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Q9ULV5

- HSF4_HUMAN

UniProt

Q9ULV5 - HSF4_HUMAN

Protein

Heat shock factor protein 4

Gene

HSF4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 126 (01 Oct 2014)
      Sequence version 2 (18 May 2010)
      Previous versions | rss
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    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: UniProt
    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. response to stress Source: UniProtKB-KW
    11. transcription, DNA-templated Source: UniProtKB-KW

    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. nucleus Source: HPA

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    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.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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

    ArrayExpressiQ9ULV5.
    BgeeiQ9ULV5.
    CleanExiHS_HSF4.
    GenevestigatoriQ9ULV5.

    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

    Protein-protein interaction databases

    BioGridi109532. 9 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.
    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. Align

    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

    MQEAPAALPT EPGPSPVPAF LGKLWALVGD PGTDHLIRWS PSGTSFLVSD    50
    QSRFAKEVLP QYFKHSNMAS FVRQLNMYGF RKVVSIEQGG LLRPERDHVE 100
    FQHPSFVRGR EQLLERVRRK VPALRGDDGR WRPEDLGRLL GEVQALRGVQ 150
    ESTEARLREL RQQNEILWRE VVTLRQSHGQ QHRVIGKLIQ CLFGPLQAGP 200
    SNAGGKRKLS LMLDEGSSCP TPAKFNTCPL PGALLQDPYF IQSPLPETNL 250
    GLSPHRARGP IISDIPEDSP SPEGTRLSPS SDGRREKGLA LLKEEPASPG 300
    GDGEAGLALA PNECDFCVTA PPPLPVAVVQ AILEGKGSFS PEGPRNAQQP 350
    EPGDPREIPD RGPLGLESGD RSPESLLPPM LLQPPQESVE PAGPLDVLGP 400
    SLQGREWTLM DLDMELSLMQ PLVPERGEPE LAVKGLNSPS PGKDPTLGAP 450
    LLLDVQAALG GPALGLPGAL TIYSTPESRT ASYLGPEASP SP 492
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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 ]
    UniGenei Hs.512156.
    Hs.710714.

    3D structure databases

    ProteinModelPortali Q9ULV5.
    SMRi Q9ULV5. Positions 13-124.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109532. 9 interactions.
    IntActi Q9ULV5. 13 interactions.
    MINTi MINT-8247415.
    STRINGi 9606.ENSP00000264009.

    PTM databases

    PhosphoSitei Q9ULV5.

    Polymorphism databases

    DMDMi 296434534.

    Proteomic databases

    PaxDbi Q9ULV5.
    PRIDEi Q9ULV5.

    Protocols and materials databases

    DNASUi 3299.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000264009 ; ENSP00000264009 ; ENSG00000102878 . [Q9ULV5-1 ]
    ENST00000521374 ; ENSP00000430947 ; ENSG00000102878 . [Q9ULV5-1 ]
    ENST00000584272 ; ENSP00000463706 ; ENSG00000102878 . [Q9ULV5-2 ]
    GeneIDi 3299.
    KEGGi hsa:3299.
    UCSCi uc002erl.2. human. [Q9ULV5-1 ]
    uc002erm.2. human. [Q9ULV5-2 ]

    Organism-specific databases

    CTDi 3299.
    GeneCardsi GC16P067197.
    HGNCi HGNC:5227. HSF4.
    HPAi HPA048584.
    MIMi 116800. phenotype.
    602438. gene.
    neXtProti NX_Q9ULV5.
    Orphaneti 98995. Zonular cataract.
    PharmGKBi PA29496.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5169.
    HOGENOMi HOG000253917.
    HOVERGENi HBG005999.
    InParanoidi Q9ULV5.
    KOi K09417.
    OMAi VEFQHPS.
    PhylomeDBi Q9ULV5.
    TreeFami TF330401.

    Miscellaneous databases

    GeneWikii HSF4.
    GenomeRNAii 3299.
    NextBioi 13087.
    PROi Q9ULV5.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9ULV5.
    Bgeei Q9ULV5.
    CleanExi HS_HSF4.
    Genevestigatori Q9ULV5.

    Family and domain databases

    Gene3Di 1.10.10.10. 1 hit.
    InterProi IPR027723. HSF4.
    IPR000232. HSF_DNA-bd.
    IPR027725. HSF_fam.
    IPR011991. WHTH_DNA-bd_dom.
    [Graphical view ]
    PANTHERi PTHR10015. PTHR10015. 1 hit.
    PTHR10015:SF43. PTHR10015:SF43. 1 hit.
    Pfami PF00447. HSF_DNA-bind. 1 hit.
    [Graphical view ]
    PRINTSi PR00056. HSFDOMAIN.
    SMARTi SM00415. HSF. 1 hit.
    [Graphical view ]
    PROSITEi PS00434. HSF_DOMAIN. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 126 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