ID HSF4_HUMAN Reviewed; 492 AA. AC Q9ULV5; Q99472; Q9ULV6; DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 2. DT 24-JAN-2024, entry version 189. DE RecName: Full=Heat shock factor protein 4; DE Short=HSF 4; DE Short=hHSF4; DE AltName: Full=Heat shock transcription factor 4; DE Short=HSTF 4; GN Name=HSF4; 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] (ISOFORM HSF4A). RC TISSUE=Heart; RX PubMed=8972228; DOI=10.1128/mcb.17.1.469; RA Nakai A., Tanabe M., Kawazoe Y., Inazawa J., Morimoto R.I., Nagata K.; RT "HSF4, a new member of the human heat shock factor family which lacks RT properties of a transcriptional activator."; RL Mol. Cell. Biol. 17:469-481(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM HSF4B), NUCLEOTIDE SEQUENCE [GENOMIC RP DNA] OF 1-396 (ISOFORM HSF4A), FUNCTION, SUBCELLULAR LOCATION, AND RP ALTERNATIVE SPLICING. 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [4] RP INTERACTION WITH DUSP26; MAPK1; MAPK2; MAPK8 AND MAP KINASE P38, AND PTM. 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 [5] RP SUMOYLATION AT LYS-293, PHOSPHORYLATION AT SER-298, FUNCTION, AND RP MUTAGENESIS OF LYS-293 AND SER-298. RX PubMed=16371476; DOI=10.1073/pnas.0503698102; RA Hietakangas V., Anckar J., Blomster H.A., Fujimoto M., Palvimo J.J., RA Nakai A., Sistonen L.; RT "PDSM, a motif for phosphorylation-dependent SUMO modification."; RL Proc. Natl. Acad. Sci. U.S.A. 103:45-50(2006). RN [6] RP FUNCTION, AND CHARACTERIZATION OF VARIANTS CTRCT5 ASP-19; VAL-86; PRO-114 RP AND CYS-119. 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 [7] RP INTERACTION WITH ALKBH4. RX PubMed=23145062; DOI=10.1371/journal.pone.0049045; RA Bjornstad L.G., Meza T.J., Otterlei M., Olafsrud S.M., Meza-Zepeda L.A., RA Falnes P.O.; RT "Human ALKBH4 interacts with proteins associated with transcription."; RL PLoS ONE 7:E49045-E49045(2012). RN [8] RP FUNCTION, AND CHARACTERIZATION OF VARIANTS CTRCT5 ASP-19; VAL-86; PRO-114 RP AND CYS-119. 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 [9] RP FUNCTION. 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 [10] RP VARIANTS CTRCT5 ASP-19; VAL-86; PRO-114 AND CYS-119, AND TISSUE RP SPECIFICITY. RX PubMed=12089525; DOI=10.1038/ng921; RA Bu L., Jin Y., Shi Y., Chu R., Ban A., Eiberg H., Andres L., Jiang H., RA Zheng G., Qian M., Cui B., Xia Y., Liu J., Hu L., Zhao G., Hayden M.R., RA Kong X.; RT "Mutant DNA-binding domain of HSF4 is associated with autosomal dominant RT lamellar and Marner cataract."; RL Nat. Genet. 31:276-278(2002). RN [11] RP VARIANT CTRCT5 HIS-73. RX PubMed=16876512; DOI=10.1016/j.ajo.2006.03.056; RA Ke T., Wang Q.K., Ji B., Wang X., Liu P., Zhang X., Tang Z., Ren X., RA Liu M.; RT "Novel HSF4 mutation causes congenital total white cataract in a Chinese RT family."; RL Am. J. Ophthalmol. 142:298-303(2006). RN [12] RP VARIANTS CTRCT5 PRO-114 AND CYS-119. RX PubMed=19182255; DOI=10.1167/iovs.08-3149; RA Hansen L., Mikkelsen A., Nuernberg P., Nuernberg G., Anjum I., Eiberg H., RA Rosenberg T.; RT "Comprehensive mutational screening in a cohort of Danish families with RT hereditary congenital cataract."; RL Invest. Ophthalmol. Vis. Sci. 50:3291-3303(2009). CC -!- FUNCTION: Heat-shock transcription factor that specifically binds heat CC shock promoter elements (HSE) (PubMed:22587838, PubMed:23507146). CC Required for denucleation and organelle rupture and degradation that CC occur during eye lens terminal differentiation, when fiber cells that CC compose the lens degrade all membrane-bound organelles in order to CC provide lens with transparency to allow the passage of light (By CC similarity). In this process, may regulate denucleation of lens fiber CC cells in part by activating DNASE2B transcription (By similarity). May CC be involved in DNA repair through the transcriptional regulation of CC RAD51 (PubMed:22587838). May up-regulate p53/TP53 protein in eye lens CC fiber cells, possibly through protein stabilization (PubMed:28981088). CC In the eye lens, controls the expression of alpha-crystallin B CC chain/CRYAB and consequently may be involved in the regulation of CC lysosomal acidification (By similarity). {ECO:0000250|UniProtKB:Q5CZP2, CC ECO:0000250|UniProtKB:Q9R0L1, ECO:0000269|PubMed:22587838, CC ECO:0000269|PubMed:23507146, ECO:0000269|PubMed:28981088}. CC -!- FUNCTION: [Isoform HSF4A]: Transcriptional repressor. CC {ECO:0000269|PubMed:10488131}. CC -!- FUNCTION: [Isoform HSF4B]: Transcriptional activator. CC {ECO:0000269|PubMed:10488131, ECO:0000269|PubMed:16371476}. CC -!- SUBUNIT: Homotrimer (By similarity). Exhibits constitutive DNA binding CC and forms trimers even in the absence of stress (By similarity). CC Interacts with ALKBH4, DUSP26, MAPK1, MAPK2, MAPK8 and MAP kinase p38 CC (PubMed:16581800, PubMed:23145062). {ECO:0000250|UniProtKB:Q9R0L1, CC ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:23145062}. CC -!- INTERACTION: CC Q9ULV5-2; Q5BKX5-3: ACTMAP; NbExp=3; IntAct=EBI-12056251, EBI-11976299; CC Q9ULV5-2; Q9ULX6: AKAP8L; NbExp=3; IntAct=EBI-12056251, EBI-357530; CC Q9ULV5-2; Q5SWW7: C10orf55; NbExp=3; IntAct=EBI-12056251, EBI-12809220; CC Q9ULV5-2; A1KXE4-2: FAM168B; NbExp=3; IntAct=EBI-12056251, EBI-12193763; CC Q9ULV5-2; O75593: FOXH1; NbExp=3; IntAct=EBI-12056251, EBI-1759806; CC Q9ULV5-2; Q12951-2: FOXI1; NbExp=3; IntAct=EBI-12056251, EBI-12018822; CC Q9ULV5-2; Q9NXC2: GFOD1; NbExp=3; IntAct=EBI-12056251, EBI-8799578; CC Q9ULV5-2; O14964: HGS; NbExp=3; IntAct=EBI-12056251, EBI-740220; CC Q9ULV5-2; Q5TA45: INTS11; NbExp=3; IntAct=EBI-12056251, EBI-748258; CC Q9ULV5-2; Q15323: KRT31; NbExp=3; IntAct=EBI-12056251, EBI-948001; CC Q9ULV5-2; O76014: KRT37; NbExp=3; IntAct=EBI-12056251, EBI-1045716; CC Q9ULV5-2; O76015: KRT38; NbExp=3; IntAct=EBI-12056251, EBI-1047263; CC Q9ULV5-2; Q6A162: KRT40; NbExp=3; IntAct=EBI-12056251, EBI-10171697; CC Q9ULV5-2; Q3LI70: KRTAP19-6; NbExp=3; IntAct=EBI-12056251, EBI-12805508; CC Q9ULV5-2; Q3SYF9: KRTAP19-7; NbExp=3; IntAct=EBI-12056251, EBI-10241353; CC Q9ULV5-2; Q9BYR8: KRTAP3-1; NbExp=3; IntAct=EBI-12056251, EBI-9996449; CC Q9ULV5-2; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-12056251, EBI-11962084; CC Q9ULV5-2; Q13064: MKRN3; NbExp=3; IntAct=EBI-12056251, EBI-2340269; CC Q9ULV5-2; P0CG21: NHLRC4; NbExp=3; IntAct=EBI-12056251, EBI-12868744; CC Q9ULV5-2; P37198: NUP62; NbExp=3; IntAct=EBI-12056251, EBI-347978; CC Q9ULV5-2; O43482: OIP5; NbExp=5; IntAct=EBI-12056251, EBI-536879; CC Q9ULV5-2; Q8WWB5: PIH1D2; NbExp=3; IntAct=EBI-12056251, EBI-10232538; CC