SIX1

SIX homeobox 1

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
4EGC

Identifiers

Symbols

SIX1 ; BOS3; DFNA23; TIP39

External IDs

OMIM: 601205 MGI: 102780 HomoloGene: 4360 GeneCards: SIX1 Gene

Gene ontology
Molecular function	• DNA binding • chromatin binding • sequence-specific DNA binding transcription factor activity • protein binding • sequence-specific DNA binding • transcription regulatory region DNA binding
Cellular component	• nucleus • transcription factor complex • nucleolus • cytoplasm
Biological process	• negative regulation of transcription from RNA polymerase II promoter • ureteric bud development • branching involved in ureteric bud morphogenesis • organ induction • kidney development • outflow tract morphogenesis • transcription, DNA-templated • regulation of transcription, DNA-templated • apoptotic process • pattern specification process • skeletal muscle tissue development • sensory perception of sound • regulation of synaptic growth at neuromuscular junction • facial nerve morphogenesis • epithelial cell differentiation • thyroid gland development • regulation of protein localization • protein localization to nucleus • aorta morphogenesis • inner ear morphogenesis • middle ear morphogenesis • negative regulation of neuron apoptotic process • regulation of neuron differentiation • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • thymus development • neuron fate specification • generation of neurons • embryonic cranial skeleton morphogenesis • embryonic skeletal system morphogenesis • inner ear development • myoblast migration • pharyngeal system development • otic vesicle development • metanephric mesenchyme development • regulation of branch elongation involved in ureteric bud branching • positive regulation of ureteric bud formation • mesonephric tubule formation • ureter smooth muscle cell differentiation • positive regulation of secondary heart field cardioblast proliferation • cochlea morphogenesis • positive regulation of branching involved in ureteric bud morphogenesis • negative regulation of branching involved in ureteric bud morphogenesis • positive regulation of mesenchymal cell proliferation involved in ureter development
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 14:
61.11 – 61.12 Mb

Chr 12:
73.04 – 73.05 Mb

PubMed search

Homeobox protein SIX1 is a protein that in humans is encoded by the SIX1 gene.^[1]^[2]^[3]

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]^[3]

Interactions

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

References

↑ Boucher CA, Carey N, Edwards YH, Siciliano MJ, Johnson KJ (June 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.
↑ Ruf RG, Xu PX, Silvius D, Otto EA, Beekmann F, Muerb UT, Kumar S, Neuhaus TJ, Kemper MJ, Raymond RM Jr, 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". Proc Natl Acad Sci U S A 101 (21): 8090–5. doi:10.1073/pnas.0308475101. PMC 419562. PMID 15141091.
↑ 3.0 3.1 "Entrez Gene: SIX1 sine oculis homeobox homolog 1 (Drosophila)".
↑ Buller, C; Xu X; Marquis V; Schwanke R; Xu P X (November 2001). "Molecular effects of Eya1 domain mutations causing organ defects in BOR syndrome". Hum. Mol. Genet. (England) 10 (24): 2775–81. doi:10.1093/hmg/10.24.2775. ISSN 0964-6906. PMID 11734542.
↑ Rual, Jean-François; Venkatesan Kavitha, Hao Tong, Hirozane-Kishikawa Tomoko, Dricot Amélie, Li Ning, Berriz Gabriel F, Gibbons Francis D, Dreze Matija, Ayivi-Guedehoussou Nono, Klitgord Niels, Simon Christophe, Boxem Mike, Milstein Stuart, Rosenberg Jennifer, Goldberg Debra S, Zhang Lan V, Wong Sharyl L, Franklin Giovanni, Li Siming, Albala Joanna S, Lim Janghoo, Fraughton Carlene, Llamosas Estelle, Cevik Sebiha, Bex Camille, Lamesch Philippe, Sikorski Robert S, Vandenhaute Jean, Zoghbi Huda Y, Smolyar Alex, Bosak Stephanie, Sequerra Reynaldo, Doucette-Stamm Lynn, Cusick Michael E, Hill David E, Roth Frederick P, Vidal Marc (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature (England) 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.

