560:
55:
586:
35:
47:
74:
320:. For example the anesthesia channel TREK-1 is activated by anesthetic displacement from GM1 lipids. The palmitoylation site is specific for palmitate over prenylation, however, the anesthetics appear to compete non-specifically. This non-selective competition of anesthetic with palmitate likely gives rise to rise to the
298:
and facilitates the clustering of proteins. The clustering can increase the proximity of two molecules. Alternatively, clustering can sequester a protein away from a substrate. For example, palmitoylation of phospholipase D (PLD) sequesters the enzyme away from its substrate phosphatidylcholine. When
332:
Scientists have appreciated the significance of attaching long hydrophobic chains to specific proteins in cell signaling pathways. A good example of its significance is in the clustering of proteins in the synapse. A major mediator of protein clustering in the synapse is the postsynaptic density
120:
proteins. The precise function of palmitoylation depends on the particular protein being considered. Palmitoylation enhances the hydrophobicity of proteins and contributes to their membrane association. Palmitoylation also appears to play a significant role in subcellular trafficking of proteins
315:
Palmitoylation is necessary for the inactivation of anesthesia inducing potassium channels and the localization of GABAAR in synapses. Anesthetics compete with palmitate in ordered lipids and this release gives rise to a component of
643:
Lanyon-Hogg, T., Faronato, M., Serwa, R. A., & Tate, E. W. (2017). Dynamic
Protein Acylation: New Substrates, Mechanisms, and Drug Targets. Trends in Biochemical Sciences, 42(7), 566–581. doi:10.1016/j.tibs.2017.04.004
491:
Rocks O, Peyker A, Kahms M, Verveer PJ, Koerner C, Lumbierres M, Kuhlmann J, Waldmann H, Wittinghofer A, Bastiaens PI (2005). "An acylation cycle regulates localization and activity of palmitoylated Ras isoforms".
157:. Because palmitoylation is a dynamic, post-translational process, it is believed to be employed by the cell to alter the subcellular localization, protein–protein interactions, or binding capacities of a protein.
242:, where the cysteine attacks the acyl-CoA to form an S-acylated DHHC, and then the acyl group is transferred to the substrate. DHHR enzymes exist, and it (as well as some DHHC enzymes) may use a
360:
seems to coordinate activity-dependent changes in synaptic adhesion molecules, synapse structure, and receptor localizations that are involved in memory formation.
337:. When this protein is palmitoylated it is restricted to the membrane. This restriction to the membrane allows it to bind to and cluster ion channels in the
705:"Proteolipids - proteins modified by covalent attachment to lipids - N-myristoylated, S-palmitoylated, prenylated proteins, ghrelin, hedgehog proteins"
1306:
774:"Curation of the Mammalian Palmitoylome Indicates a Pivotal Role for Palmitoylation in Diseases and Disorders of the Nervous System and Cancers"
321:
1301:
199:
is involved in tethering the G protein to the inner surface of the plasma membrane so that the G protein can interact with its receptor.
1135:"Molecular Mechanisms of Synaptogenesis." Edited by Alexander Dityatev and Alaa El-Husseini. Springer: New York, NY. 2006. pg. 72-75
580:
122:
300:
704:
150:
405:
317:
997:"Disruption of palmitate-mediated localization; a shared pathway of force and anesthetic activation of TREK-1 channels"
1145:
Brigidi GS, Sun Y, Beccano-Kelly D, Pitman K, Jobasser M, Borgland SL, Milnerwood AJ, Bamji SX (January 23, 2014).
390:
212:
181:
142:
729:
Rana, MS; Lee, CJ; Banerjee, A (28 February 2019). "The molecular mechanism of DHHC protein acyltransferases".
1281:
1197:
Smotrys J, Linder A (2004). "Palmitoylation of
Intracellular Signaling Proteins: Regulation and Function".
1044:
Pavel, Mahmud Arif; Petersen, E. Nicholas; Wang, Hao; Lerner, Richard A.; Hansen, Scott B. (16 June 2020).
772:
Sanders SS, Martin DD, Butland SL, Lavallée-Adam M, Calzolari D, Kay C, Yates JR, Hayden MR (August 2015).
304:
231:
188:
250:
133:, palmitoylation is usually reversible (because the bond between palmitic acid and protein is often a
902:
844:
785:
600:
Wall, MA; Coleman, DE; Lee, E; Iñiguez-Lluhi, JA; Posner, BA; Gilman, AG; Sprang, SR (Dec 15, 1995).
501:
427:
Dejanovic B, Semtner M, Ebert S, Lamkemeyer T, Neuser F, LĂĽscher B, Meier JC, Schwarz G (July 2014).
349:
complex to dissociate during vesicle fusion. This provides a role for palmitoylation in regulating
239:
1258:
1147:"Palmitoylation of [delta]-catenin by DHHC5 mediates activity-induced synapse plasticity"
754:
525:
1250:
1214:
1176:
1118:
1026:
977:
928:
872:
813:
746:
686:
623:
576:
517:
460:
429:"Palmitoylation of gephyrin controls receptor clustering and plasticity of GABAergic synapses"
395:
303:
is disrupted, the enzyme trafficks to PIP2 where it encounters its substrate and is active by
28:
1210:
253:(2-BP). 2-BP is a nonspecific inhibitor that also halts many other lipid-processing enzymes.
