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Reviewed, UniProtKB/Swiss-Prot P04198 (MYCN_HUMAN)

Last modified June 16, 2009. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    N-myc proto-oncogene protein
Gene names
Name: MYCN
Synonyms: NMYC
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length464 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

May function as a transcription factor.

Subunit structure

Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as an heterodimer with MAX. Interacts with KDM5A, KDM5B and HUWE1. Ref.12 Ref.13

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.

Defects in MYCN are the cause of Feingold syndrome [MIM:164280]; also known as oculodigitoesophagoduodenal syndrome (ODED). Feingold syndrome is characterized by variable combinations of esophageal and duodenal atresias, microcephaly, learning disability and limb malformations. Cardiac and renal malformations, vertebral anomalies, and deafness have also been described.

Defects in MYCN are the cause of microcephaly and digital abnormalities with normal intelligence [MIM:602585]. Ref.11

Sequence similarities

Contains 1 basic helix-loop-helix (bHLH) domain.

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Ontologies

Keywords
   Cellular componentNucleus
   DiseaseDisease mutation
Proto-oncogene
   LigandDNA-binding
   PTMPhosphoprotein
Gene Ontology (GO)
   Biological processregulation of transcription from RNA polymerase II promoter

Traceable author statement. Source: ProtInc

   Cellular componentchromatin

Traceable author statement. Source: ProtInc

nucleus

Inferred from direct assay. Source: UniProtKB

   Molecular functionprotein binding

Inferred from physical interaction. Source: UniProtKB

transcription factor activity

Traceable author statement. Source: ProtInc

Complete GO annotation...

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 464464N-myc proto-oncogene protein
PRO_0000127323

Regions

Domain395 – 43440Helix-loop-helix motif
Domain433 – 45422Leucine-zipper Potential
DNA binding381 – 39414Basic motif
Compositional bias262 – 27817Asp/Glu-rich (acidic)

Amino acid modifications

Modified residue581Phosphothreonine Ref.9
Modified residue621Phosphoserine Ref.9
Modified residue2611Phosphoserine; by CK2
Modified residue2631Phosphoserine; by CK2

Natural variations

Natural variant3931R → H in Feingold syndrome.
VAR_031952
Natural variant3931R → S in Feingold syndrome.
VAR_031953
Natural variant3941R → H in Feingold syndrome.
VAR_031954

Experimental info

Sequence conflict2271A → P in CAA27037. Ref.2
Sequence conflict3631I → V in CAA68678. Ref.3

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Sequences

Sequence LengthMass (Da)Tools
P04198-1 [UniParc].

Last modified July 1, 1989. Version 2.
Checksum: 560E885602E30DAD

FASTA46449,561
        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

« Hide

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References

« Hide '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: 2869488] [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: 3510398] [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: 2834684] [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: 15489334] [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: 3437890] [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: 3008339] [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: 2987858] [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: 1425701] [Abstract]
Cited for: PHOSPHORYLATION BY CK2.
[9]"Large-scale characterization of HeLa cell nuclear phosphoproteins."
Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-58 AND SER-62, MASS SPECTROMETRY.
Tissue: Epithelium.
[10]"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: 15821734] [Abstract]
Cited for: VARIANTS FEINGOLD SYNDROME HIS-393; SER-393 AND HIS-394.
[11]"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: 16906565] [Abstract]
Cited for: INVOLVEMENT IN MICROCEPHALY AND DIGITAL ABNORMALITIES WITH NORMAL INTELLIGENCE.
[12]"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: 17311883] [Abstract]
Cited for: INTERACTION WITH KDM5A AND KDM5B.
[13]"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: 18488021] [Abstract]
Cited for: INTERACTION WITH HUWE1.
+Additional computationally mapped references.

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Cross-references

Sequence databases

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.
IPIIPI00022372.
PIRTVHUMC. A01355.
TVHUM2. A25744.
RefSeqNP_005369.2.
UniGeneHs.25960

3D structure databases

HSSPHSSP built from PDB template 1AN2 based on UniProtKB P25912.
ModBaseSearch...

Protein-protein interaction databases

IntActP04198. 3 interactions.

PTM databases

PhosphoSiteP04198.

Proteomic databases

PeptideAtlasP04198.
PRIDEP04198.

Genome annotation databases

EnsemblENSG00000134323. Homo sapiens. [Contig view]
GeneID4613.
KEGGhsa:4613.

Organism-specific databases

GeneCardsGC02P016032.
H-InvDBHIX0001842.
HIX0030480.
HGNCHGNC:7559. MYCN.
MIM164280. phenotype.
164840. gene.
602585. phenotype.
Orphanet1305. Oculo-digito-esophageal-duodenal syndrome (ODED).
PharmGKBPA31359.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP04198.
HOVERGENP04198.
OMAP04198. PCFYPDE.

Gene expression databases

ArrayExpressP04198.
BgeeP04198.
CleanExHS_MYCN.
GermOnlineENSG00000134323. Homo sapiens.

Family and domain databases

InterProIPR001092. HLH_basic.
IPR011598. HLH_DNA_bd.
IPR002418. Tscrpt_reg_Myc.
IPR012682. Tscrpt_reg_Myc_N.
[Graphical view]
Gene3DG3DSA:4.10.280.10. HLH_DNA_bd. 1 hit.
PfamPF00010. HLH. 1 hit.
PF01056. Myc_N. 1 hit.
[Graphical view]
PRINTSPR00044. LEUZIPPRMYC.
SMARTSM00353. HLH. 1 hit.
[Graphical view]
PROSITEPS50888. HLH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio17758.
SOURCESearch...

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Entry information

Entry nameMYCN_HUMAN
AccessionPrimary (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: June 16, 2009
This is version 102 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents