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1 osolic region of E-Syts (i.e., the number of C2 domains).
2 sidue ordered region C-terminal to the VPS34 C2 domain.
3 ids and PTEN phospho-tail for binding to the C2 domain.
4 domain inhibitor antibodies and the isolated C2 domain.
5 cular interaction between its C-tail and the C2 domain.
6 pitopes on opposing faces of the factor VIII C2 domain.
7 1 domain by replacing it with the homologous C2 domain.
8 antibody inhibitors against the factor VIII C2 domain.
9 otyrosine-binding site within its N-terminal C2 domain.
10 tivation of NF-kappaB by CC2D1A requires its C2 domain.
11 ontains 10 predicted Armadillo repeats and a C2 domain.
12 ovel site in the cationic beta-groove of the C2 domain.
13 also binds to the membrane through a cryptic C2 domain.
14 rm a Y-shaped complex, centered on the Vps34 C2 domain.
15 von Willebrand factor, and mediation by the C2 domain.
16 nd to several distinct surfaces on the FVIII-C2 domain.
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 8I) to better occupy a cavity between A1 and C2 domains.
21 phatidylcholine, in the presence of the syt1 C2 domains.
22 the protein or via mutagenesis of its tandem C2 domains.
23 tion is a derived feature limited to the PKC-C2 domains.
24 through its tandem, lectin-homology, C1 and C2 domains.
25 tate for Unc13 mediated by the tandem C1 and C2 domains.
26 (s)--and forskolin-stimulated activity of C1/C2 domains.
27 A (HA) are primarily directed to the A2 and C2 domains.
28 ded with peptides spanning FVIII-A2, C1, and C2 domains.
29 pes of factor VIII (fVIII) are in the A2 and C2 domains.
30 mbranes are tightly tethered by Ca(2+)-bound C2 domains.
31 develop antibodies against the fVIII A2 and C2 domains.
32 iated proteins that contain a tandem pair of C2 domains.
33 ature of the linker that connects its tandem C2 domains.
34 and alter the relative orientation of these C2-domains.
35 ansmembrane, linker, and two Ca(2+)-binding (C2) domains.
37 a classical calcium-dependent lipid binding C2 domain, a specific CAR signature is likely responsibl
38 ochondria by a mechanism that depends on its C2 domain, a unique Glu residue in its activation loop,
40 s are mediated through a 10-member family of C2-domain ABA-related (CAR) proteins in Arabidopsis thal
42 n of Munc13-1, or of Munc13-1 with a mutated C2 domain all disrupted L-type channel clustering at gra
44 disrupted the interaction between the tandem C2 domains, altered the intrinsic affinity of syt-1 for
45 dylinositol 3-phosphate (PtdIns(3)P) via its C2 domain, an association that may be required for endos
48 containing 1A (CC2D1A) gene, which encodes a C2 domain and DM14 domain-containing protein, has been l
50 es a truncated form of CC2D1A that lacks the C2 domain and three of the four DM14 domains, we show th
52 min in which the Ca(2+)-binding sites in the C2 domains and a basic cluster involved in membrane bind
54 lineage-specific expansions of Zizimin-type C2 domains and functionally linked CDC42/Rac GTPases occ
56 teins that bind the plasma membrane (PM) via C2 domains and transport lipids between them via SMP dom
57 Analysis of chimeric molecules, isolated C2 domains, and point mutants revealed that the C2B doma
58 attachment protein receptor), Synaptotagmin C2 domains, and the lipid bilayer in real time during th
59 ble fragment of syt1, which contains its two C2 domains, and the neuronal core soluble N-ethylmaleimi
60 synaptotagmin-1 is used instead of isolated C2 domains, and when liposomes containing a physiologica
63 domains of synaptotagmins, the Rasal tandem C2 domains are able to sense and induce membrane curvatu
64 malian cells and showed that while wild-type C2 domains are efficiently secreted, the mutant p.D871N
69 and C2E domains and, to a lesser extent, the C2D domain are dispensable for dysferlin membrane repair
70 epitopes are on opposing sides of the fVIII C2 domain, are consistent with the solvent accessibility
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
75 n two calcium-dependent phospholipid binding C2 domains at the amino terminus and a VWA domain at the
77 ariations depending on the properties of the C2 domain-bearing protein, shedding light to understand
79 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 near the Ca(2+)-binding surface loops of the C2 domain, but binding to phosphoinositide-containing ve
87 ase by virtue of Ca(2+)-binding to their two C2 domains, but their mechanisms of action remain unclea
88 mechanism of Ca(2+) and lipid binding to the C2 domain by NMR spectroscopy and x-ray crystallography.
