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泛素连接酶表

泛素连接酶表提供 E3 泛素连接酶及其底物（已知时）、相应参考文献的列表。

泛素连接酶表

连接酶 底物 功能 参考文献
连接酶 底物 功能 参考文献
AMFR KAI1 AMFR 也称 gp78。AMFR 是一种必不可少的内质网膜蛋白，在内质网相关降解 (ERAD) 中发挥作用。AMFR 被发现通过泛素化转移抑制因子 KAI1 来促进肿瘤转移。 (1)
APC/Cdc20 Cyclin B 后期促进复合体/细胞周期体 (APC/C) 是一种有 E3 连接酶活性的多蛋白复合体，它通过降解周期素和其他有丝分裂蛋白来调节细胞周期进程。APC 见于含有 CDC20、CDC27、SPATC1 和 TUBG1 的复合体。 (2)
APC/Cdh1 Cdc20, Cyclin B, Cyclin A, Aurora A, Securin, Skp2, Claspin 后期促进复合体/细胞周期体 (APC/C) 是一种有 E3 连接酶活性的多蛋白复合体，它通过降解周期素和其他有丝分裂蛋白来调节细胞周期进程。APC/C-Cdh1 二聚复合体在后期和末期被激活，并保持活性直至开始下一个 S 期。 (3, 4, 5, 6, 7)
C6orf157 Cyclin B C6orf157 也称 H10BH。C6orf157 是一种经证实会泛素化周期素 B 的 E3 泛素连接酶。 (8)
Cbl   Cbl-b 和 c-Cbl 是 Cbl 接头蛋白家族的成员，在造血细胞中高表达。Cbl 蛋白有 E3 泛素连接酶活性，会在多种通路中使许多信号转导蛋白和 RTK 下调，如 EGFR、T 细胞和 B 细胞受体及整合素受体。Cbl 蛋白在 T 细胞受体信号转导通路中发挥重要作用。 (9, 10)
CBLL1 CDH1 CBLL1 也称 Hakai。CBLL1 是一种 E3 泛素连接酶，会泛素化磷酸化形式的上皮细胞钙粘素，从而导致降解和细胞间黏附丢失。 (11)
CHFR PLK1, Aurora A CHFR 是一种 E3 泛素连接酶，可作为有丝分裂应激检查点蛋白，会在应激刺激下延迟进入有丝分裂。CHFR 经证实会泛素化和降解激酶 PLK1 和 Aurora A。 (12, 13)
CHIP HSP70/90, iNOS, Runx1, LRRK2 CHIP 是一种 E3 泛素连接酶，可作为共伴侣分子蛋白，会与多种热休克蛋白（包括 HSP70 和 HSP90）以及非热休克蛋白 iNOS、Runx1 和 LRRK2 相互作用。 (14, 15, 16, 17)
DTL (Cdt2) p21 DTL 是一种会与 Cullin4 和 DDB1 构成复合体的 E3 泛素连接酶，它在紫外线损伤后促进 p21 降解。 (18)
E6-AP p53, Dlg E6-AP 也称 UBE3A。E6-AP 是一种 HECT 结构域 E3 泛素连接酶，会与丙型肝炎病毒 (HCV) 核心蛋白相互作用，并靶向这种蛋白进行降解。HCV 核心蛋白对包装病毒 DNA 和其他细胞进程非常重要。E6-AP 还会与人乳头瘤病毒 16 和 18 型的 E6 蛋白相互作用，并靶向 p53 抑癌基因蛋白进行降解。 (19)
HACE1   HACE1 是一种 E3 泛素连接酶，也是一种抑癌基因。HACE1 的异常甲基化频繁在维尔姆斯瘤和结直肠癌细胞中被发现。 (20)
HECTD1   HECTD1 是神经管闭合和间质正常发育所必需的 E3 泛素连接酶。 (21)
HECTD2   HECTD2 是一种可能的 E3 泛素连接酶，并且可能是神经退行性疾病和朊病毒病的易感基因。 (22)
HECTD3   HECTD3 是一种可能的 E3 泛素连接酶，并且可能在细胞骨架调节、肌动蛋白重构和囊泡运输中发挥作用。 (23)
HECW1 DVL1, mutant SOD1, p53 HECW1 也称 NEDL1。HECW1 与 p53 和 Wnt 信号转导蛋白 DVL1 相互作用，并且可能在 p53 介导的神经元细胞死亡中起作用。 (24, 25)
