ID SIX1A_DANRE Reviewed; 283 AA.
AC Q6DHF9; B8A5G7;
DT 26-JUN-2013, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2013, sequence version 2.
DT 27-MAR-2024, entry version 138.
DE RecName: Full=Homeobox protein six1a;
DE AltName: Full=Homeobox protein six1b;
DE AltName: Full=Sine oculis homeobox homolog 1a;
DE AltName: Full=Sine oculis homeobox homolog 1b;
GN Name=six1a; Synonyms=six1b;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RC STRAIN=AB;
RX PubMed=18789916; DOI=10.1016/j.ydbio.2008.08.015;
RA Bessarab D.A., Chong S.W., Srinivas B.P., Korzh V.;
RT "Six1a is required for the onset of fast muscle differentiation in
RT zebrafish.";
RL Dev. Biol. 323:216-228(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23444384; DOI=10.1242/jcs.119917;
RA Nord H., Skalman L.N., von Hofsten J.;
RT "Six1 regulates proliferation of Pax7+ muscle progenitors in zebrafish.";
RL J. Cell Sci. 126:1868-1880(2013).
CC -!- FUNCTION: Transcription factor that is involved in the regulation of
CC cell proliferation, apoptosis and embryonic development. Depending on
CC context, functions as a transcriptional repressor or activator. Plays
CC an important role in the development of the inner ear, where it
CC promotes hair cell proliferation and inhibits proliferation of neural
CC progenitor cells (By similarity). Required for normal myogenesis. Plays
CC a role in the development of fast muscle fibers throughout the body, as
CC well as the development of craniofacial muscles. {ECO:0000250,
CC ECO:0000269|PubMed:23444384}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q15475}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q15475}.
CC -!- DEVELOPMENTAL STAGE: Ubiquitous during segmentation. Detected in otic
CC vesicle and statoacoustic ganglion at later stages of development. At
CC 24 hpf, detected in developing fast muscle throughout the trunk.
CC {ECO:0000269|PubMed:18789916}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein disrupts both
CC skeletal muscle development in the trunk and cranial muscle
CC development. Disrupts myogenesis by interfering with the proliferation
CC of dermomyotomal cells expressing pax7. {ECO:0000269|PubMed:23444384}.
CC -!- SIMILARITY: Belongs to the SIX/Sine oculis homeobox family.
CC {ECO:0000305}.
CC -!- CAUTION: Zebrafish has two genes coding for six1 orthologs. This gene
CC is called six1a by ZFIN, but has also been described as six1b
CC (PubMed:18789916). {ECO:0000305|PubMed:18789916}.
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DR EMBL; EU109509; ABW83199.1; -; mRNA.
DR EMBL; BX537123; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC076015; AAH76015.1; -; mRNA.
DR RefSeq; NP_001009904.1; NM_001009904.1.
DR AlphaFoldDB; Q6DHF9; -.
DR SMR; Q6DHF9; -.
DR STRING; 7955.ENSDARP00000057431; -.
DR PaxDb; 7955-ENSDARP00000057431; -.
DR DNASU; 494168; -.
DR GeneID; 494168; -.
DR KEGG; dre:494168; -.
DR AGR; ZFIN:ZDB-GENE-040718-155; -.
DR CTD; 494168; -.
DR ZFIN; ZDB-GENE-040718-155; six1a.
DR eggNOG; KOG0775; Eukaryota.
DR HOGENOM; CLU_046914_2_0_1; -.
DR InParanoid; Q6DHF9; -.
DR OMA; MIFTAEQ; -.
DR OrthoDB; 602349at2759; -.
DR PhylomeDB; Q6DHF9; -.
DR TreeFam; TF315545; -.
DR PRO; PR:Q6DHF9; -.
DR Proteomes; UP000000437; Chromosome 13.
DR Bgee; ENSDARG00000039304; Expressed in muscle tissue and 23 other cell types or tissues.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IMP:ZFIN.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:2000980; P:regulation of inner ear receptor cell differentiation; IMP:ZFIN.
DR GO; GO:0014857; P:regulation of skeletal muscle cell proliferation; IMP:ZFIN.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0048741; P:skeletal muscle fiber development; IMP:ZFIN.
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 2: Evidence at transcript level;
KW Activator; Apoptosis; Cytoplasm; Developmental protein; DNA-binding;
KW Homeobox; Nucleus; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..283
FT /note="Homeobox protein six1a"
FT /id="PRO_0000422773"
FT DNA_BIND 124..183
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 168..264
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..236
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 241
FT /note="A -> G (in Ref. 1; ABW83199 and 3; AAH76015)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 283 AA; 31928 MW; D82E3C852C9F49A1 CRC64;
MSILPSFGFT QEQVACVCEV LQQGGNLERL GRFLWSLPAC DHLHKNESVL KAKAVVAFHR
GNFRELYKIL ESYQFSTHNH PKMQQLWLKA HYVEAEKLRG RPLGAVGKYR VRRKFPLPRT
IWDGEETSYC FKEKSRSVLR EWYTHNPYPS PREKRELAEA TGLTTTQVSN WFKNRRQRDR
AAEAKERENG ENNGVGGKQS QRSPLDGVKS LMSSSEDEFS PPQSPEHSSV LLLQGTMNNP
AAPAYPMPGL GAPHPLHGMQ GHPHQIQDSL LGSLTSSLVD LGS
//