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FLASH GENE

Symbol

HSF4

contributors: mct - updated : 17-04-2010

HGNC name	heat shock transcription factor 4
HGNC id	5227

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	6.56 kb     15 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001538 15 splicing 2532 NP_001529 - 462 heart, brain, pancreas, skeletal muscle 2006 16581800 also called HSF4a acting as an inhibitor of tissue specific heat shock gene expression chaperones NM_001040667 15 splicing 2622 NP_001035757 52.9 492 pancreas, brain 2010 20219016 also called HSF4b acting as an activator of tissue specific heat shock gene expression direct target of the mitogen-activated protein (MAP) kinase extracellular signal-related kinase (ERK) and phosphorylation by ERK leads to increased ability to bind DNA target of SKAP2 recruits BRG1 complexes to the promoters of heat shock proteins (HSPs) under physiological growth conditions

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Digestive intestine large intestine colon     Endocrine pancreas           parathyroid           thyroid         Nervous brain         Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine   Epithelial secretory glandular exocrine   Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	lacking the C terminal hydrophobic repeat shared among all vertebrate Heat shock protein
	DNA binding domain

mono polymer

homomer , trimer

HOMOLOGY

interspecies

homolog to murine Hsf4

Homologene

FAMILY

heat shock transcription factor (HSF) family

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus
text	translocated into nucleus after heat shock

basic FUNCTION	potential repressor of genes for HS proteins and molecular chaperones
	HSF4b acting as an activator of tissue specific heat shock gene expression
	HSF4a acting as an inhibitor of tissue specific heat shock gene expression chaperones
	involved in the negative regulation of DNA binding activity
	required for the lens development

CELLULAR PROCESS

nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

pathway (NBN-HSF4-HSPA4/HSPA14 axis) to induce migration, invasion, and transformation, suggesting the activation of multiple signaling events induced by NBN overexpression

a component

forming homotrimer even in the absence of stress

INTERACTION

DNA	binding specifially to heat shock promoter elements (hse)
	binding (constitutive)

RNA

small molecule

protein	essential role for HSF4-mediated SKAP2 expression in the regulation of actin reorganization during lens differentiation, likely through a mechanism that SKAP2 anchors the complex of NCK2/focal adhesion to FGF receptors at the lamellipodium in lens epithelial cells
	HSF2 and HSF4 regulate transcription of HIF1A and a critical balance between these HSF is required to maintain HIF1A expression in a repressed state
	HSF4 inhibits HSF2 expression or transcriptional activity through negative regulation of HSF2 binding to the HSP70 promoter
	HSF4 occupies only CRYAB and not HSP70 promoter in epithelial cells, while HSF1 occupies only HSP70 promoter in both cell types, and CRYAB promoter, only in heat shocked fibroblasts

cell & other

REGULATION

induced by

NBN (NBN overexpression induced the expression of HSF4, which correlated with the expression of HSPA4 and HSPA14)

ASSOCIATED DISORDERS

corresponding disease(s)

CTM

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       loss of function leads to defect in lens epithelial cell (LEC) differentiation and cataract formation

Susceptibility

to age related cataract

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed neurosensorial     HSF4-vimentin axis appears to be a new target for developing anti-cataract drugs, especially for those cataracts resulting from aberrations in HSF4 expression

ANIMAL & CELL MODELS

sf4 knockout mouse (Hsf4-/-) partially mimics the human cataract caused by HSF4 mutations