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Protein

Homeobox protein SIX5

Gene

SIX5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Transcription factor that is thought to be involved in regulation of organogenesis. May be involved in determination and maintenance of retina formation. Binds a 5'-GGTGTCAG-3' motif present in the ARE regulatory element of ATP1A1. Binds a 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 element in the myogenin promoter, and in the IGFBP5 promoter (By similarity). Thought to be regulated by association with Dach and Eya proteins, and seems to be coactivated by EYA1, EYA2 and EYA3 (By similarity).By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi201 – 260HomeoboxPROSITE-ProRule annotationAdd BLAST60

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, Developmental protein, DNA-binding
Biological processTranscription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Homeobox protein SIX5
Alternative name(s):
DM locus-associated homeodomain protein
Sine oculis homeobox homolog 5
Gene namesi
Name:SIX5
Synonyms:DMAHP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000177045.7
HGNCiHGNC:10891 SIX5
MIMi600963 gene
neXtProtiNX_Q8N196

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

Involvement in diseasei

Branchiootorenal syndrome 2 (BOR2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by branchial cleft fistulas or cysts, sensorineural and/or conductive hearing loss, pre-auricular pits, structural defects of the outer, middle or inner ear, and renal malformations.
See also OMIM:610896
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_032941158A → T in BOR2; affects Eya1 binding and the ability to activate gene transcription. 1 PublicationCorresponds to variant dbSNP:rs80356461EnsemblClinVar.1
Natural variantiVAR_032942296A → T in BOR2. 1 PublicationCorresponds to variant dbSNP:rs80356462EnsemblClinVar.1
Natural variantiVAR_032943365G → R in BOR2. 1 PublicationCorresponds to variant dbSNP:rs80356463EnsemblClinVar.1
Natural variantiVAR_032944552T → M in BOR2; affects Eya1 binding and the ability to activate gene transcription. 1 PublicationCorresponds to variant dbSNP:rs80356464EnsemblClinVar.1

Keywords - Diseasei

Deafness, Disease mutation

Organism-specific databases

DisGeNETi147912
GeneReviewsiSIX5
MalaCardsiSIX5
MIMi610896 phenotype
OpenTargetsiENSG00000177045
Orphaneti107 BOR syndrome
PharmGKBiPA35791

Polymorphism and mutation databases

BioMutaiSIX5
DMDMi150421671

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000493051 – 739Homeobox protein SIX5Add BLAST739

Proteomic databases

EPDiQ8N196
MaxQBiQ8N196
PaxDbiQ8N196
PeptideAtlasiQ8N196
PRIDEiQ8N196
ProteomicsDBi71575

PTM databases

iPTMnetiQ8N196
PhosphoSitePlusiQ8N196

Expressioni

Tissue specificityi

Expressed in adult but not in fetal eyes. Found in corneal epithelium and endothelium, lens epithelium, ciliary body epithelia, cellular layers of the retina and the sclera.1 Publication

Developmental stagei

At the begin of fourth week of development detected in cytoplasm of somite cells, and at the end of fourth week is accumulated in the nucleus. Between the sixth and eighth week of development detected in the nucleus of limb bud cells.1 Publication

Gene expression databases

BgeeiENSG00000177045
CleanExiHS_SIX5
ExpressionAtlasiQ8N196 baseline and differential
GenevisibleiQ8N196 HS

Organism-specific databases

HPAiHPA042068

Interactioni

Subunit structurei

Probably binds DNA dimer. Interacts with EYA3, and probably EYA1 and EYA2 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
ATXN1P542534EBI-946167,EBI-930964

Protein-protein interaction databases

BioGridi127096, 6 interactors
IntActiQ8N196, 6 interactors
MINTiQ8N196
STRINGi9606.ENSP00000316842

Structurei

3D structure databases

ProteinModelPortaliQ8N196
SMRiQ8N196
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
HOGENOMiHOG000154329
HOVERGENiHBG050139
InParanoidiQ8N196
KOiK19474
OMAiNGGPVII
OrthoDBiEOG091G06MV
PhylomeDBiQ8N196
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.

Q8N196-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATLPAEPSA GPAAGGEAVA AAAATEEEEE EARQLLQTLQ AAEGEAAAAA
60 70 80 90 100
GAGAGAAAAG AEGPGSPGVP GSPPEAASEP PTGLRFSPEQ VACVCEALLQ
110 120 130 140 150
AGHAGRLSRF LGALPPAERL RGSDPVLRAR ALVAFQRGEY AELYRLLESR
160 170 180 190 200
PFPAAHHAFL QDLYLRARYH EAERARGRAL GAVDKYRLRK KFPLPKTIWD
210 220 230 240 250
GEETVYCFKE RSRAALKACY RGNRYPTPDE KRRLATLTGL SLTQVSNWFK
260 270 280 290 300
NRRQRDRTGA GGGAPCKSES DGNPTTEDES SRSPEDLERG AAPVSAEAAA
310 320 330 340 350
QGSIFLAGTG PPAPCPASSS ILVNGSFLAA SGSPAVLLNG GPVIINGLAL
360 370 380 390 400
GEASSLGPLL LTGGGGAPPP QPSPQGASET KTSLVLDPQT GEVRLEEAQS
410 420 430 440 450
EAPETKGAQV AAPGPALGEE VLGPLAQVVP GPPTAATFPL PPGPVPAVAA
460 470 480 490 500
PQVVPLSPPP GYPTGLSPTS PLLNLPQVVP TSQVVTLPQA VGPLQLLAAG
510 520 530 540 550
PGSPVKVAAA AGPANVHLIN SGVGVTALQL PSATAPGNFL LANPVSGSPI
560 570 580 590 600
VTGVALQQGK IILTATFPTS MLVSQVLPPA PGLALPLKPE TAISVPEGGL
610 620 630 640 650
PVAPSPALPE AHALGTLSAQ QPPPAAATTS STSLPFSPDS PGLLPNFPAP
660 670 680 690 700
PPEGLMLSPA AVPVWSAGLE LSAGTEGLLE AEKGLGTQAP HTVLRLPDPD
710 720 730
PEGLLLGATA GGEVDEGLEA EAKVLTQLQS VPVEEPLEL
Length:739
Mass (Da):74,562
Last modified:June 26, 2007 - v3
Checksum:iD8A2E8DBBBA263A2
GO

Sequence cautioni

The sequence AAH33204 differs from that shown. Aberrant splicing.Curated
The sequence AK074826 differs from that shown. Reason: Erroneous termination at position 721. Translated as Glu.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_032941158A → T in BOR2; affects Eya1 binding and the ability to activate gene transcription. 1 PublicationCorresponds to variant dbSNP:rs80356461EnsemblClinVar.1
Natural variantiVAR_032942296A → T in BOR2. 1 PublicationCorresponds to variant dbSNP:rs80356462EnsemblClinVar.1
Natural variantiVAR_032943365G → R in BOR2. 1 PublicationCorresponds to variant dbSNP:rs80356463EnsemblClinVar.1
Natural variantiVAR_032944552T → M in BOR2; affects Eya1 binding and the ability to activate gene transcription. 1 PublicationCorresponds to variant dbSNP:rs80356464EnsemblClinVar.1
Natural variantiVAR_032945556L → V. Corresponds to variant dbSNP:rs2014377Ensembl.1
Natural variantiVAR_032946635P → S. Corresponds to variant dbSNP:rs2014576EnsemblClinVar.1
Natural variantiVAR_032947693V → M. Corresponds to variant dbSNP:rs2341097EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X84813 Genomic DNA No translation available.
AC074212 Genomic DNA No translation available.
BC033204 mRNA Translation: AAH33204.1 Sequence problems.
BU859227 mRNA No translation available.
AK074826 mRNA No translation available.
CCDSiCCDS12673.1
RefSeqiNP_787071.2, NM_175875.4
UniGeneiHs.43314

Genome annotation databases

EnsembliENST00000317578; ENSP00000316842; ENSG00000177045
ENST00000643139; ENSP00000494267; ENSG00000177045
GeneIDi147912
KEGGihsa:147912
UCSCiuc002pdb.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSIX5_HUMAN
AccessioniPrimary (citable) accession number: Q8N196
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: June 26, 2007
Last modified: June 20, 2018
This is version 143 of the entry and version 3 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

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