Pro-opiomelanocortin (POMC) is a precursor polypeptide with 241 amino acid residues. POMC is synthesized in the pituitary from the 285-amino-acid-long polypeptide precursor pre-pro-opiomelanocortin (pre-POMC), by the removal of a 44-amino-acid-long signal peptide sequence during translation.
POMC is cleaved to give rise to multiple peptide hormones. Each of these peptides is packaged in large dense-core vesicles that are released from the cells by exocytosis in response to appropriate stimulation:
The POMC gene is located on chromosome 2p23.3. The POMC gene is expressed in both the anterior and intermediate lobes of the pituitary gland. This gene encodes a 285-amino acid polypeptide hormone precursor that undergoes extensive, tissue-specific, post-translational processing via cleavage by subtilisin-like enzymes known as prohormone convertases. The encoded protein is synthesized mainly in corticotroph cells of the anterior pituitary, where four cleavage sites are used; adrenocorticotrophin (ACTH), essential for normal steroidogenesis and the maintenance of normal adrenal weight, and β-lipotropin are the major end-products. However, there are at least eight potential cleavage sites within the polypeptide precursor and, depending on tissue type and the available convertases, processing may yield as many as ten biologically active peptides involved in diverse cellular functions. Cleavage sites consist of the sequences Arg-Lys, Lys-Arg, or Lys-Lys. Enzymes responsible for processing of POMC peptides include prohormone convertase 1 (PC1), prohormone convertase 2 (PC2), carboxypeptidase E (CPE), peptidyl α-amidating monooxygenase (PAM), N-acetyltransferase (N-AT), and prolylcarboxypeptidase (PRCP).
The processing of POMC involves glycosylations, acetylations, and extensive proteolytic cleavage at sites shown to contain regions of basic protein sequences. However, the proteases that recognize these cleavage sites are tissue-specific. In some tissues, including the hypothalamus, placenta, and epithelium, all cleavage sites may be used, giving rise to peptides with roles in pain and energy homeostasis, melanocyte stimulation, and immune modulation. These include several distinct melanotropins, lipotropins, and endorphins that are contained within the adrenocorticotrophin and β-lipotropin peptides.
^Cowley MA, Smart JL, Rubinstein M, Cerdán MG, Diano S, Horvath TL, Cone RD, Low MJ (May 2001). "Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus". Nature. 411 (6836): 480–4. doi:10.1038/35078085. PMID11373681.
^Harris RM, Dijkstra PD, Hofmann HA (January 2014). "Complex structural and regulatory evolution of the pro-opiomelanocortin gene family". General and Comparative Endocrinology. 195: 107–15. doi:10.1016/j.ygcen.2013.10.007. PMID24188887.
^Kühnen P, Clément K, Wiegand S, Blankenstein O, Gottesdiener K, Martini LL, Mai K, Blume-Peytavi U, Grüters A, Krude H (July 2016). "Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist". The New England Journal of Medicine. 375 (3): 240–6. doi:10.1056/NEJMoa1512693. PMID27468060.
^Yang YK, Fong TM, Dickinson CJ, Mao C, Li JY, Tota MR, Mosley R, Van Der Ploeg LH, Gantz I (December 2000). "Molecular determinants of ligand binding to the human melanocortin-4 receptor". Biochemistry. 39 (48): 14900–11. doi:10.1021/bi001684q. PMID11101306.
^Yang YK, Ollmann MM, Wilson BD, Dickinson C, Yamada T, Barsh GS, Gantz I (March 1997). "Effects of recombinant agouti-signaling protein on melanocortin action". Molecular Endocrinology. 11 (3): 274–80. doi:10.1210/me.11.3.274. PMID9058374.
Bhardwaj RS, Luger TA (1994). "Proopiomelanocortin production by epidermal cells: evidence for an immune neuroendocrine network in the epidermis". Archives of Dermatological Research. 287 (1): 85–90. doi:10.1007/BF00370724. PMID7726641.
Raffin-Sanson ML, de Keyzer Y, Bertagna X (August 2003). "Proopiomelanocortin, a polypeptide precursor with multiple functions: from physiology to pathological conditions". European Journal of Endocrinology. 149 (2): 79–90. doi:10.1530/eje.0.1490079. PMID12887283.
König S, Luger TA, Scholzen TE (October 2006). "Monitoring neuropeptide-specific proteases: processing of the proopiomelanocortin peptides adrenocorticotropin and alpha-melanocyte-stimulating hormone in the skin". Experimental Dermatology. 15 (10): 751–61. doi:10.1111/j.1600-0625.2006.00472.x. PMID16984256.