Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
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)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi17 – 121105By similarityAdd
BLAST

GO - Molecular functioni

  1. protein phosphatase binding Source: UniProtKB
  2. sequence-specific DNA binding Source: Ensembl
  3. sequence-specific DNA binding transcription factor activity Source: ProtInc
  4. transcription corepressor activity Source: ProtInc

GO - Biological processi

  1. camera-type eye development Source: Ensembl
  2. cell development Source: Ensembl
  3. histone H3-K9 demethylation Source: Ensembl
  4. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
  5. positive regulation of cell differentiation Source: Ensembl
  6. positive regulation of cell proliferation Source: Ensembl
  7. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  8. protein homotrimerization Source: Ensembl
  9. regulation of transcription, DNA-templated Source: ProtInc
  10. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Stress response, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

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
ProteomesiUP000005640: Chromosome 16

Organism-specific databases

HGNCiHGNC:5227. HSF4.

Subcellular locationi

GO - Cellular componenti

  1. nucleoplasm Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Cataract 5, multiple types2 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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti19 – 191A → D in CTRCT5; sporadic. 1 Publication
VAR_017558
Natural varianti73 – 731R → H in CTRCT5. 1 Publication
VAR_029018
Natural varianti86 – 861I → V in CTRCT5; sporadic. 1 Publication
VAR_017559
Natural varianti114 – 1141L → P in CTRCT5. 1 Publication
VAR_017560
Natural varianti119 – 1191R → C in CTRCT5. 1 Publication
Corresponds to variant rs28937573 [ dbSNP | Ensembl ].
VAR_017561

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi293 – 2931K → R: Abolishes sumoylation. 10-fold increased in transactivational activity. 1 Publication
Mutagenesisi298 – 2981S → A: Abolishes phosphorylation. Greatly reduced sumoylation. Greatly increased transactivational activity. 1 Publication

Keywords - Diseasei

Cataract, Disease mutation

Organism-specific databases

MIMi116800. phenotype.
Orphaneti98995. Zonular cataract.
PharmGKBiPA29496.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 492492Heat shock factor protein 4PRO_0000124571Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki293 – 293Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Modified residuei298 – 2981Phosphoserine1 Publication

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.
PRIDEiQ9ULV5.

PTM databases

PhosphoSiteiQ9ULV5.

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

BgeeiQ9ULV5.
CleanExiHS_HSF4.
ExpressionAtlasiQ9ULV5. baseline and differential.
GenevestigatoriQ9ULV5.

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

Protein-protein interaction databases

BioGridi109532. 17 interactions.
IntActiQ9ULV5. 13 interactions.
MINTiMINT-8247415.
STRINGi9606.ENSP00000264009.

Structurei

3D structure databases

ProteinModelPortaliQ9ULV5.
SMRiQ9ULV5. Positions 13-124.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni129 – 20375Hydrophobic repeat HR-A/BAdd
BLAST
Regioni245 – 32278Interactions with DUSP26, MAPK1 and MAPK2Add
BLAST
Regioni364 – 38926Hydrophobic repeat HR-CAdd
BLAST

Sequence similaritiesi

Belongs to the HSF family.Curated

Phylogenomic databases

eggNOGiCOG5169.
GeneTreeiENSGT00390000001182.
HOGENOMiHOG000253917.
HOVERGENiHBG005999.
InParanoidiQ9ULV5.
KOiK09417.
OMAiVEFQHPS.
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]
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1 – 11M → MV in BAA13433 (PubMed:8972228).Curated
Sequence conflicti1 – 11M → MV in BAA84582 (PubMed:10488131).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti19 – 191A → D in CTRCT5; sporadic. 1 Publication
VAR_017558
Natural varianti73 – 731R → H in CTRCT5. 1 Publication
VAR_029018
Natural varianti86 – 861I → V in CTRCT5; sporadic. 1 Publication
VAR_017559
Natural varianti114 – 1141L → P in CTRCT5. 1 Publication
VAR_017560
Natural varianti119 – 1191R → C in CTRCT5. 1 Publication
Corresponds to variant rs28937573 [ dbSNP | Ensembl ].
VAR_017561

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei245 – 31975LPETN…DFCVT → STYSLSQRQIWALALTGPGA PSSLTSQKTLHPLRGPGFLP PVMAG in isoform HSF4A. 1 PublicationVSP_002418Add
BLAST

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

EnsembliENST00000264009; ENSP00000264009; ENSG00000102878. [Q9ULV5-1]
ENST00000521374; ENSP00000430947; ENSG00000102878. [Q9ULV5-1]
ENST00000584272; ENSP00000463706; ENSG00000102878. [Q9ULV5-2]
GeneIDi3299.
KEGGihsa:3299.
UCSCiuc002erl.2. human. [Q9ULV5-1]
uc002erm.2. human. [Q9ULV5-2]

Polymorphism databases

DMDMi296434534.

