UniProtKB - Q9ULV5 (HSF4_HUMAN)
Heat shock factor protein 4
HSF4
Functioni
Heat-shock transcription factor that specifically binds heat shock promoter elements (HSE) (PubMed:22587838, PubMed:23507146).
Required for denucleation and organelle rupture and degradation that occur during eye lens terminal differentiation, when fiber cells that compose the lens degrade all membrane-bound organelles in order to provide lens with transparency to allow the passage of light (By similarity).
In this process, may regulate denucleation of lens fiber cells in part by activating DNASE2B transcription (By similarity).
May be involved in DNA repair through the transcriptional regulation of RAD51 (PubMed:22587838).
May up-regulate p53/TP53 protein in eye lens fiber cells, possibly through protein stabilization (PubMed:28981088).
In the eye lens, controls the expression of alpha-crystallin B chain/CRYAB and consequently may be involved in the regulation of lysosomal acidification (By similarity).
By similarity3 PublicationsTranscriptional repressor.
1 PublicationTranscriptional activator.
2 PublicationsRegions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 17 – 121 | By similarityAdd BLAST | 105 |
GO - Molecular functioni
- DNA-binding transcription factor activity Source: GO_Central
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: ARUK-UCL
- identical protein binding Source: Ensembl
- protein phosphatase binding Source: UniProtKB
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: ARUK-UCL
- sequence-specific double-stranded DNA binding Source: ARUK-UCL
GO - Biological processi
- cell development Source: Ensembl
- histone H3-K9 demethylation Source: Ensembl
- lens fiber cell differentiation Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: ARUK-UCL
- positive regulation of cell differentiation Source: Ensembl
- positive regulation of cell population proliferation Source: Ensembl
- positive regulation of transcription by RNA polymerase II Source: Ensembl
- regulation of transcription by RNA polymerase II Source: GO_Central
- visual perception Source: Ensembl
Keywordsi
Molecular function | Activator, DNA-binding, Repressor |
Biological process | Stress response, Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | Q9ULV5 |
SignaLinki | Q9ULV5 |
SIGNORi | Q9ULV5 |
Names & Taxonomyi
Protein namesi | Recommended name: Heat shock factor protein 4Short name: HSF 4 Short name: hHSF4 Alternative name(s): Heat shock transcription factor 4 Short name: HSTF 4 |
Gene namesi | Name:HSF4 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:5227, HSF4 |
MIMi | 602438, gene |
neXtProti | NX_Q9ULV5 |
VEuPathDBi | HostDB:ENSG00000102878 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Nucleus
- nuclear speck Source: HPA
- nucleus Source: GO_Central
Other locations
- chromatin Source: ARUK-UCL
Keywords - Cellular componenti
NucleusPathology & Biotechi
Involvement in diseasei
Cataract 5, multiple types (CTRCT5)5 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_017558 | 19 | A → D in CTRCT5; sporadic; decreased binding to the DNASE2B promoter and decreased DNASE2B expression; impaired RAD51 induction and UVC-induced DNA damage repair. 3 PublicationsCorresponds to variant dbSNP:rs121909049EnsemblClinVar. | 1 | |
Natural variantiVAR_029018 | 73 | R → H in CTRCT5; decreased binding to the DNASE2B promoter and decreased DNASE2B expression; impaired RAD51 induction and UVC-induced DNA damage repair. 3 Publications | 1 | |
Natural variantiVAR_017559 | 86 | I → V in CTRCT5; sporadic. 1 PublicationCorresponds to variant dbSNP:rs121909050EnsemblClinVar. | 1 | |
Natural variantiVAR_017560 | 114 | L → P in CTRCT5; decreased binding to the DNASE2B promoter and decreased DNASE2B expression; impaired RAD51 induction. 4 PublicationsCorresponds to variant dbSNP:rs121909048EnsemblClinVar. | 1 | |