Oliver G, Wehr R, Jenkins NA et al. (1995). "Homeobox genes and connective tissue patterning". Development 121 (3): 693–705. PMID 7720577.
Ford HL, Kabingu EN, Bump EA et al. (1998). "Abrogation of the G2 cell cycle checkpoint associated with overexpression of HSIX1: a possible mechanism of breast carcinogenesis". Proc. Natl. Acad. Sci. U.S.A. 95 (21): 12608–13. doi:10.1073/pnas.95.21.12608. PMC 22878. PMID 9770533.
Salam AA, Häfner FM, Linder TE et al. (2001). "A novel locus (DFNA23) for prelingual autosomal dominant nonsyndromic hearing loss maps to 14q21-q22 in a Swiss German kindred". Am. J. Hum. Genet. 66 (6): 1984–8. doi:10.1086/302931. PMC 1378045. PMID 10777717.
Ford HL, Landesman-Bollag E, Dacwag CS et al. (2000). "Cell cycle-regulated phosphorylation of the human SIX1 homeodomain protein". J. Biol. Chem. 275 (29): 22245–54. doi:10.1074/jbc.M002446200. PMID 10801845.
Fan X, Brass LF, Poncz M et al. (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". J. Biol. Chem. 275 (41): 32129–34. doi:10.1074/jbc.M004577200. PMID 10906137.
Buller C, Xu X, Marquis V et al. (2002). "Molecular effects of Eya1 domain mutations causing organ defects in BOR syndrome". Hum. Mol. Genet. 10 (24): 2775–81. doi:10.1093/hmg/10.24.2775. PMID 11734542.
Li CM, Guo M, Borczuk A et al. (2002). "Gene expression in Wilms' tumor mimics the earliest committed stage in the metanephric mesenchymal-epithelial transition". Am. J. Pathol. 160 (6): 2181–90. doi:10.1016/S0002-9440(10)61166-2. PMC 1850829. PMID 12057921.
Ikeda K, Watanabe Y, Ohto H, Kawakami K (2002). "Molecular interaction and synergistic activation of a promoter by Six, Eya, and Dach proteins mediated through CREB binding protein". Mol. Cell. Biol. 22 (19): 6759–66. doi:10.1128/MCB.22.19.6759-6766.2002. PMC 134036. PMID 12215533.
López-Ríos J, Tessmar K, Loosli F et al. (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.
Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Ruf RG, Berkman J, Wolf MT et al. (2003). "A gene locus for branchio-otic syndrome maps to chromosome 14q21.3-q24.3". J. Med. Genet. 40 (7): 515–9. doi:10.1136/jmg.40.7.515. PMC 1735534. PMID 12843324.
Zheng W, Huang L, Wei ZB et al. (2003). "The role of Six1 in mammalian auditory system development". Development 130 (17): 3989–4000. doi:10.1242/dev.00628. PMID 12874121.
Li X, Oghi KA, Zhang J et al. (2003). "Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis". Nature 426 (6964): 247–54. doi:10.1038/nature02083. PMID 14628042.
Coletta RD, Christensen K, Reichenberger KJ et al. (2004). "The Six1 homeoprotein stimulates tumorigenesis by reactivation of cyclin A1". Proc. Natl. Acad. Sci. U.S.A. 101 (17): 6478–83. doi:10.1073/pnas.0401139101. PMC 404070. PMID 15123840.
Grifone R, Laclef C, Spitz F et al. (2004). "Six1 and Eya1 expression can reprogram adult muscle from the slow-twitch phenotype into the fast-twitch phenotype". Mol. Cell. Biol. 24 (14): 6253–67. doi:10.1128/MCB.24.14.6253-6267.2004. PMC 434262. PMID 15226428.
Gerhard DS, Wagner L, Feingold EA et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Rual JF, Venkatesan K, Hao T et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
Ito T, Noguchi Y, Yashima T, Kitamura K (2006). "SIX1 mutation associated with enlargement of the vestibular aqueduct in a patient with branchio-oto syndrome". Laryngoscope 116 (5): 796–9. doi:10.1097/01.mlg.0000209096.40400.96. PMID 16652090.

