ID SIX1_HUMAN Reviewed; 284 AA.
AC Q15475; Q53Y16; Q96H64;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 27-MAR-2024, entry version 202.
DE RecName: Full=Homeobox protein SIX1;
DE AltName: Full=Sine oculis homeobox homolog 1;
GN Name=SIX1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Muscle;
RX PubMed=8617500; DOI=10.1006/geno.1996.0172;
RA Boucher C.A., Carey N., Edwards Y.H., Siciliano M.J., Johnson K.J.;
RT "Cloning of the human SIX1 gene and its assignment to chromosome 14.";
RL Genomics 33:140-142(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Gallardo M.E., Rodriguez de Cordoba S.;
RT "Partial genomic sequence of human SIX1.";
RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT CYS-99.
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT CYS-99.
RC TISSUE=Muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=10801845; DOI=10.1074/jbc.m002446200;
RA Ford H.L., Landesman-Bollag E., Dacwag C.S., Stukenberg P.T., Pardee A.B.,
RA Seldin D.C.;
RT "Cell cycle-regulated phosphorylation of the human SIX1 homeodomain
RT protein.";
RL J. Biol. Chem. 275:22245-22254(2000).
RN [6]
RP FUNCTION.
RX PubMed=15123840; DOI=10.1073/pnas.0401139101;
RA Coletta R.D., Christensen K., Reichenberger K.J., Lamb J., Micomonaco D.,
RA Huang L., Wolf D.M., Muller-Tidow C., Golub T.R., Kawakami K., Ford H.L.;
RT "The Six1 homeoprotein stimulates tumorigenesis by reactivation of cyclin
RT A1.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:6478-6483(2004).
RN [7]
RP UBIQUITINATION, INTERACTION WITH CDH1, AND SUBCELLULAR LOCATION.
RX PubMed=17130831; DOI=10.1038/sj.onc.1210122;
RA Christensen K.L., Brennan J.D., Aldridge C.S., Ford H.L.;
RT "Cell cycle regulation of the human Six1 homeoprotein is mediated by
RT APC(Cdh1).";
RL Oncogene 26:3406-3414(2007).
RN [8]
RP INTERACTION WITH TBX18.
RX PubMed=26235987; DOI=10.1016/j.ajhg.2015.07.001;
RA Vivante A., Kleppa M.J., Schulz J., Kohl S., Sharma A., Chen J., Shril S.,
RA Hwang D.Y., Weiss A.C., Kaminski M.M., Shukrun R., Kemper M.J.,
RA Lehnhardt A., Beetz R., Sanna-Cherchi S., Verbitsky M., Gharavi A.G.,
RA Stuart H.M., Feather S.A., Goodship J.A., Goodship T.H., Woolf A.S.,
RA Westra S.J., Doody D.P., Bauer S.B., Lee R.S., Adam R.M., Lu W.,
RA Reutter H.M., Kehinde E.O., Mancini E.J., Lifton R.P., Tasic V.,
RA Lienkamp S.S., Jueppner H., Kispert A., Hildebrandt F.;
RT "Mutations in TBX18 cause dominant urinary tract malformations via
RT transcriptional dysregulation of ureter development.";
RL Am. J. Hum. Genet. 97:291-301(2015).
RN [9]
RP FUNCTION, AND INTERACTION WITH CEBPA; CEBPB AND EBF2.
RX PubMed=27923061; DOI=10.1371/journal.pgen.1006474;
RA Brunmeir R., Wu J., Peng X., Kim S.Y., Julien S.G., Zhang Q., Xie W.,
RA Xu F.;
RT "Comparative Transcriptomic and Epigenomic Analyses Reveal New Regulators
RT of Murine Brown Adipogenesis.";
RL PLoS Genet. 12:E1006474-E1006474(2016).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 1-189 IN COMPLEX WITH EYA2,
RP FUNCTION, SUBUNIT, DNA-BINDING, CHARACTERIZATION OF VARIANT BOS3 GLU-17,
RP AND CHARACTERIZATION OF VARIANT DFNA23 GLU-133 DEL.
