HSF4
Function
Heat-shock transcription factor that specifically binds heat shock promoter elements (HSE) (PubMed:22587838, PubMed:23507146). Required for denucleation and organelle rupture and degradation that occur during eye lens terminal differentiation, when fiber cells that compose the lens degrade all membrane-bound organelles in order to provide lens with transparency to allow the passage of light (By similarity). In this process, may regulate denucleation of lens fiber cells in part by activating DNASE2B transcription (By similarity). May be involved in DNA repair through the transcriptional regulation of RAD51 (PubMed:22587838). May up-regulate p53/TP53 protein in eye lens fiber cells, possibly through protein stabilization (PubMed:28981088). In the eye lens, controls the expression of alpha-crystallin B chain/CRYAB and consequently may be involved in the regulation of lysosomal acidification (By similarity).
Isoform HSF4A
Transcriptional repressor.
Isoform HSF4B
Transcriptional activator.
Involvement in disease
Cataract 5, multiple types
CTRCT5
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated mainly on serine residues. Phosphorylation on Ser-298 promotes sumoylation on Lys-293.
Isoform HSF4B is constitutively sumoylated. Sumoylation represses the transcriptional activity and is promoted by phosphorylation on Ser-298. HSFA is not sumoylated.
Sequence Similarities
Belongs to the HSF family.
Tissue Specificity
Expressed in heart, skeletal muscle, eye and brain, and at much lower levels in some other tissues.
Cellular localization
- Nucleus
Alternative names
Heat shock factor protein 4, HSF 4, hHSF4, Heat shock transcription factor 4, HSTF 4, HSF4