SV2A

Synaptic vesicle glycoprotein 2A (SV2A) is a transmembrane protein belonging to a family of keratan sulfate proteoglycans, located on the synaptic vesicles of mammalian neuronal and endocrine cells. It's encoded by the SV2A gene.^[5][6][7]

SV2A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4V11
Identifiers
Aliases	SV2A, SV2, synaptic vesicle glycoprotein 2A
External IDs	OMIM: 185860; MGI: 1927139; HomoloGene: 32237; GeneCards: SV2A; OMA:SV2A - orthologs
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q21.2 Start 149,903,318 bp[1] End 149,917,844 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3|3 F2.1 Start 96,088,467 bp[2] End 96,102,837 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Brodmann area 10 lateral nuclear group of thalamus paraflocculus of cerebellum pars compacta frontal pole superior frontal gyrus middle temporal gyrus postcentral gyrus primary visual cortex pars reticulata Top expressed in lateral geniculate nucleus lateral hypothalamus mammillary body ventral tegmental area pontine nuclei primary visual cortex superior colliculus cerebellar cortex dorsal tegmental nucleus ventromedial nucleus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transmembrane transporter activity transporter activity protein kinase binding signaling receptor activity Cellular component membrane synaptic vesicle cell-cell junction neuromuscular junction plasma membrane synapse presynaptic active zone cell junction endoplasmic reticulum cytoplasmic vesicle integral component of membrane integral component of synaptic vesicle membrane synaptic vesicle membrane neuron projection dendrite soma glutamatergic synapse GABA-ergic synapse Biological process cellular calcium ion homeostasis transmembrane transport neurotransmitter transport regulation of gamma-aminobutyric acid secretion chemical synaptic transmission signal transduction synaptic vesicle priming Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9900 64051 Ensembl ENSG00000159164 ENSMUSG00000038486 UniProt Q7L0J3 Q9JIS5 RefSeq (mRNA) NM_014849 NM_001278719 NM_001328674 NM_001328675 NM_022030 RefSeq (protein) NP_001265648 NP_001315603 NP_001315604 NP_055664 NP_071313 Location (UCSC) Chr 1: 149.9 – 149.92 Mb Chr 3: 96.09 – 96.1 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

SV2A is the most widely expressed isoform of the SV2 family (which also includes the SV2B and SV2C proteins) found in all brain regions.^[8] The role of the SV2 proteins is not well understood, however they are thought to be involved in regulating vesicular processes.^[8]

The SV2A protein is a target of the anti-epileptic drugs (anticonvulsants) levetiracetam and brivaracetam^[9] but it is not clear how these drug affect SV2A activity.^[10]

Localisation

SV2A is differentially expressed in both inhibitory GABAergic and excitatory glutamatergic terminals^[11] however it is not expressed in all synapses^[12] as was previously thought.^[13] There is a slightly stronger colocalisation between SV2A and GABA than glutamate^[14] and the association differs across brain regions and changes with developmental stages.^[15]

SV2A PET

Several PET radiotracers targeting SV2A have been developed, allowing for measuring SV2A density in-vivo: [11C]LEV, [11C]UCB-A, [11C]-UCB-H, [18F]UCB-J, [18F]Syn-VesT-1, [18F]Syn-VesT-2, and [18F]SDM-16. SV2A density has been used as a proxy for measuring in vivo synaptic density.^{[16][17][18][19]}

See also

• SV2B

References

1. GRCh38: Ensembl release 89: ENSG00000159164 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000038486 – 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. Bajjalieh SM, Peterson K, Linial M, Scheller RH (Mar 1993). "Brain contains two forms of synaptic vesicle protein 2". Proceedings of the National Academy of Sciences of the United States of America. 90 (6): 2150–4. Bibcode:1993PNAS...90.2150B. doi:10.1073/pnas.90.6.2150. PMC 46043. PMID 7681585.
6. Crowder KM, Gunther JM, Jones TA, Hale BD, Zhang HZ, Peterson MR, Scheller RH, Chavkin C, Bajjalieh SM (Dec 1999). "Abnormal neurotransmission in mice lacking synaptic vesicle protein 2A (SV2A)". Proceedings of the National Academy of Sciences of the United States of America. 96 (26): 15268–73. Bibcode:1999PNAS...9615268C. doi:10.1073/pnas.96.26.15268. PMC 24809. PMID 10611374.
7. "Entrez Gene: SV2A synaptic vesicle glycoprotein 2A".
8. Rossi, Rachele; Arjmand, Shokouh; Bærentzen, Simone Larsen; Gjedde, Albert; Landau, Anne M. (2022-04-28). "Synaptic Vesicle Glycoprotein 2A: Features and Functions". Frontiers in Neuroscience. 16: 864514. doi:10.3389/fnins.2022.864514. ISSN 1662-4548. PMC 9096842. PMID 35573314.
9. Ulloa CM, Towfigh A, Safdieh J (2009). "Review of levetiracetam, with a focus on the extended release formulation, as adjuvant therapy in controlling partial-onset seizures". Neuropsychiatric Disease and Treatment. 5: 467–76. doi:10.2147/ndt.s4844. PMC 2747386. PMID 19777068.
10. Contreras-García, Itzel Jatziri; Cárdenas-Rodríguez, Noemí; Romo-Mancillas, Antonio; Bandala, Cindy; Zamudio, Sergio R.; Gómez-Manzo, Saúl; Hernández-Ochoa, Beatriz; Mendoza-Torreblanca, Julieta Griselda; Pichardo-Macías, Luz Adriana (2022-04-13). "Levetiracetam Mechanisms of Action: From Molecules to Systems". Pharmaceuticals. 15 (4): 475. doi:10.3390/ph15040475. ISSN 1424-8247. PMC 9030752. PMID 35455472.
11. Mendoza-Torreblanca, Julieta G.; García-Cruz, M. Edna; Sánchez-Cruz, Itzel; Gomez-Gonzalez, Beatriz; Juárez-Méndez, Sergio; Gómez-Lira, Gisela (November 2019). "Analysis of Differential Expression of Synaptic Vesicle Protein 2A in the Adult Rat Brain". Neuroscience. 419: 108–120. doi:10.1016/j.neuroscience.2019.09.004. PMID 31520710.
12. Wong, Theresa; Qiu, Zhen; Notman, Beverly; Tavares, Adriana; Smith, Colin; Grant, Seth G. N. (2024-07-18), SV2A is expressed in synapse subpopulations in mouse and human brain: implications for PET radiotracer studies, doi:10.1101/2024.07.15.603608, retrieved 2024-10-02
13. Bajjalieh, S. M.; Frantz, G. D.; Weimann, J. M.; McConnell, S. K.; Scheller, R. H. (1994-09-01). "Differential expression of synaptic vesicle protein 2 (SV2) isoforms". Journal of Neuroscience. 14 (9): 5223–5235. doi:10.1523/JNEUROSCI.14-09-05223.1994. ISSN 0270-6474. PMC 6577109. PMID 8083732.
14. Mendoza-Torreblanca, Julieta G.; García-Cruz, M. Edna; Sánchez-Cruz, Itzel; Gomez-Gonzalez, Beatriz; Juárez-Méndez, Sergio; Gómez-Lira, Gisela (November 2019). "Analysis of Differential Expression of Synaptic Vesicle Protein 2A in the Adult Rat Brain". Neuroscience. 419: 108–120. doi:10.1016/j.neuroscience.2019.09.004. PMID 31520710.
15. Vanoye-Carlo, América; Gómez-Lira, Gisela (July 2019). "Differential expression of SV2A in hippocampal glutamatergic and GABAergic terminals during postnatal development". Brain Research. 1715: 73–83. doi:10.1016/j.brainres.2019.03.021. PMID 30905653.
16. Onwordi, Ellis Chika; Halff, Els F.; Whitehurst, Thomas; Mansur, Ayla; Cotel, Marie-Caroline; Wells, Lisa; Creeney, Hannah; Bonsall, David; Rogdaki, Maria; Shatalina, Ekaterina; Reis Marques, Tiago; Rabiner, Eugenii A.; Gunn, Roger N.; Natesan, Sridhar; Vernon, Anthony C. (2020-01-14). "Synaptic density marker SV2A is reduced in schizophrenia patients and unaffected by antipsychotics in rats". Nature Communications. 11 (1): 246. Bibcode:2020NatCo..11..246O. doi:10.1038/s41467-019-14122-0. ISSN 2041-1723. PMC 6959348. PMID 31937764.
17. Radhakrishnan, Rajiv; Skosnik, Patrick D.; Ranganathan, Mohini; Naganawa, Mika; Toyonaga, Takuya; Finnema, Sjoerd; Hillmer, Ansel T.; Esterlis, Irina; Huang, Yiyun; Nabulsi, Nabeel; Carson, Richard E.; D’Souza, Deepak C. (December 2021). "In vivo evidence of lower synaptic vesicle density in schizophrenia". Molecular Psychiatry. 26 (12): 7690–7698. doi:10.1038/s41380-021-01184-0. ISSN 1359-4184. PMID 34135473.
18. Yoon, Jong H.; Zhang, Zhener; Mormino, Elizabeth; Davidzon, Guido; Minzenberg, Michael J.; Ballon, Jacob; Kalinowski, Agnieszka; Hardy, Kate; Naganawa, Mika; Carson, Richard E.; Khalighi, Mehdi; Park, Jun Hyung; Levinson, Douglas F.; Chin, Frederick T. (May 2023). "Reductions in synaptic marker SV2A in early-course Schizophrenia". Journal of Psychiatric Research. 161: 213–217. doi:10.1016/j.jpsychires.2023.02.026. PMID 36934603.
19. Holmes, Sophie E.; Abdallah, Chadi; Esterlis, Irina (January 2023). "Imaging synaptic density in depression". Neuropsychopharmacology. 48 (1): 186–190. doi:10.1038/s41386-022-01368-4. ISSN 0893-133X. PMC 9700860. PMID 35768568.

Further reading

• Bajjalieh SM, Peterson K, Shinghal R, Scheller RH (Aug 1992). "SV2, a brain synaptic vesicle protein homologous to bacterial transporters". Science. 257 (5074): 1271–3. Bibcode:1992Sci...257.1271B. doi:10.1126/science.1519064. PMID 1519064.
• Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Oct 1998). "Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 5 (5): 277–86. doi:10.1093/dnares/5.5.277. PMID 9872452.
• Son YJ, Scranton TW, Sunderland WJ, Baek SJ, Miner JH, Sanes JR, Carlson SS (Jan 2000). "The synaptic vesicle protein SV2 is complexed with an alpha5-containing laminin on the nerve terminal surface". The Journal of Biological Chemistry. 275 (1): 451–60. doi:10.1074/jbc.275.1.451. PMID 10617638.
• Hartley JL, Temple GF, Brasch MA (Nov 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A (Mar 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
• Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (Sep 2000). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
• Lynch BA, Lambeng N, Nocka K, Kensel-Hammes P, Bajjalieh SM, Matagne A, Fuks B (Jun 2004). "The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam". Proceedings of the National Academy of Sciences of the United States of America. 101 (26): 9861–6. Bibcode:2004PNAS..101.9861L. doi:10.1073/pnas.0308208101. PMC 470764. PMID 15210974.
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A (Oct 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
• DeGiorgis JA, Jaffe H, Moreira JE, Carlotti CG, Leite JP, Pant HC, Dosemeci A (2005). "Phosphoproteomic analysis of synaptosomes from human cerebral cortex". Journal of Proteome Research. 4 (2): 306–15. doi:10.1021/pr0498436. PMID 15822905.
• Otsuki T, Ota T, Nishikawa T, Hayashi K, Suzuki Y, Yamamoto J, Wakamatsu A, Kimura K, Sakamoto K, Hatano N, Kawai Y, Ishii S, Saito K, Kojima S, Sugiyama T, Ono T, Okano K, Yoshikawa Y, Aotsuka S, Sasaki N, Hattori A, Okumura K, Nagai K, Sugano S, Isogai T (2007). "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries". DNA Research. 12 (2): 117–26. doi:10.1093/dnares/12.2.117. PMID 16303743.
• Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S (Jan 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.

External links

• Overview of all the structural information available in the PDB for UniProt: Q7L0J3 (Synaptic vesicle glycoprotein 2A) at the PDBe-KB.