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Q9ULV5 (HSF4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:HSF4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length492 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

DNA-binding protein that specifically binds heat shock promoter elements (HSE). Isoform HSF4A represses transcription while the isoform HSF4B activates transcription. Ref.5

Subunit structure

Homotrimer. Exhibits constitutive DNA binding and forms trimers even in the absence of stress. Interacts with ALKBH4, DUSP26, MAPK1, MAPK2 and MAP kinase p38. Ref.4 Ref.6

Subcellular location

Nucleus.

Tissue specificity

Expressed in heart, skeletal muscle, eye and brain, and at much lower levels in some other tissues. Ref.7

Post-translational modification

Phosphorylated mainly on serine residues. Phosphorylation on Ser-298 promotes sumoylation on Lys-293. Ref.5

Isoform HSF4B is constitutively sumoylated. Sumoylation represses the transcriptional activity and is promoted by phosphorylation on Ser-298. HSFA is not sumoylated. Ref.5

Involvement in disease

Cataract 5, multiple types (CTRCT5) [MIM:116800]: An 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.8

Sequence similarities

Belongs to the HSF family.

Ontologies

Keywords
   Biological processStress response
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DiseaseCataract
Disease mutation
   LigandDNA-binding
   Molecular functionActivator
Repressor
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcamera-type eye development

Inferred from electronic annotation. Source: Ensembl

cell development

Inferred from electronic annotation. Source: Ensembl

histone H3-K9 demethylation

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

protein homotrimerization

Inferred from electronic annotation. Source: Ensembl

regulation of transcription, DNA-templated

Traceable author statement Ref.1. Source: ProtInc

response to stress

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentnucleus

Inferred from direct assay. Source: HPA

   Molecular_functionprotein phosphatase binding

Inferred from physical interaction Ref.4. Source: UniProt

sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding transcription factor activity

Traceable author statement Ref.1. Source: ProtInc

transcription corepressor activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform HSF4B (identifier: Q9ULV5-1)

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.
Isoform HSF4A (identifier: Q9ULV5-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 492492Heat shock factor protein 4
PRO_0000124571

Regions

DNA binding17 – 121105 By similarity
Region129 – 20375Hydrophobic repeat HR-A/B
Region245 – 32278Interactions with DUSP26, MAPK1 and MAPK2
Region364 – 38926Hydrophobic repeat HR-C

Amino acid modifications

Modified residue2981Phosphoserine Ref.5
Cross-link293Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.5

Natural variations

Alternative sequence245 – 31975LPETN…DFCVT → STYSLSQRQIWALALTGPGA PSSLTSQKTLHPLRGPGFLP PVMAG in isoform HSF4A.
VSP_002418
Natural variant191A → D in CTRCT5; sporadic. Ref.7
VAR_017558
Natural variant731R → H in CTRCT5. Ref.8
VAR_029018
Natural variant861I → V in CTRCT5; sporadic. Ref.7
VAR_017559
Natural variant1141L → P in CTRCT5. Ref.7
VAR_017560
Natural variant1191R → C in CTRCT5. Ref.7
Corresponds to variant rs28937573 [ dbSNP | Ensembl ].
VAR_017561

Experimental info

Mutagenesis2931K → R: Abolishes sumoylation. 10-fold increased in transactivational activity. Ref.5
Mutagenesis2981S → A: Abolishes phosphorylation. Greatly reduced sumoylation. Greatly increased transactivational activity. Ref.5
Sequence conflict11M → MV in BAA13433. Ref.1
Sequence conflict11M → MV in BAA84582. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform HSF4B [UniParc].

Last modified May 18, 2010. Version 2.
Checksum: D5F1C0D68014BC2E

FASTA49253,011
        10         20         30         40         50         60 
MQEAPAALPT EPGPSPVPAF LGKLWALVGD PGTDHLIRWS PSGTSFLVSD QSRFAKEVLP 

        70         80         90        100        110        120 
QYFKHSNMAS FVRQLNMYGF RKVVSIEQGG LLRPERDHVE FQHPSFVRGR EQLLERVRRK 

       130        140        150        160        170        180 
VPALRGDDGR WRPEDLGRLL GEVQALRGVQ ESTEARLREL RQQNEILWRE VVTLRQSHGQ 

       190        200        210        220        230        240 
QHRVIGKLIQ CLFGPLQAGP SNAGGKRKLS LMLDEGSSCP TPAKFNTCPL PGALLQDPYF 