Natural variantiVAR_017561 | 119 | R → C in CTRCT5; unknown pathological significance; decreased binding to the DNASE2B promoter and decreased DNASE2B expression; impaired RAD51 induction and UVC-induced DNA damage repair. 4 PublicationsCorresponds to variant dbSNP:rs28937573EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 293 | K → R: Abolishes sumoylation. 10-fold increased in transactivational activity. 1 Publication | 1 | |
Mutagenesisi | 298 | S → A: Abolishes phosphorylation. Greatly reduced sumoylation. Greatly increased transactivational activity. 1 Publication | 1 |
Keywords - Diseasei
Cataract, Disease variantOrganism-specific databases
DisGeNETi | 3299 |
MalaCardsi | HSF4 |
MIMi | 116800, phenotype |
OpenTargetsi | ENSG00000102878 |
Orphaneti | 441452, Early-onset lamellar cataract 98994, Total early-onset cataract |
PharmGKBi | PA29496 |
Miscellaneous databases
Pharosi | Q9ULV5, Tbio |
Chemistry databases
ChEMBLi | CHEMBL3988631 |
Genetic variation databases
BioMutai | HSF4 |
DMDMi | 296434534 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000124571 | 1 – 492 | Heat shock factor protein 4Add BLAST | 492 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Cross-linki | 293 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication | ||
Modified residuei | 298 | Phosphoserine1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
jPOSTi | Q9ULV5 |
MassIVEi | Q9ULV5 |
MaxQBi | Q9ULV5 |
PaxDbi | Q9ULV5 |
PeptideAtlasi | Q9ULV5 |
PRIDEi | Q9ULV5 |
ProteomicsDBi | 85135 [Q9ULV5-1] 85136 [Q9ULV5-2] |
PTM databases
iPTMneti | Q9ULV5 |
PhosphoSitePlusi | Q9ULV5 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000102878, Expressed in lower esophagus muscularis layer and 172 other tissues |
ExpressionAtlasi | Q9ULV5, baseline and differential |
Genevisiblei | Q9ULV5, HS |
Organism-specific databases
HPAi | ENSG00000102878, Tissue enhanced (brain) |
Interactioni
Subunit structurei
Binary interactionsi
Isoform HSF4A [Q9ULV5-2]
GO - Molecular functioni
- identical protein binding Source: Ensembl
- protein phosphatase binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 109532, 51 interactors |
ELMi | Q9ULV5 |
IntActi | Q9ULV5, 44 interactors |
MINTi | Q9ULV5 |
STRINGi | 9606.ENSP00000264009 |
Miscellaneous databases
RNActi | Q9ULV5, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q9ULV5 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 129 – 203 | Hydrophobic repeat HR-A/BAdd BLAST | 75 | |
Regioni | 245 – 322 | Interactions with DUSP26, MAPK1 and MAPK2Add BLAST | 78 | |
Regioni | 246 – 285 | DisorderedSequence analysisAdd BLAST | 40 | |
Regioni | 337 – 400 | DisorderedSequence analysisAdd BLAST | 64 | |
Regioni | 364 – 389 | Hydrophobic repeat HR-CAdd BLAST | 26 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0627, Eukaryota |
GeneTreei | ENSGT00940000158063 |
InParanoidi | Q9ULV5 |
OMAi | GCRACPE |
PhylomeDBi | Q9ULV5 |
TreeFami | TF330401 |
Family and domain databases
Gene3Di | 1.10.10.10, 1 hit |
InterProi | View protein in InterPro IPR000232, HSF_DNA-bd IPR027725, HSF_fam IPR036388, WH-like_DNA-bd_sf IPR036390, WH_DNA-bd_sf |
PANTHERi | PTHR10015, PTHR10015, 1 hit |
Pfami | View protein in Pfam PF00447, HSF_DNA-bind, 1 hit |
PRINTSi | PR00056, HSFDOMAIN |
SMARTi | View protein in SMART SM00415, HSF, 1 hit |
SUPFAMi | SSF46785, SSF46785, 1 hit |
PROSITEi | View protein in PROSITE PS00434, HSF_DOMAIN, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 12 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MQEAPAALPT EPGPSPVPAF LGKLWALVGD PGTDHLIRWS PSGTSFLVSD
60 70 80 90 100
QSRFAKEVLP QYFKHSNMAS FVRQLNMYGF RKVVSIEQGG LLRPERDHVE
110 120 130 140 150
FQHPSFVRGR EQLLERVRRK VPALRGDDGR WRPEDLGRLL GEVQALRGVQ
160 170 180 190 200
