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Melanokortinski 4 receptor

Уреди везе

С Википедије, слободне енциклопедије

Melanokortin 4 receptor

Identifikatori

Simboli

MC4R; MGC126851; MGC138197

Vanjski ID

OMIM: 155541MGI: 99457HomoloGene: 4320IUPHAR:MC₄GeneCards:MC4R Gene

Ontologija gena
Molekularna funkcija	•rodopsinu-sličan receptorska aktivnost •receptorska aktivnost •aktivnost melanokortin receptora •proteinsko vezivanje
Celularna komponenta	•membrana plazma •integralno sa membranom
Biološki proces	•prenos signala •signalni put G-protein spregnutog receptora •G-protein signalizacija, spregnuta sa cAMP nukleotid drugim glasnikom •ishrana •regulacija metaboličkog procesa •pozitivna regulacija resorpcije kosti

Pregled RNK izražavanja

podaci

Ortolozi

Vrsta

Čovek

Miš

RefSeq (mRNA)

RefSeq (protein)

Lokacija (UCSC)

Chr 18:
56.19 - 56.19 Mb

Chr 18:
66.98 - 66.99 Mb

PubMed pretraga

[1]

[2]

Melanokortin receptor 4 jeprotein koji je kod ljudi kodiranMC4Rgenom.^[1]^[2]^[3] Ova gen kodiraMC₄ protein,G-protein spregnuti receptor koji vezuje α-melanocit stimulišući hormon (α-MSH). U modelima naglodarima za MC₄ receptore je bilo ustanovljeno da učestvuju u ishrani, regulaciji metabolizma, seksualnom ponašanju, i muškoj erektilnoj funkciji^[4]^[5]^[6]

1998 godine je bilo objavljeno da su MC4R mutacije vezane za naslednu gojaznost kod ljudi. One su nađene kod heterozigota, što sugestira autozomni dominantni nasledni trend. Međutim, na bazi drugih istraživanja i opažanja, te mutacije izgleda da imaju delimičnu penetrantnost i određeni stupanj kodominantnosti. Njihova zastupljenost od 1-2.5% kod ljudi saBMI većim od 30, čini ih najzastupljenijim među poznatim genetskim defektima koji predispozicioniraju ljude ka gojaznosti.^[7]

Interakcije

[уреди |уреди извор]

Za melanokortin 4 receptor je bilo pokazano dainteraguje saproopiomelanokortinom.^[8]^[9]

Klinički značaj

[уреди |уреди извор]

2009 godine su sprovedene dve veoma velikeBMI asocijacione studije koje su obuhvatale celokupnigenom. One su potvrdile asocijaciju varijanti sa oko 150 kilo baza nizvodno od MC4R gena sa otpornošću nainsulin,gojažnošću i drugim antropometrijskim odlikama.^[10]^[11]^[12]^[13]

Vidi još

[уреди |уреди извор]

Melanokortin receptor

Reference

[уреди |уреди извор]

