Q9Y5J3 (HEY1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hairy/enhancer-of-split related with YRPW motif protein 1

Alternative name(s):
Cardiovascular helix-loop-helix factor 2
Short name=CHF-2
Class B basic helix-loop-helix protein 31
Short name=bHLHb31
HES-related repressor protein 1
Hairy and enhancer of split-related protein 1
Short name=HESR-1
Hairy-related transcription factor 1
Short name=HRT-1
Short name=hHRT1

Gene names

Name:	HEY1
Synonyms:	BHLHB31, CHF2, HERP2, HESR1, HRT1

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	304 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Downstream effector of Notch signaling which may be required for cardiovascular development. Transcriptional repressor which binds preferentially to the canonical E box sequence 5'-CACGTG-3'. Represses transcription by the cardiac transcriptional activators GATA4 and GATA6. Ref.6 Ref.12
Subunit structure	Self-associates By similarity. Interacts with HES1 and HEYL By similarity. Interacts with HDAC1, NCOR1 and SIN3A By similarity. Interacts with GATA4 and GATA6 By similarity. Interacts with CCDC89/BOIP By similarity.
Subcellular location	Nucleus By similarity.
Tissue specificity	Expressed in the somitic mesoderm, the central nervous system, the kidney, the heart, nasal epithelium, and limbs.
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	Alternative splicing
Ligand	DNA-binding
Molecular function	Developmental protein Repressor
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Notch signaling involved in heart development Inferred by curator PubMed 17259303. Source: BHF-UCL angiogenesis Inferred from expression pattern PubMed 11866539. Source: UniProtKB anterior/posterior axis specification Inferred from electronic annotation. Source: Compara arterial endothelial cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL atrioventricular valve formation Inferred from sequence or structural similarity. Source: BHF-UCL cardiac ventricle morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL dorsal aorta morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL endocardial cushion to mesenchymal transition involved in heart valve formation Inferred from electronic annotation. Source: Compara epithelial to mesenchymal transition involved in endocardial cushion formation Inferred from sequence or structural similarity. Source: UniProtKB heart trabecula formation Inferred from sequence or structural similarity. Source: BHF-UCL labyrinthine layer blood vessel development Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of Notch signaling pathway Inferred from direct assay PubMed 18239137. Source: BHF-UCL negative regulation of transcription from RNA polymerase II promoter involved in smooth muscle cell differentiation Inferred from direct assay PubMed 18239137. Source: BHF-UCL negative regulation of transcription regulatory region DNA binding Inferred from direct assay PubMed 18239137. Source: BHF-UCL osteoblast development Inferred from electronic annotation. Source: Compara positive regulation of osteoblast differentiation Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: BHF-UCL pulmonary valve morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL regulation of vasculogenesis Inferred from sequence or structural similarity. Source: BHF-UCL umbilical cord morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL vasculogenesis Inferred from electronic annotation. Source: Compara ventricular septum morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL ventricular trabecula myocardium morphogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	RNA polymerase II core promoter sequence-specific DNA binding transcription factor activity Inferred from sequence or structural similarity. Source: UniProtKB microsatellite binding Inferred from direct assay PubMed 21290414. Source: UniProtKB protein binding transcription factor activity Inferred from direct assay PubMed 21290414. Source: UniProtKB transcription factor binding Non-traceable author statement PubMed 17611704. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q9Y5J3-1)

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 2 (identifier: Q9Y5J3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     82-82: K → KQVME

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 304

304

Hairy/enhancer-of-split related with YRPW motif protein 1

PRO_0000127217

Regions

Domain

49 – 104

56

bHLH

Domain

122 – 158

37

Orange

Region

48 – 117

70

Transcriptional repression and interaction with NCOR1 and SIN3A By similarity

Motif

294 – 297

4

YRPW motif

Natural variations

Alternative sequence

82

1

K → KQVME in isoform 2.

VSP_040997

Experimental info

Sequence conflict

237

1

L → F in AAF37297. Ref.5

Sequence conflict

237

1

L → P in BAC03890. Ref.8

Sequence conflict

252

1

P → L in AAF37297. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

304

Helix Strand Turn

Details...

