EGLN2 Q96KS0

脯氨酰羟化酶 EGLN2 (EC 1.14.11.-) (Egl nine 同源蛋白 2) (EC 1.14.11.29) (雌激素诱导标签 6) (EIT-6) (HPH-3) (缺氧诱导因子脯氨酰羟化酶 1) (HIF-PH1) (HIF-脯氨酰羟化酶 1) (HPH-1) (含脯氨酰羟化酶结构域蛋白 1) (PHD1)

功能描述

脯氨酰羟化酶，介导靶蛋白（如ATF4、IKBKB、CEP192和HIF1A）中脯氨酸残基的羟基化 (PubMed:11595184, PubMed:12039559, PubMed:15925519, PubMed:16509823, PubMed:17114296, PubMed:23932902)。靶蛋白优先通过LXXLAP基序被识别 (PubMed:11595184, PubMed:12039559, PubMed:15925519)。细胞氧传感器，在常氧条件下催化缺氧诱导因子 (HIF) alpha蛋白翻译后4-羟基脯氨酸的形成 (PubMed:11595184, PubMed:12039559, PubMed:12181324, PubMed:15925519, PubMed:19339211)。羟基化HIF1A氧依赖降解结构域 (ODD)（N末端，NODD，和C末端，CODD）中发现的特定脯氨酸 (PubMed:11595184, PubMed:12039559, PubMed:12181324, PubMed:15925519)。也羟基化HIF2A (PubMed:11595184, PubMed:12039559, PubMed:15925519)。对HIF1A和HIF2A均优先作用于CODD位点 (PubMed:11595184, PubMed:12039559, PubMed:15925519)。羟基化的HIFs随后通过von Hippel-Lindau泛素化复合物被靶向进行蛋白酶体降解 (PubMed:11595184, PubMed:12039559, PubMed:15925519)。在缺氧条件下，羟基化反应减弱，使HIFs逃避降解，导致其易位至细胞核，与HIF1B异二聚化，并增加缺氧诱导基因的表达 (PubMed:11595184, PubMed:12039559, PubMed:15925519)。EGLN2参与调节心肌和骨骼肌的缺氧耐受和细胞凋亡 (PubMed:11595184, PubMed:12039559, PubMed:15925519)。也调节对常氧氧化性神经元死亡的敏感性 (PubMed:11595184, PubMed:12039559, PubMed:15925519)。通过羟基化关键中心体组分CEP192，将氧感知与细胞周期和初级纤毛形成联系起来，这促进其泛素化及随后的蛋白酶体降解 (PubMed:23932902)。羟基化IKBKB，介导缺氧条件下的NF-kappa-B激活 (PubMed:17114296)。也介导ATF4的羟基化，导致ATF4蛋白稳定性降低 (By similarity)。 {ECO:0000250|UniProtKB:Q91YE2, ECO:0000269|PubMed:11595184, ECO:0000269|PubMed:12039559, ECO:0000269|PubMed:12181324, ECO:0000269|PubMed:15925519, ECO:0000269|PubMed:16509823, ECO:0000269|PubMed:17114296, ECO:0000269|PubMed:19339211, ECO:0000269|PubMed:23932902}。

组织特异性

Expressed in adult and fetal heart, brain, liver, lung, skeletal muscle, and kidney. Also expressed in testis and placenta. Highest levels in adult brain, placenta, lung, kidney, and testis. Expressed in hormone responsive tissues, including normal and cancerous mammary, ovarian and prostate epithelium.

亚细胞定位

Nucleus