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  Domain Name: PTKc_Kit
Catalytic domain of the Protein Tyrosine Kinase, Kit. Protein Tyrosine Kinase (PTK) family; Kit (or c-Kit); catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Kit is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor tyr kinases (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of Kit to its ligand, the stem-cell factor (SCF), leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. Kit signaling is involved in major cellular functions including cell survival, proliferation, differentiation, adhesion, and chemotaxis. Mutations in Kit, which result in constitutive ligand-independent activation, are found in human cancers such as gastrointestinal stromal tumor (GIST) and testicular germ cell tumor (TGCT). The aberrant expression of Kit and/or SCF is associated with other tumor types such as systemic mastocytosis and cancers of the breast, neurons, lung, prostate, colon, and rectum. Although the structure of the human Kit catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence.
No pairwise interactions are available for this conserved domain.

Total Mutations Found: 471
Total Disease Mutations Found: 314
This domain occurred 116 times on human genes (285 proteins).



  ADENOCARCINOMA OF LUNG, RESPONSE TO TYROS
  ADENOCARCINOMA OF LUNG, SOMATIC
  AMYOTROPHIC LATERAL SCLEROSIS 19
  BASAL GANGLIA CALCIFICATION, IDIOPATHIC, 4
  BLADDER CANCER, SOMATIC, INCLUDED
  CAMPTODACTYLY, TALL STATURE, AND HEARING LOSS SYNDROME
  CARDIOFACIOCUTANEOUS SYNDROME 1
  CATARACT 6, AGE-RELATED CORTICAL
  CHRONIC MYELOID LEUKEMIA, RESISTANT TO IMATINIB
  COLON CANCER, SOMATIC
  COLORECTAL CANCER, SOMATIC
  COLORECTAL CANCER, SOMATIC, INCLUDED;;
  CROUZON SYNDROME
  DEFICIENCY
  DIABETES MELLITUS, INSULIN-RESISTANT, WITH ACANTHOSIS NIGRICANS
  DIABETES MELLITUS, NONINSULIN-DEPENDENT
  FIBRODYSPLASIA OSSIFICANS PROGRESSIVA
  GASTRIC CANCER, SOMATIC
  GASTROINTESTINAL STROMAL TUMOR, FAMILIAL
  GASTROINTESTINAL STROMAL TUMOR, FAMILIAL, INCLUDED
  GASTROINTESTINAL STROMAL TUMOR, SOMATIC
  GERM CELL TUMOR, SOMATIC
  GLIOBLASTOMA, SOMATIC
  HARTSFIELD SYNDROME
  HEMANGIOMA, CAPILLARY INFANTILE, SOMATIC
  HEPATOCELLULAR CARCINOMA, CHILDHOOD TYPE, SOMATIC
  HIRSCHSPRUNG DISEASE, SUSCEPTIBILITY TO, 1
  HYPEREOSINOPHILIC SYNDROME, IDIOPATHIC, RESISTANT TO IMATINIB
  HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 5
  HYPOCHONDROPLASIA
  HYPOGONADOTROPIC HYPOGONADISM 2 WITH ANOSMIA
  HYPOGONADOTROPIC HYPOGONADISM 2 WITH ANOSMIA, SUSCEPTIBILITY TO
  HYPOGONADOTROPIC HYPOGONADISM 2 WITH OR WITHOUT ANOSMIA, SUSCEPTIBILITY
  HYPOGONADOTROPIC HYPOGONADISM 2 WITHOUT ANOSMIA
  HYPOGONADOTROPIC HYPOGONADISM 2 WITHOUT ANOSMIA, SUSCEPTIBILITY TO
  IN
