Q9NQ87 (HEYL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hairy/enhancer-of-split related with YRPW motif-like protein
Short name=hHeyL

Alternative name(s):
Class B basic helix-loop-helix protein 33
Short name=bHLHb33
Hairy-related transcription factor 3
Short name=HRT-3
Short name=hHRT3

Gene names

Name:	HEYL
Synonyms:	BHLHB33, HRT3

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	328 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Downstream effector of Notch signaling which may be required for cardiovascular development By similarity. Transcriptional repressor which binds preferentially to the canonical E box sequence 5'-CACGTG-3' By similarity. Represses transcription by the cardiac transcriptional activators GATA4 and GATA6. Ref.6
Subunit structure	Self-associates By similarity. Interacts with GATA4, GATA6, HES1, HEY1 and HEY2 By similarity. Interacts with HDAC1, NCOR1 and SIN3A By similarity.
Subcellular location	Nucleus By similarity.
Induction	By activation of the Notch signaling pathway. Ref.5
Sequence similarities	Belongs to the HEY family. Contains 1 bHLH (basic helix-loop-helix) domain. Contains 1 Orange domain.

Ontologies

Keywords
Biological process	Notch signaling pathway Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Ligand	DNA-binding
Molecular function	Developmental protein Repressor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Notch signaling pathway Inferred from direct assay Ref.5. Source: UniProtKB atrioventricular valve morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL cardiac ventricle morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL cellular response to BMP stimulus Inferred from electronic annotation. Source: Compara epithelial to mesenchymal transition involved in endocardial cushion formation Inferred from sequence or structural similarity. Source: UniProtKB glomerulus development Inferred from electronic annotation. Source: Compara negative regulation of androgen receptor activity Inferred from direct assay PubMed 21454491. Source: UniProtKB negative regulation of androgen receptor signaling pathway Inferred from direct assay PubMed 21454491. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from direct assay Ref.6PubMed 21454491. Source: UniProtKB outflow tract morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of neuron differentiation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 21290414. Source: UniProtKB proximal tubule development Inferred from electronic annotation. Source: Compara pulmonary valve morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL ventricular septum morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from direct assay PubMed 21454491. Source: UniProtKB
Molecular_function	RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Inferred from electronic annotation. Source: Compara RNA polymerase II core promoter sequence-specific DNA binding Inferred from electronic annotation. Source: Compara RNA polymerase II core promoter sequence-specific DNA binding transcription factor activity Inferred from sequence or structural similarity. Source: UniProtKB RNA polymerase II transcription corepressor activity Inferred from electronic annotation. Source: Compara microsatellite binding Inferred from direct assay PubMed 21290414. Source: UniProtKB protein heterodimerization activity Inferred from direct assay PubMed 21454491. Source: UniProtKB transcription corepressor activity Inferred from direct assay PubMed 21454491. Source: UniProtKB transcription factor binding Non-traceable author statement PubMed 17611704. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 328	328	Hairy/enhancer-of-split related with YRPW motif-like protein		PRO_0000286429
Regions
	Domain	43 – 98	56	bHLH
	Domain	116 – 153	38	Orange
	Region	42 – 111	70	Transcriptional repression and interaction with NCOR1 and SIN3A By similarity
	Compositional bias	162 – 309	148	Pro-rich
Natural variations
	Natural variant	47	1	H → R. Ref.1 Ref.2 Corresponds to variant rs784625 [ dbSNP | Ensembl ].		VAR_032112

Sequences

	Sequence		Length	Mass (Da)
	Q9NQ87 [UniParc]. Last modified May 1, 2007. Version 2. Checksum: C11A1EAB18611F43	FASTA	328	35,087
	10 20 30 40 50 60 MKRPKEPSGS DGESDGPIDV GQEGQLSQMA RPLSTPSSSQ MQARKKHRGI IEKRRRDRIN 70 80 90 100 110 120 SSLSELRRLV PTAFEKQGSS KLEKAEVLQM TVDHLKMLHA TGGTGFFDAR ALAVDFRSIG 130 140 150 160 170 180 FRECLTEVIR YLGVLEGPSS RADPVRIRLL SHLNSYAAEM EPSPTPTGPL AFPAWPWSFF 190 200 210 220 230 240 HSCPGLPALS NQLAILGRVP SPVLPGVSSP AYPIPALRTA PLRRATGIIL PARRNVLPSR 250 260 270 280 290 300 GASSTRRARP LERPATPVPV APSSRAARSS HIAPLLQSSS PTPPGPTGSA AYVAVPTPNS 310 320 SSPGPAGRPA GAMLYHSWVS EITEIGAF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of the human and mouse HEY1, HEY2, and HEYL genes: cloning, mapping, and mutation screening of a new bHLH gene family." Steidl C., Leimeister C., Klamt B., Maier M., Nanda I., Dixon M., Clarke R., Schmid M., Gessler M. Genomics 66:195-203(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-47.
[2]	"Members of the HRT family of basic helix-loop-helix proteins act as transcriptional repressors downstream of Notch signaling." Nakagawa O., McFadden D.G., Nakagawa M., Yanagisawa H., Hu T., Srivastava D., Olson E.N. Proc. Natl. Acad. Sci. U.S.A. 97:13655-13660(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-47.
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Muscle.
[5]	"Comparative analysis of the human and mouse Hey1 promoter: Hey genes are new Notch target genes." Maier M.M., Gessler M. Biochem. Biophys. Res. Commun. 275:652-660(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[6]	"Hairy-related transcription factors inhibit GATA-dependent cardiac gene expression through a signal-responsive mechanism." Kathiriya I.S., King I.N., Murakami M., Nakagawa M., Astle J.M., Gardner K.A., Gerard R.D., Olson E.N., Srivastava D., Nakagawa O. J. Biol. Chem. 279:54937-54943(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ272215 mRNA. Translation: CAB75716.1. AF311885 mRNA. Translation: AAG31158.1. AL035404 Genomic DNA. Translation: CAI19572.1. BC006087 mRNA. Translation: AAH06087.1.
IPI	IPI00005137.
RefSeq	NP_055386.1. NM_014571.3.
UniGene	Hs.472566.
3D structure databases
ProteinModelPortal	Q9NQ87.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NQ87. 3 interactions.
MINT	MINT-1190764.
STRING	9606.ENSP00000361943.
PTM databases
PhosphoSite	Q9NQ87.
Polymorphism databases
DMDM	146286205.
Proteomic databases
PaxDb	Q9NQ87.
PRIDE	Q9NQ87.
Protocols and materials databases
DNASU	26508.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000372852; ENSP00000361943; ENSG00000163909.
GeneID	26508.
KEGG	hsa:26508.
UCSC	uc001cdp.3. human.
Organism-specific databases
CTD	26508.
GeneCards	GC01M040119.
HGNC	HGNC:4882. HEYL.
HPA	HPA001438.
MIM	609034. gene.
neXtProt	NX_Q9NQ87.
PharmGKB	PA29260.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG310123.
HOGENOM	HOG000286035.
HOVERGEN	HBG003275.
InParanoid	Q9NQ87.
KO	K09091.
OMA	HSWVSEI.
OrthoDB	EOG4P8FJZ.
PhylomeDB	Q9NQ87.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q9NQ87.
Bgee	Q9NQ87.
CleanEx	HS_HEYL.
Genevestigator	Q9NQ87.
Family and domain databases
Gene3D	4.10.280.10. 1 hit.
InterPro	IPR011598. bHLH_dom. IPR003650. Orange. IPR018352. Orange_subgr. [Graphical view]
Pfam	PF07527. Hairy_orange. 1 hit. PF00010. HLH. 1 hit. [Graphical view]
SMART	SM00353. HLH. 1 hit. SM00511. ORANGE. 1 hit. [Graphical view]
SUPFAM	SSF47459. HLH_basic. 1 hit.
PROSITE	PS50888. BHLH. 1 hit. PS51054. ORANGE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	HEYL. human.
GenomeRNAi	26508.
NextBio	48798.
SOURCE	Search...

Entry information

Entry name

HEYL_HUMAN

Accession

Primary (citable) accession number: Q9NQ87
Secondary accession number(s): Q5TG99

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 2007
Last sequence update:	May 1, 2007
Last modified:	May 1, 2013
This is version 99 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.