脂聯素

脂連蛋白（英語：adiponectin，亦稱為脂聯素）是一種主要由脂肪細胞分泌的蛋白質激素，由ADIPOQ基因所編碼^[5]，含244個氨基酸。成人體內的脂聯素水平與脂肪儲量負相關^{[來源請求]}。

脂聯素
已知的結構 PDB 直系同源搜尋: PDBe RCSB PDBID列表 4DOU
識別號
別名	ADIPOQ；, ACDC, ACRP30, ADIPQTL1, ADPN, APM-1, APM1, GBP28, adiponectin, C1Q and collagen domain containing, Adiponectin
外部ID	OMIM：605441 MGI：106675 HomoloGene：3525 GeneCards：ADIPOQ
基因位置（人類） 染色體 3號染色體[1] 基因座 3q27.3 起始 186,842,704 bp[1] 終止 186,858,463 bp[1]
基因位置（小鼠） 染色體 小鼠16號染色體[2] 基因座 16 B1|16 13.96 cM 起始 22,965,286 bp[2] 終止 22,976,778 bp[2]
RNA表達模式
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基因本體 分子功能 • hormone activity • signaling receptor binding • 細胞因子活性 • sialic acid binding • protein homodimerization activity • 血漿蛋白結合 • 相同蛋白質結合 • extracellular matrix structural constituent 細胞組分 • cell surface • 內質網 • 膠原蛋白 • 細胞外空間 • 細胞外區域 • 大分子複合體 • collagen-containing extracellular matrix 生物學過程 • positive regulation of glucose import • positive regulation of protein phosphorylation • negative regulation of receptor binding • low-density lipoprotein particle clearance • negative regulation of blood pressure • negative regulation of macrophage differentiation • negative regulation of synaptic transmission • generation of precursor metabolites and energy • cellular response to epinephrine stimulus • negative regulation of gluconeogenesis • regulation of glucose metabolic process • 晝夜節律 • fatty acid oxidation • positive regulation of interleukin-8 production • glucose metabolic process • protein heterotrimerization • negative regulation of heterotypic cell-cell adhesion • response to ethanol • negative regulation of inflammatory response • cellular response to cAMP • positive regulation of protein kinase A signaling • negative regulation of platelet-derived growth factor receptor signaling pathway • positive regulation of signal transduction • positive regulation of protein metabolic process • negative regulation of fat cell differentiation • response to linoleic acid • detection of oxidative stress • glucose homeostasis • adiponectin-activated signaling pathway • response to tumor necrosis factor • positive regulation of blood pressure • response to nutrient levels • positive regulation of cholesterol efflux • negative regulation of MAP kinase activity • cellular response to insulin stimulus • positive regulation of peptidyl-tyrosine phosphorylation • fatty acid beta-oxidation • 腫瘤壞死因子產生的負調控 • protein localization to plasma membrane • negative regulation of hormone secretion • protein homooligomerization • response to sucrose • positive regulation of metanephric glomerular visceral epithelial cell development • positive regulation of renal albumin absorption • negative regulation of granulocyte differentiation • response to nutrient • negative regulation of protein autophosphorylation • negative regulation of intracellular protein transport • membrane depolarization • response to glucose • positive regulation of myeloid cell apoptotic process • negative regulation of I-kappaB kinase/NF-kappaB signaling • negative regulation of metanephric mesenchymal cell migration • negative regulation of cell migration • positive regulation of fatty acid metabolic process • brown fat cell differentiation • positive regulation of cAMP-dependent protein kinase activity • positive regulation of glycogen (starch) synthase activity • negative regulation of transcription, DNA-templated • negative regulation of DNA biosynthetic process • positive regulation of protein kinase activity • response to hypoxia • negative regulation of phagocytosis • membrane hyperpolarization • negative regulation of tumor necrosis factor-mediated signaling pathway • positive regulation of monocyte chemotactic protein-1 production • response to glucocorticoid • response to activity • negative regulation of platelet-derived growth factor receptor-alpha signaling pathway • positive regulation of I-kappaB kinase/NF-kappaB signaling • negative regulation of ERK1 and ERK2 cascade • negative regulation of macrophage derived foam cell differentiation • regulation of fatty acid biosynthetic process • regulation of signaling receptor activity • negative regulation of vascular associated smooth muscle cell proliferation • negative regulation of vascular associated smooth muscle cell migration • response to bacterium • positive regulation of cold-induced thermogenesis • negative regulation of cold-induced thermogenesis • 信號轉導 Sources:Amigo / QuickGO
直系同源
物種	人類	小鼠
Entrez	9370	11450
Ensembl	ENSG00000181092	ENSMUSG00000022878
UniProt	Q15848	Q60994
mRNA​序列	NM_001177800 ​NM_004797	NM_009605
蛋白序列	NP_001171271 ​NP_004788	NP_033735
基因位置​（UCSC）	Chr 3: 186.84 – 186.86 Mb	Chr 16: 22.97 – 22.98 Mb
PubMed​查找	[3]	[4]
維基數據
檢視/編輯人類 檢視/編輯小鼠

結構

脂聯素包含244個氨基酸，可分為4個結構域。從其N端起算，第一個是使其定位於細胞外的信號序列，第二個區域較短且在物種間高度變異，第三個65個氨基酸的區域與膠原蛋白相似，最後一個是脂聯素的球狀結構域。總的上看，這一蛋白與補體片段C1q（英語：C1q）相似。其中球狀結構域的三維結構已經測定，結構上與TNFα非常相似，但在氨基酸序列上卻差異巨大^[6]。

受體

脂聯素可與幾種受體結合，兩種受體與G蛋白偶聯受體有同源性，一種屬於鈣粘蛋白家族^[7][8]：

• 脂聯素受體1 – ADIPOR1
• 脂聯素受體2 – ADIPOR2
• T-cadherin - CDH13（英語：T-cadherin）

這些受體影響下游靶標AMP激酶（英語：AMP-activated protein kinase）,這是一個重要的細胞代謝率控制點。受體的表達與胰島素水平相關，並且在糖尿病小鼠模型中降低，特別是在骨骼肌和脂肪組織中^[9][10]。

參考文獻

1. GRCh38: Ensembl release 89: ENSG00000181092 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000022878 - Ensembl, May 2017
3. Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
4. Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). Biochem. Biophys. Res. Commun. April 1996, 221 (2): 286–9. PMID 8619847. doi:10.1006/bbrc.1996.0587.
6. Shapiro L, Scherer PE. The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor. Curr. Biol. March 1998, 8 (6): 335–8. PMID 9512423. doi:10.1016/S0960-9822(98)70133-2.
7. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003, 423 (6941): 762–9. PMID 12802337. doi:10.1038/nature01705.
8. Hug C, Wang J, Ahmad NS, Bogan JS, Tsao TS, Lodish HF. T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin. Proc. Natl. Acad. Sci. U.S.A. 2004, 101 (28): 10308–13. PMC 478568 . PMID 15210937. doi:10.1073/pnas.0403382101.
9. Fang X, Sweeney G. Mechanisms regulating energy metabolism by adiponectin in obesity and diabetes. Biochem. Soc. Trans. 2006, 34 (Pt 5): 798–801. PMID 17052201. doi:10.1042/BST0340798.
10. Bonnard C, Durand A, Vidal H, Rieusset J. Changes in adiponectin, its receptors and AMPK activity in tissues of diet-induced diabetic mice. Diabetes Metab. 2008, 34 (1): 52–61. PMID 18222103. doi:10.1016/j.diabet.2007.09.006.