Q14469 (HES1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transcription factor HES-1

Alternative name(s):
Class B basic helix-loop-helix protein 39
Short name=bHLHb39
Hairy and enhancer of split 1
Hairy homolog
Hairy-like protein
Short name=hHL

Gene names

Name:	HES1
Synonyms:	BHLHB39, HL, HRY

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

General annotation (Comments)

Function	Transcriptional repressor of genes that require a bHLH protein for their transcription. May act as a negative regulator of myogenesis by inhibiting the functions of MYOD1 and ASH1. Binds DNA on N-box motifs: 5'-CACNAG-3' with high affinity and on E-box motifs: 5'-CANNTG-3' with low affinity By similarity. May play a role in a functional FA core complex response to DNA cross-link damage, being required for the stability and nuclear localization of FA core complex proteins, as well as for FANCD2 monoubiquitination in response to DNA damage. Ref.6
Subunit structure	Transcription repression requires formation of a complex with a corepressor protein of the Groucho/TLE family. Interacts (via WPRW motif) with TLE1, and more weakly with TLE2. Interacts with HES6 By similarity. Interacts with SIRT1. Interacts with an FA complex, composed of FANCA, FANCF, FANCG and FANCL, but not of FANCC, nor FANCE. Ref.5 Ref.6
Subcellular location	Nucleus.
Domain	Has a particular type of basic domain (presence of a helix-interrupting proline) that binds to the N-box (CACNAG), rather than the canonical E-box (CANNTG). The C-terminal WRPW motif is a transcriptional repression domain necessary for the interaction with Groucho/TLE family members, transcriptional corepressors recruited to specific target DNA by Hairy-related proteins By similarity. The bHLH, as well as cooperation between the central Orange domain and the C-terminal WRPW motif, is required for transcriptional repressor activity By similarity.
Sequence similarities	Contains 1 bHLH (basic helix-loop-helix) domain. Contains 1 Orange domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Ligand	DNA-binding
Molecular function	Repressor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Notch signaling pathway Inferred from direct assay PubMed 16160079. Source: UniProtKB S-shaped body morphogenesis Inferred from electronic annotation. Source: Compara STAT protein import into nucleus Inferred from sequence or structural similarity. Source: UniProtKB adenohypophysis development Inferred from electronic annotation. Source: Compara ascending aorta morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL auditory receptor cell fate determination Inferred from electronic annotation. Source: Compara cardiac neural crest cell development involved in outflow tract morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL cell adhesion Inferred from electronic annotation. Source: Compara cell maturation Inferred from electronic annotation. Source: Compara cell migration Inferred from electronic annotation. Source: Compara cell morphogenesis involved in neuron differentiation Inferred from electronic annotation. Source: Compara cochlea development Inferred from electronic annotation. Source: Compara comma-shaped body morphogenesis Inferred from electronic annotation. Source: Compara common bile duct development Inferred from electronic annotation. Source: Compara embryonic heart tube morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL endocrine pancreas development Traceable author statement. Source: Reactome forebrain radial glial cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB glomerulus vasculature development Inferred from electronic annotation. Source: Compara hindbrain morphogenesis Inferred from electronic annotation. Source: Compara labyrinthine layer blood vessel development Inferred from electronic annotation. Source: Compara lateral inhibition Inferred from electronic annotation. Source: Compara liver development Inferred from electronic annotation. Source: Compara lung development Inferred from electronic annotation. Source: Compara metanephric nephron tubule morphogenesis Inferred from electronic annotation. Source: Compara midbrain development Inferred from electronic annotation. Source: Compara midbrain-hindbrain boundary morphogenesis Inferred from electronic annotation. Source: Compara negative regulation of auditory receptor cell differentiation Inferred from electronic annotation. Source: Compara negative regulation of forebrain neuron differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of glial cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of oligodendrocyte differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of pancreatic A cell differentiation Inferred from electronic annotation. Source: Compara negative regulation of pro-B cell differentiation Inferred from mutant phenotype PubMed 12032823. Source: UniProtKB negative regulation of stem cell differentiation Inferred from mutant phenotype PubMed 19682396. Source: UniProtKB negative regulation of stomach neuroendocrine cell differentiation Inferred from electronic annotation. Source: Compara neuronal stem cell maintenance Inferred from expression pattern PubMed 19682396. Source: UniProtKB oculomotor nerve development Inferred from electronic annotation. Source: Compara pharyngeal system development Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of BMP signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of DNA binding Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of Notch signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of T cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of astrocyte differentiation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell proliferation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of mitotic cell cycle, embryonic Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of tyrosine phosphorylation of Stat3 protein Inferred from sequence or structural similarity. Source: UniProtKB protein complex assembly Inferred from sequence or structural similarity. Source: UniProtKB regulation of fat cell differentiation Inferred from electronic annotation. Source: Compara regulation of secondary heart field cardioblast proliferation Inferred from sequence or structural similarity. Source: BHF-UCL regulation of timing of neuron differentiation Inferred from electronic annotation. Source: Compara renal interstitial cell development Inferred from electronic annotation. Source: Compara smoothened signaling pathway Inferred from electronic annotation. Source: Compara somatic stem cell maintenance Inferred from electronic annotation. Source: Compara telencephalon development Inferred from electronic annotation. Source: Compara thymus development Inferred from sequence or structural similarity. Source: BHF-UCL trochlear nerve development Inferred from electronic annotation. Source: Compara ureteric bud morphogenesis Inferred from electronic annotation. Source: Compara vascular smooth muscle cell development 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 electronic annotation. Source: Compara nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	N-box binding Inferred from sequence or structural similarity. Source: UniProtKB RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription Inferred from sequence or structural similarity. Source: UniProtKB protein homodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB sequence-specific DNA binding Inferred from sequence or structural similarity. Source: UniProtKB transcription factor binding Non-traceable author statement PubMed 17611704. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SIRT1	Q96EB6	4	EBI-2832522,EBI-1802965

