYGIFLW ELFSLGSSPY PGMPVDSKFY KMIKEGFRML SPEHAPAEMY 

       910        920        930        940        950        960 
DIMKTCWDAD PLKRPTFKQI VQLIEKQISE STNHIYSNLA NCSPNRQKPV VDHSVRINSV 

       970 
GSTASSSQPL LVHDDV 

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Isoform 2 (GNNK(-)) (KitA(+)) [UniParc].

Checksum: D59DEFE9AF761FDA
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FASTA972109,451
Isoform 3 (TR-KIT) [UniParc].

Checksum: 08B327362CEF1B7E
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FASTA41346,658

References

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[1]"Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand."
Yarden Y., Kuang W.-J., Yang-Feng T., Coussens L., Munemitsu S., Dull T.J., Chen E., Schlessinger J., Francke U., Ullrich A.
EMBO J. 6:3341-3351(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Fetal brain and Term placenta.
[2]"Organization and nucleotide sequence of the human KIT (mast/stem cell growth factor receptor) proto-oncogene."
Giebel L.B., Strunk K.M., Holmes S.A., Spritz R.A.
Oncogene 7:2207-2217(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORMS 1 AND 2).
[3]"Sequence analysis of two genomic regions containing the KIT and the FMS receptor tyrosine kinase genes."
Andre C., Hampe A., Lachaume P., Martin E., Wang X.P., Manus V., Hu W.X., Galibert F.
Genomics 39:216-226(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis."
Jin P., Zhang J., Sumariwalla P.F., Ni I., Jorgensen B., Crawford D., Phillips S., Feldmann M., Shepard H.M., Paleolog E.M.
Arthritis Res. Ther. 10:R73-R73(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[5]"Retinoic acid enhances sensitivity of neuroblastoma cells for imatinib mesylate."
Neumann I., Foell J.L., Bremer M., Volkmer I., Korholz D., Burdach S., Staege M.S.
Pediatr. Blood Cancer 55:464-470(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, INDUCTION.
[6]"Sequence of KIT mRNA from all-trans retinoic acid treated neuroblastoma cell lines."
Staege M.S., Neumann I., Volkmer I.
Submitted (MAR-2010) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[7]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Trachea.
[8]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[10]"Characterization of the promoter region of the human c-kit proto-oncogene."
Yamamoto K., Tojo A., Aoki N., Shibuya M.
Jpn. J. Cancer Res. 84:1136-1144(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22.
[11]"Modulation of Kit/stem cell factor receptor-induced signaling by protein kinase C."
Blume-Jensen P., Ronnstrand L., Gout I., Waterfield M.D., Heldin C.H.
J. Biol. Chem. 269:21793-21802(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF PIK3R1; RAF1 AND MAPK1, INTERACTION WITH GRB2; PIK3R1 AND PIK3 CATALYTIC SUBUNIT, ENZYME REGULATION, PHOSPHORYLATION.
[12]"Identification of the major phosphorylation sites for protein kinase C in kit/stem cell factor receptor in vitro and in intact cells."
Blume-Jensen P., Wernstedt C., Heldin C.H., Ronnstrand L.
J. Biol. Chem. 270:14192-14200(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-741; SER-746; SER-821 AND SER-959, ENZYME REGULATION, PARTIAL PROTEIN SEQUENCE, MUTAGENESIS OF SER-741 AND SER-746.
[13]"Direct association of Csk homologous kinase (CHK) with the diphosphorylated site Tyr568/570 of the activated c-KIT in megakaryocytes."
Price D.J., Rivnay B., Fu Y., Jiang S., Avraham S., Avraham H.
J. Biol. Chem. 272:5915-5920(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PIK3R1; MATK/CHK; FYN AND SHC1, PHOSPHORYLATION AT TYR-568; TYR-570 AND TYR-721.
[14]"Lyn associates with the juxtamembrane region of c-Kit and is activated by stem cell factor in hematopoietic cell lines and normal progenitor cells."
Linnekin D., DeBerry C.S., Mou S.
J. Biol. Chem. 272:27450-27455(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LYN.
