ライフサイエンスコーパス: UBL

1 UBL proteins share little amino acid sequence identity t

2 RD), an SQL database of features for all 509 UBL-containing structures in the PDB, allowing users to

3 Consistent with its predicted function as a UBL, gfISG15 formed conjugates with cellular proteins in

4 on to gp78, the Bag6 UBL domain also binds a UBL-binding motif in UbxD8, an essential component of th

5 UB and Nedd8, a UBL regulating the activity of cullin-RING UB ligases, o

6 The R42P mutation in Parkin locates to a UBL domain that interacts with C-terminal domains.

7 er, APPBP1-UBA3's failure to interact with a UBL having Arg72 is not due to a lack of this favorable

8 Depending on their abundance UBL/UBA family members can either promote or inhibit the

9 E1 enzymes activate UBLs by catalysing UBL carboxy-terminal adenylation, for

10 can be used to discover and to detect active UBL proteins, and to monitor the intracellular activity

11 Although UBL/UBA family members are reported to regulate the degr

12 teins similar to UBL-conjugating enzymes and UBL-deconjugating enzymes seem to have already been wide

13 This study of ubiquitin and UBL systems in schizophrenia found abnormalities of ubiq

14 nd E3 ligases involved in ubiquitination and UBL post-translational modifications in postmortem brain

15 ssembly of fully natural UBL-Ub, Ub-UBL, and UBL-UBL conjugates from recombinant monomers is presente

16 n air circulation and air quality in UCL and UBL.

17 near the C terminus which, in ubiquitin and UBLs, is required for covalent modification of target pr

18 In contrast, another UBL-containing protein, the deubiquitinase Ubp6, is also

19 3a ortholog (Rad23) to interact with another UBL/UBA family member (Ddi1) and to bind a common tetrau

20 ery by positioning the RING-E2 approximately UBL catalytic center, licensing the acceptor lysine, and

21 ascades, a thioester-linked E2 approximately UBL complex typically interacts with an E3 enzyme for UB

22 ably, E2-E3-target and RING-E2 approximately UBL modules are not optimized to function independently,

23 ucture of a trapped RING E3-E2 approximately UBL-target intermediate representing RBX1-UBC12 approxim

24 entral to UBL protein signaling pathways are UBL protein-activating E1 enzymes that activate the C-te

25 However, unlike E1 substrates, which are UBLs with a C-terminal di-glycine sequence, MccB's subst

26 racterize the Cuz1 protein (Cdc48-associated UBL/zinc finger protein-1), encoded by a previously unch

27 in part by a group of Ub-like/Ub-associated (UBL/UBA) proteins that help shuttle ubiquitylated protei

28 We find that in addition to gp78, the Bag6 UBL domain also binds a UBL-binding motif in UbxD8, an e

29 zinc finger domain in complex with the BAG6 UBL domain.

30 process and form a ternary complex with both UBLs, similar to what has been observed for Uba1.

31 Bound UBLs mainly regulate the interactions of proteins with o

32 zymatic pathways that govern modification by UBLs.

33 E1 enzymes activate UBLs by catalysing UBL carboxy-terminal adenylation, forming a covalent E1

34 two proteins directly interact, and the Cuz1 UBL, but not Zf_AN1, is necessary for binding to the Cdc

35 In previous work, we determined UBL/UBA domain interactions to promote intramolecular in

36 Thus, parallel residues from different UBL pathways can utilize distinct mechanisms to dictate

37 l significance, however, methods to discover UBL proteins and to monitor the intracellular activity o

38 chanisms of how Uba6 recognizes two distinct UBLs and catalyzes their activation and transfer.

39 in proteins contain a ubiquitin-like domain (UBL) and ubiquitin-associated domain(s) that interact wi

40 a region resembling a ubiquitin-like domain (UBL) that exists only in IKKbeta and that we named the U

41 proteasome through a ubiquitin-like domain (UBL) while anchoring cargo at a C-terminal polyubiquitin

42 _AN1) and a divergent ubiquitin-like domain (UBL).

43 e map the interaction to the N-terminal DUSP-UBL domain of USP15 and the coiled coil region of BRAP.

44 iceosome recycling factor, binds to the DUSP-UBL domain of USP15 and USP4, recruiting them to the nuc

45 in the apo-form and in complex with the DUSP-UBL domain of USP15 at 2.0 and 3.0 A, respectively.

46 The studies reveal a distinctive E1~UBL-E2 architecture for enzymes mediating autophagy.

47 In general, each UBL has its own E1 that serves as the entry point for a

48 proteasome through a ubiquitin-like element (UBL).

49 urally defined ubiquitin-like homology fold (UBL) can engage in several unique protein-protein intera

50 ex typically interacts with an E3 enzyme for UBL transfer to the target.

