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SIX1 Gene

protein-coding   GIFtS: 62

GC14M060182
SIX homeobox 1
(Previous names: sine oculis homeobox (Drosophila) homolog 1, sine oculis homeobox homolog 1 (Drosophila), deafness, autosomal dominant 23 )
Symbol approved by the HUGO Gene Nomenclature Committee (HGNC) database
(Previous symbol: DFNA23)
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Aliases &
Descriptions
for SIX1

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc , and/or 7Ensembl, 8miRBase)
About This Section
Aliases
BOS3 2, 5
DFNA23 2, 5
TIP39 2
Descriptions
SIX homeobox 1 2
Sine oculis homeobox homolog 1 2, 3
deafness, autosomal dominant 23 1
sine oculis homeobox (Drosophila) homolog 1 1
sine oculis homeobox homolog 1 (Drosophila) 1
External Ids
HGNC: 108871
Entrez Gene: 64952
UniProtKB: Q154753
Ensembl: ENSG000001267787
Search outside databases for aliases for SIX1 gene

Previous GC identifers: GC14M058438 GC14M054906 GC14M059102

Summaries
for SIX1

(According to Entrez Gene, Wikipedia's Gene Wiki,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

 EntrezGene summary for SIX1:
The protein encoded by this gene is a homeobox protein that is similar to the Drosophila 'sine
oculis' gene product. This gene is found in a cluster of related genes on chromosome 14 and
is thought to be involved in limb development. Defects in this gene are a cause of autosomal
dominant deafness type 23 (DFNA23) and branchiootic syndrome type 3 (BOS3). [provided by RefSeq]

UniProtKB/Swiss-Prot: SIX1_HUMAN, Q15475
Function: May be involved in limb tendon and ligament development (By similarity)

Gene Wiki entry for SIX1

Genomic Location
for SIX1

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 36),
and/or miRBase,
Genomic Views according to UCSC and Ensembl, Transcription factor binding sites according to SABiosciences)
About This Section

 Genomic View:
UCSC Golden Path with GeneCards custom track

 Transcription factor binding sites upstream to the SIX1 gene  

Entrez Gene cytogenetic band: 14q23.1   Ensembl cytogenetic band:  14q23.1   HGNC cytogenetic band: 14q23.1

SIX1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)

GeneLoc gene densities for chromosome 14         GeneLoc Exon Structure

GeneLoc location for GC14M060182:     (about GC identifiers)

Start:
 60,182,506 bp from pter
End:
 60,185,933 bp from pter
Size:
 3,428 bases
Orientation:
 minus strand
RefSeq DNA sequence:
NC_000014.7  NT_026437.11  

Proteins
for SIX1

(According to 1UniProtKB, and/or Ensembl, Phosphorylation sites according to 2Phosphosite, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from Invitrogen, Millipore, Sigma-Aldrich, R&D Systems, Enzo Life Sciences, Abnova, OriGene and/or, Abcam,
Biochemical Assays by Invitrogen, Millipore, R&D Systems, Cell Signaling Technology, and/or Enzo Life Sciences, Ontologies according to Gene Ontology Consortium 01 Apr 2009 and Entrez Gene, Antibodies by Invitrogen, Millipore, Sigma-Aldrich, R&D Systems, Cell Signaling Technology, Abcam, Abnova, and/or Novus Biologicals)
About This Section

 UniProtKB/Swiss-Prot: SIX1_HUMAN, Q15475 (See protein sequence)
Recommended Name: Homeobox protein SIX1  
Size: 284 amino acids; 32210 Da
Subcellular location: Nucleus
Secondary accessions: Q96H64

REFSEQ proteins: NP_005973.1  

ENSEMBL proteins: 
ENSP00000247182 


Human Recombinant Proteins 
Browse Drug Discovery Central at Invitrogen for human recombinant proteins
Browse Purified and Recombinant Proteins at Millipore
Browse Human Recombinant Proteins at Sigma-Aldrich  
Browse R&D Systems for human recombinant proteins
Browse recombinant and purified proteins available from Enzo Life Sciences
Recombinant Proteins from Abcam (SIX1)
Human Recombinant Proteins from Abnova (SIX1)
              OriGene Purified Recombinant Human Protein: SIX1 

4 Gene Ontology (GO) cellular component terms (links to tree view):

GO IDQualified GO termEvidencePubMed IDs
GO:0005634 nucleus IEA--
GO:0005667 transcription factor complex IEA--
GO:0005730 nucleolus IDA18029348
GO:0005737 cytoplasm IDA18029348
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Antibodies for SIX1: 
Browse Antibodies Central at Invitrogen
Browse Millipore's Extensive Line of Mono- and Polyclonal Antibodies
Sigma-Aldrich Antibodies for SIX1
Browse R&D Systems for Antibodies
Antibodies from Abcam (SIX1), each with their AbpromiseSM
Monoclonal and Polyclonal Antibodies from Abnova (SIX1)
Novus Biologicals Antibodies for SIX1

Assays for SIX1: 
Browse Invitrogen for biochemical assays
Browse Kits and Assays available from Millipore
Browse R&D Systems for biochemical assays
Browse biochemical assays available from Enzo Life Sciences

Protein Domains/
Families
for SIX1

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section
3 InterPro domains/families:
 IPR001356 Homeobox
 IPR017970 Homeobox_CS
 IPR012287 Homeodomain-rel


   GeneDecks  SIX1 for the domains selected above  
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Graphical View of Domain Structure for InterPro Entry Q15475

ProtoNet protein and cluster: Q15475

1 Blocks protein family: IPB000047 Lambda and other repressor helix-turn-helix signature

UniProtKB/Swiss-Prot: SIX1_HUMAN, Q15475
Similarity: Belongs to the SIX/Sine oculis homeobox family
Similarity: Contains 1 homeobox DNA-binding domain

Gene Function
for SIX1

(According to MGI Jun 06 2009, UniProtKB, IUBMB,and/or Genatlas,
shRNA from OriGene, Sigma-Aldrich, RNAi from Sigma-Aldrich,
RNAi Products, Clones, and Q-PCR Products from Invitrogen, Millipore, OriGene, and/or Abnova, siRNAs from Applied Biosystems, SYBR primers from OriGene, Cell-based Assays from Millipore, Ontologies according to Gene Ontology Consortium 01 Apr 2009 via Entrez Gene.)
About This Section
Inhib.
RNA:		Invitrogen RNAi Products for gene knock-down (SIX1)
Browse for Gene Knock-down Tools from Millipore
Abnova Chimera RNAi Products for Gene knock-down (SIX1)
              OriGene 29mer shRNA kit in GFP-retroviral vector: NM_005982

              Applied Biosystems Silencer® siRNAs for SIX1

              Sigma-Aldrich siRNA for SIX1  
                     Sigma-Aldrich shRNA for SIX1  
                     Explore Sigma-Aldrich super-pooled esiRNAs  

Clones:Invitrogen Clones for SIX1
Browse Clones for the Expression of Recombinant Proteins Available from Millipore
              OriGene GFP tagged cDNA clone in CMV expression vector: NM_005982
                                 Myc/DDK tagged cDNA clone in CMV expression vector: NM_005982
                                 untagged cDNA clone in CMV expression vector: NM_005982 

Primers: Browse Quantitative PCR Central at Invitrogen for Q-PCR LUX™ Primers
              OriGene genome-wide validated SYBR primer pairs: NM_005982

UniProtKB/Swiss-Prot: SIX1_HUMAN, Q15475
Function: May be involved in limb tendon and ligament development (By similarity)

Genatlas biochemistry entry for SIX1:
Drosophila sine oculis homolog SIX1 homeo box encoding gene,expressed during development in limb
tendons,also expressed in skeletal and smooth muscle

