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

Summary

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

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_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
Variants in PAX6, PITX3 and HSF4 causing autosomal dominant congenital cataracts.
Title: Variants in PAX6, PITX3 and HSF4 causing autosomal dominant congenital cataracts.
The results expand the spectrum of HSF4 mutations causing congenital cataracts.
Title: Novel mutations in HSF4 cause congenital cataracts in Chinese families.
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.
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.
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.
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.
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.
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.
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

NoName (e-PCR)
- UniSTS:494796

NoName (e-PCR)
- UniSTS:489702

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

NG_009294.1 RefSeqGene

Range

6361..11557

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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