Six4 sine oculis-related homeobox 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Six4provided by MGI
Official Full Name: sine oculis-related homeobox 4provided by MGI
Primary source: MGI:MGI:106034
See related: Ensembl:ENSMUSG00000034460 AllianceGenome:MGI:106034
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: AREC3; TrexBF
Summary: Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in several processes, including animal organ development; positive regulation of morphogenesis of an epithelium; and regulation of transcription, DNA-templated. Acts upstream of or within several processes, including embryonic organ morphogenesis; myoblast migration; and thymus development. Located in cytoplasm and nucleus. Is expressed in several structures, including exocrine gland; nervous system; sensory organ; tongue; and urinary system. Orthologous to human SIX4 (SIX homeobox 4). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Broad expression in limb E14.5 (RPKM 2.1), CNS E11.5 (RPKM 1.4) and 15 other tissues See more
Orthologs: human all
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Genomic context

Location:: 12 C3; 12 30.36 cM

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	12	NC_000078.7 (73146383..73160201, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	12	NC_000078.6 (73099609..73114031, complement)

Chromosome 12 - NC_000078.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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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?

Reciprocal regulation of pancreatic ductal adenocarcinoma growth and molecular subtype by HNF4alpha and SIX1/4.
Title: Reciprocal regulation of pancreatic ductal adenocarcinoma growth and molecular subtype by HNF4α and SIX1/4.
Time-dependent Pax3-mediated chromatin remodeling and cooperation with Six4 and Tead2 specify the skeletal myogenic lineage in developing mouse mesoderm.
Title: Time-dependent Pax3-mediated chromatin remodeling and cooperation with Six4 and Tead2 specify the skeletal myogenic lineage in developing mesoderm.
Six4 and Six5 are required for growth and morphological change of the primary abdominal wall.
Title: Mice doubly deficient in Six4 and Six5 show ventral body wall defects reproducing human omphalocele.
significant co-localization of binding sites for MyoD and Six proteins on over a thousand mouse genomic DNA regions, were found.
Title: MyoD reprogramming requires Six1 and Six4 homeoproteins: genome-wide cis-regulatory module analysis.
The results indicated that low Six4 and Six5 gene dosage improved dystrophic phenotypes of Dmd(mdx) /Y mice by enhancing muscle regeneration, and suggested that SIX4 and SIX5 are potentially useful de novo targets in therapeutic applications against muscle disorders, including DMD.
Title: Low Six4 and Six5 gene dosage improves dystrophic phenotype and prolongs life span of mdx mice.
data support a model where Eya-Six may form a complex to regulate nephron progenitor cell development before metanephric specification and are critical mesenchymal factors for inducing nephric duct development.
Title: Eya-six are necessary for survival of nephrogenic cord progenitors and inducing nephric duct development before ureteric bud formation.
results reveal a role for Six4 during adult muscle regeneration and suggest a widespread mechanism of cooperation between Six4 and MyoD.
Title: Genome-wide association between Six4, MyoD, and the histone demethylase Utx during myogenesis.
the transcription factors Six1 and Six4 are required for male gonadal differentiation.
Title: Homeoproteins Six1 and Six4 regulate male sex determination and mouse gonadal development.
Direct molecular regulation of the myogenic determination gene Myf5 by Pax3, with modulation by Six1/4 factors, is exemplified by the -111 kb-Myf5 enhancer
Title: Direct molecular regulation of the myogenic determination gene Myf5 by Pax3, with modulation by Six1/4 factors, is exemplified by the -111 kb-Myf5 enhancer.
Data show that absence of Six1 and Six4 leads to the development of dorsal myofibers lacking expression of fast-type muscle genes, and mainly expressing a slow-type muscle program.
Title: Genesis of muscle fiber-type diversity during mouse embryogenesis relies on Six1 and Six4 gene expression.

Submit: New GeneRIF Correction See all GeneRIFs (20)

Variation

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Alleles

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

Targeted (2) 1 citation
Endonuclease-mediated (3) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH135832 (e-PCR)
- UniSTS:209830

D50417 (e-PCR)
- UniSTS:124838

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	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 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 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

Process	Evidence Code	Pubs
acts_upstream_of_or_within anatomical structure development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within embryonic cranial skeleton morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within embryonic skeletal system morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in fungiform papilla morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in generation of neurons	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within inner ear morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in male gonad development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in male sex determination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in male sex differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in metanephric mesenchyme development	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 myoblast migration	IGI Inferred from Genetic Interaction more info	PubMed
involved_in myotome development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of neuron apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of satellite cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in olfactory placode formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in pharyngeal system development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of branching involved in ureteric bud morphogenesis	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
involved_in positive regulation of ureteric bud formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein localization to nucleus	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in regulation of branch elongation involved in ureteric bud branching	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of epithelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of gene expression	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within regulation of protein localization	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within regulation of synaptic assembly at neuromuscular junction	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in sarcomere organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in skeletal muscle fiber differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within skeletal muscle tissue development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in skeletal muscle tissue development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within thymus development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in tongue development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in trigeminal ganglion development	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IC Inferred by Curator more info	PubMed
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 SIX4

Names: sine oculis-related homeobox 4 homolog; skeletal muscle-specific ARE-binding protein AREC3

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_001362272.2 → NP_001349201.1 homeobox protein SIX4 isoform 2

Status: VALIDATED

Source sequence(s)

AC159274

Consensus CDS

CCDS88351.1

UniProtKB/TrEMBL

H3BL91

Related

ENSMUSP00000135699.3, ENSMUST00000175693.3

Conserved Domains (2) summary

cd00086
Location:213 → 267

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:93 → 202

SIX1_SD; Transcriptional regulator, SIX1, N-terminal SD domain
NM_001409898.1 → NP_001396827.1 homeobox protein SIX4 isoform 3

Status: VALIDATED

Source sequence(s)

AC159274
NM_011382.3 → NP_035512.1 homeobox protein SIX4 isoform 1

See identical proteins and their annotated locations for NP_035512.1

Status: VALIDATED

Source sequence(s)

AC159274

Consensus CDS

CCDS25974.1

UniProtKB/Swiss-Prot

B2RQH3, Q61321, Q61322, Q61323

Related

ENSMUSP00000036150.7, ENSMUST00000043208.8

Conserved Domains (2) summary

cd00086
Location:221 → 275

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:101 → 210

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