PCLO

Protein piccolo is a protein that in humans is encoded by the PCLO gene.[5][6][7]

PCLO
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1UJD
Identifiers
Aliases	PCLO, ACZ, PCH3, piccolo presynaptic cytomatrix protein
External IDs	OMIM: 604918 MGI: 1349390 HomoloGene: 69111 GeneCards: PCLO
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7q21.11 Start 82,754,012 bp[1] End 83,162,930 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5|5 A1 Start 14,514,918 bp[2] End 14,863,459 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • calcium-dependent phospholipid binding • profilin binding • calcium ion binding • metal ion binding • structural constituent of presynaptic active zone Cellular component • presynaptic active zone • cell junction • synapse • cytoskeleton • extracellular exosome • membrane • GO:0097483, GO:0097481 postsynaptic density • cytoskeleton of presynaptic active zone • presynaptic active zone cytoplasmic component Biological process • regulation of exocytosis • synapse assembly • insulin secretion • cytoskeleton organization • cAMP-mediated signaling • synaptic vesicle exocytosis • protein localization to synapse • presynapse to nucleus signaling pathway • maintenance of presynaptic active zone structure • synaptic vesicle clustering Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	27445	26875
Ensembl	ENSG00000186472	ENSMUSG00000061601
UniProt	Q9Y6V0	Q9QYX7
RefSeq (mRNA)	NM_033026 NM_014510	NM_001110796 NM_011995
RefSeq (protein)	NP_055325 NP_149015	NP_001104266 NP_036125
Location (UCSC)	Chr 7: 82.75 – 83.16 Mb	Chr 5: 14.51 – 14.86 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

Synaptic vesicles dock and fuse in the active zone of the plasma membrane at chemical synapses. The presynaptic cytoskeletal matrix (PCM), which is associated with the active zone and is situated between synaptic vesicles, is thought to be involved in maintaining the neurotransmitter release site in register with the postsynaptic reception apparatus. The cycling of synaptic vesicles is a multistep process involving a number of proteins (see MIM 603215). Among the components of the PCM that orchestrate these events are Bassoon (BSN; MIM 604020), RIM (RIMS1; MIM 606629), Oboe (RIMS2; MIM 606630), and Piccolo (PCLO).[supplied by OMIM][7]

Interactions

The protein product of PCLO called Piccolo has been shown to interact with number of proteins including GIT1,[8] the F-actin-binding protein Abp1,[9] PRA1,[10] TRIO,[11] DAAM1,[12] and Profilin.[13]

Clinical relevance

Recurrent mutations in this gene have been associated to cases of diffuse large B-cell lymphoma.[14] Recent evidence has shown that a homozygous, nonsense PCLO mutation is the genetic cause of the autosomal recessive neurodegenerative disorder, pontocerebellar hypoplasia type III (PCH3).[15]

References

1. GRCh38: Ensembl release 89: ENSG00000186472 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000061601 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Cases-Langhoff C, Voss B, Garner AM, Appeltauer U, Takei K, Kindler S, Veh RW, De Camilli P, Gundelfinger ED, Garner CC (Mar 1996). "Piccolo, a novel 420 kDa protein associated with the presynaptic cytomatrix". European Journal of Cell Biology. 69 (3): 214–23. PMID 8900486.
6. Nagase T, Ishikawa K, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Feb 1998). "Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Research. 5 (1): 31–9. doi:10.1093/dnares/5.1.31. PMID 9628581.
7. "Entrez Gene: PCLO piccolo (presynaptic cytomatrix protein)".
8. Kim S, Ko J, Shin H, Lee JR, Lim C, Han JH, Altrock WD, Garner CC, Gundelfinger ED, Premont RT, Kaang BK, Kim E (Feb 2003). "The GIT family of proteins forms multimers and associates with the presynaptic cytomatrix protein Piccolo". The Journal of Biological Chemistry. 278 (8): 6291–300. doi:10.1074/jbc.M212287200. PMID 12473661.
9. Fenster, Steven D.; Kessels, Michael M.; Qualmann, Britta; Chung, Wook J.; Nash, Joanne; Gundelfinger, Eckart D.; Garner, Craig C. (2003-05-30). "Interactions between Piccolo and the actin/dynamin-binding protein Abp1 link vesicle endocytosis to presynaptic active zones". The Journal of Biological Chemistry. 278 (22): 20268–20277. doi:10.1074/jbc.M210792200. PMID 12654920.
10. Fenster, S. D.; Chung, W. J.; Zhai, R.; Cases-Langhoff, C.; Voss, B.; Garner, A. M.; Kaempf, U.; Kindler, S.; Gundelfinger, E. D. (2000-01-01). "Piccolo, a presynaptic zinc finger protein structurally related to bassoon". Neuron. 25 (1): 203–214. doi:10.1016/s0896-6273(00)80883-1. PMID 10707984. S2CID 10177138.
11. Terry-Lorenzo, Ryan T.; Torres, Viviana I.; Wagh, Dhananjay; Galaz, Jose; Swanson, Selene K.; Florens, Laurence; Washburn, Michael P.; Waites, Clarissa L.; Gundelfinger, Eckart D. (2016-01-01). "Trio, a Rho Family GEF, Interacts with the Presynaptic Active Zone Proteins Piccolo and Bassoon". PLOS ONE. 11 (12): e0167535. doi:10.1371/journal.pone.0167535. PMC 5132261. PMID 27907191.
12. Wagh, Dhananjay; Terry-Lorenzo, Ryan; Waites, Clarissa L.; Leal-Ortiz, Sergio A.; Maas, Christoph; Reimer, Richard J.; Garner, Craig C. (2015-01-01). "Piccolo Directs Activity Dependent F-Actin Assembly from Presynaptic Active Zones via Daam1". PLOS ONE. 10 (4): e0120093. doi:10.1371/journal.pone.0120093. PMC 4405365. PMID 25897839.
13. Wang, X.; Kibschull, M.; Laue, M. M.; Lichte, B.; Petrasch-Parwez, E.; Kilimann, M. W. (1999-10-04). "Aczonin, a 550-kD putative scaffolding protein of presynaptic active zones, shares homology regions with Rim and Bassoon and binds profilin". The Journal of Cell Biology. 147 (1): 151–162. doi:10.1083/jcb.147.1.151. PMC 2164979. PMID 10508862.
14. Lohr JG, Stojanov P, Lawrence MS, Auclair D, Chapuy B, Sougnez C, Cruz-Gordillo P, Knoechel B, Asmann YW, Slager SL, Novak AJ, Dogan A, Ansell SM, Link BK, Zou L, Gould J, Saksena G, Stransky N, Rangel-Escareño C, Fernandez-Lopez JC, Hidalgo-Miranda A, Melendez-Zajgla J, Hernández-Lemus E, Schwarz-Cruz y Celis A, Imaz-Rosshandler I, Ojesina AI, Jung J, Pedamallu CS, Lander ES, Habermann TM, Cerhan JR, Shipp MA, Getz G, Golub TR (Mar 2012). "Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing". Proceedings of the National Academy of Sciences of the United States of America. 109 (10): 3879–84. doi:10.1073/pnas.1121343109. PMC 3309757. PMID 22343534.
15. Ahmed, Mustafa Y.; Chioza, Barry A.; Rajab, Anna; Schmitz-Abe, Klaus; Al-Khayat, Aisha; Al-Turki, Saeed; Baple, Emma L.; Patton, Michael A.; Al-Memar, Ali Y. (2015-04-28). "Loss of PCLO function underlies pontocerebellar hypoplasia type III". Neurology. 84 (17): 1745–1750. doi:10.1212/WNL.0000000000001523. PMC 4424132. PMID 25832664.

Further reading

• Sanger Centre, The; Washington University Genome Sequencing Cente, The (Nov 1998). "Toward a complete human genome sequence". Genome Research. 8 (11): 1097–108. doi:10.1101/gr.8.11.1097. PMID 9847074.
• Wang X, Kibschull M, Laue MM, Lichte B, Petrasch-Parwez E, Kilimann MW (Oct 1999). "Aczonin, a 550-kD putative scaffolding protein of presynaptic active zones, shares homology regions with Rim and Bassoon and binds profilin". The Journal of Cell Biology. 147 (1): 151–62. doi:10.1083/jcb.147.1.151. PMC 2164979. PMID 10508862.
• Fenster SD, Chung WJ, Zhai R, Cases-Langhoff C, Voss B, Garner AM, Kaempf U, Kindler S, Gundelfinger ED, Garner CC (Jan 2000). "Piccolo, a presynaptic zinc finger protein structurally related to bassoon". Neuron. 25 (1): 203–14. doi:10.1016/S0896-6273(00)80883-1. PMID 10707984. S2CID 10177138.
• Fenster SD, Garner CC (2002). "Gene structure and genetic localization of the PCLO gene encoding the presynaptic active zone protein Piccolo". International Journal of Developmental Neuroscience. 20 (3–5): 161–71. doi:10.1016/S0736-5748(02)00046-1. PMID 12175852. S2CID 21515091.
• Takao-Rikitsu E, Mochida S, Inoue E, Deguchi-Tawarada M, Inoue M, Ohtsuka T, Takai Y (Jan 2004). "Physical and functional interaction of the active zone proteins, CAST, RIM1, and Bassoon, in neurotransmitter release". The Journal of Cell Biology. 164 (2): 301–11. doi:10.1083/jcb.200307101. PMC 2172332. PMID 14734538.

External links

• Overview of all the structural information available in the PDB for UniProt: Q9Y6V0 (Protein piccolo) at the PDBe-KB.