SIX5_MOUSE
ID SIX5_MOUSE Reviewed; 719 AA.
AC P70178;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2004, sequence version 2.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Homeobox protein SIX5;
DE AltName: Full=DM locus-associated homeodomain protein homolog;
DE AltName: Full=Sine oculis homeobox homolog 5;
GN Name=Six5; Synonyms=Dmahp;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 53-719, AND DNA-BINDING.
RC STRAIN=BALB/cJ; TISSUE=Retina;
RX PubMed=8814301; DOI=10.1016/0014-5793(96)00899-x;
RA Kawakami K., Ohto H., Takizawa T., Saito T.;
RT "Identification and expression of Six family genes in mouse retina.";
RL FEBS Lett. 393:259-263(1996).
RN [3]
RP FUNCTION, AND INTERACTION WITH EYA1; EYA2 AND EYA3.
RX PubMed=10490620; DOI=10.1128/mcb.19.10.6815;
RA Ohto H., Kamada S., Tago K., Tominaga S., Ozaki H., Sato S., Kawakami K.;
RT "Cooperation of six and eya in activation of their target genes through
RT nuclear translocation of Eya.";
RL Mol. Cell. Biol. 19:6815-6824(1999).
RN [4]
RP DNA-BINDING.
RX PubMed=11978764; DOI=10.1093/hmg/11.9.1045;
RA Sato S., Nakamura M., Cho D.H., Tapscott S.J., Ozaki H., Kawakami K.;
RT "Identification of transcriptional targets for Six5: implication for the
RT pathogenesis of myotonic dystrophy type 1.";
RL Hum. Mol. Genet. 11:1045-1058(2002).
RN [5]
RP INTERACTION WITH EYA3.
RX PubMed=12215533; DOI=10.1128/mcb.22.19.6759-6766.2002;
RA Ikeda K., Watanabe Y., Ohto H., Kawakami K.;
RT "Molecular interaction and synergistic activation of a promoter by Six,
RT Eya, and Dach proteins mediated through CREB binding protein.";
RL Mol. Cell. Biol. 22:6759-6766(2002).
CC -!- FUNCTION: Transcription factor that is thought to be involved in
CC regulation of organogenesis. May be involved in determination and
CC maintenance of retina formation. Binds a 5'-GGTGTCAG-3' motif present
CC in the ARE regulatory element of ATP1A1. Binds a 5'-TCA[AG][AG]TTNC-3'
CC motif present in the MEF3 element in the myogenin promoter, and in the
CC IGFBP5 promoter (By similarity). Thought to be regulated by association
CC with Dach and Eya proteins, and seems to be coactivated by EYA1, EYA2
CC and EYA3. {ECO:0000250, ECO:0000269|PubMed:10490620}.
CC -!- SUBUNIT: Probably binds DNA dimer. Interacts with EYA3, and probably
CC EYA1 and EYA2. {ECO:0000269|PubMed:10490620,
CC ECO:0000269|PubMed:12215533}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108}.
CC -!- SIMILARITY: Belongs to the SIX/Sine oculis homeobox family.
CC {ECO:0000305}.
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DR EMBL; AC145199; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; D83146; BAA11824.1; -; mRNA.
DR CCDS; CCDS20889.1; -.
DR PIR; S74254; S74254.
DR RefSeq; NP_035513.1; NM_011383.1.
DR AlphaFoldDB; P70178; -.
DR SMR; P70178; -.
DR BioGRID; 203263; 1.
DR IntAct; P70178; 2.
DR STRING; 10090.ENSMUSP00000045973; -.
DR iPTMnet; P70178; -.
DR PhosphoSitePlus; P70178; -.
DR MaxQB; P70178; -.
DR PaxDb; P70178; -.
DR PRIDE; P70178; -.
DR ProteomicsDB; 261180; -.
DR Antibodypedia; 31386; 185 antibodies from 28 providers.
DR DNASU; 20475; -.
DR Ensembl; ENSMUST00000049454; ENSMUSP00000045973; ENSMUSG00000040841.
DR GeneID; 20475; -.
DR KEGG; mmu:20475; -.
DR UCSC; uc009fkr.1; mouse.
DR CTD; 147912; -.
DR MGI; MGI:106220; Six5.
DR VEuPathDB; HostDB:ENSMUSG00000040841; -.
DR eggNOG; KOG0775; Eukaryota.
DR GeneTree; ENSGT00940000162237; -.
DR HOGENOM; CLU_022250_0_0_1; -.
DR InParanoid; P70178; -.
DR OMA; AAMPIWP; -.
DR OrthoDB; 1061244at2759; -.
DR PhylomeDB; P70178; -.
DR TreeFam; TF315545; -.
DR BioGRID-ORCS; 20475; 4 hits in 73 CRISPR screens.
DR ChiTaRS; Six5; mouse.
DR PRO; PR:P70178; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P70178; protein.
DR Bgee; ENSMUSG00000040841; Expressed in ascending aorta and 190 other tissues.
DR Genevisible; P70178; MM.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
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:MGI.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0002088; P:lens development in camera-type eye; IMP:MGI.
DR GO; GO:0160024; P:Leydig cell proliferation; IMP:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:MGI.
DR GO; GO:1902723; P:negative regulation of skeletal muscle satellite cell proliferation; IMP:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007286; P:spermatid development; IMP:MGI.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR031701; SIX1_SD.
DR Pfam; PF00046; Homeodomain; 1.
DR Pfam; PF16878; SIX1_SD; 1.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW Activator; Developmental protein; DNA-binding; Homeobox; Nucleus;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..719
FT /note="Homeobox protein SIX5"
FT /id="PRO_0000049306"
FT DNA_BIND 194..253
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 1..73
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 241..287
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 265..279
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 719 AA; 73717 MW; B559618D3C831CD6 CRC64;
MATSPAEPSA GPAARGEAAA ATEEQEEEAR QLLQTLQAAE GEAAAAGAGD AAAAADSGSP
SGPGSPRETV TEVPTGLRFS PEQVACVCEA LLQAGHAGRL SRFLGALPPA ERLRGSDPVL
RARALVAFQR GEYAELYQLL ESRPFPAAHH AFLQDLYLRA RYHEAERARG RALGAVDKYR
LRKKFPLPKT IWDGEETVYC FKERSRAALK ACYRGNRYPT PDEKRRLATL TGLSLTQVSN
WFKNRRQRDR TGTGGGAPCK SESDGNPTTE DESSRSPEDL ERGVASMAAE APAQSSIFLA
GATSPATCPA SSSILVNGSF LAASSPPAVL LNGSPVIINS LALGENSSLG PLLLTGGSAP
QPQPSLQGVS EAKNSLVLDP QTGEVRLDEA QSEAPETKGV HGTTGEEIPG ALPQVVPGPP
PASTFPLTPG AVPAVAAPQV VPLSPSSGYP TGLSPTSPRL NLPQVVPTSQ VVTLPQAVGP
LQLLAAGPGS PVKVAAAAGP TNVHLINSSV GVTALQLPSS TAPGNFLLAN PVSGSPIVTG
VAVQQGKIIL TATFPTSMLV SQVLPPAPSL ALPLKQEPAI TVPEGALPVG PSPTLPEGHT
LGPISTQPLP PASVVTSGTS LPFSPDSSGL LSSFSAPLPE GLMLSPAAVP VWPAGLELST
GVEGLGTQAT HTVLRLPDPD PQGLLLGATT GTEVDEGLEA EAKVLTQLQS VPVEEPLEL