脂联素

脂连蛋白（英语：adiponectin，亦称为脂联素）是一种主要由脂肪细胞分泌的蛋白质激素，由ADIPOQ基因所编码^[5]，含244个氨基酸。成人体内的脂联素水平与脂肪储量负相关^{[来源请求]}。

脂联素
已知的结构 PDB 直系同源搜索: PDBe RCSB PDBID列表 4DOU
识别号
别名	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（人类） 染色体 3号染色体[1] 基因座 3q27.3 起始 186,842,704 bp[1] 终止 186,858,463 bp[1]
基因位置（小鼠） 染色体 小鼠16号染色体[2] 基因座 16 B1|16 13.96 cM 起始 22,965,286 bp[2] 终止 22,976,778 bp[2]
RNA表达模式
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基因本体 分子功能 • hormone activity • signaling receptor binding • 细胞因子活性 • sialic acid binding • protein homodimerization activity • 血浆蛋白结合 • 相同蛋白质结合 • extracellular matrix structural constituent 细胞组分 • cell surface • 内质网 • 胶原蛋白 • 细胞外空间 • 细胞外区域 • 大分子复合体 • collagen-containing extracellular matrix 生物学过程 • 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 • 昼夜节律 • 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 • 肿瘤坏死因子产生的负调控 • 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 • 讯息传递 Sources:Amigo / QuickGO
直系同源
物种	人类	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]
维基数据
查看/编辑人类 查看/编辑小鼠

结构

脂联素包含244个氨基酸，可分为4个结构域。从其N端起算，第一个是使其定位于细胞外的信号序列，第二个区域较短且在物种间高度变异，第三个65个氨基酸的区域与胶原蛋白相似，最后一个是脂联素的球状结构域。总的上看，这一蛋白与补体片段C1q（英语：C1q）相似。其中球状结构域的三维结构已经测定，结构上与TNFα非常相似，但在氨基酸序列上却差异巨大^[6]。

受体

脂联素可与几种受体结合，两种受体与G蛋白偶联受体有同源性，一种属于钙粘蛋白家族^[7][8]：

• 脂联素受体1 – ADIPOR1
• 脂联素受体2 – ADIPOR2
• T-cadherin - CDH13（英语：T-cadherin）

这些受体影响下游靶标AMP激酶（英语：AMP-activated protein kinase）,这是一个重要的细胞代谢率控制点。受体的表达与胰岛素水平相关，并且在糖尿病小鼠模型中降低，特别是在骨骼肌和脂肪组织中^[9][10]。

参考文献

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.