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Protein

Heat shock factor protein 4

Gene

HSF4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

DNA-binding protein that specifically binds heat shock promoter elements (HSE). Isoform HSF4A represses transcription while the isoform HSF4B activates transcription.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi17 – 121By similarityAdd BLAST105

GO - Molecular functioni

  • DNA-binding transcription factor activity Source: GO_Central
  • DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
  • protein phosphatase binding Source: UniProtKB
  • RNA polymerase II proximal promoter sequence-specific DNA binding Source: GO_Central
  • sequence-specific DNA binding Source: GO_Central
  • transcription corepressor activity Source: ProtInc

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding, Repressor
Biological processStress response, Transcription, Transcription regulation

Enzyme and pathway databases

SIGNORiQ9ULV5

Names & Taxonomyi

Protein namesi
Recommended name:
Heat shock factor protein 4
Short name:
HSF 4
Short name:
hHSF4
Alternative name(s):
Heat shock transcription factor 4
Short name:
HSTF 4
Gene namesi
Name:HSF4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000102878.16
HGNCiHGNC:5227 HSF4
MIMi602438 gene
neXtProtiNX_Q9ULV5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Cataract 5, multiple types (CTRCT5)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT5 includes infantile, lamellar, zonular, nuclear, anterior polar, stellate, and Marner-type cataracts, among others. Finger malformation is observed in some kindreds.
See also OMIM:116800
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01755819A → D in CTRCT5; sporadic. 1 PublicationCorresponds to variant dbSNP:rs121909049EnsemblClinVar.1
Natural variantiVAR_02901873R → H in CTRCT5. 1 Publication1
Natural variantiVAR_01755986I → V in CTRCT5; sporadic. 1 PublicationCorresponds to variant dbSNP:rs121909050EnsemblClinVar.1
Natural variantiVAR_017560114L → P in CTRCT5. 1 PublicationCorresponds to variant dbSNP:rs121909048EnsemblClinVar.1
Natural variantiVAR_017561119R → C in CTRCT5. 1 PublicationCorresponds to variant dbSNP:rs28937573EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi293K → R: Abolishes sumoylation. 10-fold increased in transactivational activity. 1 Publication1
Mutagenesisi298S → A: Abolishes phosphorylation. Greatly reduced sumoylation. Greatly increased transactivational activity. 1 Publication1

Keywords - Diseasei

Cataract, Disease mutation

Organism-specific databases

DisGeNETi3299
MalaCardsiHSF4
MIMi116800 phenotype
OpenTargetsiENSG00000102878
Orphaneti441452 Early-onset lamellar cataract
98994 Total early-onset cataract
PharmGKBiPA29496

Chemistry databases

ChEMBLiCHEMBL3988631

Polymorphism and mutation databases

BioMutaiHSF4
DMDMi296434534

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001245711 – 492Heat shock factor protein 4Add BLAST492

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki293Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication
Modified residuei298Phosphoserine1 Publication1

Post-translational modificationi

Phosphorylated mainly on serine residues. Phosphorylation on Ser-298 promotes sumoylation on Lys-293.1 Publication
Isoform HSF4B is constitutively sumoylated. Sumoylation represses the transcriptional activity and is promoted by phosphorylation on Ser-298. HSFA is not sumoylated.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9ULV5
PeptideAtlasiQ9ULV5
PRIDEiQ9ULV5
ProteomicsDBi85135
85136 [Q9ULV5-2]

PTM databases

iPTMnetiQ9ULV5
PhosphoSitePlusiQ9ULV5

Expressioni

Tissue specificityi

Expressed in heart, skeletal muscle, eye and brain, and at much lower levels in some other tissues.1 Publication

Gene expression databases

BgeeiENSG00000102878 Expressed in 155 organ(s), highest expression level in lower esophagus muscularis layer
CleanExiHS_HSF4
ExpressionAtlasiQ9ULV5 baseline and differential
GenevisibleiQ9ULV5 HS

Organism-specific databases

HPAiHPA048584

Interactioni

Subunit structurei

Homotrimer. Exhibits constitutive DNA binding and forms trimers even in the absence of stress. Interacts with ALKBH4, DUSP26, MAPK1, MAPK2 and MAP kinase p38.2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109532, 18 interactors
ELMiQ9ULV5
IntActiQ9ULV5, 46 interactors
MINTiQ9ULV5
STRINGi9606.ENSP00000264009

