Cell Signaling Technology

泛素与蛋白酶体系统

泛素连接酶表提供了E3泛素连接酶的清单,连同其公认的底物和相应的参考文献。此表的很多信息来源于PhosphoSitePlus®,这是由CST开发和维护的一个全面的蛋白质修饰数据库。

泛素连接酶表

连接酶 底物 功能 参考文献
AMFR KAI1 AMFR也被称为gp78。 AMFR是一个结合于完整内质网膜的蛋白,并参与ER相关降解(ERAD)过程。 AMFR已被发现通过对转移抑制因子KAI1的泛素化促进肿瘤转移 (1)
APC/Cdc20 Cyclin B 细胞周期后期促进复合物/ cyclosome(APC/ C),是一个具有E3泛素连接酶活性的多蛋白复合物,通过控制细胞周期蛋白和其他有丝分裂相关蛋白降解来调节细胞周期进程。APC 会与CDC20、CDC27、SPATC1和TUBG1共同组成一个复合物。 (2)
APC/Cdh1 细胞周期后期促进复合物/ cyclosome(APC/ C),是一个具有E3泛素连接酶活性的多蛋白复合物,通过控制细胞周期蛋白和其他有丝分裂相关蛋白降解来调节细胞周期进程。APC/C-Cdh1二聚体复合物在细胞分裂后期和末期被激活,在进入后续的S期之前仍然保持活性。 (3, 4, 5, 6, 7)
C6orf157 Cyclin B C6orf157也被称为H10BH。 C6orf157是一个E3泛素连接酶,已被证明参与Cyclin B的泛素化修饰。 (8)
Cbl Cbl-b和c-Cbl,是在造血干细胞中高度表达的接头蛋白CBL家族的成员。 Cbl蛋白具有E3泛素连接酶活性,在多个信号途径,如表皮生长因子受体、T细胞和B细胞受体和整合素受体途径中下调许多信号蛋白和受体酪氨酸激酶。 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也被称为Hakai。 CBLL1是一个E3泛素连接酶, 磷酸化形式E - cadherin蛋白的泛素化修饰,从而导致其降解和细胞 - 细胞间粘附的缺失。 (11)
CHFR PLK1, Aurora A CHFR是一个E3泛素连接酶,作为一种有丝分裂的应激反应检查点蛋白在应激反应发生时发挥延迟细胞进入有丝分裂的功能。CHFR已被显示参与PLK1和Aurora A 激酶的泛素化修饰和降解。 (12, 13)
CHIP HSP70/90, iNOS, Runx1, LRRK2 CHIP是一种E3泛素连接酶,作为一个伴侣蛋白与包括HSP70和HSP90在内的热休克蛋白,以及非热休克蛋白如iNOS的,RUNX1和LRRK2相互作用 (14, 15, 16, 17)
DTL (Cdt2) p21 DTL与Cullin4和DDB1构成一个E3泛素连接酶复合物,在紫外线造成伤害后促进p21的降解。 (18)
E6-AP p53, Dlg E6 - AP也被称为UBE3A。 E6 - AP是一个含有HECT结构域的E3泛素连接酶,与丙型肝炎病毒(HCV)核心蛋白相互作用并造成其降解。丙型肝炎病毒核心蛋白参与病毒DNA的包装和其他细胞过程。 E6 - AP也与人类16和18型乳头状瘤病毒的E6蛋白相互作用,并可导致P53肿瘤抑制蛋白的降解。 (19)
HACE1 HACE1是一个E3泛素连接酶和抑癌基因。 HACE1的异常甲基化经常在肾母细胞瘤和直肠癌出现。 (20)
HECTD1 HECTD1是神经管闭合和间质细胞的正常发育过程所需的泛素E3连接酶。 (21)
HECTD2 HECTD2很可能是一种E3泛素连接酶,可能作为一种神经退行性疾病和朊病毒疾病易感性基因。 (22)
HECTD3 HECTD3很可能是一种E3泛素连接酶,可能在细胞骨架调节、肌动蛋白重塑和囊泡运输中发挥作用。 (23)
HECW1 DVL1, mutant SOD1, p53 HECW1也被称为NEDL1。 HECW1与p53、Wnt信号蛋白DVL1相互作用,并在p53介导的神经元细胞死亡中发挥作用。 (24, 25)
HECW2 p73 HECW2也被称为NEDL2。 HECW2 参与p53家族成员P73的泛素化修饰,泛素化的p73蛋白稳定性增加。 (26)
HERC2 RNF8 HERC2属于膜转运事件所涉及的E3泛素连接酶家族。 HERC2在DNA损伤反应中与RNF8相互作用。 (27)
HERC3 HERC3属于膜转运事件所涉及的E3泛素连接酶家族。 HERC3与 hPLIC- 1和hPLIC- 2相互作用并定位于晚期内涵体和溶酶体。 (28)
HERC4 HERC4属于膜转运事件所涉及的E3泛素连接酶家族。HERC4在睾丸高表达并可能在精子生成中发挥作用。 (29)
HERC5 HERC4属于膜转运事件所涉及的E3泛素连接酶家族。HERC5被干扰素和其他促炎症细胞因子诱导,并在先天免疫反应中参与干扰素诱导的ISG15偶联作用。 (30, 31)
HUWE1 N-Myc, C-Myc, p53, Mcl-1, TopBP1 HUWE1也被称为Mule。 HUWE1是一个含有HECT域的E3泛素连接酶,调节Mcl - 1的降解,因此调节DNA损伤诱导的细胞凋亡。HUWE1还通过降解N - Myc控制神经元分化,并通过ARF因子调节p53依赖和非依赖的肿瘤抑制。 (32)
HYD CHK2 HYD也称为EDD或UBR5。HYD是DNA损伤反应的调节因子,并在多种癌症中过度表达。 (33)
ITCH MKK4, RIP2, Foxp3 ITCH在T细胞受体激活过程中发挥作用,并通过对包括MKK4、RIP2和Foxp3在内的多种蛋白质进行泛素化修饰而影响T细胞受体信号传递。ITCH的功能缺失导致免疫应答和辅助性T细胞分化的异常。 (34, 35, 36)
LNX1 NUMB LNX1是一个E3泛素连接酶,通过调节Notch信号途径的负调节因子NUMB,在胚胎发育的细胞命运决定过程中发挥作用。 (37)
mahogunin Mahogunin是一个E3泛素连接酶,参与黑皮质信号传递。 mahogunin功能的丧失,导致神经退行性病变和色素沉着损失,同时可能是朊病毒疾病的发病机制。 (38, 39)
MARCH-I HLA-DRβ MARCH1是一个抗原提呈细胞(APCs)中发现的E3泛素连接酶。 MARCH1泛素化修饰MHC II类蛋白,并下调其在细胞表面的表达。 (40)
MARCH-II MARCH-II是MARCHE3泛素连接酶家族的成员。在内涵体与syntaxin6相偶联,有助于调节囊泡运输。 (41)
MARCH-III MARCH-III 是MARCH E3泛素连接酶家族的成员。在内涵体与syntaxin6相偶联,有助于调节囊泡运输。 (42)
MARCH-IV MHC class I MARCH-IV是MARCH E3泛素连接酶家族的成员。MARCH-IV泛素化修饰Ⅰ类MHC分子并下调其在细胞表面的表达。 (43)
MARCH-VI MARCH-IV是MARCH E3泛素连接酶家族的成员,又被称为TEB4。它定位于内质网,并参与雌激素受体相关蛋白降解。 (44)
MARCH-VII gp190 MARCH-VII也被称为axotrophin。MARCH-VII最初作为神经干细胞特有基因而被发现,但后来被证明是通过参与LIF受体亚基gp190的降解而在T淋巴细胞的LIF信号通路中发挥作用。 (45)
MARCH-VIII B7-2, MHC class II MARCH-VIII也被称为C - MIR。 MARCH-VIII导致抗原提呈的共刺激分子B7- 2的泛素化/降解,MARCH-VIII也被证明参与II类MHC分子的泛素化修饰。 (46)
MARCH-X MARCH-X也被称为RNF190。MARCH-X是MARCH E3泛素连接酶家族的成员。 MARCH-X的作用目前未知。
MDM2 p53 MDM2蛋白是一个E3泛素连接酶,在调节p53的稳定性方面起着核心作用,。 AKT 介导MDM2蛋白Ser166和Ser186的磷酸化,增加MDM2与P300的相互作用,有助于MDM2蛋白介导的p53泛素化和降解。 (47)
MEKK1 c-Jun, Erk MEKK1是一个众所周知的STE11蛋白激酶家族的成员。 MEKK1磷酸化并激活MKK4/ 7,又进一步激活JNK1/2/3。 MEKK1包含一个环指结构域,具有E3泛素连接酶的活性,能够使c - Jun和ERK降解。 (48, 49)
MIB1 Delta, Jagged Mindbomb同源1(MIB1)蛋白是一个E3泛素连接酶,有利于Notch配体——Delta和Jagged的泛素化和随后的内吞。 (50)
MIB2 Delta, Jagged Mind Bomb 2(MIB2)是一个正向调节Notch信号的E3泛素连接酶。 MIB2已被证明在肌管分化和肌肉的稳定性中发挥作用。 MIB2泛素化修饰NMDA受体亚基,以参与神经元突触可塑性的调节。 (51, 52, 53)
MycBP2 Fbxo45, TSC2 MycBP2是一个又称作为PAM的E3泛素连接酶,。 MycBP2与Fbxo45相互作用,在神经元发育中发挥作用。 MycBP2还通过泛素化修饰TSC2来调节mTOR通路。 (54, 55)
NEDD4 NEDD4是一个在小鼠早期胚胎的中枢神经系统高表达的E3泛素连接酶。 NEDD4回应细胞内Na+浓度增加,下调神经元中的电压门控Na +通道(NaVs)和上皮钠离子通道(ENaCs)。 (56, 57)
NEDD4L Smad2 NEDD4L是一个在小鼠早期胚胎的中枢神经系统高表达的E3泛素连接酶。NEDD4L已被证明通过参与Smad2的降解负调节TGF-β信号通路。 (58)
Parkin Parkin是一个E3泛素连接酶,已被证明是一个自噬途径的关键调节因子。Parkin突变可以导致帕金森氏症。 (59)
PELI1 TRIP, IRAK PELI1是一个E3泛素连接酶, 在Toll样受体(TLR3和TLR4)通过TRIP接头蛋白传递信号到NF -κB的过程中发挥负调节作用。PELI1还被证明泛素化修饰 IRAK。 (60, 61)
Pirh2 TP53 Pirh2也被称为RCHY1,是一个含有Ring结构域的E3泛素连接酶。 Pirh2结合p53并促进MDM2非依赖的p53的蛋白酶体降解过程。Pirh2基因表达由p53控制,构成这个自抑制反馈环路的互动部分。 (62, 63)
PJA1 ELF PJA1也被称为PRAJA,在胃癌中通过对SMAD4的接头蛋白ELF的泛素化修饰而下调TGF-β信号通路。 (64)
PJA2 PJA2是一个在神经突触发现的E3泛素连接酶。PJA2的确切作用和底物目前还不清楚。 (65)
RFFL p53 RFFL是一个E3泛素连接酶,也被称为CARP2,抑制内吞体循环过程。 RFFL也通过提高MDM2蛋白的稳定性而造成P53降解。 (66, 67)
RFWD2 MTA1, p53, FoxO1 RFWD2是一个E3泛素连接酶,也被称为COP1。 RFWD2参与DNA损伤反应和凋亡相关蛋白MTA1、p53和FOXO1的泛素化修饰。 (68, 69, 70)
Rictor SGK1 Rictor 与Cullin1- Rbx1相互作用,形成一个E3泛素连接酶复合物,并促进SGK1的泛素化和降解。
RNF5 JAMP, paxillin RNF5也被称为RMA5。 RNF5通过泛素化修饰JAMP,在内质网相关错误折叠蛋白的降解过程和内质网应激反应中发挥作用。RNF5也在细胞运动中发挥调节作用,已被证明参与Paxillin的泛素化修饰。 (71, 72)
RNF8 H2A,H2AX RNF8是一个含有Ring结构域的E3泛素连接酶,在修复受损染色体中发挥作用。 RNF8在DNA双链断裂(DSB)处泛素化修饰组蛋白亚基H2A和H2A.X,并招募53BP1和BRCA1等DNA修复蛋白。 (73)
