CleftGeneDB-Search

Gene: SIX1

Basic information

Tag	Content
Uniprot ID	Q15475; Q53Y16; Q96H64;
Entrez ID	6495
Genbank protein ID	AAH08874.1; CAA62974.1; AAP35746.1; AAK06772.1;
Genbank nucleotide ID	NM_005982.3
Ensembl protein ID	ENSP00000494686
Ensembl nucleotide ID	ENSG00000126778
Gene name	Homeobox protein SIX1
Gene symbol	SIX1
Organism	Homo sapiens
NCBI taxa ID	9606
Cleft type
Developmental stage
Data sources	Homology search
Reference
Functional description	Transcription factor that is involved in the regulation of cell proliferation, apoptosis and embryonic development (By similarity). Plays an important role in the development of several organs, including kidney, muscle and inner ear (By similarity). Depending on context, functions as transcriptional repressor or activator (By similarity). Lacks an activation domain, and requires interaction with EYA family members for transcription activation (PubMed:15141091). Mediates nuclear translocation of EYA1 and EYA2 (PubMed:19497856). Binds the 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 element in the MYOG promoter and CIDEA enhancer (PubMed:27923061, PubMed:23435380, PubMed:15141091, PubMed:19497856). Regulates the expression of numerous genes, including MYC, CCND1 and EZR (By similarity). Acts as activator of the IGFBP5 promoter, probably coactivated by EYA2 (By similarity). Repression of precursor cell proliferation in myoblasts is switched to activation through recruitment of EYA3 to the SIX1-DACH1 complex (By similarity). During myogenesis, seems to act together with EYA2 and DACH2 (By similarity). Regulates the expression of CCNA1 (PubMed:15123840). Promotes brown adipocyte differentiation (By similarity).
Sequence	MSMLPSFGFT QEQVACVCEV LQQGGNLERL GRFLWSLPAC DHLHKNESVL KAKAVVAFHR 60 GNFRELYKIL ESHQFSPHNH PKLQQLWLKA HYVEAEKLRG RPLGAVGKYR VRRKFPLPRT 120 IWDGEETSYC FKEKSRGVLR EWYAHNPYPS PREKRELAEA TGLTTTQVSN WFKNRRQRDR 180 AAEAKERENT ENNNSSSNKQ NQLSPLEGGK PLMSSSEEEF SPPQSPDQNS VLLLQGNMGH 240 ARSSNYSLPG LTASQPSHGL QTHQHQLQDS LLGPLTSSLV DLGS 284

Abbreviation :
CLO : cleft lip only. CPO : cleft palate only. CLP : cleft lip and palate. CL/P : cleft lip with/without cleft palate.
For humans: CL/P, CLO, CPO, and CLP. For mice: CLO, CLP, and CPO.

Gene expression information

Gene expression in different tissues (GTEx V7)

Gene expression in different tissues (ENCODE)

Protein structural annotations

3D structure in PDB database

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PDB ID
4EGC

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Protein disorder information

Orthologous information

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Relation	Gene symbol	Entrez ID	UniProt ID	Cleft type	Species	Evidence	Details
1:1 ortholog	Six1	20471	Q62231	CPO	Mus musculus	Publication	More>>
1:1 ortholog	SIX1		Q08DI4		Bos taurus	Prediction	More>>
1:1 ortholog	SIX1	490719	J9P3S7		Canis lupus familiaris	Prediction	More>>
1:1 ortholog	SIX1	106502564	A0A452G009		Capra hircus	Prediction	More>>
1:1 ortholog	SIX1	6495	Q15475		Homo sapiens	Prediction	More>>
1:1 ortholog	SIX1	452952	H2Q8E8		Pan troglodytes	Prediction	More>>
1:1 ortholog	SIX1	100156847	E5DCJ4		Sus scrofa	Prediction	More>>
1:1 ortholog	SIX1	100349440	G1T717		Oryctolagus cuniculus	Prediction	More>>
1:1 ortholog	Six1	114634	G3V970		Rattus norvegicus	Prediction	More>>

