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P04198 (MYCN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 155. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length464 AA.
Sequence statusComplete.
Protein existenceEvidence 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.14 Ref.15

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.12 Ref.13

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 componentNucleus
   DiseaseDisease mutation
Proto-oncogene
   LigandDNA-binding
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbranching morphogenesis of an epithelial tube

Inferred from electronic annotation. Source: Ensembl

cartilage condensation

Inferred from electronic annotation. Source: Ensembl

embryonic digit morphogenesis

Inferred from electronic annotation. Source: Ensembl

embryonic skeletal system morphogenesis

Inferred from electronic annotation. Source: Ensembl

lung development

Inferred from electronic annotation. Source: Ensembl

negative regulation of astrocyte differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of reactive oxygen species metabolic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell death

Inferred from electronic annotation. Source: Ensembl

positive regulation of mesenchymal cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

regulation of transcription from RNA polymerase II promoter

Traceable author statement PubMed 3796607. Source: ProtInc

   Cellular_componentchromatin

Traceable author statement PubMed 3796607. Source: ProtInc

nucleus

Inferred from direct assay PubMed 10597290. Source: UniProtKB

   Molecular_functionDNA 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...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 464464N-myc proto-oncogene protein
PRO_0000127323

Regions

Domain381 – 43353bHLH
Region433 – 45422Leucine-zipper
Compositional bias262 – 27817Asp/Glu-rich (acidic)

Amino acid modifications

Modified residue2611Phosphoserine; by CK2
Modified residue2631Phosphoserine; by CK2

Natural variations

Natural variant3931R → H in FGLDS1. Ref.12
VAR_031952
Natural variant3931R → S in FGLDS1. Ref.12
VAR_031953
Natural variant3941R → H in FGLDS1. Ref.12
VAR_031954

Experimental info

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

Sequences

Sequence LengthMass (Da)Tools
P04198 [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

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] [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]"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].
[5]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton 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. expand/collapse author list , 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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.
[8]"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.
[9]"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.
[10]"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.
[11]"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.
[12]"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.
[13]"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.
[14]"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.
[15]"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.

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.
BT007384 mRNA. Translation: AAP36048.1.
AC010145 Genomic DNA. Translation: AAY14952.1.
CH471053 Genomic DNA. Translation: EAX00885.1.
CH471053 Genomic DNA. Translation: EAX00886.1.
CH471053 Genomic DNA. Translation: EAX00887.1.
CH471053 Genomic DNA. Translation: EAX00888.1.
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.
PIRTVHUMC. A01355.
TVHUM2. A25744.
RefSeqNP_005369.2. NM_005378.4.
UniGeneHs.25960.

3D structure databases

ProteinModelPortalP04198.
SMRP04198. Positions 382-460.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110698. 18 interactions.
IntActP04198. 9 interactions.
MINTMINT-1671085.
STRING9606.ENSP00000281043.

PTM databases

PhosphoSiteP04198.

Polymorphism databases

DMDM127604.

Proteomic databases

PaxDbP04198.
PeptideAtlasP04198.
PRIDEP04198.

Protocols and materials databases

DNASU4613.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000281043; ENSP00000281043; ENSG00000134323.
GeneID4613.
KEGGhsa:4613.
UCSCuc002rci.3. human.

Organism-specific databases

CTD4613.
GeneCardsGC02P016080.
H-InvDBHIX0117705.
HGNCHGNC:7559. MYCN.
MIM164280. phenotype.
164840. gene.
neXtProtNX_P04198.
Orphanet1305. Feingold syndrome.
635. Neuroblastoma.
PharmGKBPA31359.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG83719.
HOGENOMHOG000043075.
HOVERGENHBG000472.
InParanoidP04198.
KOK09109.
OMAGMICKNP.
OrthoDBEOG7GJ6CX.
PhylomeDBP04198.
TreeFamTF106001.

Enzyme and pathway databases

SignaLinkP04198.

Gene expression databases

ArrayExpressP04198.
BgeeP04198.
CleanExHS_MYCN.
GenevestigatorP04198.

Family and domain databases

Gene3D4.10.280.10. 1 hit.
InterProIPR011598. bHLH_dom.
IPR002418. Tscrpt_reg_Myc.
IPR012682. Tscrpt_reg_Myc_N.
[Graphical view]
PfamPF00010. HLH. 1 hit.
PF01056. Myc_N. 1 hit.
[Graphical view]
PIRSFPIRSF001705. Myc_protein. 1 hit.
PRINTSPR00044. LEUZIPPRMYC.
SMARTSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
PROSITEPS50888. BHLH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiN-Myc.
GenomeRNAi4613.
NextBio17758.
PROP04198.
SOURCESearch...

Entry information

Entry nameMYCN_HUMAN
AccessionPrimary (citable) accession number: P04198
Secondary accession number(s): Q53XS5, Q6LDT9
Entry history
Integrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: July 1, 1989
Last modified: April 16, 2014
This is version 155 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

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