P04198 · MYCN_HUMAN
- ProteinN-myc proto-oncogene protein
- GeneMYCN
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids464 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Positively regulates the transcription of MYCNOS in neuroblastoma cells.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | chromatin | |
Cellular Component | nucleolus | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Molecular Function | DNA binding | |
Molecular Function | DNA-binding transcription activator activity, RNA polymerase II-specific | |
Molecular Function | DNA-binding transcription factor activity | |
Molecular Function | DNA-binding transcription factor activity, RNA polymerase II-specific | |
Molecular Function | kinase binding | |
Molecular Function | protein dimerization activity | |
Molecular Function | RNA polymerase II cis-regulatory region sequence-specific DNA binding | |
Molecular Function | sequence-specific double-stranded DNA binding | |
Biological Process | negative regulation of gene expression | |
Biological Process | positive regulation of DNA-templated transcription | |
Biological Process | positive regulation of gene expression | |
Biological Process | positive regulation of miRNA transcription | |
Biological Process | positive regulation of transcription by RNA polymerase II | |
Biological Process | regulation of transcription by RNA polymerase II |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameN-myc proto-oncogene protein
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP04198
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Feingold syndrome 1 (FGLDS1)
- Note
- DescriptionA syndrome characterized by variable combinations of esophageal and duodenal atresias, microcephaly, learning disability, intellectual disability, 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 alsoMIM:164280
Natural variants in FGLDS1
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_031952 | 393 | R>H | in FGLDS1; dbSNP:rs104893646 | |
VAR_031953 | 393 | R>S | in FGLDS1; dbSNP:rs104893647 | |
VAR_031954 | 394 | R>H | in FGLDS1; dbSNP:rs104893648 |
Megalencephaly-polydactyly syndrome (MPAPA)
- Note
- DescriptionAn autosomal dominant syndrome characterized by megalencephaly, ventriculomegaly, postaxial polydactyly, and increased risk of neuroblastoma.
- See alsoMIM:620748
Natural variants in MPAPA
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_089416 | 58 | T>M | in MPAPA; pathogenic; mice with the orthologous mutation have polydactyly and higher brain weight than wild-type animals; results in loss of T-58 phosphorylation; results in increased protein levels | |
VAR_089417 | 60 | P>L | in MPAPA; likely pathogenic; results in reduced T-58 phosphorylation |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 28 | Reduces interaction with AURKA; when associated with A-35. | ||||
Sequence: F → A | ||||||
Mutagenesis | 29 | Reduces interaction with AURKA; when associated with A-36. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 35 | Reduces interaction with AURKA; when associated with A-28. | ||||
Sequence: F → A | ||||||
Mutagenesis | 36 | Reduces interaction with AURKA; when associated with A-29. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 52-56 | Does not affect AURKA binding. | ||||
Sequence: KFELL → AAAAA | ||||||
Natural variant | VAR_089416 | 58 | in MPAPA; pathogenic; mice with the orthologous mutation have polydactyly and higher brain weight than wild-type animals; results in loss of T-58 phosphorylation; results in increased protein levels | |||
Sequence: T → M | ||||||
Natural variant | VAR_089417 | 60 | in MPAPA; likely pathogenic; results in reduced T-58 phosphorylation | |||
Sequence: P → L | ||||||
Mutagenesis | 73 | Reduces binding to AURKA. | ||||
Sequence: E → K | ||||||
Mutagenesis | 77 | Reduces binding to AURKA. | ||||
Sequence: W → A | ||||||
Mutagenesis | 88 | Abrogates the interaction with AURKA. | ||||
Sequence: W → A | ||||||
Natural variant | VAR_031952 | 393 | in FGLDS1; dbSNP:rs104893646 | |||
Sequence: R → H | ||||||
Natural variant | VAR_031953 | 393 | in FGLDS1; dbSNP:rs104893647 | |||
Sequence: R → S | ||||||
Natural variant | VAR_031954 | 394 | in FGLDS1; dbSNP:rs104893648 | |||
Sequence: R → H |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,104 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000127323 | 1-464 | UniProt | N-myc proto-oncogene protein | |||
Sequence: MPSCSTSTMPGMICKNPDLEFDSLQPCFYPDEDDFYFGGPDSTPPGEDIWKKFELLPTPPLSPSRGFAEHSSEPPSWVTEMLLENELWGSPAEEDAFGLGGLGGLTPNPVILQDCMWSGFSAREKLERAVSEKLQHGRGPPTAGSTAQSPGAGAASPAGRGHGGAAGAGRAGAALPAELAHPAAECVDPAVVFPFPVNKREPAPVPAAPASAPAAGPAVASGAGIAAPAGAPGVAPPRPGGRQTSGGDHKALSTSGEDTLSDSDDEDDEEEDEEEEIDVVTVEKRRSSSNTKAVTTFTITVRPKNAALGPGRAQSSELILKRCLPIHQQHNYAAPSPYVESEDAPPQKKIKSEASPRPLKSVIPPKAKSLSPRNSDSEDSERRRNHNILERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSLQAEEHQLLLEKEKLQARQQQLLKKIEHARTC | |||||||
Modified residue | 58 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 58 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 62 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 64 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 149 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 156 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 261 | UniProt | Phosphoserine; by CK2 | ||||
Sequence: S | |||||||
Modified residue | 263 | UniProt | Phosphoserine; by CK2 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 315 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylated by GSK3-beta which may promote its degradation (PubMed:24391509).
