乙酰肝素酶 (EC 3.2.1.166) (内切葡萄糖醛酸酶) (乙酰肝素酶-1) (Hpa1) [切割为：乙酰肝素酶 8 kDa 亚基；乙酰肝素酶 50 kDa 亚基]
乙酰肝素酶 (EC 3.2.1.166) (内切葡萄糖醛酸酶) (乙酰肝素酶-1) (Hpa1) [切割为：乙酰肝素酶 8 kDa 亚基；乙酰肝素酶 50 kDa 亚基]
Q9Y251功能描述
内切糖苷酶，将硫酸乙酰肝素蛋白聚糖 (HSPGs) 裂解为硫酸乙酰肝素侧链和核心蛋白聚糖。参与细胞外基质 (ECM) 的降解和重塑。选择性裂解葡萄糖醛酸单元与带有3-O-磺酸或6-O-磺酸基团的N-磺酸葡萄糖胺单元之间的连接。也能裂解葡萄糖醛酸单元与带有2-O-磺酸基团的N-磺酸葡萄糖胺单元之间的连接，但不能裂解葡萄糖醛酸单元与2-O-硫酸化艾杜糖醛酸部分之间的连接。在中性pH下基本无活性，但在酸性条件下变得活跃，例如在肿瘤侵袭和炎症过程中。促进与转移、伤口愈合和炎症相关的细胞迁移。增强多配体蛋白聚糖的脱落，并增加骨髓瘤中的内皮侵袭和血管生成。作为促凝剂，在组织因子和活化因子VII存在下增加活化因子X的生成。增加细胞对细胞外基质 (ECM) 的粘附，该作用不依赖其酶活性。通过脂筏诱导AKT1/PKB磷酸化，从而增加细胞运动性和侵袭能力。肝素增强这种AKT1/PKB活化。调节骨发生。通过上调SRC介导的VEGF活化来增强血管生成。参与毛囊内根鞘分化和毛发稳态。 {ECO:0000269|PubMed:12213822, ECO:0000269|PubMed:12773484, ECO:0000269|PubMed:15044433, ECO:0000269|PubMed:16452201, ECO:0000269|PubMed:18557927, ECO:0000269|PubMed:18798279, ECO:0000269|PubMed:19244131, ECO:0000269|PubMed:20097882, ECO:0000269|PubMed:20181948, ECO:0000269|PubMed:20309870, ECO:0000269|PubMed:20561914, ECO:0000269|PubMed:21131364}.
组织特异性
Highly expressed in placenta and spleen and weakly expressed in lymph node, thymus, peripheral blood leukocytes, bone marrow, endothelial cells, fetal liver and tumor tissues. Also expressed in hair follicles, specifically in both Henle's and Huxley's layers of inner the root sheath (IRS) at anagen phase.
亚细胞定位
Lysosome membrane; Peripheral membrane protein. Secreted. Nucleus. Note=Proheparanase is secreted via vesicles of the Golgi. Interacts with cell membrane heparan sulfate proteoglycans (HSPGs). Endocytosed and accumulates in endosomes. Transferred to lysosomes where it is proteolytically cleaved to produce the active enzyme. Under certain stimuli, transferred to the cell surface. Associates with lipid rafts. Colocalizes with SDC1 in endosomal/lysosomal vesicles. Accumulates in perinuclear lysosomal vesicles. Heparin retains proheparanase in the extracellular medium (By similarity).
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