15/20 MGI mutant phenotypes (inferred from 4 alleles) (MGI details for Six1) (see all 20 ):

behavior/neurologicalcellularcraniofacialdigestive/alimentary
embryogenesisendocrine/exocrine glandgrowth/sizehearing/vestibular/earhematopoietic system
immune systemlethality-prenatal/perinatallimbs/digits/tailmusclenervous system

3 Gene Ontology (GO) molecular function terms (links to tree view):

GO IDQualified GO termEvidencePubMed IDs
GO:0003700 transcription factor activity IEA--
GO:0005515 protein binding IPI16189514
GO:0043565 sequence-specific DNA binding IEA--
About this table

Pathways & Interactions
for SIX1

(Pathways according to Invitrogen (maps by GeneGo), Millipore, Cell Signaling Technology, Sigma-Aldrich, KEGG and/or UniProtKB,
Sets of similar genes according to GeneDecks, Proteins Network according to SABiosciences, Interactions according to 1UniProtKB, 2MINT, and/or 3STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2009 via Entrez Gene.)
About This Section


 Gene Network CentralTM Interacting Genes and Proteins Network for  SIX1 


5/25 Interacting proteins for SIX1 (Q154751, 2 ENSP000002471823) via UniProtKB, MINT, and/or STRING (see all 25 )
InteractantInteraction Details
GeneCardExternal ID(s)
MDFIQ997501, 2EBI-743675, EBI-724076 MINT-66374 EBI-743675, EBI-724076 MINT-66374
MDFIQ997501, 2EBI-743675, EBI-724076 MINT-66374 EBI-743675, EBI-724076 MINT-66374
EYA1ENSP000003733963STRING (score=.999)
DACH1ENSP000003527123STRING (score=.984)
MYOGENSP000002416513STRING (score=.981)
About this table

5/14 Gene Ontology (GO) biological process terms (links to tree view) (see all 14 ):

GO IDQualified GO termEvidencePubMed IDs
GO:0001658 ureteric bud branching IEA--
GO:0001759 induction of an organ IEA--
GO:0006355 regulation of transcription, DNA-dependent IEA--
GO:0007389 pattern specification process IEA--
GO:0007517 muscle development TAS8617500
About this table

Drugs & Compounds
for SIX1

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, Sigma-Aldrich, Tocris Bioscience, and/or Novoseek and Drugs according to Enzo Life Sciences and/or PharmGKB)
About This Section

Browse drugs & compounds from Enzo Life Sciences
Browse Small Molecules at Sigma-Aldrich

Browse Tocris compounds for SIX1

Transcripts
for SIX1

(GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 219 Homo sapiens; Jun 2 2009) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView,
non coding RNAs according to RNAdb,
ESTs according to GeneTide,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from Invitrogen, Millipore, and/or Abnova,
siRNAs from Applied Biosystems, Sigma-Aldrich,
shRNA from Sigma-Aldrich, OriGene,
Tagged/untagged cDNA clones from OriGene,
Expression Assays from Applied Biosystems)
About This Section
Inhib.
RNA:		Invitrogen RNAi Products for gene knock-down (SIX1)
Browse for Gene Knock-down Tools from Millipore
Abnova Chimera RNAi Products for Gene knock-down (SIX1)
              OriGene 29mer shRNA kit in GFP-retroviral vector: NM_005982

              Sigma-Aldrich siRNA for SIX1  
                     Sigma-Aldrich shRNA for SIX1  
                     Explore Sigma-Aldrich super-pooled esiRNAs  

Applied Biosystems Silencer® siRNAs: 

NM_005982  

REFSEQ mRNAs for SIX1 gene: 

NM_005982.3   

Applied Biosystems TaqMan ® Gene Expression Assays: 

NM_005982  

              OriGene GFP tagged cDNA clone in CMV expression vector: NM_005982
                                 Myc/DDK tagged cDNA clone in CMV expression vector: NM_005982
                                 untagged cDNA clone in CMV expression vector: NM_005982 

Additional cDNA sequence: 

AK093780.1 BC008874.2 BT007083.1 X91868.1 

6 DOTS entries:

DT.210942  DT.110833  DT.92421992  DT.206169  DT.99950944  DT.75173967 

24/130 AceView cDNA sequences (see all 130 ):

AA988491 AW016919 BQ182990 BE220876 AW409771 AI298421 AI375023 BE350547 
AW770317 BE791327 BI495857 AI701028 BE671377 BE670478 BM975666 AI860806 
BF433117 AW341127 BU607471 BE765761 BE765452 BF436137 BF111239 AI952353 

highest scoring ESTs for SIX1:

X91868 AA378158 AA988653 AA992433 AI281952 AI824256 AI829946 AI971422 AW002152 AW166639 

Unigene Cluster for SIX1:

SIX homeobox 1
Hs.716658  [show with all ESTs]
Unigene Representative Sequence: NM_005982


GeneLoc Exon Structure

1 Ensembl transcript including schematic representation:
ENST00000247182  

Expression
for SIX1

(Experimental results according to 1GeneNote and GNF BioGPS,
probe sets-to-genes annotations according to 2GeneAnnot , 3GeneTide , Sets of similar genes according to GeneDecks, Electronic Northern calculations according to data from UniGene (Build 219 Homo sapiens), SAGE tags according to CGAP, plus additional links to SOURCE, and/or GNF BioGPS, and/or EXPOLDB, and/or UniProtKB,
Expression Assays from Applied Biosystems )
About This Section

SIX1 expression in normal and diseased human tissues

 Applied Biosystems TaqMan ® Gene Expression Assays for SIX1

1 / 2 / 3

6 probe-sets matching SIX1 gene


Affymetrix
probe-set		 Array  GeneAnnot data GeneNote data GeneTide data
# genes Sensitivity Specificity Correlation Length Gb_Accession Consensus Uniqueness Score Rank
62110_at2, 3 U95-C 1 1.00 1.00 0.98 1.22 N79004 0.40 1.00 0.76 1
40004_at2, 3 U95-A 1 1.00 1.00 0.99 0.80 X91868 1.00 1.00 1.00 1

228347_at2, 3 U133-B 1 1.00 1.00 -- -- N79004 0.40 1.00 0.76 1

205817_at2, 3 U133-A 1 1.00 1.00 -- -- NM_005982 0.60 1.00 0.82 1

228347_at2 U133Plus2 1 1.00 1.00 -- -- -- -- -- -- --

205817_at2 U133Plus2 1 1.00 1.00 -- -- -- -- -- -- --
GeneDecks  SIX1 for binary patterns associated with the probe-sets selected above  
About GeneDecksing
About this table    
Data from (Publications) and GNF BioGPS
    About these images
About these images

CGAP SAGE TAG: --

SOURCE GeneReport for Unigene cluster: Hs.716658

Expression variation in blood from EXPOLDB for SIX1

UniProtKB/Swiss-Prot: SIX1_HUMAN, Q15475
Tissue specificity: Specifically expressed in skeletal muscle

Orthologs
for SIX1

(Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD and/or 5MGI Jun 06 2009, with possible further links to Flybase and/or WormBase, Gene Trees according to Ensembl)
About This Section
Orthologs for SIX1 gene from 5/14 species (see all 14 )
Organism Gene Locus Description Human
Similarity		 NCBI accessions
dog
(Canis familiaris)		 SIX11   -- SIX homeobox 1 94.48(n)
99.65(a)		 490719  XM_547841.2  XP_547841.2 
chimpanzee
(Pan troglodytes)		 SIX11   -- SIX homeobox 1 100(n)
100(a)		 452952  XM_509988.2  XP_509988.2 
cow
(Bos taurus)		 SIX11   -- SIX homeobox 1 93.19(n)
98.59(a)		 511371  XM_588692.3  XP_588692.2 
rat
(Rattus norvegicus)		 Six11   -- SIX homeobox 1 93.19(n)
99.3(a)		 114634  XM_343079.3  XP_343080.3 
mouse
(Mus musculus)		 Six11, 5 12 (31.00 cM)5
 sine oculis-related homeobox 1 homolog (Drosophila)1, 5 93.19(n)1
98.94(a)1		 204711  NM_009189.21  NP_033215.11 
 AK0311225  AK1319255  (see all 12)
About this table        Species with no ortholog for SIX1

