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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/15 17:30:28」(JST)

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プロオピオメラノコルチン(英: Pro-opiomelanocortin, POMC)は、241個のアミノ酸残基からなるポリペプチド前駆体。285個のアミノ酸残基からなるポリペプチドのプレプロオピオメラノコルチン(pre-POMC)から作られる。pre-POMCの翻訳後プロセッシングにて44個のアミノ酸残基のシグナルペプチド配列が切除されPOMCとなる。POMC遺伝子は、2p23.3 染色体に位置する。

POMC産生

POMCは次の組織で産生されるが、主に産生されるのは下垂体の前葉と中葉である。

脳下垂体前葉の副腎皮質刺激ホルモン産生細胞
下垂体中葉のメラニン細胞刺激ホルモン産生細胞
視床下部弓状核にある約3000個の神経細胞^[1]
視床下部背内側核および脳幹にある少数の細胞
皮膚のメラニン細胞

翻訳後プロセッシング

右図(POMCの切断)を参照

pre-POMCは、スブチリシン_(英)様プロホルモン変換酵素による切断を経由して組織特異的な翻訳後プロセッシングを受ける。 POMCのプロセッシングにはグリコシル化、アセチル化、タンパク質分解性の切断がある。ただし、タンパク質分解酵素が切断する箇所は組織特異的である。

例えば、POMCが下垂体前葉の副腎皮質刺激ホルモン産生細胞において産生されると、4ヶ所切断されて副腎皮質刺激ホルモン(ACTH)とβ-リポトロピン(英)となる。

POMC内には、この他に少なくとも８つの切断可能な箇所があり、組織や変換酵素によって次に示す最大10の活性ペプチドが産生されうる。

N-Terminal Peptide of Proopiomelanocortin(英) (NPP, or pro-γ-MSH)
γ-メラニン細胞刺激ホルモン (γ-MSH)
副腎皮質刺激ホルモン (ACTH)
α-メラニン細胞刺激ホルモン (α-MSH)
Corticotropin-like Intermediate Peptide(英) (CLIP)
β-リポトロピン(英) (β-LPH)
γ-リポトロピン(英) (γ-LPH)
β-メラニン細胞刺激ホルモン (β-MSH)
β-エンドルフィン
メチオニン-エンケファリン

切断箇所は、Arg-Lys, Lys-Arg あるいは Lys-Lys配列からなり、POMCペプチドのプロセッシングを行う酵素には、

プロホルモン変換酵素1(英) (PC1)
プロホルモン変換酵素2(英) (PC2)
Carboxypeptidase E (英)(CPE)
peptidyl α-amidating monooxygenase(英) (PAM)
N-acetyltrasferase(英) (N-AT)
prolylcarboxypeptidase(英) (PRCP)

がある。

脚注

^ Cowley et al, Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus, Nature. 2001 May 24;411(6836):480-4.

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[Wiki en表示]

Proopiomelanocortin

Identifiers

Symbols

POMC ; ACTH; CLIP; LPH; MSH; NPP; POC

External IDs

OMIM: 176830 MGI: 97742 HomoloGene: 723 GeneCards: POMC Gene

Gene ontology
Molecular function	• G-protein coupled receptor binding • receptor binding • hormone activity • type 3 melanocortin receptor binding • type 4 melanocortin receptor binding • type 1 melanocortin receptor binding
Cellular component	• extracellular region • extracellular space • cytoplasm • peroxisome • peroxisomal matrix • secretory granule • secretory granule lumen
Biological process	• generation of precursor metabolites and energy • signal transduction • neuropeptide signaling pathway • cell-cell signaling • regulation of blood pressure • peptide hormone processing • regulation of appetite • negative regulation of tumor necrosis factor production • cellular pigmentation • cellular protein metabolic process • positive regulation of transcription from RNA polymerase II promoter
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

Entrez

5443

18976

Ensembl

ENSG00000115138

ENSMUSG00000020660

UniProt

P01189

P01193

RefSeq (mRNA)

NM_000939

NM_001278581

RefSeq (protein)

NP_000930

NP_001265510

Location (UCSC)

Chr 2:
25.38 – 25.39 Mb

Chr 12:
3.95 – 3.96 Mb

PubMed search

[1]

[2]

Opioids neuropeptide

Identifiers

Symbol

Op_neuropeptide

Pfam

PF08035

InterPro

IPR013532

PROSITE

PDOC00964

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Pro-opiomelanocortin (POMC) is a precursor polypeptide with 241 amino acid residues. POMC is synthesized 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.

Function

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:

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.

Synthesis

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.

It is synthesized by:

Corticotrope cells of the anterior pituitary gland
Melanotrope cells of the intermediate lobe of the pituitary gland
3,148±62 Neurons in the arcuate nucleus of the hypothalamus^[1]
Smaller populations of neurons in the dorsomedial hypothalamus and brainstem
Melanocytes in the skin

Derivatives

proopiomelanocortin derivatives
POMC

γ-MSH	ACTH		β-lipotropin

	α-MSH	CLIP	γ-lipotropin		β-endorphin

				β-MSH

The large molecule of POMC is the source of several important biologically active substances. POMC can be cleaved enzymatically into the following peptides:

N-Terminal Peptide of Proopiomelanocortin (NPP, or pro-γ-MSH)
γ-Melanotropin (γ-MSH)
Corticotropin (Adrenocorticotropic Hormone, or ACTH)
α-Melanotropin (α-Melanocyte-Stimulating Hormone, or α-MSH)
Corticotropin-like Intermediate Peptide (CLIP)
β-Lipotropin (β-LPH)
Lipotropin Gamma (γ-LPH)
β-Melanotropin (β-MSH)
β-Endorphin
[Met]Enkephalin

Although the N-terminal 5 amino acids of β-endorphin are identical to the sequence of [Met]enkephalin, it is not generally thought that β-endorphin is converted into [Met]enkephalin.^{[citation needed]} Instead, [Met]enkephalin is produced from its own precursor, proenkephalin A.

The production of β-MSH occurs in humans but not in mice or rats due to the absence of the enzymatic processing site in the rodent POMC.

Clinical significance

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.^[2]^[3]

Interactions

Proopiomelanocortin has been shown to interact with melanocortin 4 receptor.^[4]^[5]

References

^ Cowley MA, Smart JL, Rubinstein M, Cerdán MG, Diano S, Horvath TL et al. (May 2001). "Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus". Nature 411 (6836): 480–4. doi:10.1038/35078085. PMID 11373681.
^ "Entrez Gene: POMC proopiomelanocortin (adrenocorticotropin/ beta-lipotropin/ alpha-melanocyte stimulating hormone/ beta-melanocyte stimulating hormone/ beta-endorphin)".
^ Kuehnen P, Mischke M, Wiegand S, Sers C, Horsthemke B, Lau S et al. (2012). Yeo GS, ed. "An Alu element-associated hypermethylation variant of the POMC gene is associated with childhood obesity". PLoS Genet. 8 (3): e1002543. doi:10.1371/journal.pgen.1002543. PMC 3305357. PMID 22438814.
^ Yang YK, Fong TM, Dickinson CJ, Mao C, Li JY, Tota MR et al. (December 2000). "Molecular determinants of ligand binding to the human melanocortin-4 receptor". Biochemistry 39 (48): 14900–11. doi:10.1021/bi001684q. PMID 11101306.
^ Yang YK, Ollmann MM, Wilson BD, Dickinson C, Yamada T, Barsh GS et al. (March 1997). "Effects of recombinant agouti-signaling protein on melanocortin action". Mol. Endocrinol. 11 (3): 274–80. doi:10.1210/me.11.3.274. PMID 9058374.

External links

Pro-Opiomelanocortin at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates public domain material from websites or documents of the National Center for Biotechnology Information (Reference Sequence collection).

UpToDate Contents

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1. コルチコトロピン-放出ホルモン（CRH）の生理学 physiology of corticotropin releasing hormone
2. ACTH、CRH、および他の視床下部／下垂体ペプチドの測定 measurement of acth crh and other hypothalamic and pituitary peptides
3. 肥満の病因 pathogenesis of obesity
4. 小児および思春期における肥満の定義、疫学および病因 definition epidemiology and etiology of obesity in children and adolescents
5. レプチンの生理学 physiology of leptin

English Journal

Identification of reproduction-related genes and SSR-markers through expressed sequence tags analysis of a monsoon breeding carp rohu, Labeo rohita (Hamilton).

Sahu DK, Panda SP, Panda S, Das P, Meher PK, Hazra RK, Peatman E, Liu ZJ, Eknath AE, Nandi S.SourceCentral Institute of Freshwater Aquaculture, Bhubaneswar, Orissa 75 1002, India.
Gene.Gene.2013 Jul 15;524(1):1-14. doi: 10.1016/j.gene.2013.03.111. Epub 2013 Apr 9.
Labeo rohita (Ham.) also called rohu is the most important freshwater aquaculture species on the Indian sub continent. Monsoon dependent breeding restricts its seed production beyond season indicating a strong genetic control about which very limited information is available. Additionally, few genom
PMID 23583682

Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity.

Cousminer DL, Berry DJ, Timpson NJ, Ang W, Thiering E, Byrne EM, Taal HR, Huikari V, Bradfield JP, Kerkhof M, Groen-Blokhuis MM, Kreiner-Møller E, Marinelli M, Holst C, Leinonen JT, Perry JR, Surakka I, Pietiläinen O, Kettunen J, Anttila V, Kaakinen M, Sovio U, Pouta A, Das S, Lagou V, Power C, Prokopenko I, Evans DM, Kemp JP, St Pourcain B, Ring S, Palotie A, Kajantie E, Osmond C, Lehtimäki T, Viikari JS, Kähönen M, Warrington NM, Lye SJ, Palmer LJ, Tiesler CM, Flexeder C, Montgomery GW, Medland SE, Hofman A, Hakonarson H, Guxens M, Bartels M, Salomaa V; ReproGen Consortium, Murabito JM, Kaprio J, Sørensen TI, Ballester F, Bisgaard H, Boomsma DI, Koppelman GH, Grant SF, Jaddoe VW, Martin NG, Heinrich J, Pennell CE, Raitakari OT, Eriksson JG, Smith GD, Hyppönen E, Järvelin MR, McCarthy MI, Ripatti S, Widén E; Early Growth Genetics (EGG) Consortium.SourceA full list of members is provided in the Supplementary Material.
Human molecular genetics.Hum Mol Genet.2013 Jul 1;22(13):2735-47. doi: 10.1093/hmg/ddt104. Epub 2013 Feb 27.
The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. Although little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and
PMID 23449627

Japanese Journal

Hypothalamic Melanocortin System on Feeding Regulation in Birds : A Review

BUNGO Takashi,SHIRAISHI Jun-ichi,KAWAKAMI Shin-Ichi
The journal of poultry science 48(1), 1-13, 2011-01-25
NAID 10027817305

レプチンによる摂食・代謝制御機構とその破綻 (第1土曜特集神経消化器病学の進歩) -- (内分泌ペプチドと消化器の生理)

諸岡留美,竹井謙之
医学のあゆみ 238(10), 986-992, 2011-09-03
NAID 40018962513

食欲・摂食行動と内分泌ペプチド (第1土曜特集神経消化器病学の進歩) -- (内分泌ペプチドと消化器の生理)