89 ated the apparent synergy between the tandem C2 domains by altering the length and rigidity of the li
90 t containing a disulfide bond between A1 and C2 domains by mutating Arg-121 and Leu-2302 to Cys (R121
97 nd a fragment containing the synaptotagmin-1 C2 domains (C2AB) to membrane-anchored SNARE complex.
101 ring the plasma membrane-sensing role of the C2 domain, causes phorbol ester-triggered redistribution
102 requires the binding of Ca(2+) to two tandem C2 domains, CBD1 and CBD2, which are an integral part of
105 luorescence measurements indicate that multi-C2 domain constructs of myoferlin, dysferlin, and otofer
106 variants in unrelated probands: WWC1 (WW and C2 domain containing 1), CELSR3 (Cadherin EGF LAG seven-
107 oforms (Syt2, Syt7, Syt9) as well as related C2 domain containing protein, Doc2B and extended Synapto
108 asts lacking one of these gene products, the C2-domain containing protein, SMURF1, are deficient in t
111 We have recently demonstrated that a novel C2 domain-containing protein kinase, EhC2PK is involved
113 by screening all ( approximately 139) human C2 domain-containing proteins by RNA interference in neu
114 The mammalian ferlins are calcium-sensing, C2 domain-containing proteins involved in vesicle traffi
116 hat the C1 domain, in addition to the A2 and C2 domains, contributes significantly to the humoral ant
117 xplore the molecular mechanisms by which the C2 domain controls the initial step in the activation of
118 t participate in such tethering function via C2 domain-dependent interactions with the PM that requir
119 We constructed a FVIII variant lacking the C2 domain (designated DeltaC2) to characterize the contr
120 We found that mutations of aspartates in the C2 domains did not alter plasma membrane localization bu
121 Upon activation by Ca(2+), the PKCalpha C2 domain directs the kinase protein to the plasma membr
122 senses Ca(2+); moreover, the tethered tandem C2 domains display properties distinct from the isolated
124 ns within the soluble calcium-binding double C2 domain (Doc2)-like protein family to selectively redu
125 membrane docking geometries of the PKCalpha C2 domain docked to (i) PS alone and (ii) both PS and PI
126 plex suggests that antibody 3E6 recognizes a C2 domain epitope consisting of the Arg(2209)-Ser(2216)
127 no detectable internal rearrangement of its C2 domains, even as it rapidly inserts into the bilayer.
129 ations that disrupted Ca(2+) binding to both C2 domains failed to rescue evoked release, but supporte
130 C1 domains, indicating that the A1, A2, and C2 domains fold independently into antigenically intact
131 in constructs, each lacking one of the seven C2 domains, for their ability to localize to the plasma
135 ce that Munc13-4 with its two Ca(2+)-binding C2 domains functions as a Ca(2+) sensor for SG exocytosi
137 additional regulatory protein, Doc2b (double C2 domain), has recently been implicated in exocytosis f
140 e structures of the loops at the apex of the C2 domain implicated in membrane recognition and Jagged1
141 domains, in addition to the critical role of C2 domain in ASK1 activity, are important for modulating
142 rystallographic structure of the factor VIII C2 domain in complex with 2 antibodies that illuminates
143 These data underscore the key role of the C2 domain in driving conventional PKC isozymes to the pl
145 erve clustering of anionic lipids around the C2 domain in preference to the phosphatase domain, sugge
146 eate the unique and shared functions of each C2 domain in regulation of synaptic vesicle fusion.
147 inding protein (SMP) domain followed by five C2 domains in E-Syt1 and three C2 domains in E-Syt2/3.
149 We expressed wild-type and mutant alpha2(VI) C2 domains in mammalian cells and showed that while wild
150 shown that EHD proteins bind directly to the C2 domains in myoferlin, a protein that regulates myobla
152 ins including those respectively typified by C2 domains in the Aida (axin interactor, dorsalization a
153 , we identified several distinct families of C2 domains including those respectively typified by C2 d
155 opological similarity to an integral fold of C2 domains, including a putative basic binding pocket.
