UniProt Accession

 BHE40_HUMAN; O14503; Q96TD3 

Genbank Protein ID

 AB004066; AB043885; BC082238; AH010709 

Genbank Nucleotide ID

 BAA21720.1; BAB18565.1; AAH82238.1; AAK49525.1 

Protein Name

 Class E basic helix-loop-helix protein 40 

Protein Synonyms/Alias

 bHLHe40; Class B basic helix-loop-helix protein 2; bHLHb2; Differentially expressed in chondrocytes protein 1; DEC1; Enhancer-of-split and hairy-related protein 2; SHARP-2; Stimulated by retinoic acid gene 13 protein 

Gene Name

 BHLHE40 

Gene Synonyms/Alias

 BHLHB2; DEC1; SHARP2; STRA13 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
105	ELTLKHVKALTNLID	ubiquitination	[1]
117	LIDQQQQKIIALQSG	ubiquitination	[1, 2, 3]
159	EVLQYLAKHENTRDL	sumoylation	[4, 5]
159	EVLQYLAKHENTRDL	ubiquitination	[1, 6, 7]
167	HENTRDLKSSQLVTH	ubiquitination	[6, 7]
217	KGSEGPGKNCVPVIQ	ubiquitination	[6]
251	GYGGESEKGDLRSEQ	ubiquitination	[1]
262	RSEQPCFKSDHGRRF	ubiquitination	[6]
279	GERIGAIKQESEEPP	sumoylation	[4, 5]

Reference

 [1] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [4] SUMOylation of DEC1 protein regulates its transcriptional activity and enhances its stability.
 Hong Y, Xing X, Li S, Bi H, Yang C, Zhao F, Liu Y, Ao X, Chang AK, Wu H.
 PLoS One. 2011;6(8):e23046. [PMID: 21829689]
 [5] SUMO modification of Stra13 is required for repression of cyclin D1 expression and cellular growth arrest.
 Wang Y, Rao VK, Kok WK, Roy DN, Sethi S, Ling BM, Lee MB, Taneja R.
 PLoS One. 2012;7(8):e43137. [PMID: 22905217]
 [6] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [7] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 

Functional Description

 May function as a transcriptional factor to modulate chondrogenesis in response to the cAMP pathway. 

Sequence Annotation

 DOMAIN 52 107 bHLH.
 DOMAIN 142 175 Orange.
 MOD_RES 383 383 Phosphoserine (By similarity).  

Keyword

 Complete proteome; DNA-binding; Nucleus; Phosphoprotein; Reference proteome; Transcription; Transcription regulation; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 412 AA 

Protein Sequence

Gene Ontology

 GO:0005794; C:Golgi apparatus; IDA:HPA.
 GO:0005730; C:nucleolus; IDA:HPA.
 GO:0070888; F:E-box binding; IDA:BHF-UCL.
 GO:0043426; F:MRF binding; ISS:BHF-UCL.
 GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL.
 GO:0001102; F:RNA polymerase II activating transcription factor binding; ISS:BHF-UCL.
 GO:0001078; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription; IDA:BHF-UCL.
 GO:0003705; F:RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity; ISS:BHF-UCL.
 GO:0001191; F:RNA polymerase II transcription factor binding transcription factor activity involved in negative regulation of transcription; IDA:BHF-UCL.
 GO:0032922; P:circadian regulation of gene expression; IDA:BHF-UCL.
 GO:0043153; P:entrainment of circadian clock by photoperiod; ISS:BHF-UCL.
 GO:0043433; P:negative regulation of sequence-specific DNA binding transcription factor activity; IDA:BHF-UCL. 

Interpro

 IPR011598; bHLH_dom.
 IPR003650; Orange.
 IPR018352; Orange_subgr. 

Pfam

 PF07527; Hairy_orange
 PF00010; HLH 

SMART

 SM00353; HLH
 SM00511; ORANGE 

PROSITE

 PS50888; BHLH
 PS51054; ORANGE 

PRINTS