Helix

115 – 120

6

Helix

122 – 140

19

Helix

149 – 164

16

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: F130991A99E9CA54	FASTA	304	32,613
	10 20 30 40 50 60 MKRAHPEYSS SDSELDETIE VEKESADENG NLSSALGSMS PTTSSQILAR KRRRGIIEKR 70 80 90 100 110 120 RRDRINNSLS ELRRLVPSAF EKQGSAKLEK AEILQMTVDH LKMLHTAGGK GYFDAHALAM 130 140 150 160 170 180 DYRSLGFREC LAEVARYLSI IEGLDASDPL RVRLVSHLNN YASQREAASG AHAGLGHIPW 190 200 210 220 230 240 GTVFGHHPHI AHPLLLPQNG HGNAGTTASP TEPHHQGRLG SAHPEAPALR APPSGSLGPV 250 260 270 280 290 300 LPVVTSASKL SPPLLSSVAS LSAFPFSFGS FHLLSPNALS PSAPTQAANL GKPYRPWGTE IGAF
	Isoform 2 [UniParc]. Checksum: 99A47C7EE29AC7B8	FASTA	308	33,100
	10 20 30 40 50 60 MKRAHPEYSS SDSELDETIE VEKESADENG NLSSALGSMS PTTSSQILAR KRRRGIIEKR 70 80 90 100 110 120 RRDRINNSLS ELRRLVPSAF EKQVMEQGSA KLEKAEILQM TVDHLKMLHT AGGKGYFDAH 130 140 150 160 170 180 ALAMDYRSLG FRECLAEVAR YLSIIEGLDA SDPLRVRLVS HLNNYASQRE AASGAHAGLG 190 200 210 220 230 240 HIPWGTVFGH HPHIAHPLLL PQNGHGNAGT TASPTEPHHQ GRLGSAHPEA PALRAPPSGS 250 260 270 280 290 300 LGPVLPVVTS ASKLSPPLLS SVASLSAFPF SFGSFHLLSP NALSPSAPTQ AANLGKPYRP WGTEIGAF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and expression of a novel family of bHLH cDNAs related to Drosophila hairy and enhancer of split." Kokubo H., Lun Y., Johnson R.L. Biochem. Biophys. Res. Commun. 260:459-465(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"Hey genes: a novel subfamily of hairy- and enhancer of split related genes specifically expressed during mouse embryogenesis." Leimeister C., Externbrinck A., Klamt B., Gessler M. Mech. Dev. 85:173-177(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"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] (ISOFORM 1).
[4]	"Cardiovascular basic helix loop helix factor 1, a novel transcriptional repressor expressed preferentially in the developing and adult cardiovascular system." Chin M.T., Maemura K., Fukumoto S., Jain M.K., Layne M.D., Watanabe M., Hsieh C.-M., Lee M.-E. J. Biol. Chem. 275:6381-6387(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]	"The HERP repressors, novel partners for HES/hairy in notch signaling." Iso T., Sartorelli V., Poizat C., Chen T., Sucov H.M., Chung G., Wu H.-Y., Kedes L., Hamamori Y. Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[6]	"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] (ISOFORM 1), FUNCTION, DNA-BINDING.
[7]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[8]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Placenta.
[9]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	"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] (ISOFORM 1). Tissue: Lung.
[12]	"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

AF151522 mRNA. Translation: AAD38967.1.
AF176422 mRNA. Translation: AAD51749.1.
AJ272214 mRNA. Translation: CAB75715.1.
AF232239 mRNA. Translation: AAF37297.1.
AF311883 mRNA. Translation: AAG31156.1.
BT020065 mRNA. Translation: AAV38868.1.
AK092437 mRNA. Translation: BAC03890.1.
AK313271 mRNA. Translation: BAG36080.1.
AC016240 Genomic DNA. No translation available.
CH471068 Genomic DNA. Translation: EAW87066.1.
BC001873 mRNA. Translation: AAH01873.1.

IPI

IPI00550054.
IPI00742738.

RefSeq

NP_001035798.1. NM_001040708.1.
NP_036390.3. NM_012258.3.

UniGene

Hs.234434.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DB7	X-ray	1.90	A/B	111-167	[»]

ProteinModelPortal

Q9Y5J3.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-1179634.

STRING

9606.ENSP00000338272.

PTM databases

PhosphoSite

Q9Y5J3.

Polymorphism databases

DMDM

13124298.

Proteomic databases

PaxDb

Q9Y5J3.

PRIDE

Q9Y5J3.

Protocols and materials databases

DNASU

23462.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000337919; ENSP00000338272; ENSG00000164683.
ENST00000354724; ENSP00000346761; ENSG00000164683.
ENST00000542205; ENSP00000445025; ENSG00000164683.

GeneID

23462.

KEGG

hsa:23462.

UCSC

uc003ybl.3. human.
uc003ybm.3. human.

Organism-specific databases

CTD

23462.

GeneCards

GC08M080676.

HGNC

HGNC:4880. HEY1.

HPA

HPA055599.

MIM

602953. gene.

neXtProt

NX_Q9Y5J3.

PharmGKB

PA29258.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG241271.

HOGENOM

HOG000286035.

HOVERGEN

HBG003275.

KO

K09091.

OMA

AHPDYSS.

OrthoDB

EOG4GB77H.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

Q9Y5J3.

Bgee

Q9Y5J3.

CleanEx

HS_HEY1.

Genevestigator

Q9Y5J3.

GermOnline

ENSG00000164683. Homo sapiens.

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

HEY1. human.

EvolutionaryTrace

Q9Y5J3.

GenomeRNAi

23462.

NextBio

45771.

SOURCE

Search...

Entry information

Entry name

HEY1_HUMAN

Accession

Primary (citable) accession number: Q9Y5J3
Secondary accession number(s): B2R883 , Q5TZS3, Q8NAM2, Q9NYP4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	November 1, 1999
Last modified:	May 29, 2013
This is version 129 of the entry and version 1 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.