MELANOCORTIN SYSTEM PATHWAY (PW:0000365)

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Description

The melanocortin peptides - a collective term for the alpha-, beta- and gamma-melanocyte-stimulating hormones and the adenocorticotropin hormone (ACTH) - are derived from the sequential processing of the pro-opiomelanocortin (POMC) gene product. They bind to specific G-protein coupled melanocortin receptors (Mcr) to elicit a range of responses that include anti-inflammatory and immunomodulatory effects, regulation of energy homeostasis and feeding behavior and induction of melanogenesis. The fiv

Pathway Diagram:

Ariadne Genomics Inc. immunomodulation energy homeostasis cortisol biosynthetic pathway protein kinase A (PKA) signaling pathway G protein mediated signaling pathway via Galphas family Mgrn1 HPA axis POMC processing enzymes MSH peptides stress conditions --+> corticotropin-releasing hormone signaling pathway stress conditions Pomc ---> MSH peptides Atrn corticotropin-releasing hormone signaling pathway MRAP2 Pomc ---> ACTH Agrp Pomc corticotropin-releasing hormone signaling pathway --+> Pomc Gnas Mgrn1 ---| MC1R Mrap --+> Mc2r MC1R ---> melanogenesis melanogenesis steroidogenesis Asip ---| MC1R ACTH ---- Mc3r ACTH ---- MC1R ACTH ---- Mc5r ACTH Mc3r ---> immunomodulation Mc3r Mc3r ---> energy homeostasis Mc4r ---> energy homeostasis Asip ---- Atrn Agrp ---| Mc4r Agrp ---| Mc3r Agrp ---- Mc4r Agrp ---- Mc3r Gnas ---- Mc2r Gnas ---- MC1R Asip Mc2r Gnas ---- Mc3r Atrnl1 ---- Mc4r Mc4r Atrnl1 Mc5r Asip ---- MC1R Mc5r ---> immunomodulation Gnas ---- Mc4r cAMP --+> protein kinase A (PKA) signaling pathway G protein mediated signaling pathway via Galphas family --+> cAMP cAMP Gnas ---- Mc5r ACTH ---- Mc2r MC1R ---- MSH peptides Mc3r ---- MSH peptides Mc4r ---- MSH peptides Mc5r ---- MSH peptides ACTH ---- Mc4r Mc2r --+> cortisol biosynthetic pathway MC1R Mrap
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melanocortin system pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Adcy2 adenylate cyclase 2 JBrowse link 1 37,043,071 37,698,390 RGD:10402751
G Agrp agouti related neuropeptide JBrowse link 19 37,525,941 37,584,875 RGD:632165
RGD:1357925
G Asip agouti signaling protein JBrowse link 3 150,492,010 150,579,870 RGD:1357925