Phosphorylated by AURKA (PubMed:27837025).
Phosphorylated by AURKA (PubMed:27837025).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in the neuronal cells of the cerebrum, neuroblastomas and thyroid tumors (at protein level).
Developmental stage
Expressed during fetal development.
Gene expression databases
Organism-specific databases
Interaction
Subunit
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).
Interacts with FBXW7; FBXW7 competes with AURKA for binding to unphosphorylated MYCN but not for binding to phosphorylated MYCN (PubMed:27837025).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P04198 | AURKA O14965 | 12 | EBI-878369, EBI-448680 | |
BINARY | P04198 | CDKN2A Q8N726 | 3 | EBI-878369, EBI-625922 | |
BINARY | P04198 | MAX P61244 | 10 | EBI-878369, EBI-751711 | |
BINARY | P04198 | NMI Q13287 | 3 | EBI-878369, EBI-372942 | |
BINARY | P04198 | SIRT1 Q96EB6 | 3 | EBI-878369, EBI-1802965 | |
BINARY | P04198 | ZBTB17 Q13105 | 3 | EBI-878369, EBI-372156 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, motif, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 19-47 | Interaction with AURKA | ||||
Sequence: LEFDSLQPCFYPDEDDFYFGGPDSTPPGE | ||||||
Region | 61-89 | Interaction with AURKA and FBXW7 | ||||
Sequence: LSPSRGFAEHSSEPPSWVTEMLLENELWG | ||||||
Motif | 76-84 | 9aaTAD | ||||
Sequence: SWVTEMLLE | ||||||
Region | 129-172 | Disordered | ||||
Sequence: AVSEKLQHGRGPPTAGSTAQSPGAGAASPAGRGHGGAAGAGRAG | ||||||
Region | 196-294 | Disordered | ||||
Sequence: PVNKREPAPVPAAPASAPAAGPAVASGAGIAAPAGAPGVAPPRPGGRQTSGGDHKALSTSGEDTLSDSDDEDDEEEDEEEEIDVVTVEKRRSSSNTKAV | ||||||
Compositional bias | 259-278 | Acidic residues | ||||
Sequence: TLSDSDDEDDEEEDEEEEID | ||||||
Region | 334-392 | Disordered | ||||
Sequence: APSPYVESEDAPPQKKIKSEASPRPLKSVIPPKAKSLSPRNSDSEDSERRRNHNILERQ | ||||||
Compositional bias | 372-392 | Basic and acidic residues | ||||
Sequence: PRNSDSEDSERRRNHNILERQ | ||||||
Domain | 381-433 | bHLH | ||||
Sequence: ERRRNHNILERQRRNDLRSSFLTLRDHVPELVKNEKAAKVVILKKATEYVHSL | ||||||
Region | 433-454 | Leucine-zipper | ||||
Sequence: LQAEEHQLLLEKEKLQARQQQL |
Domain
The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length464
- Mass (Da)49,561
- Last updated1989-07-01 v2
- Checksum560E885602E30DAD
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A1W2PPD9 | A0A1W2PPD9_HUMAN | MYCN | 253 |
Sequence caution
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 227 | in Ref. 2; CAA27037 | ||||
Sequence: A → P | ||||||
Compositional bias | 259-278 | Acidic residues | ||||
Sequence: TLSDSDDEDDEEEDEEEEID | ||||||
Sequence conflict | 363 | in Ref. 3; CAA68678 | ||||
Sequence: I → V | ||||||
Compositional bias | 372-392 | Basic and acidic residues | ||||
Sequence: PRNSDSEDSERRRNHNILERQ |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X03294 EMBL· GenBank· DDBJ | CAA27037.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X03295 EMBL· GenBank· DDBJ | CAA27038.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M13241 EMBL· GenBank· DDBJ | AAA36371.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
M13228 EMBL· GenBank· DDBJ | AAA36370.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BT007384 EMBL· GenBank· DDBJ | AAP36048.1 EMBL· GenBank· DDBJ | mRNA | ||
AC010145 EMBL· GenBank· DDBJ | AAY14952.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAX00885.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAX00886.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAX00887.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAX00888.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC002712 EMBL· GenBank· DDBJ | AAH02712.1 EMBL· GenBank· DDBJ | mRNA | ||
M18090 EMBL· GenBank· DDBJ | AAA59885.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X02363 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
Y00664 EMBL· GenBank· DDBJ | CAA68678.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation |