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Corticotropin-releasing hormone (CRH) and CRH-relate urocortin (UCN) peptides exert a wide range of functions, from setting in motion the stress-responding hypothalamus-pituitary-adrenal (HPA) axis to various actions in central nervous system (CNS) and the periphery. The signaling initiated by these peptides engages two receptor types belonging to the secretin family of G-protein coupled receptors (GPCR). CRH is a main component of the HPA axis; released by the hypothalamus in response to stres

Pathway Diagram:

Ariadne Genomics Inc. receptor - G protein uncoupling melanocortin system pathway G protein mediated signaling pathway via Galphas family protein kinase A (PKA) signaling pathway HPA axis Crh Gnas receptor internalization CRH neurons stress Crhr2 Crhbp ---- Ucn Crh ---- Crhbp Crhr2 ---- Ucn Ucn ---> cardiovascular functions Ucn2 ---> cardiovascular functions Crh ---- Crhr1 Ucn cAMP --+> protein kinase A (PKA) signaling pathway G protein mediated signaling pathway via Galphas family --+> cAMP receptor desensitization Arrb2 ---- Crhr1 Arrb1 Arrb2 Arrb1 ---- Crhr1 Adrbk2 Grk6 Adrbk2 ---| Crhr1 Ucn3 Ucn2 Crhbp Crhr2 ---- Ucn2 Grk6 ---| Crhr1 Crhr1 ---- Gnas Crhr1 ---- Ucn Crhr2 ---- Gnas cardiovascular functions gene expression cAMP Ucn3 ---> cardiovascular functions Crhr1 Crhr2 ---- Ucn3 stress --+> CRH neurons Crh --+> melanocortin system pathway

Genes in Pathway:

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corticotropin-releasing hormone signaling pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Arrb1 arrestin, beta 1 JBrowse link 1 164,502,099 164,573,947 RGD:5147673
G Arrb2 arrestin, beta 2 JBrowse link 10 57,040,252 57,048,045 RGD:5147673
G Crh corticotropin releasing hormone JBrowse link 2 104,459,999 104,461,863 RGD:1358326
G Crhbp corticotropin releasing hormone binding protein JBrowse link 2 25,141,471 25,153,334 RGD:5147387
G Crhr1 corticotropin releasing hormone receptor 1 JBrowse link 10 92,191,473 92,233,662 RGD:1358326
G Crhr2 corticotropin releasing hormone receptor 2 JBrowse link 4 85,286,371 85,329,374 RGD:1358326
G Gnas GNAS complex locus JBrowse link 3 172,374,957 172,434,988 RGD:5147387
G Grk3 G protein-coupled receptor kinase 3 JBrowse link 12 49,626,871 49,750,389 RGD:5147387
G Grk6 G protein-coupled receptor kinase 6 JBrowse link 17 9,705,917 9,721,921 RGD:5147387
G Ucn urocortin JBrowse link 6 26,602,144 26,602,974 RGD:5147387
G Ucn2 urocortin 2 JBrowse link 8 117,727,216 117,728,765 RGD:5147387
G Ucn3 urocortin 3 JBrowse link 17 69,959,879 69,966,532 RGD:5147387

Additional Elements in Pathway:

(includes Gene Groups, Small Molecules, Other Pathways..etc.)
Object TypePathway ObjectPathway Object Description
PathwayG protein mediated signaling pathway via Galphas familybased on sequence similarity, the Galpha genes have been grouped into four classes. Effectors of activated Galphas are adenylyl cyclases that catalyze the formation of cAMP
Small MoleculecAMPcAMP binding to the PKA complex leads to dissociation of the catalytic subunits
Pathwayprotein kinase A (PKA) signaling pathwayProtein kinase A (PKA) signaling is a widely used intracellular pathway and the major route for channeling the second messenger cAMP signal
Pathwaymelanocortin system pathwayThe melanocortin peptides derived from the processing of POMC gene product, bind to specifc G-protein coupled receptors to elicit a range of responses. Activation of HPA axis leads to expression of POMC gene

