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Protein

Homeobox protein SIX1

Gene

Six1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Transcription factor that is involved in the regulation of cell proliferation, apoptosis and embryonic development. Plays an important role in the development of several organs, including kidney, muscle and inner ear. Depending on context, functions as transcriptional repressor or activator. Lacks an activation domain, and requires interaction with EYA family members for transcription activation. Mediates nuclear translocation of EYA1 and EYA2. Binds the 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 element in the MYOG promoter. Regulates the expression of numerous genes, including MYC, CCNA1, CCND1 and EZR. Acts as activator of the IGFBP5 promoter, probably coactivated by EYA2. Repression of precursor cell proliferation in myoblasts is switched to activation through recruitment of EYA3 to the SIX1-DACH1 complex. During myogenesis, seems to act together with EYA2 and DACH2.8 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi124 – 183HomeoboxPROSITE-ProRule annotationAdd BLAST60

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, Developmental protein, DNA-binding, Repressor
Biological processApoptosis, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Homeobox protein SIX1
Alternative name(s):
Sine oculis homeobox homolog 1
Gene namesi
Name:Six1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:102780 Six1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Perinatal lethality. Mice show failure in renal organogenesis, a severe reduction of most migratory hypaxial muscles including those of the forelimb, diaphragm and tongue, and severe rib-cage deformation. Besides, mice display craniofacial defects, including loss of inner ear structures. Pax2, Six2 and Sall1 expression is markedly reduced in the metanephric mesenchyme at E10.5 during kidney development. Mice lacking both Six1 and Eya1 show defects in kidney development, complete absence of hypaxial muscle, severe reduction in epaxial muscle and a 5-10-fold by volume smaller pituarity than the wild-type gland.5 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000492961 – 284Homeobox protein SIX1Add BLAST284

Post-translational modificationi

Phosphorylated during interphase; becomes hyperphosphorylated during mitosis. Hyperphosphorylation impairs binding to promoter elements (By similarity).By similarity
Ubiquitinated by the anaphase promoting complex (APC), leading to its proteasomal degradation.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ62231
PRIDEiQ62231

PTM databases

PhosphoSitePlusiQ62231

Expressioni

Tissue specificityi

Expressed in phalangeal tendons and in skeletal muscle and in head and body mesenchyme.

Developmental stagei

First expressed at E8.2-8.5 of embryo development in the anterior head mesoderm and developing pharyngeal pouches. Expression in the developing limb begins at E11 and is more pronounced dorsally. It progresses into the developing phalanges at E13.5. In the developing inner ear detected in the otic placode and the surrounding surface ectoderm at E8.5. Expression became prominent at the invaginating otic pit and the nascent otic vesicle at E9.5. At E10.5, expression was limited to the ventral half of the otic vesicle. Subsequently, the expression became gradually restricted to the cochlear region at E11.5 and E12.5. At later stages detected exclusively in the cochlea at E14.5, and the expression in the cochlear duct persisted in the neonate. In the developing kidney, is expressed in the uninduced metanephric mesenchyme at E10.5 and in the induced mesenchyme around the ureteric bud at E11.5. At E17.5 to P0, expression becomes restricted to a subpopulation of collecting tubule epithelial cells.2 Publications

Gene expression databases

BgeeiENSMUSG00000051367 Expressed in 193 organ(s), highest expression level in quadriceps femoris
ExpressionAtlasiQ62231 baseline and differential
GenevisibleiQ62231 MM

Interactioni

Subunit structurei

Interacts with EYA1. Interacts with CDC20 (By similarity). Interacts with DACH1, EYA2 and EYA3. Interacts with TBX18 (By similarity).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Eya1P977673EBI-1368483,EBI-1368503

GO - Molecular functioni

Protein-protein interaction databases

BioGridi203259, 10 interactors
CORUMiQ62231
IntActiQ62231, 1 interactor
STRINGi10090.ENSMUSP00000059026

Structurei

3D structure databases

ProteinModelPortaliQ62231
SMRiQ62231
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the SIX/Sine oculis homeobox family.Curated

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiKOG0775 Eukaryota
ENOG410XRPB LUCA
GeneTreeiENSGT00540000070251
HOGENOMiHOG000261680
HOVERGENiHBG003609
InParanoidiQ62231
KOiK15614
OMAiSAYPMSG
OrthoDBiEOG091G083I
PhylomeDBiQ62231
TreeFamiTF315545

Family and domain databases

CDDicd00086 homeodomain, 1 hit
InterProiView protein in InterPro
IPR009057 Homeobox-like_sf
IPR017970 Homeobox_CS
IPR001356 Homeobox_dom
IPR031278 SIX1
IPR031701 SIX1_SD
PANTHERiPTHR10390:SF13 PTHR10390:SF13, 1 hit
PfamiView protein in Pfam
PF00046 Homeobox, 1 hit
PF16878 SIX1_SD, 1 hit
SMARTiView protein in SMART
SM00389 HOX, 1 hit
SUPFAMiSSF46689 SSF46689, 1 hit
PROSITEiView protein in PROSITE
PS00027 HOMEOBOX_1, 1 hit
PS50071 HOMEOBOX_2, 1 hit

Sequencei

Sequence statusi: Complete.

Q62231-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSMLPSFGFT QEQVACVCEV LQQGGNLERL GRFLWSLPAC DHLHKNESVL
60 70 80 90 100
KAKAVVAFHR GNFRELYKIL ESHQFSPHNH PKLQQLWLKA HYVEAEKLRG
110 120 130 140 150
RPLGAVGKYR VRRKFPLPRT IWDGEETSYC FKEKSRGVLR EWYAHNPYPS
160 170 180 190 200
PREKRELAEA TGLTTTQVSN WFKNRRQRDR AAEAKERENT ENNNSSSNKQ
210 220 230 240 250
NQLSPLEGGK PLMSSSEEEF SPPQSPDQNS VLLLQSNMGH ARSSNYSLPG
260 270 280
LTASQPSHGL QAHQHQLQDS LLGPLTSSLV DLGS
Length:284
Mass (Da):32,210
Last modified:April 13, 2004 - v2
Checksum:i4A6F88000FB9F8EB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti12 – 14EQV → GQG in CAA56585 (PubMed:7720577).Curated3

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X80339 mRNA Translation: CAA56585.1
BC023304 mRNA Translation: AAH23304.1
CCDSiCCDS25973.1
PIRiS60751
RefSeqiNP_033215.2, NM_009189.3
UniGeneiMm.4645

Genome annotation databases

EnsembliENSMUST00000050029; ENSMUSP00000059026; ENSMUSG00000051367
GeneIDi20471
KEGGimmu:20471
UCSCiuc007nwa.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X80339 mRNA Translation: CAA56585.1
BC023304 mRNA Translation: AAH23304.1
CCDSiCCDS25973.1
PIRiS60751
RefSeqiNP_033215.2, NM_009189.3
UniGeneiMm.4645

3D structure databases

ProteinModelPortaliQ62231
SMRiQ62231
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi203259, 10 interactors
CORUMiQ62231
IntActiQ62231, 1 interactor
STRINGi10090.ENSMUSP00000059026

PTM databases

PhosphoSitePlusiQ62231

Proteomic databases

PaxDbiQ62231
PRIDEiQ62231

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000050029; ENSMUSP00000059026; ENSMUSG00000051367
GeneIDi20471
KEGGimmu:20471
UCSCiuc007nwa.2 mouse

Organism-specific databases

CTDi6495
MGIiMGI:102780 Six1

Phylogenomic databases

eggNOGiKOG0775 Eukaryota
ENOG410XRPB LUCA
GeneTreeiENSGT00540000070251
HOGENOMiHOG000261680
HOVERGENiHBG003609
InParanoidiQ62231
KOiK15614
OMAiSAYPMSG
OrthoDBiEOG091G083I
PhylomeDBiQ62231
TreeFamiTF315545

Miscellaneous databases

PROiPR:Q62231
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000051367 Expressed in 193 organ(s), highest expression level in quadriceps femoris
ExpressionAtlasiQ62231 baseline and differential
GenevisibleiQ62231 MM

Family and domain databases

CDDicd00086 homeodomain, 1 hit
InterProiView protein in InterPro
IPR009057 Homeobox-like_sf
IPR017970 Homeobox_CS
IPR001356 Homeobox_dom
IPR031278 SIX1
IPR031701 SIX1_SD
PANTHERiPTHR10390:SF13 PTHR10390:SF13, 1 hit
PfamiView protein in Pfam
PF00046 Homeobox, 1 hit
PF16878 SIX1_SD, 1 hit
SMARTiView protein in SMART
SM00389 HOX, 1 hit
SUPFAMiSSF46689 SSF46689, 1 hit
PROSITEiView protein in PROSITE
PS00027 HOMEOBOX_1, 1 hit
PS50071 HOMEOBOX_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSIX1_MOUSE
AccessioniPrimary (citable) accession number: Q62231
Secondary accession number(s): Q8CIL7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: April 13, 2004
Last modified: November 7, 2018
This is version 157 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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