Structurei

3D structure databases

ProteinModelPortaliQ9ULV5
SMRiQ9ULV5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni129 – 203Hydrophobic repeat HR-A/BAdd BLAST75
Regioni245 – 322Interactions with DUSP26, MAPK1 and MAPK2Add BLAST78
Regioni364 – 389Hydrophobic repeat HR-CAdd BLAST26

Sequence similaritiesi

Belongs to the HSF family.Curated

Phylogenomic databases

eggNOGiKOG0627 Eukaryota
COG5169 LUCA
GeneTreeiENSGT00390000001182
HOGENOMiHOG000253917
HOVERGENiHBG005999
InParanoidiQ9ULV5
KOiK09417
OMAiMLIKEEP
OrthoDBiEOG091G087O
PhylomeDBiQ9ULV5
TreeFamiTF330401

Family and domain databases

Gene3Di1.10.10.10, 1 hit
InterProiView protein in InterPro
IPR000232 HSF_DNA-bd
IPR027725 HSF_fam
IPR036388 WH-like_DNA-bd_sf
IPR036390 WH_DNA-bd_sf
PANTHERiPTHR10015 PTHR10015, 1 hit
PfamiView protein in Pfam
PF00447 HSF_DNA-bind, 1 hit
PRINTSiPR00056 HSFDOMAIN
SMARTiView protein in SMART
SM00415 HSF, 1 hit
SUPFAMiSSF46785 SSF46785, 1 hit
PROSITEiView protein in PROSITE
PS00434 HSF_DOMAIN, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 12 potential isoforms that are computationally mapped.Show allAlign All

Isoform HSF4B (identifier: Q9ULV5-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        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
Length:492
Mass (Da):53,011
Last modified:May 18, 2010 - v2
Checksum:iD5F1C0D68014BC2E
GO
Isoform HSF4A (identifier: Q9ULV5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     245-319: LPETNLGLSP...APNECDFCVT → STYSLSQRQI...PGFLPPVMAG

Show »
Length:462
Mass (Da):49,952
Checksum:iF850CE8843CF4DDB
GO

Computationally mapped potential isoform sequencesi

There are 12 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E5RK26E5RK26_HUMAN
Heat shock factor protein 4
HSF4
416Annotation score:
E5RJV4E5RJV4_HUMAN
Heat shock factor protein 4
HSF4
318Annotation score:
E7EWW4E7EWW4_HUMAN
Heat shock factor protein 4
HSF4
315Annotation score:
E5RG51E5RG51_HUMAN
Heat shock factor protein 4
HSF4
194Annotation score:
H0YBT7H0YBT7_HUMAN
Heat shock factor protein 4
HSF4
185Annotation score:
H0YC39H0YC39_HUMAN
Heat shock factor protein 4
HSF4
141Annotation score:
H0YAU2H0YAU2_HUMAN
Heat shock factor protein 4
HSF4
223Annotation score:
E5RHY0E5RHY0_HUMAN
Heat shock factor protein 4
HSF4
47Annotation score:
H0YBS6H0YBS6_HUMAN
Heat shock factor protein 4
HSF4
182Annotation score:
H0YBG9H0YBG9_HUMAN
Heat shock factor protein 4
HSF4
63Annotation score:
There are more potential isoformsShow all

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1M → MV in BAA13433 (PubMed:8972228).Curated1
Sequence conflicti1M → MV in BAA84582 (PubMed:10488131).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01755819A → D in CTRCT5; sporadic. 1 PublicationCorresponds to variant dbSNP:rs121909049EnsemblClinVar.1
Natural variantiVAR_02901873R → H in CTRCT5. 1 Publication1
Natural variantiVAR_01755986I → V in CTRCT5; sporadic. 1 PublicationCorresponds to variant dbSNP:rs121909050EnsemblClinVar.1
Natural variantiVAR_017560114L → P in CTRCT5. 1 PublicationCorresponds to variant dbSNP:rs121909048EnsemblClinVar.1
Natural variantiVAR_017561119R → C in CTRCT5. 1 PublicationCorresponds to variant dbSNP:rs28937573EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_002418245 – 319LPETN…DFCVT → STYSLSQRQIWALALTGPGA PSSLTSQKTLHPLRGPGFLP PVMAG in isoform HSF4A. 1 PublicationAdd BLAST75

