Defective ACTH does not bind MCR2

Stable Identifier
R-HSA-5603251
Type
Reaction [transition]
Species
Homo sapiens
Compartment
extracellular region, plasma membrane
Synonyms
Defective POMC(138-176) does not bind MCR2, Defective ACTH does not bind MC2R, Defective POMC(138-176) does not bind MC2R
ReviewStatus
5/5
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Defective ACTH does not bind MCR2
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Adrenocorticotropic hormone (ACTH, POMC(138-176)) stimulates the adrenal glands, via its binding to adrenocorticotropic hormone receptor (MC2R) and subsequent downstream signaling, to release cortisol, a glucocorticoid released in response to stress whose primary functions are to stimulate gluconeogenesis, suppress the immune system and aid metabolism of fats, proteins and carbohydrates.

Defects in ACTH can cause obesity (MIM:601665) resulting in excessive accumulation of body fat. Defects in ACTH can also cause pro-opiomelanocortinin deficiency (POMCD; MIM:609734) where affected individuals present early-onset obesity, adrenal insufficiency and red hair. Mutations causing POMCD include E79*, R236G and L25* (Krude et al. 1998, Challis et al. 2003, Krude et al. 2003).
Literature References
PubMed ID Title Journal Year
12165561 A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism

Farooqi, IS, Wareham, NJ, Challis, BG, O'Rahilly, S, Pritchard, LE, Creemers, JW, White, A, Luan, J, Yeo, GS, Delplanque, J, Keogh, JM, Froguel, P, Bhattacharyya, S

Hum. Mol. Genet. 2002
9620771 Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans

Horn, R, Luck, W, Biebermann, H, Krude, H, Brabant, G, Grüters, A

Nat. Genet. 1998
14557433 Obesity due to proopiomelanocortin deficiency: three new cases and treatment trials with thyroid hormone and ACTH4-10

Schnabel, D, Grüters, A, Theunissen, P, Tansek, MZ, Biebermann, H, Krude, H, Mullis, PE

J. Clin. Endocrinol. Metab. 2003
Participants
Input
Participates
as an event of
Normal reaction
POMC(138-176) binds MC2R (Homo sapiens)
Functional status

Loss of function of ACTH mutants [extracellular region]

Normal Entity
Disease Entity
Status
Disease
Authored
Jassal, B  (2014-06-30)
Reviewed
Nakaki, T  (2014-11-03)
Created
Jassal, B  (2014-06-30)
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