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Protein

Homeobox protein SIX2

Gene

SIX2

Organism
Homo sapiens (Human)
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. During stomach organogenesis, controls pyloric sphincter formation and mucosal growth through regulation of a gene network including NKX2-5, BMPR1B, BMP4, SOX9 and GREM1. During branchial arch development, acts to mediate HOXA2 control over the insulin-like growth factor pathway. Also may be involved in limb tendon and ligament development (By similarity). Plays a role in cell proliferation and migration.By similarity1 Publication

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000170577.7
HGNCiHGNC:10888 SIX2
MIMi604994 gene
neXtProtiNX_Q9NPC8

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

Organism-specific databases

DisGeNETi10736
MalaCardsiSIX2
OpenTargetsiENSG00000170577
PharmGKBiPA35788

Polymorphism and mutation databases

BioMutaiSIX2
DMDMi12230598

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000492971 – 291Homeobox protein SIX2Add BLAST291

Proteomic databases

EPDiQ9NPC8
MaxQBiQ9NPC8
PaxDbiQ9NPC8
PeptideAtlasiQ9NPC8
PRIDEiQ9NPC8
ProteomicsDBi81972

PTM databases

iPTMnetiQ9NPC8
PhosphoSitePlusiQ9NPC8

Expressioni

Tissue specificityi

Strongly expressed in skeletal muscle. Expressed in Wilms' tumor and in the cap mesenchyme of fetal kidney (at protein level).1 Publication

Developmental stagei

Found at 48 dpc in the anterior cranial base with detection concentrated in the sphenoid precursor. Expression is also detected in the pituitary gland.1 Publication

Gene expression databases

BgeeiENSG00000170577
CleanExiHS_SIX2
GenevisibleiQ9NPC8 HS

Organism-specific databases

HPAiHPA056958

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.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115959, 22 interactors
IntActiQ9NPC8, 2 interactors
STRINGi9606.ENSP00000304502

Structurei

3D structure databases

ProteinModelPortaliQ9NPC8
SMRiQ9NPC8
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
InParanoidiQ9NPC8
KOiK19472
OMAiHSLHHET
OrthoDBiEOG091G083I
PhylomeDBiQ9NPC8
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.

Q9NPC8-1 [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 AAEAKERENN ENSNSNSHNP
210 220 230 240 250
LNGSGKSVLG SSEDEKTPSG TPDHSSSSPA LLLSPPPPGL PSLHSLGHPP
260 270 280 290
GPSAVPVPVP GGGGADPLQH HHGLQDSILN PMSANLVDLG S
Length:291
Mass (Da):32,286
Last modified:October 1, 2000 - v1
Checksum:i8388C3C331575BDD
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07120743L → F in a renal hypodysplasia patient. 1 PublicationCorresponds to variant dbSNP:rs142188105Ensembl.1
Natural variantiVAR_071208241P → L in a renal hypodysplasia patient. 1 PublicationCorresponds to variant dbSNP:rs147806994Ensembl.1
Natural variantiVAR_071209276D → N in a renal hypodysplasia patient. 1 PublicationCorresponds to variant dbSNP:rs201675842Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF136939 Genomic DNA Translation: AAF69031.1
AF136940 mRNA Translation: AAF69032.1
AF332196 mRNA Translation: AAK16581.1
AF332197 mRNA Translation: AAK16582.1
AF332198 Genomic DNA Translation: AAK16583.1
AF323498 Genomic DNA Translation: AAK06773.1
BT020100 mRNA Translation: AAV38903.1
CCDSiCCDS1822.1
RefSeqiNP_058628.3, NM_016932.4
UniGeneiHs.101937

Genome annotation databases

EnsembliENST00000303077; ENSP00000304502; ENSG00000170577
GeneIDi10736
KEGGihsa:10736
UCSCiuc002ruo.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSIX2_HUMAN
AccessioniPrimary (citable) accession number: Q9NPC8
Secondary accession number(s): Q9BXH7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: October 1, 2000
Last modified: July 18, 2018
This is version 141 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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