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1 osolic region of E-Syts (i.e., the number of C2 domains).
2 also binds to the membrane through a cryptic C2 domain.
3 rm a Y-shaped complex, centered on the Vps34 C2 domain.
4 von Willebrand factor, and mediation by the C2 domain.
5 nd to several distinct surfaces on the FVIII-C2 domain.
6 sidue ordered region C-terminal to the VPS34 C2 domain.
7 ids and PTEN phospho-tail for binding to the C2 domain.
8 domain inhibitor antibodies and the isolated C2 domain.
9 cular interaction between its C-tail and the C2 domain.
10 pitopes on opposing faces of the factor VIII C2 domain.
11 1 domain by replacing it with the homologous C2 domain.
12 antibody inhibitors against the factor VIII C2 domain.
13 otyrosine-binding site within its N-terminal C2 domain.
14 develop antibodies against the fVIII A2 and C2 domains.
15 iated proteins that contain a tandem pair of C2 domains.
16 ature of the linker that connects its tandem C2 domains.
17 branes with antiparallel orientations of the C2 domains.
18 ain, and two conserved tandem Ca(2+)-binding C2 domains.
19 tructures show close contacts between A1 and C2 domains.
20 branes as the C2AB tandem than as individual C2 domains.
21 8I) to better occupy a cavity between A1 and C2 domains.
22 phatidylcholine, in the presence of the syt1 C2 domains.
23 the protein or via mutagenesis of its tandem C2 domains.
24 ns (cytoplasmic membrane) binding of its two C2 domains.
25 A (HA) are primarily directed to the A2 and C2 domains.
26 tate for Unc13 mediated by the tandem C1 and C2 domains.
27 ded with peptides spanning FVIII-A2, C1, and C2 domains.
28 pes of factor VIII (fVIII) are in the A2 and C2 domains.
29 mbranes are tightly tethered by Ca(2+)-bound C2 domains.
30 and alter the relative orientation of these C2-domains.
31 ansmembrane, linker, and two Ca(2+)-binding (C2) domains.
33 a classical calcium-dependent lipid binding C2 domain, a specific CAR signature is likely responsibl
34 ochondria by a mechanism that depends on its C2 domain, a unique Glu residue in its activation loop,
36 s are mediated through a 10-member family of C2-domain ABA-related (CAR) proteins in Arabidopsis thal
39 n of Munc13-1, or of Munc13-1 with a mutated C2 domain all disrupted L-type channel clustering at gra
41 disrupted the interaction between the tandem C2 domains, altered the intrinsic affinity of syt-1 for
42 dylinositol 3-phosphate (PtdIns(3)P) via its C2 domain, an association that may be required for endos
45 containing 1A (CC2D1A) gene, which encodes a C2 domain and DM14 domain-containing protein, has been l
46 es a truncated form of CC2D1A that lacks the C2 domain and three of the four DM14 domains, we show th
48 KY (QKY), a member of the family of multiple C2 domain and transmembrane region proteins (MCTPs), to
49 plicated noncatalytic regions, including the C2 domain and/or WW domain linkers in NEDD4-1 and WWP2,
50 min in which the Ca(2+)-binding sites in the C2 domains and a basic cluster involved in membrane bind
51 egion in C2A domain is longer than classical C2 domains and a novel Ca(2+) binding site in the vWA do
55 teins that bind the plasma membrane (PM) via C2 domains and transport lipids between them via SMP dom
56 Analysis of chimeric molecules, isolated C2 domains, and point mutants revealed that the C2B doma
57 attachment protein receptor), Synaptotagmin C2 domains, and the lipid bilayer in real time during th
60 domains of synaptotagmins, the Rasal tandem C2 domains are able to sense and induce membrane curvatu
61 malian cells and showed that while wild-type C2 domains are efficiently secreted, the mutant p.D871N
68 and C2E domains and, to a lesser extent, the C2D domain are dispensable for dysferlin membrane repair
69 epitopes are on opposing sides of the fVIII C2 domain, are consistent with the solvent accessibility
70 In full-length Syt1, both Pb(2+)-complexed C2 domains associate with phosphatidylserine-containing
71 The 3E6 epitope forms direct contacts to the C2 domain at 2 loops consisting of Glu2181-Ala2188 and T
73 his interaction was facilitated by a cryptic C2 domain at the extreme N terminus of Psd2p (C2-1) as w
74 tanding of Notch signalling by identifying a C2 domain at the N-terminus of Notch ligands, which has
76 ariations depending on the properties of the C2 domain-bearing protein, shedding light to understand
78 ally, sedimentation assays suggest all seven C2 domains bind lipid membranes, and that Ca(2+) enhance
84 ined in flexible top-loop sequences of their C2 domains--blocked the ability of these synaptotagmins
86 ase by virtue of Ca(2+)-binding to their two C2 domains, but their mechanisms of action remain unclea
87 mechanism of Ca(2+) and lipid binding to the C2 domain by NMR spectroscopy and x-ray crystallography.