       250        260        270        280        290        300 
IQSPLPETNL GLSPHRARGP IISDIPEDSP SPEGTRLSPS SDGRREKGLA LLKEEPASPG 

       310        320        330        340        350        360 
GDGEAGLALA PNECDFCVTA PPPLPVAVVQ AILEGKGSFS PEGPRNAQQP EPGDPREIPD 

       370        380        390        400        410        420 
RGPLGLESGD RSPESLLPPM LLQPPQESVE PAGPLDVLGP SLQGREWTLM DLDMELSLMQ 

       430        440        450        460        470        480 
PLVPERGEPE LAVKGLNSPS PGKDPTLGAP LLLDVQAALG GPALGLPGAL TIYSTPESRT 

       490 
ASYLGPEASP SP 

« Hide

Isoform HSF4A [UniParc].

Checksum: F850CE8843CF4DDB
Show »

FASTA46249,952

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"PDSM, a motif for phosphorylation-dependent SUMO modification."
Hietakangas V., Anckar J., Blomster H.A., Fujimoto M., Palvimo J.J., Nakai A., Sistonen L.
Proc. Natl. Acad. Sci. U.S.A. 103:45-50(2006) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Web resources

Eye disease Heat shock transcription factor 4 (HSF4)

Leiden Open Variation Database (LOVD)

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D87673 mRNA. Translation: BAA13433.1.
AB029347 Genomic DNA. Translation: BAA84581.1.
AB029348 mRNA. Translation: BAA84582.1.
AC074143 Genomic DNA. No translation available.
CCDSCCDS42175.1. [Q9ULV5-1]
CCDS45510.1. [Q9ULV5-2]
RefSeqNP_001035757.1. NM_001040667.2. [Q9ULV5-1]
NP_001529.2. NM_001538.3. [Q9ULV5-2]
UniGeneHs.512156.
Hs.710714.

3D structure databases

ProteinModelPortalQ9ULV5.
SMRQ9ULV5. Positions 13-124.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109532. 9 interactions.
IntActQ9ULV5. 4 interactions.
MINTMINT-8247415.
STRING9606.ENSP00000264009.

PTM databases

PhosphoSiteQ9ULV5.

Polymorphism databases

DMDM296434534.

Proteomic databases

PaxDbQ9ULV5.
PRIDEQ9ULV5.

Protocols and materials databases

DNASU3299.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264009; ENSP00000264009; ENSG00000102878. [Q9ULV5-1]
ENST00000421453; ENSP00000408815; ENSG00000102878. [Q9ULV5-2]
ENST00000521374; ENSP00000430947; ENSG00000102878. [Q9ULV5-1]
ENST00000584272; ENSP00000463706; ENSG00000102878. [Q9ULV5-2]
GeneID3299.
KEGGhsa:3299.
UCSCuc002erl.2. human. [Q9ULV5-1]
uc002erm.2. human. [Q9ULV5-2]

Organism-specific databases

CTD3299.
GeneCardsGC16P067197.
HGNCHGNC:5227. HSF4.
HPAHPA048584.
MIM116800. phenotype.
602438. gene.
neXtProtNX_Q9ULV5.
Orphanet98995. Zonular cataract.
PharmGKBPA29496.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5169.
HOGENOMHOG000253917.
HOVERGENHBG005999.
InParanoidQ9ULV5.
KOK09417.
OMAVEFQHPS.
PhylomeDBQ9ULV5.
TreeFamTF330401.

Gene expression databases

ArrayExpressQ9ULV5.
BgeeQ9ULV5.
CleanExHS_HSF4.
GenevestigatorQ9ULV5.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
InterProIPR027723. HSF4.
IPR000232. HSF_DNA-bd.
IPR027725. HSF_fam.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PANTHERPTHR10015. PTHR10015. 1 hit.
PTHR10015:SF43. PTHR10015:SF43. 1 hit.
PfamPF00447. HSF_DNA-bind. 1 hit.
[Graphical view]
PRINTSPR00056. HSFDOMAIN.
SMARTSM00415. HSF. 1 hit.
[Graphical view]
PROSITEPS00434. HSF_DOMAIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiHSF4.
GenomeRNAi3299.
NextBio13087.
PROQ9ULV5.
SOURCESearch...

Entry information

Entry nameHSF4_HUMAN
AccessionPrimary (citable) accession number: Q9ULV5
Secondary accession number(s): Q99472, Q9ULV6
Entry history
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: May 18, 2010
Last modified: July 9, 2014
This is version 125 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM