SOX3

Transcription factor SOX-3 is a protein that in humans is encoded by the SOX3 gene.[5][6][5] This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic brain development and in determination of cell fate. The encoded protein acts as a transcriptional activator.[7]

SOX3
Identifiers
Aliases	SOX3, GHDX, MRGH, PHP, PHPX, SOXB, SRY-box 3, SRY-box transcription factor 3
External IDs	OMIM: 313430 MGI: 98365 HomoloGene: 4118 GeneCards: SOX3
Gene location (Human) Chr. X chromosome (human)[1] Band Xq27.1 Start 140,502,985 bp[1] End 140,505,116 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X A6|X 33.66 cM Start 60,891,366 bp[2] End 60,893,430 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • DNA binding • GO:0001106 transcription corepressor activity • RNA polymerase II core promoter sequence-specific DNA binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component • cell nucleus • nucleoplasm Biological process • multicellular organism development • sensory organ development • central nervous system development • face development • pituitary gland development • regulation of transcription, DNA-templated • negative regulation of neuron differentiation • transcription, DNA-templated • hypothalamus development • negative regulation of transcription from RNA polymerase II promoter • sex determination • negative regulation of nucleic acid-templated transcription • regulation of transcription from RNA polymerase II promoter • cell differentiation • neuron differentiation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	6658	20675
Ensembl	ENSG00000134595	ENSMUSG00000045179
UniProt	P41225	P53784
RefSeq (mRNA)	NM_005634	NM_009237
RefSeq (protein)	NP_005625	n/a
Location (UCSC)	Chr X: 140.5 – 140.51 Mb	Chr X: 60.89 – 60.89 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Mutations in this gene have been associated with X-linked hypopituitarism (XH) and X-linked mental retardation. Patients with XH are male, have short stature, exhibit a mild form of mental retardation and present pan-hypopituitarism.[6][8] A duplication of the SOX3 gene has also been discovered to cause XX male sex reversal.[9]

SRY-box transcription factor 3, SOX3, is a transcription factor that is encoded by the SOX3 gene. This gene is responsible for ensuring proper embryonic development and determining the fate of different cells. Regarding its developmental facet, SOX3, alongside other SOX transcription factors, ensures the proper formation of the hypothalamo-pituitary axis.[10] The proper development of the hypothalamo-pituitary axis is necessary as it serves to ensure proper systemic hormonal function. When SOX3 expression is affected, the development of different structures can be affected as well. Specifically, both the hypothalamus and the pituitary gland can suffer in accomplishing proper growth. Due to this, conditions such as hypopituitarism and mental retardation are found in cases with a lack of SOX3. Also, craniofacial abnormalities can be seen as a result of a lack of the SOX3 gene. To aid in the further understanding of the SOX3 gene, mice have been used as knockout models to study the effects of the gene’s absence.[11]

Function

SOX3 belongs to the family of SRY-related HMG-box containing genes which behave as transcription factors. SOX3 has been found to be involved in the regulation of embryonic brain development, the determination of cell fate and in XX male sex reversal.[7]

SOX3 contains a single exon and is found in a highly conserved region of the X chromosome. The SOX3 gene shares some conservation with the SRY gene, and encodes a protein that is similar, sharing 67% amino acid identity across the DNA-binding HMG domain.[12] This has led to the hypothesis that the SRY gene arose from SOX3 through a gain of function mutation within the proto-Y chromosome. Evidence to support this hypothesis arose from the discovery of a rare human case of XX sex reversal, that is thought to have occurred through a de novo duplication of the SOX3 gene.[13] Such a duplication is thought to result in a gain of function expression of SOX3 in the genital ridge of the developing embryo leading to XX male sex reversal.

See also

• SOX gene family

References

1. GRCh38: Ensembl release 89: ENSG00000134595 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000045179 - 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. Woods KS, Cundall M, Turton J, Rizotti K, Mehta A, Palmer R, Wong J, Chong WK, Al-Zyoud M, El-Ali M, Otonkoski T, Martinez-Barbera JP, Thomas PQ, Robinson IC, Lovell-Badge R, Woodward KJ, Dattani MT (May 2005). "Over- and underdosage of SOX3 is associated with infundibular hypoplasia and hypopituitarism". American Journal of Human Genetics. 76 (5): 833–49. doi:10.1086/430134. PMC 1199372. PMID 15800844.
6. "Entrez Gene: SOX3 SRY (sex determining region Y)-box 3".
7. Bylund M, Andersson E, Novitch BG, Muhr J (November 2003). "Vertebrate neurogenesis is counteracted by Sox1-3 activity". Nature Neuroscience. 6 (11): 1162–8. doi:10.1038/nn1131. PMID 14517545.
8. Barber, TM, Cheetham T, Ball SG (2004). "X-linked hypopituitarism: clinical and biochemical features of a rare cause of short stature". Endocrine Abstracts. 7 (1): 248.
9. Moalem S, Babul-Hirji R, Stavropolous DJ, Wherrett D, Bägli DJ, Thomas P, Chitayat D (July 2012). "XX male sex reversal with genital abnormalities associated with a de novo SOX3 gene duplication". American Journal of Medical Genetics. Part A. 158A (7): 1759–64. doi:10.1002/ajmg.a.35390. PMID 22678921.
10. “SOX3 SRY-Box Transcription Factor 3 [Homo Sapiens (Human)] - Gene - NCBI.” National Center for Biotechnology Information, U.S. National Library of Medicine, www.ncbi.nlm.nih.gov/gene/6658.
11. Rizzoti, K., et al. “SOX3 Is Required during the Formation of the Hypothalamo-Pituitary Axis.” NATURE GENETICS, no. 3, 2004, p. 247. EBSCOhost, search.ebscohost.com/login.aspx?direct=true&db=edsbl&AN=RN146168291&site=eds-live.
12. Foster, JW; Graves, JA (1 March 1994). "An SRY-related sequence on the marsupial X chromosome: implications for the evolution of the mammalian testis-determining gene". Proceedings of the National Academy of Sciences of the United States of America. 91 (5): 1927–31. doi:10.1073/pnas.91.5.1927. PMC 43277. PMID 8127908.
13. Moalem S, Babul-Hirji R, Stavropolous DJ, Wherrett D, Bägli DJ, Thomas P, Chitayat D (July 2012). "XX male sex reversal with genital abnormalities associated with a de novo SOX3 gene duplication". American Journal of Medical Genetics. Part A. 158A (7): 1759–64. doi:10.1002/ajmg.a.35390. PMID 22678921.

