O14503 (BHE40_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Class E basic helix-loop-helix protein 40
Short name=bHLHe40

Alternative name(s):
Class B basic helix-loop-helix protein 2
Short name=bHLHb2
Differentially expressed in chondrocytes protein 1
Short name=DEC1
Enhancer-of-split and hairy-related protein 2
Short name=SHARP-2
Stimulated by retinoic acid gene 13 protein

Gene names

Name:	BHLHE40
Synonyms:	BHLHB2, DEC1, SHARP2, STRA13

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

General annotation (Comments)

Function	May function as a transcriptional factor to modulate chondrogenesis in response to the cAMP pathway.
Subunit structure	Able to homodimerize or heterodimerize with TCF3/E47. Interacts with ubiquitin-conjugating enzyme UBE2I/UBC9. Ref.5
Subcellular location	Nucleus Ref.5.
Tissue specificity	Expressed in cartilage, spleen, intestine, lung, and to a lesser extent in heart, brain, liver, muscle and stomach.
Post-translational modification	Ubiquitinated; which may lead to proteasomal degradation. Ref.5
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
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	circadian regulation of gene expression Inferred from direct assay PubMed 18411297. Source: BHF-UCL entrainment of circadian clock by photoperiod Inferred from sequence or structural similarity PubMed 18411297. Source: BHF-UCL negative regulation of sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 18411297. Source: BHF-UCL
Cellular_component	Golgi apparatus Inferred from direct assay. Source: HPA nucleolus Inferred from direct assay. Source: HPA
Molecular_function	E-box binding Inferred from direct assay PubMed 12397359PubMed 12624110PubMed 14672706PubMed 15193144PubMed 15560782PubMed 18411297. Source: BHF-UCL MRF binding Inferred from sequence or structural similarity. Source: BHF-UCL RNA polymerase II activating transcription factor binding Inferred from sequence or structural similarity. Source: BHF-UCL RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription Inferred from direct assay PubMed 12624110PubMed 15193144PubMed 18411297. Source: BHF-UCL RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Inferred from sequence or structural similarity. Source: BHF-UCL RNA polymerase II transcription factor binding transcription factor activity involved in negative regulation of transcription Inferred from direct assay PubMed 12397359PubMed 18411297. Source: BHF-UCL protein homodimerization activity Inferred from direct assay PubMed 15560782. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
UBE2I	P63279	3	EBI-711810,EBI-80168

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 412	412	Class E basic helix-loop-helix protein 40		PRO_0000127144
Regions
	Domain	52 – 107	56	bHLH
	Domain	142 – 175	34	Orange
Amino acid modifications
	Modified residue	383	1	Phosphoserine By similarity

Sequences

	Sequence		Length	Mass (Da)
	O14503 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 2D73A3D4980793E5	FASTA	412	45,510
	10 20 30 40 50 60 MERIPSAQPP PACLPKAPGL EHGDLPGMYP AHMYQVYKSR RGIKRSEDSK ETYKLPHRLI 70 80 90 100 110 120 EKKRRDRINE CIAQLKDLLP EHLKLTTLGH LEKAVVLELT LKHVKALTNL IDQQQQKIIA 130 140 150 160 170 180 LQSGLQAGEL SGRNVETGQE MFCSGFQTCA REVLQYLAKH ENTRDLKSSQ LVTHLHRVVS 190 200 210 220 230 240 ELLQGGTSRK PSDPAPKVMD FKEKPSSPAK GSEGPGKNCV PVIQRTFAHS SGEQSGSDTD 250 260 270 280 290 300 TDSGYGGESE KGDLRSEQPC FKSDHGRRFT MGERIGAIKQ ESEEPPTKKN RMQLSDDEGH 310 320 330 340 350 360 FTSSDLISSP FLGPHPHQPP FCLPFYLIPP SATAYLPMLE KCWYPTSVPV LYPGLNASAA 370 380 390 400 410 ALSSFMNPDK ISAPLLMPQR LPSPLPAHPS VDSSVLLQAL KPIPPLNLET KD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular characterization of the novel basic helix-loop-helix protein DEC1 expressed in differentiated human embryo chondrocytes." Shen M., Kawamoto T., Yan W., Nakamasu K., Tamagami M., Koyano Y., Noshiro M., Kato Y. Biochem. Biophys. Res. Commun. 236:294-298(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Cartilage.
[2]	"Gene structure and chromosomal location of a human bHLH transcriptional factor DEC1 x Stra13 x SHARP-2/BHLHB2." Teramoto M., Nakamasu K., Noshiro M., Matsuda Y., Gotoh O., Shen M., Tsutsumi S., Kawamoto T., Iwamoto Y., Kato Y. J. Biochem. 129:391-396(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Leukocyte.
[3]	"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: Skin.
[4]	"Exon-intron structure of the human STRA13(DEC1) bHLH transcription factor gene." Ivanov S.V., Lerman M.I. Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 4-412.
[5]	"Regulation of STRA13 by the von Hippel-Lindau tumor suppressor protein, hypoxia, and the UBC9/ubiquitin proteasome degradation pathway." Ivanova A.V., Ivanov S.V., Danilkovitch-Miagkova A., Lerman M.I. J. Biol. Chem. 276:15306-15315(2001) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION, INTERACTION WITH UBE2I, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB004066 mRNA. Translation: BAA21720.1. AB043885 Genomic DNA. Translation: BAB18565.1. BC082238 mRNA. Translation: AAH82238.1. AH010709 Genomic DNA. Translation: AAK49525.1.
IPI	IPI00021143.
PIR	JC5547.
RefSeq	NP_003661.1. NM_003670.2.
UniGene	Hs.740380.
3D structure databases
ProteinModelPortal	O14503.
ModBase	Search...
Protein-protein interaction databases
IntAct	O14503. 46 interactions.
MINT	MINT-1374397.
STRING	9606.ENSP00000256495.
PTM databases
PhosphoSite	O14503.
Proteomic databases
PaxDb	O14503.
PRIDE	O14503.
Protocols and materials databases
DNASU	8553.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000256495; ENSP00000256495; ENSG00000134107.
GeneID	8553.
KEGG	hsa:8553.
UCSC	uc003bqf.3. human.
Organism-specific databases
CTD	8553.
GeneCards	GC03P004997.
HGNC	HGNC:1046. BHLHE40.
HPA	HPA028921.
MIM	604256. gene.
neXtProt	NX_O14503.
PharmGKB	PA25347.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG281955.
HOGENOM	HOG000234381.
InParanoid	O14503.
KO	K03729.
OMA	EQPYFKS.
OrthoDB	EOG4DZ1VV.
PhylomeDB	O14503.
Enzyme and pathway databases
Pathway_Interaction_DB	circadianpathway. Circadian rhythm pathway. hif1_tfpathway. HIF-1-alpha transcription factor network.
Reactome	REACT_24941. Circadian Clock.
Gene expression databases
ArrayExpress	O14503.
Bgee	O14503.
CleanEx	HS_DEC1. HS_STRA13.
Genevestigator	O14503.
GermOnline	ENSG00000134107. 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	BHLHE40. human.
GenomeRNAi	8553.
NextBio	32049.
SOURCE	Search...

Entry information

Entry name

BHE40_HUMAN

Accession

Primary (citable) accession number: O14503
Secondary accession number(s): Q96TD3

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 5, 2002
Last sequence update:	January 1, 1998
Last modified:	May 1, 2013
This is version 115 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.