ENSEMBL Gene Tree for SIX1

Paralogs
for SIX1

(Paralogs according to 1HomoloGene
and 2Ensembl, Pseudogenes according to 3Pseudogene.org)
About This Section

Paralogs for SIX1 gene
SIX22  SIX62  SIX32  

SNPs/Variants
for SIX1

(According to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, and UniProtKB, Linkage Disequilibrium by HapMap, Genotyping Reagents from Applied Biosystems)
About This Section


10/39 NCBI SNPs in SIX1 are shown (see all 39 )
(Click for Applied Biosystems TaqMan ® Genotyping Assay)  (see all 25)
ABGenomic DataTranscription DataAllele Frequencies
SNP IDValidChr 14 posSequenceRecsAA
Chg		TypeMoreRecsAllele
freq		PopTotal
sample		More
------------
--
rs101444151,2
A,C60182420(+) GAAAGC/GCTGCT 1 -- ut310--------
rs37426381,2
H60181634(-) GAATTG/ACAGGG 1 -- ut314Minor allele frequency- A:0.00EU EA WA 416
rs46272541,2
H60186453(+) GCTTAT/AGGAAC 1 -- ng314Minor allele frequency- A:0.00EU EA WA 418
--
rs116236831,2
A60187082(+) TGTGTA/GTGTGT 1 -- ng310--------
rs65733221,2
C60187635(+) TTTCCC/TCTTTT 1 -- ng31 tfbs3 trp30--------
rs128881571,2
H60186418(+) AATGTT/GGGAAT 1 -- ng314Minor allele frequency- G:0.00EU EA WA 416
rs80033661,2
A60187873(+) TTTTTA/TAAAAA 1 -- ng31 trp30--------
rs121010951,2
H60182774(+) CACCAG/AACTGG 1 L/L syn1 ese34Minor allele frequency- A:0.00EU EA WA 418
--
rs37426371,2
--60181710(-) TGAGTG/TGTGTA 1 -- ut310--------
--
rs339432161,2
--60181988(+) CATTT-/AAAAAA 1 -- ut310--------
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HapMap Linkage Disequilibrium images for SIX1 (up to first 250kb)

Disorders & Mutations
for SIX1

(in which this Gene is Involved, According to OMIM, UniProtKB, Novoseek, PharmGKB, Genatlas, GeneTests, Blood group antigen gene mutations by BGMUT, HGMD, GAD, HuGE Navigator, BCGD, and/or TGDB.)
About This Section

 OMIM: 601205   disorders: 608389  605192  

UniProtKB/Swiss-Prot: SIX1_HUMAN, Q15475

  • Defects in SIX1 are the cause of autosomal dominant deafness type 23 (DFNA23) [MIM:605192]
  • Defects in SIX1 are the cause of branchiootic syndrome type 3 (BOS3) [MIM:608389]. Urinary
    tract malformations constitute the most frequent cause of chronic renal failure in the first two
    decades of life. Branchio-oto-renal syndrome (BOR) is an autosomal dominant developmental disorder
    of kidney and urinary tract malformations with hearing loss. The major feature of BOR is hearing
    loss (93% of patients), which can be conductive, sensorineural, or both and varies in age of onset

    • 8 Novoseek disease relationships for SIX1 gene

    Disease   Score   Articles   PubMed IDs for Articles with Shared Sentences (# sentences)
    bor syndrome 96.04 16 16491411 (3), 19389353 (2), 17238186 (2), 17637804 (2) (see all 9)
    renal anomaly 81.97 1 18177466 (1)
    urinary tract anomaly 67.63 1 16971658 (1)
    rhabdomyosarcoma 38.59 1 15805264 (1)
    metastasis 20.50 4 17409410 (1), 15805264 (1), 18381426 (1), 19331807 (1)
    renal failure chronic 9.54 1 16971658 (1)
    cancer 0.00 2 17409410 (1), 18381426 (1)
    tumors 0.00 12 15805264 (4), 17409410 (2)
    About this table

    GeneTests: SIX1
    Branchiootorenal Syndrome

    Human Gene Mutation Database: SIX1

    Medical News
    for SIX1

    (Possibly Related Articles in Doctor's Guide)
    About This Section

    Publications
    for SIX1

    (in PubMed. Associations of this gene to articles via 1Novoseek, 2HGNC, 3Entrez Gene, 4UniProtKB/Swiss-Prot, 5UniProtKB/TrEMBL, 6GAD, and/or 7PharmGKB)
    About This Section

    		10/52 PubMed articles for SIX1 gene (see all 52 ):

    Search for SIX1

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section

     ANDOR
    Aliases
    Disorders
    Free Text  
      Query String
    		PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    Genome Databases showing SIX1

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, and/or H-InvDB)
    About This Section
    Entrez Gene: 6495 HGNC: 10887 AceView: SIX1 Ensembl:ENSG00000126778 euGenes: HUgn6495
    ECgene: SIX1 H-InvDB: SIX1

    Other Databases showing SIX1

    (According to HUGE)
    About This Section

    		   --

    Specialized Databases showing SIX1

    (According to ATLAS, HORDE, IMGT, MTDB, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    ATLAS Chromosomes in Cancer entry for SIX1 Genetics and Cytogenetics in Oncology and Haematology
    GeneReviewshttp://www.genetests.org/query?gene=SIX1

    Licensable Technologies
    for SIX1

    (Available from WIS Yeda, Salk, Tufts)
    About This Section

    		  --

    Services
    for SIX1

    (Reagents available from Applied Biosystems, Antibodies and assays by Cell Signaling Technology, Abcam, Novus Biologicals,
    Sigma-Aldrich, R&D Systems, Millipore, Abnova, and/or Invitrogen, Clones available from OriGene,and/or Invitrogen, Drugs and/or compounds by Sigma-Aldrich,
    Enzo Life Sciences, and/or Tocris Bioscience)
    About This Section



    Products for SIX1:
     TaqMan ® Gene Expression Assays
     TaqMan ® Genotyping Assays
    		  Free SNP selection tool



      Invitrogen iPath Pathways  Invitrogen BLOCK-iT™ RNAi
      Invitrogen Antibodies  Invitrogen Assays
      Invitrogen Clones  Invitrogen Q-PCR Products
      Invitrogen Human Recombinant Kinases  Invitrogen Custom Antibody and Peptide Service
      Invitrogen Proteins / Assays / Screening Services  Search Invitrogen catalog for SIX1-related products

     Millipore Custom Antibody & Bulk Services
     Millipore Preclinical / Clinical Development Services
     Millipore Immunoassay Services
     Millipore Target Screening & Profiling Services


     Predesigned and custom siRNAs for SIX1 Antibodies for SIX1
     Explore super-pooled esiRNAs Browse proteins at Sigma-Aldrich
     Lentivirus-delivered shRNAs for SIX1 Browse small molecules at Sigma-Aldrich
     "Your Favorite Gene" Pathwaysfeedback


      
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     Recombinant & Natural Proteins  

     Recombinant Proteins (SIX1)
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     Recombinant Proteins
    (SIX1)
     Antibodies (SIX1)
     Tagged/untagged cDNA clones
     Validated SYBR primer pairs
     Purified proteins from HEK293T cells
     Western blot validated antibodies
     shRNA in GFP-retroviral vector
     Search Tocris compounds for SIX1




     Search www.enzolifesicences.com for proteins, assays, substrates, inhibitors & antibodies
     Antibodies for SIX1

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