Further reading

• Kamachi Y, Uchikawa M, Kondoh H (April 2000). "Pairing SOX off: with partners in the regulation of embryonic development". Trends in Genetics. 16 (4): 182–7. doi:10.1016/S0168-9525(99)01955-1. PMID 10729834.
• Bowles J, Schepers G, Koopman P (November 2000). "Phylogeny of the SOX family of developmental transcription factors based on sequence and structural indicators". Developmental Biology. 227 (2): 239–55. doi:10.1006/dbio.2000.9883. PMID 11071752.
• Schepers GE, Teasdale RD, Koopman P (August 2002). "Twenty pairs of sox: extent, homology, and nomenclature of the mouse and human sox transcription factor gene families". Developmental Cell. 3 (2): 167–70. doi:10.1016/S1534-5807(02)00223-X. PMID 12194848.
• Denny P, Swift S, Brand N, Dabhade N, Barton P, Ashworth A (June 1992). "A conserved family of genes related to the testis determining gene, SRY". Nucleic Acids Research. 20 (11): 2887. doi:10.1093/nar/20.11.2887. PMC 336939. PMID 1614875.
• Stevanović M, Lovell-Badge R, Collignon J, Goodfellow PN (December 1993). "SOX3 is an X-linked gene related to SRY". Human Molecular Genetics. 2 (12): 2013–8. doi:10.1093/hmg/2.12.2013. PMID 8111369.
• Collignon J, Sockanathan S, Hacker A, Cohen-Tannoudji M, Norris D, Rastan S, Stevanovic M, Goodfellow PN, Lovell-Badge R (February 1996). "A comparison of the properties of Sox-3 with Sry and two related genes, Sox-1 and Sox-2". Development. 122 (2): 509–20. PMID 8625802.
• Laumonnier F, Ronce N, Hamel BC, Thomas P, Lespinasse J, Raynaud M, Paringaux C, Van Bokhoven H, Kalscheuer V, Fryns JP, Chelly J, Moraine C, Briault S (December 2002). "Transcription factor SOX3 is involved in X-linked mental retardation with growth hormone deficiency". American Journal of Human Genetics. 71 (6): 1450–5. doi:10.1086/344661. PMC 420004. PMID 12428212.
• Aota S, Nakajima N, Sakamoto R, Watanabe S, Ibaraki N, Okazaki K (May 2003). "Pax6 autoregulation mediated by direct interaction of Pax6 protein with the head surface ectoderm-specific enhancer of the mouse Pax6 gene". Developmental Biology. 257 (1): 1–13. doi:10.1016/S0012-1606(03)00058-7. PMID 12710953.
• Weiss J, Meeks JJ, Hurley L, Raverot G, Frassetto A, Jameson JL (November 2003). "Sox3 is required for gonadal function, but not sex determination, in males and females". Molecular and Cellular Biology. 23 (22): 8084–91. doi:10.1128/MCB.23.22.8084-8091.2003. PMC 262333. PMID 14585968.
• Dattani MT (December 2003). "Borjeson-Forssman-Lehmann syndrome: a novel pituitary phenotype due to mutation in a novel gene". Journal of Pediatric Endocrinology & Metabolism. 16 (9): 1207–9. doi:10.1515/jpem.2003.16.9.1207. PMID 14714741.
• Raverot G, Lejeune H, Kotlar T, Pugeat M, Jameson JL (August 2004). "X-linked sex-determining region Y box 3 (SOX3) gene mutations are uncommon in men with idiopathic oligoazoospermic infertility". The Journal of Clinical Endocrinology and Metabolism. 89 (8): 4146–8. doi:10.1210/jc.2004-0191. PMID 15292361.
• Solomon NM, Ross SA, Morgan T, Belsky JL, Hol FA, Karnes PS, Hopwood NJ, Myers SE, Tan AS, Warne GL, Forrest SM, Thomas PQ (September 2004). "Array comparative genomic hybridisation analysis of boys with X linked hypopituitarism identifies a 3.9 Mb duplicated critical region at Xq27 containing SOX3". Journal of Medical Genetics. 41 (9): 669–78. doi:10.1136/jmg.2003.016949. PMC 1735898. PMID 15342697.
• Savare J, Bonneaud N, Girard F (June 2005). "SUMO represses transcriptional activity of the Drosophila SoxNeuro and human Sox3 central nervous system-specific transcription factors". Molecular Biology of the Cell. 16 (6): 2660–9. doi:10.1091/mbc.E04-12-1062. PMC 1142414. PMID 15788563.

External links

• SOX3+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.