HECW2 p73 HECW2 也称 NEDL2。HECW2 泛素化 p73，p73 是 p53 家族的一员。p73 泛素化可增强蛋白质稳定性。 (26)
HERC2 RNF8 HERC2 属于参与膜转运活动的 E3 泛素连接酶家族。HERC2 与 RNF8 相互作用，从而在 DNA 损伤应答中发挥作用。 (27)
HERC3   HERC3 属于参与膜转运活动的 E3 泛素连接酶家族。HERC3 与 hPLIC-1 和 hPLIC-2 相互作用，位于晚期内体和溶酶体。 (28)
HERC4   HERC4 属于参与膜转运活动的 E3 泛素连接酶家族。HERC4 在睾丸中高表达，并且可能在精子形成中起作用。 (29)
HERC5   HERC5 属于参与膜转运活动的 E3 泛素连接酶家族。HERC5 受干扰素和其他促炎性细胞因子诱导，并在天然免疫应答期间的干扰素诱导的 ISG15 偶联中起作用。 (30, 31)
HUWE1 N-Myc, C-Myc, p53, Mcl-1, TopBP1 HUWE1 也称 Mule。HUWE1 是一种 HECT 结构域 E3 泛素连接酶，可调控 Mcl-1 降解，从而调节 DNA 损伤诱导的凋亡。HUWE1 还通过使 N-Myc 变得不稳定来调控神经元分化，并通过 ARF 调节依赖于/不依赖于 p53 的肿瘤抑制。 (32)
HYD CHK2 HYD 也称 EDD 或 UBR5。HYD 是一种 DNA 损伤应答调节分子，在许多类型的癌细胞中过表达。 (33)
ITCH MKK4, RIP2, Foxp3 ITCH 泛素化 MKK4、RIP2 和 Foxp3 等多种蛋白，从而在 T 细胞受体激活和信号转导中发挥作用。ITCH 功能缺失会导致异常免疫应答和 T 辅助细胞分化。 (34, 35, 36)
LNX1 NUMB LNX1 是一种 E3 泛素连接酶，在胚胎形成期间，它通过调节 Notch 信号转导的负调节分子 NUMB 来决定细胞命运。 (37)
mahogunin   Mahogunin 是一种与黑皮素信号转导有关的 E3 泛素连接酶。mahogunin 功能缺失会导致神经退行性疾病和色素沉着缺失，并且可能是朊病毒病的作用机制。 (38, 39)
MARCH-I HLA-DRβ MARCH1 是一种在抗原呈递细胞 (APC) 中被发现的 E3 泛素连接酶。MARCH1 泛素化 MHC II 类蛋白，并使其细胞表面表达下调。 (40)
MARCH-II   MARCH-II 是 E3 泛素连接酶 MARCH 家族的一员。它在内体结合 syntaxin6，并辅助调节囊泡运输。 (41)
MARCH-III   MARCH-III 是 E3 泛素连接酶 MARCH 家族的一员。MARCH-III 在内体结合 syntaxin6，并辅助调节囊泡运输。 (42)
MARCH-IV MHC I 类 MARCH-IV 是 E3 泛素连接酶 MARCH 家族的一员。MARCH-IV 泛素化 MHC I 类蛋白，并使其细胞表面表达下调。 (43)
MARCH-VI   MARCH-VI 也称 TEB4，它是 E3 泛素连接酶 MARCH 家族的一员。它位于内质网，并参与内质网相关蛋白降解。 (44)
MARCH-VII gp190 MARCH-VII 也称 axotrophin。MARCH-VII 最初被发现是一种神经干细胞基因，但经证实一直通过降解 LIF 受体亚基 gp190 在 T 淋巴细胞的 LIF 信号转导中发挥作用。 (45)
MARCH-VIII B7-2、MHC II 类 MARCH-VIII 也称 c-MIR。MARCH-VIII 会导致 B7-2 泛素化/降解，B7-2 是抗原呈递的共刺激分子。MARCH-VIII 经证实还泛素化 MHC II 类蛋白。 (46)
MARCH-X   MARCH-X 也称 RNF190。MARCH-X 是 E3 泛素连接酶 MARCH 家族的一员。MARCH-X 的假定作用目前未知。  
MDM2 p53 MDM2（p53 的一种 E3 泛素连接酶）在调节 p53 的稳定性中起核心作用。Akt 介导的 MDM2 Ser166 和 Ser186 磷酸化会增加其与 p300 的相互作用，导致 MDM2 介导的 p53 泛素化和降解。 (47)
MEKK1 c-Jun, Erk MEKK1 是 STE11 家族的一个有名蛋白激酶。MEKK1 磷酸化并激活 MKK4/7，MKK4/7 反过来会激活 JNK1/2/3。MEKK1 含有 RING 指形结构域，并显示出对 c-Jun 和 Erk 有 E3 泛素连接酶活性。 (48, 49)
MIB1 Delta、Jagged Mindbomb 同源物 1 (MIB1) 是促进 Notch 配体、Delta 和 Jagged 泛素化和后续内吞的 E3 连接酶。 (50)
MIB2 Delta、Jagged Mind Bomb 2 (MIB2) 是一种正调控 Notch 信号转导的 E3 连接酶。MIB2 经证实在肌管分化和肌肉稳定性中起作用。MIB2 泛素化 NMDAR 亚基，从而辅助调控神经元突触可塑性。 (51, 52, 53)
MycBP2 Fbxo45, TSC2 MycBP2 是一种 E3 泛素连接酶，也称 PAM。MycBP2 结合 Fbxo45，从而在神经元发育中发挥作用。MycBP2 还通过泛素化 TSC2 来调控 mTOR 通路。 (54, 55)
NEDD4   NEDD4 是一种 E3 泛素连接酶，在早期小鼠胚胎中枢神经系统中高表达。在胞内 Na+ 浓度升高时，NEDD4 会使神经元电压门控 Na+ 通道 (NaV) 和上皮 Na+ 通道 (ENaC) 下调。 (56, 57)
NEDD4L Smad2 NEDD4L 是一种 E3 泛素连接酶，在早期小鼠胚胎中枢神经系统中高表达。NEDD4L 经证实通过靶向 Smad2 进行降解来负调控 TGF-β 信号转导。 (58)
Parkin   Parkin 是一种 E3 泛素连接酶，经证实是自噬通路的一个关键调节分子。Parkin 突变会导致帕金森病。 (59)
PELI1 TRIP, IRAK PELI1 是一种 E3 泛素连接酶，它通过 TRIP 接头蛋白在 Toll 样受体（TLR3 和 TLR4）至 NF-κB 的信号转导中起作用。PELI1 经证实还可泛素化 IRAK。 (60, 61)
Pirh2 TP53 Pirh2 也称 RCHY1。Pirh2 是一种 RING 结构域 E3 泛素连接酶。Pirh2 结合 p53，并促进不依赖于 MDM2 的 p53 蛋白酶体降解。Pirh2 基因表达受 p53 调控，使得这种相互作用成为自抑制性反馈环的一部分。 (62, 63)
PJA1 ELF PJA1 也称 PRAJA。PJA1 泛素化 SMAD4 接头蛋白 ELF，从而使胃癌细胞中的 TGF-β 信号转导下调。 (64)
PJA2   PJA2 是一种在神经元突触中被发现的 E3 泛素连接酶。PJA2 的具体作用和底物不清楚。 (65)
RFFL p53 RFFL 也称 CARP2，它是一种会抑制内体再循环的 E3 泛素连接酶。RFFL 还会通过使 MDM2 变得稳定来降解 p53。 (66, 67)
RFWD2 MTA1, p53, FoxO1 RFWD2 也称 COP1。RFWD2 是一种 E3 泛素连接酶，它会泛素化与 DNA 损伤应答和凋亡有关的多种蛋白，包括 MTA1、p53 和 FoxO1。 (68, 69, 70)
Rictor SGK1 Rictor 与 Cullin1-Rbx1 相互作用，形成 E3 泛素连接酶复合体，并促进 SGK1 泛素化和降解。  
RNF5 JAMP, paxillin RNF5 也称 RMA5。RNF5 泛素化 JAMP，从而在与内质网相关的错误折叠蛋白的降解以及内质网应激反应中起作用。RNF5 还在细胞迁移中起作用，并且经证实会泛素化桩蛋白。 (71, 72)
RNF8 H2A,H2AX RNF8 是一个 RING 结构域 E3 泛素连接酶，在受损染色体的修复中起作用。RNF8 在双链断裂 (DSB) 处泛素化组蛋白 H2A 和 H2A.X，从而募集 53BP1 和 BRCA1 修复蛋白。 (73)
