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  Domain Name: PTKc_HER4
Catalytic domain of the Protein Tyrosine Kinase, HER4. Protein Tyrosine Kinase (PTK) family; HER4 (ErbB4); 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. HER4 is a member of the EGFR (HER, ErbB) subfamily of proteins, which 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, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands that bind HER4 fall into two groups, the neuregulins (or heregulins) and some EGFR (HER1) ligands including betacellulin, HBEGF, and epiregulin. All four neuregulins (NRG1-4) interact with HER4. Upon ligand binding, HER4 forms homo- or heterodimers with other HER proteins. HER4 is essential in embryonic development. It is implicated in mammary gland, cardiac, and neural development. As a postsynaptic receptor of NRG1, HER4 plays an important role in synaptic plasticity and maturation. The impairment of NRG1/HER4 signaling may contribute to schizophrenia.
No pairwise interactions are available for this conserved domain.

Total Mutations Found: 569
Total Disease Mutations Found: 319
This domain occurred 256 times on human genes (592 proteins).



  ADENOCARCINOMA OF LUNG, RESPONSE TO TYROS
  ADENOCARCINOMA OF LUNG, SOMATIC
  AMYOTROPHIC LATERAL SCLEROSIS 19
  AORTIC ANEURYSM, FAMILIAL THORACIC 7
  BASAL GANGLIA CALCIFICATION, IDIOPATHIC, 4
  BLADDER CANCER, SOMATIC, INCLUDED
  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, SOMATIC
  COLORECTAL CANCER, SOMATIC
  COLORECTAL CANCER, SOMATIC, INCLUDED;;
  CROUZON SYNDROME
  DEFICIENCY
  DIABETES MELLITUS, INSULIN-RESISTANT, WITH ACANTHOSIS NIGRICANS
  DIABETES MELLITUS, NONINSULIN-DEPENDENT
  FG SYNDROME 4
  GASTRIC CANCER, SOMATIC
  GASTROINTESTINAL STROMAL TUMOR, FAMILIAL
  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
  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
  MALFORMATIONS
  MAST CELL DISEASE, SYSTEMIC
  MAST CELL LEUKEMIA
  MASTOCYTOSIS WITH ASSOCIATED HEMATOLOGIC DISORDER, INCLUDED;;
  MASTOCYTOSIS, ADULT SPORADIC, INCLUDE
  MASTOCYTOSIS, SPORADIC, CHILDHOOD-ONSET
  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;;
  MYASTHENIC SYNDROME, CONGENITAL, ASSOCIATED WITH ACETYLCHOLINE RECEPTOR
  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
  OVARIAN CANCER, SOMATIC
  PARKINSON DISEASE 8, AUTOSOMAL DOMINANT
  PFEIFFER SYNDROME
  PHEOCHROMOCYTOMA, INCLUDED
  PHEOCHROMOCYTOMA, SOMATIC, IN
  PIEBALDISM
  PIEBALDISM WITH SENSORINEURAL DEAFNESS
  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
  SADDAN DYSPLASIA
  SCAPHOCEPHALY, MAXILLARY RETRUSION, AND MENTAL RETARDATION, INCLUDED
  SELECTIVE T-CELL DEFECT
  SHORT RIB-POLYDACTYLY SYNDROME 2A (SRPS2A)
  SHORT RIB-POLYDACTYLY SYNDROME, TYPE IIA
  SOMATIC
  SPERMATOCYTIC SEMINOMA, SOMATIC, INCLUDED
  SPONDYLOMETAEPIPHYSEAL DYSPLASIA, SHORT LIMB-HAND TYPE
  T-CELL IMMUNODEFICIENCY, RECURRENT INFECTIONS, AUTOIMMUNITY, AND CARDIAC
  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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