157 lonal antibody (mAb) ESH8, against the fVIII C2 domain, inhibited binding of fVIII to SF and platelet
158 ctions between two different classes of anti-C2 domain inhibitor antibodies and the isolated C2 domai
160 asurements indicate that all seven dysferlin C2 domains interact with Ca(2+) with a wide range of bin
161 he absence of calcium, consistent with intra-C2 domain interactions forming a "closed" tertiary struc
162 opy, we found that the synergy between these C2 domains involved intra-molecular interactions between
168 the phosphatase domain, suggesting that the C2 domain is involved in nonspecific interactions with n
169 s unknown if Ca(2+) interactions with either C2 domain is required for suppression of asynchronous re
170 indicate that cooperation between the C1 and C2 domains is necessary for full activity of the factor
171 ion to Ca2+ influx, but Ca2+ binding by both C2 domains is required to flip the electrostatic switch
172 rol in Arabidopsis, demonstrating that these C2 domains may be cooperative to mediate FTIP1 function
173 rt, we demonstrate that calcium releases the C2 domain-mediated auto-inhibition in both Nedd4-1 and N
174 nally, previously described Ca(2+)-dependent C2 domain-mediated autoinhibition of Nedd4-2 is not obse
178 -mediated membrane translocation through the C2 domain might be an activation mechanism of Nedd4 in v
180 and analyzed Pten knock-in mice harboring a C2 domain missense mutation at phenylalanine 341 (Pten(F
181 dynamic folding options; 3) C-terminal four-C2 domain module; and 4) calpain-cleaved mini-dysferlinC
182 ction of the SYT tubes shows that one of the C2 domains (most likely C2B, based on its biochemical pr
185 ike protein MbSrc4, contains a lipid-binding C2 domain N-terminal to the conserved SH3-SH2-kinase dom
187 o alternative splicing to include DBL/PH and C2 domains not present in invertebrate Itsn proteins.
188 ween otoferlin C2F domain and intramolecular C2 domains occurred in the absence of calcium, consisten
191 ssion of the II-III loop of the channel, the C2 domain of Munc13-1, or of Munc13-1 with a mutated C2
192 sine-independent, and GRB10 SH2 can bind the C2 domain of NEDD4 and the kinase domain of IGF1R simult
195 Collectively, these studies establish the C2 domain of PKCtheta as a Tyr(P)-binding domain and sug
196 taining peptide derived from CDCP1 binds the C2 domain of PKCtheta with high affinity and activates t
197 The identified motifs are located in the C2 domain of plant PLCs and are not found in any other p
200 lly, it is the first mutation located in the C2 domain of PLCZ1, a domain involved in targeting prote
201 ltiscale metal-ion-dependent dynamics of the C2 domain of protein kinase Calpha (C2alpha) using NMR s
202 e used to determine the configuration of the C2 domain of protein kinase Calpha (PKCalpha-C2) bound t
206 been shown that GRB10 can interact with the C2 domain of the E3 ubiquitin ligase NEDD4 through its S
208 and membrane binding properties of all seven C2 domains of dysferlin as well as a multi-C2 domain con
210 e (EGF) domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch1 d
212 roteins, we demonstrate that five of the six C2 domains of otoferlin sense calcium with apparent diss
213 fusion assay, we found that five of the six C2 domains of otoferlin stimulate membrane fusion in a c
214 we investigate the effects of binding of the C2 domains of otoferlin, dysferlin, and myoferlin on the
215 an acceptor membrane complex containing the C2 domains of Psd2p, PstB2p, and Pbi1p that ligate to Sc
216 Ca-dependent interaction between the tandem C2 domains of Rasal and lipids of the membrane is also r
217 e of interfacial residues between the tandem C2 domains of synaptotagmin (syt)-1, a Ca(2+) sensor for
220 hat physical interactions between the tandem C2 domains of syt-1 contribute to excitation-secretion c
221 ulated by Syt1 multimerization and that both C2 domains of Syt1 are uniquely required for modulating
226 ly interacted with the lipid-binding domain (C2 domain) of PTEN and sequestered it in the nucleus.