^Magenis RE, Smith L, Nadeau JH, Johnson KR, Mountjoy KG, Cone RD (1994). „Mapping of the ACTH, MSH, and neural (MC3 and MC4) melanocortin receptors in the mouse and human”.Mamm Genome.5 (8): 503—8.PMID 7949735.doi:10.1007/BF00369320.
^Sundaramurthy D, Campbell DA, Leek JP, Markham AF, Pieri LF (1998). „Assignment of the melanocortin 4 receptor (MC4R) gene to human chromosome band 18q22 by in situ hybridisation and radiation hybrid mapping”.Cytogenet Cell Genet.82 (1-2): 97—8.PMID 9763669.doi:10.1159/000015074.
^„Entrez Gene: MC4R melanocortin 4 receptor”.
^Fan W, Boston BA, Kesterson RA, Hruby VJ, Cone RD (1997).„Role of melanocortinergic neurons in feeding and the agouti obesity syndrome”.Nature.385 (6612): 165—168.PMID 8990120.doi:10.1038/385165a0.
^Huszar D, Lynch CA, Fairchild-Huntress V, Dunmore JH, Fang Q, Berkemeier LR, Gu W, Kesterson RA, Boston BA, Cone RD, Smith FJ, Campfield LA, Burn P, Lee F (1997). „Targeted disruption of the melanocortin-4 receptor results in obesity in mice”.Cell.88 (1): 131—141.PMID 9019399.doi:10.1016/S0092-8674(00)81865-6.
^Van der Ploeg LH, Martin WJ, Howard AD, Nargund RP, Austin CP, Guan X, Drisko J, Cashen D, Sebhat I, Patchett AA, Figueroa DJ, DiLella AG, Connolly BM, Weinberg DH, Tan CP, Palyha OC, Pong SS, MacNeil T, Rosenblum C, Vongs A, Tang R, Yu H, Sailer AW, Fong TM, Huang C, Tota MR, Chang RS, Stearns R, Tamvakopoulos C, Christ G, Drazen DL, Spar BD, Nelson RJ, MacIntyre DE (2002).„A role for the melanocortin 4 receptor in sexual function”.Proc Natl Acad Sci USA.99 (17): 11381—11386.PMC 123265 .PMID 12172010.doi:10.1073/pnas.172378699.
^Farooqi S, O'Rahilly S (2006). „Genetics of obesity in humans”.Endocrine Reviews.27 (7): 710—718.PMID 17122358.doi:10.1210/er.2006-0040.
^Yang, Y K; Fong T M; et al. (2000). „Molecular determinants of ligand binding to the human melanocortin-4 receptor”.Biochemistry. UNITED STATES.39 (48): 14900—11.ISSN 0006-2960.PMID 11101306.doi:10.1021/bi001684q.
^Yang, Y K; Ollmann M M; et al. (1997). „Effects of recombinant agouti-signaling protein on melanocortin action”.Mol. Endocrinol. UNITED STATES.11 (3): 274—80.ISSN 0888-8809.PMID 9058374.doi:10.1210/me.11.3.274.
^Chambers JC; Elliott P; Zabaneh D; et al. (2008). „Common genetic variation near MC4R is associated with waist circumference and insulin resistance.”.Nat. Genet.40 (6): 716—18.PMID 18454146.doi:10.1038/ng.156.
^Loos RJ; Lindgren CM; Li S; Wheeler E; et al. (2008).„Common variants near MC4R are associated with fat mass, weight and risk of obesity.”.Nat. Genet.40 (6): 768—75.PMC 2669167 .PMID 18454148.doi:10.1038/ng.140.
^Thorleifsson G; Walters GB; Gudbjartsson DF; et al. (2009). „Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity.”.Nat. Genet.41 (1): 18—24.PMID 19079260.doi:10.1038/ng.274.
^Willer CJ; Speliotes EK; Loos RJ; et al. (2009).„Six new loci associated with body mass index highlight a neuronal influence on body weight regulation.”.Nat. Genet.41 (1): 24—34.PMC 2695662 .PMID 19079261.doi:10.1038/ng.287.

Literatura

[уреди |уреди извор]