Transcription factors and intracellular receptors

(1) Basic domains

(1.1) Basic leucine zipper (bZIP)	Activating transcription factor AATF 1 2 3 4 5 6 7 AP-1 c-Fos FOSB FOSL1 FOSL2 JDP2 c-Jun JUNB JunD BACH 1 2 BATF BLZF1 C/EBP α β γ δ ε ζ CREB 1 3 L1 CREM DBP DDIT3 GABPA HLF MAF B F G K NFE 2 L1 L2 L3 NFIL3 NRL NRF 1 2 3 XBP1

(1.2) Basic helix-loop-helix (bHLH)	ATOH1 AhR AHRR ARNT ASCL1 BHLH 2 3 9 ARNTL ARNTL ARNTL2 CLOCK EPAS1 FIGLA HAND 1 2 HES 5 6 HEY 1 2 L HES1 HIF 1A 3A ID 1 2 3 4 LYL1 MESP2 MXD4 MYCL1 MYCN Myogenic regulatory factors MyoD Myogenin MYF5 MYF6 Neurogenins 1 2 3 NeuroD 1 2 NPAS 1 2 3 OLIG 1 2 Pho4 Scleraxis SIM 1 2 TAL 1 2 Twist USF1

(1.3) bHLH-ZIP	AP-4 MAX MXD3 MITF MNT MLX MXI1 Myc SREBP 1 2

(1.4) NF-1	NFI A B C X SMAD R-SMAD 1 2 3 5 9 I-SMAD 6 7 4)

(1.5) RF-X	RFX 1 2 3 4 5 6 ANK

(1.6) Basic helix-span-helix (bHSH)	AP-2 α β γ δ ε

(2) Zinc finger DNA-binding domains

(2.1) Nuclear receptor (Cys₄)

subfamily 1	Thyroid hormone α β CAR FXR LXR α β PPAR α β/δ γ PXR RAR α β γ ROR α β γ Rev-ErbA α β VDR

subfamily 2	COUP-TF (I II Ear-2 HNF4 α γ PNR RXR α β γ Testicular receptor 2 4 TLX

subfamily 3	Steroid hormone Androgen Estrogen α β Glucocorticoid Mineralocorticoid Progesterone Estrogen related α β γ

subfamily 4	NUR NGFIB NOR1 NURR1

subfamily 5	LRH-1 SF1

subfamily 6	GCNF

subfamily 0	DAX1 SHP

(2.2) Other Cys₄

GATA
- 1
- 2
- 3
- 4
- 5
- 6
MTA
- 1
- 2
- 3
TRPS1

(2.3) Cys₂His₂

General transcription factors
- TFIIA
- TFIIB
- TFIID
- TFIIE
  - 1
  - 2
- TFIIF
- 1
- 2
  - TFIIH
  - 1
  - 2
  - 4
  - 2I
  - 3A
  - 3C1
  - 3C2

ATBF1
BCL
- 6
- 11A
- 11B
CTCF
E4F1
EGR
- 1
- 2
- 3
- 4
ERV3
GFI1
GLI-Krüppel family
- 1
- 2
- 3
- REST
- S1
- S2
- YY1
HIC
- 1
- 2
HIVEP
- 1
- 2
- 3
IKZF
- 1
- 2
- 3
ILF
- 2
- 3
KLF
- 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11
- 12
- 13
- 14
- 15
- 17
MTF1
MYT1
OSR1
PRDM9
SALL
- 1
- 2
- 3
- 4
SP
- 1
- 2
- 4
- 7
- 8
TSHZ3
WT1
Zbtb7
- 7A
- 7B
ZBTB
- 11
- 16
- 17
- 20
- 32
- 33
- 40
zinc finger
- 3
- 7
- 9
- 10
- 19
- 22
- 24
- 33B
- 34
- 35
- 41
- 43
- 44
- 51
- 74
- 143
- 146
- 148
- 165
- 202
- 217
- 219
- 238
- 239
- 259
- 267
- 268
- 281
- 295
- 300
- 318
- 330
- 346
- 350
- 365
- 366
- 384
- 423
- 451
- 452
- 471
- 593
- 638
- 644
- 649
- 655

(2.4) Cys₆

HIVEP1

(2.5) Alternating composition

AIRE
DIDO1
GRLF1
ING
- 1
- 2
- 4
JARID
- 1A
- 1B
- 1C
- 1D
- 2
JMJD1B

(2.6) WRKY

WRKY

(3) Helix-turn-helix domains

(3.1) Homeodomain	ARX CDX 1 2 CRX CUTL1 DBX 1 2 DLX 3 4 5 EMX 1 2 EN 1 2 FHL 1 2 3 HESX1 HHEX HLX Homeobox A1 A2 A3 A4 A5 A7 A9 A10 A11 A13 B1 B2 B3 B4 B5 B6 B7 B8 B9 B13 C4 C5 C6 C8 C9 C10 C11 C12 C13 D1 D3 D4 D8 D9 D10 D11 D12 D13 HOPX IRX 1 2 3 4 5 6 MKX LMX 1A 1B MEIS 1 2 MEOX2 MNX1 MSX 1 2 NANOG NKX 2-1 2-2 2-3 2-5 3-1 3-2 6-1 6-2 NOBOX PBX 1 2 3 PHF 1 3 6 8 10 16 17 20 21A PHOX 2A 2B PITX 1 2 3 POU domain PIT-1 BRN-3: A B C Octamer transcription factor: 1 2 3/4 6 7 11 OTX 1 2 PDX1 SATB2 SHOX2 SIX 1 2 3 4 5 VAX1 ZEB 1 2

(3.2) Paired box	PAX 1 2 3 4 5 6 7 8 9 PRRX 1 2 RAX

(3.3) Fork head / winged helix	E2F 1 2 3 4 5 FOX proteins A1 A2 A3 C1 C2 D3 D4 E1 E3 F1 G1 H1 I1 J1 J2 K1 K2 L2 M1 N1 N3 O1 O3 O4 P1 P2 P3 P4

(3.4) Heat shock factors	HSF 1 2 4

(3.5) Tryptophan clusters	ELF 2 4 5 EGF ELK 1 3 4 ERF ETS 1 2 ERG SPIB ETV 1 4 5 6 FLI1 Interferon regulatory factors 1 2 3 4 5 6 7 8 MYB MYBL2

(3.6) TEA domain	transcriptional enhancer factor 1 2 3 4

(4) β-Scaffold factors with minor groove contacts

(4.1) Rel homology region	NF-κB NFKB1 NFKB2 REL RELA RELB NFAT C1 C2 C3 C4 5

(4.2) STAT	STAT 1 2 3 4 5 6

(4.3) p53	p53 TBX 1 2 3 5 19 21 22 TBR1 TBR2 TFT MYRF TP63

(4.4) MADS box	Mef2 A B C D SRF

(4.6) TATA-binding proteins	TBP TBPL1

(4.7) High-mobility group	BBX HMGB 1 2 3 4 HMGN 1 2 3 4 HNF 1A 1B LEF1 SOX 1 2 3 4 5 6 8 9 10 11 12 13 14 15 18 21 SRY SSRP1 TCF 3 4 TOX 1 2 3 4

(4.9) Grainyhead	TFCP2

(4.10) Cold-shock domain	CSDA YBX1

(4.11) Runt	CBF CBFA2T2 CBFA2T3 RUNX1 RUNX2 RUNX3 RUNX1T1

(0) Other transcription factors

(0.2) HMGI(Y)	HMGA 1 2 HBP1

(0.3) Pocket domain	Rb RBL1 RBL2

(0.5) AP-2/EREBP-related factors	Apetala 2 EREBP B3

(0.6) Miscellaneous	ARID 1A 1B 2 3A 3B 4A CAP IFI 16 35 MLL 2 3 T1 MNDA NFY A B C Rho/Sigma

see also transcription factor/coregulator deficiencies

Index of genetics

Description	Gene expression DNA replication cycle recombination repair binding proteins Transcription factors regulators nucleic acids RNA RNA binding proteins ribonucleoproteins repeated sequence modification Translation ribosome modification nexins Proteins domains Structure primary secondary tertiary quaternary

Disease	Replication and repair Transcription factor Transcription Translation

SIX1

Interactions

References

Further reading