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.
CCDSiCCDS42175.1 [Q9ULV5-1]
CCDS45510.1 [Q9ULV5-2]
RefSeqiNP_001035757.1, NM_001040667.2 [Q9ULV5-1]
NP_001529.2, NM_001538.3 [Q9ULV5-2]
UniGeneiHs.512156
Hs.710714

Genome annotation databases

EnsembliENST00000521374; ENSP00000430947; ENSG00000102878 [Q9ULV5-1]
ENST00000584272; ENSP00000463706; ENSG00000102878 [Q9ULV5-2]
GeneIDi3299
KEGGihsa:3299
UCSCiuc002erl.2 human [Q9ULV5-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar 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.
CCDSiCCDS42175.1 [Q9ULV5-1]
CCDS45510.1 [Q9ULV5-2]
RefSeqiNP_001035757.1, NM_001040667.2 [Q9ULV5-1]
NP_001529.2, NM_001538.3 [Q9ULV5-2]
UniGeneiHs.512156
Hs.710714

3D structure databases

ProteinModelPortaliQ9ULV5
SMRiQ9ULV5
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109532, 18 interactors
ELMiQ9ULV5
IntActiQ9ULV5, 46 interactors
MINTiQ9ULV5
STRINGi9606.ENSP00000264009

Chemistry databases

ChEMBLiCHEMBL3988631

PTM databases

iPTMnetiQ9ULV5
PhosphoSitePlusiQ9ULV5

Polymorphism and mutation databases

BioMutaiHSF4
DMDMi296434534

Proteomic databases

PaxDbiQ9ULV5
PeptideAtlasiQ9ULV5
PRIDEiQ9ULV5
ProteomicsDBi85135
85136 [Q9ULV5-2]

Protocols and materials databases

DNASUi3299
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000521374; ENSP00000430947; ENSG00000102878 [Q9ULV5-1]
ENST00000584272; ENSP00000463706; ENSG00000102878 [Q9ULV5-2]
GeneIDi3299
KEGGihsa:3299
UCSCiuc002erl.2 human [Q9ULV5-1]

Organism-specific databases

CTDi3299
DisGeNETi3299
EuPathDBiHostDB:ENSG00000102878.16
GeneCardsiHSF4
HGNCiHGNC:5227 HSF4
HPAiHPA048584
MalaCardsiHSF4
MIMi116800 phenotype
602438 gene
neXtProtiNX_Q9ULV5
OpenTargetsiENSG00000102878
Orphaneti441452 Early-onset lamellar cataract
98994 Total early-onset cataract
PharmGKBiPA29496
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0627 Eukaryota
COG5169 LUCA
GeneTreeiENSGT00390000001182
HOGENOMiHOG000253917
HOVERGENiHBG005999
InParanoidiQ9ULV5
KOiK09417
OMAiMLIKEEP
OrthoDBiEOG091G087O
PhylomeDBiQ9ULV5
TreeFamiTF330401

Enzyme and pathway databases

SIGNORiQ9ULV5

Miscellaneous databases

GeneWikiiHSF4
GenomeRNAii3299
PROiPR:Q9ULV5
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000102878 Expressed in 155 organ(s), highest expression level in lower esophagus muscularis layer
CleanExiHS_HSF4
ExpressionAtlasiQ9ULV5 baseline and differential
GenevisibleiQ9ULV5 HS

Family and domain databases

Gene3Di1.10.10.10, 1 hit
InterProiView protein in InterPro
IPR000232 HSF_DNA-bd
IPR027725 HSF_fam
IPR036388 WH-like_DNA-bd_sf
IPR036390 WH_DNA-bd_sf
PANTHERiPTHR10015 PTHR10015, 1 hit
PfamiView protein in Pfam
PF00447 HSF_DNA-bind, 1 hit
PRINTSiPR00056 HSFDOMAIN
SMARTiView protein in SMART
SM00415 HSF, 1 hit
SUPFAMiSSF46785 SSF46785, 1 hit
PROSITEiView protein in PROSITE
PS00434 HSF_DOMAIN, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiHSF4_HUMAN
AccessioniPrimary (citable) accession number: Q9ULV5
Secondary accession number(s): Q99472, Q9ULV6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: May 18, 2010
Last modified: November 7, 2018
This is version 160 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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