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14-September-2008 18:02:48 - Proopiomelanocortin Proopiomelanocortin adrenocorticotropin/ beta-lipotropin/ alpha-melanocyte stimulating hormone/ beta-melanocyte stimulating hormone/ beta-endorphin Identifiers Symbols POMC; LPH; MSH; ACTH; CLIP; NPP; POC External IDs OMIM: 176830 MGI: 97742 HomoloGene: 723 Gene ontology Molecular function: hormone activity Cellular component: extracellular region soluble fraction Biological process: generation of precursor metabolites and energy signal transduction neuropeptide signaling pathway cell-cell signaling blood pressure regulation RNA expression pattern More reference expression data Orthologs Human Mouse Entrez 5443 18976 Ensembl ENSG00000115138 ENSMUSG00000020660 Uniprot P01189 P01193 Refseq NM_000939 mRNA NP_000930 protein NM_008895 mRNA NP_032921 protein Location Chr 2: 25.24 - 25.25 Mb Chr 12: 3.95 - 3.96 Mb Pubmed search 1 2 Pro-opiomelanocortin POMC is a precursor polypeptide with 241 amino acid residues. This gene encodes a polypeptide hormone precursor that undergoes extensive, tissue-specific, post-translational processing via cleavage by subtilisin-like enzymes known as prohormone convertases. There are 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. The encoded protein is synthesized mainly in corticotroph cells of the anterior pituitary where four cleavage sites are used; adrenocorticotrophin, essential for normal steroidogenesis and the maintenance of normal adrenal weight, and lipotropin beta are the major end products. In other 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 beta-lipotropin peptides. Mutations in this gene have been associated with early onset obesity, adrenal insufficiency, and red hair pigmentation. Alternatively spliced transcript variants encoding the same protein have been described.1 Contents 1 Production 2 Derivatives 3 Functions 4 See also 5 External links 6 References 7 Further reading Production It is synthesised by corticotrope cells of the anterior pituitary gland melanotrope cells of the intermediate lobe of the pituitary gland about 3000 neurons in the arcuate nucleus of the hypothalamus smaller populations of neurons in the dorsomedial hypothalamus and brainstem melanocytes in the skin Derivatives The large molecule of POMC is the source of several important biologically active substances. POMC can be cleaved enzymatically into the following peptides: adrenocorticotropic hormone ACTH and β-LPH in the anterior pituitary gland CLIP, γ-LPH, α-MSH and β-endorphin in the intermediate lobe γ-MSH β-MSH Although the N-terminal 5 amino acids of beta-endorphin are identical to the sequence of Met-enkephalin, it is not generally thought that beta-endorphin is converted into Met-enkephalin. Instead, Met-enkephalin is produced from its own precursor, proenkephalin. The production of beta-MSH occurs in humans but not in mice or rats due to the absence of the enzymatic processing site in the rodent POMC. Functions Processing of POMC. Processing of POMC. Each of these peptides is packaged in large dense-core vesicles that are released from the cells by exocytosis in response to appropriate stimulation. α-MSH produced by neurons in the arcuate nucleus has important roles in the regulation of appetite and sexual behavior, while α-MSH secreted from the intermediate lobe of the pituitary regulates the production of melanin. ACTH is a peptide hormone that regulates the secretion of glucocorticoids from the adrenal cortex. β-endorphin and met-enkephalin are endogenous opioid peptides with widespread actions in the brain. See also Melanocortin Melanotan External links MeSH Pro-Opiomelanocortin References ^ Entrez Gene: POMC proopiomelanocortin adrenocorticotropin/ beta-lipotropin/ alpha-melanocyte stimulating hormone/ beta-melanocyte stimulating hormone/ beta-endorphin. Further reading Millington GW May 2006. Proopiomelanocortin POMC: the cutaneous roles of its melanocortin products and receptors. Clin. Exp. Dermatol. 