Reviewed, UniProtKB/Swiss-Prot P10721 (KIT_HUMAN)

Names and origin

Protein names

Recommended name:
    Mast/stem cell growth factor receptor
      Short name=SCFR
    EC=2.7.10.1
Alternative name(s):
    Proto-oncogene tyrosine-protein kinase Kit
      Short name=c-kit
    CD_antigen=CD117

Gene names

Name:

KIT

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	976 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	This is the receptor for stem cell factor (mast cell growth factor). It has a tyrosine-protein kinase activity. Binding of the ligands leads to the autophosphorylation of KIT and its association with substrates such as phosphatidylinositol 3-kinase (Pi3K).
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Interacts with APS. Interacts with MPDZ (via the tenth PDZ domain). Interacts with PTPRU.
Subcellular location	Membrane; Single-pass type I membrane protein.
Involvement in disease	Defects in KIT are a cause of piebaldism [MIM:172800]. Piebaldism is an autosomal dominant genetic developmental abnormality of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes. Defects in KIT are a cause of gastrointestinal stromal tumor (GIST) [MIM:606764]. Defects in KIT have been associated with testicular tumors [MIM:273300]. It includes germ cell tumor (GCT) or testicular germ cell tumor (TGCT).
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 component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Proto-oncogene
Domain	Immunoglobulin domain Repeat Signal Transmembrane
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	transmembrane receptor protein tyrosine kinase signaling pathway Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from direct assay. Source: HPA integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from direct assay. Source: HPA
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: IntAct receptor signaling protein tyrosine kinase activity Ref.21 Traceable author statement. Source: ProtInc vascular endothelial growth factor receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
KITLG	P21583	1	EBI-1379503,EBI-1379527

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 25

25

Potential

Chain

26 – 976

951

Mast/stem cell growth factor receptor

PRO_0000016754

Regions

Topological domain

26 – 524

499

Extracellular Potential

Transmembrane

525 – 545

21

Potential

Topological domain

546 – 976

431

Cytoplasmic Potential

Domain

27 – 112

86

Ig-like C2-type 1

Domain

121 – 205

85

Ig-like C2-type 2

Domain

212 – 308

97

Ig-like C2-type 3

Domain

317 – 410

94

Ig-like C2-type 4

Domain

413 – 507

95

Ig-like C2-type 5

Domain

589 – 937

349

Protein kinase

Nucleotide binding

595 – 603

9

ATP By similarity

Sites

Active site

792

1

Proton acceptor By similarity

Binding site

623

1

ATP By similarity

Site

568

1

Interaction with APS

Site

936

1

Interaction with APS

Amino acid modifications

Modified residue

568

1

Phosphotyrosine By similarity

Modified residue

570

1

Phosphotyrosine By similarity

Modified residue

703

1

Phosphotyrosine By similarity

Modified residue

823

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

936

1

Phosphotyrosine

Glycosylation

130

1

N-linked (GlcNAc...)

Glycosylation

145

1

N-linked (GlcNAc...) Potential

Glycosylation

283

1

N-linked (GlcNAc...) Potential

Glycosylation

293

1

N-linked (GlcNAc...) Potential

Glycosylation

300

1

N-linked (GlcNAc...) Potential

Glycosylation

320

1

N-linked (GlcNAc...) Potential

Glycosylation

352

1

N-linked (GlcNAc...) Potential

Glycosylation

367

1

N-linked (GlcNAc...) Potential

Glycosylation

463

1

N-linked (GlcNAc...) Potential

Glycosylation

486

1

N-linked (GlcNAc...) Potential

Disulfide bond

58 ↔ 97

By similarity

Disulfide bond

151 ↔ 183

By similarity

Disulfide bond

233 ↔ 290

By similarity

Disulfide bond

428 ↔ 491

By similarity

Natural variations

Natural variant

532

1

V → I

VAR_042021

Natural variant

541

1

M → L

VAR_042022

Natural variant

550 – 558

9

Missing in GIST; somatic mutation.

VAR_033124

Natural variant

550

1

K → I in GIST; somatic mutation.

VAR_033123

Natural variant

551 – 555

5

Missing in GIST; somatic mutation.

VAR_033125

Natural variant

559 – 560

2

Missing in GIST; somatic mutation.

VAR_033128

Natural variant

559

1

V → A in GIST.

VAR_033126

Natural variant

559

1

V → D in GIST; somatic mutation.

VAR_033127

Natural variant

559

1

Missing in GIST.

VAR_007965

Natural variant

583

1

E → K in piebaldism.

VAR_004104

Natural variant

584

1

F → C in piebaldism.

VAR_033129

Natural variant

584

1

F → L in piebaldism.

VAR_004105

Natural variant

601

1

G → R in piebaldism.

VAR_033130

Natural variant

656

1

L → P in piebaldism.

VAR_033131

Natural variant

664

1

G → R in piebaldism.

VAR_004106

Natural variant

691

1

C → S

VAR_042023

Natural variant

715

1

S → N

VAR_042024

Natural variant

737

1

D → N in a colorectal adenocarcinoma sample; somatic mutation.

VAR_042025

Natural variant

791

1

R → G in piebaldism.

VAR_004107

Natural variant

796

1

R → G in piebaldism; with sensorineural deafness.

VAR_033132

Natural variant

804

1

R → W in a colorectal adenocarcinoma sample; somatic mutation.

VAR_042026

Natural variant

812

1

G → V in piebaldism.

VAR_004108

Natural variant

816

1

D → F in mastocytosis; requires 2 nucleotide substitutions; somatic mutation; constitutively activated.

VAR_033133

Natural variant

816

1

D → H in GCT; somatic mutation; constitutively activated.

VAR_033134

Natural variant

816

1

D → V in mast cell leukemia and mastocytosis; somatic mutation; constitutively activated; loss of interaction with MPDZ.

VAR_004109

Natural variant

816

1

D → Y in acute myeloid leukemia, mastocytosis and TGCT; somatic mutation; constitutively activated.

VAR_023828

Natural variant

820

1

D → G in mast cell disease; systemic.

VAR_033135

Natural variant

822

1

N → K in TGCT; somatic mutation.

VAR_023829

Natural variant

829

1

A → P in TGCT; somatic mutation.

VAR_023830

Natural variant

839

1

E → K in mastocytosis; somatic mutation; dominant negative mutation; loss of autophosphorylation.

VAR_033136

Natural variant

847

1

T → P in piebaldism.

VAR_033137

Natural variant

893 – 896

4

Missing in piebaldism; severe.

VAR_004110

Experimental info

Mutagenesis

571

1

I → A: Reduction in APS binding. Abolishes APS binding; when associated with A-939

Mutagenesis

623

1

K → M: Stronger interaction with MPDZ

Mutagenesis

939

1

L → A: Reduction in APS binding. Abolishes APS binding; when associated with A-571

Secondary structure

1

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976

Helix Strand Turn

Details...

Beta strand

556 – 560

5

Helix

580 – 582

3

Helix

586 – 588

3

Beta strand

589 – 597

9

Beta strand

599 – 613

15

Beta strand

617 – 625

9

Helix

631 – 647

17

Beta strand

656 – 660

5

Beta strand

662 – 665

4

Beta strand

667 – 671

5

Helix

678 – 690

13

Helix

766 – 785

20

Helix

795 – 797

3

Beta strand

798 – 801

4

Helix

802 – 804

3

Beta strand

805 – 808

4