Home News About DMDM Database Statistics Research Publications Contact  

 
  Domain Name: PTKc_EGFR_like
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases. Protein Tyrosine Kinase (PTK) family; Epidermal Growth Factor Receptor (EGFR) subfamily; catalytic (c) domain. EGFR (HER, ErbB) subfamily members include EGFR (HER1, ErbB1), HER2 (ErbB2), HER3 (ErbB3), HER4 (ErbB4), and similar proteins. 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. The EGFR proteins are receptor tyr kinases (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other tyr kinases, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, resulting in the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Collectively, they can recognize a variety of ligands including EGF, TGFalpha, and neuregulins, among others. All four subfamily members can form homo- or heterodimers. HER3 contains an impaired kinase domain and depends on its heterodimerization partner for activation. EGFR subfamily members are involved in signaling pathways leading to a broad range of cellular responses including cell proliferation, differentiation, migration, growth inhibition, and apoptosis. Gain of function alterations, through their overexpression, deletions, or point mutations in their kinase domains, have been implicated in various cancers. These receptors are targets of many small molecule inhibitors and monoclonal antibodies used in cancer therapy.
No pairwise interactions are available for this conserved domain.

Total Mutations Found: 845
Total Disease Mutations Found: 442
This domain occurred 368 times on human genes (846 proteins).