31 3: 407-12. doi:10.1111/j.1365-2230.2006.02128.x. PMID 16681590. Millington GW 2007. The role of proopiomelanocortin POMC neurones in feeding behaviour. Nutr Metab Lond 4: 18. doi:10.1186/1743-7075-4-18. PMID 17764572. Bhardwaj RS, Luger TA 1995. Proopiomelanocortin production by epidermal cells: evidence for an immune neuroendocrine network in the epidermis.. Arch. Dermatol. Res. 287 1: 85-90. doi:10.1007/BF00370724. PMID 7726641. Raffin-Sanson ML, de Keyzer Y, Bertagna X 2003. Proopiomelanocortin, a polypeptide precursor with multiple functions: from physiology to pathological conditions.. Eur. J. Endocrinol. 149 2: 79-90. doi:10.1530/eje.0.1490079. PMID 12887283. Dores RM, Lecaude S 2005. Trends in the evolution of the proopiomelanocortin gene.. Gen. Comp. Endocrinol. 142 1-2: 81-93. doi:10.1016/j.ygcen.2005.02.003. PMID 15862552. König S, Luger TA, Scholzen TE 2006. Monitoring neuropeptide-specific proteases: processing of the proopiomelanocortin peptides adrenocorticotropin and alpha-melanocyte-stimulating hormone in the skin.. Exp. Dermatol. 15 10: 751-61. doi:10.1111/j.1600-0625.2006.00472.x. PMID 16984256. Farooqi S, O'Rahilly S 2007. Genetics of obesity in humans.. Endocr. Rev. 27 7: 710-18. doi:10.1210/er.2006-0040. PMID 17122358. v d e Endocrine system: hormones/endocrine glands Peptide hormones, Steroid hormones Hypothalamic-pituitary Hypothalamus: TRH, CRH , GnRH, GHRH, somatostatin, dopamine - Posterior pituitary: vasopressin, oxytocin - Anterior pituitary: α FSH, LH, TSH, GH, prolactin, POMC ACTH, MSH, endorphins, lipotropin Adrenal axis Adrenal medulla: epinephrine, norepinephrine - Adrenal cortex: aldosterone, cortisol, DHEA Thyroid axis Thyroid: thyroid hormone T3 and T4 - calcitonin - Parathyroid: PTH Gonadal axis Testis: testosterone, AMH, inhibin - Ovary: estradiol, progesterone, inhibin/activin, relaxin pregnancy Other end. glands Pancreas: glucagon, insulin, somatostatin - Pineal gland: melatonin Non-end. glands Placenta: hCG, HPL, estrogen, progesterone - Kidney: renin, EPO, calcitriol, prostaglandin - Heart atrium: ANP - Stomach: gastrin, ghrelin - Duodenum: CCK, GIP, secretin, motilin, VIP - Ileum: enteroglucagon - Adipose tissue: leptin, adiponectin, resistin - Thymus: Thymosin - Thymopoietin - Thymulin - Skeleton: Osteocalcin - Liver/other: Insulin-like growth factor IGF-1, IGF-2 Target-derived NGF, BDNF, NT-3 v d e Peptides: neuropeptides Hypothalamic Somatostatin - CRH - GnRH - GHRH - Orexins - TRH - POMC ACTH, MSH, Lipotropin Gastrointestinal hormones Cholecystokinin - Gastric inhibitory polypeptide - Gastrin - Motilin - Secretin - Vasoactive intestinal peptide Other hormones Vasopressin - Calcitonin - Other Angiotensin - Bombesin/Neuromedin B - Calcitonin gene-related peptide - Carnosine - Delta sleep-inducing peptide - FMRFamide - Galanin - Gastrin releasing peptide - Kinins Bradykinin, Tachykinins - Neuromedin B, N, U - Neuropeptide Y - Neurophysins - Neurotensin - Opioid peptide - Pancreatic polypeptide - Pituitary adenylate cyclase activating peptide Retrieved from http://en..org/wiki/Proopiomelanocortin Categories: Genes on chromosome 2 | Human proteins | Neuropeptides | NeuroendocrinologyHidden category: Protein pages needing a picture Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Deutsch Français РуÑ?Ñ?кий This page was last modified on 25 August 2008, at 03:17
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