Six3 sine oculis-related homeobox 3 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Six3provided by MGI
Official Full Name: sine oculis-related homeobox 3provided by MGI
Primary source: MGI:MGI:102764
See related: Ensembl:ENSMUSG00000038805 AllianceGenome:MGI:102764
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Six3a; Six3b; Six3beta; Six3alpha; E130112M24Rik
Summary: Enables several functions, including DNA-binding transcription activator activity, RNA polymerase II-specific; histone deacetylase binding activity; and transcription corepressor binding activity. Involved in several processes, including animal organ development; lens fiber cell apoptotic process; and neuroblast migration. Acts upstream of or within several processes, including animal organ development; circadian behavior; and protein import into nucleus. Located in nucleus. Is expressed in several structures, including embryo ectoderm; limb; maxillary process; nervous system; and sensory organ. Used to study holoprosencephaly 2. Human ortholog(s) of this gene implicated in holoprosencephaly and holoprosencephaly 2. Orthologous to human SIX3 (SIX homeobox 3). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in whole brain E14.5 (RPKM 5.7), CNS E14 (RPKM 5.3) and 2 other tissues See more
Orthologs: human all
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Genomic context

Location:: 17 E4; 17 55.42 cM

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	17	NC_000083.7 (85921036..85933619)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	17	NC_000083.6 (85613608..85626191)

Chromosome 17 - NC_000083.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Chd5 Regulates the Transcription Factor Six3 to Promote Neuronal Differentiation.
Title: Chd5 Regulates the Transcription Factor Six3 to Promote Neuronal Differentiation.
Deletion of the homeodomain gene Six3 from kisspeptin neurons causes subfertility in female mice.
Title: Deletion of the homeodomain gene Six3 from kisspeptin neurons causes subfertility in female mice.
The transcription factors SIX3 and VAX1 are required for suprachiasmatic nucleus circadian output and fertility in female mice.
Title: The transcription factors SIX3 and VAX1 are required for suprachiasmatic nucleus circadian output and fertility in female mice.
Homeobox Gene Six3 is Required for the Differentiation of D2-Type Medium Spiny Neurons.
Title: Homeobox Gene Six3 is Required for the Differentiation of D2-Type Medium Spiny Neurons.
Heterozygous deletion of Otx2, Vax1, or Six3 is sufficient to produce subfertility. Review shows that that all 3 have reduced numbers of GnRH neurons and are subfertile. However, there is specificity to the subfertility by sex and by mechanisms of action.
Title: Haploinsufficiency of Homeodomain Proteins Six3, Vax1, and Otx2 Causes Subfertility in Mice via Distinct Mechanisms.
Six3 and Six6 together directly or indirectly suppress Wnt/beta-catenin signaling but promote retinogenic factors for the maintenance of multipotent neuroretinal progenitors.
Title: Six3 and Six6 Are Jointly Required for the Maintenance of Multipotent Retinal Progenitors through Both Positive and Negative Regulation.
Six3 is haploinsufficient for main olfactory epithelium development, GnRH neuron migration, and fertility.
Title: Haploinsufficiency of SIX3 Abolishes Male Reproductive Behavior Through Disrupted Olfactory Development, and Impairs Female Fertility Through Disrupted GnRH Neuron Migration.
SP8 and SP9 coordinately promote D2-type medium spiny neuron production by activating Six3 expression
Title: SP8 and SP9 coordinately promote D2-type medium spiny neuron production by activating Six3 expression.
Six3 in a small population of progenitors expressing Six3-Cre at E8.5 is required for neuroretinal specification via regulating cell signaling and survival in mice.
Title: Six3 in a small population of progenitors at E8.5 is required for neuroretinal specification via regulating cell signaling and survival in mice.
variations in Six3 dosage result in different forms of Holoprosencephaly
Title: Six3 dosage mediates the pathogenesis of holoprosencephaly.

Submit: New GeneRIF Correction See all GeneRIFs (26)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (8) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:548464

Six3 (e-PCR), detects polymorphism
- UniSTS:536466

RH143896 (e-PCR)
- UniSTS:233142

Six3 (e-PCR), detects polymorphism
- UniSTS:527034

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	ISO Inferred from Sequence Orthology more info
enables histone deacetylase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables sequence-specific double-stranded DNA binding	ISO Inferred from Sequence Orthology more info
enables signaling receptor binding	ISO Inferred from Sequence Orthology more info
enables transcription corepressor binding	IPI Inferred from Physical Interaction more info	PubMed
enables transcription corepressor binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in apoptotic process involved in development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in brain development	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within brain development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within camera-type eye development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in cell proliferation in forebrain	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within circadian behavior	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within diencephalon development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in epithelial cell maturation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in eye development	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within eye development	IDA Inferred from Direct Assay more info	PubMed
involved_in eye development	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within forebrain anterior/posterior pattern specification	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within forebrain anterior/posterior pattern specification	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in forebrain dorsal/ventral pattern formation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within gonad development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in lens development in camera-type eye	IDA Inferred from Direct Assay more info	PubMed
involved_in lens fiber cell apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in lens fiber cell differentiation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within lens induction in camera-type eye	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within multicellular organism development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within multicellular organism growth	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within negative regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of Wnt signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of neuron differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in neuroblast differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neuroblast migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in optic vesicle morphogenesis	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within pituitary gland development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in pituitary gland development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within protein import into nucleus	IDA Inferred from Direct Assay more info	PubMed
involved_in proximal/distal axis specification	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cell cycle phase transition	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of neural precursor cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of neural retina development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of neuroblast proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within telencephalon development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in telencephalon development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in telencephalon regionalization	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within thyroid gland development	IGI Inferred from Genetic Interaction more info	PubMed

Component	Evidence Code	Pubs
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of transcription regulator complex	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: homeobox protein SIX3

Names: sine oculis homeobox homolog 3; sine oculis-related homeobox 3 homolog

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_011381.4 → NP_035511.2 homeobox protein SIX3

See identical proteins and their annotated locations for NP_035511.2

Status: VALIDATED

Source sequence(s)

AC166821, BC098096, CD351258

Consensus CDS

CCDS50203.1

UniProtKB/Swiss-Prot

P70176, P70177, Q4QQQ3, Q62233

UniProtKB/TrEMBL

Q52KB8

Related

ENSMUSP00000135312.3, ENSMUST00000176081.3

Conserved Domains (2) summary

cd00086
Location:209 → 257

homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.

pfam16878
Location:88 → 201

SIX1_SD; Transcriptional regulator, SIX1, N-terminal SD domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000083.7 Reference GRCm39 C57BL/6J

Range

85921036..85933619

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017317367.2 → XP_017172856.1 homeobox protein SIX3 isoform X1

UniProtKB/TrEMBL

Q52KB8

Conserved Domains (2) summary

cd00086
Location:230 → 278

homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.

pfam16878
Location:109 → 222

SIX1_SD; Transcriptional regulator, SIX1, N-terminal SD domain