Mountjoy KG; Mortrud MT; Low MJ; et al. (1995). „Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain.”.Mol. Endocrinol.8 (10): 1298—308.PMID 7854347.doi:10.1210/me.8.10.1298.
Gantz I; Miwa H; Konda Y; et al. (1993).„Molecular cloning, expression, and gene localization of a fourth melanocortin receptor.”.J. Biol. Chem.268 (20): 15174—9.PMID 8392067.
Alvaro JD; Tatro JB; Quillan JM; et al. (1996). „Morphine down-regulates melanocortin-4 receptor expression in brain regions that mediate opiate addiction.”.Mol. Pharmacol.50 (3): 583—91.PMID 8794897.
Yang YK; Ollmann MM; Wilson BD; et al. (1997). „Effects of recombinant agouti-signaling protein on melanocortin action.”.Mol. Endocrinol.11 (3): 274—80.PMID 9058374.doi:10.1210/me.11.3.274.
Chagnon YC; Chen WJ; Pérusse L; et al. (1998).„Linkage and association studies between the melanocortin receptors 4 and 5 genes and obesity-related phenotypes in the Québec Family Study.”.Mol. Med.3 (10): 663—73.PMC 2230227 .PMID 9392003.
Yeo GS; Farooqi IS; Aminian S; et al. (1998). „A frameshift mutation in MC4R associated with dominantly inherited human obesity.”.Nat. Genet.20 (2): 111—2.PMID 9771698.doi:10.1038/2404.
Vaisse C, Clement K, Guy-Grand B, Froguel P (1998). „A frameshift mutation in human MC4R is associated with a dominant form of obesity.”.Nat. Genet.20 (2): 113—4.PMID 9771699.doi:10.1038/2407.
Hinney A; Schmidt A; Nottebom K; et al. (1999). „Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans.”.J. Clin. Endocrinol. Metab.84 (4): 1483—6.PMID 10199800.doi:10.1210/jc.84.4.1483.
Yang YK; Dickinson CJ; Zeng Q; et al. (1999).„Contribution of melanocortin receptor exoloops to Agouti-related protein binding.”.J. Biol. Chem.274 (20): 14100—6.PMID 10318826.doi:10.1074/jbc.274.20.14100.
Ho G, MacKenzie RG (2000). „Functional characterization of mutations in melanocortin-4 receptor associated with human obesity.”.J. Biol. Chem.274 (50): 35816—22.PMID 10585465.doi:10.1074/jbc.274.50.35816.
Yang YK; Fong TM; Dickinson CJ; et al. (2001). „Molecular determinants of ligand binding to the human melanocortin-4 receptor.”.Biochemistry.39 (48): 14900—11.PMID 11101306.doi:10.1021/bi001684q.
Mergen M; Mergen H; Ozata M; et al. (2001). „A novel melanocortin 4 receptor (MC4R) gene mutation associated with morbid obesity.”.J. Clin. Endocrinol. Metab.86 (7): 3448.PMID 11443223.doi:10.1210/jc.86.7.3448.
McNulty JC; Thompson DA; Bolin KA; et al. (2002). „High-resolution NMR structure of the chemically-synthesized melanocortin receptor binding domain AGRP(87-132) of the agouti-related protein.”.Biochemistry.40 (51): 15520—7.PMID 11747427.doi:10.1021/bi0117192.
Brocke KS; Neu-Yilik G; Gehring NH; et al. (2002). „The human intronless melanocortin 4-receptor gene is NMD insensitive.”.Hum. Mol. Genet.11 (3): 331—5.PMID 11823452.doi:10.1093/hmg/11.3.331.
Yang Y; Chen M; Lai Y; et al. (2002).„Molecular determinants of human melanocortin-4 receptor responsible for antagonist SHU9119 selective activity.”.J. Biol. Chem.277 (23): 20328—35.PMID 11912210.doi:10.1074/jbc.M201343200.
Hansen MJ, Morris MJ (2002).„Evidence for an interaction between neuropeptide Y and the melanocortin-4 receptor on feeding in the rat.”.Neuropharmacology.42 (6): 792—7.PMID 12015205.doi:10.1016/S0028-3908(02)00025-4.
Miraglia Del Giudice E; Cirillo G; Nigro V; et al. (2002). „Low frequency of melanocortin-4 receptor (MC4R) mutations in a Mediterranean population with early-onset obesity.”.Int. J. Obes. Relat. Metab. Disord.26 (5): 647—51.PMID 12032748.doi:10.1038/sj.ijo.0801983.
Kim CS; Lee SH; Kim RY; et al. (2002).„Identification of domains directing specificity of coupling to G-proteins for the melanocortin MC3 and MC4 receptors.”.J. Biol. Chem.277 (35): 31310—7.PMID 12045190.doi:10.1074/jbc.M112085200.
„Melanocortin Receptors: MC₄”.IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Архивирано изоригинала 03. 03. 2016. г.

Transmembranski receptor:receptori spregnuti s G proteinom

Klasa A:Rodopsinu slični

Neurotransmiter

Adrenergički	α1 (A,B,D) • α2 (A,B,C) • β1 • β2 • β3
Purinski	Adenozinski (A1,A2A,A2B,A3) • P2Y (1,2,4,5,6,8,9,10,11,12,13,14)
Serotoninski	(svi osim 5-HT3)5-HT1 (A,B,D,E,F) • 5-HT2 (A,B,C) • 5-HT (4,5A,6,7)
Drugi	Acetilholin (M1,M2,M3,M4,M5) • Dopamin (D1,D2,D3,D4,D5) • Histamin (H1,H2,H3,H4) • Melatonin (1A,1B,1C) • TAAR (1,2,3,5,6,8,9)

Metaboliti i
signalni molekuli

Eikozanoidni	CysLT (1,2) • LTB4 (1,2) • FPRL1 • OXE • Prostaglandin (DP (1,2),EP (1,2,3,4),FP) • Prostaciklin • Tromboksan
Drugi	Žučna kiselina • Kanabinoidni (CB1,CB2,GPR (18,55,119)) • EBI2 • Estrogen • Slobodna masna kiselina (1,2,3,4) • Laktat • Lizofosfatidna kiselina (1,2,3,4,5,6) • Lizofosfolipid (1,2,3,4,5,6,7,8) • Niacin (1,2) • Oksoglutarat • PAF • Sfingozin-1-fosfat (1,2,3,4,5) • Sukcinat

Peptid

Neuropeptidni

B/W (1,2) • FF (1,2) • S • Y (1,2,4,5) • Neuromedin (B,U (1,2)) • Neurotenzin (1,2)

Drugi

Anafilatoksin (C3a,C5a) • Angiotenzin (1,2) • Apelin • Bombezin (BRS3,GRPR,NMBR) • Bradikinin (B1,B2) • Hemokin • Holecistokinin (A,B) • Endotelin (A,B) • Formil peptid (1,2,3) • FSH • Galanin (1,2,3) • GHB receptor • Gonadotropin-oslobađajući hormon (1,2) • Grelin • Kispeptin • Luteinizirajući hormon/horiogonadotropin • MAS (1,1L,D,E,F,G,X1,X2,X3,X4) • Melanokortin (1,2,3,4,5) • MCHR (1,2) • Motilin • Opioidni (δ,κ,μ,Nociceptin &ζ, ali neσ) • Oreksin (1,2) • Oksitocin • Prokineticin (1,2) • Prolaktin-oslobađajući peptid • Relaksin (1,2,3,4) • Somatostatin (1,2,3,4,5) • Tahikinin (1,2,3) • Tirotropin • Tirotropin-oslobađajući hormon • Urotenzin-II • Vazopresin (1A,1B,2)

Razno

Orfan	GPR (1,3,4,6,12,15,17,18,19,20,21,22,23,25,26,27,31,32,33,34,35,37,39,42,44,45,50,52,55,61,62,63,65,68,75,77,78,81,82,83,84,85,87,88,92,101,103,109A,109B,119,120,132,135,137B,139,141,142,146,148,149,150,151,152,153,160,161,162,171,173,174,176,177,182,183)
Drugi	Adrenomedulin • Mirisni • Opsin (3,4,5,1LW,1MW,1SW,RGR,RRH) • Proteazom-aktivirani (1,2,3,4) • SREB (1,2,3)

Klasa B:Sekretinu slični

Orfan	GPR (56,64,97,98,110,111,112,113,114,115,116,123,124,125,126,128,133,143,144,155,157)
Drugi	Moždano specifični angiogenezni inhibitor (1,2,3) • Kadherin (1,2,3) • Kalcitonin • CALCRL • CD97 • Kortikotropin-oslobađajući hormon (1,2) • EMR (1,2,3) • Glukagon (GR,GIPR,GLP1R,GLP2R) • Hormon rasta • PACAPR1 • GPR • Latrofilin (1,2,3,ELTD1) • Metuzalemski protein • Paratiroidni hormon (1,2) • Sekretin • Vazoaktivni intestinalni peptid (1,2)

Klasa C:Metabotropni
glutamat /feromon

Ukus	TAS1R (1,2,3) • TAS2R (1,3,4,5,8,9,10,12,13,14,16,19,20,30,31,38,39,40,41,42,43,45,46,50)
Drugi	Kalcijum-detektujući receptor • GABA B (1,2) • Glutamatni receptor (Metabotropni glutamat (1,2,3,4,5,6,7,8)) • GPRC6A • GPR (156,158,179) • RAIG (1,2,3,4) • VNR (1,2,3,5)

Klasa F:
Frizzled /Zaglađeni

Uvojiti	Frizzled (1,2,3,4,5,6,7,8,9,10)
Zaglađeni	Zaglađeni

Neuropeptidni ligandi

Holecistokinin

CCK_A	Agonisti:Holecistokinin •CCK-4 Antagonisti:Asperlicin •Proglumid •Lorglumid •Devazepid •Deksloksiglumid
CCK_B	Agonisti:Holecistokinin •CCK-4 •Gastrin Antagonisti:Proglumid •CI-988

CRH

CRF₁	Agonisti:Kortikotropin-oslobađajuči hormon Antagonisti:Antalarmin •CP-154,526 •Peksacerfont
CRF₂	Agonisti:Kortikotropin-oslobađajuči hormon

Galanin

GAL₁	Agonisti:Galanin •Galaninu-sličan peptid •Galmic •Galnon
GAL₂	Agonisti:Galanin •Galaninu-sličan peptid •Galmic •Galnon
GAL₃	Agonisti:Galanin •Galmic •Galnon

Grelin

Agonisti:Grelin •Kapromorelin •MK-677 •Sermorelin •SM-130,686 •Tabimorelin

MCH

MCH₁	Agonisti:Melanin-koncentrirajući hormon Antagonisti:ATC-0175 •GW-803,430 •NGD-4715 •SNAP-7941 •SNAP-94847
MCH₂	Agonisti:Melanin-koncentrirajući hormon

Melanokortin

MC₁	Agonisti:alfa-MSH •Afamelanotid •Bremelanotid •Melanotan II Antagonisti:Agouti signalni peptid
MC₂	Agonisti:ACTH •Kosintropin •Tetrakosaktid
MC₃	Agonisti:alfa-MSH •Bremelanotid •Melanotan II
MC₄	Agonisti:alfa-MSH •Bremelanotid •Melanotan II •THIQ Antagonisti:Agutiju srodni peptid
MC₅	Agonisti:alfa-MSH •Melanotan II

Neuropeptid S

Agonisti:Neuropeptid S
Antagonisti:SHA-68

Neuropeptid Y

Y₁	Agonisti:Neuropeptid Y •Peptid YY Antagonisti:BIBP-3226
Y₂	Agonisti:Neuropeptid Y •Peptid YY Antagonisti:BIIE-0246
Y₄	Agonisti:Neuropeptid Y •Pankreasni polipeptid •Peptid YY Antagonisti:UR-AK49
Y₅	Agonisti:Neuropeptid Y •Peptid YY Antagonisti:Lu AA-33810

Neurotenzin

NTS₁	Agonisti:Neurotenzin •Neuromedin N Antagonisti:SR-48692 •SR-142,948
NTS₂	Agonisti:Neurotenzin Antagonisti:Levokabastin •SR-142,948

Opioid

vidiOpioidi

Oreksin

OX₁	Agonisti:Oreksin-A Antagonisti:Almoreksant •SB-334,867 •SB-408,124 •SB-649,868
OX₂	Agonisti:Oreksin-A Antagonisti:Almoreksant •SB-649,868 •TCS-OX2-29

Oksitocin

Agonisti:Karbetocin •Demoksitocin •Oksitocin •WAY-267,464
Antagonisti:Atosiban •L-371,257 •L-368,899

Tahikinin

NK₁	Agonisti:Supstanca P Antagonisti:Aprepitant •Befetupitant •Kasopitant •CI-1021 •CP-96,345 •CP-99,994 •CP-122,721 •Dapitant •Ezlopitant •FK-888 •Fosaprepitant •GR-203,040 •GW-597,599 •HSP-117 •L-733,060 •L-741,671 •L-743,310 •L-758,298 •Lanepitant •LY-306,740 •Maropitant •Netupitant •NKP-608 •Nolpitantium •Orvepitant •RP-67,580 •SDZ NKT 343 •Vestipitant •Vofopitant
NK₂	Agonisti:Neurokinin A Antagonisti:GR-159897 •Ibodutant •Saredutant
NK₃	Agonisti:Neurokinin B Antagonisti:Osanetant •Talnetant

Vazopresin

V_1A	Agonisti:Dezmopresin •Felipresin •Ornipresin •Terlipresin •Vazopresin Antagonisti:Konivaptan •Demeklociklin •Relkovaptan
V_1B	Agonisti:Felipresin •Ornipresin •Terlipresin •Vazopresin Antagonisti:Demeklociklin •Nelivaptan
V₂	Agonisti:Dezmopresin •Ornipresin •Vazopresin Antagonisti:Konivaptan •Demeklociklin •Liksivaptan •Mozavaptan •Satavaptan •Tolvaptan

Преузето из „https://sr.wikipedia.org/w/index.php?title=Melanokortinski_4_receptor&oldid=30647445”

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