RNF19 SOD1 RNF19也被称为Dorfin。突变SOD1的积累和聚集,导致ALS疾病。 RNF19泛素化修饰突变的SOD1蛋白并造成其降解,减少神经毒性。 (74)
RNF190 参看MARCH-X
RNF20 Histone H2B RNF20是一个E3泛素连接酶,也被称为BRE1。 RNF20对组蛋白H2B进行单泛素化修饰。 泛素化H2B偶联区域转录活跃。 (75)
RNF34 Caspase-8, -10 RNF34也称为RFI, RNF34通过泛素化修饰造成caspase - 8和-10的降解,抑制死亡受体介导的细胞凋亡。 (76)
RNF40 Histone H2B RNF40也被称为BRE1-B。 RNF40与RNF20蛋白形成复合物,导致组蛋白H2B泛素化。泛素化H2B偶联区域转录活跃。 (77)
RNF125 RNF125也被称为TRAC-1。 RNF125被证明正向调节T细胞的活化。 (78)
RNF128 RNF128也被称为GRAIL。 RNF128促进T细胞失能,并可能在T细胞/ APC的相互作用中的肌动蛋白细胞骨架组建中发挥作用。 (79)
RNF138 TCF/LEF RNF138也被称为NARF。 RNF138与Nemo样激酶NLK结合,并通过泛素化修饰TCF / LEF造成其降解来抑制Wnt/β- catenin信号通路。 (80)
RNF168 H2A, H2A.X RNF168是一个E3泛素连接酶,与RNF8一起在双链断裂(DSB)处泛素化修饰DNA组蛋白H2A和H2A.X,有助于保护基因组的完整性 (81)
SCF/β-TrCP IκBα, Wee1, Cdc25A, β-Catenin SCF/β- Trcp是一个包含SCF(SKP1-CUL1-F-box蛋白)和底物识别组分β-Trcp(也被称作BTRC)的E3泛素连接酶复合体。SCF/β-Trcp介导参与细胞周期进程、信号转导和转录的多种蛋白质的泛素化修饰。 SCF/β-Trcp还通过控制β- catenin的稳定性参与Wnt信号调节。 (82, 83, 84, 85)
SCF/FBW7 Cyclin E, c-Myc, c-Jun SCF/FBW7是一个包含SCF(SKP1-CUL1-F-box蛋白)和底物识别组分FBW7的E3泛素连接酶复合体。SCF/FBW7介导参与细胞周期进程、信号转导和转录的多种蛋白质的泛素化修饰。SCF/FBW7的靶蛋白包括磷酸化形式c – Myc、Cyclin E、Notch胞内结构域NICD和c - Jun。FBXW7的缺陷可能导致乳腺癌的发生。 (86, 87, 88)
SCF/Skp2 p27, p21, Fox01 SCF/Skp2是一个包含SCF(SKP1-CUL1-F-box蛋白)和底物识别组分Skp2的E3泛素连接酶复合体。SCF/Skp2介导参与细胞周期进程(特别是G1/S期转换)、信号转导和转录的多种蛋白质的泛素化修饰。SCF/Skp2的靶蛋白包括磷酸化形式的p27Kip1, p21Waf1/Cip1, 和FoxO1。 (89, 90)
SHPRH PCNA SHPRH是一个E3泛素连接酶,通过泛素化修饰PCNA而参与DNA复制的调节。 PCNA的泛素化,防止DNA损伤后的复制叉停滞而造成的基因组不稳定。 (91)
SIAH1 β-catenin, Bim, TRB3 SIAH1是一个E3泛素连接酶,通过对β- catenin的泛素化修饰起着抑制Wnt信号的作用。 SIAH1也已被证明通过上调BIM,促进细胞凋亡。同时SIAH1还泛素化修饰信号接头蛋白TRB3。 (92, 93, 94)
SIAH2 HIPK2, PHD1/3 SIAH2是一个E3泛素连接酶,通过泛素化和降解HIPK2参与缺氧调节。 SIAH2也泛素化修饰PHD1/ 3,调节缺氧状态下的HIF-1α水平。 (95, 96)
SMURF1 Smads SMURF1是一个E3泛素连接酶,与BMP通路中效应分子Smad相互作用,导致Smad蛋白泛素化和降解。 SMURF1负调控体内成骨细胞分化和骨形成。 (97, 98)
SMURF2 Smads, Mad2 SMURF2是一个E3泛素连接酶,与BMP和TGF-β通路中效应分子Smad相互作用。 SMURF2还通过泛素化修饰MAD2泛素化调节有丝分裂纺锤体检查点。 (99, 100)
TOPORS p53, NKX3.1 TOPORS是一个E3泛素连接酶和SUMO连接酶。 TOPORS泛素化和SUMO化修饰 P53,调节p53的稳定性。 TOPORS也被显示泛素化修饰肿瘤抑制因子 NKX3.1。 (101, 102)
TRAF6 NEMO, Akt1 TRAF6 作为IL-1R,CD40,TLR信号通路的接头蛋白,是一个E3泛素连接酶。 TRAF6通过多泛素化修饰IKK K63导致IKK的激活,以促进NF - kB信号的传递。TRAF6也被证明泛素化修饰Akt1,导致其易位至细胞膜。 (103, 104)
TRAF7 TRAF7的作为TNF受体和TLR信号通路的接头蛋白,是一个E3泛素连接酶和SUMO连接酶。 TRAF7已被证明具有自我泛素的能力,在通过MEKK3介导的NF -κB活化过程中发挥作用而调节细胞凋亡。 (105)
TRIM63 Troponin I, MyBP-C, MyLC1/2 TRIM63也被称为Murf-1。 TRIM63是一个肌肉特异性的E3泛素连接酶,在肌肉萎缩时其表达上调。 TRIM63已被证明泛素化修饰几个重要的肌肉蛋白,包括Troponin I、MyBP- C和MyLC1/2。 (106)
UBE3B UBE3B是一个通过序列分析确定的E3泛素连接酶,具体底物和细胞功能目前还不清楚。 (107)
UBE3C UBE3C是一个E3泛素连接酶,又称作为KIAA10。 UBE3C在肌肉中高表达,可能与转录调节因子TIP120B相互作用。 (108)
UBR1 UBR1是一个参与细胞质内错误折叠蛋白的蛋白酶体降解过程的E3泛素连接酶。 UBR1也被证明是一个参与调节短寿命蛋白质降解相关的蛋白N -端水解途径的泛素连接酶。 (109, 110)
UBR2 Histone H2A UBR2是一个E3泛素连接酶,已被证明泛素化修饰组蛋白H2A,导致转录沉默。 UBR2也是蛋白N -端水解途径的调节分子。 (111, 112)
UHRF2 PCNP UHRF2也被称为NIRF。 UHRF2是一个核蛋白,可通过结合CHK2调节细胞周期进程。 UHRF2也泛素化修饰PCNP,并在含有多聚谷氨酰胺重复的核内聚集体的降解中发挥作用。 (113, 114, 115)
VHL HIF-1α VHL是调控转录因子HIF-1α降解的ECV((Elongin B/C, Cullen-2, VHL)E3泛素连接酶复合物的底物识别组分。只在有氧状态下而不是缺氧状态下参与HIF-1α的泛素化修饰和降解,从而在氧调节基因的表达调控中发挥了核心作用。 (116)
WWP1 ErbB4 WWP1是一个E3泛素连接酶,通常在乳腺癌中被发现过度表达。 WWP1已被证明参与ErbB4的泛素化修饰和降解。有趣的是,发现WWP1线虫同源蛋白在限制饮食情况下增加线虫寿命。 (117, 118)
WWP2 Oct-4 WWP2已被证明是一个参与干细胞多能性因子Oct -4的泛素化修饰和降解的E3泛素连接酶。 WWP2也泛素化修饰转录因子EGR2而抑制活化诱导的T细胞死亡。 (119, 120)
ZNRF1 ZNRF1是一个在神经细胞中高表达的E3泛素连接酶。 ZNRF1被发现位于突触囊泡膜上,可能调节神经传输和可塑性。 (121)

感谢哈佛医学学校Beth Israel Deaconess 医学中心Wenyi Wei教授对这个表格的贡献。

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created November 2010

References