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Other genetic variants/mutations

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ID	Variant	Type	Disease	Chromosome\Coordinate	Evidence
rs397515562	p.Val17Glu	missense variant	Branchiootic syndrome 3 (BOS3)	NC_000014.9:g.60649140A>T	UniProt,dbSNP
rs17850414	p.Arg99Cys	missense variant	-	NC_000014.9:g.60648895G>A	UniProt,dbSNP
rs397515560	p.Val106Gly	missense variant	Branchiootic syndrome 3 (BOS3)	NC_000014.9:g.60648873A>C	UniProt,dbSNP
rs1064794308	p.Arg110Gln	missense variant	Branchiootic syndrome 3 (BOS3)	NC_000014.9:g.60648861C>T	UniProt,dbSNP
rs80356459	p.Arg110Trp	missense variant	Branchiootic syndrome 3 (BOS3)	NC_000014.9:g.60648862G>A	UniProt,dbSNP
rs397515561	p.Arg112Cys	missense variant	Branchiootic syndrome 3 (BOS3)	NC_000014.9:g.60648856G>A	UniProt,dbSNP
rs121909770	p.Trp122Arg	missense variant	Branchiootic syndrome 3 (BOS3)	NC_000014.9:g.60648826A>T	UniProt,dbSNP
rs104894478	p.Tyr129Cys	missense variant	Branchiootic syndrome 3 (BOS3)	NC_000014.9:g.60648804T>C	UniProt,dbSNP
rs368974927	p.Pro249Leu	missense variant	-	NC_000014.9:g.60646392G>A	UniProt,dbSNP
VAR_064948	p.Val17Glu	missense variant	Branchiootic syndrome 3 (BOS3)	NC_000014.9:g.60649140A>T	UniProt
VAR_064949	p.His73Pro	Missense	Branchiootic syndrome 3 (BOS3) [MIM:608389]	-	UniProt
VAR_067446	p.Arg99Cys	missense variant	-	NC_000014.9:g.60648895G>A	UniProt
VAR_064950	p.Val106Gly	missense variant	Branchiootic syndrome 3 (BOS3)	NC_000014.9:g.60648873A>C	UniProt
VAR_064951	p.Arg110Gln	missense variant	Branchiootic syndrome 3 (BOS3)	NC_000014.9:g.60648861C>T	UniProt
VAR_031024	p.Arg110Trp	missense variant	Branchiootic syndrome 3 (BOS3)	NC_000014.9:g.60648862G>A	UniProt
VAR_064952	p.Arg112Cys	missense variant	Branchiootic syndrome 3 (BOS3)	NC_000014.9:g.60648856G>A	UniProt
VAR_064953	p.Trp122Arg	missense variant	Branchiootic syndrome 3 (BOS3)	NC_000014.9:g.60648826A>T	UniProt
VAR_031025	p.Tyr129Cys	missense variant	Branchiootic syndrome 3 (BOS3)	NC_000014.9:g.60648804T>C	UniProt
VAR_031026	p.Glu133del	inframe_deletion	Deafness, autosomal dominant, 23 (DFNA23) [MIM:605192]	-	UniProt
VAR_064954	p.Pro249Leu	missense variant	-	NC_000014.9:g.60646392G>A	UniProt

Showing 1 to 20 of 249 entries

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Disease or phenotype associated information

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Disease ID	Disease Name	Disease Type	Source
C0000768	Congenital Abnormality	group	BEFREE;CTD_human
C0001418	Adenocarcinoma	group	BEFREE
C0006131	Branchioma	disease	HPO
C0006142	Malignant neoplasm of breast	disease	BEFREE
C0006272	Bronchiolitis Obliterans	disease	BEFREE
C0006826	Malignant Neoplasms	group	BEFREE
C0007124	Noninfiltrating Intraductal Carcinoma	disease	BEFREE
C0007131	Non-Small Cell Lung Carcinoma	disease	BEFREE
C0007137	Squamous cell carcinoma	disease	BEFREE
C0007847	Malignant tumor of cervix	disease	BEFREE
C0008373	Cholesteatoma	disease	HPO
C0009402	Colorectal Carcinoma	disease	BEFREE
C0010278	Craniosynostosis	disease	GENOMICS_ENGLAND
C0011053	Deafness	phenotype	HPO
C0012236	DiGeorge Syndrome	disease	BEFREE
C0014170	Endometrial Neoplasms	group	CTD_human
C0017601	Glaucoma	disease	BEFREE
C0017612	Glaucoma, Open-Angle	disease	BEFREE
C0017638	Glioma	disease	BEFREE
C0018772	Hearing Loss, Partial	phenotype	HPO

Showing 1 to 20 of 143 entries

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Gene Ontology (GO)/biological pathways

GO:Molecular Function

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GO ID	GO Term	Evidence
GO:0000976	transcription regulatory region sequence-specific DNA binding	IBA
GO:0000978	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA
GO:0000978	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IMP
GO:0000981	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0000981	DNA-binding transcription factor activity, RNA polymerase II-specific	ISM
GO:0000981	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA
GO:0001223	transcription coactivator binding	IEA
GO:0001228	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA
GO:0001228	DNA-binding transcription activator activity, RNA polymerase II-specific	IMP
GO:0003677	DNA binding	IDA
GO:0003682	chromatin binding	IEA
GO:0003700	DNA-binding transcription factor activity	ISS
GO:0003700	DNA-binding transcription factor activity	IDA
GO:0005515	protein binding	IPI
GO:0043565	sequence-specific DNA binding	IDA
GO:0044212	transcription regulatory region DNA binding	IDA

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GO:Biological Process

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GO ID	GO Term	Evidence
GO:0000122	negative regulation of transcription by RNA polymerase II	IEA
GO:0001657	ureteric bud development	ISS
GO:0001658	branching involved in ureteric bud morphogenesis	ISS
GO:0001759	organ induction	ISS
GO:0001822	kidney development	ISS
GO:0003151	outflow tract morphogenesis	IEA
GO:0006355	regulation of transcription, DNA-templated	ISS
GO:0006915	apoptotic process	IEA
GO:0007389	pattern specification process	ISS
GO:0007519	skeletal muscle tissue development	ISS
GO:0007519	skeletal muscle tissue development	IBA
GO:0007605	sensory perception of sound	IEA
GO:0008582	regulation of synaptic growth at neuromuscular junction	IEA
GO:0014842	regulation of skeletal muscle satellite cell proliferation	IEA
GO:0014857	regulation of skeletal muscle cell proliferation	IBA
GO:0021610	facial nerve morphogenesis	IEA
GO:0030855	epithelial cell differentiation	ISS
GO:0030878	thyroid gland development	ISS
GO:0030910	olfactory placode formation	IEA
GO:0032880	regulation of protein localization	IEA

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GO:Cellular Component

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GO ID	GO Term	Evidence
GO:0000790	nuclear chromatin	ISA
GO:0005634	nucleus	IDA
GO:0005634	nucleus	IBA
GO:0005654	nucleoplasm	IDA
GO:0005667	transcription factor complex	ISS
GO:0005667	transcription factor complex	IBA
GO:0005730	nucleolus	IDA
GO:0005737	cytoplasm	IEA

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Reactome Pathway

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Reactome ID	Reactome Term	Evidence
No data available in table

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Drugs and compounds information