G Atrn attractin JBrowse link 3 123,434,409 123,567,922 RGD:5144214
G Atrnl1 attractin like 1 JBrowse link 1 278,546,113 279,098,977 RGD:5144214
G Cpe carboxypeptidase E JBrowse link 16 26,906,716 27,014,811 RGD:1357926
G Gnas GNAS complex locus JBrowse link 3 172,374,957 172,434,988 RGD:5144213
RGD:10402751
G Gnb1 G protein subunit beta 1 JBrowse link 5 172,914,025 172,981,403 RGD:10402751
G Gng12 G protein subunit gamma 12 JBrowse link 4 97,634,925 97,763,478 RGD:10402751
G Mc1r melanocortin 1 receptor JBrowse link 19 56,215,420 56,219,987 RGD:5144213
G Mc2r melanocortin 2 receptor JBrowse link 18 64,166,959 64,178,729 RGD:5144213
RGD:10402751
G Mc3r melanocortin 3 receptor JBrowse link 3 170,252,901 170,253,998 RGD:69884
RGD:5144213
G Mc4r melanocortin 4 receptor JBrowse link 18 62,612,838 62,614,725 RGD:729360
RGD:5144213
G Mc5r melanocortin 5 receptor JBrowse link 18 64,113,659 64,118,700 RGD:1626223
RGD:5144213
G Mgrn1 mahogunin ring finger 1 JBrowse link 10 10,832,573 10,881,999 RGD:5144214
G Mrap melanocortin 2 receptor accessory protein JBrowse link 11 30,904,733 30,915,225 RGD:5144214
G Pam peptidylglycine alpha-amidating monooxygenase JBrowse link 9 111,028,543 111,177,588 RGD:1357926
G Pcsk1 proprotein convertase subtilisin/kexin type 1 JBrowse link 2 91,450,162 91,497,091 RGD:1357925
RGD:1357926
G Pcsk2 proprotein convertase subtilisin/kexin type 2 JBrowse link 3 137,618,891 137,923,385 RGD:1357926
G Pomc proopiomelanocortin JBrowse link 6 28,382,937 28,388,771 RGD:1357925
RGD:1357926
RGD:10402751
G Prkacb protein kinase cAMP-activated catalytic subunit beta JBrowse link 2 252,602,197 252,691,886 RGD:10402751
G Sdc1 syndecan 1 JBrowse link 6 33,885,576 33,908,038 RGD:1357925
G Sdc3 syndecan 3 JBrowse link 5 148,923,098 148,956,404 RGD:1357925
altered melanocortin system pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Agrp agouti related neuropeptide JBrowse link 19 37,525,941 37,584,875 RGD:1357925
G Mc4r melanocortin 4 receptor JBrowse link 18 62,612,838 62,614,725 RGD:1357925
G Pcsk1 proprotein convertase subtilisin/kexin type 1 JBrowse link 2 91,450,162 91,497,091 RGD:1357925
RGD:1357926
G Pomc proopiomelanocortin JBrowse link 6 28,382,937 28,388,771 RGD:1357925
RGD:1357926
G Sdc1 syndecan 1 JBrowse link 6 33,885,576 33,908,038 RGD:1357925

