Homeobox protein SIX1 explained

Homeobox protein SIX1 (Sine oculis homeobox homolog 1) is a protein that in humans is encoded by the SIX1 gene.^{[1] [2] [3]}

Function

The vertebrate SIX genes are homologs of the Drosophila 'sine oculis' (so) gene, which is expressed primarily in the developing visual system of the fly. Members of the SIX gene family encode proteins that are characterized by a divergent DNA-binding homeodomain and an upstream SIX domain, which may be involved both in determining DNA-binding specificity and in mediating protein–protein interactions. Genes in the SIX family have been shown to play roles in vertebrate and insect development or have been implicated in maintenance of the differentiated state of tissues.[supplied by OMIM]

Interactions

SIX1 has been shown to interact with EYA1,^[4] DACH, GRO and MDFI.^[5]

Further reading

• Oliver G, Wehr R, Jenkins NA, Copeland NG, Cheyette BN, Hartenstein V, Zipursky SL, Gruss P . Homeobox genes and connective tissue patterning . Development . 121 . 3 . 693–705 . March 1995 . 10.1242/dev.121.3.693 . 7720577 . 11858/00-001M-0000-0013-037D-E . free .
• Adrados I, Larrasa-Alonso J, Galarreta A, López-Antona I, Menéndez C, Abad M, Palmero I . 2015 . The homeoprotein SIX1 controls cellular senescence through the regulation of p16INK4A and differentiation-related genes . Oncogene . 35. 27. 3485–3494. 10.1038/onc.2015.408 . 26500063 . 5730042 .
• Ford HL, Kabingu EN, Bump EA, Mutter GL, Pardee AB . Abrogation of the G2 cell cycle checkpoint associated with overexpression of HSIX1: a possible mechanism of breast carcinogenesis . Proceedings of the National Academy of Sciences of the United States of America . 95 . 21 . 12608–13 . October 1998 . 9770533 . 22878 . 10.1073/pnas.95.21.12608 . 1998PNAS...9512608F . free .
• Salam AA, Häfner FM, Linder TE, Spillmann T, Schinzel AA, Leal SM . A novel locus (DFNA23) for prelingual autosomal dominant nonsyndromic hearing loss maps to 14q21-q22 in a Swiss German kindred . American Journal of Human Genetics . 66 . 6 . 1984–8 . June 2000 . 10777717 . 1378045 . 10.1086/302931 .
• Ford HL, Landesman-Bollag E, Dacwag CS, Stukenberg PT, Pardee AB, Seldin DC . Cell cycle-regulated phosphorylation of the human SIX1 homeodomain protein . The Journal of Biological Chemistry . 275 . 29 . 22245–54 . July 2000 . 10801845 . 10.1074/jbc.M002446200 . free .
• Fan X, Brass LF, Poncz M, Spitz F, Maire P, Manning DR . The alpha subunits of Gz and Gi interact with the eyes absent transcription cofactor Eya2, preventing its interaction with the six class of homeodomain-containing proteins . The Journal of Biological Chemistry . 275 . 41 . 32129–34 . October 2000 . 10906137 . 10.1074/jbc.M004577200 . free .
• Buller C, Xu X, Marquis V, Schwanke R, Xu PX . Molecular effects of Eya1 domain mutations causing organ defects in BOR syndrome . Human Molecular Genetics . 10 . 24 . 2775–81 . November 2001 . 11734542 . 10.1093/hmg/10.24.2775 . free .
• Li CM, Guo M, Borczuk A, Powell CA, Wei M, Thaker HM, Friedman R, Klein U, Tycko B . Gene expression in Wilms' tumor mimics the earliest committed stage in the metanephric mesenchymal-epithelial transition . The American Journal of Pathology . 160 . 6 . 2181–90 . June 2002 . 12057921 . 1850829 . 10.1016/S0002-9440(10)61166-2 .
• Ikeda K, Watanabe Y, Ohto H, Kawakami K . Molecular interaction and synergistic activation of a promoter by Six, Eya, and Dach proteins mediated through CREB binding protein . Molecular and Cellular Biology . 22 . 19 . 6759–66 . October 2002 . 12215533 . 134036 . 10.1128/MCB.22.19.6759-6766.2002 .
• López-Ríos J, Tessmar K, Loosli F, Wittbrodt J, Bovolenta P . Six3 and Six6 activity is modulated by members of the groucho family . Development . 130 . 1 . 185–95 . January 2003 . 12441302 . 10.1242/dev.00185 . free .
• Ruf RG, Berkman J, Wolf MT, Nurnberg P, Gattas M, Ruf EM, Hyland V, Kromberg J, Glass I, Macmillan J, Otto E, Nurnberg G, Lucke B, Hennies HC, Hildebrandt F . A gene locus for branchio-otic syndrome maps to chromosome 14q21.3-q24.3 . Journal of Medical Genetics . 40 . 7 . 515–9 . July 2003 . 12843324 . 1735534 . 10.1136/jmg.40.7.515 .
• Zheng W, Huang L, Wei ZB, Silvius D, Tang B, Xu PX . The role of Six1 in mammalian auditory system development . Development . 130 . 17 . 3989–4000 . September 2003 . 12874121 . 10.1242/dev.00628 . 3873880 .
• Li X, Oghi KA, Zhang J, Krones A, Bush KT, Glass CK, Nigam SK, Aggarwal AK, Maas R, Rose DW, Rosenfeld MG . Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis . Nature . 426 . 6964 . 247–54 . November 2003 . 14628042 . 10.1038/nature02083 . 2003Natur.426..247L . 4348941 .
• Coletta RD, Christensen K, Reichenberger KJ, Lamb J, Micomonaco D, Huang L, Wolf DM, Müller-Tidow C, Golub TR, Kawakami K, Ford HL . The Six1 homeoprotein stimulates tumorigenesis by reactivation of cyclin A1 . Proceedings of the National Academy of Sciences of the United States of America . 101 . 17 . 6478–83 . April 2004 . 15123840 . 404070 . 10.1073/pnas.0401139101 . 2004PNAS..101.6478C . free .
• Grifone R, Laclef C, Spitz F, Lopez S, Demignon J, Guidotti JE, Kawakami K, Xu PX, Kelly R, Petrof BJ, Daegelen D, Concordet JP, Maire P . Six1 and Eya1 expression can reprogram adult muscle from the slow-twitch phenotype into the fast-twitch phenotype . Molecular and Cellular Biology . 24 . 14 . 6253–67 . July 2004 . 15226428 . 434262 . 10.1128/MCB.24.14.6253-6267.2004 .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein–protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Ito T, Noguchi Y, Yashima T, Kitamura K . SIX1 mutation associated with enlargement of the vestibular aqueduct in a patient with branchio-oto syndrome . The Laryngoscope . 116 . 5 . 796–9 . May 2006 . 16652090 . 10.1097/01.mlg.0000209096.40400.96 . 19273457 .

Notes and References

1. Boucher CA, Carey N, Edwards YH, Siciliano MJ, Johnson KJ . Cloning of the human SIX1 gene and its assignment to chromosome 14 . Genomics . 33 . 1 . 140–2 . April 1996 . 8617500 . 10.1006/geno.1996.0172 .
2. Ruf RG, Xu PX, Silvius D, Otto EA, Beekmann F, Muerb UT, Kumar S, Neuhaus TJ, Kemper MJ, Raymond RM, Brophy PD, Berkman J, Gattas M, Hyland V, Ruf EM, Schwartz C, Chang EH, Smith RJ, Stratakis CA, Weil D, Petit C, Hildebrandt F . SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes . Proceedings of the National Academy of Sciences of the United States of America . 101 . 21 . 8090–5 . May 2004 . 15141091 . 419562 . 10.1073/pnas.0308475101 . 2004PNAS..101.8090R . free .
3. Web site: Entrez Gene: SIX1 sine oculis homeobox homolog 1 (Drosophila).
4. Buller C, Xu X, Marquis V, Schwanke R, Xu PX . Molecular effects of Eya1 domain mutations causing organ defects in BOR syndrome . Human Molecular Genetics . 10 . 24 . 2775–81 . November 2001 . 11734542 . 10.1093/hmg/10.24.2775 . free .
5. Huda Zoghbi . Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein–protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .