Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

N-myc proto-oncogene protein

Gene

MYCN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Positively regulates the transcription of MYCNOS in neuroblastoma cells.1 Publication

GO - Molecular functioni

  • DNA binding Source: UniProtKB
  • kinase binding Source: UniProtKB
  • protein dimerization activity Source: InterPro
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: NTNU_SB
  • transcription factor activity, sequence-specific DNA binding Source: ProtInc

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

SignaLinkiP04198.
SIGNORiP04198.

Names & Taxonomyi

Protein namesi
Recommended name:
N-myc proto-oncogene protein
Alternative name(s):
Class E basic helix-loop-helix protein 37
Short name:
bHLHe37
Gene namesi
Name:MYCN
Synonyms:BHLHE37, NMYC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000134323.10.
HGNCiHGNC:7559. MYCN.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

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.1 Publication
Feingold syndrome 1 (FGLDS1)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:164280
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_031952393R → H in FGLDS1. 1 PublicationCorresponds to variant dbSNP:rs104893646Ensembl.1
Natural variantiVAR_031953393R → S in FGLDS1. 1 PublicationCorresponds to variant dbSNP:rs104893647Ensembl.1
Natural variantiVAR_031954394R → H in FGLDS1. 1 PublicationCorresponds to variant dbSNP:rs104893648Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi28F → A: Reduces interaction with AURKA; when associated with A-35. 1 Publication1
Mutagenesisi29Y → A: Reduces interaction with AURKA; when associated with A-36. 1 Publication1
Mutagenesisi35F → A: Reduces interaction with AURKA; when associated with A-28. 1 Publication1
Mutagenesisi36Y → A: Reduces interaction with AURKA; when associated with A-29. 1 Publication1
Mutagenesisi52 – 56KFELL → AAAAA: Does not affect AURKA binding. 1 Publication5
Mutagenesisi73E → K: Reduces binding to AURKA. 1 Publication1
Mutagenesisi77W → A: Reduces binding to AURKA. 1 Publication1
Mutagenesisi88W → A: Abrogates the interaction with AURKA. 1 Publication1

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

DisGeNETi4613.
GeneReviewsiMYCN.
MalaCardsiMYCN.
MIMi164280. phenotype.
OpenTargetsiENSG00000134323.
Orphaneti391641. Feingold syndrome type 1.
635. Neuroblastoma.
357034. Unilateral retinoblastoma.
PharmGKBiPA31359.

Polymorphism and mutation databases

BioMutaiMYCN.
DMDMi127604.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001273231 – 464N-myc proto-oncogene proteinAdd BLAST464

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei261Phosphoserine; by CK21 Publication1
Modified residuei263Phosphoserine; by CK21 Publication1

Post-translational modificationi

Phosphorylated by GSK3-beta which may promote its degradation (PubMed:24391509). Phosphorylated by AURKA (PubMed:27837025).2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP04198.
PaxDbiP04198.
PeptideAtlasiP04198.
PRIDEiP04198.

PTM databases

iPTMnetiP04198.
PhosphoSitePlusiP04198.

Expressioni

Tissue specificityi

Expressed in the neuronal cells of the cerebrum, neuroblastomas and thyroid tumors (at protein level).1 Publication

Developmental stagei

Expressed during fetal development.

Gene expression databases

BgeeiENSG00000134323.
CleanExiHS_MYCN.
GenevisibleiP04198. HS.

Organism-specific databases

HPAiHPA057420.

Interactioni

Subunit structurei

Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MAX. Interacts with KDM5A, KDM5B and HUWE1. Interacts with MYCNOS. Interacts with AURKA; interaction is phospho-independent and triggers AURKA activation; AURKA competes with FBXW7 for binding to unphosphorylated MYCN but not for binding to unphosphorylated MYCN (PubMed:27837025). Interacts with FBXW7; FBXW7 competes with AURKA for binding to unphosphorylated MYCN but not for binding to phosphorylated MYCN (PubMed:27837025).4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • kinase binding Source: UniProtKB
  • protein dimerization activity Source: InterPro

Protein-protein interaction databases

BioGridi110698. 21 interactors.
DIPiDIP-36822N.
IntActiP04198. 17 interactors.
MINTiMINT-1671085.
STRINGi9606.ENSP00000281043.