Altered Pathway:

Additional Elements in Pathway:

(includes Gene Groups, Small Molecules, Other Pathways..etc.)
Object TypePathway ObjectPathway Object Description
Pathwaycorticotropin-releasing hormone signaling pathwayActivation of HPA axis by various stresses leads to release of corticotropin-releasing hormone from the hypothalamus and initiation of its signaling pathway which leads to activation of POMC gene expression
PathwayG protein mediated signaling via Gaphas 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
Pathwaycortisol biosynthetic pathwayCortisol, the main C21 glucocorticoid, is primarily synthesized in the cortex of the adrenal gland. Like all steroid hormones, glucocorticoids are derived from cholesterol; their biosynthesis is tightly regulated by the hypothalamus-pituitary-gonadal axis. The chronic steroidogenic response involves the change in the expression of steroidogenic genes while the acute response involves the quick delivery of cholesterol to the site of the first enzymatic reaction
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

Pathway Gene Annotations

Disease Annotations Associated with Genes in the melanocortin system pathway
Disease TermsGene Symbols
Abnormalities, MultipleGnas , Pomc
AcromegalyGnas
ACTH Syndrome, EctopicPomc
Acth-Independent Macronodular Adrenal HyperplasiaGnas
ACTH-Secreting Pituitary AdenomaGnas
Acute-Phase ReactionMc1r , Mc2r , Mc3r , Mc4r , Mc5r
Adenoma, Islet CellPcsk1
Adrenal Cortex DiseasesPomc
Adrenal Gland NeoplasmsGnas
Adrenal InsufficiencyPomc
Albright's Hereditary OsteodystrophyGnas
Alzheimer DiseaseGnas
AmnesiaPomc
AnoxiaGnas , Pomc
Anxiety DisordersGnb1 , Pam
Aortic Stenosis, SubvalvularPomc
Arthritis, ExperimentalPam
Arthritis, GoutyPomc
AsthmaAdcy2
Autistic DisorderPomc
Biliary Tract NeoplasmsPrkacb
Bipolar DisorderPomc
Blindness, CorticalGnb1
Body Mass Index Quantitative Trait Locus 12Pcsk1
Body Mass Index Quantitative Trait Locus 9Mc3r
Body WeightMc4r , Pcsk1 , Pomc
Bone Diseases, MetabolicGnas
BrachydactylyGnas
BradycardiaPomc
Brain Diseases, Metabolic, InbornMc2r
Brain IschemiaPrkacb
BurnsPomc
CachexiaMc4r
Cafe-au-Lait SpotsGnas
CalcinosisPomc
Carcinoma, Basal CellAsip , Mc1r
Carcinoma, Renal CellPomc
CardiomegalyPomc
CardiomyopathiesPomc
Cardiomyopathy, HypertrophicPomc
CatalepsyPomc
Cerebral HemorrhagePomc
Cerebral PalsyPomc
CholangiocarcinomaGnas , Prkacb
CholestasisPomc
ChondrocalcinosisPomc
Cleft PalateGnb1
Cocaine-Related DisordersPomc
Cognition DisordersGnas
ColitisMc1r
ConstipationPomc
Cushing SyndromeGnas , Pomc
CystitisPomc
DehydrationPcsk1
Depressive DisorderGnb1 , Pomc
Depressive Disorder, MajorMc1r
Dermatitis, Allergic ContactMc1r
Dermatitis, AtopicMc1r
Developmental DisabilitiesGnb1
Diabetes InsipidusPomc
Diabetes MellitusAsip , Pomc
Diabetes Mellitus, ExperimentalPcsk1 , Pcsk2
Diabetes Mellitus, Type 1Pcsk1
Diabetes Mellitus, Type 2Agrp , Asip , Cpe , Pam , Pcsk1 , Pcsk2
DwarfismPcsk1
DystoniaGnb1
EdemaPomc
Endocrine System DiseasesCpe , Gnas
EndotoxemiaMc4r , Pcsk1 , Pcsk2
Epilepsies, MyoclonicPomc
EpilepsyGnb1 , Pomc
Epilepsy, Tonic-ClonicGnb1 , Pomc
Eye DiseasesPomc
Eye PainPomc
Facial ParalysisPomc
Failure to ThriveGnb1
Familial Glucocorticoid Deficiency 1Mc2r
Familial Mediterranean FeverPomc
Fatty LiverPomc
Femur Head NecrosisPomc
FeverPomc
Fibrous Dysplasia, PolyostoticGnas
GallstonesGnas
Gastrointestinal DiseasesPomc
Genetic Diseases, InbornGnas , Gnb1 , Pomc
GlomerulonephritisPomc
Glucocorticoid Deficiency 2Mrap
Glucocorticoid Deficiency 3Mrap
Glucose IntolerancePcsk1
Growth Hormone-Secreting Pituitary AdenomaGnas
Heart FailurePomc
HematuriaPomc
HemorrhagePomc
Hemorrhagic DisordersGnas
Heroin DependencePomc
HirsutismPomc
Hodgkin DiseaseSdc1
HyperalgesiaMc1r , Mc4r
HypercalciuriaPomc
HyperglycemiaMgrn1 , Pcsk1 , Sdc1
HyperinsulinismMc4r , Mgrn1
HyperlipidemiasSdc1
HypernatremiaPomc
HyperoxiaMc1r , Mc2r
HyperphagiaAgrp , Mc4r , Pomc
HyperplasiaPam
HypertensionGnas , Mc2r , Pomc
HyperthyroidismPcsk1
HypocalcemiaGnas , Pomc
Hypoglossal Nerve InjuriesPrkacb
HypogonadismPcsk1
HypokalemiaPomc
HypopigmentationMc1r
HypotensionPomc
Hypotension, OrthostaticGnas
HypothyroidismGnb1 , Pam , Pcsk1
Hypoxia, BrainPam
Immune System DiseasesPomc
InfectionPomc
InflammationPcsk1 , Pcsk2 , Pomc , Sdc1
Inflammatory Bowel DiseasesPomc
Insulin ResistanceCpe , Gnas , Mc4r
Intellectual DisabilityGnas , Gnb1
Kidney CalculiPomc
Kidney DiseasesPomc
Kidney Reperfusion InjuryMc1r
Kidney Tubular Necrosis, AcutePomc
Leukemia, Lymphocytic, Chronic, B-CellGnas
Liver Cirrhosis, ExperimentalAtrn , Pomc
Liver Diseases, ParasiticGnas
Liver Failure, AcutePomc
Liver NeoplasmsAsip
Long QT SyndromePomc , Sdc1
Lymphoma, AIDS-RelatedSdc1
MelanomaAsip , Mc1r , Mc2r , Pomc
Melanoma, Cutaneous Malignant, Susceptibility To, 1Mc1r , Mc2r
Melanoma, Cutaneous Malignant, Susceptibility To, 5Mc1r
Melanoma, ExperimentalMc1r
Memory DisordersCpe
Mental DisordersPomc
Mesothelioma, MalignantSdc1
Multiple SclerosisPomc
Muscle HypotoniaGnb1
Myasthenia GravisPomc
MYCOBACTERIUM TUBERCULOSIS, SUSCEPTIBILITY TOMc3r
Myelodysplastic SyndromesGnb1
Myocardial InfarctionPcsk2 , Sdc1
Myocardial IschemiaPomc
NauseaPomc
NecrosisPomc
NeoplasmsAsip
NephrocalcinosisPomc
NeuroblastomaGnas
Neurogenic InflammationPomc
Nociceptive PainPomc
ObesityAgrp , Asip , Atrn , Cpe , Gnas , Mc3r , Mc4r , Mc5r , Mgrn1 , Pcsk1 , Pomc , Sdc1 , Sdc3
Obesity, MorbidMc4r , Pcsk1 , Pomc
Oculocutaneous Albinism Type 2Mc1r
OliguriaPomc
Opsoclonus-Myoclonus SyndromePomc
Osseous Heteroplasia, ProgressiveGnas
Ossification, HeterotopicGnas
OsteoarthritisPomc
OsteoporosisPomc
PainPomc
Pancreatic DiseasesPomc
Pancreatic NeoplasmsGnas
Parkinson DiseaseMc1r
Parkinson Disease, Late-OnsetMc1r
Penile DiseasesPomc
Pigmentation DisordersAsip
Pituitary ACTH HypersecretionGnas , Pomc
Pituitary NeoplasmsGnas
PneumoniaPomc
Pneumonia, BacterialMc1r
Polycystic Ovary SyndromeGnas
Postoperative ComplicationsPomc
Precursor Cell Lymphoblastic Leukemia-LymphomaGnb1
Prolonged Bleeding Time, Brachydactyly, and Mental RetardationGnas
Proopiomelanocortin DeficiencyPomc