[15]"SHP-1 binds and negatively modulates the c-Kit receptor by interaction with tyrosine 569 in the c-Kit juxtamembrane domain."
Kozlowski M., Larose L., Lee F., Le D.M., Rottapel R., Siminovitch K.A.
Mol. Cell. Biol. 18:2089-2099(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PTPN6, AUTOPHOSPHORYLATION, FUNCTION IN PHOSPHORYLATION OF PTPN6.
[16]"Identification of Tyr-703 and Tyr-936 as the primary association sites for Grb2 and Grb7 in the c-Kit/stem cell factor receptor."
Thommes K., Lennartsson J., Carlberg M., Ronnstrand L.
Biochem. J. 341:211-216(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GRB2 AND GRB7, PARTIAL PROTEIN SEQUENCE, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT TYR-703 AND TYR-936.
[17]"The receptor protein tyrosine phosphatase, PTP-RO, is upregulated during megakaryocyte differentiation and is associated with the c-Kit receptor."
Taniguchi Y., London R., Schinkmann K., Jiang S., Avraham H.
Blood 94:539-549(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PTPRU, FUNCTION IN PHOSPHORYLATION OF PTPRU.
[18]"The direct association of the multiple PDZ domain containing proteins (MUPP-1) with the human c-Kit C-terminus is regulated by tyrosine kinase activity."
Mancini A., Koch A., Stefan M., Niemann H., Tamura T.
FEBS Lett. 482:54-58(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MPDZ, CHARACTERIZATION OF VARIANT VAL-816, MUTAGENESIS OF LYS-623.
[19]"Phosphatidylinositol 3-kinase and Src family kinases are required for phosphorylation and membrane recruitment of Dok-1 in c-Kit signaling."
Liang X., Wisniewski D., Strife A., Shivakrupa R., Clarkson B., Resh M.D.
J. Biol. Chem. 277:13732-13738(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LYN; TEC AND DOK1.
[20]"The adapter protein APS associates with the multifunctional docking sites Tyr-568 and Tyr-936 in c-Kit."
Wollberg P., Lennartsson J., Gottfridsson E., Yoshimura A., Ronnstrand L.
Biochem. J. 370:1033-1038(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SH2B2/APS, FUNCTION IN PHOSPHORYLATION OF SH2B2/APS, MUTAGENESIS OF ILE-571 AND LEU-939.
[21]"Identification of Tyr900 in the kinase domain of c-Kit as a Src-dependent phosphorylation site mediating interaction with c-Crk."
Lennartsson J., Wernstedt C., Engstrom U., Hellman U., Ronnstrand L.
Exp. Cell Res. 288:110-118(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-891 AND TYR-900, PARTIAL PROTEIN SEQUENCE, INTERACTION WITH CRK AND PIK3R1, FUNCTION IN PHOSPHORYLATION OF CRK; AKT1 AND MAP KINASES, IDENTIFICATION BY MASS SPECTROMETRY.
[22]"Src family kinases are involved in the differential signaling from two splice forms of c-Kit."
Voytyuk O., Lennartsson J., Mogi A., Caruana G., Courtneidge S., Ashman L.K., Ronnstrand L.
J. Biol. Chem. 278:9159-9166(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ALTERNATIVE SPLICING.
[23]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-130.
Tissue: Plasma.
[24]"The tyrosine kinase FES is an essential effector of KITD816V proliferation signal."
Voisset E., Lopez S., Dubreuil P., De Sepulveda P.
Blood 110:2593-2599(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FES/FPS, CHARACTERIZATION OF VARIANT VAL-816.
[25]"Grb2 mediates negative regulation of stem cell factor receptor/c-Kit signaling by recruitment of Cbl."
Sun J., Pedersen M., Bengtsson S., Ronnstrand L.
Exp. Cell Res. 313:3935-3942(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GRB2 AND CBL, UBIQUITINATION, FUNCTION IN PHOSPHORYLATION OF CBL.
[26]"The D816V mutation of c-Kit circumvents a requirement for Src family kinases in c-Kit signal transduction."
Sun J., Pedersen M., Ronnstrand L.
J. Biol. Chem. 284:11039-11047(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ACTIVATION OF SIGNALING PATHWAYS AND CELL SURVIVAL, FUNCTION IN PHOSPHORYLATION OF CBL, PHOSPHORYLATION AT TYR-568; TYR-703; TYR-721 AND TYR-936, UBIQUITINATION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT VAL-816.
