UniProtKB - Q8N196 (SIX5_HUMAN)
Homeobox protein SIX5
SIX5
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 similarityRegions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 201 – 260 | HomeoboxPROSITE-ProRule annotationAdd BLAST | 60 |
GO - Molecular functioni
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: Ensembl
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: GO_Central
GO - Biological processi
- lens development in camera-type eye Source: Ensembl
- negative regulation of skeletal muscle satellite cell proliferation Source: Ensembl
- negative regulation of transcription, DNA-templated Source: Ensembl
- regulation of transcription by RNA polymerase II Source: GO_Central
- spermatid development Source: Ensembl
Keywordsi
Molecular function | Activator, Developmental protein, DNA-binding |
Biological process | Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | Q8N196 |
SignaLinki | Q8N196 |
Names & Taxonomyi
Protein namesi | Recommended name: Homeobox protein SIX5Alternative name(s): DM locus-associated homeodomain protein Sine oculis homeobox homolog 5 |
Gene namesi | Name:SIX5 Synonyms:DMAHP |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:10891, SIX5 |
MIMi | 600963, gene |
neXtProti | NX_Q8N196 |
VEuPathDBi | HostDB:ENSG00000177045 |
Subcellular locationi
Nucleus
- nucleus Source: GO_Central
Other locations
- chromatin Source: NTNU_SB
- cytoplasm Source: UniProtKB-SubCell
- transcription regulator complex Source: GO_Central
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Involvement in diseasei
Branchiootorenal syndrome 2 (BOR2)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_032941 | 158 | A → T in BOR2; affects Eya1 binding and the ability to activate gene transcription. 1 PublicationCorresponds to variant dbSNP:rs80356461EnsemblClinVar. | 1 | |
Natural variantiVAR_032942 | 296 | A → T in BOR2. 1 PublicationCorresponds to variant dbSNP:rs80356462EnsemblClinVar. | 1 | |
Natural variantiVAR_032943 | 365 | G → R in BOR2. 1 PublicationCorresponds to variant dbSNP:rs80356463EnsemblClinVar. | 1 | |
Natural variantiVAR_032944 | 552 | T → M in BOR2; affects Eya1 binding and the ability to activate gene transcription. 1 PublicationCorresponds to variant dbSNP:rs80356464EnsemblClinVar. | 1 |
Keywords - Diseasei
Deafness, Disease variantOrganism-specific databases
DisGeNETi | 147912 |
GeneReviewsi | SIX5 |
MalaCardsi | SIX5 |
MIMi | 610896, phenotype |
OpenTargetsi | ENSG00000177045 |
Orphaneti | 107, BOR syndrome |
PharmGKBi | PA35791 |
Miscellaneous databases
Pharosi | Q8N196, Tbio |
Genetic variation databases
BioMutai | SIX5 |
DMDMi | 150421671 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000049305 | 1 – 739 | Homeobox protein SIX5Add BLAST | 739 |
Proteomic databases
EPDi | Q8N196 |
jPOSTi | Q8N196 |
MassIVEi | Q8N196 |
MaxQBi | Q8N196 |
PaxDbi | Q8N196 |
PeptideAtlasi | Q8N196 |
PRIDEi | Q8N196 |
ProteomicsDBi | 71575 |
PTM databases
GlyGeni | Q8N196, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q8N196 |
PhosphoSitePlusi | Q8N196 |
Expressioni
Tissue specificityi
Developmental stagei
Gene expression databases
Bgeei | ENSG00000177045, Expressed in muscle tissue and 187 other tissues |
ExpressionAtlasi | Q8N196, baseline and differential |
Genevisiblei | Q8N196, HS |
Organism-specific databases
HPAi | ENSG00000177045, Low tissue specificity |
Interactioni
Subunit structurei
Probably binds DNA dimer.
Interacts with EYA3, and probably EYA1 and EYA2 (By similarity).
By similarityBinary interactionsi
Q8N196
With | #Exp. | IntAct |
---|---|---|
ATXN1 [P54253] | 4 | EBI-946167,EBI-930964 |
Protein-protein interaction databases
BioGRIDi | 127096, 73 interactors |
IntActi | Q8N196, 13 interactors |
MINTi | Q8N196 |
STRINGi | 9606.ENSP00000316842 |
Miscellaneous databases
RNActi | Q8N196, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 84 | DisorderedSequence analysisAdd BLAST | 84 | |
Regioni | 251 – 294 | DisorderedSequence analysisAdd BLAST | 44 | |
Regioni | 361 – 381 | DisorderedSequence analysisAdd BLAST | 21 | |
Regioni | 617 – 650 | DisorderedSequence analysisAdd BLAST | 34 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 272 – 286 | Basic and acidic residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 621 – 639 | Polar residuesSequence analysisAdd BLAST | 19 |
Sequence similaritiesi
Keywords - Domaini
HomeoboxPhylogenomic databases
eggNOGi | KOG0775, Eukaryota |
GeneTreei | ENSGT00940000162237 |
HOGENOMi | CLU_022250_0_0_1 |
InParanoidi | Q8N196 |
OMAi | AAMPIWP |
OrthoDBi | 1061244at2759 |
PhylomeDBi | Q8N196 |
TreeFami | TF315545 |
Family and domain databases
CDDi | cd00086, homeodomain, 1 hit |
InterProi | View protein in InterPro IPR009057, Homeobox-like_sf IPR017970, Homeobox_CS IPR001356, Homeobox_dom IPR031701, SIX1_SD |
Pfami | View protein in Pfam PF00046, Homeodomain, 1 hit PF16878, SIX1_SD, 1 hit |
SMARTi | View protein in SMART SM00389, HOX, 1 hit |
SUPFAMi | SSF46689, SSF46689, 1 hit |
PROSITEi | View protein in PROSITE PS00027, HOMEOBOX_1, 1 hit PS50071, HOMEOBOX_2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH0YLK1 | H0YLK1_HUMAN | Homeobox protein SIX5 | SIX5 | 255 | Annotation score: | ||
H0YLF6 | H0YLF6_HUMAN | Homeobox protein SIX5 | SIX5 | 69 | Annotation score: |
Sequence cautioni
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_032941 | 158 | A → T in BOR2; affects Eya1 binding and the ability to activate gene transcription. 1 PublicationCorresponds to variant dbSNP:rs80356461EnsemblClinVar. | 1 | |
Natural variantiVAR_032942 | 296 | A → T in BOR2. 1 PublicationCorresponds to variant dbSNP:rs80356462EnsemblClinVar. | 1 | |
Natural variantiVAR_032943 | 365 | G → R in BOR2. 1 PublicationCorresponds to variant dbSNP:rs80356463EnsemblClinVar. | 1 | |
Natural variantiVAR_032944 | 552 | T → M in BOR2; affects Eya1 binding and the ability to activate gene transcription. 1 PublicationCorresponds to variant dbSNP:rs80356464EnsemblClinVar. | 1 | |
Natural variantiVAR_032945 | 556 | L → V. Corresponds to variant dbSNP:rs2014377Ensembl. | 1 | |
Natural variantiVAR_032946 | 635 | P → S. Corresponds to variant dbSNP:rs2014576EnsemblClinVar. | 1 | |
Natural variantiVAR_032947 | 693 | V → 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. |
CCDSi | CCDS12673.1 |
RefSeqi | NP_787071.2, NM_175875.4 |
Genome annotation databases
Ensembli | ENST00000317578.7; ENSP00000316842.4; ENSG00000177045.11 |
GeneIDi | 147912 |
KEGGi | hsa:147912 |
MANE-Selecti | ENST00000317578.7; ENSP00000316842.4; NM_175875.5; NP_787071.3 |
UCSCi | uc002pdb.4, human |
Similar proteinsi
Cross-referencesi
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. |
CCDSi | CCDS12673.1 |
RefSeqi | NP_787071.2, NM_175875.4 |
3D structure databases
AlphaFoldDBi | Q8N196 |
SMRi | Q8N196 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 127096, 73 interactors |
IntActi | Q8N196, 13 interactors |
MINTi | Q8N196 |
STRINGi | 9606.ENSP00000316842 |
PTM databases
GlyGeni | Q8N196, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q8N196 |
PhosphoSitePlusi | Q8N196 |
Genetic variation databases
BioMutai | SIX5 |
DMDMi | 150421671 |
Proteomic databases
EPDi | Q8N196 |
jPOSTi | Q8N196 |
MassIVEi | Q8N196 |
MaxQBi | Q8N196 |
PaxDbi | Q8N196 |
PeptideAtlasi | Q8N196 |
PRIDEi | Q8N196 |
ProteomicsDBi | 71575 |
Protocols and materials databases
Antibodypediai | 31386, 186 antibodies from 28 providers |
DNASUi | 147912 |
Genome annotation databases
Ensembli | ENST00000317578.7; ENSP00000316842.4; ENSG00000177045.11 |
GeneIDi | 147912 |
KEGGi | hsa:147912 |
MANE-Selecti | ENST00000317578.7; ENSP00000316842.4; NM_175875.5; NP_787071.3 |
UCSCi | uc002pdb.4, human |
Organism-specific databases
CTDi | 147912 |
DisGeNETi | 147912 |
GeneCardsi | SIX5 |
GeneReviewsi | SIX5 |
HGNCi | HGNC:10891, SIX5 |
HPAi | ENSG00000177045, Low tissue specificity |
MalaCardsi | SIX5 |
MIMi | 600963, gene 610896, phenotype |
neXtProti | NX_Q8N196 |
OpenTargetsi | ENSG00000177045 |
Orphaneti | 107, BOR syndrome |
PharmGKBi | PA35791 |
VEuPathDBi | HostDB:ENSG00000177045 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0775, Eukaryota |
GeneTreei | ENSGT00940000162237 |
HOGENOMi | CLU_022250_0_0_1 |
InParanoidi | Q8N196 |
OMAi | AAMPIWP |
OrthoDBi | 1061244at2759 |
PhylomeDBi | Q8N196 |
TreeFami | TF315545 |
Enzyme and pathway databases
PathwayCommonsi | Q8N196 |
SignaLinki | Q8N196 |
Miscellaneous databases
BioGRID-ORCSi | 147912, 18 hits in 1097 CRISPR screens |
GeneWikii | SIX5 |
GenomeRNAii | 147912 |
Pharosi | Q8N196, Tbio |
PROi | PR:Q8N196 |
RNActi | Q8N196, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000177045, Expressed in muscle tissue and 187 other tissues |
ExpressionAtlasi | Q8N196, baseline and differential |
Genevisiblei | Q8N196, HS |
Family and domain databases
CDDi | cd00086, homeodomain, 1 hit |
InterProi | View protein in InterPro IPR009057, Homeobox-like_sf IPR017970, Homeobox_CS IPR001356, Homeobox_dom IPR031701, SIX1_SD |
Pfami | View protein in Pfam PF00046, Homeodomain, 1 hit PF16878, SIX1_SD, 1 hit |
SMARTi | View protein in SMART SM00389, HOX, 1 hit |
SUPFAMi | SSF46689, SSF46689, 1 hit |
PROSITEi | View protein in PROSITE PS00027, HOMEOBOX_1, 1 hit PS50071, HOMEOBOX_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | SIX5_HUMAN | |
Accessioni | Q8N196Primary (citable) accession number: Q8N196 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 13, 2004 |
Last sequence update: | June 26, 2007 | |
Last modified: | May 25, 2022 | |
This is version 165 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families