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  Domain Name: STKc_MAPK15
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15. Serine/Threonine Kinases (STKs), Mitogen-Activated Protein Kinase 15 (MAPK15) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MAPK15 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. MAPKs are important mediators of cellular responses to extracellular signals. Human MAPK15 is also called Extracellular signal Regulated Kinase 8 (ERK8) while the rat protein is called ERK7. ERK7 and ERK8 display both similar and different biochemical properties. They autophosphorylate and activate themselves and do not require upstream activating kinases. ERK7 is constitutively active and is not affected by extracellular stimuli whereas ERK8 shows low basal activity and is activated by DNA-damaging agents. ERK7 and ERK8 also have different substrate profiles. Genome analysis shows that they are orthologs with similar gene structures. ERK7 and ERK 8 may be involved in the signaling of some nuclear receptor transcription factors. ERK7 regulates hormone-dependent degradation of estrogen receptor alpha while ERK8 down-regulates the transcriptional co-activation androgen and glucocorticoid receptors.
No pairwise interactions are available for this conserved domain.

Total Mutations Found: 651
Total Disease Mutations Found: 279
This domain occurred 367 times on human genes (854 proteins).



  ADENOCARCINOMA OF LUNG, SOMATIC
  AMYOTROPHIC LATERAL SCLEROSIS 19
  AORTIC ANEURYSM, FAMILIAL THORACIC 7
  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
  COLON CANCER, SOMATIC
  COLORECTAL CANCER, SOMATIC
  COLORECTAL CANCER, SOMATIC, INCLUDED;;
  COWDEN DISEASE 6
  CROUZON SYNDROME
  DEFICIENCY
  DIABETES MELLITUS, INSULIN-RESISTANT, WITH ACANTHOSIS NIGRICANS
  DIABETES MELLITUS, NONINSULIN-DEPENDENT
  DIABETES MELLITUS, TYPE II
  ENDOCRINE-CEREBROOSTEODYSPLASIA
  ENDOCRINE-CEREBROOSTEODYSPLASIA (ECO)
  EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
  EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2 (EIEE2)
  FG SYNDROME 4
  GASTROINTESTINAL STROMAL TUMOR, FAMILIAL
  GASTROINTESTINAL STROMAL TUMOR, SOMATIC
  GERM CELL TUMOR, SOMATIC
  GLYCOGEN STORAGE DISEASE IXC
  HARTSFIELD SYNDROME
  HEMANGIOMA, CAPILLARY INFANTILE, SOMATIC
  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
  INSENSITIVITY TO PAIN, CONGENITAL, WITH ANHIDROSIS
  INSULIN RESISTANCE
  INSULIN RESISTANCE, INCLUDED
  IRAK4 DEFICIENCY
  JUVENILE POLYPOSIS SYNDROME
  LADD SYNDROME
  LEUKEMIA, ACUTE MYELOID
  LEUKEMIA, PHILADELPHIA CHROMOSOME-POSITIVE, RESISTANT TO IMATINIB
  LYMPHOMA, NON-HODGKIN, SOMATIC
  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 30
  MENTAL RETARDATION, X-LINKED, WITH NYSTAGMUS
  MULTIPLE MYELOMA, SOMATIC, INCLUDED;;
  MYASTHENIC SYNDROME, CONGENITAL, ASSOCIATED WITH ACETYLCHOLINE RECEPTOR
  NEPHRONOPHTHISIS 9 (NPHP9)
  NEUROPATHY, HEREDITARY SENSORY, TYPE II
  NOONAN SYNDROME 7
  OBESITY, HYPERPHAGIA, AND DEVELOPMENTAL DELAY
  OGUCHI DISEASE 2
  PARKINSON DISEASE 8, AUTOSOMAL DOMINANT
  PEUTZ-JEGHERS SYNDROME
  PFEIFFER SYNDROME
  PIEBALDISM
  PIEBALDISM WITH SENSORINEURAL DEAFNESS
  PROSTATE CANCER, PROGRESSION AND METASTASIS OF
  RETINITIS PIGMENTOSA 62
  RETINITIS PIGMENTOSA 62 (RP62)
  SADDAN DYSPLASIA
  SCAPHOCEPHALY, MAXILLARY RETRUSION, AND MENTAL RETARDATION, INCLUDED
  SHORT RIB-POLYDACTYLY SYNDROME 2A (SRPS2A)
  SHORT RIB-POLYDACTYLY SYNDROME, TYPE IIA
  SPERMATOCYTIC SEMINOMA, SOMATIC, INCLUDED
  SPERMATOGENIC FAILURE 5
  SPINOCEREBELLAR ATAXIA 14
  T-CELL IMMUNODEFICIENCY, RECURRENT INFECTIONS, AUTOIMMUNITY, AND CARDIAC
  TESTICULAR TUMOR, SOMATIC
  THANATOPHORIC DYSPLASIA, TYPE I
  THANATOPHORIC DYSPLASIA, TYPE I, INCLUDED
  THANATOPHORIC DYSPLASIA, TYPE II
  THROMBOCYTOPENIA 2
  THYROID CARCINOMA, FAMILIAL MEDULLARY
  THYROID CARCINOMA, FOLLICULAR, SOMATIC, INCLUDED
  THYROID CARCINOMA, PAPILLARY, SOMATIC, INCLUDED;;|
  TO
  VARIANT OF UNKNOWN SIGNIFICANCE


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