Proprotein Convertase 1 3 DeficiencyPcsk1
Prostatic NeoplasmsMc2r , Pam , Prkacb
Protein-Losing EnteropathiesMc1r
ProteinuriaPomc , Sdc1
PseudohypoaldosteronismGnas
PseudohypoparathyroidismGnas
Pseudohypoparathyroidism Type 1AGnas
Pseudohypoparathyroidism Type 1BGnas
Pseudohypoparathyroidism Type 1CGnas
PseudopseudohypoparathyroidismGnas
Puberty, PrecociousGnas
RecurrencePomc
Renal Insufficiency, ChronicPcsk2
Reperfusion InjuryMc1r , Pcsk2
Respiration DisordersGnas
Restless Legs SyndromePomc
RhabdomyomaPomc
Rhinitis, Allergic, SeasonalMc1r
SacroiliitisPomc
SchizophreniaMc4r
Sciatic NeuropathyMc4r
SeizuresGnb1 , Pam , Pcsk1 , Pomc
Sex Cord-Gonadal Stromal TumorsGnas
Shock, SepticMc2r
Sick Sinus SyndromePomc
Skin NeoplasmsAsip
Skin/Hair/Eye Pigmentation, Variation In, 9Asip
Sleep Wake DisordersPomc
Spasms, InfantileMc2r , Pomc
StrabismusGnb1
Substance Withdrawal SyndromeGnas , Pomc
SynovitisPomc
TachycardiaGnas
TetanyGnas
ThinnessAgrp
TremorAtrn
Urinary Tract InfectionsPomc
UV-Induced Skin DamageMc1r
VitiligoMc1r
Weight GainPomc
Weight LossPomc
Pathway Annotations Associated with Genes in the melanocortin system pathway
Pathway TermsGene Symbols
adenosine signaling pathwayAdcy2 , Gnas , Gnb1 , Gng12 , Prkacb
alfentanil pharmacodynamics pathwayPcsk2 , Pomc
altered energy homeostasis pathwayMc4r , Pcsk1 , Pomc
altered melanocortin system pathwayAgrp , Mc4r , Pcsk1 , Pomc , Sdc1
apoptotic cell death pathwayPrkacb
bile acid transport pathwayAdcy2 , Gnas , Prkacb
bupivacaine pharmacodynamics pathwayPcsk2 , Pomc
buprenorphine pharmacodynamics pathwayPcsk2 , Pomc
calcium/calcium-mediated signaling pathwayAdcy2 , Gnas , Prkacb
cell-extracellular matrix signaling pathwaySdc1 , Sdc3
chemokine mediated signaling pathwayAdcy2 , Gnb1 , Gng12 , Prkacb
chloroprocaine pharmacodynamics pathwayPcsk2 , Pomc
citalopram pharmacodynamics pathwayPcsk2 , Pomc
cocaine pharmacodynamics pathwayPcsk2 , Pomc
codeine and morphine pharmacodynamics pathwayPcsk2 , Pomc
corticotropin-releasing hormone signaling pathwayGnas
desipramine pharmacodynamics pathwayPcsk2 , Pomc
dilated cardiomyopathy pathwayAdcy2 , Gnas , Prkacb
diphenoxylate pharmacodynamics pathwayPcsk2 , Pomc
dopamine signaling pathwayPrkacb
dopamine signaling pathway via D1 family of receptorsAdcy2 , Gnas , Gnb1 , Gng12 , Prkacb
eicosanoid signaling pathwayGnb1
endothelin signaling pathwayAdcy2
Entamoeba histolyca infection pathwayGnas , Prkacb
epinephrine signaling pathway via adrenergic receptor betaGnas
escitalopram pharmacodynamics pathwayPcsk2 , Pomc
ethylmorphine pharmacodynamics pathwayPcsk2 , Pomc
fentanyl pharmacodynamics pathwayPcsk2 , Pomc
fluoxetine pharmacodynamics pathwayPcsk2 , Pomc
follicle-stimulating hormone signaling pathwayAdcy2 , Gnas , Gnb1 , Gng12 , Prkacb
G protein mediated signaling pathway via Galpha12/Galpha13 familyGnb1
G protein mediated signaling pathway via Galphas familyAdcy2 , Gnas , Mc1r , Mc2r , Mc3r , Mc4r , Mc5r
glucagon signaling pathwayGnas
glutamate signaling pathwayAdcy2 , Gnas , Gnb1 , Gng12 , Prkacb