ESTEARLREL RQQNEILWRE VVTLRQSHGQ QHRVIGKLIQ CLFGPLQAGP
210 220 230 240 250
SNAGGKRKLS LMLDEGSSCP TPAKFNTCPL PGALLQDPYF IQSPLPETNL
260 270 280 290 300
GLSPHRARGP IISDIPEDSP SPEGTRLSPS SDGRREKGLA LLKEEPASPG
310 320 330 340 350
GDGEAGLALA PNECDFCVTA PPPLPVAVVQ AILEGKGSFS PEGPRNAQQP
360 370 380 390 400
EPGDPREIPD RGPLGLESGD RSPESLLPPM LLQPPQESVE PAGPLDVLGP
410 420 430 440 450
SLQGREWTLM DLDMELSLMQ PLVPERGEPE LAVKGLNSPS PGKDPTLGAP
460 470 480 490
LLLDVQAALG GPALGLPGAL TIYSTPESRT ASYLGPEASP SP
The sequence of this isoform differs from the canonical sequence as follows:
245-319: LPETNLGLSP...APNECDFCVT → STYSLSQRQI...PGFLPPVMAG
Computationally mapped potential isoform sequencesi
There are 12 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE5RK26 | E5RK26_HUMAN | Heat shock factor protein 4 | HSF4 | 416 | Annotation score: | ||
E7EWW4 | E7EWW4_HUMAN | Heat shock factor protein 4 | HSF4 | 315 | Annotation score: | ||
E5RJV4 | E5RJV4_HUMAN | Heat shock factor protein 4 | HSF4 | 318 | Annotation score: | ||
E5RG51 | E5RG51_HUMAN | Heat shock factor protein 4 | HSF4 | 194 | Annotation score: | ||
H0YBT7 | H0YBT7_HUMAN | Heat shock factor protein 4 | HSF4 | 185 | Annotation score: | ||
H0YAU2 | H0YAU2_HUMAN | Heat shock factor protein 4 | HSF4 | 223 | Annotation score: | ||
H0YC39 | H0YC39_HUMAN | Heat shock factor protein 4 | HSF4 | 141 | Annotation score: | ||
H0YBS6 | H0YBS6_HUMAN | Heat shock factor protein 4 | HSF4 | 182 | Annotation score: | ||
H0YBG9 | H0YBG9_HUMAN | Heat shock factor protein 4 | HSF4 | 63 | Annotation score: | ||
H0YC14 | H0YC14_HUMAN | Heat shock factor protein 4 | HSF4 | 77 | Annotation score: | ||
There are more potential isoformsShow all |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 1 | M → MV in BAA13433 (PubMed:8972228).Curated | 1 | |
Sequence conflicti | 1 | M → MV in BAA84582 (PubMed:10488131).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_017558 | 19 | A → D in CTRCT5; sporadic; decreased binding to the DNASE2B promoter and decreased DNASE2B expression; impaired RAD51 induction and UVC-induced DNA damage repair. 3 PublicationsCorresponds to variant dbSNP:rs121909049EnsemblClinVar. | 1 | |
Natural variantiVAR_029018 | 73 | R → H in CTRCT5; decreased binding to the DNASE2B promoter and decreased DNASE2B expression; impaired RAD51 induction and UVC-induced DNA damage repair. 3 Publications | 1 | |
Natural variantiVAR_017559 | 86 | I → V in CTRCT5; sporadic. 1 PublicationCorresponds to variant dbSNP:rs121909050EnsemblClinVar. | 1 | |
Natural variantiVAR_017560 | 114 | L → P in CTRCT5; decreased binding to the DNASE2B promoter and decreased DNASE2B expression; impaired RAD51 induction. 4 PublicationsCorresponds to variant dbSNP:rs121909048EnsemblClinVar. | 1 | |
Natural variantiVAR_017561 | 119 | R → C in CTRCT5; unknown pathological significance; decreased binding to the DNASE2B promoter and decreased DNASE2B expression; impaired RAD51 induction and UVC-induced DNA damage repair. 4 PublicationsCorresponds to variant dbSNP:rs28937573EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_002418 | 245 – 319 | LPETN…DFCVT → STYSLSQRQIWALALTGPGA PSSLTSQKTLHPLRGPGFLP PVMAG in isoform HSF4A. 1 PublicationAdd BLAST | 75 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D87673 mRNA Translation: BAA13433.1 AB029347 Genomic DNA Translation: BAA84581.1 AB029348 mRNA Translation: BAA84582.1 AC074143 Genomic DNA No translation available. |
CCDSi | CCDS42175.1 [Q9ULV5-1] CCDS45510.1 [Q9ULV5-2] |
RefSeqi | NP_001035757.1, NM_001040667.2 [Q9ULV5-1] NP_001529.2, NM_001538.3 [Q9ULV5-2] |
Genome annotation databases
Ensembli | ENST00000521374; ENSP00000430947; ENSG00000102878 ENST00000584272; ENSP00000463706; ENSG00000102878 [Q9ULV5-2] |
GeneIDi | 3299 |
KEGGi | hsa:3299 |
MANE-Selecti | ENST00000521374.6; ENSP00000430947.2; NM_001374675.1; NP_001361604.1 |
UCSCi | uc002erl.2, human [Q9ULV5-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Eye disease Heat shock transcription factor 4 (HSF4) Leiden Open Variation Database (LOVD) |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D87673 mRNA Translation: BAA13433.1 AB029347 Genomic DNA Translation: BAA84581.1 AB029348 mRNA Translation: BAA84582.1 AC074143 Genomic DNA No translation available. |
CCDSi | CCDS42175.1 [Q9ULV5-1] CCDS45510.1 [Q9ULV5-2] |
RefSeqi | NP_001035757.1, NM_001040667.2 [Q9ULV5-1] NP_001529.2, NM_001538.3 [Q9ULV5-2] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6J6V | X-ray | 1.20 | A | 17-121 | [»] | |
6J6W | X-ray | 1.69 | A/B | 17-121 | [»] | |
SMRi | Q9ULV5 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 109532, 51 interactors |
ELMi | Q9ULV5 |
IntActi | Q9ULV5, 44 interactors |
MINTi | Q9ULV5 |
STRINGi | 9606.ENSP00000264009 |
Chemistry databases
ChEMBLi | CHEMBL3988631 |
PTM databases
iPTMneti | Q9ULV5 |
PhosphoSitePlusi | Q9ULV5 |
Genetic variation databases
BioMutai | HSF4 |
DMDMi | 296434534 |
Proteomic databases
jPOSTi | Q9ULV5 |
MassIVEi | Q9ULV5 |
MaxQBi | Q9ULV5 |
PaxDbi | Q9ULV5 |
PeptideAtlasi | Q9ULV5 |
PRIDEi | Q9ULV5 |
ProteomicsDBi | 85135 [Q9ULV5-1] 85136 [Q9ULV5-2] |
Protocols and materials databases
Antibodypediai | 29424, 326 antibodies from 32 providers |
DNASUi | 3299 |
Genome annotation databases
Ensembli | ENST00000521374; ENSP00000430947; ENSG00000102878 ENST00000584272; ENSP00000463706; ENSG00000102878 [Q9ULV5-2] |
GeneIDi | 3299 |
KEGGi | hsa:3299 |
MANE-Selecti | ENST00000521374.6; ENSP00000430947.2; NM_001374675.1; NP_001361604.1 |
UCSCi | uc002erl.2, human [Q9ULV5-1] |
Organism-specific databases
CTDi | 3299 |
DisGeNETi | 3299 |
GeneCardsi | HSF4 |
HGNCi | HGNC:5227, HSF4 |
HPAi | ENSG00000102878, Tissue enhanced (brain) |
MalaCardsi | HSF4 |
MIMi | 116800, phenotype 602438, gene |
neXtProti | NX_Q9ULV5 |
OpenTargetsi | ENSG00000102878 |
Orphaneti | 441452, Early-onset lamellar cataract 98994, Total early-onset cataract |
PharmGKBi | PA29496 |
VEuPathDBi | HostDB:ENSG00000102878 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0627, Eukaryota |
GeneTreei | ENSGT00940000158063 |
InParanoidi | Q9ULV5 |
OMAi | GCRACPE |
PhylomeDBi | Q9ULV5 |
TreeFami | TF330401 |
Enzyme and pathway databases
PathwayCommonsi | Q9ULV5 |
SignaLinki | Q9ULV5 |
SIGNORi | Q9ULV5 |
Miscellaneous databases
BioGRID-ORCSi | 3299, 10 hits in 1068 CRISPR screens |
ChiTaRSi | HSF4, human |
GeneWikii | HSF4 |
GenomeRNAii | 3299 |
Pharosi | Q9ULV5, Tbio |
PROi | PR:Q9ULV5 |
RNActi | Q9ULV5, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000102878, Expressed in lower esophagus muscularis layer and 172 other tissues |
ExpressionAtlasi | Q9ULV5, baseline and differential |
Genevisiblei | Q9ULV5, HS |
Family and domain databases
Gene3Di | 1.10.10.10, 1 hit |
InterProi | View protein in InterPro IPR000232, HSF_DNA-bd IPR027725, HSF_fam IPR036388, WH-like_DNA-bd_sf IPR036390, WH_DNA-bd_sf |
PANTHERi | PTHR10015, PTHR10015, 1 hit |
Pfami | View protein in Pfam PF00447, HSF_DNA-bind, 1 hit |
PRINTSi | PR00056, HSFDOMAIN |
SMARTi | View protein in SMART SM00415, HSF, 1 hit |
SUPFAMi | SSF46785, SSF46785, 1 hit |
PROSITEi | View protein in PROSITE PS00434, HSF_DOMAIN, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | HSF4_HUMAN | |
Accessioni | Q9ULV5Primary (citable) accession number: Q9ULV5 Secondary accession number(s): Q99472, Q9ULV6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 11, 2001 |
Last sequence update: | May 18, 2010 | |
Last modified: | February 23, 2022 | |
This is version 179 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 16
Human chromosome 16: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families