88 ated the apparent synergy between the tandem C2 domains by altering the length and rigidity of the li
89 t containing a disulfide bond between A1 and C2 domains by mutating Arg-121 and Leu-2302 to Cys (R121
90 es by IHCs is controlled by otoferlin, a six-C2-domain (C2-ABCDEF) protein that functions as a high-a
94 inker region, and contains tandem C-terminal C2 domains (C2A and C2B) with affinity for phosphatidyli
96 ne protein whose phospholipid-binding tandem C2 domains, C2A and C2B, act as Ca(2+) sensors of neurot
97 ptotagmin-7 (Syt-7) contain analogous tandem C2 domains, C2A and C2B, which together sense Ca(2+) to
100 nd a fragment containing the synaptotagmin-1 C2 domains (C2AB) to membrane-anchored SNARE complex.
104 ring the plasma membrane-sensing role of the C2 domain, causes phorbol ester-triggered redistribution
105 requires the binding of Ca(2+) to two tandem C2 domains, CBD1 and CBD2, which are an integral part of
108 luorescence measurements indicate that multi-C2 domain constructs of myoferlin, dysferlin, and otofer
109 variants in unrelated probands: WWC1 (WW and C2 domain containing 1), CELSR3 (Cadherin EGF LAG seven-
111 oforms (Syt2, Syt7, Syt9) as well as related C2 domain containing protein, Doc2B and extended Synapto
113 asts lacking one of these gene products, the C2-domain containing protein, SMURF1, are deficient in t
116 ntification of an IRT1 inhibitor, namely the C2 domain-containing peripheral membrane protein ENHANCE
117 ss of the signaling scaffold coiled-coil and C2 domain-containing protein 1A (CC2D1A), which is mutat
118 We have recently demonstrated that a novel C2 domain-containing protein kinase, EhC2PK is involved
120 by screening all ( approximately 139) human C2 domain-containing proteins by RNA interference in neu
122 The molecular events by which each otoferlin C2 domain contributes to the regulation of the synaptic
123 hat the C1 domain, in addition to the A2 and C2 domains, contributes significantly to the humoral ant
124 xplore the molecular mechanisms by which the C2 domain controls the initial step in the activation of
125 asured during confinement, we find that both C2 domains cooperate in membrane binding, with the C2B d
126 t participate in such tethering function via C2 domain-dependent interactions with the PM that requir
127 We constructed a FVIII variant lacking the C2 domain (designated DeltaC2) to characterize the contr
128 We found that mutations of aspartates in the C2 domains did not alter plasma membrane localization bu
129 senses Ca(2+); moreover, the tethered tandem C2 domains display properties distinct from the isolated
131 oteins in the synaptotagmin (syt) and double C2 domain (Doc2) families regulate exocytotic membrane f
133 ns within the soluble calcium-binding double C2 domain (Doc2)-like protein family to selectively redu
134 membrane docking geometries of the PKCalpha C2 domain docked to (i) PS alone and (ii) both PS and PI
135 plex suggests that antibody 3E6 recognizes a C2 domain epitope consisting of the Arg(2209)-Ser(2216)
136 no detectable internal rearrangement of its C2 domains, even as it rapidly inserts into the bilayer.
139 ations that disrupted Ca(2+) binding to both C2 domains failed to rescue evoked release, but supporte
140 C1 domains, indicating that the A1, A2, and C2 domains fold independently into antigenically intact
141 in constructs, each lacking one of the seven C2 domains, for their ability to localize to the plasma
144 ce that Munc13-4 with its two Ca(2+)-binding C2 domains functions as a Ca(2+) sensor for SG exocytosi
146 additional regulatory protein, Doc2b (double C2 domain), has recently been implicated in exocytosis f
149 e structures of the loops at the apex of the C2 domain implicated in membrane recognition and Jagged1
150 rystallographic structure of the factor VIII C2 domain in complex with 2 antibodies that illuminates
151 n astrocytes triggers the interaction of the C2 domain in cytosolic phospholipase A2 (cPLA2) with the
152 These data underscore the key role of the C2 domain in driving conventional PKC isozymes to the pl
154 erve clustering of anionic lipids around the C2 domain in preference to the phosphatase domain, sugge
155 eate the unique and shared functions of each C2 domain in regulation of synaptic vesicle fusion.