[27]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-959, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[28]"Expression of a truncated form of KIT tyrosine kinase in human spermatozoa correlates with sperm DNA integrity."
Muciaccia B., Sette C., Paronetto M.P., Barchi M., Pensini S., D'Agostino A., Gandini L., Geremia R., Stefanini M., Rossi P.
Hum. Reprod. 25:2188-2202(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
[29]"Function of activation loop tyrosine phosphorylation in the mechanism of c-Kit auto-activation and its implication in sunitinib resistance."
DiNitto J.P., Deshmukh G.D., Zhang Y., Jacques S.L., Coli R., Worrall J.W., Diehl W., English J.M., Wu J.C.
J. Biochem. 147:601-609(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-547; TYR-553; TYR-703; TYR-721; TYR-730; TYR-823 AND TYR-900, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF TYR-823, CHARACTERIZATION OF VARIANT HIS-816.
[30]"Mechanism of activation of human c-KIT kinase by internal tandem duplications of the juxtamembrane domain and point mutations at aspartic acid 816."
Kim S.Y., Kang J.J., Lee H.H., Kang J.J., Kim B., Kim C.G., Park T.K., Kang H.
Biochem. Biophys. Res. Commun. 410:224-228(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, AUTOPHOSPHORYLATION, SUBUNIT, CHARACTERIZATION OF VARIANT VAL-816.
[31]"Mechanisms of STAT protein activation by oncogenic KIT mutants in neoplastic mast cells."
Chaix A., Lopez S., Voisset E., Gros L., Dubreuil P., De Sepulveda P.
J. Biol. Chem. 286:5956-5966(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ACTIVATION AND PHOSPHORYLATION OF STAT1; STAT3; STAT5A AND STAT5B.
[32]"Signal transduction via the stem cell factor receptor/c-Kit."
Ronnstrand L.
Cell. Mol. Life Sci. 61:2535-2548(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[33]"Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor."
Roskoski R. Jr.
Biochem. Biophys. Res. Commun. 337:1-13(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON KIT SIGNALING.
[34]"Normal and oncogenic forms of the receptor tyrosine kinase kit."
Lennartsson J., Jelacic T., Linnekin D., Shivakrupa R.
Stem Cells 23:16-43(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[35]"Regulation of hematopoietic stem cells by the steel factor/KIT signaling pathway."
Kent D., Copley M., Benz C., Dykstra B., Bowie M., Eaves C.
Clin. Cancer Res. 14:1926-1930(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[36]"Tumor-intrinsic and -extrinsic roles of c-Kit: mast cells as the primary off-target of tyrosine kinase inhibitors."
Pittoni P., Piconese S., Tripodo C., Colombo M.P.
Oncogene 30:757-769(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[37]"Structure of a c-kit product complex reveals the basis for kinase transactivation."
Mol C.D., Lim K.B., Sridhar V., Zou H., Chien E.Y., Sang B.C., Nowakowski J., Kassel D.B., Cronin C.N., McRee D.E.
J. Biol. Chem. 278:31461-31464(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 549-931 IN COMPLEX WITH ADP AND MAGNESIUM IONS, SUBUNIT, AUTOPHOSPHORYLATION AT TYR-568 AND TYR-570, IDENTIFICATION BY MASS SPECTROMETRY.
[38]"Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase."
Mol C.D., Dougan D.R., Schneider T.R., Skene R.J., Kraus M.L., Scheibe D.N., Snell G.P., Zou H., Sang B.C., Wilson K.P.
J. Biol. Chem. 279:31655-31663(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 565-935 IN COMPLEXES WITH INHIBITOR IMATINIB AND PHOSPHATE, ENZYME REGULATION.
[39]"Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor."
Yuzawa S., Opatowsky Y., Zhang Z., Mandiyan V., Lax I., Schlessinger J.
Cell 130:323-334(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 1-519 IN COMPLEX WITH KITLG/SCF, INTERACTION WITH KITLG/SCF, SUBUNIT, DISULFIDE BONDS, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, MUTAGENESIS OF ARG-381 AND GLU-386, GLYCOSYLATION AT ASN-130; ASN-283; ASN-293; ASN-300; ASN-320; ASN-352 AND ASN-367.
