hsp70 genes in the human genome: Conservation and differentiation patterns predict a wide array of overlapping and specialized functions.
hsp70 genes in the human genome: Conservation and differentiation patterns predict a wide array of overlapping and specialized functions.
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DOI：
10.1186/1471-2148-8-19
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发表时间：
2008-01-23
影响因子：
3.4
通讯作者：
Macario AJ
中科院分区：
文献类型：
--
作者：
Brocchieri L;Conway de Macario E;Macario AJ
热休克蛋白70分子伴侣是关键的细胞过程和对环境变化和生存的反应所必需的，但它们尚未被完全表征。人类热休克蛋白70基因家族的成员数目不详（10年前统计为11个）;有些已经被描述，但信息不完整和不一致。缺乏一套涵盖家庭所有组成部分的连贯的知识体系，以促进他们作为一个群体单独学习。目前，分子伴侣基因的研究得益于基因组序列的获得和一种新的研究方法--分子伴侣组学，我们将其应用于人类hsp 70家族的研究。我们鉴定了47个hsp 70序列，17个基因和30个假基因。根据系统发育和其他数据，如外显子-内含子和蛋白质特征，这些基因可分为7个进化上不同的组和可区分的亚组。N-末端ATP结合结构域（ABD）在大多数蛋白质中至少部分保守，但C-末端底物结合结构域（SBD）不保守。9个蛋白是典型的Hsp 70（65-80 kDa），具有ABD和SBD，2个较轻，部分或全部缺乏SBD，6个较重（>80 kDa），具有不同的C-末端结构域。我们还分析了外显子-内含子的功能，转录变体和蛋白质结构和亚型，以及在不同组织和发育阶段的表达方式和模式。进化分析，包括人类hsp 70基因和假基因，和其他真核hsp 70基因，显示6个人类基因编码胞质Hsp 70和27个假基因起源于HSPA 8，一个基因在大多数组织和发育阶段的高度表达的逆转录转座。人类热休克蛋白70基因家族具有显著的进化多样性，其主要原因是高表达基因HSPA 8的多次重复和逆转录转座。人类Hsp 70蛋白质被聚成七个进化组，不同的C-末端结构域可能定义了它们独特的功能。这些功能还可以通过观察到的N-末端结构域的差异来进一步定义。
Hsp70 chaperones are required for key cellular processes and response to environmental changes and survival but they have not been fully characterized yet. The human hsp70-gene family has an unknown number of members (eleven counted over ten years ago); some have been described but the information is incomplete and inconsistent. A coherent body of knowledge encompassing all family components that would facilitate their study individually and as a group is lacking. Nowadays, the study of chaperone genes benefits from the availability of genome sequences and a new protocol, chaperonomics, which we applied to elucidate the human hsp70 family. We identified 47 hsp70 sequences, 17 genes and 30 pseudogenes. The genes distributed into seven evolutionarily distinct groups with distinguishable subgroups according to phylogenetic and other data, such as exon-intron and protein features. The N-terminal ATP-binding domain (ABD) was conserved at least partially in the majority of the proteins but the C-terminal substrate-binding domain (SBD) was not. Nine proteins were typical Hsp70s (65–80 kDa) with ABD and SBD, two were lighter lacking partly or totally the SBD, and six were heavier (>80 kDa) with divergent C-terminal domains. We also analyzed exon-intron features, transcriptional variants and protein structure and isoforms, and modality and patterns of expression in various tissues and developmental stages. Evolutionary analyses, including human hsp70 genes and pseudogenes, and other eukaryotic hsp70 genes, showed that six human genes encoding cytosolic Hsp70s and 27 pseudogenes originated from retro-transposition of HSPA8, a gene highly expressed in most tissues and developmental stages. The human hsp70-gene family is characterized by a remarkable evolutionary diversity that mainly resulted from multiple duplications and retrotranspositions of a highly expressed gene, HSPA8. Human Hsp70 proteins are clustered into seven evolutionary Groups, with divergent C-terminal domains likely defining their distinctive functions. These functions may also be further defined by the observed differences in the N-terminal domain.
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DOI：
10.1073/pnas.89.22.10915
发表时间：
1992-11-15
影响因子：
11.1
作者：
HENIKOFF, S;HENIKOFF, JG
通讯作者：
HENIKOFF, JG
DOI：
10.1196/annals.1391.009
发表时间：
2007-01-01
期刊：
STRESS RESPONSES IN BIOLOGY AND MEDICINE
影响因子：
--
作者：
Macario, Alberto J. L.;De Macario, Everly Conway
通讯作者：
De Macario, Everly Conway
影响因子：
5.6
作者：
Morshauser, RC;Hu, WD;Zuiderweg, ERP
通讯作者：
Zuiderweg, ERP
影响因子：
4.4
作者：
LEUNG, TKC;HALL, C;LIM, L
通讯作者：
LIM, L
影响因子：
3.5
作者：
Kaye, FJ;Modi, S;Rose, MD
通讯作者：
Rose, MD