  ADENOCARCINOMA OF LUNG, RESPONSE TO TYROS
  ADENOCARCINOMA OF LUNG, SOMATIC
  AMYOTROPHIC LATERAL SCLEROSIS 19
  AORTIC ANEURYSM, FAMILIAL THORACIC 7
  B CELL-POSITIVE, NK CELL-NEGATIVE
  BASAL GANGLIA CALCIFICATION, IDIOPATHIC, 4
  BLADDER CANCER, SOMATIC, INCLUDED
  BRACHYDACTYLY, TYPE A2
  BREAST CANCER, SUSCEPTIBILITY TO
  CAMPTODACTYLY, TALL STATURE, AND HEARING LOSS SYNDROME
  CARDIOFACIOCUTANEOUS SYNDROME 1
  CARDIOFACIOCUTANEOUS SYNDROME 3
  CARDIOFACIOCUTANEOUS SYNDROME 4
  CATARACT 6, AGE-RELATED CORTICAL
  CHRONIC MYELOID LEUKEMIA, RESISTANT TO IMATINIB
  COFFIN-LOWRY SYNDROME
  COFFIN-LOWRY SYNDROME, MILD
  COLON CANCER, HEREDITARY NONPOLYPOSIS, TYPE 6, SOMATIC, INCLUDED
  COLON CANCER, SOMATIC
  COLORECTAL CANCER, HEREDITARY NONPOLYPOSIS, TYPE 6
  COLORECTAL CANCER, SOMATIC
  COLORECTAL CANCER, SOMATIC, INCLUDED;;
  CROUZON SYNDROME
  DEFICIENCY
  DIABETES MELLITUS, INSULIN-RESISTANT, WITH ACANTHOSIS NIGRICANS
  DIABETES MELLITUS, NONINSULIN-DEPENDENT
  DIABETES MELLITUS, TYPE II
  ENDOCRINE-CEREBROOSTEODYSPLASIA (ECO)
  EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
  EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2 (EIEE2)
  ESOPHAGEAL CANCER, SOMATIC
  FG SYNDROME 4
  FIBRODYSPLASIA OSSIFICANS PROGRESSIVA
  GASTRIC CANCER, SOMATIC
  GASTROINTESTINAL STROMAL TUMOR, FAMILIAL
  GASTROINTESTINAL STROMAL TUMOR, SOMATIC
  GERM CELL TUMOR, SOMATIC
  GLIOBLASTOMA, SOMATIC
  GLYCOGEN STORAGE DISEASE 9C (GSD9C)
  GLYCOGEN STORAGE DISEASE IXC
  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
  JUVENILE POLYPOSIS SYNDROME
  LADD SYNDROME
  LEUKEMIA, ACUTE LYMPHOBLASTIC, SOMATIC, INCLUDED
  LEUKEMIA, ACUTE MYELOID
  LEUKEMIA, ACUTE MYELOID, SOMATIC
  LEUKEMIA, PHILADELPHIA CHROMOSOME-POSITIVE, RESISTANT TO IMATINIB
  LOEYS-DIETZ SYNDROME, TYPE 1A
  LOEYS-DIETZ SYNDROME, TYPE 1B
  LOEYS-DIETZ SYNDROME, TYPE 1B, INCLUDED
  LOEYS-DIETZ SYNDROME, TYPE 2A
  LOEYS-DIETZ SYNDROME, TYPE 2A, INCLUDED
  LOEYS-DIETZ SYNDROME, TYPE 2B
  LYMPHEDEMA, HEREDITARY, I
  LYMPHEDEMA, HEREDITARY, IA
  LYMPHOMA, NON-HODGKIN, SOMATIC
  LYMPHOPROLIFERATIVE SYNDROME 1
  MALFORMATIONS
  MAST CELL DISEASE, SYSTEMIC
  MAST CELL LEUKEMIA
  MASTOCYTOSIS WITH ASSOCIATED HEMATOLOGIC DISORDER, INCLUDED;;
  MASTOCYTOSIS, ADULT SPORADIC, INCLUDE
  MASTOCYTOSIS, SPORADIC, CHILDHOOD-ONSET
  MEGALENCEPHALY-POLYMICROGYRIA-POLYDACTYLY-HYDROCEPHALUS SYNDROME
  MELANOMA, MALIGNANT, SOMATIC
  MENTAL RETARDATION AND MICROCEPHALY WITH PONTINE AND CEREBELLAR HYPOPLASIA
  MENTAL RETARDATION AND MICROCEPHALY WITH PONTINE AND CEREBELLAR HYPOPLASIA (MICPCH)
  MENTAL RETARDATION, X-LINKED 19
  MENTAL RETARDATION, X-LINKED 30
  MENTAL RETARDATION, X-LINKED, WITH NYSTAGMUS
  MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIA
  MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIB
  MULTIPLE MYELOMA, SOMATIC, INCLUDED;;
  MULTIPLE SELF-HEALING SQUAMOUS EPITHELIOMA, SUSCEPTIBILITY TO
  MYASTHENIC SYNDROME, CONGENITAL, ASSOCIATED WITH ACETYLCHOLINE RECEPTOR
  MYOFIBROMATOSIS, INFANTILE, 1
  NEPHRONOPHTHISIS 9 (NPHP9)
  NEUROBLASTOMA, SUSCEPTIBILITY TO, 3
  NEUROPATHY, HEREDITARY SENSORY, TYPE II
  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
  OGUCHI DISEASE 2
  PARKINSON DISEASE 8, AUTOSOMAL DOMINANT
  PEUTZ-JEGHERS SYNDROME
  PFEIFFER SYNDROME
  PHEOCHROMOCYTOMA, INCLUDED
  PHEOCHROMOCYTOMA, SOMATIC, IN
  PIEBALDISM
  PIEBALDISM WITH SENSORINEURAL DEAFNESS
  PIEBALDISM, PROGRESSIVE
  PROSTATE CANCER, PROGRESSION AND METASTASIS OF
  PULMONARY HYPERTENSION, PRIMARY, 1
  PULMONARY HYPERTENSION, PRIMARY, 1, WITH HEREDITARY HEMORRHAGIC TELANGIECTASIA
  PULMONARY HYPERTENSION, PRIMARY, DEXFENFLURAMINE-ASSOCIATED, INCLUDED
  PULMONARY VENOOCCLUSIVE DISEASE
  RENAL AGENESIS
  RENAL CELL CARCINOMA, PAPILLARY, 1
  RENAL CELL CARCINOMA, PAPILLARY, 1, SOMATIC
  RETINITIS PIGMENTOSA 38
  RETINITIS PIGMENTOSA 62
  RETINITIS PIGMENTOSA 62 (RP62)
  SADDAN DYSPLASIA
  SCAPHOCEPHALY, MAXILLARY RETRUSION, AND MENTAL RETARDATION, INCLUDED
  SELECTIVE T-CELL DEFECT
  SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE,
  SHORT RIB-POLYDACTYLY SYNDROME 2A (SRPS2A)
  SHORT RIB-POLYDACTYLY SYNDROME, TYPE IIA
  SOMATIC
  SPERMATOCYTIC SEMINOMA, SOMATIC, INCLUDED
  SPERMATOGENIC FAILURE 5
  SPINOCEREBELLAR ATAXIA 14
  SPONDYLOMETAEPIPHYSEAL DYSPLASIA, SHORT LIMB-HAND TYPE
  T-CELL IMMUNODEFICIENCY, RECURRENT INFECTIONS, AUTOIMMUNITY, AND CARDIAC
  TESTICULAR TUMOR, SOMATIC
  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
  VARIANT OF UNKNOWN SIGNIFICANCE
  VENOUS MALFORMATIONS, MULTIPLE CUTANEOUS AND MUCOSAL


Tips:
 If you've navigated here from a protein, hovering over a position on the weblogo will display the corresponding protein position for that domain position.

 The histograms below the weblogo indicate mutations found on the domain. Red is for disease (OMIM) and blue is for SNPs.

 Functional Features are displayed as orange boxes under the histograms. You can choose which features are displayed in the box below.



Range on the Protein:  

   Protein ID            Protein Position