HSF4_DANRE
ID HSF4_DANRE Reviewed; 441 AA.
AC Q5CZP2; A0A2R8QAT5;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 2.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Heat shock factor protein 4;
GN Name=hsf4 {ECO:0000312|ZFIN:ZDB-GENE-050306-18};
GN ORFNames=zgc:113344 {ECO:0000312|EMBL:AAH90769.1,
GN ECO:0000312|ZFIN:ZDB-GENE-050306-18};
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 [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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22587838; DOI=10.1016/j.bbadis.2012.05.005;
RA Cui X., Zhang J., Du R., Wang L., Archacki S., Zhang Y., Yuan M., Ke T.,
RA Li H., Li D., Li C., Li D.W., Tang Z., Yin Z., Liu M.;
RT "HSF4 is involved in DNA damage repair through regulation of Rad51.";
RL Biochim. Biophys. Acta 1822:1308-1315(2012).
RN [4]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=22528049; DOI=10.1007/s12192-012-0337-3;
RA Swan C.L., Evans T.G., Sylvain N., Krone P.H.;
RT "Zebrafish HSF4: a novel protein that shares features of both HSF1 and HSF4
RT of mammals.";
RL Cell Stress Chaperones 17:623-637(2012).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=23507146; DOI=10.1016/j.bbadis.2013.03.007;
RA Cui X., Wang L., Zhang J., Du R., Liao S., Li D., Li C., Ke T., Li D.W.,
RA Huang H., Yin Z., Tang Z., Liu M.;
RT "HSF4 regulates DLAD expression and promotes lens de-nucleation.";
RL Biochim. Biophys. Acta 1832:1167-1172(2013).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=28981088; DOI=10.1038/cddis.2017.478;
RA Gao M., Huang Y., Wang L., Huang M., Liu F., Liao S., Yu S., Lu Z., Han S.,
RA Hu X., Qu Z., Liu X., Assefa Yimer T., Yang L., Tang Z., Li D.W., Liu M.;
RT "HSF4 regulates lens fiber cell differentiation by activating p53 and its
RT downstream regulators.";
RL Cell Death Dis. 8:e3082-e3082(2017).
RN [7]
RP FUNCTION.
RX PubMed=32061775; DOI=10.1016/j.bbadis.2020.165724;
RA Zhang J., Cui W.W., Du C., Huang Y., Pi X., Guo W., Wang J., Huang W.,
RA Chen D., Li J., Li H., Zhang J., Ma Y., Mu H., Zhang S., Liu M., Cui X.,
RA Hu Y.;
RT "Knockout of DNase1l1l abrogates lens denucleation process and causes
RT cataract in zebrafish.";
RL Biochim. Biophys. Acta 1866:165724-165724(2020).
RN [8]
RP FUNCTION.
RX PubMed=31786107; DOI=10.1016/j.bbagen.2019.129496;
RA Cui X., Feng R., Wang J., Du C., Pi X., Chen D., Li J., Li H., Zhang J.,
RA Zhang J., Mu H., Zhang F., Liu M., Hu Y.;
RT "Heat shock factor 4 regulates lysosome activity by modulating the alphaB-
RT crystallin-ATP6V1A-mTOR complex in ocular lens.";
RL Biochim. Biophys. Acta 1864:129496-129496(2020).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=33854238; DOI=10.1038/s41586-021-03439-w;
RA Morishita H., Eguchi T., Tsukamoto S., Sakamaki Y., Takahashi S., Saito C.,
RA Koyama-Honda I., Mizushima N.;
RT "Organelle degradation in the lens by PLAAT phospholipases.";
RL Nature 592:634-638(2021).
CC -!- FUNCTION: Heat-shock transcription factor that specifically binds heat
CC shock promoter elements (HSE) (PubMed:22528049). Required for
CC denucleation and organelle rupture and degradation that occur during
CC eye lens terminal differentiation, when fiber cells that compose the
CC lens degrade all membrane-bound organelles in order to provide lens
CC with transparency to allow the passage of light (PubMed:32061775,
CC PubMed:33854238). In this process, may regulate denucleation of lens
CC fiber cells in part by activating dnase1l1l and dnase2b transcription
CC (PubMed:32061775). May be involved in DNA repair through the
CC transcriptional regulation of rad51 (PubMed:22587838). May up-regulate
CC TP53 protein in lens fiber cells, possibly through protein
CC stabilization (PubMed:28981088). In the eye lens, controls the
CC expression of alpha-crystallin B chain/CRYAB and consequently may be
CC involved in the regulation of lysosomal acidification
CC (PubMed:31786107). {ECO:0000269|PubMed:22528049,
CC ECO:0000269|PubMed:22587838, ECO:0000269|PubMed:28981088,
CC ECO:0000269|PubMed:31786107, ECO:0000269|PubMed:32061775,
CC ECO:0000269|PubMed:33854238}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9ULV5}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5CZP2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5CZP2-2; Sequence=VSP_061246;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in the eye.