156 y restricted loop regions and positioning of C2 domains in close proximity to anionic lipid headgroup
157 inding protein (SMP) domain followed by five C2 domains in E-Syt1 and three C2 domains in E-Syt2/3.
159 We expressed wild-type and mutant alpha2(VI) C2 domains in mammalian cells and showed that while wild
160 shown that EHD proteins bind directly to the C2 domains in myoferlin, a protein that regulates myobla
162 opological similarity to an integral fold of C2 domains, including a putative basic binding pocket.
163 ch more slowly than either of its individual C2 domains, indicating cooperativity, whereas the major
165 lonal antibody (mAb) ESH8, against the fVIII C2 domain, inhibited binding of fVIII to SF and platelet
166 ctions between two different classes of anti-C2 domain inhibitor antibodies and the isolated C2 domai
168 asurements indicate that all seven dysferlin C2 domains interact with Ca(2+) with a wide range of bin
170 he absence of calcium, consistent with intra-C2 domain interactions forming a "closed" tertiary struc
171 opy, we found that the synergy between these C2 domains involved intra-molecular interactions between
175 the phosphatase domain, suggesting that the C2 domain is involved in nonspecific interactions with n
176 s unknown if Ca(2+) interactions with either C2 domain is required for suppression of asynchronous re
177 ion to Ca2+ influx, but Ca2+ binding by both C2 domains is required to flip the electrostatic switch
178 ith the p.VYEEDM1161V indel suggest that the C2 domain may have a role in regulating PLCgamma1 activi
179 rol in Arabidopsis, demonstrating that these C2 domains may be cooperative to mediate FTIP1 function
180 rt, we demonstrate that calcium releases the C2 domain-mediated auto-inhibition in both Nedd4-1 and N
181 nally, previously described Ca(2+)-dependent C2 domain-mediated autoinhibition of Nedd4-2 is not obse
186 and analyzed Pten knock-in mice harboring a C2 domain missense mutation at phenylalanine 341 (Pten(F
187 dynamic folding options; 3) C-terminal four-C2 domain module; and 4) calpain-cleaved mini-dysferlinC
188 ction of the SYT tubes shows that one of the C2 domains (most likely C2B, based on its biochemical pr
192 o alternative splicing to include DBL/PH and C2 domains not present in invertebrate Itsn proteins.
193 ween otoferlin C2F domain and intramolecular C2 domains occurred in the absence of calcium, consisten
196 ssion of the II-III loop of the channel, the C2 domain of Munc13-1, or of Munc13-1 with a mutated C2
199 We previously identified the amino-terminal C2 domain of PKCtheta as a phosphotyrosine (pTyr)-bindin
200 Collectively, these studies establish the C2 domain of PKCtheta as a Tyr(P)-binding domain and sug
201 taining peptide derived from CDCP1 binds the C2 domain of PKCtheta with high affinity and activates t
202 The identified motifs are located in the C2 domain of plant PLCs and are not found in any other p
205 lly, it is the first mutation located in the C2 domain of PLCZ1, a domain involved in targeting prote
206 ltiscale metal-ion-dependent dynamics of the C2 domain of protein kinase Calpha (C2alpha) using NMR s
212 and membrane binding properties of all seven C2 domains of dysferlin as well as a multi-C2 domain con
214 e (EGF) domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch1 d
216 inactivation, confirming that the C-terminal C2 domains of otoferlin are essential for normal gating
217 roteins, we demonstrate that five of the six C2 domains of otoferlin sense calcium with apparent diss
218 we investigate the effects of binding of the C2 domains of otoferlin, dysferlin, and myoferlin on the
219 an acceptor membrane complex containing the C2 domains of Psd2p, PstB2p, and Pbi1p that ligate to Sc
221 Ca-dependent interaction between the tandem C2 domains of Rasal and lipids of the membrane is also r
222 e of interfacial residues between the tandem C2 domains of synaptotagmin (syt)-1, a Ca(2+) sensor for
225 hat physical interactions between the tandem C2 domains of syt-1 contribute to excitation-secretion c
226 ntrast, we previously suggested that the two C2 domains of Syt-7 bind membranes independently, based
227 ulated by Syt1 multimerization and that both C2 domains of Syt1 are uniquely required for modulating
232 ly interacted with the lipid-binding domain (C2 domain) of PTEN and sequestered it in the nucleus.