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. Positions 13-124.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109532. 17 interactions.
IntActiQ9ULV5. 13 interactions.
MINTiMINT-8247415.
STRINGi9606.ENSP00000264009.

PTM databases

PhosphoSiteiQ9ULV5.

Polymorphism databases

DMDMi296434534.

Proteomic databases

PaxDbiQ9ULV5.
PRIDEiQ9ULV5.

Protocols and materials databases

DNASUi3299.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264009; ENSP00000264009; ENSG00000102878. [Q9ULV5-1]
ENST00000521374; ENSP00000430947; ENSG00000102878. [Q9ULV5-1]
ENST00000584272; ENSP00000463706; ENSG00000102878. [Q9ULV5-2]
GeneIDi3299.
KEGGihsa:3299.
UCSCiuc002erl.2. human. [Q9ULV5-1]
uc002erm.2. human. [Q9ULV5-2]

Organism-specific databases

CTDi3299.
GeneCardsiGC16P067197.
HGNCiHGNC:5227. HSF4.
MIMi116800. phenotype.
602438. gene.
neXtProtiNX_Q9ULV5.
Orphaneti98995. Zonular cataract.
PharmGKBiPA29496.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5169.
GeneTreeiENSGT00390000001182.
HOGENOMiHOG000253917.
HOVERGENiHBG005999.
InParanoidiQ9ULV5.
KOiK09417.
OMAiVEFQHPS.
PhylomeDBiQ9ULV5.
TreeFamiTF330401.

Miscellaneous databases

GeneWikiiHSF4.
GenomeRNAii3299.
NextBioi13087.
PROiQ9ULV5.
SOURCEiSearch...

Gene expression databases

BgeeiQ9ULV5.
CleanExiHS_HSF4.
ExpressionAtlasiQ9ULV5. baseline and differential.
GenevestigatoriQ9ULV5.

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]
PROSITEiPS00434. HSF_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "HSF4, a new member of the human heat shock factor family which lacks properties of a transcriptional activator."
    Nakai A., Tanabe M., Kawazoe Y., Inazawa J., Morimoto R.I., Nagata K.
    Mol. Cell. Biol. 17:469-481(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM HSF4A).
    Tissue: Heart.
  2. "The mammalian HSF4 gene generates both an activator and a repressor of heat shock genes by alternative splicing."
    Tanabe M., Sasai N., Nagata K., Liu X.-D., Liu P.C.C., Thiele D.J., Nakai A.
    J. Biol. Chem. 274:27845-27856(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM HSF4B), NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-396 (ISOFORM HSF4A), ALTERNATIVE SPLICING, CHARACTERIZATION.
  3. "The sequence and analysis of duplication-rich human chromosome 16."
    Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.
    , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
    Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "Association and regulation of heat shock transcription factor 4b with both extracellular signal-regulated kinase mitogen-activated protein kinase and dual-specificity tyrosine phosphatase DUSP26."
    Hu Y., Mivechi N.F.
    Mol. Cell. Biol. 26:3282-3294(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DUSP26; MAPK1; MAPK2 AND MAP KINASE P38, PTM.
  5. Cited for: SUMOYLATION AT LYS-293, PHOSPHORYLATION AT SER-298, FUNCTION, MUTAGENESIS OF LYS-293 AND SER-298.
  6. "Human ALKBH4 interacts with proteins associated with transcription."
    Bjornstad L.G., Meza T.J., Otterlei M., Olafsrud S.M., Meza-Zepeda L.A., Falnes P.O.
    PLoS ONE 7:E49045-E49045(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ALKBH4.
  7. "Mutant DNA-binding domain of HSF4 is associated with autosomal dominant lamellar and Marner cataract."
    Bu L., Jin Y., Shi Y., Chu R., Ban A., Eiberg H., Andres L., Jiang H., Zheng G., Qian M., Cui B., Xia Y., Liu J., Hu L., Zhao G., Hayden M.R., Kong X.
    Nat. Genet. 31:276-278(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS CTRCT5 ASP-19; VAL-86; PRO-114 AND CYS-119, TISSUE SPECIFICITY.
  8. "Novel HSF4 mutation causes congenital total white cataract in a Chinese family."
    Ke T., Wang Q.K., Ji B., Wang X., Liu P., Zhang X., Tang Z., Ren X., Liu M.
    Am. J. Ophthalmol. 142:298-303(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CTRCT5 HIS-73.

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: March 4, 2015
This is version 130 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

External Data

Dasty 3

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 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.