Q9ULV5 (HSF4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

HSF4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	492 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	DNA-binding protein that specifically binds heat shock promoter elements (HSE). Isoform HSF4A represses transcription while the isoform HSF4B activates transcription. Ref.5
Subunit structure	Homotrimer. Exhibits constitutive DNA binding and forms trimers even in the absence of stress. Interacts with DUSP26, MAPK1, MAPK2 and MAP kinase p38. Ref.4
Subcellular location	Nucleus.
Tissue specificity	Expressed in heart, skeletal muscle, eye and brain, and at much lower levels in some other tissues. Ref.6
Post-translational modification	Phosphorylated mainly on serine residues. Phosphorylation on Ser-298 promotes sumoylation on Lys-293. Ref.5 Isoform HSF4B is constitutively sumoylated. Sumoylation represses the transcriptional activity and is promoted by phosphorylation on Ser-298. HSFA is not sumoylated. Ref.5
Involvement in disease	Cataract, zonular (CZ) [MIM:116800]: A form of zonular cataract. Zonular or lamellar cataracts are opacities, broad or narrow, usually consisting of powdery white dots affecting only certain layers or zones between the cortex and nucleus of an otherwise clear lens. The opacity may be so dense as to render the entire central region of the lens completely opaque, or so translucent that vision is hardly if at all impeded. Zonular cataracts generally do not involve the embryonic nucleus, though sometimes they involve the fetal nucleus. Usually sharply separated from a clear cortex outside them, they may have projections from their outer edges known as riders or spokes. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.7 Cataract Marner type (CAM) [MIM:116800]: A form of cataract with variable and progressive opacities. Affected individuals present with zonular cataract, although some have nuclear, anterior polar, or stellate cataract. Finger malformation is observed in some kindreds. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6
Sequence similarities	Belongs to the HSF family.

Ontologies

Keywords
Biological process	Stress response Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Disease	Cataract Disease mutation
Ligand	DNA-binding
Molecular function	Activator Repressor
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	camera-type eye development Inferred from electronic annotation. Source: Compara cell development Inferred from electronic annotation. Source: Compara histone H3-K9 demethylation Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara positive regulation of cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara protein homotrimerization Inferred from electronic annotation. Source: Compara response to stress Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	sequence-specific DNA binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding transcription factor activity Traceable author statement Ref.1. Source: ProtInc transcription corepressor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform HSF4B (identifier: Q9ULV5-1)

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.

Isoform HSF4A (identifier: Q9ULV5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     245-319: LPETNLGLSP...APNECDFCVT → STYSLSQRQI...PGFLPPVMAG

