E3泛素蛋白连接酶SIAH1 (EC 2.3.2.27) (RING型E3泛素转移酶SIAH1) (Seven in absentia同源物1) (Siah-1) (Siah-1a)
E3泛素蛋白连接酶SIAH1 (EC 2.3.2.27) (RING型E3泛素转移酶SIAH1) (Seven in absentia同源物1) (Siah-1) (Siah-1a)
Q8IUQ4功能描述
E3 ubiquitin-protein ligase，介导靶蛋白的泛素化及随后的蛋白酶体降解 (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:28546513, PubMed:32430360, PubMed:33591310, PubMed:9334332, PubMed:9858595)。E3 ubiquitin ligases以硫酯的形式从E2 ubiquitin-conjugating enzyme接受泛素，然后直接将泛素转移至靶底物 (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595)。通过直接结合底物或作为更大E3复合物中关键的RING结构域亚基来介导E3 ubiquitin ligase活性 (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595)。触发多种底物的泛素介导的降解，包括参与转录调控的蛋白 (ELL2, MYB, POU2AF1, PML 和 RBBP8)、细胞表面受体 (DCC)、细胞表面受体型酪氨酸激酶 FLT3、细胞质信号转导分子 (KLF10/TIEG1 和 NUMB)、抗凋亡蛋白 (BAG1)、微管马达蛋白 (KIF22)、神经元突触囊泡功能相关蛋白 (SYP)、结构蛋白 (CTNNB1) 以及 SNCAIP (PubMed:10747903, PubMed:11146551, PubMed:11389839, PubMed:11389840, PubMed:11483517, PubMed:11483518, PubMed:11752454, PubMed:12072443)。通过蛋白酶体降解赋予HIPK2固有的不稳定性 (PubMed:18536714, PubMed:33591310)。因此参与许多细胞过程，如细胞凋亡、肿瘤抑制、细胞周期、轴突导向、转录调控、精子发生和TNF信号传导 (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595)。与SIAH2具有一些重叠的功能 (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595)。与PEG3协同诱导细胞凋亡 (By similarity)。在凋亡刺激后产生一氧化氮 (NO) 时，与S-亚硝基化GAPDH相互作用，介导GAPDH向细胞核的转位 (By similarity)。GAPDH作为SIAH1的稳定因子，促进核蛋白的降解。介导EGLN2和EGLN3在未折叠蛋白反应 (UPR) 中的泛素化和降解，导致它们降解并随后稳定ATF4 (By similarity)。也是Wnt信号通路的一部分，在该通路中它介导Wnt诱导的AXIN1泛素介导的蛋白酶体降解 (PubMed:28546513, PubMed:32430360)。 {ECO:0000250|UniProtKB:P61092, ECO:0000250|UniProtKB:Q920M9, ECO:0000269|PubMed:10747903, ECO:0000269|PubMed:11146551, ECO:0000269|PubMed:11389839, ECO:0000269|PubMed:11389840, ECO:0000269|PubMed:11483517, ECO:0000269|PubMed:11483518, ECO:0000269|PubMed:11752454, ECO:0000269|PubMed:12072443, ECO:0000269|PubMed:14506261, ECO:0000269|PubMed:14645235, ECO:0000269|PubMed:14654780, ECO:0000269|PubMed:15064394, ECO:0000269|PubMed:16085652, ECO:0000269|PubMed:18536714, ECO:0000269|PubMed:19224863, ECO:0000269|PubMed:20508617, ECO:0000269|PubMed:22483617, ECO:0000269|PubMed:28546513, ECO:0000269|PubMed:32430360, ECO:0000269|PubMed:9334332, ECO:0000269|PubMed:9858595}.
组织特异性
Widely expressed at a low level. Down-regulated in advanced hepatocellular carcinomas.
亚细胞定位
Cytoplasm. Nucleus. Note=Predominantly cytoplasmic. Partially nuclear.
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