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Protein

Homeobox protein SIX2

Gene

Six2

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

Functioni

Transcription factor that plays an important role in the development of several organs, including kidney, skull and stomach. During kidney development, maintains cap mesenchyme multipotent nephron progenitor cells in an undifferentiated state by opposing the inductive signals emanating from the ureteric bud and cooperates with WNT9B to promote renewing progenitor cells proliferation. Acts through its interaction with TCF7L2 and OSR1 in a canonical Wnt signaling independent manner preventing transcription of differentiation genes in cap mesenchyme such as WNT4. Also acts independently of OSR1 to activate expression of many cap mesenchyme genes, including itself, GDNF and OSR1. During craniofacial development plays a role in growth and elongation of the cranial base through regulation of chondrocyte differentiation (PubMed:20515681). During stomach organogenesis, controls pyloric sphincter formation and mucosal growth through regulation of a gene network including NKX2-5, BMPR1B, BMP4, SOX9 and GREM1 (PubMed:19660448). During branchial arch development, acts to mediate HOXA2 control over the insulin-like growth factor pathway (PubMed:18321982). Also may be involved in limb tendon and ligament development (PubMed:7720577). Plays a role in cell proliferation and migration (By similarity).By similarity9 Publications

Regions

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Homeobox protein SIX2
Alternative name(s):
Sine oculis homeobox homolog 2
Gene namesi
Name:Six2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:102778 Six2

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

Nucleus

Pathology & Biotechi

Disruption phenotypei

Six2 knockout heterozygous mice not exhibit any obvious abnormalities. However, Six2 knockout nullizygous mice die soon after birth.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000492981 – 296Homeobox protein SIX2Add BLAST296

Proteomic databases

PaxDbiQ62232
PRIDEiQ62232

PTM databases

PhosphoSitePlusiQ62232

Expressioni

Tissue specificityi

Expressed in phalangeal tendons, in smooth muscle and in head and body mesenchyme.

Developmental stagei

First expressed at E8.5 of embryo development in a restricted mesodermal subpopulation at the anterior hindbrain level. Expression of SIX2 in the developing limb begins at E11 and is more pronounced ventrally. It progresses into the developing phalanges at E12.5. At E10.5 expressed in the metanephric blastema, which signals the ureteric bud to evaginate from the Wolffian duct. At E11.5 expressed at high levels in the dorsal anephric mesenchyme and is down-regulated where pretubular aggregates will form on the ventral side of the ureteric bud. At E14.5, expression persists in the peripheral mesenchyme of the renal cortex. At E9.5, expressed in the splanchnic mesoderm of the stomach anlage. By E10.5, expressed in the mesoderm of the posterior stomach. Expression is seen in the presumptive glandular stomach primordium at E11.5. At E12.5, becomes restricted to the mesenchyme of the antral region of the posterior stomach. At E14.5, expression remains in the antrum, just anterior to the pyloric sphincter.2 Publications

Inductioni

Down-regulated by CTNNB1 upon differentiarion. Activated by TLX1 in the kidney and repressed by HOXA2 in the branchial arch and facial mesenchyme.3 Publications

Gene expression databases

BgeeiENSMUSG00000024134 Expressed in 176 organ(s), highest expression level in pharyngeal arch 1
GenevisibleiQ62232 MM

Interactioni

Subunit structurei

Interacts with TCF7L2; in a canonical Wnt signaling independent manner; prevents transcription of differentiation genes in cap mesenchyme. Interacts with OSR1; form a strong repressor complex with TCF7L2, TLE2 and TLE3 to prevent the activation of Wnt/beta-catenin target genes in the cap mesenchyme. Interacts with HOXA11, EYA1 and EYA3.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Eya1P977673EBI-1368736,EBI-1368503

GO - Molecular functioni

Protein-protein interaction databases

BioGridi203260, 1 interactor
IntActiQ62232, 1 interactor
STRINGi10090.ENSMUSP00000024947

Structurei

3D structure databases

ProteinModelPortaliQ62232
SMRiQ62232
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
InParanoidiQ62232
KOiK19472
OMAiASMNGNK
OrthoDBiEOG091G083I
PhylomeDBiQ62232
TreeFamiTF315545

Family and domain databases

CDDicd00086 homeodomain, 1 hit
InterProiView protein in InterPro
IPR009057 Homeobox-like_sf
IPR017970 Homeobox_CS
IPR001356 Homeobox_dom
IPR031701 SIX1_SD
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.