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ID	Drug Name	Action	PubMed
C000611646	bisphenol F	[INS protein co-treated with Dexamethasone co-treated with 1-Methyl-3-isobutylxanthine co-treated with Indomethacin co-treated with bisphenol F] results in increased expression of SIX1 mRNA	28628672
C000611646	bisphenol F	bisphenol F results in increased expression of SIX1 mRNA	30951980
C004925	methylmercuric chloride	methylmercuric chloride results in increased expression of SIX1 mRNA	28001369
C006253	pirinixic acid	[pirinixic acid binds to and results in increased activity of PPARA protein] which results in decreased expression of SIX1 mRNA	19710929
C006253	pirinixic acid	pirinixic acid results in increased expression of SIX1 mRNA	20813756
C006703	benzo(b)fluoranthene	benzo(b)fluoranthene results in decreased expression of SIX1 mRNA	26377693
C006780	bisphenol A	bisphenol A affects the methylation of SIX1 promoter	27334623
C006780	bisphenol A	bisphenol A results in increased expression of SIX1 mRNA	30951980
C006780	bisphenol A	bisphenol A results in decreased expression of SIX1 mRNA	30816183
C009495	titanium dioxide	titanium dioxide affects the expression of SIX1 mRNA	23557971
C009495	titanium dioxide	titanium dioxide results in decreased expression of SIX1 mRNA	29264374
C012589	trichostatin A	[NOG protein co-treated with trichostatin A co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in increased expression of SIX1 mRNA	27188386
C012589	trichostatin A	trichostatin A results in increased expression of SIX1 mRNA	24935251; 26272509;
C017947	sodium arsenite	sodium arsenite affects the methylation of SIX1 gene	28589171
C026486	1,2,5,6-dibenzanthracene	1,2,5,6-dibenzanthracene results in decreased expression of SIX1 mRNA	26377693
C028007	nickel monoxide	nickel monoxide results in decreased expression of SIX1 mRNA	19167457
C034028	vanadyl sulfate	vanadyl sulfate results in decreased expression of SIX1 mRNA	16330358
C042720	mercuric bromide	mercuric bromide results in increased expression of SIX1 mRNA	26272509
C042720	mercuric bromide	[NOG protein co-treated with mercuric bromide co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide] results in increased expression of SIX1 mRNA	27188386
C046760	15-acetyldeoxynivalenol	15-acetyldeoxynivalenol results in increased expression of SIX1 mRNA	23792671

Showing 1 to 20 of 97 entries

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Functional annotations

Keywords

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Keyword ID	Keyword Term
KW-0002	3D-structure
KW-0010	Activator
KW-0053	Apoptosis
KW-0209	Deafness
KW-0217	Developmental protein
KW-0225	Disease mutation
KW-0238	DNA-binding
KW-0371	Homeobox
KW-0539	Nucleus
KW-0597	Phosphoprotein
KW-0678	Repressor
KW-0804	Transcription
KW-0805	Transcription regulation
KW-0832	Ubl conjugation
KW-0963	Cytoplasm
KW-1010	Non-syndromic deafness
KW-1185	Reference proteome

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Interpro

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InterPro ID	InterPro Term
IPR001356	Homeobox_dom
IPR009057	Homeobox-like_sf
IPR017970	Homeobox_CS
IPR031278	SIX1
IPR031701	SIX1_SD

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PROSITE

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PROSITE ID	PROSITE Term
PS00027	HOMEOBOX_1
PS50071	HOMEOBOX_2

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Pfam

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Pfam ID	Pfam Term
PF00046	Homeodomain
PF16878	SIX1_SD

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Gene: SIX1

Basic information

Gene expression information

Gene expression in different tissues (GTEx V7)

Gene expression in different tissues (ENCODE)

Protein structural annotations

3D structure in PDB database

Protein disorder information

Orthologous information

Other genetic variants/mutations

Disease or phenotype associated information

Gene Ontology (GO)/biological pathways

GO:Molecular Function

GO:Biological Process

GO:Cellular Component

Reactome Pathway

Drugs and compounds information

Functional annotations

Keywords

Interpro

PROSITE

Pfam

Protein-protein interaction

Protein-miRNA interaction