RNF19 SOD1 RNF19 也称 Dorfin。突变体 SOD1 的聚集和聚合会导致 ALS 疾病。RNF19 泛素化突变体 SOD1 蛋白，导致神经毒性减弱。 (74)
RNF190   见 MARCH-X  
RNF20 Histone H2B RNF20 也称 BRE1。RNF20 是一种会单泛素化组蛋白 H2B 的 E3 泛素连接酶。H2B 泛素化与激活转录的区域有关。 (75)
RNF34 Caspase-8, -10 RNF34 也称 RFI。RNF34 会泛素化/降解 caspase-8 和 -10，从而抑制死亡受体介导的凋亡。 (76)
RNF40 Histone H2B RNF40 也称 BRE1-B。RNF40 与 RNF20 形成蛋白复合体，导致组蛋白 H2B 泛素化。H2B 泛素化与激活转录的区域有关。 (77)
RNF125   RNF125 也称 TRAC-1。RNF125 经证实会正调控 T 细胞激活。 (78)
RNF128   RNF128 也称 GRAIL。RNF128 促进 T 细胞无能，并且可能在 T 细胞/APC 相互作用中的肌动蛋白细胞骨架组织方面发挥作用。 (79)
RNF138 TCF/LEF RNF138 也称 NARF。RNF138 结合 Nemo 样激酶 (NLK)，并通过泛素化/降解 TCF/LEF 来抑制 Wnt/ß-catenin 信号转导。 (80)
RNF168 H2A, H2A.X RNF168 是一种 E3 泛素连接酶，它会与 RNF8 一起在 DNA 双链断裂 (DSB) 处泛素化组蛋白 H2A 和 H2A.X，从而辅助保护基因组完整性。 (81)
SCF/β-TrCP IκBα, Wee1, Cdc25A, β-Catenin SCF/β-TrCP 是一种 E3 泛素连接酶复合体，包含 SCF（SKP1-CUL1-F-盒蛋白）和底物识别组分 β-TrCP（也称 BTRC）。SCF/β-TrCP 介导与细胞周期进程、信号转导和转录有关的蛋白的泛素化。SCF/β-TrCP 还能调节 β-catenin 的稳定性，并参与 Wnt 信号转导。 (82, 83, 84, 85)
SCF/FBW7 Cyclin E, c-Myc, c-Jun SCF/FBW7 是一种 E3 泛素连接酶复合体，包含 SCF（SKP1-CUL1-F-盒蛋白）和底物识别组分 FBW7。SCF/FBW7 介导与细胞周期进程、信号转导和转录有关的蛋白的泛素化。SCF/FBW7 的靶蛋白包括磷酸化形式的 c-Myc、周期素 E、Notch 胞内域 (NICD) 和 c-Jun。FBXW7 缺陷可能是乳腺癌的一个病因。 (86, 87, 88)
SCF/Skp2 p27, p21, Fox01 SCF/Skp2 是一种 E3 泛素连接酶复合体，包含 SCF（SKP1-CUL1-F-盒蛋白）和底物识别组分 Skp2。SCF/Skp2 介导与细胞周期进程（特别是 G1/S 过渡）、信号转导和转录有关的蛋白的泛素化。SCF/Skp2 的靶蛋白包括磷酸化形式的 p27Kip1、p21Waf1/Cip1 和 FoxO1。 (89, 90)
SHPRH PCNA SHPRH 是一种 E3 泛素连接酶，它通过泛素化 PCNA 在 DNA 复制中发挥作用。DNA 损伤后，PCNA 泛素化会防止停滞复制叉所引起的基因组不稳定性。 (91)
SIAH1 β-catenin, Bim, TRB3 SIAH1 是一种 E3 泛素连接酶，它通过泛素化 β-catenin 在 Wnt 信号转导抑制中发挥作用。SIAH1 经证实还会通过使 Bim 上调来促进凋亡，并泛素化信号转导接头蛋白 TRB3。 (92, 93, 94)
SIAH2 HIPK2, PHD1/3 SIAH2 是一种 E3 泛素连接酶，它通过泛素化和降解 HIPK2 在缺氧中起作用。SIAH2 还会泛素化 PHD1/3，从而在缺氧情况下调节 HIF-1α 的水平。 (95, 96)
SMURF1 Smads SMURF1 是一种 E3 泛素连接酶，它与 BMP 通路 Smad 效应子相互作用，从而导致 Smad 蛋白质泛素化和降解。Smurf1 在体内负调控成骨细胞分化和骨形成。 (97, 98)