RX PubMed=23435380; DOI=10.1038/nsmb.2505;
RA Patrick A.N., Cabrera J.H., Smith A.L., Chen X.S., Ford H.L., Zhao R.;
RT "Structure-function analyses of the human SIX1-EYA2 complex reveal insights
RT into metastasis and BOR syndrome.";
RL Nat. Struct. Mol. Biol. 20:447-453(2013).
RN [11]
RP VARIANTS BOS3 TRP-110 AND CYS-129, VARIANT DFNA23 GLU-133 DEL,
RP CHARACTERIZATION OF VARIANTS BOS3 TRP-110 AND CYS-129, CHARACTERIZATION OF
RP VARIANT DFNA23 GLU-133 DEL, FUNCTION, AND POSSIBLE INVOLVEMENT IN BOR.
RX PubMed=15141091; DOI=10.1073/pnas.0308475101;
RA Ruf R.G., Xu P.-X., Silvius D., Otto E.A., Beekmann F., Muerb U.T.,
RA Kumar S., Neuhaus T.J., Kemper M.J., Raymond R.M. Jr., Brophy P.D.,
RA Berkman J., Gattas M., Hyland V., Ruf E.-M., Schwartz C., Chang E.H.,
RA Smith R.J.H., Stratakis C.A., Weil D., Petit C., Hildebrandt F.;
RT "SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-
RT SIX1-DNA complexes.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:8090-8095(2004).
RN [12]
RP VARIANT BOS3 ARG-122.
RX PubMed=17637804; DOI=10.1038/sj.ejhg.5201900;
RA Sanggaard K.M., Rendtorff N.D., Kjaer K.W., Eiberg H., Johnsen T.,
RA Gimsing S., Dyrmose J., Nielsen K.O., Lage K., Tranebjaerg L.;
RT "Branchio-oto-renal syndrome: detection of EYA1 and SIX1 mutations in five
RT out of six Danish families by combining linkage, MLPA and sequencing
RT analyses.";
RL Eur. J. Hum. Genet. 15:1121-1131(2007).
RN [13]
RP VARIANTS BOS3 GLU-17; PRO-73; GLY-106; GLN-110; TRP-110; CYS-112 AND
RP CYS-129.
RX PubMed=18330911; DOI=10.1002/humu.20714;
RA Kochhar A., Orten D.J., Sorensen J.L., Fischer S.M., Cremers C.W.,
RA Kimberling W.J., Smith R.J.;
RT "SIX1 mutation screening in 247 branchio-oto-renal syndrome families: a
RT recurrent missense mutation associated with BOR.";
RL Hum. Mutat. 29:565-565(2008).
RN [14]
RP CHARACTERIZATION OF VARIANTS BOS3 GLU-17; GLY-106; TRP-110 AND CYS-112,
RP CHARACTERIZATION OF VARIANT DFNA23 GLU-133 DEL, FUNCTION, DNA-BINDING,
RP SUBCELLULAR LOCATION, INTERACTION WITH EYA2, AND POSSIBLE INVOLVEMENT IN
RP BOR.
RX PubMed=19497856; DOI=10.1074/jbc.m109.016832;
RA Patrick A.N., Schiemann B.J., Yang K., Zhao R., Ford H.L.;
RT "Biochemical and functional characterization of six SIX1 Branchio-oto-renal
RT syndrome mutations.";
RL J. Biol. Chem. 284:20781-20790(2009).
RN [15]
RP VARIANT BOS3 CYS-129, AND VARIANT BOR LEU-249.
RX PubMed=21280147; DOI=10.1002/humu.21402;
RA Krug P., Moriniere V., Marlin S., Koubi V., Gabriel H.D., Colin E.,
RA Bonneau D., Salomon R., Antignac C., Heidet L.;
RT "Mutation screening of the EYA1, SIX1, and SIX5 genes in a large cohort of
RT patients harboring branchio-oto-renal syndrome calls into question the
RT pathogenic role of SIX5 mutations.";
RL Hum. Mutat. 32:183-190(2011).
CC -!- FUNCTION: Transcription factor that is involved in the regulation of
CC cell proliferation, apoptosis and embryonic development (By
CC similarity). Plays an important role in the development of several
CC organs, including kidney, muscle and inner ear (By similarity).
CC Depending on context, functions as a transcriptional repressor or
CC activator (By similarity). Lacks an activation domain, and requires
CC interaction with EYA family members for transcription activation
CC (PubMed:15141091). Mediates nuclear translocation of EYA1 and EYA2
CC (PubMed:19497856). Binds the 5'-TCA[AG][AG]TTNC-3' motif present in the
CC MEF3 element in the MYOG promoter and CIDEA enhancer (PubMed:27923061,
CC PubMed:23435380, PubMed:15141091, PubMed:19497856). Regulates the
CC expression of numerous genes, including MYC, CCND1 and EZR (By
CC similarity). Acts as an activator of the IGFBP5 promoter, probably
CC coactivated by EYA2 (By similarity). Repression of precursor cell
CC proliferation in myoblasts is switched to activation through
CC recruitment of EYA3 to the SIX1-DACH1 complex (By similarity). During
CC myogenesis, seems to act together with EYA2 and DACH2 (By similarity).
CC Regulates the expression of CCNA1 (PubMed:15123840). Promotes brown
CC adipocyte differentiation (By similarity).
CC {ECO:0000250|UniProtKB:Q62231, ECO:0000269|PubMed:15123840,
CC ECO:0000269|PubMed:15141091, ECO:0000269|PubMed:19497856,
CC ECO:0000269|PubMed:23435380, ECO:0000269|PubMed:27923061}.
CC -!- SUBUNIT: Interacts with DACH1 (By similarity). Interacts with EYA1 (By
CC similarity). Interacts with EYA2 (PubMed:23435380, PubMed:19497856).
CC Interacts with CDH1 (PubMed:17130831). Interacts with TBX18
CC (PubMed:26235987). Interacts with CEBPA (PubMed:27923061). Interacts
CC with CEBPB (PubMed:27923061). Interacts with EBF2 (PubMed:27923061).
CC {ECO:0000250|UniProtKB:Q62231, ECO:0000269|PubMed:17130831,
CC ECO:0000269|PubMed:19497856, ECO:0000269|PubMed:23435380,
CC ECO:0000269|PubMed:26235987, ECO:0000269|PubMed:27923061}.
CC -!- INTERACTION:
CC Q15475; Q99502: EYA1; NbExp=4; IntAct=EBI-743675, EBI-12244764;
CC Q15475; O00167: EYA2; NbExp=4; IntAct=EBI-743675, EBI-750211;
CC Q15475; O00167-1: EYA2; NbExp=3; IntAct=EBI-743675, EBI-16038245;
CC Q15475; O00167-2: EYA2; NbExp=3; IntAct=EBI-743675, EBI-12807776;
CC Q15475; O75409: H2AP; NbExp=3; IntAct=EBI-743675, EBI-6447217;
CC Q15475; Q99750: MDFI; NbExp=2; IntAct=EBI-743675, EBI-724076;
CC Q15475; Q58EX7: PLEKHG4; NbExp=3; IntAct=EBI-743675, EBI-949255;
CC Q15475; P78424: POU6F2; NbExp=3; IntAct=EBI-743675, EBI-12029004;
CC Q15475; Q04864-2: REL; NbExp=3; IntAct=EBI-743675, EBI-10829018;
CC Q15475; Q04726-4: TLE3; NbExp=3; IntAct=EBI-743675, EBI-12014388;
CC Q15475; Q08117: TLE5; NbExp=3; IntAct=EBI-743675, EBI-717810;
CC Q15475; Q08117-2: TLE5; NbExp=6; IntAct=EBI-743675, EBI-11741437;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10801845,
CC ECO:0000269|PubMed:17130831, ECO:0000269|PubMed:19497856}. Cytoplasm.
CC -!- TISSUE SPECIFICITY: Specifically expressed in skeletal muscle.
CC -!- PTM: Phosphorylated during interphase; becomes hyperphosphorylated
CC during mitosis. Hyperphosphorylation impairs binding to promoter
CC elements. {ECO:0000269|PubMed:10801845}.
CC -!- PTM: Ubiquitinated by the anaphase promoting complex (APC), leading to
CC its proteasomal degradation. {ECO:0000269|PubMed:17130831}.
CC -!- DISEASE: Deafness, autosomal dominant, 23 (DFNA23) [MIM:605192]: A form
CC of non-syndromic deafness characterized by prelingual, bilateral,
CC symmetric hearing loss with a conductive component present in some but
CC not all patients. {ECO:0000269|PubMed:15141091,
CC ECO:0000269|PubMed:19497856, ECO:0000269|PubMed:23435380}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Branchiootic syndrome 3 (BOS3) [MIM:608389]: A syndrome
CC characterized by usually bilateral branchial cleft fistulas or cysts,
CC sensorineural and/or conductive hearing loss, pre-auricular pits, and
CC structural defects of the outer, middle or inner ear. Otic defects
CC include malformed and hypoplastic pinnae, a narrowed external ear
CC canal, bulbous internal auditory canal, stapes fixation, malformed and
CC hypoplastic cochlea. Branchial and otic anomalies overlap with those
CC seen in individuals with the branchiootorenal syndrome. However renal
CC anomalies are absent in branchiootic syndrome patients.
CC {ECO:0000269|PubMed:15141091, ECO:0000269|PubMed:17637804,
CC ECO:0000269|PubMed:18330911, ECO:0000269|PubMed:19497856,
CC ECO:0000269|PubMed:21280147, ECO:0000269|PubMed:23435380}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Note=Defects in SIX1 could be a cause of branchiootorenal
CC syndrome (BOR). BOR is an autosomal dominant disorder manifested by
CC various combinations of preauricular pits, branchial fistulae or cysts,
CC lacrimal duct stenosis, hearing loss, structural defects of the outer,
CC middle, or inner ear, and renal dysplasia. Associated defects include
CC asthenic habitus, long narrow facies, constricted palate, deep
CC overbite, and myopia. Hearing loss may be due to mondini type cochlear
CC defect and stapes fixation. Penetrance of BOR syndrome is high,
CC although expressivity can be extremely variable.
CC {ECO:0000305|PubMed:15141091, ECO:0000305|PubMed:19497856}.
CC -!- SIMILARITY: Belongs to the SIX/Sine oculis homeobox family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="https://atlasgeneticsoncology.org/gene/42302/SIX1";
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DR EMBL; X91868; CAA62974.1; -; mRNA.
DR EMBL; AF323497; AAK06772.1; -; Genomic_DNA.
DR EMBL; BT007083; AAP35746.1; -; mRNA.
DR EMBL; BC008874; AAH08874.1; -; mRNA.
DR CCDS; CCDS9748.1; -.
DR RefSeq; NP_005973.1; NM_005982.3.
DR PDB; 4EGC; X-ray; 1.99 A; A=1-189.
DR PDBsum; 4EGC; -.
DR AlphaFoldDB; Q15475; -.
DR SMR; Q15475; -.
DR BioGRID; 112386; 42.
DR CORUM; Q15475; -.
DR DIP; DIP-34448N; -.
DR IntAct; Q15475; 19.
DR MINT; Q15475; -.
DR STRING; 9606.ENSP00000494686; -.
DR ChEMBL; CHEMBL4630826; -.
DR GlyGen; Q15475; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q15475; -.
DR PhosphoSitePlus; Q15475; -.
DR BioMuta; SIX1; -.
DR DMDM; 2495290; -.
DR jPOST; Q15475; -.
DR MassIVE; Q15475; -.
DR MaxQB; Q15475; -.
DR PaxDb; 9606-ENSP00000247182; -.
DR PeptideAtlas; Q15475; -.
DR ProteomicsDB; 60606; -.
DR Pumba; Q15475; -.
DR Antibodypedia; 39; 248 antibodies from 30 providers.
DR DNASU; 6495; -.
DR Ensembl; ENST00000645694.3; ENSP00000494686.1; ENSG00000126778.12.
DR GeneID; 6495; -.
DR KEGG; hsa:6495; -.