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 280	280	Transcription factor HES-1		PRO_0000127202
Regions
	Domain	34 – 91	58	bHLH
	Domain	110 – 143	34	Orange
	Motif	275 – 278	4	WRPW motif
	Compositional bias	156 – 246	91	Pro-rich
	Compositional bias	249 – 273	25	Ser/Thr-rich

Sequences

	Sequence		Length	Mass (Da)
	Q14469 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: F9342A88FC749E3C	FASTA	280	29,541
	10 20 30 40 50 60 MPADIMEKNS SSPVAATPAS VNTTPDKPKT ASEHRKSSKP IMEKRRRARI NESLSQLKTL 70 80 90 100 110 120 ILDALKKDSS RHSKLEKADI LEMTVKHLRN LQRAQMTAAL STDPSVLGKY RAGFSECMNE 130 140 150 160 170 180 VTRFLSTCEG VNTEVRTRLL GHLANCMTQI NAMTYPGQPH PALQAPPPPP PGPGGPQHAP 190 200 210 220 230 240 FAPPPPLVPI PGGAAPPPGG APCKLGSQAG EAAKVFGGFQ VVPAPDGQFA FLIPNGAFAH 250 260 270 280 SGPVIPVYTS NSGTSVGPNA VSPSSGPSLT ADSMWRPWRN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Genomic cloning and chromosomal localization of HRY, the human homolog to the Drosophila segmentation gene, hairy." Feder J.N., Li L., Jan L.Y., Jan Y.-N. Genomics 20:56-61(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Functional analysis of human HRY in Drosophila." Yao J., Yeung S., Sun H., Chen N. Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Kidney.
[3]	"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].
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression." Takata T., Ishikawa F. Biochem. Biophys. Res. Commun. 301:250-257(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SIRT1.
[6]	"HES1 is a novel interactor of the Fanconi anemia core complex." Tremblay C.S., Huang F.F., Habi O., Huard C.C., Godin C., Levesque G., Carreau M. Blood 112:2062-2070(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH FA COMPLEX.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L19314 Genomic DNA. Translation: AAA65220.1. AF264785 mRNA. Translation: AAF73060.1. AK000415 mRNA. Translation: BAA91149.1. CR541843 mRNA. Translation: CAG46641.1.
IPI	IPI00030964.
PIR	A53027.
RefSeq	NP_005515.1. NM_005524.3.
UniGene	Hs.250666.
3D structure databases
ProteinModelPortal	Q14469.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q14469. 6 interactions.
STRING	9606.ENSP00000232424.
PTM databases
PhosphoSite	Q14469.
Polymorphism databases
DMDM	3913825.
Proteomic databases
PaxDb	Q14469.
PRIDE	Q14469.
Protocols and materials databases
DNASU	3280.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000232424; ENSP00000232424; ENSG00000114315.
GeneID	3280.
KEGG	hsa:3280.
UCSC	uc003ftq.2. human.
Organism-specific databases
CTD	3280.
GeneCards	GC03P193853.
HGNC	HGNC:5192. HES1.
MIM	139605. gene.
neXtProt	NX_Q14469.
PharmGKB	PA29465.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG319418.
HOGENOM	HOG000236346.
HOVERGEN	HBG005960.
InParanoid	Q14469.
KO	K06054.
OMA	TKVYGGF.
OrthoDB	EOG4TTGK6.
PhylomeDB	Q14469.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology. REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q14469.
Bgee	Q14469.
CleanEx	HS_HES1.
Genevestigator	Q14469.
GermOnline	ENSG00000114315. 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
GenomeRNAi	3280.
NextBio	13023.
SOURCE	Search...

Entry information

Entry name

HES1_HUMAN

Accession

Primary (citable) accession number: Q14469
Secondary accession number(s): Q6FHB2

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 123 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.