Homeobox protein SIX1

SIX1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4EGC
Identifiers
Aliases	SIX1 , BOS3, DFNA23, TIP39, SIX homeobox 1
External IDs	OMIM: 601205 MGI: 102780 HomoloGene: 4360 GeneCards: SIX1
Gene location (Human) Chr. Chromosome 14 (human) [1] Band 14q23.1 Start 60,643,421 bp [1] End 60,658,259 bp [1]
Gene location (Mouse) Chr. Chromosome 12 (mouse) [2] Band 12 C3|12 30.34 cM Start 73,086,789 bp [2] End 73,100,661 bp [2]
RNA expression pattern Bgee Top expressed in parotid gland bronchial epithelial cell vastus lateralis muscle body of tongue triceps brachii muscle palpebral conjunctiva gastrocnemius muscle deltoid muscle Achilles tendon synovial joint More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding sequence-specific DNA binding GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific chromatin binding GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding GO:0001948 protein binding GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific transcription coactivator binding GO:0000975 transcription cis-regulatory region binding Cellular component cytoplasm transcription regulator complex nucleolus nucleus Biological process pattern specification process negative regulation of neuron apoptotic process regulation of neuron differentiation embryonic skeletal system morphogenesis mesonephric tubule formation neurogenesis animal organ development ureteric bud development myoblast migration positive regulation of branching involved in ureteric bud morphogenesis renal system development regulation of transcription, DNA-templated epithelial cell differentiation olfactory placode formation regulation of skeletal muscle cell differentiation tongue development organ induction kidney development anatomical structure development thymus development ureter smooth muscle cell differentiation neuron fate specification myotome development skeletal system morphogenesis outflow tract morphogenesis trigeminal ganglion development negative regulation of apoptotic process negative regulation of transcription by RNA polymerase II sensory perception of sound aorta morphogenesis regulation of branch elongation involved in ureteric bud branching fungiform papilla morphogenesis transcription, DNA-templated generation of neurons otic vesicle development regulation of protein localization positive regulation of transcription, DNA-templated multicellular organism development branching involved in ureteric bud morphogenesis thyroid gland development inner ear morphogenesis cochlea morphogenesis positive regulation of ureteric bud formation positive regulation of mesenchymal cell proliferation involved in ureter development middle ear morphogenesis regulation of synaptic assembly at neuromuscular junction protein localization to nucleus regulation of gene expression embryonic cranial skeleton morphogenesis inner ear development positive regulation of secondary heart field cardioblast proliferation negative regulation of branching involved in ureteric bud morphogenesis cell population proliferation regulation of epithelial cell proliferation regulation of skeletal muscle satellite cell proliferation skeletal muscle tissue development metanephric mesenchyme development facial nerve morphogenesis positive regulation of transcription by RNA polymerase II pharyngeal system development apoptotic process transcription by RNA polymerase II cellular response to 3,3',5-triiodo-L-thyronine negative regulation of transcription, DNA-templated regulation of skeletal muscle cell proliferation skeletal muscle fiber development Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	6495	20471
Ensembl	ENSG00000126778	ENSMUSG00000051367
UniProt	Q15475	Q62231
RefSeq (mRNA)	NM_005982	NM_009189
RefSeq (protein)	NP_005973	NP_033215
Location (UCSC)	Chr 14: 60.64 – 60.66 Mb	Chr 12: 73.09 – 73.1 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Homeobox protein SIX1 (Sine oculis homeobox homolog 1) is a protein that in humans is encoded by the SIX1 gene. ^{[5] [6] [7]}

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] ^[7]

Interactions

SIX1 has been shown to interact with EYA1, ^[8] DACH, GRO and MDFI. ^[9]

References

1. GRCh38: Ensembl release 89: ENSG00000126778 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000051367 - 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. Boucher CA, Carey N, Edwards YH, Siciliano MJ, Johnson KJ (April 1996). "Cloning of the human SIX1 gene and its assignment to chromosome 14". Genomics. 33 (1): 140–2. doi:10.1006/geno.1996.0172. PMID   8617500.
6. 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 (May 2004). "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. Bibcode:2004PNAS..101.8090R. doi: 10.1073/pnas.0308475101 . PMC   419562 . PMID   15141091.
7. "Entrez Gene: SIX1 sine oculis homeobox homolog 1 (Drosophila)".
8. Buller C, Xu X, Marquis V, Schwanke R, Xu PX (November 2001). "Molecular effects of Eya1 domain mutations causing organ defects in BOR syndrome". Human Molecular Genetics. 10 (24): 2775–81. doi:10.1093/hmg/10.24.2775. PMID   11734542.
9. 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 (October 2005). "Towards a proteome-scale map of the human protein–protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.

Further reading

• Oliver G, Wehr R, Jenkins NA, Copeland NG, Cheyette BN, Hartenstein V, Zipursky SL, Gruss P (March 1995). "Homeobox genes and connective tissue patterning". Development. 121 (3): 693–705. doi:10.1242/dev.121.3.693. PMID   7720577.
• 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. doi:10.1038/onc.2015.408. PMC   5730042 . PMID   26500063.
• Ford HL, Kabingu EN, Bump EA, Mutter GL, Pardee AB (October 1998). "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. Bibcode:1998PNAS...9512608F. doi: 10.1073/pnas.95.21.12608 . PMC   22878 . PMID   9770533.
• Salam AA, Häfner FM, Linder TE, Spillmann T, Schinzel AA, Leal SM (June 2000). "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. doi:10.1086/302931. PMC   1378045 . PMID   10777717.
• Ford HL, Landesman-Bollag E, Dacwag CS, Stukenberg PT, Pardee AB, Seldin DC (July 2000). "Cell cycle-regulated phosphorylation of the human SIX1 homeodomain protein". The Journal of Biological Chemistry. 275 (29): 22245–54. doi: 10.1074/jbc.M002446200 . PMID   10801845.
• Fan X, Brass LF, Poncz M, Spitz F, Maire P, Manning DR (October 2000). "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. doi: 10.1074/jbc.M004577200 . PMID   10906137.
• Buller C, Xu X, Marquis V, Schwanke R, Xu PX (November 2001). "Molecular effects of Eya1 domain mutations causing organ defects in BOR syndrome". Human Molecular Genetics. 10 (24): 2775–81. doi:10.1093/hmg/10.24.2775. PMID   11734542.
• Li CM, Guo M, Borczuk A, Powell CA, Wei M, Thaker HM, Friedman R, Klein U, Tycko B (June 2002). "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. doi:10.1016/S0002-9440(10)61166-2. PMC   1850829 . PMID   12057921.
• Ikeda K, Watanabe Y, Ohto H, Kawakami K (October 2002). "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. doi:10.1128/MCB.22.19.6759-6766.2002. PMC   134036 . PMID   12215533.
• López-Ríos J, Tessmar K, Loosli F, Wittbrodt J, Bovolenta P (January 2003). "Six3 and Six6 activity is modulated by members of the groucho family". Development. 130 (1): 185–95. doi: 10.1242/dev.00185 . PMID   12441302.
• 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 (July 2003). "A gene locus for branchio-otic syndrome maps to chromosome 14q21.3-q24.3". Journal of Medical Genetics. 40 (7): 515–9. doi:10.1136/jmg.40.7.515. PMC   1735534 . PMID   12843324.
• Zheng W, Huang L, Wei ZB, Silvius D, Tang B, Xu PX (September 2003). "The role of Six1 in mammalian auditory system development". Development. 130 (17): 3989–4000. doi:10.1242/dev.00628. PMC   3873880 . PMID   12874121.
• Li X, Oghi KA, Zhang J, Krones A, Bush KT, Glass CK, Nigam SK, Aggarwal AK, Maas R, Rose DW, Rosenfeld MG (November 2003). "Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis". Nature. 426 (6964): 247–54. Bibcode:2003Natur.426..247L. doi:10.1038/nature02083. PMID   14628042. S2CID   4348941.
• Coletta RD, Christensen K, Reichenberger KJ, Lamb J, Micomonaco D, Huang L, Wolf DM, Müller-Tidow C, Golub TR, Kawakami K, Ford HL (April 2004). "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. Bibcode:2004PNAS..101.6478C. doi: 10.1073/pnas.0401139101 . PMC   404070 . PMID   15123840.
• 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 (July 2004). "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. doi:10.1128/MCB.24.14.6253-6267.2004. PMC   434262 . PMID   15226428.
• 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 (October 2005). "Towards a proteome-scale map of the human protein–protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.
• Ito T, Noguchi Y, Yashima T, Kitamura K (May 2006). "SIX1 mutation associated with enlargement of the vestibular aqueduct in a patient with branchio-oto syndrome". The Laryngoscope. 116 (5): 796–9. doi:10.1097/01.mlg.0000209096.40400.96. PMID   16652090. S2CID   19273457.