MYCN_MOUSE
ID MYCN_MOUSE Reviewed; 462 AA.
AC P03966; Q61978;
DT 23-OCT-1986, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-1998, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=N-myc proto-oncogene protein;
GN Name=Mycn; Synonyms=Nmyc, Nmyc1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3513190; DOI=10.1073/pnas.83.6.1827;
RA DePinho R.A., Legouy E., Feldman L.B., Kohl N.E., Yancopoulos G.D.,
RA Alt F.W.;
RT "Structure and expression of the murine N-myc gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:1827-1831(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3015591; DOI=10.1002/j.1460-2075.1986.tb04349.x;
RA Taya Y., Mizusawa S., Nishimura S.;
RT "Nucleotide sequence of the coding region of the mouse N-myc gene.";
RL EMBO J. 5:1215-1219(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE OF 1-456.
RC STRAIN=BALB/cJ;
RA Nasu N., Setoguchi M., Yoshiyama K., Matsuura K., Yamamoto S.;
RT "Expression of murine N-myc by insertion of retrovirus sequences in murine
RT macrophage cell lines.";
RL Submitted (APR-1992) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 327-462.
RX PubMed=2555695; DOI=10.1128/mcb.9.10.4515-4522.1989;
RA Setoguchi M., Higuchi Y., Yoshida S., Nasu N., Miyazaki Y., Akizuki S.,
RA Yamamoto S.;
RT "Insertional activation of N-myc by endogenous Moloney-like murine
RT retrovirus sequences in macrophage cell lines derived from myeloma cell
RT line-macrophage hybrids.";
RL Mol. Cell. Biol. 9:4515-4522(1989).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-39.
RX PubMed=3287334; DOI=10.1093/nar/16.8.3589;
RA Katoh K., Sawai S., Ueno K., Kondoh H.;
RT "Complete nucleotide sequence and exon-intron boundaries of the 5' non-
RT coding region of the mouse N-myc gene.";
RL Nucleic Acids Res. 16:3589-3589(1988).
RN [6]
RP DEVELOPMENTAL STAGE.
RX PubMed=8521822; DOI=10.1002/j.1460-2075.1995.tb00252.x;
RA Hurlin P.J., Queva C., Koskinen P.J., Steingrimsson E., Ayer D.E.,
RA Copeland N.G., Jenkins N.A., Eisenman R.N.;
RT "Mad3 and Mad4: novel Max-interacting transcriptional repressors that
RT suppress c-myc dependent transformation and are expressed during neural and
RT epidermal differentiation.";
RL EMBO J. 14:5646-5659(1995).
RN [7]
RP ERRATUM OF PUBMED:8521822.
RX PubMed=8617250; DOI=10.1002/j.1460-2075.1996.tb00555.x;
RA Hurlin P.J., Queva C., Koskinen P.J., Steingrimsson E., Ayer D.E.,
RA Copeland N.G., Jenkins N.A., Eisenman R.N.;
RL EMBO J. 15:2030-2030(1996).
CC -!- FUNCTION: Positively regulates the transcription of MYCNOS in
CC neuroblastoma cells. {ECO:0000250|UniProtKB:P04198}.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC protein. Binds DNA as a heterodimer with MAX. Interacts with KDM5A,
CC KDM5B and HUWE1. Interacts with MYCNOS. Interacts with AURKA;
CC interaction is phospho-independent and triggers AURKA activation; AURKA
CC competes with FBXW7 for binding to unphosphorylated MYCN but not for
CC binding to unphosphorylated MYCN. Interacts with FBXW7; FBXW7 competes
CC with AURKA for binding to unphosphorylated MYCN but not for binding to
CC phosphorylated MYCN. {ECO:0000250|UniProtKB:P04198}.
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- DEVELOPMENTAL STAGE: Expressed in the proliferating cells of the
CC developing CNS and the epidermis. In the spinal cord at embryonic days
CC 10.5, 11.5 and 12.5 dpc, expressed in the proliferating cells of the
CC ventricular zone of the neural tube and is expressed at reduced levels
CC in the intermediate zone. At 14.5 dpc, found in regions containing
CC differentiating post-mitotic neurons. In the developing epidermis at 17
CC dpc, expression is restricted to primary hair germ cells only.
CC {ECO:0000269|PubMed:8521822}.
CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large
CC number of yeast and animal transcription factors.
CC {ECO:0000250|UniProtKB:P04198}.
CC -!- PTM: Phosphorylated by GSK3-beta which may promote its degradation.
CC Phosphorylated by AURKA. {ECO:0000250|UniProtKB:P04198}.
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DR EMBL; M12731; AAA39788.1; -; Genomic_DNA.
DR EMBL; X03919; CAA27557.1; -; Genomic_DNA.
DR EMBL; M36277; AAA39833.1; -; mRNA.
DR EMBL; M29208; AAA39830.1; -; Genomic_DNA.
DR EMBL; X06993; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS25818.1; -.
DR PIR; A01356; TVMSMC.
DR PIR; A01357; TVMSM2.
DR RefSeq; NP_032735.3; NM_008709.3.
DR AlphaFoldDB; P03966; -.
DR SMR; P03966; -.
DR BioGRID; 201795; 8.
DR DIP; DIP-49592N; -.
DR IntAct; P03966; 7.
DR STRING; 10090.ENSMUSP00000045993; -.