Q9ULV5-2; P78337: PITX1; NbExp=3; IntAct=EBI-12056251, EBI-748265; CC Q9ULV5-2; O15496: PLA2G10; NbExp=3; IntAct=EBI-12056251, EBI-726466; CC Q9ULV5-2; Q8ND30: PPFIBP2; NbExp=3; IntAct=EBI-12056251, EBI-744056; CC Q9ULV5-2; Q86VW0: SESTD1; NbExp=3; IntAct=EBI-12056251, EBI-6117072; CC Q9ULV5-2; P56693: SOX10; NbExp=3; IntAct=EBI-12056251, EBI-1167533; CC Q9ULV5-2; P06753: TPM3; NbExp=3; IntAct=EBI-12056251, EBI-355607; CC Q9ULV5-2; Q6NVU6: UFSP1; NbExp=3; IntAct=EBI-12056251, EBI-12068150; CC Q9ULV5-2; Q9BYJ9: YTHDF1; NbExp=3; IntAct=EBI-12056251, EBI-1051237; CC Q9ULV5-2; Q9H0C1: ZMYND12; NbExp=3; IntAct=EBI-12056251, EBI-12030590; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10488131}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=HSF4B {ECO:0000303|PubMed:10488131}; CC IsoId=Q9ULV5-1; Sequence=Displayed; CC Name=HSF4A {ECO:0000303|PubMed:10488131}; CC IsoId=Q9ULV5-2; Sequence=VSP_002418; CC -!- TISSUE SPECIFICITY: Expressed in heart, skeletal muscle, eye and brain, CC and at much lower levels in some other tissues. CC {ECO:0000269|PubMed:12089525}. CC -!- PTM: Phosphorylated mainly on serine residues. Phosphorylation on Ser- CC 298 promotes sumoylation on Lys-293. {ECO:0000269|PubMed:16371476}. 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. {ECO:0000269|PubMed:16371476}. CC -!- DISEASE: Cataract 5, multiple types (CTRCT5) [MIM:116800]: An CC opacification of the crystalline lens of the eye that frequently CC results in visual impairment or blindness. Opacities vary in CC morphology, are often confined to a portion of the lens, and may be CC static or progressive. CTRCT5 includes infantile, lamellar, zonular, CC nuclear, anterior polar, stellate, and Marner-type cataracts, among CC others. Finger malformation is observed in some kindreds. CC {ECO:0000269|PubMed:12089525, ECO:0000269|PubMed:16876512, CC ECO:0000269|PubMed:19182255, ECO:0000269|PubMed:22587838, CC ECO:0000269|PubMed:23507146}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the HSF family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Eye disease Heat shock transcription factor 4 CC (HSF4); Note=Leiden Open Variation Database (LOVD); CC URL="https://databases.lovd.nl/shared/genes/HSF4"; 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; D87673; BAA13433.1; -; mRNA. DR EMBL; AB029347; BAA84581.1; -; Genomic_DNA. DR EMBL; AB029348; BAA84582.1; -; mRNA. DR EMBL; AC074143; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS42175.1; -. [Q9ULV5-1] DR CCDS; CCDS45510.1; -. [Q9ULV5-2] DR RefSeq; NP_001035757.1; NM_001040667.2. [Q9ULV5-1] DR RefSeq; NP_001529.2; NM_001538.3. [Q9ULV5-2] DR PDB; 6J6V; X-ray; 1.20 A; A=17-121. DR PDB; 6J6W; X-ray; 1.69 A; A/B=17-121. DR PDBsum; 6J6V; -. DR PDBsum; 6J6W; -. DR AlphaFoldDB; Q9ULV5; -. DR SMR; Q9ULV5; -. DR BioGRID; 109532; 61. DR ELM; Q9ULV5; -. DR IntAct; Q9ULV5; 44. DR MINT; Q9ULV5; -. DR STRING; 9606.ENSP00000430947; -. DR ChEMBL; CHEMBL3988631; -. DR GlyGen; Q9ULV5; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q9ULV5; -. DR PhosphoSitePlus; Q9ULV5; -. DR BioMuta; HSF4; -. DR DMDM; 296434534; -. DR jPOST; Q9ULV5; -. DR MassIVE; Q9ULV5; -. DR MaxQB; Q9ULV5; -. DR PaxDb; 9606-ENSP00000264009; -. DR PeptideAtlas; Q9ULV5; -. DR ProteomicsDB; 