gonadotropin-releasing hormone signaling pathwayAdcy2 , Gnas , Prkacb
granulocyte-macrophage colony-stimulating factor signaling pathwayPrkacb
Hedgehog signaling pathwayGnb1 , Prkacb
heroin pharmacodynamics pathwayPcsk2 , Pomc
histamine signaling pathway, immunologicalAdcy2 , Gnas , Gnb1 , Gng12 , Prkacb
hydrocodone pharmacodynamics pathwayPcsk2 , Pomc
hydromorphone pharmacodynamics pathwayPcsk2 , Pomc
imipramine pharmacodynamics pathwayPcsk2 , Pomc
insulin responsive facilitative sugar transporter mediated glucose transport pathwayAsip
insulin signaling pathwayPrkacb
interleukin-3 signaling pathwayPrkacb
levacetylmethadol pharmacodynamics pathwayPcsk2 , Pomc
levobupivacaine phgarmacodynamics pathwayPcsk2 , Pomc
levorphanol pharmacodynamics pathwayPcsk2 , Pomc
lidocaine pharmacodynamics pathwayPcsk2 , Pomc
long term depressionGnas
long term potentiationPrkacb
luteinizing hormone signaling pathwayAdcy2 , Gnas , Gnb1 , Gng12 , Prkacb
melanocortin system pathwayAdcy2 , Agrp , Asip , Atrn , Atrnl1 , Cpe , Gnas , Gnb1 , Gng12 , Mc1r , Mc2r , Mc3r , Mc4r , Mc5r , Mgrn1 , Mrap , Pam , Pcsk1 , Pcsk2 , Pomc , Prkacb , Sdc1 , Sdc3
mepivacaine pharmacodynamics pathwayPcsk2 , Pomc
methadone pharmacodynamics pathwayPcsk2 , Pomc
mitogen activated protein kinase signaling pathwayGng12 , Prkacb
nalbuphine pharmacodynamics pathwayPcsk2 , Pomc
naloxone pharmacodynamics pathwayPcsk2 , Pomc
naltrexone pharmacodynamics pathwayPcsk2 , Pomc
nicotine pharmacodynamics pathwayPcsk2 , Pomc
obesity disease pathwayAgrp , Mc4r , Pcsk1 , Pomc , Sdc1
orexin/hypocretin signaling pathwayPcsk1
oxybuprocaine pharmacodynamics pathwayPcsk2 , Pomc
oxycodone pharmacodynamics pathwayPcsk2 , Pomc
oxymorphone pharmacodynamics pathwayPcsk2 , Pomc
pentazocine pharmacodynamics pathwayPcsk2 , Pomc
Plasmodium infection pathwaySdc1 , Sdc3
prilocaine pharmacodynamics pathwayPcsk2 , Pomc
prion diseases pathwayPrkacb
procaine pharmacodynamics pathwayPcsk2 , Pomc
prostaglandin D2 signaling pathwayAdcy2 , Gnas , Gnb1 , Gng12 , Prkacb
prostaglandin I2 signaling pathwayAdcy2 , Gnas , Gnb1 , Gng12 , Prkacb
protein kinase A (PKA) signaling pathwayAdcy2 , Prkacb
purine metabolic pathwayAdcy2
remifentanil pharmacodynamics pathwayPcsk2 , Pomc
ropivacaine pharmacodynamics pathwayPcsk2 , Pomc
serotonin signaling pathway via receptors engaging G alphas protein familyAdcy2 , Gnas , Gnb1 , Gng12 , Prkacb
syndecan signaling pathwayAgrp , Mc4r , Pomc , Sdc1 , Sdc3
tramadol pharmacodynamics pathwayPcsk2 , Pomc
Trypanosoma cruzi infection pathwayGnas
type 1 diabetes mellitus pathwayCpe
ubiquitin/proteasome degradation pathwayMgrn1
vasopressin signaling pathwayGnas
vasopressin signaling pathway via receptor type 2Adcy2 , Gnas , Gnb1 , Gng12 , Prkacb
visual phototransduction pathwayGnb1
Wnt signaling pathwayPrkacb
Phenotype Annotations Associated with Genes in the melanocortin system pathway

References Associated with the melanocortin system pathway:

Ontology Path Diagram:

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Import into Pathway Studio: