SV2A

SV2A
Identifiers
Aliases	SV2A, SV2, synaptic vesicle glycoprotein 2A
External IDs	OMIM: 185860; MGI: 1927139; GeneCards: SV2A
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	4V11
Gene location (Human)
Chr.	Chromosome 1 (human)
End	149,917,844 bp
Gene location (Mouse)
Chr.	Chromosome 3 (mouse)
End	96,102,837 bp
RNA expression pattern
	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
	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
Databases	NCBI: entry; OMA: entry
	9900
	64051
	ENSG00000159164
	ENSMUSG00000038486
	Q7L0J3
	Q9JIS5
	NM_014849; NM_001278719; NM_001328674; NM_001328675
	NM_022030
	NP_001265648; NP_001315603; NP_001315604; NP_055664
	NP_071313
	Wikidata
View/Edit Human	View/Edit Mouse

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 is encoded by the SV2A gene.

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

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

Localisation

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

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. A 2024 systematic review and meta-analysis of [11C]UCB-J PET studies reported lower SV2A binding in individuals with psychotic disorders compared with healthy controls.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000159164 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000038486 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Bajjalieh SM, Peterson K, Linial M, Scheller RH (March 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): 2150–2154. Bibcode:1993PNAS...90.2150B. doi:10.1073/pnas.90.6.2150. PMC 46043. PMID 7681585.
↑ Crowder KM, Gunther JM, Jones TA, Hale BD, Zhang HZ, Peterson MR, et al. (December 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): 15268–15273. Bibcode:1999PNAS...9615268C. doi:10.1073/pnas.96.26.15268. PMC 24809. PMID 10611374.
↑ "Entrez Gene: SV2A synaptic vesicle glycoprotein 2A".
1 2 Rossi R, Arjmand S, Bærentzen SL, Gjedde A, Landau AM (2022). "Synaptic Vesicle Glycoprotein 2A: Features and Functions". Frontiers in Neuroscience. 16 864514. doi:10.3389/fnins.2022.864514. PMC 9096842. PMID 35573314.
↑ 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: 467–476. doi:10.2147/ndt.s4844. PMC 2747386. PMID 19777068.
↑ Contreras-García IJ, Cárdenas-Rodríguez N, Romo-Mancillas A, Bandala C, Zamudio SR, Gómez-Manzo S, et al. (April 2022). "Levetiracetam Mechanisms of Action: From Molecules to Systems". Pharmaceuticals. 15 (4). Basel, Switzerland: 475. doi:10.3390/ph15040475. PMC 9030752. PMID 35455472.
1 2 Mendoza-Torreblanca JG, García-Cruz ME, Sánchez-Cruz I, Gomez-Gonzalez B, Juárez-Méndez S, Gómez-Lira G (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.
↑ Wong T, Qiu Z, Notman B, Tavares A, Smith C, Grant SG (2025). "SV2A is expressed in synapse subpopulations in mouse and human brain: implications for PET radiotracer studies". Wellcome Open Research. 10: 415. bioRxiv 10.1101/2024.07.15.603608. doi:10.12688/wellcomeopenres.24668.1. PMC 12603525. PMID 41229902.
↑ Bajjalieh SM, Frantz GD, Weimann JM, McConnell SK, Scheller RH (September 1994). "Differential expression of synaptic vesicle protein 2 (SV2) isoforms". The Journal of Neuroscience. 14 (9): 5223–5235. doi:10.1523/JNEUROSCI.14-09-05223.1994. PMC 6577109. PMID 8083732.
↑ Vanoye-Carlo A, Gómez-Lira G (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.
↑ Onwordi EC, Halff EF, Whitehurst T, Mansur A, Cotel MC, Wells L, et al. (January 2020). "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. PMC 6959348. PMID 31937764.
↑ Radhakrishnan R, Skosnik PD, Ranganathan M, Naganawa M, Toyonaga T, Finnema S, et al. (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. PMID 34135473.
↑ Yoon JH, Zhang Z, Mormino E, Davidzon G, Minzenberg MJ, Ballon J, et al. (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.
↑ Holmes SE, Abdallah C, Esterlis I (January 2023). "Imaging synaptic density in depression". Neuropsychopharmacology. 48 (1): 186–190. doi:10.1038/s41386-022-01368-4. PMC 9700860. PMID 35768568.
↑ Husain MO, Jones B, Arshad U, Ameis SH, Mirfallah G, Schifani C, et al. (June 2024). "A systematic review and meta-analysis of neuroimaging studies examining synaptic density in individuals with psychotic spectrum disorders". BMC Psychiatry. 24 (1) 460. doi:10.1186/s12888-024-05788-y. PMC 11188231. PMID 38898401.

External links

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

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000159164 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 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.

[Bajjalieh_1993-5] Bajjalieh SM, Peterson K, Linial M, Scheller RH (March 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): 2150–2154. Bibcode:1993PNAS...90.2150B. doi:10.1073/pnas.90.6.2150. PMC 46043. PMID 7681585.

[Crowder_1999-6] Crowder KM, Gunther JM, Jones TA, Hale BD, Zhang HZ, Peterson MR, et al. (December 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): 15268–15273. Bibcode:1999PNAS...9615268C. doi:10.1073/pnas.96.26.15268. PMC 24809. PMID 10611374.

[entrez-7] "Entrez Gene: SV2A synaptic vesicle glycoprotein 2A".

[Rossi_2022-8] 1 2 Rossi R, Arjmand S, Bærentzen SL, Gjedde A, Landau AM (2022). "Synaptic Vesicle Glycoprotein 2A: Features and Functions". Frontiers in Neuroscience. 16 864514. doi:10.3389/fnins.2022.864514. PMC 9096842. PMID 35573314.

[Ulloa_2009-9] 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: 467–476. doi:10.2147/ndt.s4844. PMC 2747386. PMID 19777068.

[10] Contreras-García IJ, Cárdenas-Rodríguez N, Romo-Mancillas A, Bandala C, Zamudio SR, Gómez-Manzo S, et al. (April 2022). "Levetiracetam Mechanisms of Action: From Molecules to Systems". Pharmaceuticals. 15 (4). Basel, Switzerland: 475. doi:10.3390/ph15040475. PMC 9030752. PMID 35455472.

[linkinghub.elsevier.com-11] 1 2 Mendoza-Torreblanca JG, García-Cruz ME, Sánchez-Cruz I, Gomez-Gonzalez B, Juárez-Méndez S, Gómez-Lira G (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 T, Qiu Z, Notman B, Tavares A, Smith C, Grant SG (2025). "SV2A is expressed in synapse subpopulations in mouse and human brain: implications for PET radiotracer studies". Wellcome Open Research. 10: 415. bioRxiv 10.1101/2024.07.15.603608. doi:10.12688/wellcomeopenres.24668.1. PMC 12603525. PMID 41229902.

[13] Bajjalieh SM, Frantz GD, Weimann JM, McConnell SK, Scheller RH (September 1994). "Differential expression of synaptic vesicle protein 2 (SV2) isoforms". The Journal of Neuroscience. 14 (9): 5223–5235. doi:10.1523/JNEUROSCI.14-09-05223.1994. PMC 6577109. PMID 8083732.

[14] Vanoye-Carlo A, Gómez-Lira G (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.

[15] Onwordi EC, Halff EF, Whitehurst T, Mansur A, Cotel MC, Wells L, et al. (January 2020). "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. PMC 6959348. PMID 31937764.

[16] Radhakrishnan R, Skosnik PD, Ranganathan M, Naganawa M, Toyonaga T, Finnema S, et al. (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. PMID 34135473.

[17] Yoon JH, Zhang Z, Mormino E, Davidzon G, Minzenberg MJ, Ballon J, et al. (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.

[18] Holmes SE, Abdallah C, Esterlis I (January 2023). "Imaging synaptic density in depression". Neuropsychopharmacology. 48 (1): 186–190. doi:10.1038/s41386-022-01368-4. PMC 9700860. PMID 35768568.

[19] Husain MO, Jones B, Arshad U, Ameis SH, Mirfallah G, Schifani C, et al. (June 2024). "A systematic review and meta-analysis of neuroimaging studies examining synaptic density in individuals with psychotic spectrum disorders". BMC Psychiatry. 24 (1) 460. doi:10.1186/s12888-024-05788-y. PMC 11188231. PMID 38898401.

SV2A

Localisation

SV2A PET

See also

References

Further reading

External links