SMURF2 Smads, Mad2 SMURF2 是一种会与 BMP 和 TGF-β 通路中的 Smad 相互作用的 E3 泛素连接酶。SMURF2 还通过泛素化 Mad2 来调节有丝分裂纺锤体检查点。 (99, 100)
TOPORS p53, NKX3.1 TOPORS 是一种 E3 泛素连接酶，也是一种 SUMO 连接酶。TOPORS 泛素化并 sumo 化 p53，从而调节 p53 稳定性。TOPORS 经证实还会泛素化抑癌基因 NKX3.1。 (101, 102)
TRAF6 NEMO, Akt1 TRAF6 是一种在 IL-1R、CD40 和 TLR 信号转导中充当接头蛋白的 E3 泛素连接酶。TRAF6 通过 IKK 的 K63 聚泛素化促进 NF-kB 信号转导，从而导致 IKK 激活。TRAF6 经证实还会泛素化 Akt1，导致它转位到细胞膜。 (103, 104)
TRAF7   TRAF7 是一种 E3 泛素连接酶，也是一种 SUMO 连接酶，可在 TNF 受体和 TLR 信号转导中充当接头蛋白。TRAF7 经证实能自泛素化，并通过 MEKK3 介导的 NF-κB 激活在凋亡中发挥作用。 (105)
TRIM63 Troponin I, MyBP-C, MyLC1/2 TRIM63 也称 Murf-1。TRIM63 是一种肌肉特异性 E3 泛素连接酶，其表达在肌萎缩期间上调。TRIM63 经证实会泛素化多种重要的肌蛋白，包括肌钙蛋白 I、MyBP-C 和 MyLC1/2。 (106)
UBE3B   UBE3B 是一种通过序列分析检测到的 E3 泛素连接酶。UBE3B 的特定底物和细胞功能目前尚不清楚。 (107)
UBE3C   UBE3C 是一种 E3 泛素连接酶，也称 KIAA10。UBE3C 在肌细胞中高表达，并且可能会与转录调节分子 TIP120B 相互作用。 (108)
UBR1   UBR1 是一种 E3 泛素连接酶，负责错误折叠的细胞浆蛋白的蛋白酶体降解。UBR1 经证实是 N 端法则蛋白水解通路的泛素连接酶，可调节短寿命蛋白的降解。 (109, 110)
UBR2 Histone H2A UBR2 是一种 E3 泛素连接酶，经证实会泛素化组蛋白 H2A，从而导致转录沉默。UBR2 还是 N 端法则蛋白水解通路的一部分。 (111, 112)
UHRF2 PCNP UHRF2 也称 NIRF。UHRF2 是一种可能通过结合 Chk2 来调控细胞周期进程的胞核蛋白。UHRF2 还会泛素化 PCNP，并且经证实可降解含有多聚谷氨酰胺重复序列的胞核聚合物。 (113, 114, 115)
VHL HIF-1α VHL 是 ECV（延伸蛋白 B/C、Cullen-2、VHL）E3 泛素连接酶复合体的底物识别组分，负责降解转录因子 HIF-1α。HIF-1α 的泛素化和降解仅发生在常氧期间，而不是缺氧期间，因此在调节氧诱导的基因表达中发挥核心作用。 (116)
WWP1 ErbB4 WWP1 是一种通常在乳腺癌细胞中过表达的 E3 泛素连接酶。WWP1 经证实会泛素化和降解 ErbB4。有趣的是，在限制饮食的情况下，发现秀丽隐杆线虫中的 WWP1 同源物出现寿命延长。 (117, 118)
WWP2 Oct-4 WWP2 是一种 E3 泛素连接酶，经证实会泛素化/降解干细胞多能性因子 Oct-4。WWP2 还会泛素化转录因子 EGR2，从而抑制激活诱导的 T 细胞死亡。 (119, 120)
ZNRF1   ZNRF1 是一种在神经元细胞中高表达的 E3 泛素连接酶。ZNRF1 在突触囊泡膜中被发现，并且可能会调节神经元传递和可塑性。 (121)

非常感谢哈佛大学医学院贝斯以色列女执事医疗中心的 Wenyi Wei 教授贡献这个表格。

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创建于 2010 年 11 月

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