CC {ECO:0000269|PubMed:22528049, ECO:0000269|PubMed:28981088}.
CC -!- DEVELOPMENTAL STAGE: Expression in the ocular lens starts at as early
CC as 24 hours post fertilization (hpf). {ECO:0000269|PubMed:23507146}.
CC -!- DISRUPTION PHENOTYPE: In knockout animals, the eye lens grows normally,
CC but during lens differentiation, denucleation is impaired and the
CC degradation of mitochondria and endoplasmic reticulum is suppressed.
CC {ECO:0000269|PubMed:22587838, ECO:0000269|PubMed:23507146,
CC ECO:0000269|PubMed:28981088, ECO:0000269|PubMed:33854238}.
CC -!- SIMILARITY: Belongs to the HSF family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BX088710; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC090769; AAH90769.1; -; mRNA.
DR EMBL; BC165271; AAI65271.1; -; mRNA.
DR RefSeq; NP_001315137.1; NM_001328208.1.
DR SMR; Q5CZP2; -.
DR STRING; 7955.ENSDARP00000111022; -.
DR PaxDb; Q5CZP2; -.
DR Ensembl; ENSDART00000009912; ENSDARP00000025988; ENSDARG00000013251. [Q5CZP2-2]
DR Ensembl; ENSDART00000181589; ENSDARP00000150156; ENSDARG00000013251. [Q5CZP2-1]
DR GeneID; 503739; -.
DR KEGG; dre:503739; -.
DR CTD; 3299; -.
DR ZFIN; ZDB-GENE-050306-18; hsf4.
DR eggNOG; KOG0627; Eukaryota.
DR GeneTree; ENSGT00940000158063; -.
DR HOGENOM; CLU_038829_0_0_1; -.
DR OMA; HESFYIQ; -.
DR PhylomeDB; Q5CZP2; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 18.
DR Bgee; ENSDARG00000013251; Expressed in lens of camera-type eye and 3 other tissues.
DR ExpressionAtlas; Q5CZP2; baseline.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:InterPro.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:ZFIN.
DR GO; GO:0070306; P:lens fiber cell differentiation; IMP:UniProtKB.
DR GO; GO:0002089; P:lens morphogenesis in camera-type eye; IMP:ZFIN.
DR GO; GO:0032077; P:positive regulation of deoxyribonuclease activity; IMP:ZFIN.
DR GO; GO:1902746; P:regulation of lens fiber cell differentiation; IMP:ZFIN.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR000232; HSF_DNA-bd.
DR InterPro; IPR027725; HSF_fam.
DR InterPro; IPR010542; Vert_HSTF_C.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR10015; PTHR10015; 1.
DR Pfam; PF00447; HSF_DNA-bind; 1.
DR Pfam; PF06546; Vert_HS_TF; 1.
DR PRINTS; PR00056; HSFDOMAIN.
DR SMART; SM00415; HSF; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS00434; HSF_DOMAIN; 1.
PE 2: Evidence at transcript level;
KW Activator; Alternative splicing; DNA-binding; Nucleus; Reference proteome;
KW Stress response; Transcription; Transcription regulation.
FT CHAIN 1..441
FT /note="Heat shock factor protein 4"
FT /id="PRO_0000454112"
FT DNA_BIND 17..121
FT /evidence="ECO:0000250"
FT REGION 130..205
FT /note="Hydrophobic repeat HR-A/B"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV5"
FT VAR_SEQ 287..441
FT /note="Missing (in isoform 2)"
FT /id="VSP_061246"
SQ SEQUENCE 441 AA; 49773 MW; DE84B4C91209138F CRC64;
MQENPGSIGV DGGYASNVPA FLTKLWTLVE DPETNHLICW SATGTSFHVF DQGRFAKEVL
PKYFKHNNMA SFVRQLNMYG FRKVVNIEQS GLVKPERDDT EFQHLYFLQG HEHLLEHIKR
KVSIVKSEET KVRQEDLSKL LYEVQVLRSQ QENMEMQMQD MKQQNDVLWR EVVSLRQNHT
QQQKVMNKLI QFLFSQMQSN SPSTVGMKRK LPLMLDDGCS TPPASKFSHN HSMESLQESF
YIQSPSTESA SCSTSSVMTG GPIISDVTEI PQSSSMALQM QAEESREKCL MLIKEEPVSP
GVQGRAEGVP LGSCEVCAEP PVLPVAMVQS VLEGRGSNLG ERRAKRPMLE RPEIPDGVEN
VDMSLEDLQL LLRSHQQSME NNAAAMDQFT FSLPLNEWNF AEMDPNLKSE LANALIPAAV
SQYMFQGQEG ELYPTAGYEE Q