DR iPTMnet; P03966; -.
DR PhosphoSitePlus; P03966; -.
DR PaxDb; P03966; -.
DR PRIDE; P03966; -.
DR DNASU; 18109; -.
DR Ensembl; ENSMUST00000043396; ENSMUSP00000045993; ENSMUSG00000037169.
DR Ensembl; ENSMUST00000130990; ENSMUSP00000114225; ENSMUSG00000037169.
DR GeneID; 18109; -.
DR KEGG; mmu:18109; -.
DR UCSC; uc007nbf.2; mouse.
DR CTD; 4613; -.
DR MGI; MGI:97357; Mycn.
DR VEuPathDB; HostDB:ENSMUSG00000037169; -.
DR eggNOG; KOG2588; Eukaryota.
DR GeneTree; ENSGT00940000158432; -.
DR HOGENOM; CLU_052560_0_0_1; -.
DR InParanoid; P03966; -.
DR OMA; PFPINKR; -.
DR OrthoDB; 877891at2759; -.
DR PhylomeDB; P03966; -.
DR TreeFam; TF106001; -.
DR BioGRID-ORCS; 18109; 5 hits in 73 CRISPR screens.
DR ChiTaRS; Mycn; mouse.
DR PRO; PR:P03966; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; P03966; protein.
DR Bgee; ENSMUSG00000037169; Expressed in primitive streak and 272 other tissues.
DR ExpressionAtlas; P03966; baseline and differential.
DR Genevisible; P03966; MM.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0019900; F:kinase binding; ISO:MGI.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0048708; P:astrocyte differentiation; IDA:MGI.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; IMP:MGI.
DR GO; GO:0001502; P:cartilage condensation; IMP:MGI.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IMP:MGI.
DR GO; GO:0048704; P:embryonic skeletal system morphogenesis; IMP:MGI.
DR GO; GO:0050673; P:epithelial cell proliferation; IMP:MGI.
DR GO; GO:0030324; P:lung development; IMP:MGI.
DR GO; GO:0048712; P:negative regulation of astrocyte differentiation; IDA:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IDA:UniProtKB.
DR GO; GO:0010942; P:positive regulation of cell death; IMP:MGI.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0045607; P:regulation of inner ear auditory receptor cell differentiation; IGI:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR002418; Tscrpt_reg_Myc.
DR InterPro; IPR012682; Tscrpt_reg_Myc_N.
DR Pfam; PF00010; HLH; 1.
DR Pfam; PF01056; Myc_N; 1.
DR PIRSF; PIRSF001705; Myc_protein; 1.
DR PRINTS; PR00044; LEUZIPPRMYC.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 2: Evidence at transcript level;
KW DNA-binding; Nucleus; Phosphoprotein; Proto-oncogene; Reference proteome.
FT CHAIN 1..462
FT /note="N-myc proto-oncogene protein"
FT /id="PRO_0000127325"
FT DOMAIN 379..431
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 19..47
FT /note="Interaction with AURKA"
FT /evidence="ECO:0000250|UniProtKB:P04198"
FT REGION 61..90
FT /note="Interaction with AURKA and FBXW7"
FT /evidence="ECO:0000250|UniProtKB:P04198"
FT REGION 134..177
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 232..289
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 332..390
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 431..452
FT /note="Leucine-zipper"
FT MOTIF 76..85
FT /note="9aaTAD"
FT /evidence="ECO:0000250|UniProtKB:P04198"
FT COMPBIAS 161..177
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 257..276
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 370..390
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 259
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:P04198"
FT MOD_RES 261
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:P04198"
FT CONFLICT 28..29
FT /note="FY -> LH (in Ref. 1; AAA39788)"
FT /evidence="ECO:0000305"
FT CONFLICT 36
FT /note="Y -> H (in Ref. 1; AAA39788)"
FT /evidence="ECO:0000305"
FT CONFLICT 246..247
FT /note="EA -> GT (in Ref. 1; AAA39788)"
FT /evidence="ECO:0000305"
FT CONFLICT 313
FT /note="P -> L (in Ref. 1; AAA39788)"
FT /evidence="ECO:0000305"
FT CONFLICT 390
FT /note="Q -> E (in Ref. 2; CAA27557)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 462 AA; 49572 MW; E7AFD3DCBCABF290 CRC64;
MPSCTASTMP GMICKNPDLE FDSLQPCFYP DEDDFYFGGP DSTPPGEDIW KKFELLPTPP
LSPSRAFPEH SPEPSNWATE MLLPEADLWG NPAEEDAFGL GGLGGLTPNP VILQDCMWSG
FSAREKLERA VNEKLQHGHG PPGVSSACSA PGVGASSPGG RALGGSSSAS HTGATLPTDL
SHPAAECVDP AVVFPFPVNK RESASVPAAP TSAPATSAAV TSVSVPATAP VAAPARAGGR
PASSGEAKAL STSGEDTLSD SDDEDDEEED EEEEIDVVTV EKRRSSSNNK AVTTFTITVR
PKTSALGLGR AQPGELILKR CVPIHQQHNY AAPSPYVESE DAPPQKKIKS EASPRPLKSV
VPAKAKSLSP RNSDSEDSER RRNHNILERQ RRNDLRSSFL TLRDHVPELV KNEKAAKVVI
LKKATEYVHA LQANEHQLLL EKEKLQARQQ QLLKKIEHAR TC
