Focus on molecules: heparanase.
Focus on molecules: heparanase.
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DOI：
10.1016/j.exer.2010.05.004
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发表时间：
2010-10
影响因子：
3.4
通讯作者：
Laurie, Gordon W.
中科院分区：
文献类型：
--
作者：
Zhang, Yinghui;Ryan, Denise S.;Bower, Kraig S.;Ilan, Neta;Vlodavsky, Israel;Laurie, Gordon W.
肝素酶（NP_001092010）是正常泪腺（GEO Profiles: GDS1361）、角膜上皮（Berk et al, 2004）、视网膜色素上皮/脉络膜、晶体（NEIBank）和一些非眼组织中表达的一种肝素结合内do-β- d -葡萄糖醛酸酶。肝素酶在所有人类肿瘤中都过表达。Western blotting表明，肝素酶是正常泪液的组成部分（Ma, Laurie，未发表）。正常唾液中检测到活性肝素酶119+/−37 pg/ml。肝素酶属于糖苷水解酶家族。肝素酶基因“HPSE”包括人类4号染色体39.8 kb的14个外显子，43个同源物已被记录（Ensembl release 57）。HPSE在硬骨鱼和人类之间具有良好的保守性。人类分泌的肝素酶全长508个氨基酸，理论分子量为57.7 kDa， pI为9.2。SDS PAGE上的迁移量约为65 kDa，与多达6个预测位点的N-linked高甘露糖基化保持一致（NetNGlyc 1.0）。预测没有超过阈值的o -糖基化（NetOGlyc 3.1）。最近报道了三种剪接变体（Barash et al, 2010），它们的氨基酸长度不同，预测分子量和电荷如下：1)' T5 ': 15.6 kDa和pI 6.9；2) T4: 28.3 kDa, pI 8.8；3)“Skip 10”：39.2 kDa, pI 8.4。Aceview还预测了其他几个剪接变体。肝素酶活化是一个分泌和内吞两步过程。分泌需要Cys437和Cys542之间的二硫键。内吞使肝素酶对组织蛋白酶L切除Ser110和Gln157之间6 kDa的连接片段，从而释放N-(8 kDa)和C-(50 kDa)末端亚基，这些亚基随后异二聚成TIM桶状折叠（图1，残基36-417），这是其他糖苷酶的特征。该折叠与130个氨基酸的c端结构域一起，负责结合和切割硫酸肝素（Fux等，2009）。
Heparanase (NP_001092010) is a heparin-binding endo-β-D-glucuronidase expressed by normal lacrimal gland (GEO Profiles: GDS1361), corneal epithelia (Berk et al, 2004), retinal pigment epithelium/choroid, lens (NEIBank) and some non-ocular tissues. Heparanase is overexpressed in essentially all human tumors examined. Western blotting suggests that heparanase is a constituent of normal tears (Ma, Laurie, unpublished). 119+/− 37 pg/ml of active heparanase has been detected in normal saliva. Heparanase belongs to the glycoside hydrolase family 79. The heparanase gene ‘HPSE’comprises fourteen exons over 39.8 kb of human chromosome 4, and forty-three orthologues have been documented (Ensembl release 57). HPSE is well-conserved from bony fish to human. Secreted heparanase in humans is 508 amino acids long, with a theoretical molecular weight and pI of 57.7 kDa and 9.2, respectively. Migration in SDS PAGE is approximately 65 kDa, in keeping with N-linked high mannose glycosylation at as many as six predicted sites (NetNGlyc 1.0). No O-glycosylation is predicted above threshold (NetOGlyc 3.1). Three splice variants have been recently reported (Barash et al, 2010) which vary in amino acid length, predicted molecular weight and charge as follows: 1)‘T5’: 15.6 kDa and pI 6.9; 2)‘T4’: 28.3 kDa and pI 8.8; and 3)‘Skip 10’: 39.2 kDa and pI 8.4. Several other splice variants are predicted by Aceview. Heparanase activation is a twostep process of secretion and endocytic uptake. Secretion requires a disulfide bond between Cys437 and Cys542. Endocytocytic uptake subjects heparanase to cathepsin L excision of a 6 kDa linker segment between Ser110 and Gln157, thereby releasing N-(8 kDa) and C-(50 kDa) terminal subunits that subsequently heterodimerize into a TIM barrel fold (Fig. 1, residues 36-417) characteristic of other glycosidases. The fold, together with a 130 amino acid C-terminal domain, is responsible for binding and cleaving heparan sulfate (Fux et al, 2009).
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影响因子：
4.8
作者：
Barash, Uri;Cohen-Kaplan, Victoria;Vlodavsky, Israel
通讯作者：
Vlodavsky, Israel
影响因子：
13.8
作者：
Fux, Liat;Ilan, Neta;Sanderson, Ralph D.;Vlodavsky, Israel
通讯作者：
Vlodavsky, Israel
影响因子：
4.4
作者：
Berk, RS;Dong, Z;Vlodavsky, I
通讯作者：
Vlodavsky, I
影响因子：
7.8
作者：
Ma, Peisong;Beck, Shannon L.;Laurie, Gordon W.
通讯作者：
Laurie, Gordon W.