Q62232-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSMLPTFGFT QEQVACVCEV LQQGGNIERL GRFLWSLPAC EHLHKNESVL
60 70 80 90 100
KAKAVVAFHR GNFRELYKIL ESHQFSPHNH AKLQQLWLKA HYIEAEKLRG
110 120 130 140 150
RPLGAVGKYR VRRKFPLPRS IWDGEETSYC FKEKSRSVLR EWYAHNPYPS
160 170 180 190 200
PREKRELAEA TGLTTTQVSN WFKNRRQRDR AAEAKERENS ENSNSSSHNP
210 220 230 240 250
LASSLNGSGK SVLGSSEDEK TPSGTPDHSS SSPALLLSPP PPPGLPSLHS
260 270 280 290
LGHPPGPSAV PVPVPGGGGA DPLQHHHSLQ DSILNPMSAN LVDLGS
Length:296
Mass (Da):32,718
Last modified:July 15, 1998 - v2
Checksum:i0FFAB002014D8E60
GO

Sequence cautioni

The sequence CAA56584 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1 – 6MSMLPT → HVHARH in CAA56584 (PubMed:7720577).Curated6
Sequence conflicti105A → R in CAA56584 (PubMed:7720577).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X80338 mRNA Translation: CAA56584.1 Different initiation.
D83147 mRNA Translation: BAA11825.1
BC068021 mRNA Translation: AAH68021.1
CCDSiCCDS29007.1
PIRiS74253
RefSeqiNP_035510.1, NM_011380.2
UniGeneiMm.5039

Genome annotation databases

EnsembliENSMUST00000024947; ENSMUSP00000024947; ENSMUSG00000024134
ENSMUST00000163568; ENSMUSP00000125871; ENSMUSG00000024134
GeneIDi20472
KEGGimmu:20472
UCSCiuc008duc.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X80338 mRNA Translation: CAA56584.1 Different initiation.
D83147 mRNA Translation: BAA11825.1
BC068021 mRNA Translation: AAH68021.1
CCDSiCCDS29007.1
PIRiS74253
RefSeqiNP_035510.1, NM_011380.2
UniGeneiMm.5039

3D structure databases

ProteinModelPortaliQ62232
SMRiQ62232
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi203260, 1 interactor
IntActiQ62232, 1 interactor
STRINGi10090.ENSMUSP00000024947

PTM databases

PhosphoSitePlusiQ62232

Proteomic databases

PaxDbiQ62232
PRIDEiQ62232

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000024947; ENSMUSP00000024947; ENSMUSG00000024134
ENSMUST00000163568; ENSMUSP00000125871; ENSMUSG00000024134
GeneIDi20472
KEGGimmu:20472
UCSCiuc008duc.2 mouse

Organism-specific databases

CTDi10736
MGIiMGI:102778 Six2

Phylogenomic databases

eggNOGiKOG0775 Eukaryota
ENOG410XRPB LUCA
GeneTreeiENSGT00540000070251
HOGENOMiHOG000261680
HOVERGENiHBG003609
InParanoidiQ62232
KOiK19472
OMAiASMNGNK
OrthoDBiEOG091G083I
PhylomeDBiQ62232
TreeFamiTF315545

Miscellaneous databases

PROiPR:Q62232
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000024134 Expressed in 176 organ(s), highest expression level in pharyngeal arch 1
GenevisibleiQ62232 MM

Family and domain databases

CDDicd00086 homeodomain, 1 hit
InterProiView protein in InterPro
IPR009057 Homeobox-like_sf
IPR017970 Homeobox_CS
IPR001356 Homeobox_dom
IPR031701 SIX1_SD
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 nameiSIX2_MOUSE
AccessioniPrimary (citable) accession number: Q62232
Secondary accession number(s): P70179
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 15, 1998
Last modified: November 7, 2018
This is version 139 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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