Six2 sine oculis-related homeobox 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Six2provided by MGI
Official Full Name: sine oculis-related homeobox 2provided by MGI
Primary source: MGI:MGI:102778
See related: Ensembl:ENSMUSG00000024134 AllianceGenome:MGI:102778
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
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 embryonic morphogenesis; kidney development; and positive regulation of chondrocyte proliferation. Acts upstream of or within several processes, including animal organ development; condensed mesenchymal cell proliferation; and protein import into nucleus. Located in nucleus. Is expressed in several structures, including alimentary system; central nervous system; embryo mesenchyme; genitourinary system; and sensory organ. Orthologous to human SIX2 (SIX homeobox 2). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in limb E14.5 (RPKM 11.3), CNS E11.5 (RPKM 10.4) and 6 other tissues See more
Orthologs: human all
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Genomic context

Location:: 17 E4; 17 55.72 cM

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	17	NC_000083.7 (85970276..85995682, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	17	NC_000083.6 (85662736..85688254, complement)

Chromosome 17 - NC_000083.7 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?

Tet2- and Tet3- Mediated Cytosine Hydroxymethylation in Six2 Progenitor Cells in Mice Is Critical for Nephron Progenitor Differentiation and Nephron Endowment.
Title: Tet2- and Tet3- Mediated Cytosine Hydroxymethylation in Six2 Progenitor Cells in Mice Is Critical for Nephron Progenitor Differentiation and Nephron Endowment.
Chromatin Remodelers Interact with Eya1 and Six2 to Target Enhancers to Control Nephron Progenitor Cell Maintenance.
Title: Chromatin Remodelers Interact with Eya1 and Six2 to Target Enhancers to Control Nephron Progenitor Cell Maintenance.
Generation and characterization of Six2 conditional mice.
Title: Generation and characterization of Six2 conditional mice.
identified a lncRNA, Gm29418, in nephron progenitor cells that has an enhancer-like function on a key regulatory gene, Six2.
Title: Comprehensive analysis of chromatin signature and transcriptome uncovers functional lncRNAs expressed in nephron progenitor cells.
Six2 facilitates NSCLC cell stemness and attenuates chemotherapeutic sensitivity via suppressing E-cadherin expression.
Title: Six2 promotes non-small cell lung cancer cell stemness via transcriptionally and epigenetically regulating E-cadherin.
Six2 expression is regulated by Gulo in the metanephric mesenchyme cells.
Title: Gulo regulates the proliferation, apoptosis and mesenchymal-to-epithelial transformation of metanephric mesenchyme cells via inhibiting Six2.
Reveal a unique dose response of nephron progenitors to the level of SIX2 protein in which the role of SIX2 in progenitor proliferation versus self-renewal is separable.
Title: Haploinsufficiency for the Six2 gene increases nephron progenitor proliferation promoting branching and nephron number.
Embryonic day 18.5 Six2Frs2alphaKO kidneys were hypoplastic and not cystic, postnatal day (P) 7 mutants had proximal tubular-derived cysts that nearly replaced the renal parenchyma by P21. Mutants had high proximal tubular proliferation rates and interstitial fibrosis, similar to known polycystic kidney disease models.
Title: Six2creFrs2α knockout mice are a novel model of renal cystogenesis.
GATA1 may be a potential regulator of Six2-maintained population of nephron progenitor cells.
Title: Six2 is involved in GATA1-mediated cell apoptosis in mouse embryonic kidney-derived cell lines.
Six2 mediates the protective effects of GDNF on damaged DA neurons by regulating Smurf1 expression.
Title: Transcription factor Six2 mediates the protection of GDNF on 6-OHDA lesioned dopaminergic neurons by regulating Smurf1 expression.

Submit: New GeneRIF Correction See all GeneRIFs (40)

Variation

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Alleles

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

Targeted (5) 1 citation
Endonuclease-mediated (4) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

X80338 (e-PCR)
- UniSTS:125859

Six2 (e-PCR), detects polymorphism
- UniSTS:547307

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables DNA binding	IEA Inferred from Electronic Annotation more info
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 protein-containing complex binding	IDA Inferred from Direct Assay 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 transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in anterior/posterior axis specification	IDA Inferred from Direct Assay more info	PubMed
involved_in cell migration	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell population proliferation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within chondrocyte differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within condensed mesenchymal cell proliferation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within embryonic cranial skeleton morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in embryonic digestive tract morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within embryonic skeletal system morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of epithelial cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in kidney development	IBA Inferred from Biological aspect of Ancestor more info
involved_in kidney development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in kidney development	ISO Inferred from Sequence Orthology more info
involved_in mesenchymal cell differentiation involved in kidney development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mesenchymal stem cell maintenance involved in nephron morphogenesis	IDA Inferred from Direct Assay more info	PubMed
involved_in mesenchymal stem cell maintenance involved in nephron morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mesenchymal stem cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mesenchymal to epithelial transition involved in metanephros morphogenesis	IEP Inferred from Expression Pattern more info	PubMed
involved_in mesodermal cell fate specification	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within metanephros development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within middle ear morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within multicellular organism development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of epithelial cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nephron development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nephron morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of chondrocyte proliferation	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 regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in regulation of branching involved in ureteric bud morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of chondrocyte differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of ossification	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

Component	Evidence Code	Pubs
located_in nucleoplasm	TAS Traceable Author Statement more info
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 SIX2

Names: sine oculis homeobox homolog 2; sine oculis-related homeobox 2 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_011380.2 → NP_035510.1 homeobox protein SIX2

See identical proteins and their annotated locations for NP_035510.1

Status: VALIDATED

Source sequence(s)

AC166821, BC068021

Consensus CDS

CCDS29007.1

UniProtKB/Swiss-Prot

P70179, Q62232

Related

ENSMUSP00000125871.3, ENSMUST00000163568.4

Conserved Domains (2) summary

cd00086
Location:129 → 180

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:9 → 118

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

85970276..85995682 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011246335.4 → XP_011244637.1 homeobox protein SIX2 isoform X2

Conserved Domains (2) summary

cd00086
Location:129 → 180

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:9 → 118

SIX1_SD; Transcriptional regulator, SIX1, N-terminal SD domain
XM_006523931.5 → XP_006523994.1 homeobox protein SIX2 isoform X1

Conserved Domains (2) summary

cd00086
Location:129 → 180

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:9 → 118

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