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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
Abnormalities, MultipleGnas
ACTH Deficiency, IsolatedCrh
Acth-Independent Macronodular Adrenal HyperplasiaGnas
ACTH-Secreting Pituitary AdenomaGnas
Adenocarcinoma of LungGnas
Adrenal Gland NeoplasmsGnas
Adrenocortical CarcinomaGnas
Adrenocorticotropic Hormone DeficiencyCrh
Albright's Hereditary OsteodystrophyGnas
AlcoholismCrh , Crhr1
Alzheimer DiseaseCrh , Gnas
Amphetamine-Related DisordersArrb2
AnorexiaCrh , Crhr1 , Crhr2 , Ucn2
Anxiety DisordersCrh , Crhr1 , Crhr2 , Ucn
Arteriovenous FistulaArrb1 , Arrb2
Arthritis, ExperimentalArrb1 , Arrb2 , Crhr1
Arthritis, RheumatoidGrk6
AsthmaCrhr1 , Crhr2 , Ucn
Autosomal Dominant Nocturnal Frontal Lobe EpilepsyCrh
Bipolar DisorderGrk3
Bone Diseases, MetabolicGnas
Brain IschemiaCrh
breast cancerGnas
Breast NeoplasmsGnas
Cafe-au-Lait SpotsGnas
Carcinoma, HepatocellularGnas
Carcinoma, Squamous Cell of Head and NeckGnas
Cardiomyopathy, DilatedUcn
Cardiomyopathy, HypertrophicUcn
Chest PainCrh
Cholestasis, ExtrahepaticCrh
Cocaine-Related DisordersCrh , Crhbp , Crhr1 , Crhr2
Cognition DisordersCrh
Cognitive DysfunctionGnas
ColitisArrb1 , Crhr2 , Ucn , Ucn2
Colonic Diseases, FunctionalCrhr1 , Crhr2
Colorectal NeoplasmsGnas
Cushing SyndromeCrh , Gnas
Depressive DisorderCrh , Crhbp , Crhr1 , Crhr2
Depressive Disorder, MajorCrhr1
Dermatitis, ContactCrhr1
Diabetes Mellitus, ExperimentalCrh
Diabetes Mellitus, Type 2Crhr1
Dyskinesia, Drug-InducedGrk6
Endocrine System DiseasesGnas
Epilepsy, Temporal LobeCrh , Crhbp
Fetal HypoxiaCrh , Crhr1 , Crhr2
Fibrous Dysplasia, PolyostoticGnas
Genetic Diseases, InbornGnas
Giant Cell ArteritisCrh
Growth Hormone-Secreting Pituitary AdenomaGnas
Heart FailureArrb1 , Ucn , Ucn2
Hemorrhagic DisordersGnas
HypertensionCrhr1 , Crhr2 , Gnas , Ucn , Ucn2
Hypertrophy, Left VentricularCrhr2 , Ucn
HypotensionCrh , Crhr2 , Ucn
Hypotension, OrthostaticGnas
Infarction, Middle Cerebral ArteryCrh
InflammationCrhr2 , Ucn , Ucn3
Insulin ResistanceGnas
Intellectual DisabilityGnas
Irritable Bowel SyndromeCrhr1 , Crhr2
Leukemia, Lymphocytic, Chronic, B-CellGnas
liver cancerGnas
Liver CirrhosisArrb1
Liver Cirrhosis, ExperimentalArrb2
Liver Diseases, ParasiticGnas
Liver NeoplasmsGnas
Liver Neoplasms, ExperimentalArrb2
Lung DiseasesCrhr2 , Ucn3
McCune Albright syndromeGnas
Movement DisordersCrh
Muscular AtrophyCrhr2
Myocardial Reperfusion InjuryUcn
ObesityCrh , Crhbp , Crhr1 , Gnas , Ucn
Osseous Heteroplasia, ProgressiveGnas
Ossification, HeterotopicGnas
Pain, PostoperativeCrhr1
Pancreatic AdenocarcinomaGnas
Pancreatic NeoplasmsGnas
Panic DisorderCrh
Parkinson DiseaseCrh , Grk3 , Grk6
Parkinsonian DisordersUcn
Pituitary ACTH HypersecretionGnas
Pituitary ApoplexyCrh
Pituitary NeoplasmsGnas
Pleomorphic Xanthoastrocytoma Crhr2
Pneumonia, PneumococcalCrhr1 , Crhr2
Polycystic Ovary SyndromeGnas
Polymyalgia RheumaticaCrh
Prolonged Bleeding Time, Brachydactyly, and Mental RetardationGnas
Pseudohypoparathyroidism Type 1AGnas
Pseudohypoparathyroidism Type 1BGnas
Pseudohypoparathyroidism Type 1CGnas
Psychomotor DisordersCrh
Puberty, DelayedCrh
Puberty, PrecociousGnas
Pulmonary Disease, Chronic ObstructiveCrhr1
Respiration DisordersGnas
RhinitisCrhr1 , Crhr2
Sciatic NeuropathyCrh
Sex Cord-Gonadal Stromal TumorsGnas
Smith-Magenis SyndromeCrhr1
Spasms, InfantileCrh
Spinal Cord InjuriesCrh
Status EpilepticusCrh
Stereotypic Movement DisorderCrh
Substance Withdrawal SyndromeCrh , Gnas
Thromboangiitis ObliteransCrhr1 , Ucn
Uterine Cervical NeoplasmsGnas
Weight LossCrh
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
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
Entamoeba histolyca infection pathwayGnas
epinephrine signaling pathway via adrenergic receptor betaArrb1 , Arrb2 , Gnas
follicle-stimulating hormone signaling pathwayGnas
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
Trypanosoma cruzi infection pathwayGnas
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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