DR MANE-Select; ENST00000645694.3; ENSP00000494686.1; NM_005982.4; NP_005973.1.
DR UCSC; uc001xfb.5; human.
DR AGR; HGNC:10887; -.
DR CTD; 6495; -.
DR DisGeNET; 6495; -.
DR GeneCards; SIX1; -.
DR GeneReviews; SIX1; -.
DR HGNC; HGNC:10887; SIX1.
DR HPA; ENSG00000126778; Tissue enhanced (parathyroid gland, salivary gland, skeletal muscle, tongue).
DR MalaCards; SIX1; -.
DR MIM; 601205; gene.
DR MIM; 605192; phenotype.
DR MIM; 608389; phenotype.
DR neXtProt; NX_Q15475; -.
DR OpenTargets; ENSG00000126778; -.
DR Orphanet; 107; BOR syndrome.
DR Orphanet; 52429; Branchiootic syndrome.
DR Orphanet; 90635; Rare autosomal dominant non-syndromic sensorineural deafness type DFNA.
DR PharmGKB; PA35787; -.
DR VEuPathDB; HostDB:ENSG00000126778; -.
DR eggNOG; KOG0775; Eukaryota.
DR GeneTree; ENSGT00940000156487; -.
DR HOGENOM; CLU_046914_2_0_1; -.
DR InParanoid; Q15475; -.
DR OMA; YKAHYVE; -.
DR OrthoDB; 602349at2759; -.
DR PhylomeDB; Q15475; -.
DR TreeFam; TF315545; -.
DR PathwayCommons; Q15475; -.
DR SignaLink; Q15475; -.
DR SIGNOR; Q15475; -.
DR BioGRID-ORCS; 6495; 20 hits in 1169 CRISPR screens.
DR ChiTaRS; SIX1; human.
DR GeneWiki; SIX1; -.
DR GenomeRNAi; 6495; -.
DR Pharos; Q15475; Tbio.
DR PRO; PR:Q15475; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q15475; Protein.
DR Bgee; ENSG00000126778; Expressed in skeletal muscle tissue of biceps brachii and 138 other cell types or tissues.
DR ExpressionAtlas; Q15475; baseline and differential.
DR Genevisible; Q15475; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0001223; F:transcription coactivator binding; IEA:Ensembl.
DR GO; GO:0035909; P:aorta morphogenesis; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
DR GO; GO:1905243; P:cellular response to 3,3',5-triiodo-L-thyronine; IEA:Ensembl.
DR GO; GO:0090103; P:cochlea morphogenesis; IEA:Ensembl.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; ISS:UniProtKB.
DR GO; GO:0048704; P:embryonic skeletal system morphogenesis; ISS:UniProtKB.
DR GO; GO:0086100; P:endothelin receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0030855; P:epithelial cell differentiation; ISS:UniProtKB.
DR GO; GO:0021610; P:facial nerve morphogenesis; IEA:Ensembl.
DR GO; GO:0061197; P:fungiform papilla morphogenesis; IEA:Ensembl.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0048699; P:generation of neurons; ISS:UniProtKB.
DR GO; GO:0048839; P:inner ear development; ISS:UniProtKB.
DR GO; GO:0042472; P:inner ear morphogenesis; ISS:UniProtKB.
DR GO; GO:0001822; P:kidney development; ISS:UniProtKB.
DR GO; GO:0072198; P:mesenchymal cell proliferation involved in ureter development; IEA:Ensembl.
DR GO; GO:0072172; P:mesonephric tubule formation; ISS:UniProtKB.
DR GO; GO:0072075; P:metanephric mesenchyme development; ISS:UniProtKB.
DR GO; GO:0042474; P:middle ear morphogenesis; IEA:Ensembl.
DR GO; GO:0051451; P:myoblast migration; ISS:UniProtKB.
DR GO; GO:0051450; P:myoblast proliferation; IEA:Ensembl.
DR GO; GO:0061055; P:myotome development; IEA:Ensembl.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0014033; P:neural crest cell differentiation; IEA:Ensembl.