  INSENSITIVITY TO PAIN, CONGENITAL, WITH ANHIDROSIS
  INSULIN RESISTANCE
  INSULIN RESISTANCE, INCLUDED
  IRAK4 DEFICIENCY
  LADD SYNDROME
  LEUKEMIA, ACUTE LYMPHOBLASTIC, SOMATIC, INCLUDED
  LEUKEMIA, ACUTE MYELOID
  LEUKEMIA, ACUTE MYELOID, SOMATIC
  LEUKEMIA, PHILADELPHIA CHROMOSOME-POSITIVE, RESISTANT TO IMATINIB
  LYMPHEDEMA, HEREDITARY, I
  LYMPHEDEMA, HEREDITARY, IA
  LYMPHOMA, NON-HODGKIN, SOMATIC
  LYMPHOPROLIFERATIVE SYNDROME 1
  MAST CELL DISEASE, SYSTEMIC
  MAST CELL LEUKEMIA
  MASTOCYTOSIS WITH ASSOCIATED HEMATOLOGIC DISORDER, INCLUDED;;
  MASTOCYTOSIS, ADULT SPORADIC, INCLUDE
  MASTOCYTOSIS, SPORADIC, CHILDHOOD-ONSET
  MECONIUM ILEUS
  MELANOMA, MALIGNANT, SOMATIC
  MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIA
  MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIB
  MULTIPLE MYELOMA, SOMATIC, INCLUDED;;
  MYASTHENIC SYNDROME, CONGENITAL, ASSOCIATED WITH ACETYLCHOLINE RECEPTOR
  MYOFIBROMATOSIS, INFANTILE, 1
  NEUROBLASTOMA, SUSCEPTIBILITY TO, 3
  NONSMALL CELL LUNG CANCER, RESISTANCE TO TYROSINE KINASE INHIBITOR
  NONSMALL CELL LUNG CANCER, RESPONSE TO TYROSINE KINASE INHIBITOR IN,
  NOONAN SYNDROME 7
  OBESITY, HYPERPHAGIA, AND DEVELOPMENTAL DELAY
  OVARIAN CANCER, SOMATIC
  PFEIFFER SYNDROME
  PHEOCHROMOCYTOMA, INCLUDED
  PHEOCHROMOCYTOMA, SOMATIC, IN
  PIEBALDISM
  PIEBALDISM WITH SENSORINEURAL DEAFNESS
  PIEBALDISM, PROGRESSIVE
  PROSTATE CANCER, PROGRESSION AND METASTASIS OF
  RABSON-MENDENHALL SYNDROME
  RENAL AGENESIS
  RENAL CELL CARCINOMA, PAPILLARY, 1
  RENAL CELL CARCINOMA, PAPILLARY, 1, SOMATIC
  RETINITIS PIGMENTOSA 38
  SADDAN DYSPLASIA
  SCAPHOCEPHALY, MAXILLARY RETRUSION, AND MENTAL RETARDATION, INCLUDED
  SELECTIVE T-CELL DEFECT
  SOMATIC
  SPERMATOCYTIC SEMINOMA, SOMATIC, INCLUDED
  SPONDYLOMETAEPIPHYSEAL DYSPLASIA, SHORT LIMB-HAND TYPE
  THANATOPHORIC DYSPLASIA, TYPE I
  THANATOPHORIC DYSPLASIA, TYPE I, INCLUDED
  THANATOPHORIC DYSPLASIA, TYPE II
  THYROID CARCINOMA, FAMILIAL MEDULLARY
  THYROID CARCINOMA, FAMILIAL MEDULLARY, INCLUDED
  THYROID CARCINOMA, FOLLICULAR, SOMATIC, INCLUDED
  THYROID CARCINOMA, PAPILLARY, SOMATIC, INCLUDED;;|
  THYROID CARCINOMA, SPORADIC MEDULLARY, INCLUDED;;
  TO
  VENOUS MALFORMATIONS, MULTIPLE CUTANEOUS AND MUCOSAL


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Range on the Protein:  

   Protein ID            Protein Position

Domain Position:  


Feature Name:Total Found:
active site
ATP binding site
substrate binding site
activation loop (A-loop)


















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Please Cite: Peterson, T.A., Adadey, A., Santana-Cruz ,I., Sun, Y., Winder A, Kann, M.G., (2010) DMDM: Domain Mapping of Disease Mutations. Bioinformatics 26 (19), 2458-2459.

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