235 We further analyze in vivo effects of three C2 domains on the regulatory role of MCTP1 (FTIP1) in fl
236 (PIP2) complexes, revealing how Rabphilin-3A C2 domains operate in cooperation with PIP2/Ca(2+) and S
237 Syt 1 transgenes containing only individual C2 domains, or dual C2A-C2A or C2B-C2B chimeras, failed
239 nase Calpha (PKCalpha) possesses a conserved C2 domain (PKCalpha C2 domain) that acts as a Ca(2+)-reg
240 in VWF binding, and suggest that the A3 and C2 domains play ancillary roles in this interaction.
243 ns and antibody binding to human A2, C1, and C2 domains presented as human serum albumin (HSA) fusion
244 In contrast, antibody G99 recognizes the C2 domain primarily through the Pro(2221)-Trp(2229) loop
245 on blocks Cdc15 binding to paxillin Pxl1 and C2 domain protein Fic1 and enhances Cdc15 dynamics.
248 IGNIFICANCE STATEMENT Otoferlin, a large six-C2-domain protein, is essential for synaptic vesicle exo
252 ory factors such as Sec1/Munc18 (SM), double C2-domain proteins (DOC2), and additional interacting pr
253 and beta (Doc2alpha and Doc2beta) are tandem C2-domain proteins proposed to function as Ca(2+) sensor
257 e changes in the relative disposition of the C2-domains result from changing the length of the poly-p
258 d that binding of one divalent metal ion per C2 domain results in loss of conformational plasticity o
260 ue structure of dysferlin, with seven tandem C2 domains separated by linkers, suggests dysferlin may
261 Disruption of Ca(2+) binding to the PKCbeta C2 domain specifically prevents PTP without impairing ot
262 notype combined with similar findings in the C2 domain stress the importance of inhibitor properties
267 hinge region and its phosphotyrosine-binding C2 domain that controls PKCdelta's enzymology indirectly
268 eakest affinity site triggers changes in the C2 domain that facilitate its interaction with lipid mem
269 nvestigated the properties of its N-terminal C2 domain that functions as an autoinhibitory domain.
270 to identify the conserved amino acids of the C2 domain that regulate the targeting of PLCZ1 and its s
271 delta structure reveals an unexpected second C2 domain that was previously unrecognized from sequence
272 membrane domain, two DysF domains, and seven C2 domains that mediate lipid- and protein-binding inter
273 13 and Tctex-1 (dynein light chain), and two C2-domains that bind to phospholipids, Ca(2+) and SNAREs
274 a) possesses a conserved C2 domain (PKCalpha C2 domain) that acts as a Ca(2+)-regulated membrane targ
277 hrough binding of high local Ca(2+) to their C2 domains, the proteins that sense smaller global Ca(2+
278 hat are able to inhibit binding of the FVIII C2 domain to a model membrane by application of a combin
280 he major driving force in the binding of the C2 domain to anionic membranes, whereas electrostatic in
283 sozymes is initiated by the binding of their C2 domains to membranes in response to elevations in int
284 led a correlation between the ability of the C2 domains to penetrate membranes in response to Ca(2+)
286 ral explanation for the ability of different C2 domains to pull plasma and vesicle membranes close to
287 differentially regulate binding of otoferlin C2 domains to target SNARE (t-SNARE) proteins and phosph
292 yses of intrinsic Ca(2+)-binding to the Syt7 C2 domains using isothermal titration calorimetry, did n
293 We study the diffusion of membrane-targeting C2 domains using single-molecule tracking in supported l
294 ersely, an RCP mutant lacking the PA-binding C2 domain was not capable of being tethered at pseudopod
295 alues in the tens of micromolar, whereas the C2D domain was least sensitive, with a near millimolar K
296 Finally, transfection of the PLA(2)IValpha C2 domain (which is directly involved in PLA(2)IValpha m
297 s to the kinase domain of PIPKIgamma via its C2 domain while Lysine 255 in PIPKIgamma acts as the maj
298 t step in this process is interaction of its C2 domain with target cell membranes, which is a calcium
300 soforms containing common C-terminal PDZ and C2 domains with homology to vertebrate active zone prote