51 To target and identify UBL-modifying enzymes, we produced Nedd8, ISG15, and SUM

52 ction networks to drive consecutive steps in UBL cascades.

53 ion of polypeptides reactive with individual UBL probes.

54 domain, normally bound to an intramolecular UBL domain, and stabilizes the Ubiquilin-client complex.

55 tion, Vpr binding disrupts an intramolecular UBL-UBA2 interaction.

56 Disrupting the intramolecular UBL-UBA domain interactions in HHR23A indeed potentiates

57 rectly interacts with the proteasome via its UBL domain and is exclusively localized in the nucleus.

58 ds to a Gln in ubiquitin's E1 UBA1, is a key UBL selectivity determinant.

59 In the overlying urban boundary layer (UBL), ambient temperature and PM2.5 variations were corr

60 id recognized ubiquitin and ubiquitin-like ( UBL: ) domains of substrate shuttling factors.

61 conjugates of ubiquitin (Ub) and/or Ub-like (UBL) proteins such as Rub1 to serve as distinct molecula

62 The attachment of ubiquitin (Ub) or Ub-like (UBL) proteins to target proteins is achieved by parallel

63 ied group that contains both ubiquitin-like (UBL) and ubiquitin-associated (UBA) domains: Rad23, Ddi1

64 , contains an amino-terminal ubiquitin-like (UBL) domain and a carboxy-terminal ubiquitin-associated

65 ein containing an N-terminal ubiquitin-like (UBL) domain and two ubiquitin-associated domains (UBA1 a

66 ith and without the putative ubiquitin-like (UBL) domain at the N terminus were found to possess prot

67 Deletion of the NUB1 ubiquitin-like (UBL) domain did not impair the interaction with tau and

68 (NT) domain of Sgt2 and the ubiquitin-like (UBL) domain of Get5.

69 nity of this complex for the ubiquitin-like (UBL) domain of hHR23B and elution with a competing polyp

70 nteracts with the N-terminal ubiquitin-like (UBL) domain of Ytm1/WDR12 as well as the UBL domain of R

71 served domains of Mpe1 are a ubiquitin-like (UBL) domain, a zinc knuckle, and a RING finger domain ch

72 ss-inducible protein with an ubiquitin-like (UBL) domain, aggravates ER stress-mediated cell death in

73 biquitin ligase gp78 via its ubiquitin-like (UBL) domain, but the relative low affinity of this inter

74 ibited state mediated by its ubiquitin-like (UBL) domain.

75 hrough docking via the Rad23 ubiquitin-like (UBL) domain.

76 dem domain in USP (DUSP) and ubiquitin-like (UBL) domain.

77 uitin receptors that contain ubiquitin-like (UBL) domains, which interact with the proteasome, and ub

78 ral domain of BMI1 adopts an ubiquitin-like (UBL) fold and binds PHC2 in a beta-hairpin conformation.

79 A novel ubiquitin-like (UBL) gene, 40.1, was identified by differential display

80 Pathways of ubiquitin-like (UBL) molecule transfer regulate a myriad of cellular cas

81 Ubiquitin and ubiquitin-like (UBL) proteins regulate a vast variety of cellular functi

82 to investigate ubiquitin and ubiquitin-like (UBL) systems (SUMOylation, NEDD8ylation, and Ufmylation)

83 Thus, the misfolded UBL is apparently masked by the intramolecular interacti

84 These C-terminally modified UBL probes reacted with purified UBL-activating (E1), -c

85 Modified UBLs were radioiodinated and incubated with cell lysates

86 ontrolled chemical assembly of fully natural UBL-Ub, Ub-UBL, and UBL-UBL conjugates from recombinant

87 New UBL substrates continue to be identified and further exp

88 Here, we describe the collection of UBL/UBA proteins in Arabidopsis thaliana, including four

89 d further expand the functional diversity of UBL pathways in cellular homeostasis and physiology.

90 esidues conserved among the larger family of UBL-containing proteins and IKKbeta, and alanine scannin

91 quilin/PLIC proteins belong to the family of UBL-UBA proteins implicated in the regulation of the ubi

92 general strategy for selective inhibition of UBL conjugation pathways.

93 kinetic analysis revealed that the rates of UBL-adenylate (step 1) and thioester (step 2) formation

94 This highlights the central role of UBL systems in regulation of ubiquitous as well as speci

95 g E1 enzymes that activate the C-terminus of UBL proteins for subsequent conjugation to the protein s

96 mes, indicating tissue-specific functions of UBLs.

97 vel substrates, mechanisms, and functions of UBLs.

98 deconjugating enzymes that remove the Ub or UBL adduct.

99 in activating the C-terminus of ubiquitin or UBL, which is an essential step that triggers subsequent

100 ntly, we also find that the ability of other UBL/UBA proteins to associate with Ufd2 correlates with

101 ecifically activates ubiquitin but not other UBLs in vitro and in vivo.

102 w a marked preference for polyubiquitin over UBLs.

103 anism of NEDD8 ligation and how a particular UBL and acceptor lysine are matched by a multifunctional

104 e report the structure of the phosphorylated UBL domain from parkin.

105 -like protein (UBL) intermediate and promote UBL transfer to a remotely bound target protein.

106 two E3s function synergistically to promote UBL transfer from one E2 to a target.

107 of the UBL's C-terminus, prior to promoting UBL transfer to a downstream E2.

108 r DVE-1 and the small ubiquitin-like protein UBL-5, both of which are encoded by genes required for s

109 ccB is homologous to ubiquitin-like protein (UBL) activating enzyme (E1) adenylation domains.

110 e conjugation of the ubiquitin-like protein (UBL) Atg8 during autophagy.

111 In ubiquitin-like protein (UBL) cascades, a thioester-linked E2 approximately UBL c

112 ked E2 approximately ubiquitin-like protein (UBL) intermediate and promote UBL transfer to a remotely

113 ng these is ISG15, a ubiquitin-like protein (UBL) that can be covalently attached to both host and vi

114 Ubiquitin-like proteins (UBLs) are conjugated by dynamic E1-E2-E3 enzyme cascades

115 Ubiquitin and ubiquitin-like proteins (UBLs) are directed to targets by cascades of E1, E2, and

116 s with ubiquitin or ubiquitin-like proteins (UBLs) by means of an E1-E2-E3 cascade controls many sign

117 adducts with other ubiquitin-like proteins (UBLs) catalyzed by their cognate-activating enzymes.

118 on by ubiquitin and ubiquitin-like proteins (UBLs) is a major eukaryotic mechanism for regulating pro

119 ides of ubiquitin (UB) and UB-like proteins (UBLs) play a key role in their recognition by the specif

120 of proteins by ubiquitin (Ub)-like proteins (UBLs) plays an important role in many cellular processes

121 The ubiquitin-like proteins (UBLs) that are part of this family adopt the beta-grasp

122 ds to the effects of other Ub-like proteins (UBLs), and deconjugating enzymes that remove the Ub or U

123 , and activates two ubiquitin-like proteins (UBLs), ubiquitin and FAT10.

124 on to ubiquitin and ubiquitin-like proteins (UBLs), which controls an enormous range of physiological

125 er of the family of ubiquitin-like proteins (UBLs).

126 ly modified UBL probes reacted with purified UBL-activating (E1), -conjugating (E2), and -deconjugati

127 Interestingly, fusion of the isolated R42P UBL to NAT1 WT results in a fusion product that is traff

128 tionally, the analogous surface on the Rad23 UBL domain overlaps with that required for interaction w

129 Although structurally related, UBLs regulate a strikingly diverse set of cellular proce

130 R12 as well as Nle1 through their respective UBL domains.

131 NK1 phosphorylation of serine 65 in parkin's UBL and serine 65 of ubiquitin fully activate ubiquitin

132 nt, while simultaneously freeing Ubiquilin's UBL domain for targeting to the proteasome.

133 mal to T1 within the Rpn1 toroid is a second UBL-binding site ( T2: ) that assists in ubiquitin chain

134 Some UBL proteins are present in all cell types, while others

135 less, RING E3 mechanisms matching a specific UBL and acceptor lysine remain elusive, including for RB

136 stems use related enzymes to attach specific UBLs to proteins (or other molecules), and most of these

137 h ISG15, a 15 kD interferon-(IFN) stimulated UBL found in mammals.

138 is increasing evidence suggesting that such UBL-protein modification evolved from prokaryotic sulphu

139 l stress promotes accumulation of GFP-tagged UBL-5 in nuclei of transgenic worms, suggesting that UBL

140 analysis revealed that 40.1 contains tandem UBL domains, and shares homology with ISG15, a 15 kD int

141 bind ubiquitin in addition to an N-terminal UBL domain that binds S5a and S2, two components of the

142 nd dissociation of the regulatory N-terminal UBL domain.

143 asome Ub receptor RPN10 via their N-terminal UBL domains.

144 We demonstrate that UBL/UBA proteins can bind a common tetraubiquitin molecu

145 turbed in ubl-5(RNAi) worms, indicating that UBL-5 also counteracts physiological levels of mitochond

146 nuclei of transgenic worms, suggesting that UBL-5 effects a nuclear step required for mounting a res

147 olvement in the UFD pathway, suggesting that UBL-mediated interactions may contribute to the substrat

148 mmon ancestor of eukaryotes, suggesting that UBL-protein conjugation did not first evolve in eukaryot

149 The UBL and target regulate the catalytic machinery by posit

150 The UBL probes described here will be valuable tools for the

151 rich) that forms homo-oligomer, allowing the UBL domain to form multivalent interactions with gp78 an

152 it more weakly, with the proteasome, and the UBL is dispensable for this interaction.