DR GO; GO:0048665; P:neuron fate specification; IEA:Ensembl.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0030910; P:olfactory placode formation; IEA:Ensembl.
DR GO; GO:0001759; P:organ induction; ISS:UniProtKB.
DR GO; GO:0071599; P:otic vesicle development; IEA:Ensembl.
DR GO; GO:0003151; P:outflow tract morphogenesis; IEA:Ensembl.
DR GO; GO:0007389; P:pattern specification process; ISS:UniProtKB.
DR GO; GO:0060037; P:pharyngeal system development; IEA:Ensembl.
DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
DR GO; GO:0090336; P:positive regulation of brown fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IMP:UniProtKB.
DR GO; GO:2000729; P:positive regulation of mesenchymal cell proliferation involved in ureter development; IEA:Ensembl.
DR GO; GO:2000288; P:positive regulation of myoblast proliferation; IEA:Ensembl.
DR GO; GO:0072513; P:positive regulation of secondary heart field cardioblast proliferation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0072107; P:positive regulation of ureteric bud formation; ISS:UniProtKB.
DR GO; GO:0034504; P:protein localization to nucleus; IDA:UniProtKB.
DR GO; GO:0072095; P:regulation of branch elongation involved in ureteric bud branching; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of DNA-templated transcription; ISS:UniProtKB.
DR GO; GO:0050678; P:regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0045664; P:regulation of neuron differentiation; ISS:UniProtKB.
DR GO; GO:0032880; P:regulation of protein localization; IEA:Ensembl.
DR GO; GO:2001014; P:regulation of skeletal muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0014857; P:regulation of skeletal muscle cell proliferation; IBA:GO_Central.
DR GO; GO:0014842; P:regulation of skeletal muscle satellite cell proliferation; IEA:Ensembl.
DR GO; GO:0008582; P:regulation of synaptic assembly at neuromuscular junction; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl.
DR GO; GO:0048741; P:skeletal muscle fiber development; IBA:GO_Central.
DR GO; GO:0007519; P:skeletal muscle tissue development; ISS:UniProtKB.
DR GO; GO:0048538; P:thymus development; ISS:UniProtKB.
DR GO; GO:0030878; P:thyroid gland development; ISS:UniProtKB.
DR GO; GO:0061551; P:trigeminal ganglion development; IEA:Ensembl.
DR GO; GO:0072193; P:ureter smooth muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0001657; P:ureteric bud development; ISS:UniProtKB.
DR CDD; cd00086; homeodomain; 1.
DR Gene3D; 1.10.10.60; Homeodomain-like; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR008422; Homeobox_KN_domain.
DR InterPro; IPR031701; SIX1_SD.
DR PANTHER; PTHR10390; HOMEOBOX PROTEIN SIX; 1.
DR PANTHER; PTHR10390:SF13; HOMEOBOX PROTEIN SIX1; 1.
DR Pfam; PF05920; Homeobox_KN; 1.
DR Pfam; PF16878; SIX1_SD; 1.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; Homeodomain-like; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Apoptosis; Cytoplasm; Deafness;
KW Developmental protein; Disease variant; DNA-binding; Homeobox;
KW Non-syndromic deafness; Nucleus; Phosphoprotein; Reference proteome;
KW Repressor; Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..284
FT /note="Homeobox protein SIX1"
FT /id="PRO_0000049295"
FT DNA_BIND 124..183
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 168..269
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 173..192
