HSF4_HUMAN
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 03-AUG-2022, entry version 181.
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; Q9ULX6: AKAP8L; NbExp=3; IntAct=EBI-12056251, EBI-357530;
CC Q9ULV5-2; Q5SWW7: C10orf55; NbExp=3; IntAct=EBI-12056251, EBI-12809220;
CC Q9ULV5-2; Q5BKX5-3: C19orf54; NbExp=3; IntAct=EBI-12056251, EBI-11976299;
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";
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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.ENSP00000264009; -.
DR ChEMBL; CHEMBL3988631; -.
DR iPTMnet; Q9ULV5; -.
DR PhosphoSitePlus; Q9ULV5; -.
DR BioMuta; HSF4; -.
DR DMDM; 296434534; -.
DR jPOST; Q9ULV5; -.
DR MassIVE; Q9ULV5; -.
DR MaxQB; Q9ULV5; -.
DR PaxDb; Q9ULV5; -.
DR PeptideAtlas; Q9ULV5; -.
DR PRIDE; Q9ULV5; -.
DR ProteomicsDB; 85135; -. [Q9ULV5-1]
DR ProteomicsDB; 85136; -. [Q9ULV5-2]
DR Antibodypedia; 29424; 327 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 CTD; 3299; -.
DR DisGeNET; 3299; -.
DR GeneCards; HSF4; -.
DR HGNC; HGNC:5227; HSF4.
DR HPA; ENSG00000102878; Tissue enhanced (brain).
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; GCRACPE; -.
DR PhylomeDB; Q9ULV5; -.
DR TreeFam; TF330401; -.
DR PathwayCommons; Q9ULV5; -.
DR SignaLink; Q9ULV5; -.
DR SIGNOR; Q9ULV5; -.
DR BioGRID-ORCS; 3299; 15 hits in 1102 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 115 other tissues.
DR ExpressionAtlas; Q9ULV5; baseline and differential.
DR Genevisible; Q9ULV5; HS.
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:0048468; P:cell development; IEA:Ensembl.
DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0033169; P:histone H3-K9 demethylation; IEA:Ensembl.
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:0045597; P:positive regulation of cell differentiation; IEA:Ensembl.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0007601; P:visual perception; IEA:Ensembl.
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 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; unknown pathological
FT significance; decreased binding to the DNASE2B promoter and
FT decreased DNASE2B expression; impaired RAD51 induction and
FT UVC-induced DNA 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
