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 similarity

Regions

Feature key	Position(s)	DescriptionActions	Graphical view	Length
DNA bindingⁱ	201 – 260	HomeoboxPROSITE-ProRule annotationAdd BLAST		60

GO - Molecular functionⁱ

RNA polymerase II proximal promoter sequence-specific DNA binding Source: Ensembl
RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: NTNU_SB

View the complete GO annotation on QuickGO ...

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
positive regulation of transcription by RNA polymerase II Source: Ensembl
spermatid development Source: Ensembl
transcription, DNA-templated Source: UniProtKB-KW

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Activator, Developmental protein, DNA-binding
Biological process	Transcription, 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
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 19

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000177045.7
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:10891 SIX5
MIMⁱ	600963 gene
neXtProtⁱ	NX_Q8N196

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.

Keywords - Diseaseⁱ

Deafness, Disease mutation

Organism-specific databases

DisGeNET More...DisGeNETⁱ	147912
GeneReviewsⁱ	SIX5
MalaCards human disease database More...MalaCardsⁱ	SIX5
MIMⁱ	610896 phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000177045
Orphanetⁱ	107 BOR syndrome
PharmGKBⁱ	PA35791

Polymorphism and mutation 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
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q8N196
PaxDbⁱ	Q8N196
PeptideAtlas More...PeptideAtlasⁱ	Q8N196
PRIDEⁱ	Q8N196
ProteomicsDBⁱ	71575

PTM databases

iPTMnetⁱ	Q8N196
PhosphoSitePlusⁱ	Q8N196

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

Bgeeⁱ	ENSG00000177045
CleanExⁱ	HS_SIX5
ExpressionAtlasⁱ	Q8N196 baseline and differential
Genevisibleⁱ	Q8N196 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	HPA042068

HPAⁱ

HPA042068

Interactionⁱ

Subunit structureⁱ

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

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
ATXN1	P54253	4	EBI-946167,EBI-930964

With

Entry

#Exp.

IntAct

Notes

ATXN1

P54253

4

EBI-946167,EBI-930964

Protein-protein interaction databases

BioGridⁱ	127096, 6 interactors
IntActⁱ	Q8N196, 6 interactors
Molecular INTeraction database More...MINTⁱ	Q8N196
STRINGⁱ	9606.ENSP00000316842

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q8N196
SMRⁱ	Q8N196
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Sequence similaritiesⁱ

Belongs to the SIX/Sine oculis homeobox family.Curated

Keywords - Domainⁱ

Homeobox

Phylogenomic databases

eggNOGⁱ	KOG0775 Eukaryota ENOG410XRPB LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00540000070251
HOGENOMⁱ	HOG000154329
HOVERGENⁱ	HBG050139
InParanoidⁱ	Q8N196
KEGG Orthology (KO) More...KOⁱ	K19474
OMAⁱ	NGGPVII
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G06MV
PhylomeDBⁱ	Q8N196
TreeFamⁱ	TF315545

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00086 homeodomain, 1 hit
InterProⁱ	View protein in InterPro IPR009057 Homeobox-like_sf IPR017970 Homeobox_CS IPR001356 Homeobox_dom IPR031701 SIX1_SD
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00046 Homeobox, 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

Sequenceⁱ

Sequence statusⁱ: Complete.

Q8N196-1 [UniParc]FASTA Add 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 key	Position(s)	DescriptionActions	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.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS12673.1
NCBI Reference Sequences More...RefSeqⁱ	NP_787071.2, NM_175875.4
UniGeneⁱ	Hs.43314

Genome annotation databases

Ensemblⁱ	ENST00000317578; ENSP00000316842; ENSG00000177045 ENST00000643139; ENSP00000494267; ENSG00000177045
GeneIDⁱ	147912
KEGGⁱ	hsa:147912
UCSC genome browser More...UCSCⁱ	uc002pdb.4 human

Keywords - Coding sequence diversityⁱ

Polymorphism

Similar proteinsⁱ

90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length
Q8N196	SIX homeobox 5		RHIRO		815
Homeobox protein SIX5 (Fragment)		MACMU		93
SIX homeobox 5		PAPAN		741
SIX homeobox 5		MACFA		740
SIX homeobox 5		RHIBE		740
+13

Protein	Similar proteins		Species	Score	Length
Q8N196	SIX homeobox 5		RHIRO		815
Homeobox protein SIX5 (Fragment)		MACMU		93
SIX homeobox 5		PAPAN		741
SIX homeobox 5		MACFA		740
SIX homeobox 5		RHIBE		740
+38

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.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS12673.1
NCBI Reference Sequences More...RefSeqⁱ	NP_787071.2, NM_175875.4
UniGeneⁱ	Hs.43314

3D structure databases

ProteinModelPortalⁱ	Q8N196
SMRⁱ	Q8N196
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	127096, 6 interactors
IntActⁱ	Q8N196, 6 interactors
Molecular INTeraction database More...MINTⁱ	Q8N196
STRINGⁱ	9606.ENSP00000316842

PTM databases

iPTMnetⁱ	Q8N196
PhosphoSitePlusⁱ	Q8N196

Polymorphism and mutation databases

BioMutaⁱ	SIX5
DMDMⁱ	150421671

Proteomic databases

EPDⁱ	Q8N196
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q8N196
PaxDbⁱ	Q8N196
PeptideAtlas More...PeptideAtlasⁱ	Q8N196
PRIDEⁱ	Q8N196
ProteomicsDBⁱ	71575

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	147912
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000317578; ENSP00000316842; ENSG00000177045 ENST00000643139; ENSP00000494267; ENSG00000177045
GeneIDⁱ	147912
KEGGⁱ	hsa:147912
UCSC genome browser More...UCSCⁱ	uc002pdb.4 human

Organism-specific databases

CTDⁱ	147912
DisGeNET More...DisGeNETⁱ	147912
EuPathDBⁱ	HostDB:ENSG00000177045.7
GeneCardsⁱ	SIX5
GeneReviewsⁱ	SIX5
H-InvDBⁱ	HIX0202857
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:10891 SIX5
Human Protein Atlas More...HPAⁱ	HPA042068
MalaCards human disease database More...MalaCardsⁱ	SIX5
MIMⁱ	600963 gene 610896 phenotype
neXtProtⁱ	NX_Q8N196
Open Targets More...OpenTargetsⁱ	ENSG00000177045
Orphanetⁱ	107 BOR syndrome
PharmGKBⁱ	PA35791
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG0775 Eukaryota ENOG410XRPB LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00540000070251
HOGENOMⁱ	HOG000154329
HOVERGENⁱ	HBG050139
InParanoidⁱ	Q8N196
KEGG Orthology (KO) More...KOⁱ	K19474
OMAⁱ	NGGPVII
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G06MV
PhylomeDBⁱ	Q8N196
TreeFamⁱ	TF315545

Miscellaneous databases

ChiTaRSⁱ	SIX5 human
GeneWikiⁱ	SIX5
GenomeRNAiⁱ	147912
Protein Ontology More...PROⁱ	PR:Q8N196
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000177045
CleanExⁱ	HS_SIX5
ExpressionAtlasⁱ	Q8N196 baseline and differential
Genevisibleⁱ	Q8N196 HS

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00086 homeodomain, 1 hit
InterProⁱ	View protein in InterPro IPR009057 Homeobox-like_sf IPR017970 Homeobox_CS IPR001356 Homeobox_dom IPR031701 SIX1_SD
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00046 Homeobox, 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
ProtoNetⁱ	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:	June 20, 2018
	This is version 143 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

Complete proteome, Reference proteome

Documents

Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
SIMILARITY comments
Index of protein domains and families

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UniProtKB - Q8N196 (SIX5_HUMAN)

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Homeobox protein SIX5

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Biological processi

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Nucleus

Other locations

Nucleus

Other locations

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Organism-specific databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

Natural variant

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Sequence cautionⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