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 492	492	Heat shock factor protein 4		PRO_0000124571
Regions
	DNA binding	17 – 121	105	By similarity
	Region	129 – 203	75	Hydrophobic repeat HR-A/B
	Region	245 – 322	78	Interactions with DUSP26, MAPK1 and MAPK2
	Region	364 – 389	26	Hydrophobic repeat HR-C
Amino acid modifications
	Modified residue	298	1	Phosphoserine Ref.5
	Cross-link	293		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.5
Natural variations
	Alternative sequence	245 – 319	75	LPETN…DFCVT → STYSLSQRQIWALALTGPGA PSSLTSQKTLHPLRGPGFLP PVMAG in isoform HSF4A.		VSP_002418
	Natural variant	19	1	A → D in CZ; sporadic. Ref.6		VAR_017558
	Natural variant	73	1	R → H in CZ. Ref.7		VAR_029018
	Natural variant	86	1	I → V in CZ; sporadic. Ref.6		VAR_017559
	Natural variant	114	1	L → P in CZ. Ref.6		VAR_017560
	Natural variant	119	1	R → C in CAM. Ref.6 Corresponds to variant rs28937573 [ dbSNP | Ensembl ].		VAR_017561
Experimental info
	Mutagenesis	293	1	K → R: Abolishes sumoylation. 10-fold increased in transactivational activity. Ref.5
	Mutagenesis	298	1	S → A: Abolishes phosphorylation. Greatly reduced sumoylation. Greatly increased transactivational activity. Ref.5
	Sequence conflict	1	1	M → MV in BAA13433. Ref.1
	Sequence conflict	1	1	M → MV in BAA84582. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform HSF4B [UniParc]. Last modified May 18, 2010. Version 2. Checksum: D5F1C0D68014BC2E	FASTA	492	53,011
	10 20 30 40 50 60 MQEAPAALPT EPGPSPVPAF LGKLWALVGD PGTDHLIRWS PSGTSFLVSD QSRFAKEVLP 70 80 90 100 110 120 QYFKHSNMAS FVRQLNMYGF RKVVSIEQGG LLRPERDHVE FQHPSFVRGR EQLLERVRRK 130 140 150 160 170 180 VPALRGDDGR WRPEDLGRLL GEVQALRGVQ ESTEARLREL RQQNEILWRE VVTLRQSHGQ 190 200 210 220 230 240 QHRVIGKLIQ CLFGPLQAGP SNAGGKRKLS LMLDEGSSCP TPAKFNTCPL PGALLQDPYF 250 260 270 280 290 300 IQSPLPETNL GLSPHRARGP IISDIPEDSP SPEGTRLSPS SDGRREKGLA LLKEEPASPG 310 320 330 340 350 360 GDGEAGLALA PNECDFCVTA PPPLPVAVVQ AILEGKGSFS PEGPRNAQQP EPGDPREIPD 370 380 390 400 410 420 RGPLGLESGD RSPESLLPPM LLQPPQESVE PAGPLDVLGP SLQGREWTLM DLDMELSLMQ 430 440 450 460 470 480 PLVPERGEPE LAVKGLNSPS PGKDPTLGAP LLLDVQAALG GPALGLPGAL TIYSTPESRT 490 ASYLGPEASP SP
	Isoform HSF4A [UniParc]. Checksum: F850CE8843CF4DDB	FASTA	462	49,952
	10 20 30 40 50 60 MQEAPAALPT EPGPSPVPAF LGKLWALVGD PGTDHLIRWS PSGTSFLVSD QSRFAKEVLP 70 80 90 100 110 120 QYFKHSNMAS FVRQLNMYGF RKVVSIEQGG LLRPERDHVE FQHPSFVRGR EQLLERVRRK 130 140 150 160 170 180 VPALRGDDGR WRPEDLGRLL GEVQALRGVQ ESTEARLREL RQQNEILWRE VVTLRQSHGQ 190 200 210 220 230 240 QHRVIGKLIQ CLFGPLQAGP SNAGGKRKLS LMLDEGSSCP TPAKFNTCPL PGALLQDPYF 250 260 270 280 290 300 IQSPSTYSLS QRQIWALALT GPGAPSSLTS QKTLHPLRGP GFLPPVMAGA PPPLPVAVVQ 310 320 330 340 350 360 AILEGKGSFS PEGPRNAQQP EPGDPREIPD RGPLGLESGD RSPESLLPPM LLQPPQESVE 370 380 390 400 410 420 PAGPLDVLGP SLQGREWTLM DLDMELSLMQ PLVPERGEPE LAVKGLNSPS PGKDPTLGAP 430 440 450 460 LLLDVQAALG GPALGLPGAL TIYSTPESRT ASYLGPEASP SP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	"PDSM, a motif for phosphorylation-dependent SUMO modification." Hietakangas V., Anckar J., Blomster H.A., Fujimoto M., Palvimo J.J., Nakai A., Sistonen L. Proc. Natl. Acad. Sci. U.S.A. 103:45-50(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION AT LYS-293, PHOSPHORYLATION AT SER-298, FUNCTION, MUTAGENESIS OF LYS-293 AND SER-298.
[6]	"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 CZ ASP-19; VAL-86 AND PRO-114, VARIANT CAM CYS-119, TISSUE SPECIFICITY.
[7]	"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 CZ HIS-73.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D87673 mRNA. Translation: BAA13433.1. AB029347 Genomic DNA. Translation: BAA84581.1. AB029348 mRNA. Translation: BAA84582.1. AC074143 Genomic DNA. No translation available.
IPI	IPI00008456. IPI00220197.
RefSeq	NP_001035757.1. NM_001040667.2. NP_001529.2. NM_001538.3.
UniGene	Hs.512156. Hs.710714.
3D structure databases
ProteinModelPortal	Q9ULV5.
SMR	Q9ULV5. Positions 13-124.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9ULV5. 1 interaction.
STRING	9606.ENSP00000264009.
PTM databases
PhosphoSite	Q9ULV5.
Polymorphism databases
DMDM	296434534.
Proteomic databases
PaxDb	Q9ULV5.
PRIDE	Q9ULV5.
Protocols and materials databases
DNASU	3299.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264009; ENSP00000264009; ENSG00000102878. ENST00000421453; ENSP00000408815; ENSG00000102878. ENST00000521374; ENSP00000430947; ENSG00000102878. ENST00000584272; ENSP00000463706; ENSG00000102878.
GeneID	3299.
KEGG	hsa:3299.
UCSC	uc002erl.2. human. uc002erm.2. human.
Organism-specific databases
CTD	3299.
GeneCards	GC16P067197.
HGNC	HGNC:5227. HSF4.
MIM	116800. phenotype. 602438. gene.
neXtProt	NX_Q9ULV5.
Orphanet	98995. Zonular cataract.
PharmGKB	PA29496.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5169.
HOGENOM	HOG000253917.
HOVERGEN	HBG005999.
InParanoid	Q9ULV5.
KO	K09417.
OMA	RDHVEFQ.
OrthoDB	EOG48WC1Z.
Gene expression databases
ArrayExpress	Q9ULV5.
Bgee	Q9ULV5.
CleanEx	HS_HSF4.
Genevestigator	Q9ULV5.
GermOnline	ENSG00000102878. Homo sapiens.
Family and domain databases
Gene3D	1.10.10.10. 1 hit.
InterPro	IPR000232. HSF_DNA-bd. IPR011991. WHTH_DNA-bd_dom. [Graphical view]
Pfam	PF00447. HSF_DNA-bind. 1 hit. [Graphical view]
PRINTS	PR00056. HSFDOMAIN.
SMART	SM00415. HSF. 1 hit. [Graphical view]
PROSITE	PS00434. HSF_DOMAIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	3299.
NextBio	13087.
SOURCE	Search...

Entry information

Entry name

HSF4_HUMAN

Accession

Primary (citable) accession number: Q9ULV5
Secondary accession number(s): Q99472, Q9ULV6

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 11, 2001
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 113 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.