85135; -. [Q9ULV5-1] DR ProteomicsDB; 85136; -. [Q9ULV5-2] DR Antibodypedia; 29424; 356 antibodies from 32 providers. DR DNASU; 3299; -. DR Ensembl; ENST00000521374.6; ENSP00000430947.2; ENSG00000102878.18. [Q9ULV5-1] DR Ensembl; ENST00000584272.5; ENSP00000463706.1; ENSG00000102878.18. [Q9ULV5-2] DR GeneID; 3299; -. DR KEGG; hsa:3299; -. DR MANE-Select; ENST00000521374.6; ENSP00000430947.2; NM_001374675.1; NP_001361604.1. DR UCSC; uc002erl.2; human. [Q9ULV5-1] DR AGR; HGNC:5227; -. DR CTD; 3299; -. DR DisGeNET; 3299; -. DR GeneCards; HSF4; -. DR HGNC; HGNC:5227; HSF4. DR HPA; ENSG00000102878; Low tissue specificity. DR MalaCards; HSF4; -. DR MIM; 116800; phenotype. DR MIM; 602438; gene. DR neXtProt; NX_Q9ULV5; -. DR OpenTargets; ENSG00000102878; -. DR Orphanet; 441452; Early-onset lamellar cataract. DR Orphanet; 98994; Total early-onset cataract. DR PharmGKB; PA29496; -. DR VEuPathDB; HostDB:ENSG00000102878; -. DR eggNOG; KOG0627; Eukaryota. DR GeneTree; ENSGT00940000158063; -. DR InParanoid; Q9ULV5; -. DR OMA; ACPGKDV; -. DR OrthoDB; 1117127at2759; -. DR PhylomeDB; Q9ULV5; -. DR TreeFam; TF330401; -. DR PathwayCommons; Q9ULV5; -. DR SignaLink; Q9ULV5; -. DR SIGNOR; Q9ULV5; -. DR BioGRID-ORCS; 3299; 15 hits in 1179 CRISPR screens. DR ChiTaRS; HSF4; human. DR GeneWiki; HSF4; -. DR GenomeRNAi; 3299; -. DR Pharos; Q9ULV5; Tbio. DR PRO; PR:Q9ULV5; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q9ULV5; Protein. DR Bgee; ENSG00000102878; Expressed in right hemisphere of cerebellum and 117 other cell types or tissues. DR ExpressionAtlas; Q9ULV5; baseline and differential. DR GO; GO:0000785; C:chromatin; IDA:ARUK-UCL. DR GO; GO:0016607; C:nuclear speck; IDA:HPA. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. 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; IDA:ARUK-UCL. DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl. DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:ARUK-UCL. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0070306; P:lens fiber cell differentiation; ISS:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:ARUK-UCL. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 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:SF213; HEAT SHOCK FACTOR PROTEIN 4; 1. DR PANTHER; PTHR10015; HEAT SHOCK TRANSCRIPTION FACTOR; 1. DR Pfam; PF00447; HSF_DNA-bind; 1. DR PRINTS; PR00056; HSFDOMAIN. DR SMART; SM00415; HSF; 1. DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1. DR PROSITE; PS00434; HSF_DOMAIN; 1. DR Genevisible; Q9ULV5; HS. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Cataract; Disease variant; KW DNA-binding; Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome; KW Repressor; Stress response; Transcription; Transcription regulation; KW Ubl conjugation. FT CHAIN 1..492 FT /note="Heat shock factor protein 4" FT /id="PRO_0000124571" FT DNA_BIND 17..121 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 REGION 246..285 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 337..400 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:0000269|PubMed:16371476" FT CROSSLNK 293 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:16371476" FT VAR_SEQ 245..319 FT /note="LPETNLGLSPHRARGPIISDIPEDSPSPEGTRLSPSSDGRREKGLALLKEEP FT ASPGGDGEAGLALAPNECDFCVT -> STYSLSQRQIWALALTGPGAPSSLTSQKTLHP FT LRGPGFLPPVMAG (in isoform HSF4A)" FT /evidence="ECO:0000303|PubMed:8972228" FT /id="VSP_002418" FT VARIANT 19 FT /note="A -> D (in CTRCT5; sporadic; decreased binding to FT the DNASE2B promoter and decreased DNASE2B expression; FT impaired RAD51 induction and UVC-induced DNA damage repair; FT dbSNP:rs121909049)" FT /evidence="ECO:0000269|PubMed:12089525, FT ECO:0000269|PubMed:22587838, ECO:0000269|PubMed:23507146" FT /id="VAR_017558" FT VARIANT 73 FT /note="R -> H (in CTRCT5; decreased binding to the DNASE2B FT promoter and decreased DNASE2B expression; impaired RAD51 FT induction and UVC-induced DNA damage repair)" FT /evidence="ECO:0000269|PubMed:16876512, FT ECO:0000269|PubMed:22587838, ECO:0000269|PubMed:23507146" FT /id="VAR_029018" FT VARIANT 86 FT /note="I -> V (in CTRCT5; sporadic; dbSNP:rs121909050)" FT /evidence="ECO:0000269|PubMed:12089525" FT /id="VAR_017559" FT VARIANT 114 FT /note="L -> P (in CTRCT5; decreased binding to the DNASE2B FT promoter and decreased DNASE2B expression; impaired RAD51 FT induction; dbSNP:rs121909048)" FT /evidence="ECO:0000269|PubMed:12089525, FT ECO:0000269|PubMed:19182255, ECO:0000269|PubMed:22587838, FT ECO:0000269|PubMed:23507146" FT /id="VAR_017560" FT VARIANT 119 FT /note="R -> C (in CTRCT5; uncertain significance; decreased FT binding to the DNASE2B promoter and decreased DNASE2B FT expression; impaired RAD51 induction and UVC-induced DNA FT damage repair; dbSNP:rs28937573)" FT /evidence="ECO:0000269|PubMed:12089525, FT ECO:0000269|PubMed:19182255, ECO:0000269|PubMed:22587838, FT ECO:0000269|PubMed:23507146" FT /id="VAR_017561" FT MUTAGEN 293 FT /note="K->R: Abolishes sumoylation. 10-fold increased in FT transactivational activity." FT /evidence="ECO:0000269|PubMed:16371476" FT MUTAGEN 298 FT /note="S->A: Abolishes phosphorylation. Greatly reduced FT sumoylation. Greatly increased transactivational activity." FT /evidence="ECO:0000269|PubMed:16371476" FT CONFLICT 1 FT /note="M -> MV (in Ref. 1; BAA13433 and 2; BAA84582)" FT /evidence="ECO:0000305" FT HELIX 19..29 FT /evidence="ECO:0007829|PDB:6J6V" FT HELIX 31..33 FT /evidence="ECO:0007829|PDB:6J6V" FT TURN 34..36 FT /evidence="ECO:0007829|PDB:6J6V" FT STRAND 37..39 FT /evidence="ECO:0007829|PDB:6J6V" FT STRAND 43..49 FT /evidence="ECO:0007829|PDB:6J6V" FT HELIX 51..57 FT /evidence="ECO:0007829|PDB:6J6V" FT HELIX 59..63 FT /evidence="ECO:0007829|PDB:6J6V" FT HELIX 68..77 FT /evidence="ECO:0007829|PDB:6J6V" FT STRAND 81..85 FT /evidence="ECO:0007829|PDB:6J6W" FT STRAND 99..102 FT /evidence="ECO:0007829|PDB:6J6V" FT HELIX 113..116 FT /evidence="ECO:0007829|PDB:6J6V" SQ SEQUENCE 492 AA; 53011 MW; D5F1C0D68014BC2E CRC64; MQEAPAALPT EPGPSPVPAF LGKLWALVGD PGTDHLIRWS PSGTSFLVSD QSRFAKEVLP QYFKHSNMAS FVRQLNMYGF RKVVSIEQGG LLRPERDHVE FQHPSFVRGR EQLLERVRRK VPALRGDDGR WRPEDLGRLL GEVQALRGVQ ESTEARLREL RQQNEILWRE VVTLRQSHGQ QHRVIGKLIQ CLFGPLQAGP SNAGGKRKLS LMLDEGSSCP TPAKFNTCPL PGALLQDPYF IQSPLPETNL GLSPHRARGP IISDIPEDSP SPEGTRLSPS SDGRREKGLA LLKEEPASPG GDGEAGLALA PNECDFCVTA PPPLPVAVVQ AILEGKGSFS PEGPRNAQQP EPGDPREIPD RGPLGLESGD RSPESLLPPM LLQPPQESVE PAGPLDVLGP SLQGREWTLM DLDMELSLMQ PLVPERGEPE LAVKGLNSPS PGKDPTLGAP LLLDVQAALG GPALGLPGAL TIYSTPESRT ASYLGPEASP SP //