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    HSF4 heat shock transcription factor 4 [ Homo sapiens (human) ]

    Gene ID: 3299, updated on 14-Nov-2024

    Summary

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    Official Symbol
    HSF4provided by HGNC
    Official Full Name
    heat shock transcription factor 4provided by HGNC
    Primary source
    HGNC:HGNC:5227
    See related
    Ensembl:ENSG00000102878 MIM:602438; AllianceGenome:HGNC:5227
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    CTM; CTRCT5
    Summary
    Heat-shock transcription factors (HSFs) activate heat-shock response genes under conditions of heat or other stresses. HSF4 lacks the carboxyl-terminal hydrophobic repeat which is shared among all vertebrate HSFs and has been suggested to be involved in the negative regulation of DNA binding activity. Two alternatively spliced transcripts encoding distinct isoforms and possessing different transcriptional activity have been described. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in prostate (RPKM 12.6), skin (RPKM 8.5) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See HSF4 in Genome Data Viewer
    Location:
    16q22.1
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (67163761..67169941)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (72958053..72964234)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (67197664..67203844)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene phagophore assembly factor 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7580 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7581 Neighboring gene UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 9 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7582 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:67189519-67190420 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10952 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7584 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7585 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:67195788-67196300 Neighboring gene TNFRSF1A associated via death domain Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:67196374-67197322 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:67197323-67198271 Neighboring gene Sharpr-MPRA regulatory region 11796 Neighboring gene F-box and leucine rich repeat protein 8 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10954 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10955 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7588 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:67206328-67206491 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:67207408-67208330 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:67209861-67210290 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:67211873-67212416 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:67212417-67212958 Neighboring gene nucleolar protein 3 Neighboring gene microtubule associated tyrosine carboxypeptidase 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10956 Neighboring gene exocyst complex component 3 like 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. A novel HSF4 gene mutation (p.R405X) causing autosomal recessive congenital cataracts in a large consanguineous family from Pakistan. Sajjad N, et al. BMC Med Genet, 2008 Nov 11. PMID 19014451, Free PMC Article
    2. A novel HSF4 mutation in a Chinese family with autosomal dominant congenital cataract. Liu L, et al. J Huazhong Univ Sci Technolog Med Sci, 2015 Apr. PMID 25877371
    3. DNA-binding and transcriptional activities of human HSF4 containing mutations that associate with congenital and age-related cataracts. Enoki Y, et al. Biochim Biophys Acta, 2010 Sep. PMID 20670914
    4. Mutation screening of HSF4 in 150 age-related cataract patients. Shi Y, et al. Mol Vis, 2008. PMID 18941546, Free PMC Article
    5. A novel homozygous mutation in HSF4 causing autosomal recessive congenital cataract. Behnam M, et al. J Hum Genet, 2016 Feb. PMID 26490182

    See all (56) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. miR-330-5p Suppress Cell Growth and Invasion via Disrupting HSF4-mediated MACC1/STAT3 Pathway in Colorectal Cancer.
      Title: miR-330-5p Suppress Cell Growth and Invasion via Disrupting HSF4-mediated MACC1/STAT3 Pathway in Colorectal Cancer.
    2. Variants in PAX6, PITX3 and HSF4 causing autosomal dominant congenital cataracts.
      Title: Variants in PAX6, PITX3 and HSF4 causing autosomal dominant congenital cataracts.
    3. The results expand the spectrum of HSF4 mutations causing congenital cataracts.
      Title: Novel mutations in HSF4 cause congenital cataracts in Chinese families.
    4. Ectopic UAP56 upregulated HSF4-controlled HSP25 and alpha B-crystallin proteins expression, while knocking down UAP56 by shRNA reversed it.
      Title: Heat shock factor 4 regulates the expression of HSP25 and alpha B-crystallin by associating with DEXD/H-box RNA helicase UAP56.
    5. We have identified a novel mutation in HSF4 in a large British pedigree causing dominant congenital lamellar cataract
      Title: A novel missense mutation in HSF4 causes autosomal-dominant congenital lamellar cataract in a British family.
    6. High HSF4 expression is an independent indicator of poor overall survival and recurrence free survival in patients with primary colorectal cancer.
      Title: High HSF4 expression is an independent indicator of poor overall survival and recurrence free survival in patients with primary colorectal cancer.
    7. In the cultured human lens epithelial cells, HSF4 could stabilize and retain p53 in the nucleus to activate its target genes such as fas cell surface death receptor (Fas) and Bcl-2-associated X apoptosis regulator (Bax).
      Title: HSF4 regulates lens fiber cell differentiation by activating p53 and its downstream regulators.
    8. HMOX-1, an anti-oxidase, is a bona fide transcriptional target gene of HSF4 in HLECs (human lens epithelial cells). HSF4 directly binds to the HSE element in HMOX-1 promoter to mediate its mRNA transcription and protein accumulation.
      Title: HSF4 transcriptional regulates HMOX-1 expression in HLECs.
    9. report on a novel homozygous HSF4 mutation (c.521T>C, p.Leu174Pro) in two sibs with congenital cataracts
      Title: A novel homozygous mutation in HSF4 causing autosomal recessive congenital cataract.
    10. BCAS2 interacts with HSF4 and negatively regulates its protein stability via ubiquitination.
      Title: BCAS2 interacts with HSF4 and negatively regulates its protein stability via ubiquitination.
    Submit: New GeneRIF Correction See all GeneRIFs (36)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Cataract 5 multiple types
    MedGen: C0266537 OMIM: 116800 GeneReviews: Not available
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA-binding transcription factor activity, RNA polymerase II-specific IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables DNA-binding transcription factor activity, RNA polymerase II-specific ISA
    Inferred from Sequence Alignment
    more info
    		  
    enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables identical protein binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein phosphatase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables sequence-specific double-stranded DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in lens fiber cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in chromatin IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in chromatin ISA
    Inferred from Sequence Alignment
    more info
    		  
    located_in nuclear speck IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    heat shock factor protein 4
    Names
    HSF 4
    HSTF 4
    hHSF4

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_009294.1 RefSeqGene

      Range
      6361..11557
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001040667.3 → NP_001035757.1  heat shock factor protein 4 isoform b

      See identical proteins and their annotated locations for NP_001035757.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses two alternate in-frame splice sites in the 3' coding region, compared to variant 1, resulting in a longer protein (isoform b). This variant, alternatively referred to as HSF4b, functions as a transcriptional activator of the constitutive expression of heat shock genes.
      Source sequence(s)
      AC074143, AK307211, BC130383, BX348481, CA412687
      Consensus CDS
      CCDS42175.1
      UniProtKB/Swiss-Prot
      Q99472, Q9ULV5, Q9ULV6
      UniProtKB/TrEMBL
      E5RK26
      Conserved Domains (3) summary
      smart00415
      Location:16 → 120
      HSF; heat shock factor
      pfam06546
      Location:259 → 443
      Vert_HS_TF; Vertebrate heat shock transcription factor
      pfam15035
      Location:110 → 175
      Rootletin; Ciliary rootlet component, centrosome cohesion

    2. NM_001374674.1 → NP_001361603.1  heat shock factor protein 4 isoform a

      Status: REVIEWED

      Source sequence(s)
      AK225152, AK293631, D87673
      Consensus CDS
      CCDS45510.1
      UniProtKB/TrEMBL
      E5RK26
      Related
      ENSP00000463706.1, ENST00000584272.5
      Conserved Domains (2) summary
      smart00415
      Location:16 → 120
      HSF; heat shock factor
      pfam15035
      Location:110 → 175
      Rootletin; Ciliary rootlet component, centrosome cohesion

    3. NM_001374675.1 → NP_001361604.1  heat shock factor protein 4 isoform b

      Status: REVIEWED

      Source sequence(s)
      AB029348, AC074143, AK293631, D87673
      Consensus CDS
      CCDS42175.1
      UniProtKB/Swiss-Prot
      Q99472, Q9ULV5, Q9ULV6
      UniProtKB/TrEMBL
      E5RK26
      Related
      ENSP00000430947.2, ENST00000521374.6
      Conserved Domains (3) summary
      smart00415
      Location:16 → 120
      HSF; heat shock factor
      pfam06546
      Location:259 → 443
      Vert_HS_TF; Vertebrate heat shock transcription factor
      pfam15035
      Location:110 → 175
      Rootletin; Ciliary rootlet component, centrosome cohesion

    4. NM_001538.4 → NP_001529.2  heat shock factor protein 4 isoform a

      See identical proteins and their annotated locations for NP_001529.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the shorter protein (isoform a). This variant, alternatively referred to as HSF4a, functions as an inhibitor of the constitutive expression of heat shock genes.
      Source sequence(s)
      AK307211, BX348481, CA412687, D87673
      Consensus CDS
      CCDS45510.1
      UniProtKB/TrEMBL
      E5RK26
      Conserved Domains (2) summary
      smart00415
      Location:16 → 120
      HSF; heat shock factor
      pfam15035
      Location:110 → 175
      Rootletin; Ciliary rootlet component, centrosome cohesion

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000016.10 Reference GRCh38.p14 Primary Assembly

      Range
      67163761..67169941
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060940.1 Alternate T2T-CHM13v2.0

      Range
      72958053..72964234
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9ULV5.2 GenPept UniProtKB/Swiss-Prot:Q9ULV5

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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