Pathway Gene Annotations

Disease Annotations Associated with Genes in the corticotropin-releasing hormone signaling pathway
Disease TermsGene Symbols
ACTH-Independent Macronodular Adrenal Hyperplasia 1Gnas
ACTH-secreting pituitary adenomaGnas
adrenal carcinomaGnas
Adrenal Gland NeoplasmsGnas
adrenocortical carcinomaGnas
adrenocorticotropic hormone deficiencyCrh
Albright's hereditary osteodystrophyGnas
alcohol use disorderCrh , Crhr1
Alzheimer's diseaseCrh , Gnas
amphetamine abuseArrb2
AnorexiaCrh , Crhr1 , Crhr2 , Ucn2
anxiety disorderCrh , Crhr1 , Crhr2 , Ucn
Arteriovenous FistulaArrb1 , Arrb2
asthmaCrhr1 , Crhr2 , Ucn
autosomal dominant nocturnal frontal lobe epilepsyCrh
B-Cell Chronic Lymphocytic LeukemiaGnas
bipolar disorderGrk3
brain ischemiaCrh
breast cancerGnas
Breast NeoplasmsCrhr1 , Gnas
Cafe-au-Lait SpotsGnas
Chest PainCrh
chronic obstructive pulmonary diseaseCrhr1
Cocaine-Related DisordersCrh , Crhbp , Crhr1 , Crhr2 , Grk3
cognitive disorderCrh
colitisArrb1 , Crhr2 , Ucn , Ucn2
Colorectal NeoplasmsGnas
congestive heart failureArrb1 , Grk3 , Ucn , Ucn2
contact dermatitisCrhr1
Cushing syndromeCrh , Gnas
Delayed PubertyCrh
Diabetes Mellitus, Experimental Crh
Diabetic NephropathiesGrk3 , Grk6
dilated cardiomyopathyUcn
disease of cellular proliferationGnas
Drug-Induced DyskinesiaGrk6
endocrine system diseaseGnas
Experimental ArthritisArrb1 , Arrb2 , Crhr1
Experimental Liver CirrhosisArrb2
Experimental Liver NeoplasmsArrb2
extrahepatic cholestasisCrh
Fetal HypoxiaCrh , Crhr1 , Crhr2
functional colonic diseaseCrhr1 , Crhr2
gastric adenocarcinomaGnas
genetic diseaseGnas
growth hormone secreting pituitary adenomaGnas
head and neck squamous cell carcinomaGnas
hemorrhagic diseaseGnas
hepatocellular carcinomaCrhbp , Gnas
hypertensionArrb2 , Crhr1 , Crhr2 , Gnas , Grk3 , Ucn , Ucn2
hypertrophic cardiomyopathyUcn
hypoparathyroidism-deafness-renal disease syndromeUcn3
HypotensionCrh , Crhr2 , Ucn
Hypotension, OrthostaticGnas
InflammationCrhr2 , Ucn , Ucn3
Insulin ResistanceGnas
intellectual disabilityGnas
irritable bowel syndromeCrhr1 , Crhr2
Left Ventricular HypertrophyCrhr2 , Ucn
liver cancerGnas
liver cirrhosisArrb1
lung adenocarcinomaGnas
lung diseaseCrhr2 , Ucn3
major depressive disorderArrb1 , Crhr1
McCune Albright syndromeGnas
mental depressionCrh , Crhbp , Crhr1 , Crhr2
Metabolic Bone DiseasesGnas
middle cerebral artery infarctionCrh
movement diseaseCrh
Multiple AbnormalitiesGnas
muscular atrophyCrhr2
Myocardial Reperfusion InjuryArrb2 , Ucn
obesityCrh , Crhbp , Crhr1 , Gnas , Ucn
Ossification, HeterotopicGnas
Osteoarthritis, HipCrhr1
Pain, PostoperativeCrhr1
pancreatic adenocarcinomaGnas
pancreatic cancerGnas
panic disorderCrh
Parasitic Liver DiseasesGnas
Parkinson's diseaseCrh , Grk3 , Grk6
Parkinsonian DisordersUcn
pituitary apoplexyCrh
Pituitary NeoplasmsGnas
pituitary-dependent Cushing's diseaseGnas
pleomorphic xanthoastrocytomaCrhr2
Pneumococcal PneumoniaCrhr1 , Crhr2
polycystic ovary syndromeGnas
polymyalgia rheumaticaCrh
portal hypertensionArrb2
Precocious PubertyGnas
primary hyperaldosteronismCrh , Gnas
Progressive Osseous HeteroplasiaGnas
Prolonged Bleeding Time, Brachydactyly, and Mental RetardationGnas
Pseudohypoparathyroidism Type 1CGnas
pseudohypoparathyroidism type IBGnas
Psychomotor DisordersCrh
renal fibrosisArrb2
Respiration DisordersGnas
rheumatoid arthritisGrk6
rhinitisCrhr1 , Crhr2
schizophreniaGnas , Ucn3
sciatic neuropathyCrh
sex cord-gonadal stromal tumorGnas
Spinal Cord InjuriesCrh , Grk6
status epilepticusCrh
stereotypic movement disorderCrh
temporal arteritisCrh
temporal lobe epilepsyCrh , Crhbp
thromboangiitis obliteransCrhr1 , Ucn
Transplant RejectionArrb1 , Arrb2
type 2 diabetes mellitusArrb2 , Crhr1
Uterine Cervical NeoplasmsGnas
visual epilepsyCrh
Weight LossCrh
West syndromeCrh
withdrawal disorderCrh , Gnas
Pathway Annotations Associated with Genes in the corticotropin-releasing hormone signaling pathway
Pathway TermsGene Symbols
adenosine signaling pathwayGnas
angiotensin II signaling pathway via AT1 receptorArrb1 , Arrb2 , Grk3 , Grk6
bile acid transport pathwayGnas
calcium signaling pathway via the calcium-sensing receptorArrb1 , Arrb2 , Grk3
calcium/calcium-mediated signaling pathwayGnas
Chagas disease pathwayGnas
chemokine mediated signaling pathwayArrb1 , Arrb2 , Grk3 , Grk6
corticotropin-releasing hormone signaling pathwayArrb1 , Arrb2 , Crh , Crhbp , Crhr1 , Crhr2 , Gnas , Grk3 , Grk6 , Ucn , Ucn2 , Ucn3
dilated cardiomyopathy pathwayGnas
dopamine signaling pathway via D1 family of receptorsArrb1 , Arrb2 , Gnas , Grk3 , Grk6
dopamine signaling pathway via D2 family of receptorsArrb1 , Arrb2 , Grk3 , Grk6
eicosanoid signaling pathwayArrb2 , Grk3
endocytosis pathwayArrb1 , Arrb2 , Grk3 , Grk6
Entamoebiasis pathwayGnas
epinephrine signaling pathway via adrenergic receptor betaArrb1 , Arrb2 , Gnas
follicle-stimulating hormone signaling pathwayGnas
G protein mediated signaling pathwayGrk3
G protein mediated signaling pathway via Galphas familyCrhr1 , Crhr2 , Gnas , Grk3
glucagon signaling pathwayGnas
glutamate signaling pathwayGnas , Grk3
gonadotropin-releasing hormone signaling pathwayGnas
Hedgehog signaling pathwayArrb2
histamine signaling pathway, immunologicalGnas
kinin signaling pathwayArrb1 , Arrb2
long term depressionCrh , Crhr1 , Gnas
luteinizing hormone signaling pathwayGnas
melanocortin system pathwayGnas
mitogen activated protein kinase signaling pathwayArrb1 , Arrb2
nuclear factor kappa B signaling pathwayArrb2
parathyroid hormone signaling pathwayArrb1 , Arrb2
prostaglandin D2 signaling pathwayGnas
prostaglandin I2 signaling pathwayGnas
protein kinase A (PKA) signaling pathwayCrhr2
serotonin signaling pathway via receptors engaging G alphas protein familyGnas
transforming growth factor-beta Smad dependent signaling pathwayArrb2
vasopressin signaling pathwayGnas
vasopressin signaling pathway via receptor type 2Gnas
visual phototransduction pathwayArrb1 , Arrb2
Wnt signaling, non-canonical pathwayArrb2
Phenotype Annotations Associated with Genes in the corticotropin-releasing hormone signaling pathway

References Associated with the corticotropin-releasing hormone signaling pathway:

Ontology Path Diagram:

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