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  Domain Name: STKc_GRK4
Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4. Serine/Threonine Kinases (STKs), G protein-coupled Receptor Kinase (GRK) subfamily, GRK4 isoform, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The GRK 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. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. There are seven types of GRKs, named GRK1 to GRK7. GRK4 has a limited tissue distribution. It is mainly found in the testis, but is also present in the cerebellum and kidney. It is expressed as multiple splice variants with different domain architectures. It is post-translationally palmitoylated and localized in the membrane. GRK4 polymorphisms are associated with hypertension and salt sensitivity, as they cause hyperphosphorylation, desensitization, and internalization of the dopamine 1 (D1) receptor while increasing the expression of the angiotensin II type 1 receptor. GRK4 plays a crucial role in the D1 receptor regulation of sodium excretion and blood pressure.
No pairwise interactions are available for this conserved domain.

Total Mutations Found: 410
Total Disease Mutations Found: 160
This domain occurred 322 times on human genes (724 proteins).



  ADENOCARCINOMA OF LUNG, SOMATIC
  AORTIC ANEURYSM, FAMILIAL THORACIC 7
  BREAST CANCER, SUSCEPTIBILITY TO
  CARDIOFACIOCUTANEOUS SYNDROME 1
  CARDIOFACIOCUTANEOUS SYNDROME 3
  CARDIOFACIOCUTANEOUS SYNDROME 4
  CEREBRAL INFARCTION, SUSCEPTIBILITY TO
  COFFIN-LOWRY SYNDROME
  COFFIN-LOWRY SYNDROME, MILD
  COLON CANCER, SOMATIC
  COLORECTAL CANCER, SOMATIC
  COLORECTAL CANCER, SOMATIC, INCLUDED;;
  DIABETES MELLITUS, INSULIN-RESISTANT, WITH ACANTHOSIS NIGRICANS
  DIABETES MELLITUS, NONINSULIN-DEPENDENT
  DIABETES MELLITUS, TYPE II
  ENDOCRINE-CEREBROOSTEODYSPLASIA
  EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 2
  FG SYNDROME 4
  GASTRIC CANCER, SOMATIC
  GLIOBLASTOMA, SOMATIC
  GLYCOGEN STORAGE DISEASE IXC
  HEPATOCELLULAR CARCINOMA, CHILDHOOD TYPE, SOMATIC
  HIRSCHSPRUNG DISEASE, SUSCEPTIBILITY TO, 1
  HYPERINSULINEMIC HYPOGLYCEMIA, FAMILIAL, 5
  INSULIN RESISTANCE
  INSULIN RESISTANCE, INCLUDED
  IRAK4 DEFICIENCY
  LYMPHOMA, NON-HODGKIN, SOMATIC
  MALFORMATIONS
  MEGALENCEPHALY-POLYMICROGYRIA-POLYDACTYLY-HYDROCEPHALUS SYNDROME
  MELANOMA, MALIGNANT, SOMATIC
  MENTAL RETARDATION AND MICROCEPHALY WITH PONTINE AND CEREBELLAR HYPOPLASIA
  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
  NEPHRONOPHTHISIS 9 (NPHP9)
  NEUROPATHY, HEREDITARY SENSORY, TYPE II
  NOONAN SYNDROME 7
  OGUCHI DISEASE 2
  PEUTZ-JEGHERS SYNDROME
  PHEOCHROMOCYTOMA, INCLUDED
  PHEOCHROMOCYTOMA, SOMATIC, IN
  PROSTATE CANCER, PROGRESSION AND METASTASIS OF
  RENAL AGENESIS
  RENAL CELL CARCINOMA, PAPILLARY, 1
  RENAL CELL CARCINOMA, PAPILLARY, 1, SOMATIC
  RETINITIS PIGMENTOSA 62
  RETINITIS PIGMENTOSA 62 (RP62)
  SELECTIVE T-CELL DEFECT
  SHORT RIB-POLYDACTYLY SYNDROME 2A (SRPS2A)
  SHORT RIB-POLYDACTYLY SYNDROME, TYPE IIA
  SPERMATOGENIC FAILURE 5
  SPINOCEREBELLAR ATAXIA 14
  SPONDYLOMETAEPIPHYSEAL DYSPLASIA, SHORT LIMB-HAND TYPE
  T-CELL IMMUNODEFICIENCY, RECURRENT INFECTIONS, AUTOIMMUNITY, AND CARDIAC
  TESTICULAR TUMOR, SOMATIC
  THROMBOCYTOPENIA 2
  THYROID CARCINOMA, FAMILIAL MEDULLARY
  THYROID CARCINOMA, FAMILIAL MEDULLARY, INCLUDED
  THYROID CARCINOMA, FOLLICULAR, SOMATIC, INCLUDED
  THYROID CARCINOMA, PAPILLARY, SOMATIC, INCLUDED;;|
  THYROID CARCINOMA, SPORADIC MEDULLARY, INCLUDED;;
  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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