[40]"KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients."
Gajiwala K.S., Wu J.C., Christensen J., Deshmukh G.D., Diehl W., DiNitto J.P., English J.M., Greig M.J., He Y.A., Jacques S.L., Lunney E.A., McTigue M., Molina D., Quenzer T., Wells P.A., Yu X., Zhang Y., Zou A. expand/collapse author list , Emmett M.R., Marshall A.G., Zhang H.M., Demetri G.D.
Proc. Natl. Acad. Sci. U.S.A. 106:1542-1547(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 544-935 IN COMPLEX WITH SUNITINIB, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, CHARACTERIZATION OF VARIANTS HIS-816 AND VAL-816, ENZYME REGULATION.
[41]"Structural basis for c-KIT inhibition by the suppressor of cytokine signaling 6 (SOCS6) ubiquitin ligase."
Zadjali F., Pike A.C., Vesterlund M., Sun J., Wu C., Li S.S., Ronnstrand L., Knapp S., Bullock A.N., Flores-Morales A.
J. Biol. Chem. 286:480-490(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 564-574 IN COMPLEX WITH SOCS6, PHOSPHORYLATION AT TYR-568.
[42]"Human piebald trait resulting from a dominant negative mutant allele of the c-kit membrane receptor gene."
Fleischman R.A.
J. Clin. Invest. 89:1713-1717(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PBT LYS-583.
[43]"Dominant negative and loss of function mutations of the c-kit (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism."
Spritz R.A., Giebel L.B., Holmes S.A.
Am. J. Hum. Genet. 50:261-269(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PBT LEU-584.
[44]"Mutation of the KIT (mast/stem cell growth factor receptor) protooncogene in human piebaldism."
Giebel L.B., Spritz R.A.
Proc. Natl. Acad. Sci. U.S.A. 88:8696-8699(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PBT ARG-664.
[45]"Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product."
Furitsu T., Tsujimura T., Tono T., Ikeda H., Kitayama H., Koshimizu U., Sugahara H., Butterfield J.H., Ashman L.K., Kanayama Y., Matsuzawa Y., Kitamura Y., Kanakura Y.
J. Clin. Invest. 92:1736-1744(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MAST CELL LEUKEMIA VAL-816.
[46]"Novel mutations of the KIT (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism."
Spritz R.A., Holmes S.A., Itin P., Kuester W.
J. Invest. Dermatol. 101:22-25(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PBT GLY-791 AND VAL-812.
[47]"A 12-bp deletion (7818del12) in the c-kit protooncogene in a large Italian kindred with piebaldism."
Riva P., Milani N., Gandolfi P., Larizza L.
Hum. Mutat. 6:343-345(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PBT 893-GLU--PRO-896 DEL.
[48]"A new c-kit mutation in a case of aggressive mast cell disease."
Pignon J.-M., Giraudier S., Duquesnoy P., Jouault H., Imbert M., Vainchenker W., Vernant J.-P., Tulliez M.
Br. J. Haematol. 96:374-376(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MAST CELL DISEASE GLY-820.
[49]"Piebaldism with deafness: molecular evidence for an expanded syndrome."
Spritz R.A., Beighton P.
Am. J. Med. Genet. 75:101-103(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PBT GLY-796.
[50]"c-kit activating mutations and mast cell proliferation in human leukemia."
Beghini A., Larizza L., Cairoli R., Morra E.
Blood 92:701-702(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ACUTE MYELOID LEUKEMIA TYR-816.
[51]"A novel KIT gene missense mutation in a Japanese family with piebaldism."
Nomura K., Hatayama I., Narita T., Kaneko T., Shiraishi M.
J. Invest. Dermatol. 111:337-338(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PBT PRO-847.
[52]"Familial gastrointestinal stromal tumours with germline mutation of the KIT gene."
Nishida T., Hirota S., Taniguchi M., Hashimoto K., Isozaki K., Nakamura H., Kanakura Y., Tanaka T., Takabayashi A., Matsuda H., Kitamura Y.
Nat. Genet. 19:323-324(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GIST VAL-559 DEL.
