Biology:SRPX2
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Sushi repeat-containing protein SRPX2 is a protein that in humans is encoded by the SRPX2 gene, on the X chromosome.[1][2] It has roles in glutamatergic synapse formation in the cerebral cortex and is more highly expressed in childhood.[3] Bioinformatics analysis suggests the SRPX2 protein is a peroxiredoxin.[4]
Function
SRPX2 is distributed on synapses throughout the cerebral cortex and hippocampus, largely in the same areas as vesicular glutamate transporter 1 and DLG4. It is involved in synapse formation and is more highly expressed in childhood. Overexpression of SRPX2 results in increased density of vesicular glutamate transporter 1 and DLG4 clusters on cortical neurons. Deficiency results in decreased dendritic spine density of excitatory glutamatergic synapses, while inhibitory GABAergic synapses are unaffected. Length or shape of spines is not affected by SPRX2, however.[3]
Clinical significance
Mutations in SRPX2 were linked in one 2006 study to a family with a form of Rolandic epilepsy with intellectual disability and speech dyspraxia, however later studies showed that mutations in SRPX2 do not necessarily lead to epilepsy or intellectual disability. Additionally, no mutations in SRPX2 have been reported with Rolandic epilepsy since.[5] In mice, mutations in SRPX2 lead to decreased frequency of ultrasonic vocalisations in pups when separated from mothers.[3]
Interactions
FOXP2 directly reduces SRPX2 expression, by binding to its promoter. However, FOXP2 also reduces dendritic length, which SRPX2 does not affect, indicating it has other regulatory roles in dendritic morphology.[3]
References
- ↑ "Two candidate downstream target genes for E2A-HLF". Blood 93 (1): 321–32. January 1999. doi:10.1182/blood.V93.1.321. PMID 9864177.
- ↑ "Entrez Gene: SRPX2 sushi-repeat-containing protein, X-linked 2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27286.
- ↑ 3.0 3.1 3.2 3.3 "The human language-associated gene SRPX2 regulates synapse formation and vocalization in mice". Science 342 (6161): 987–91. November 2013. doi:10.1126/science.1245079. PMID 24179158. Bibcode: 2013Sci...342..987S.
- ↑ "A widespread peroxiredoxin-like domain present in tumor suppression- and progression-implicated proteins". BMC Genomics 11: 590. 2010. doi:10.1186/1471-2164-11-590. PMID 20964819.
- ↑ "OMIM Entry - # 300643 - ROLANDIC EPILEPSY, MENTAL RETARDATION, AND SPEECH DYSPRAXIA, X-LINKED; RESDX". https://omim.org/entry/300643?search=srpx2&highlight=srpx2.
Further reading
- "Diverse transcriptional initiation revealed by fine, large-scale mapping of mRNA start sites". EMBO Reports 2 (5): 388–93. May 2001. doi:10.1093/embo-reports/kve085. PMID 11375929.
- "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions". Genome Research 14 (9): 1711–8. September 2004. doi:10.1101/gr.2435604. PMID 15342556.
- "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. 2007. doi:10.1093/dnares/12.2.117. PMID 16303743.
- "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research 16 (1): 55–65. January 2006. doi:10.1101/gr.4039406. PMID 16344560.
- "SRPX2 mutations in disorders of language cortex and cognition". Human Molecular Genetics 15 (7): 1195–207. April 2006. doi:10.1093/hmg/ddl035. PMID 16497722.
- "Molecular evolution of the human SRPX2 gene that causes brain disorders of the Rolandic and Sylvian speech areas". BMC Genetics 8: 72. 2008. doi:10.1186/1471-2156-8-72. PMID 17942002.
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