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Protein

Heat shock factor protein 4

Gene

HSF4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • protein phosphatase binding Source: UniProtKB
  • sequence-specific DNA binding Source: Ensembl
  • transcription corepressor activity Source: ProtInc
  • transcription factor activity, sequence-specific DNA binding Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Stress response, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000102878-MONOMER.

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

HGNCiHGNC:5227. HSF4.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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 rs121909049dbSNPEnsembl.1
Natural variantiVAR_02901873R → H in CTRCT5. 1 Publication1
Natural variantiVAR_01755986I → V in CTRCT5; sporadic. 1 PublicationCorresponds to variant rs121909050dbSNPEnsembl.1
Natural variantiVAR_017560114L → P in CTRCT5. 1 PublicationCorresponds to variant rs121909048dbSNPEnsembl.1
Natural variantiVAR_017561119R → C in CTRCT5. 1 PublicationCorresponds to variant rs28937573dbSNPEnsembl.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.
Orphaneti98995. Zonular cataract.
PharmGKBiPA29496.

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.

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.
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 phosphatase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109532. 16 interactors.
IntActiQ9ULV5. 21 interactors.
MINTiMINT-8247415.
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.
OMAiRGPIISD.
OrthoDBiEOG091G087O.
PhylomeDBiQ9ULV5.
TreeFamiTF330401.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR027723. HSF4.
IPR000232. HSF_DNA-bd.
IPR027725. HSF_fam.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PANTHERiPTHR10015. PTHR10015. 1 hit.
PTHR10015:SF43. PTHR10015:SF43. 1 hit.
PfamiPF00447. HSF_DNA-bind. 1 hit.
[Graphical view]
PRINTSiPR00056. HSFDOMAIN.
SMARTiSM00415. HSF. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00434. HSF_DOMAIN. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

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

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 rs121909049dbSNPEnsembl.1
Natural variantiVAR_02901873R → H in CTRCT5. 1 Publication1
Natural variantiVAR_01755986I → V in CTRCT5; sporadic. 1 PublicationCorresponds to variant rs121909050dbSNPEnsembl.1
Natural variantiVAR_017560114L → P in CTRCT5. 1 PublicationCorresponds to variant rs121909048dbSNPEnsembl.1
Natural variantiVAR_017561119R → C in CTRCT5. 1 PublicationCorresponds to variant rs28937573dbSNPEnsembl.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

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. 16 interactors.
IntActiQ9ULV5. 21 interactors.
MINTiMINT-8247415.
STRINGi9606.ENSP00000264009.

PTM databases

iPTMnetiQ9ULV5.
PhosphoSitePlusiQ9ULV5.

Polymorphism and mutation databases

BioMutaiHSF4.
DMDMi296434534.

Proteomic databases

PaxDbiQ9ULV5.
PeptideAtlasiQ9ULV5.
PRIDEiQ9ULV5.

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.
GeneCardsiHSF4.
HGNCiHGNC:5227. HSF4.
HPAiHPA048584.
MalaCardsiHSF4.
MIMi116800. phenotype.
602438. gene.
neXtProtiNX_Q9ULV5.
OpenTargetsiENSG00000102878.
Orphaneti98995. Zonular cataract.
PharmGKBiPA29496.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000102878-MONOMER.

Miscellaneous databases

GeneWikiiHSF4.
GenomeRNAii3299.
PROiQ9ULV5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000102878.
CleanExiHS_HSF4.
ExpressionAtlasiQ9ULV5. baseline and differential.
GenevisibleiQ9ULV5. HS.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR027723. HSF4.
IPR000232. HSF_DNA-bd.
IPR027725. HSF_fam.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PANTHERiPTHR10015. PTHR10015. 1 hit.
PTHR10015:SF43. PTHR10015:SF43. 1 hit.
PfamiPF00447. HSF_DNA-bind. 1 hit.
[Graphical view]
PRINTSiPR00056. HSFDOMAIN.
SMARTiSM00415. HSF. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00434. HSF_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHSF4_HUMAN
AccessioniPrimary (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: November 30, 2016
This is version 147 of the entry and version 2 of the sequence. [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. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.