[53]"Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors."
Hirota S., Isozaki K., Moriyama Y., Hashimoto K., Nishida T., Ishiguro S., Kawano K., Hanada M., Kurata A., Takeda M., Muhammad Tunio G., Matsuzawa Y., Kanakura Y., Shinomura Y., Kitamura Y.
Science 279:577-580(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GIST ILE-550; 550-LYS--LYS-558 DEL; 551-PRO--VAL-555 DEL; ASP-559 AND 559-VAL-VAL-560 DEL.
[54]"Activating c-kit gene mutations in human germ cell tumors."
Tian Q., Frierson H.F. Jr., Krystal G.W., Moskaluk C.A.
Am. J. Pathol. 154:1643-1647(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HIS-816, CHARACTERIZATION OF VARIANT HIS-816.
[55]"Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis."
Longley B.J. Jr., Metcalfe D.D., Tharp M., Wang X., Tyrrell L., Lu S.-Z., Heitjan D., Ma Y.
Proc. Natl. Acad. Sci. U.S.A. 96:1609-1614(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MASTOCYTOSIS VAL-816; PHE-816; TYR-816 AND LYS-839, CHARACTERIZATION OF VARIANTS MASTOCYTOSIS VAL-816; PHE-816; TYR-816 AND LYS-839.
[56]"Three novel mutations of the proto-oncogene KIT cause human piebaldism."
Syrris P., Malik N.M., Murday V.A., Patton M.A., Carter N.D., Hughes H.E., Metcalfe K.
Am. J. Med. Genet. 95:79-81(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PBT CYS-584; ARG-601 AND PRO-656.
[57]"Germline mutation in the juxtamembrane domain of the kit gene in a family with gastrointestinal stromal tumors and urticaria pigmentosa."
Beghini A., Tibiletti M.G., Roversi G., Chiaravalli A.M., Serio G., Capella C., Larizza L.
Cancer 92:657-662(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GIST ALA-559.
[58]"A mutation-created novel intra-exonic pre-mRNA splice site causes constitutive activation of KIT in human gastrointestinal stromal tumors."
Chen L.L., Sabripour M., Wu E.F., Prieto V.G., Fuller G.N., Frazier M.L.
Oncogene 24:4271-4280(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GIST 550-LYS--LYS-558 DEL.
[59]"Sequence analysis of the protein kinase gene family in human testicular germ-cell tumors of adolescents and adults."
Bignell G., Smith R., Hunter C., Stephens P., Davies H., Greenman C., Teague J., Butler A., Edkins S., Stevens C., O'meara S., Parker A., Avis T., Barthorpe S., Brackenbury L., Buck G., Clements J., Cole J. expand/collapse author list , Dicks E., Edwards K., Forbes S., Gorton M., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jones D., Kosmidou V., Laman R., Lugg R., Menzies A., Perry J., Petty R., Raine K., Shepherd R., Small A., Solomon H., Stephens Y., Tofts C., Varian J., Webb A., West S., Widaa S., Yates A., Gillis A.J.M., Stoop H.J., van Gurp R.J.H.L.M., Oosterhuis J.W., Looijenga L.H.J., Futreal P.A., Wooster R., Stratton M.R.
Genes Chromosomes Cancer 45:42-46(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS TYR-816; LYS-822 AND PRO-829.
[60]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ILE-532; LEU-541; SER-691; ASN-715; ASN-737; TRP-804; TYR-816; LYS-822 AND PRO-829.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X06182 mRNA. Translation: CAA29548.1.
X69301 expand/collapse EMBL AC list , 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.
PIRTVHUKT. S01426.
RefSeqNP_000213.1. NM_000222.2.
NP_001087241.1. NM_001093772.1.
UniGeneHs.479754.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1PKGX-ray2.90A/B549-931[»]
1QZJmodel-A576-932[»]
1QZKmodel-A576-932[»]
1R01model-A576-932[»]
1T45X-ray1.90A547-935[»]
1T46X-ray1.60A565-935[»]
2E9WX-ray3.50A/B26-514[»]
2EC8X-ray3.00A1-519[»]
2VIFX-ray1.45P564-574[»]
3G0EX-ray1.60A544-935[»]
3G0FX-ray2.60A/B544-935[»]
4HVSX-ray1.90A551-934[»]
4K94X-ray2.40C308-518[»]
4K9EX-ray2.70C308-518[»]
ProteinModelPortalP10721.
SMRP10721. Positions 33-507, 547-931.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110015. 41 interactions.
DIPDIP-1055N.
IntActP10721. 12 interactions.
MINTMINT-146746.
STRING9606.ENSP00000288135.

