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关于人类和小鼠脂肪钙蛋白(LCN)基因家族的最新研究,包括小鼠 Mup 簇是“进化繁荣”的结果的证据。

Update on the human and mouse lipocalin (LCN) gene family, including evidence the mouse Mup cluster is result of an "evolutionary bloom".

机构信息

Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, 06520-8034, USA.

Mouse Genome Informatics, The Jackson Laboratory, 600 Main Street, Bar Harbor, ME, 04609, USA.

出版信息

Hum Genomics. 2019 Feb 19;13(1):11. doi: 10.1186/s40246-019-0191-9.

Abstract

Lipocalins (LCNs) are members of a family of evolutionarily conserved genes present in all kingdoms of life. There are 19 LCN-like genes in the human genome, and 45 Lcn-like genes in the mouse genome, which include 22 major urinary protein (Mup) genes. The Mup genes, plus 29 of 30 Mup-ps pseudogenes, are all located together on chromosome (Chr) 4; evidence points to an "evolutionary bloom" that resulted in this Mup cluster in mouse, syntenic to the human Chr 9q32 locus at which a single MUPP pseudogene is located. LCNs play important roles in physiological processes by binding and transporting small hydrophobic molecules -such as steroid hormones, odorants, retinoids, and lipids-in plasma and other body fluids. LCNs are extensively used in clinical practice as biochemical markers. LCN-like proteins (18-40 kDa) have the characteristic eight β-strands creating a barrel structure that houses the binding-site; LCNs are synthesized in the liver as well as various secretory tissues. In rodents, MUPs are involved in communication of information in urine-derived scent marks, serving as signatures of individual identity, or as kairomones (to elicit fear behavior). MUPs also participate in regulation of glucose and lipid metabolism via a mechanism not well understood. Although much has been learned about LCNs and MUPs in recent years, more research is necessary to allow better understanding of their physiological functions, as well as their involvement in clinical disorders.

摘要

脂联素(LCNs)是一类进化上保守的基因家族成员,存在于所有生命王国中。人类基因组中有 19 个 LCN 样基因,小鼠基因组中有 45 个 Lcn 样基因,其中包括 22 个主要尿蛋白(Mup)基因。Mup 基因,加上 30 个 Mup-ps 假基因中的 29 个,都位于染色体(Chr)4 上;有证据表明,这种小鼠 Mup 簇是由于“进化繁荣”而产生的,与人类 Chr 9q32 位点上的一个 MUPP 假基因具有同源性。LCNs 通过结合和转运小疏水分子(如甾体激素、气味、视黄醇和脂质)在血浆和其他体液中,在生理过程中发挥重要作用。LCNs 被广泛应用于临床实践中作为生化标志物。LCN 样蛋白(18-40 kDa)具有特征性的 8 个β-链,形成容纳结合部位的桶状结构;LCNs 在肝脏以及各种分泌组织中合成。在啮齿动物中,MUPs 参与尿液衍生气味标记物中的信息传递,作为个体身份的特征,或作为信息素(引起恐惧行为)。MUPs 还通过一种尚未完全理解的机制参与葡萄糖和脂质代谢的调节。尽管近年来对 LCNs 和 MUPs 有了很多了解,但仍需要更多的研究来更好地理解它们的生理功能,以及它们在临床疾病中的参与。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8948/6381713/8ce864b0c713/40246_2019_191_Fig1_HTML.jpg

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