153 in ubiquitin-dependent proteolysis, and the UBL method offers many advantages for studies of the div

154 Compound 1 is less potent with FAT10 as the UBL compared with ubiquitin in ATP-PP(i) exchange assays

155 ke (UBL) domain of Ytm1/WDR12 as well as the UBL domain of Rsa4/Nle1 in a later step in the ribosome

156 investigate how the interaction between the UBL and UBA domains may modulate ubiquitin recognition a

157 ubiquitin chain disassembly, by binding the UBL of deubiquitinating enzyme Ubp6.

158 The E1 first binds the UBL and catalyzes adenylation of the UBL's C-terminus, p

159 er, we show that phosphorylation of both the UBL domain and ubiquitin are required to activate parkin

160 ntly, but instead require integration by the UBL and target for maximal reactivity.

161 various UBL-interacting proteins, dubbed the UBL interactome, represent a network of proteins that fu

162 -specific labeling patterns observed for the UBL probes reflect distinct expression profiles of activ

163 However, the UBL motif was necessary for GSK3beta degradation.

164 inding model using specific mutations in the UBL domain.

165 's Arg 72, which corresponds to Ala72 in the UBL NEDD8, is a key E1 selectivity determinant: swapping

166 Mutations in the UBL of Rad23 alter its interactions with Ufd2 and the pr

167 exists only in IKKbeta and that we named the UBL-like domain (ULD).

168 Here we present the crystal structure of the UBL domain of the WDR12 homologue from S. cerevisiae at

169 Deletion of the UBL domain or pharmacological inhibition of proteasomes

170 CRLs are activated by ligation of the UBL NEDD8 to a conserved cullin lysine.

171 bit caspases by promoting conjugation of the UBL NEDD8.

172 We find that destabilization of the UBL results from rearrangements to hydrophobic core pack

173 two E3s, Hrt1 and Dcn1, for ligation of the UBL Rub1 to Cdc53's WHB subdomain.

174 nds the UBL and catalyzes adenylation of the UBL's C-terminus, prior to promoting UBL transfer to a d

175 required to activate parkin by releasing the UBL domain, forming an extended structure needed to faci

176 Unexpectedly, we find that the UBL domain is involved in homo-oligomerization of BMI1.

177 Here, we demonstrate that the UBL domain of Bag6 is required for interaction with the

178 Our evidence further suggests that the UBL domain of Dsk2 is critical for inclusion body format

179 We present evidence that the UBL domain of HHR23A negatively regulates polyubiquitin/

180 Here, we demonstrate that the UBL motif of Rad23 also binds Ufd2, an E4 enzyme essenti

181 We propose that the UBL motif, a protein-protein interaction module, may be

182 and were not previously known to bind to the UBL domain of hHR23B.

183 Thus, transferring the UBL's thioester linkage between successive conjugation e

184 adenylation, forming a covalent E1 throught UBL thioester intermediate, and generating a thioester-l

185 nd generating a thioester-linked E2 throught UBL product, which must be released for subsequent react

186 Central to UBL protein signaling pathways are UBL protein-activatin

187 Moreover, proteins similar to UBL-conjugating enzymes and UBL-deconjugating enzymes se

188 report the structural analysis of a trapped UBL activation complex for the human NEDD8 pathway, cont

189 hemical assembly of fully natural UBL-Ub, Ub-UBL, and UBL-UBL conjugates from recombinant monomers is

190 ication, a quantitative method to measure Ub/UBL activation by E1 is lacking.

191 y to accurately measure the activation of Ub/UBL by E1 independent of the E2/E3 enzymes.

192 nate E2s resulting in the fidelity of the Ub/UBL conjugation machinery.

193 n understanding the specificities underlying UBL pathways.

194 3 and Ddi1 interact with each other by using UBL/UBA domain interactions in a manner that does not pr

195 The various UBL systems use related enzymes to attach specific UBLs

196 These various UBL-interacting proteins, dubbed the UBL interactome, re

197 reveal that hHR23a interacts with hPLIC2 via UBL/UBA domain interactions and to map their binding sur

198 Protein modification occurs via UBL-conjugating and -deconjugating enzymes, which presum

199 meotic proteins and homo-oligomerization via UBL domain are necessary for H2A ubiquitination activity

200 ur results suggest a mechanism through which UBL/UBA proteins could protect chains from premature de-