Chemistry

BindingDBP10721.
ChEMBLCHEMBL1936.
DrugBankDB01254. Dasatinib.
DB00619. Imatinib.
DB00398. Sorafenib.
DB01268. Sunitinib.
GuidetoPHARMACOLOGY1805.

PTM databases

PhosphoSiteP10721.

Polymorphism databases

DMDM125472.

Proteomic databases

PaxDbP10721.
PRIDEP10721.

Protocols and materials databases

DNASU3815.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000288135; ENSP00000288135; ENSG00000157404. [P10721-1]
ENST00000412167; ENSP00000390987; ENSG00000157404. [P10721-2]
GeneID3815.
KEGGhsa:3815.
UCSCuc010igr.3. human. [P10721-1]
uc010igs.3. human. [P10721-2]

Organism-specific databases

CTD3815.
GeneCardsGC04P055524.
HGNCHGNC:6342. KIT.
HPACAB003288.
HPA004471.
MIM164920. gene.
172800. phenotype.
273300. phenotype.
601626. phenotype.
606764. phenotype.
neXtProtNX_P10721.
Orphanet98834. Acute myeloblastic leukemia with maturation.
98829. 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.
98850. Aggressive systemic mastocytosis.
158799. Aleukemic mast cell leukemia.
280785. Bullous diffuse cutaneous mastocytosis.
158796. Classic mast cell leukemia.
79455. Cutaneous mastocytoma.
44890. Gastrointestinal stromal tumor.
98848. Indolent systemic mastocytosis.
79457. Maculopapular cutaneous mastocytosis.
2884. Piebaldism.
280794. Pseudoxanthomatous diffuse cutaneous mastocytosis.
98849. Systemic mastocytosis with an associated clonal hematologic non-mast cell lineage disease.
90389. Telangiectasia macularis eruptiva perstans.
PharmGKBPA30128.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000112008.
HOVERGENHBG104348.
InParanoidP10721.
KOK05091.
OMAYFCPGTE.
OrthoDBEOG7S7SCZ.
PhylomeDBP10721.
TreeFamTF325768.

Enzyme and pathway databases

BRENDA2.7.10.1. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.
SignaLinkP10721.

Gene expression databases

ArrayExpressP10721.
BgeeP10721.
CleanExHS_KIT.
GenevestigatorP10721.

Family and domain databases

Gene3D2.60.40.10. 5 hits.
InterProIPR007110. 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]
PfamPF00047. ig. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFPIRSF500951. SCGF_recepter. 1 hit.
PIRSF000615. TyrPK_CSF1-R. 1 hit.
SMARTSM00409. IG. 1 hit.
SM00408. IGc2. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 2 hits.
PROSITEPS50835. 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.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP10721.
GeneWikiCD117.
GenomeRNAi3815.
NextBio14995.
PROP10721.
SOURCESearch...

Entry information

Entry nameKIT_HUMAN
AccessionPrimary (citable) accession number: P10721
Secondary accession number(s): B5A956 expand/collapse secondary AC list , D5LXN2, D5M931, F5H8F8, Q6IQ28, Q99662, Q9UM99
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: April 16, 2014
This is version 177 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries