P15172 (MYOD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Myoblast determination protein 1

Alternative name(s):
Class C basic helix-loop-helix protein 1
Short name=bHLHc1
Myogenic factor 3
Short name=Myf-3

Gene names

Name:	MYOD1
Synonyms:	BHLHC1, MYF3, MYOD

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

General annotation (Comments)

Function	Involved in muscle differentiation (myogenic factor). Induces fibroblasts to differentiate into myoblasts. Activates muscle-specific promoters. Interacts with and is inhibited by the twist protein. This interaction probably involves the basic domains of both proteins By similarity.
Subunit structure	Efficient DNA binding requires dimerization with another bHLH protein. Seems to form active heterodimers with ITF-2. Interacts with SUV39H1 and CDK9. Interacts with DDX5 By similarity. Ref.9 Ref.10
Subcellular location	Nucleus.
Post-translational modification	Phosphorylated by CDK9. This phosphorylation promotes its function in muscle differentiation. Ref.9 Acetylated by a complex containing EP300 and PCAF. The acetylation is essential to activate target genes. Conversely, its deacetylation by SIRT1 inhibits its function By similarity. Ubiquitinated on the N-terminus; which is required for proteasomal degradation. Ref.7
Sequence similarities	Contains 1 bHLH (basic helix-loop-helix) domain.

Ontologies

Keywords
Biological process	Differentiation Myogenesis Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Ligand	DNA-binding
Molecular function	Developmental protein
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cardiac muscle cell differentiation Inferred from electronic annotation. Source: Compara cellular response to glucocorticoid stimulus Inferred from electronic annotation. Source: Compara cellular response to oxygen levels Inferred from electronic annotation. Source: Compara cellular response to starvation Inferred from electronic annotation. Source: Compara muscle cell fate commitment Inferred from sequence or structural similarity. Source: BHF-UCL myoblast cell fate determination Inferred from electronic annotation. Source: Compara myotube cell development Inferred from direct assay PubMed 10672515. Source: BHF-UCL myotube differentiation involved in skeletal muscle regeneration Inferred from electronic annotation. Source: Compara positive regulation of muscle cell differentiation Inferred from direct assay PubMed 10672515. Source: BHF-UCL positive regulation of myoblast fusion Inferred from direct assay PubMed 10672515. Source: BHF-UCL positive regulation of skeletal muscle tissue regeneration Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: BHF-UCL protein phosphorylation Traceable author statement PubMed 3175662. Source: ProtInc regulation of RNA splicing Inferred from direct assay PubMed 10672515. Source: BHF-UCL regulation of alternative mRNA splicing, via spliceosome Inferred from electronic annotation. Source: Compara skeletal muscle fiber adaptation Inferred from electronic annotation. Source: Compara skeletal muscle fiber development Inferred from electronic annotation. Source: Compara
Cellular_component	myofibril Inferred from electronic annotation. Source: Compara nuclear chromatin Inferred from sequence or structural similarity. Source: BHF-UCL transcription factor complex Inferred from sequence or structural similarity. Source: BHF-UCL
Molecular_function	E-box binding Inferred from sequence or structural similarity. Source: BHF-UCL RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Traceable author statement PubMed 1846704. Source: ProtInc protein heterodimerization activity Inferred from sequence or structural similarity. Source: BHF-UCL transcription coactivator activity Traceable author statement PubMed 1846704. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TCF3	P15923-1	2	EBI-488878,EBI-769645

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 320	320	Myoblast determination protein 1		PRO_0000127360
Regions
	Domain	109 – 160	52	bHLH
Amino acid modifications
	Cross-link	1		Peptide (Met-Gly) (interchain with G-Cter in ubiquitin)
Natural variations
	Natural variant	262	1	E → K in a breast cancer sample; somatic mutation. Ref.11		VAR_036392
	Natural variant	309	1	A → V in a breast cancer sample; somatic mutation. Ref.11		VAR_036393
Experimental info
	Sequence conflict	124	1	K → E in CAA35640. Ref.6
	Sequence conflict	177	1	Missing in CAA40000. Ref.1
	Sequence conflict	177	1	Missing in CAA35640. Ref.6
	Sequence conflict	251	1	C → Y in CAA40000. Ref.1
	Sequence conflict	251	1	C → Y in CAA35640. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	P15172 [UniParc]. Last modified October 14, 2008. Version 3. Checksum: 75E624D2ED5B0B33	FASTA	320	34,501
	10 20 30 40 50 60 MELLSPPLRD VDLTAPDGSL CSFATTDDFY DDPCFDSPDL RFFEDLDPRL MHVGALLKPE 70 80 90 100 110 120 EHSHFPAAVH PAPGAREDEH VRAPSGHHQA GRCLLWACKA CKRKTTNADR RKAATMRERR 130 140 150 160 170 180 RLSKVNEAFE TLKRCTSSNP NQRLPKVEIL RNAIRYIEGL QALLRDQDAA PPGAAAAFYA 190 200 210 220 230 240 PGPLPPGRGG EHYSGDSDAS SPRSNCSDGM MDYSGPPSGA RRRNCYEGAY YNEAPSEPRP 250 260 270 280 290 300 GKSAAVSSLD CLSSIVERIS TESPAAPALL LADVPSESPP RRQEAAAPSE GESSGDPTQS 310 320 PDAAPQCPAG ANPNPIYQVL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human MyoD: cDNA and deduced amino acid sequence." Pearson-White S.H. Nucleic Acids Res. 19:1148-1148(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Methylation alterations of the MyoD1 upstream region are predictive of subclassification of human rhabdomyosarcomas." Chen B., Dias P., Jenkins J.J. III, Savell V.H., Parham D.M. Am. J. Pathol. 152:1071-1079(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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 (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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.
[6]	"Differential expression of myogenic determination genes in muscle cells: possible autoactivation by the Myf gene products." Braun T., Bober E., Buschhausen-Denker G., Kohtz S., Grzeschik K.-H., Arnold H.H. EMBO J. 8:3617-3625(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 53-320. Tissue: Skeletal muscle.
[7]	"A novel site for ubiquitination: the N-terminal residue, and not internal lysines of MyoD, is essential for conjugation and degradation of the protein." Breitschopf K., Bengal E., Ziv T., Admon A., Ciechanover A. EMBO J. 17:5964-5973(1998) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION AT MET-1.
[8]	"Control of muscle development by dueling HATs and HDACs." McKinsey T.A., Zhang C.L., Olson E.N. Curr. Opin. Genet. Dev. 11:497-504(2001) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON ACETYLATION/DEACETYLATION.
[9]	"Activation of MyoD-dependent transcription by cdk9/cyclin T2." Simone C., Stiegler P., Bagella L., Pucci B., Bellan C., De Falco G., De Luca A., Guanti G., Puri P.L., Giordano A. Oncogene 21:4137-4148(2002) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY CDK9, INTERACTION WITH CDK9.
[10]	"Histone methyltransferase Suv39h1 represses MyoD-stimulated myogenic differentiation." Mal A.K. EMBO J. 25:3323-3334(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SUV39H1.
[11]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LYS-262 AND VAL-309.
+	Additional computationally mapped references.

Web resources

Wikipedia

MyoD entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	X56677 mRNA. Translation: CAA40000.1. AF027148 Genomic DNA. Translation: AAC29001.1. BT007157 mRNA. Translation: AAP35821.1. CH471064 Genomic DNA. Translation: EAW68427.1. BC064493 mRNA. Translation: AAH64493.1. X17650 mRNA. Translation: CAA35640.1.
IPI	IPI00102339.
PIR	S26827.
RefSeq	NP_002469.2. NM_002478.4.
UniGene	Hs.181768.
3D structure databases
ProteinModelPortal	P15172.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-704N.
IntAct	P15172. 7 interactions.
MINT	MINT-128965.
STRING	9606.ENSP00000250003.
PTM databases
PhosphoSite	P15172.
Polymorphism databases
DMDM	209572729.
Proteomic databases
PaxDb	P15172.
PRIDE	P15172.
Protocols and materials databases
DNASU	4654.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000250003; ENSP00000250003; ENSG00000129152.
GeneID	4654.
KEGG	hsa:4654.
UCSC	uc001mni.3. human.
Organism-specific databases
CTD	4654.
GeneCards	GC11P017741.
H-InvDB	HIX0035989.
HGNC	HGNC:7611. MYOD1.
MIM	159970. gene.
neXtProt	NX_P15172.
PharmGKB	PA31416.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG292792.
HOGENOM	HOG000234800.
HOVERGEN	HBG006429.
InParanoid	P15172.
KO	K09064.
OMA	TYYSEAP.
OrthoDB	EOG47WNPM.
PhylomeDB	P15172.
Enzyme and pathway databases
Pathway_Interaction_DB	smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling. hdac_classiii_pathway. Signaling events mediated by HDAC Class III.
Reactome	REACT_111045. Developmental Biology.
Gene expression databases
Bgee	P15172.
CleanEx	HS_MYOD1.
Genevestigator	P15172.
GermOnline	ENSG00000129152. Homo sapiens.
Family and domain databases
Gene3D	4.10.280.10. 1 hit.
InterPro	IPR002546. Basic. IPR011598. bHLH_dom. IPR022032. Myf5. [Graphical view]
Pfam	PF01586. Basic. 1 hit. PF00010. HLH. 1 hit. PF12232. Myf5. 1 hit. [Graphical view]
SMART	SM00520. BASIC. 1 hit. SM00353. HLH. 1 hit. [Graphical view]
SUPFAM	SSF47459. HLH_basic. 1 hit.
PROSITE	PS50888. BHLH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	4654.
NextBio	17940.
SOURCE	Search...

Entry information

Entry name

MYOD1_HUMAN

Accession

Primary (citable) accession number: P15172
Secondary accession number(s): O75321

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	October 14, 2008
Last modified:	May 1, 2013
This is version 138 of the entry and version 3 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.