HSF4_MOUSE
ID HSF4_MOUSE Reviewed; 492 AA.
AC Q9R0L1; Q9R0L2;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2001, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Heat shock factor protein 4;
DE Short=HSF 4;
DE Short=mHSF4;
DE AltName: Full=Heat shock transcription factor 4;
DE Short=HSTF 4;
GN Name=Hsf4;
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 [MRNA] (ISOFORMS HSF4A AND HSF4B), FUNCTION, AND
RP SUBUNIT.
RX PubMed=10488131; DOI=10.1074/jbc.274.39.27845;
RA Tanabe M., Sasai N., Nagata K., Liu X.-D., Liu P.C.C., Thiele D.J.,
RA Nakai A.;
RT "The mammalian HSF4 gene generates both an activator and a repressor of
RT heat shock genes by alternative splicing.";
RL J. Biol. Chem. 274:27845-27856(1999).
RN [2]
RP TISSUE SPECIFICITY.
RX PubMed=16581800; DOI=10.1128/mcb.26.8.3282-3294.2006;
RA Hu Y., Mivechi N.F.;
RT "Association and regulation of heat shock transcription factor 4b with both
RT extracellular signal-regulated kinase mitogen-activated protein kinase and
RT dual-specificity tyrosine phosphatase DUSP26.";
RL Mol. Cell. Biol. 26:3282-3294(2006).
RN [3]
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).
CC -!- FUNCTION: Heat-shock transcription factor that specifically binds heat
CC shock promoter elements (HSE) (By similarity). 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 (By similarity). In
CC this process, may regulate denucleation of lens fiber cells in part by
CC activating DNASE2B transcription (By similarity). May be involved in
CC DNA repair through the transcriptional regulation of RAD51 (By
CC similarity). May up-regulate p53/TP53 protein in eye lens fiber cells,
CC possibly through protein stabilization (By similarity). In the eye
CC lens, controls the expression of alpha-crystallin B chain/CRYAB and
CC consequently may be involved in the regulation of lysosomal
CC acidification (PubMed:31786107). {ECO:0000250|UniProtKB:Q5CZP2,
CC ECO:0000250|UniProtKB:Q9ULV5, ECO:0000269|PubMed:31786107}.
CC -!- FUNCTION: [Isoform HSF4A]: Transcriptional repressor.
CC {ECO:0000269|PubMed:10488131}.
CC -!- FUNCTION: [Isoform HSF4B]: Transcriptional activator.
CC {ECO:0000269|PubMed:10488131}.
CC -!- SUBUNIT: Homotrimer (PubMed:10488131). Exhibits constitutive DNA
CC binding and forms trimers even in the absence of stress
CC (PubMed:10488131). Interacts with ALKBH4, DUSP26, MAPK1, MAPK2, MAPK8
CC and MAP kinase p38 (By similarity). {ECO:0000250|UniProtKB:Q9ULV5,
CC ECO:0000269|PubMed:10488131}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9ULV5}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=HSF4B;
CC IsoId=Q9R0L1-1; Sequence=Displayed;
CC Name=HSF4A;
CC IsoId=Q9R0L1-2; Sequence=VSP_002419;
CC -!- TISSUE SPECIFICITY: Preferentially expressed in brain and lung. Also
CC found in the eye. Slightly detected in liver and skeletal muscle.
CC Isoform B is the major species in various tissues.
CC {ECO:0000269|PubMed:16581800}.
CC -!- PTM: Phosphorylated mainly on serine residues. Phosphorylation on Ser-
CC 298 promotes sumoylation on Lys-293 (By similarity). {ECO:0000250}.
CC -!- PTM: Isoform HSF4B is constitutively sumoylated. Sumoylation represses
CC the transcriptional activity and is promoted by phosphorylation on Ser-
CC 298. HSFA is not sumoylated (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the HSF family. {ECO:0000305}.
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DR EMBL; AB029349; BAA84583.1; -; mRNA.
DR EMBL; AB029350; BAA84584.1; -; mRNA.
DR CCDS; CCDS57638.1; -. [Q9R0L1-2]
DR CCDS; CCDS57639.1; -. [Q9R0L1-1]
DR RefSeq; NP_001242971.1; NM_001256042.1. [Q9R0L1-1]
DR RefSeq; NP_036069.1; NM_011939.3. [Q9R0L1-2]
DR AlphaFoldDB; Q9R0L1; -.
DR SMR; Q9R0L1; -.
DR STRING; 10090.ENSMUSP00000048904; -.
DR iPTMnet; Q9R0L1; -.
DR PhosphoSitePlus; Q9R0L1; -.
DR MaxQB; Q9R0L1; -.
DR PaxDb; Q9R0L1; -.
DR PRIDE; Q9R0L1; -.
DR ProteomicsDB; 273141; -. [Q9R0L1-1]
DR ProteomicsDB; 273142; -. [Q9R0L1-2]
DR Antibodypedia; 29424; 327 antibodies from 32 providers.
DR DNASU; 26386; -.
DR Ensembl; ENSMUST00000036127; ENSMUSP00000048904; ENSMUSG00000033249. [Q9R0L1-1]
DR Ensembl; ENSMUST00000173859; ENSMUSP00000134213; ENSMUSG00000033249. [Q9R0L1-2]
DR GeneID; 26386; -.
DR KEGG; mmu:26386; -.
DR UCSC; uc009nca.2; mouse. [Q9R0L1-2]
DR UCSC; uc009ncb.2; mouse. [Q9R0L1-1]
DR CTD; 3299; -.
DR MGI; MGI:1347058; Hsf4.
DR VEuPathDB; HostDB:ENSMUSG00000033249; -.
DR eggNOG; KOG0627; Eukaryota.
DR GeneTree; ENSGT00940000158063; -.
DR InParanoid; Q9R0L1; -.
DR OMA; GCRACPE; -.
DR PhylomeDB; Q9R0L1; -.
DR TreeFam; TF330401; -.
DR BioGRID-ORCS; 26386; 2 hits in 75 CRISPR screens.
DR PRO; PR:Q9R0L1; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q9R0L1; protein.
DR Bgee; ENSMUSG00000033249; Expressed in lens of camera-type eye and 94 other tissues.
DR ExpressionAtlas; Q9R0L1; baseline and differential.
DR Genevisible; Q9R0L1; MM.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0043010; P:camera-type eye development; IMP:MGI.
DR GO; GO:0048468; P:cell development; IMP:MGI.
DR GO; GO:0030154; P:cell differentiation; IMP:MGI.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0050673; P:epithelial cell proliferation; IMP:MGI.
DR GO; GO:0001654; P:eye development; IMP:MGI.
DR GO; GO:0033169; P:histone H3-K9 demethylation; IDA:MGI.
DR GO; GO:0070306; P:lens fiber cell differentiation; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0045597; P:positive regulation of cell differentiation; IMP:MGI.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0007601; P:visual perception; IMP:MGI.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR000232; HSF_DNA-bd.
DR InterPro; IPR027725; HSF_fam.
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 PRINTS; PR00056; HSFDOMAIN.
DR SMART; SM00415; HSF; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS00434; HSF_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; DNA-binding; Isopeptide bond; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Stress response;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..492
FT /note="Heat shock factor protein 4"
FT /id="PRO_0000124572"
FT DNA_BIND 17..122
FT /evidence="ECO:0000250"
FT REGION 129..203
FT /note="Hydrophobic repeat HR-A/B"
FT REGION 245..322
FT /note="Interactions with DUSP26, MAPK1 and MAPK2"
FT /evidence="ECO:0000250"
FT REGION 263..282
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 337..378
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 364..389
FT /note="Hydrophobic repeat HR-C"
FT MOD_RES 298
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ULV5"
FT CROSSLNK 293
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 245..319
FT /note="LPETTLGLSPHRARGPIISDIPEDSPSPEGHRLSPSGGCRRVKGLALLKEEP
FT ASPGGDGEAGLALAPNECDFCVT -> SPCSPSQRPRWASALTGPEGPSSLTSQKILHL
FT LKDTGFLPPVVAG (in isoform HSF4A)"
FT /evidence="ECO:0000303|PubMed:10488131"
FT /id="VSP_002419"
SQ SEQUENCE 492 AA; 53255 MW; 952AB78255AD3CA0 CRC64;
MQEAPAALPT EPGPSPVPAF LGKLWALVGD PGTDHLIRWS PSGTSFLVSD QSRFAKEVLP
QYFKHSNMAS FVRQLNMYGF RKVVSIEQGG LLRPERDHVE FQHPSFVRGR EQLLERVRRK
VPALRGDDSR WRPEDLSRLL GEVQALRGVQ ESTEARLQEL RQQNEILWRE VVTLRQSHSQ
QHRVIGKLIQ CLFGPLQTGP SSTGAKRKLS LMLDEGSACS ASAKFNACPV SGALLQDPYF
IQSPLPETTL GLSPHRARGP IISDIPEDSP SPEGHRLSPS GGCRRVKGLA LLKEEPASPG
GDGEAGLALA PNECDFCVTA PPPLPVAVVQ AILEGKGSYS PEGPRSVQQP EPRGPREVPD
RGTLGLDRGN RSPESLLPPM LLRPAPETLE PVAPVDVLGP SLHGREWTLM DLDMELSLMQ
PLAPETDEAE LTVKELNSSG VGKDHTLGTP LMLDVQADLE GAALSVPGAL TLYNVTESNA
SYLDPGASPS SP
