蛋白质单ADP-核糖基转移酶PARP9 (EC 2.4.2.-) (白喉毒素样ADP-核糖基转移酶9) (ARTD9) (B侵袭性淋巴瘤蛋白) (聚[ADP-核糖]聚合酶9) (PARP-9)
蛋白质单ADP-核糖基转移酶PARP9 (EC 2.4.2.-) (白喉毒素样ADP-核糖基转移酶9) (ARTD9) (B侵袭性淋巴瘤蛋白) (聚[ADP-核糖]聚合酶9) (PARP-9)
Q8IXQ6功能描述
ADP-ribosyltransferase，与E3 ligase DTX3L结合，在DNA损伤修复和免疫反应（包括干扰素介导的抗病毒防御）中发挥作用 (PubMed:16809771, PubMed:23230272, PubMed:26479788, PubMed:27796300)。在该复合物中，增强DTX3L E3 ligase活性，该活性在PARP9结合poly(ADP-ribose)后进一步增强 (PubMed:28525742)。与DTX3L结合并在E1和E2 enzyme存在下，介导ubiquitin的NAD(+)-依赖性单ADP-核糖基化，从而阻止ubiquitin与底物（如histone）结合 (PubMed:28525742)。在DNA修复过程中，PARP1通过PARP9结合核糖基化的PARP1，将PARP9/BAL1-DTX3L复合物募集到DNA损伤位点 (PubMed:23230272)。随后的PARP1依赖性PARP9/BAL1-DTX3L介导的泛素化促进53BP1/TP53BP1、UIMC1/RAP80和BRCA1快速且特异性地募集到DNA损伤位点 (PubMed:23230272, PubMed:28525742)。响应DNA损伤时，PARP9-DTX3L复合物是高效非同源末端连接 (NHEJ) 所必需的；该复合物的功能受PARP9活性负调节 (PubMed:28525742)。对于通过V(D)J重组和类别转换重组 (CSR) 进行的B细胞受体 (BCR) 组装是非必需的 (By similarity)。在巨噬细胞中，通过抑制PARP14介导的STAT1 ADP-核糖基化进而促进STAT1磷酸化，从而正调节IFNG刺激下的促炎细胞因子产生 (PubMed:27796300)。也抑制PARP14介导的STAT6 ADP-核糖基化 (PubMed:27796300)。 {ECO:0000250|UniProtKB:Q8CAS9, ECO:0000269|PubMed:16809771, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:27796300, ECO:0000269|PubMed:28525742}.
组织特异性
Expressed in lymphocyte-rich tissues, spleen, lymph nodes, peripheral blood lymphocytes and colonic mucosa (PubMed:11110709, PubMed:16809771). Expressed in macrophages (PubMed:27796300). Also expressed in nonhematopoietic tissues such as heart and skeletal muscle (PubMed:11110709, PubMed:16809771). Isoform 2 is the predominant form (PubMed:11110709). Most abundantly expressed in lymphomas with a brisk host inflammatory response (PubMed:11110709, PubMed:16809771). In diffuse large B-cell lymphomas tumors, expressed specifically by malignant B-cells (PubMed:11110709, PubMed:16809771).
亚细胞定位
Cytoplasm, cytosol
关键词