網谷真理恵,浅川明弘,乾明夫
医学のあゆみ 238(10), 979-985, 2011-09-03
NAID 40018962512

Related Pictures

★リンクテーブル★

リンク元	「下垂体前葉ホルモン」「メラニン細胞刺激ホルモン」「プロオピオメラノコルチン」「βリポトロピン」「pro-opiomelanocortin peptide family」
関連記事	「PO」「POM」

「下垂体前葉ホルモン」

Opioids neuropeptide
識別子
略号	Op_neuropeptide
Pfam	PF08035
InterPro	IPR013532
PROSITE	PDOC00964
利用可能な蛋白質構造:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

POMCの切断
	POMC

プロオピオメラノコルチン（副腎皮質刺激ホルモン/ β-リポトロピン/ α-メラノサイト刺激ホルモン/ β-メラノサイト刺激ホルモン/ β-エンドルフィン）
識別記号
記号（英語版）	POMC; LPH; MSH; ACTH; CLIP; NPP; POC
その他ID	OMIM（英語版）: 176830 MGI（英語版）: 97742 HomoloGene（英語版）: 723 GeneCards: POMC Gene
遺伝子オントロジー
分子機能	• hormone activity;
細胞の構成要素	• extracellular region; • soluble fraction;
生物学的プロセス	• generation of precursor metabolites and energy; • signal transduction; • neuropeptide signaling pathway; • cell-cell signaling; • blood pressure regulation;
	出典: Amigo / EGO
RNA発現パターン
	その他参照発現データ
オルソログ

　　[★]

英: anterior pituitary hormone
関: 下垂体前葉、下垂体、下垂体ホルモン、ホルモン

分泌されるホルモン

単純ペプチドホルモン

糖タンパク質ホルモン

GOO. chapter 55

名称		構造	分泌細胞	下垂体前葉細胞全細胞に対する産生細胞の割合	染色性		サブユニット	残基数 (aa.)	分子量 (kDa)	その他
成長ホルモン	GH	ペプチド	somatotroph	40-50%	好酸性		1	191	22
プロラクチン	PRL		mammotroph	10-25%	好酸性		1	199	23
副腎皮質刺激ホルモン	ACTH		corticotroph	0.1	好塩基性	嫌色素性	1	39	4.5	POMC由来
甲状腺刺激ホルモン	TSH	糖タンパク	thyrotroph	0.05	好塩基性		2	α: 92, β:118	28	αサブユニットは共通
卵胞刺激ホルモン	FSH		gonadotroph	10-15%	好塩基性		2	α: 92, β:111	32.6
黄体形成ホルモン	LH		gonadotroph	10-15%	好塩基性		2	α: 92, β:121	29.4

HIM.2196

Table 333-1 Anterior Pituitary Hormone Expression and Regulation
Cell	corticotrope	somatotrope	lactotrope	thyrotrope	gonadotrope
Tissue-specific transcription factor	T-Pit	Prop-1, Pit-1	Prop-1, Pit-1	Prop-1, Pit-1, TEF	SF-1, DAX-1
Fetal appearance	6 weeks	8 weeks	12 weeks	12 weeks	12 weeks
Hormone	POMC	GH	PRL	TSH	FSH LH
Chromosomal locus	2p	17q	6	－6q; －1p	－11p; －19q
Protein	ポリペプチド			糖タンパク
Amino acids	266 (ACTH 1–39)	191	199	211	210 204
Stimulators	CRH, AVP, gp-130 cytokines	GHRH, ghrelin, bromocriptine⁽¹⁾	estrogen, TRH, VIP	TRH	GnRH, activins, estrogen
Inhibitors	glucocorticoids	somatostatin, IGF-I	dopamine	T3, T4, dopamine, somatostatin, glucocorticoids	sex steroids, inhibin
Target gland	adrenal	liver, other tissues	breast, other tissues	thyroid	ovary, testis
Trophic effect	steroid production	IGF-I production, growth induction, insulin antagonism	milk production	T4 synthesis and secretion	sex steroid production, follicle growth, germ cell maturation