Defective ACTH does not bind MCR2

Stable Identifier
Reaction [transition]
Homo sapiens
Defective POMC(138-176) does not bind MCR2, Defective ACTH does not bind MC2R, Defective POMC(138-176) does not bind MC2R
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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, GrĂ¼ters, A

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

Schnabel, D, GrĂ¼ters, A, Theunissen, P, Tansek, MZ, Biebermann, H, Krude, H, Mullis, PE

J. Clin. Endocrinol. Metab. 2003
Normal reaction
Functional status

Loss of function of ACTH mutants [extracellular region]

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