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 193..209
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 217..269
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 17
FT /note="V -> E (in BOS3; crucial for interaction with EYA1
FT and EYA2 and transcription factor activity;
FT dbSNP:rs397515562)"
FT /evidence="ECO:0000269|PubMed:18330911,
FT ECO:0000269|PubMed:19497856, ECO:0000269|PubMed:23435380"
FT /id="VAR_064948"
FT VARIANT 73
FT /note="H -> P (in BOS3)"
FT /evidence="ECO:0000269|PubMed:18330911"
FT /id="VAR_064949"
FT VARIANT 99
FT /note="R -> C (in dbSNP:rs17850414)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3"
FT /id="VAR_067446"
FT VARIANT 106
FT /note="V -> G (in BOS3; crucial for protein stability, DNA
FT binding and transcription factor activity;
FT dbSNP:rs397515560)"
FT /evidence="ECO:0000269|PubMed:18330911,
FT ECO:0000269|PubMed:19497856"
FT /id="VAR_064950"
FT VARIANT 110
FT /note="R -> Q (in BOS3; dbSNP:rs1064794308)"
FT /evidence="ECO:0000269|PubMed:18330911"
FT /id="VAR_064951"
FT VARIANT 110
FT /note="R -> W (in BOS3; crucial for interaction with EYA1,
FT DNA binding and transcription factor activity;
FT dbSNP:rs80356459)"
FT /evidence="ECO:0000269|PubMed:15141091,
FT ECO:0000269|PubMed:18330911, ECO:0000269|PubMed:19497856"
FT /id="VAR_031024"
FT VARIANT 112
FT /note="R -> C (in BOS3; crucial for DNA binding and
FT transcription factor activity; dbSNP:rs397515561)"
FT /evidence="ECO:0000269|PubMed:18330911,
FT ECO:0000269|PubMed:19497856"
FT /id="VAR_064952"
FT VARIANT 122
FT /note="W -> R (in BOS3; dbSNP:rs121909770)"
FT /evidence="ECO:0000269|PubMed:17637804"
FT /id="VAR_064953"
FT VARIANT 129
FT /note="Y -> C (in BOS3; crucial for interaction with EYA1,
FT DNA binding and transcription factor activity;
FT dbSNP:rs104894478)"
FT /evidence="ECO:0000269|PubMed:15141091,
FT ECO:0000269|PubMed:18330911, ECO:0000269|PubMed:21280147"
FT /id="VAR_031025"
FT VARIANT 133
FT /note="Missing (in DFNA23; in addition to deafness the
FT patient had renal anomalies suggesting a branchiootorenal
FT syndrome; crucial for interaction with EYA1, DNA binding
FT and transcription factor activity; dbSNP:rs80356460)"
FT /evidence="ECO:0000269|PubMed:15141091,
FT ECO:0000269|PubMed:19497856, ECO:0000269|PubMed:23435380"
FT /id="VAR_031026"
FT VARIANT 249
FT /note="P -> L (in BOR; uncertain significance;
FT dbSNP:rs368974927)"
FT /evidence="ECO:0000269|PubMed:21280147"
FT /id="VAR_064954"
FT HELIX 11..23
FT /evidence="ECO:0007829|PDB:4EGC"
FT HELIX 27..36
FT /evidence="ECO:0007829|PDB:4EGC"
FT HELIX 47..60
FT /evidence="ECO:0007829|PDB:4EGC"
FT HELIX 63..72
FT /evidence="ECO:0007829|PDB:4EGC"
FT HELIX 77..79
FT /evidence="ECO:0007829|PDB:4EGC"
FT HELIX 80..99
FT /evidence="ECO:0007829|PDB:4EGC"
FT HELIX 105..114
FT /evidence="ECO:0007829|PDB:4EGC"
FT HELIX 135..145
FT /evidence="ECO:0007829|PDB:4EGC"
FT HELIX 151..161
FT /evidence="ECO:0007829|PDB:4EGC"
FT HELIX 165..184
FT /evidence="ECO:0007829|PDB:4EGC"
SQ SEQUENCE 284 AA; 32210 MW; A4195376CFB9E3EA CRC64;
MSMLPSFGFT QEQVACVCEV LQQGGNLERL GRFLWSLPAC DHLHKNESVL KAKAVVAFHR
GNFRELYKIL ESHQFSPHNH PKLQQLWLKA HYVEAEKLRG RPLGAVGKYR VRRKFPLPRT
IWDGEETSYC FKEKSRGVLR EWYAHNPYPS PREKRELAEA TGLTTTQVSN WFKNRRQRDR
AAEAKERENT ENNNSSSNKQ NQLSPLEGGK PLMSSSEEEF SPPQSPDQNS VLLLQGNMGH
ARSSNYSLPG LTASQPSHGL QTHQHQLQDS LLGPLTSSLV DLGS
//