1242:
1206:
1166:
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676:
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613:
568:
509:
450:
440:
350:
1226:
243:
235:
1233:
Linder M, Deschenes R (2007). "Palmitoylation: policing protein stability and traffic".
906:
848:
789:
505:
1171:
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1113:
1088:
1072:
1045:
1021:
996:
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947:
923:
891:
867:
832:
808:
773:
681:
654:
477:
Linder, M.E., "Reversible modification of proteins with thioester-linked fatty acids,"
455:
428:
385:
274:
269:
proteins that are palmitoylated. The highest associations of the palmitoylome are with
196:
130:
547:
1295:
618:
601:
481:, F. Tamanoi and D.S. Sigman, eds., pp. 215-40 (San Diego, CA: Academic Press, 2000).
357:
262:
161:
117:
93:
39:
1262:
758:
529:
833:"Palmitoylation regulates raft affinity for the majority of integral raft proteins"
831:
Levental, I.; Lingwood, D.; Grzybek, M.; Coskun, U.; Simons, K. (3 December 2010).
338:
216:
54:
223:(C18:1) are also frequently accepted, more so in plant and viral proteins, making
1012:
798:
445:
1277:
CSS-Palm - Palmitoylation Site
Prediction with a Clustering and Scoring Strategy
542:
Basu, J., "Protein palmitoylation and dynamic modulation of protein function,"
400:
380:
295:
208:
192:
185:
126:
963:
191:(eNOS). In signal transduction via G protein, palmitoylation of the α subunit,
168:
to attach to host cell receptors. The palmitoylation cycles of a wide array of
17:
89:
1227:"Palmitoylation of Ligands, Receptors, and Intracellular Signaling Molecules"
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892:"Kinetic disruption of lipid rafts is a mechanosensor for phospholipase D."
876:
817:
750:
690:
572:
521:
464:
34:
1089:"Differential palmitoylation regulates intracellular patterning of SNAP25"
655:"Progress toward Understanding Protein S-acylation: Prospective in Plants"
627:
364:
97:
78:
914:
890:
Petersen, EN; Chung, HW; Nayebosadri, A; Hansen, SB (15 December 2016).
742:
1104:
602:"The structure of the G protein heterotrimer Gi alpha 1 beta 1 gamma 2"
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278:
146:
62:
73:
334:
270:
220:
169:
105:
1246:
1162:
948:"Tools for Understanding Nanoscale Lipid Regulation of Ion Channels"
177:
346:
173:
72:
53:
45:
33:
230:
Several structures of the DHHC domain have been determined using
81:
Controls
Receptor Clustering and Plasticity of GABAergic Synapses
1276:
995:
Petersen, EN; Pavel, MA; Wang, H; Hansen, SB (28 October 2019).
215:(APT) catalyses the reverse reaction. Other acyl groups such as
561:"INFLUENZA VIRUSES (ORTHOMYXOVIRIDAE) | Molecular Biology"
341:
membrane. Also, in the presynaptic neuron, palmitoylation of
345:
directs it to partition in the cell membrane and allows the
265:
of 15 studies produced a compendium of approximately 2,000
116:-palmitoylation) residues of proteins, which are typically
172:
have been characterized in the past few years, including
160:
An example of a protein that undergoes palmitoylation is
1286:
299:
cholesterol levels decrease or PIP2 levels increase the
207:
S-palmitoylation is generally done by proteins with the
121:
between membrane compartments, as well as in modulating
946:
Robinson, CV; Rohacs, T; Hansen, SB (September 2019).
294:
Palmitoylation mediates the affinity of a protein for
548:
http://www.ias.ac.in/currsci/jul252004/contents.htm
38:In palmitoylation, a palmitoyl group (derived from
1001:Biochimica et Biophysica Acta (BBA) - Biomembranes
1046:"Studies on the mechanism of general anesthesia"
1050:Proceedings of the National Academy of Sciences
837:Proceedings of the National Academy of Sciences
211:. Exceptions exist in non-enzymatic reactions.
639:
637:
559:Palese, Peter; GarcĂa-Sastre, Adolfo (1999).
546:, Vol. 87, No. 2, pp. 212-17 (25 July 2004),
8:
249:An inhibitor of S-palmitoylation by DHHC is
238:of Asp153, His154, and Cys156. It runs on a
422:
420:
1170:
1112:
1071:
1061:
1020:
971:
922:
866:
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281:proteins were found in the palmitoylome.
1211:10.1146/annurev.biochem.73.011303.073954
104:-palmitoylation) and less frequently to
416:
1287:Swisspalm - S-Palmitoylation database
1235:Nature Reviews Molecular Cell Biology
69:Close up. Palmityl residue in yellow.
7:
50:Palmitoylation of a cysteine residue
234:. It contains a linearly-arranged
164:, a membrane glycoprotein used by
25:
143:acyl-protein thioesterases (APTs)
1087:Greaves, Jennifer (March 2011).
731:Biochemical Society Transactions
1307:Post-translational modification
367:has been reported to influence
301:palmitate mediated localization
151:palmitoyl protein thioesterases
137:bond). The reverse reaction in
952:Trends in Biochemical Sciences
88:is the covalent attachment of
1:
61:Palmitoylation (red) anchors
1302:Peripheral membrane proteins
1013:10.1016/j.bbamem.2019.183091
799:10.1371/journal.pcbi.1004405
619:10.1016/0092-8674(95)90220-1
446:10.1371/journal.pbio.1001908
406:Membrane-mediated anesthesia
318:membrane-mediated anesthesia
123:protein–protein interactions
42:, pictured above) is added.
1323:
1229:. Sci STK. 359 October 31.
964:10.1016/j.tibs.2019.04.001
778:PLOS Computational Biology
659:Frontiers in Plant Science
391:Myelin proteolipid protein
65:G to the plasma membrane.
26:
213:Acyl-protein thioesterase
565:Encyclopedia of Virology
322:Myer-Overton correlation
27:Not to be confused with
1093:Journal of Cell Science
1063:10.1073/pnas.2004259117
858:10.1073/pnas.1016184107
709:www.lipidmaps.org.co.uk
672:10.3389/fpls.2017.00346
514:10.1126/science.1105654
277:. Approximately 40% of
573:10.1006/rwvi.1999.0157
305:substrate presentation
290:Substrate presentation
195:of the Îł subunit, and
182:β2-adrenergic receptor
141:cells is catalyzed by
82:
70:
51:
43:
895:Nature Communications
653:Li, Y; Qi, B (2017).
273:and disorders of the
232:X-ray crystallography
189:nitric oxide synthase
76:
57:
49:
37:
567:. pp. 830–836.
227:a more useful name.
1151:Nature Neuroscience
1056:(24): 13757–13766.
915:10.1038/ncomms13873
907:2016NatCo...713873P
849:2010PNAS..10722050L
843:(51): 22050–22054.
790:2015PLSCB..11E4405S
743:10.1042/BST20180429
506:2005Sci...307.1746R
500:(5716): 1746–1752.
285:Biological function
246:mechanism instead.
240:ping-pong mechanism
1105:10.1242/jcs.079095
479:Protein Lipidation
363:Palmitoylation of
356:Palmitoylation of
311:General Anesthesia
83:
77:Palmitoylation of
71:
52:
44:
396:Palmitoleoylation
328:Synapse formation
125:. In contrast to
29:Palmitoleoylation
16:(Redirected from
1314:
1266:
1225:Resh, M. (2006)
1222:
1199:Annu Rev Biochem
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351:neurotransmitter
257:The palmitoylome
251:2-Bromopalmitate
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333:(95kD) protein
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244:ternary complex
236:catalytic triad
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32:
23:
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18:Palmitoyl group
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5:
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1271:External links
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1157:(4): 522–532.
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275:nervous system
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131:myristoylation
86:Palmitoylation
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40:palmitic acid
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712:. Retrieved
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587:the original
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339:postsynaptic
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85:
84:
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58:
1282:CKSAAP-Palm
401:Prenylation
381:DHHC domain
296:lipid rafts
225:S-acylation
219:(C18:0) or
209:DHHC domain
193:prenylation
186:endothelial
127:prenylation
90:fatty acids
1296:Categories
1205:: 559–87.
412:References
371:synapses.
92:, such as
901:: 13873.
369:GABAergic
353:release.
267:mammalian
203:Mechanism
166:influenza
155:lysosomes
139:mammalian
135:thioester
110:threonine
1263:26339042
1255:17183362
1219:15189153
1181:24562000
1123:21429935
1031:31672538
982:31060927
933:27976674
877:21131568
818:26275289
759:56175691
751:30559274
691:28392791
530:12408991
522:15705808
465:25025157
375:See also
365:gephyrin
279:synaptic
217:stearate
118:membrane
98:cysteine
79:Gephyrin
1172:5025286
1114:3065388
1073:7306821
1022:6907892
973:6729126
924:5171650
903:Bibcode
868:3009825
845:Bibcode
809:4537140
786:Bibcode
714:19 July
682:5364179
665:: 346.
628:8521505
502:Bibcode
494:Science
456:4099074
343:SNAP-25
271:cancers
170:enzymes
147:cytosol
145:in the
63:Ankyrin
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335:PSD-95
221:oleate
184:, and
180:, the
106:serine
1259:S2CID
755:S2CID
526:S2CID
347:SNARE
174:H-Ras
96:, to
67:Right
1251:PMID
1215:PMID
1177:PMID
1119:PMID
1027:PMID
1005:1862
978:PMID
929:PMID
873:PMID
814:PMID
747:PMID
716:2021
687:PMID
624:PMID
606:Cell
577:ISBN
518:PMID
461:PMID
149:and
129:and
108:and
59:Left
1243:doi
1207:doi
1167:PMC
1159:doi
1109:PMC
1101:doi
1097:124
1068:PMC
1058:doi
1054:117
1017:PMC
1009:doi
968:PMC
960:doi
919:PMC
911:doi
863:PMC
853:doi
841:107
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