229 We further analyze in vivo effects of three C2 domains on the regulatory role of MCTP1 (FTIP1) in fl
230 (PIP2) complexes, revealing how Rabphilin-3A C2 domains operate in cooperation with PIP2/Ca(2+) and S
231 Syt 1 transgenes containing only individual C2 domains, or dual C2A-C2A or C2B-C2B chimeras, failed
233 nase Calpha (PKCalpha) possesses a conserved C2 domain (PKCalpha C2 domain) that acts as a Ca(2+)-reg
234 in VWF binding, and suggest that the A3 and C2 domains play ancillary roles in this interaction.
235 pholipid-binding modules such as PH, C1, and C2 domains play crucial roles in location-dependent regu
236 ammalian Src substrates, suggesting that the C2 domain plays a specific role in M. brevicollis signal
239 ns and antibody binding to human A2, C1, and C2 domains presented as human serum albumin (HSA) fusion
240 In contrast, antibody G99 recognizes the C2 domain primarily through the Pro(2221)-Trp(2229) loop
242 on blocks Cdc15 binding to paxillin Pxl1 and C2 domain protein Fic1 and enhances Cdc15 dynamics.
244 Pxl1 and Fic1, a previously uncharacterized C2 domain protein, add structural integrity to the contr
249 and beta (Doc2alpha and Doc2beta) are tandem C2-domain proteins proposed to function as Ca(2+) sensor
253 stabilize an interface between the p110alpha C2 domain (residue N345) and the p85 iSH2 domain (residu
254 e changes in the relative disposition of the C2-domains result from changing the length of the poly-p
255 EF for Rac1), and show that DHR-1 utilizes a C2 domain scaffold and surface loops to create a basic p
257 ue structure of dysferlin, with seven tandem C2 domains separated by linkers, suggests dysferlin may
258 Disruption of Ca(2+) binding to the PKCbeta C2 domain specifically prevents PTP without impairing ot
259 notype combined with similar findings in the C2 domain stress the importance of inhibitor properties
264 hinge region and its phosphotyrosine-binding C2 domain that controls PKCdelta's enzymology indirectly
265 eakest affinity site triggers changes in the C2 domain that facilitate its interaction with lipid mem
266 nvestigated the properties of its N-terminal C2 domain that functions as an autoinhibitory domain.
267 to identify the conserved amino acids of the C2 domain that regulate the targeting of PLCZ1 and its s
268 delta structure reveals an unexpected second C2 domain that was previously unrecognized from sequence
269 membrane domain, two DysF domains, and seven C2 domains that mediate lipid- and protein-binding inter
270 13 and Tctex-1 (dynein light chain), and two C2-domains that bind to phospholipids, Ca(2+) and SNAREs
271 a) possesses a conserved C2 domain (PKCalpha C2 domain) that acts as a Ca(2+)-regulated membrane targ
273 gions are likely to be shared by majority of C2 domains, the actual constellation of lipid-binding re
275 hrough binding of high local Ca(2+) to their C2 domains, the proteins that sense smaller global Ca(2+
276 hat are able to inhibit binding of the FVIII C2 domain to a model membrane by application of a combin
278 he major driving force in the binding of the C2 domain to anionic membranes, whereas electrostatic in
281 y high Ca(2+) concentrations, binding of the C2 domain to the target lipid phosphatidylserine (PS) is
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+)
285 ral explanation for the ability of different C2 domains to pull plasma and vesicle membranes close to
286 differentially regulate binding of otoferlin C2 domains to target SNARE (t-SNARE) proteins and phosph
291 yses of intrinsic Ca(2+)-binding to the Syt7 C2 domains using isothermal titration calorimetry, did n
292 We study the diffusion of membrane-targeting C2 domains using single-molecule tracking in supported l
293 ersely, an RCP mutant lacking the PA-binding C2 domain was not capable of being tethered at pseudopod
294 alues in the tens of micromolar, whereas the C2D domain was least sensitive, with a near millimolar K
295 Finally, transfection of the PLA(2)IValpha C2 domain (which is directly involved in PLA(2)IValpha m
296 s to the kinase domain of PIPKIgamma via its C2 domain while Lysine 255 in PIPKIgamma acts as the maj
297 Direct binding measurements titrating the C2 domain with PIP(2) in lipid bilayers yield a 1:1 stoi
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
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