P04198 (MYCN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
N-myc proto-oncogene protein

Alternative name(s):
Class E basic helix-loop-helix protein 37
Short name=bHLHe37

Gene names

Name:	MYCN
Synonyms:	BHLHE37, NMYC

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

General annotation (Comments)

Function	May function as a transcription factor.
Subunit structure	Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MAX. Interacts with KDM5A, KDM5B and HUWE1. Ref.11 Ref.12
Subcellular location	Nucleus.
Developmental stage	Expressed during fetal development.
Involvement in disease	Amplification of the N-MYC gene is associated with a variety of human tumors, most frequently neuroblastoma, where the level of amplification appears to increase as the tumor progresses. Feingold syndrome 1 (FGLDS1) [MIM:164280]: A syndrome characterized by variable combinations of esophageal and duodenal atresias, microcephaly, learning disability, mental retardation, and limb malformations. Hand and foot abnormalities may include hypoplastic thumbs, clinodactyly of second and fifth fingers, syndactyly (characteristically between second and third and fourth and fifth toes), and shortened or absent middle phalanges. Cardiac and renal malformations, vertebral anomalies, and deafness have also been described. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.10
Sequence similarities	Contains 1 bHLH (basic helix-loop-helix) domain.
Sequence caution	The sequence AAA36371.1 differs from that shown. Reason: Erroneous initiation. The sequence CAA68678.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Nucleus
Disease	Disease mutation Proto-oncogene
Ligand	DNA-binding
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	branching morphogenesis of an epithelial tube Inferred from electronic annotation. Source: Compara cartilage condensation Inferred from electronic annotation. Source: Compara embryonic digit morphogenesis Inferred from electronic annotation. Source: Compara embryonic skeletal system morphogenesis Inferred from electronic annotation. Source: Compara lung development Inferred from electronic annotation. Source: Compara negative regulation of astrocyte differentiation Inferred from electronic annotation. Source: Compara negative regulation of reactive oxygen species metabolic process Inferred from electronic annotation. Source: Compara positive regulation of cell death Inferred from electronic annotation. Source: Compara positive regulation of mesenchymal cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara regulation of transcription from RNA polymerase II promoter Traceable author statement PubMed 3796607. Source: ProtInc
Cellular_component	chromatin Traceable author statement PubMed 3796607. Source: ProtInc nucleus Inferred from direct assay PubMed 10597290. Source: UniProtKB
Molecular_function	DNA binding Traceable author statement PubMed 10597290. Source: UniProtKB sequence-specific DNA binding transcription factor activity Traceable author statement PubMed 3796607. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AURKA	O14965	2	EBI-878369,EBI-448680
NMI	Q13287	3	EBI-878369,EBI-372942
SIRT1	Q96EB6	3	EBI-878369,EBI-1802965

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 464	464	N-myc proto-oncogene protein		PRO_0000127323
Regions
	Domain	381 – 433	53	bHLH
	Region	433 – 454	22	Leucine-zipper
	Compositional bias	262 – 278	17	Asp/Glu-rich (acidic)
Amino acid modifications
	Modified residue	261	1	Phosphoserine; by CK2
	Modified residue	263	1	Phosphoserine; by CK2
Natural variations
	Natural variant	393	1	R → H in FGLDS1. Ref.9		VAR_031952
	Natural variant	393	1	R → S in FGLDS1. Ref.9		VAR_031953
	Natural variant	394	1	R → H in FGLDS1. Ref.9		VAR_031954
Experimental info
	Sequence conflict	227	1	A → P in CAA27037. Ref.2
	Sequence conflict	363	1	I → V in CAA68678. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P04198 [UniParc]. Last modified July 1, 1989. Version 2. Checksum: 560E885602E30DAD	FASTA	464	49,561
	10 20 30 40 50 60 MPSCSTSTMP GMICKNPDLE FDSLQPCFYP DEDDFYFGGP DSTPPGEDIW KKFELLPTPP 70 80 90 100 110 120 LSPSRGFAEH SSEPPSWVTE MLLENELWGS PAEEDAFGLG GLGGLTPNPV ILQDCMWSGF 130 140 150 160 170 180 SAREKLERAV SEKLQHGRGP PTAGSTAQSP GAGAASPAGR GHGGAAGAGR AGAALPAELA 190 200 210 220 230 240 HPAAECVDPA VVFPFPVNKR EPAPVPAAPA SAPAAGPAVA SGAGIAAPAG APGVAPPRPG 250 260 270 280 290 300 GRQTSGGDHK ALSTSGEDTL SDSDDEDDEE EDEEEEIDVV TVEKRRSSSN TKAVTTFTIT 310 320 330 340 350 360 VRPKNAALGP GRAQSSELIL KRCLPIHQQH NYAAPSPYVE SEDAPPQKKI KSEASPRPLK 370 380 390 400 410 420 SVIPPKAKSL SPRNSDSEDS ERRRNHNILE RQRRNDLRSS FLTLRDHVPE LVKNEKAAKV 430 440 450 460 VILKKATEYV HSLQAEEHQL LLEKEKLQAR QQQLLKKIEH ARTC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of the human N-myc gene." Stanton L.W., Schwab M., Bishop J.M. Proc. Natl. Acad. Sci. U.S.A. 83:1772-1776(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Human N-myc is closely related in organization and nucleotide sequence to c-myc." Kohl N.E., Legouy E., DePinho R.A., Nisen P.D., Smith R.K., Gee C.E., Alt F.W. Nature 319:73-77(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Sequence of a germ-line N-myc gene and amplification as a mechanism of activation." Ibson J.M., Rabbitts P.H. Oncogene 2:399-402(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"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: Brain.
[5]	"Alternative processing of RNA transcribed from NMYC." Stanton L.W., Bishop J.M. Mol. Cell. Biol. 7:4266-4272(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-40.
[6]	"Identification and characterization of the protein encoded by the human N-myc oncogene." Slamon D.J., Boone T.C., Seeger R.C., Keith D.E., Chazin V., Lee H.C., Souza L.M. Science 232:768-772(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 71-464.
[7]	"Nucleotide sequence of the 3' exon of the human N-myc gene." Michitsch R.W., Melera P.W. Nucleic Acids Res. 13:2545-2558(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 313-464.
[8]	"Specific phosphorylation of the acidic central region of the N-myc protein by casein kinase II." Hagiwara T., Nakaya K., Nakamura Y., Nakajima H., Nishimura S., Taya Y. Eur. J. Biochem. 209:945-950(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY CK2.
[9]	"MYCN haploinsufficiency is associated with reduced brain size and intestinal atresias in Feingold syndrome." van Bokhoven H., Celli J., van Reeuwijk J., Rinne T., Glaudemans B., van Beusekom E., Rieu P., Newbury-Ecob R.A., Chiang C., Brunner H.G. Nat. Genet. 37:465-467(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS FGLDS1 HIS-393; SER-393 AND HIS-394.
[10]	"Expanding the clinical spectrum of MYCN-related Feingold syndrome." Teszas A., Meijer R., Scheffer H., Gyuris P., Kosztolanyi G., van Bokhoven H., Kellermayer R. Am. J. Med. Genet. A 140:2254-2256(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN FGLDS1.
[11]	"The Trithorax group protein Lid is a trimethyl histone H3K4 demethylase required for dMyc-induced cell growth." Secombe J., Li L., Carlos L., Eisenman R.N. Genes Dev. 21:537-551(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KDM5A AND KDM5B.
[12]	"The HECT-domain ubiquitin ligase Huwe1 controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein." Zhao X., Heng J.I.-T., Guardavaccaro D., Jiang R., Pagano M., Guillemot F., Iavarone A., Lasorella A. Nat. Cell Biol. 10:643-653(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HUWE1.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	X03294 Genomic DNA. Translation: CAA27037.1. X03295 Genomic DNA. Translation: CAA27038.1. M13241 Genomic DNA. Translation: AAA36371.1. Different initiation. M13228 Genomic DNA. Translation: AAA36370.1. BC002712 mRNA. Translation: AAH02712.1. M18090 Genomic DNA. Translation: AAA59885.1. X02363 Genomic DNA. No translation available. Y00664 Genomic DNA. Translation: CAA68678.1. Different initiation.
IPI	IPI00022372.
PIR	TVHUMC. A01355. TVHUM2. A25744.
RefSeq	NP_005369.2. NM_005378.4.
UniGene	Hs.25960.
3D structure databases
ProteinModelPortal	P04198.
ModBase	Search...
Protein-protein interaction databases
IntAct	P04198. 7 interactions.
MINT	MINT-1671085.
STRING	9606.ENSP00000281043.
PTM databases
PhosphoSite	P04198.
Polymorphism databases
DMDM	127604.
Proteomic databases
PaxDb	P04198.
PeptideAtlas	P04198.
PRIDE	P04198.
Protocols and materials databases
DNASU	4613.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000281043; ENSP00000281043; ENSG00000134323.
GeneID	4613.
KEGG	hsa:4613.
UCSC	uc002rci.3. human.
Organism-specific databases
CTD	4613.
GeneCards	GC02P016080.
H-InvDB	HIX0117705.
HGNC	HGNC:7559. MYCN.
MIM	164280. phenotype. 164840. gene.
neXtProt	NX_P04198.
Orphanet	1305. Feingold syndrome. 635. Neuroblastoma.
PharmGKB	PA31359.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG83719.
HOGENOM	HOG000043075.
HOVERGEN	HBG000472.
InParanoid	P04198.
KO	K09109.
OMA	PEADLWG.
OrthoDB	EOG4D7Z65.
PhylomeDB	P04198.
Gene expression databases
ArrayExpress	P04198.
Bgee	P04198.
CleanEx	HS_MYCN.
Genevestigator	P04198.
GermOnline	ENSG00000134323. Homo sapiens.
Family and domain databases
Gene3D	4.10.280.10. 1 hit.
InterPro	IPR011598. bHLH_dom. IPR002418. Tscrpt_reg_Myc. IPR012682. Tscrpt_reg_Myc_N. [Graphical view]
Pfam	PF00010. HLH. 1 hit. PF01056. Myc_N. 1 hit. [Graphical view]
PIRSF	PIRSF001705. Myc_protein. 1 hit.
PRINTS	PR00044. LEUZIPPRMYC.
SMART	SM00353. HLH. 1 hit. [Graphical view]
SUPFAM	SSF47459. HLH_basic. 1 hit.
PROSITE	PS50888. BHLH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	4613.
NextBio	17758.
SOURCE	Search...

Entry information

Entry name

MYCN_HUMAN

Accession

Primary (citable) accession number: P04198
Secondary accession number(s): Q6LDT9

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 20, 1987
Last sequence update:	July 1, 1989
Last modified:	May 1, 2013
This is version 145 of the entry and version 2 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.