KIT_HUMAN
Source:
BD_CD
Marked as 'Integral membrane protein'
Confidence:
high (a blood group or CD marker)
Search PubMed for
(RBC AND this entry)
Gene names:
KIT
, SCFR
Protein names and data:
KIT_HUMAN
, Mast/stem cell growth factor receptor Kit; SCFR; 2.7.10.1
, Piebald trait protein; PBT; Proto-oncogene c-Kit; Tyrosine-protein kinase Kit; p145 c-kit; v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog; CD117; Flags: Precursor
Lenght: 976 a.a.
Mass: 109865 Da
fasta formatted sequence
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.
Catalytic activity:
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Disease:
( OMIM:
164920
172800
273300
601626
606764
)
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. 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. 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. 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.
Cellular location:
Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Cell membrane; Single-pass type I membrane protein. Isoform 3: Cytoplasm. Note=Detected in the cytoplasm of spermatozoa, especially in the equatorial and subacrosomal region of the sperm head.
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.
Genetic variants
532 - 532
V -> I (in dbSNP:rs55792975). VAR_042021
55792975
541 - 541
M -> L (in dbSNP:rs3822214). VAR_042022
3822214
541 - 541
M -> V (in dbSNP:rs3822214). VAR_061289
3822214
550 - 558
Missing (in GIST; somatic mutation). VAR_033124
550 - 550
K -> I (in GIST; somatic mutation; dbSNP:rs28933968). VAR_033123
28933968
551 - 555
Missing (in GIST; somatic mutation). VAR_033125
559 - 560
Missing (in GIST; somatic mutation). VAR_033128
559 - 559
V -> A (in GIST). VAR_033126
559 - 559
V -> D (in GIST; somatic mutation). VAR_033127
559 - 559
Missing (in GIST). VAR_007965
583 - 583
E -> K (in PBT). VAR_004104
584 - 584
F -> C (in PBT; dbSNP:rs28933371). VAR_033129
28933371
584 - 584
F -> L (in PBT). VAR_004105
601 - 601
G -> R (in PBT). VAR_033130
656 - 656
L -> P (in PBT). VAR_033131
664 - 664
G -> R (in PBT). VAR_004106
691 - 691
C -> S (in dbSNP:rs35200131). VAR_042023
35200131
715 - 715
S -> N (in dbSNP:rs56094246). VAR_042024
56094246
737 - 737
D -> N (in a colorectal adenocarcinoma sample; somatic mutation). VAR_042025
791 - 791
R -> G (in PBT). VAR_004107
796 - 796
R -> G (in PBT; with sensorineural deafness). VAR_033132
804 - 804
R -> W (in a colorectal adenocarcinoma sample; somatic mutation). VAR_042026
812 - 812
G -> V (in PBT). VAR_004108
816 - 816
D -> F (in mastocytosis; requires 2 nucleotide substitutions; somatic mutation; constitutively activated and is much more rapidly autophosphorylated than wild type). VAR_033133
816 - 816
D -> H (in a testicular tumor; seminoma; somatic mutation; constitutively activated; dbSNP:rs28933969). VAR_033134
28933969
816 - 816
D -> V (in mast cell leukemia and mastocytosis; somatic mutation; constitutively activated; loss of interaction with MPDZ). VAR_004109
816 - 816
D -> Y (in acute myeloid leukemia, mastocytosis and a germ cell tumor of the testis; somatic mutation; constitutively activated). VAR_023828
820 - 820
D -> G (in mast cell disease; systemic). VAR_033135
822 - 822
N -> K (in a germ cell tumor of the testis; somatic mutation). VAR_023829
829 - 829
A -> P (in a germ cell tumor of the testis; somatic mutation). VAR_023830
839 - 839
E -> K (in mastocytosis; somatic mutation; dominant negative mutation; loss of autophosphorylation). VAR_033136
847 - 847
T -> P (in PBT). VAR_033137
893 - 896
Missing (in PBT; severe). VAR_004110
Database cross-references
UniProt:
P10721
Ensembl:
ENST00000288135
Ensembl:
ENST00000412167
MIM:
164920
MIM:
172800
MIM:
273300
MIM:
601626
MIM:
606764
neXtProt:
NX_P10721
Antibodypedia:
P10721
(may not find the protein thus also not any antibody)
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