Structurei

Secondary structure

1464
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi69 – 71Combined sources3
Helixi76 – 88Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5G1XX-ray1.72B28-89[»]
ProteinModelPortaliP04198.
SMRiP04198.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini381 – 433bHLHPROSITE-ProRule annotationAdd BLAST53

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni19 – 47Interaction with AURKA1 PublicationAdd BLAST29
Regioni61 – 89Interaction with AURKA and FBXW71 PublicationAdd BLAST29
Regioni433 – 454Leucine-zipperAdd BLAST22

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi262 – 278Asp/Glu-rich (acidic)Add BLAST17

Phylogenomic databases

eggNOGiENOG410IJ8V. Eukaryota.
ENOG41105VW. LUCA.
GeneTreeiENSGT00510000046414.
HOGENOMiHOG000043075.
HOVERGENiHBG000472.
InParanoidiP04198.
KOiK09109.
OMAiFAEHSSE.
OrthoDBiEOG091G0ZJQ.
PhylomeDBiP04198.
TreeFamiTF106001.

Family and domain databases

CDDicd00083. HLH. 1 hit.
Gene3Di4.10.280.10. 1 hit.
InterProiView protein in InterPro
IPR011598. bHLH_dom.
IPR036638. HLH_DNA-bd_sf.
IPR002418. Tscrpt_reg_Myc.
IPR012682. Tscrpt_reg_Myc_N.
PfamiView protein in Pfam
PF00010. HLH. 1 hit.
PF01056. Myc_N. 1 hit.
PIRSFiPIRSF001705. Myc_protein. 1 hit.
PRINTSiPR00044. LEUZIPPRMYC.
SMARTiView protein in SMART
SM00353. HLH. 1 hit.
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiView protein in PROSITE
PS50888. BHLH. 1 hit.

Sequencei

Sequence statusi: Complete.

P04198-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPSCSTSTMP GMICKNPDLE FDSLQPCFYP DEDDFYFGGP DSTPPGEDIW
60 70 80 90 100
KKFELLPTPP LSPSRGFAEH SSEPPSWVTE MLLENELWGS PAEEDAFGLG
110 120 130 140 150
GLGGLTPNPV ILQDCMWSGF SAREKLERAV SEKLQHGRGP PTAGSTAQSP
160 170 180 190 200
GAGAASPAGR GHGGAAGAGR AGAALPAELA HPAAECVDPA VVFPFPVNKR
210 220 230 240 250
EPAPVPAAPA SAPAAGPAVA SGAGIAAPAG APGVAPPRPG GRQTSGGDHK
260 270 280 290 300
ALSTSGEDTL SDSDDEDDEE EDEEEEIDVV TVEKRRSSSN TKAVTTFTIT
310 320 330 340 350
VRPKNAALGP GRAQSSELIL KRCLPIHQQH NYAAPSPYVE SEDAPPQKKI
360 370 380 390 400
KSEASPRPLK SVIPPKAKSL SPRNSDSEDS ERRRNHNILE RQRRNDLRSS
410 420 430 440 450
FLTLRDHVPE LVKNEKAAKV VILKKATEYV HSLQAEEHQL LLEKEKLQAR
460
QQQLLKKIEH ARTC
Length:464
Mass (Da):49,561
Last modified:July 1, 1989 - v2
Checksum:i560E885602E30DAD
GO

Sequence cautioni

The sequence AAA36371 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAA68678 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti227A → P in CAA27037 (PubMed:3510398).Curated1
Sequence conflicti363I → V in CAA68678 (PubMed:2834684).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_031952393R → H in FGLDS1. 1 PublicationCorresponds to variant dbSNP:rs104893646Ensembl.1
Natural variantiVAR_031953393R → S in FGLDS1. 1 PublicationCorresponds to variant dbSNP:rs104893647Ensembl.1
Natural variantiVAR_031954394R → H in FGLDS1. 1 PublicationCorresponds to variant dbSNP:rs104893648Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS1687.1.
PIRiA01355. TVHUMC.
A25744. TVHUM2.
RefSeqiNP_001280157.1. NM_001293228.1.
NP_001280160.1. NM_001293231.1.
NP_001280162.1. NM_001293233.1.
NP_005369.2. NM_005378.5.
XP_016859657.1. XM_017004168.1.
UniGeneiHs.25960.

Genome annotation databases

EnsembliENST00000281043; ENSP00000281043; ENSG00000134323.
GeneIDi4613.
KEGGihsa:4613.
UCSCiuc002rci.4. human.

Similar proteinsi

Entry informationi

Entry nameiMYCN_HUMAN
AccessioniPrimary (citable) accession number: P04198
Secondary accession number(s): Q53XS5, Q6LDT9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: July 1, 1989
Last modified: October 25, 2017
This is version 192 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references