P01108 (MYC_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Myc proto-oncogene protein

Alternative name(s):
Proto-oncogene c-Myc
Transcription factor p64

Gene names

Name:

Myc

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	439 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Participates in the regulation of gene transcription. Binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Seems to activate the transcription of growth-related genes.
Subunit structure	Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MAX. Interacts with TAF1C. Interacts with PARP10. Interacts with KDM5A and KDM5B. Interacts (when phosphorylated at Thr-58 and Ser-62) with FBXW7 By similarity. Interacts with NO66 By similarity. Interacts with SPAG9. Interacts with PIM2. Ref.8 Ref.10
Subcellular location	Nucleus › nucleoplasm By similarity. Nucleus › nucleolus By similarity.
Developmental stage	Expressed in the proliferating cells of the developing CNS and the epidermis. In the spinal cord at embryonic days 10.5, 11.5 and 12.5 dpc, expressed within a subset of cells in the proliferative ventricular zone, as well as in the differentiating cells at the ventral portion of the intermediate zone. Also detected in the roof plate and in the neural crest. At 14.5 dpc, found in regions containing differentiating post-mitotic neurons. In the developing epidermis at 14.5 dpc, found in the dorsal lateral epidermis. At 17 dpc, expression is confined primarily to the proliferative malphigian layer of the epidermis and to the dermal papilla and primary germ cells in the dermis. Ref.6
Post-translational modification	Phosphorylated by PRKDC. Phosphorylated at Ser-62 by DYRK2; this primes the protein for subsequent phosphorylation by GSK3B at Thr-58. Phosphorylation at Thr-58 and Ser-62 by GSK3 is required for ubiquitination and degradation by the proteasome. Phosphorylation at Ser-62 by CDK2 prevents Ras-induced senescence By similarity. Phosphorylation at Ser-329 by PIM2 leads to the stabilization of MYC. Ref.10 Ubiquitinated by the SCF(FBXW7) complex when phosphorylated at Thr-58 and Ser-62, leading to its degradation by the proteasome. In the nucleoplasm, ubiquitination is counteracted by USP28, which interacts with of FBXW7 (FBW7alpha), leading to its deubiquitination and preventing degradation. Also polyubiquitinated by the DCX(TRUSS) complex By similarity. Ref.10
Involvement in disease	Overexpression of C-Myc is implicated in the etiology of a variety of hematopoietic tumors.
Biotechnological use	POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 are the four Yamanaka factors. When combined, these factors are sufficient to reprogram differentiated cells to an embryonic-like state designated iPS (induced pluripotent stem) cells. iPS cells exhibit the morphology and growth properties of ES cells and express ES cell marker genes. Ref.9
Sequence similarities	Contains 1 bHLH (basic helix-loop-helix) domain.
Sequence caution	The sequence AAH06728.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Disease	Proto-oncogene
Ligand	DNA-binding
Molecular function	Activator
PTM	Acetylation Glycoprotein Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell apoptotic process Inferred from mutant phenotype PubMed 12970677. Source: MGI MAPK cascade Inferred from sequence or structural similarity. Source: UniProtKB activation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from direct assay PubMed 14517295. Source: MGI apoptotic DNA fragmentation Inferred from direct assay PubMed 14517295. Source: MGI branching involved in ureteric bud morphogenesis Inferred from mutant phenotype PubMed 19161241. Source: UniProtKB canonical Wnt receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB cellular iron ion homeostasis Inferred from sequence or structural similarity. Source: UniProtKB cellular response to drug Inferred from direct assay PubMed 19179467. Source: UniProtKB chromatin remodeling Inferred from sequence or structural similarity. Source: UniProtKB detection of mechanical stimulus involved in sensory perception of sound Inferred from mutant phenotype PubMed 17523175. Source: MGI intrinsic apoptotic signaling pathway Inferred from direct assay PubMed 14517295. Source: MGI middle ear morphogenesis Inferred from mutant phenotype PubMed 17523175. Source: MGI negative regulation of cell division Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of monocyte differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of protein binding Inferred from direct assay PubMed 18045875. Source: MGI negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 12196193. Source: MGI pigmentation Inferred from mutant phenotype PubMed 17523175. Source: MGI positive regulation of B cell apoptotic process Inferred from genetic interaction PubMed 11604501. Source: MGI positive regulation of DNA biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of apoptotic signaling pathway Inferred from direct assay PubMed 14517295. Source: MGI positive regulation of epithelial cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of fibroblast proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of metanephric cap mesenchymal cell proliferation Inferred from mutant phenotype PubMed 19161241. Source: UniProtKB positive regulation of response to DNA damage stimulus Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 17382917. Source: MGI protein processing Inferred from mutant phenotype PubMed 12970677. Source: MGI regulation of telomere maintenance Inferred from sequence or structural similarity. Source: UniProtKB release of cytochrome c from mitochondria Inferred from direct assay PubMed 14517295. Source: MGI response to DNA damage stimulus Inferred from sequence or structural similarity. Source: UniProtKB response to alkaloid Inferred from mutant phenotype PubMed 12970677. Source: MGI response to gamma radiation Inferred from sequence or structural similarity. Source: UniProtKB skeletal muscle cell differentiation Inferred from mutant phenotype PubMed 22147266. Source: MGI skeletal system morphogenesis Inferred from mutant phenotype PubMed 17523175. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	axon Inferred from direct assay PubMed 10482234. Source: MGI nuclear body Inferred from direct assay PubMed 15735755. Source: MGI nucleolus Inferred from sequence or structural similarity. Source: UniProtKB spindle Inferred from direct assay PubMed 15509711. Source: MGI
Molecular_function	E-box binding Inferred from sequence or structural similarity. Source: UniProtKB core promoter proximal region sequence-specific DNA binding Inferred from direct assay PubMed 15511642. Source: MGI protein complex binding Inferred from sequence or structural similarity. Source: UniProtKB sequence-specific DNA binding transcription factor activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Max	P28574	6	EBI-1183114,EBI-1183003
Trim32	Q8CH72	2	EBI-1183114,EBI-773837

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 439	439	Myc proto-oncogene protein		PRO_0000127296
Regions
	Domain	354 – 406	53	bHLH
	Region	413 – 434	22	Leucine-zipper
	Compositional bias	34 – 37	4	Poly-Gln
	Compositional bias	89 – 92	4	Poly-Gly
Amino acid modifications
	Modified residue	8	1	Phosphothreonine By similarity
	Modified residue	58	1	Phosphothreonine; by GSK3; alternate By similarity
	Modified residue	62	1	Phosphoserine; by DYRK2, GSK3 and CDK2 By similarity
	Modified residue	71	1	Phosphoserine By similarity
	Modified residue	144	1	N6-acetyllysine; by PCAF By similarity
	Modified residue	149	1	N6-acetyllysine By similarity
	Modified residue	158	1	N6-acetyllysine; by PCAF By similarity
	Modified residue	162	1	Phosphoserine By similarity
	Modified residue	275	1	N6-acetyllysine; by PCAF By similarity
	Modified residue	317	1	N6-acetyllysine; by PCAF By similarity
	Modified residue	323	1	N6-acetyllysine; by PCAF By similarity
	Modified residue	329	1	Phosphoserine; by PIM2; in vitro Ref.10
	Modified residue	371	1	N6-acetyllysine; by PCAF By similarity
	Glycosylation	58	1	O-linked (GlcNAc); alternate By similarity
Experimental info
	Mutagenesis	329	1	S → A: Reduces phosphorylation by PIM2 by 60%, and decreases the transcriptional activity of MYC. Ref.10
	Sequence conflict	39	1	E → D in K00683. Ref.5
	Sequence conflict	101	1	E → Q in AAB59728. Ref.1
	Sequence conflict	284	1	S → F in AAB59728. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P01108 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 3FCA39BFFD6FC59E	FASTA	439	48,971
	10 20 30 40 50 60 MPLNVNFTNR NYDLDYDSVQ PYFICDEEEN FYHQQQQSEL QPPAPSEDIW KKFELLPTPP 70 80 90 100 110 120 LSPSRRSGLC SPSYVAVATS FSPREDDDGG GGNFSTADQL EMMTELLGGD MVNQSFICDP 130 140 150 160 170 180 DDETFIKNII IQDCMWSGFS AAAKLVSEKL ASYQAARKDS TSLSPARGHS VCSTSSLYLQ 190 200 210 220 230 240 DLTAAASECI DPSVVFPYPL NDSSSPKSCT SSDSTAFSPS SDSLLSSESS PRASPEPLVL 250 260 270 280 290 300 HEETPPTTSS DSEEEQEDEE EIDVVSVEKR QTPAKRSESG SSPSRGHSKP PHSPLVLKRC 310 320 330 340 350 360 HVSTHQHNYA APPSTRKDYP AAKRAKLDSG RVLKQISNNR KCSSPRSSDT EENDKRRTHN 370 380 390 400 410 420 VLERQRRNEL KRSFFALRDQ IPELENNEKA PKVVILKKAT AYILSIQADE HKLTSEKDLL 430 RKRREQLKHK LEQLRNSGA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of the murine and human cellular myc oncogenes and two modes of myc transcription resulting from chromosome translocation in B lymphoid tumours." Bernard O., Cory S., Gerondakis S., Webb E., Adams J.M. EMBO J. 2:2375-2383(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: BALB/c. Tissue: Spleen.
[2]	"Nucleotide sequence comparison of normal and translocated murine c-myc genes." Stanton L.W., Fahrlander P.D., Tesser P.M., Marcu K.B. Nature 310:423-425(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J and NOD. Tissue: Embryo, Mammary gland and Thymus.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Mammary gland.
[5]	"Reciprocal chromosome translocation between c-myc and immunoglobulin gamma 2b genes." Neuberger M.S., Calabi F. Nature 305:240-243(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-252.
[6]	"Mad3 and Mad4: novel Max-interacting transcriptional repressors that suppress c-myc dependent transformation and are expressed during neural and epidermal differentiation." Hurlin P.J., Queva C., Koskinen P.J., Steingrimsson E., Ayer D.E., Copeland N.G., Jenkins N.A., Eisenman R.N. EMBO J. 14:5646-5659(1995) [PubMed] [Europe PMC] [Abstract] Cited for: DEVELOPMENTAL STAGE.
[7]	Erratum Hurlin P.J., Queva C., Koskinen P.J., Steingrimsson E., Ayer D.E., Copeland N.G., Jenkins N.A., Eisenman R.N. EMBO J. 15:2030-2030(1996) [PubMed] [Europe PMC] [Abstract]
[8]	"JLP: a scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors." Lee C.M., Onesime D., Reddy C.D., Dhanasekaran N., Reddy E.P. Proc. Natl. Acad. Sci. U.S.A. 99:14189-14194(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SPAG9.
[9]	"Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors." Takahashi K., Yamanaka S. Cell 126:663-676(2006) [PubMed] [Europe PMC] [Abstract] Cited for: BIOTECHNOLOGY.
[10]	"Pim kinase-dependent inhibition of c-Myc degradation." Zhang Y., Wang Z., Li X., Magnuson N.S. Oncogene 27:4809-4819(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-329, MUTAGENESIS OF SER-329, INTERACTION WITH PIM2.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L00039, L00038 Genomic DNA. Translation: AAB59728.1. X01023 mRNA. Translation: CAA25508.1. AK087961 mRNA. Translation: BAC40060.1. AK133952 mRNA. Translation: BAE21948.1. AK145084 mRNA. Translation: BAE26228.1. BC006728 mRNA. Translation: AAH06728.2. Different initiation. K00683 Genomic DNA. No translation available.
IPI	IPI00956837.
PIR	TVMS. A93337.
RefSeq	NP_001170823.1. NM_001177352.1. NP_001170824.1. NM_001177353.1. NP_001170825.1. NM_001177354.1.
UniGene	Mm.2444.
3D structure databases
ProteinModelPortal	P01108.
SMR	P01108. Positions 353-434.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-1064N.
IntAct	P01108. 11 interactions.
PTM databases
PhosphoSite	P01108.
Proteomic databases
PRIDE	P01108.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000159327; ENSMUSP00000124758; ENSMUSG00000022346. ENSMUST00000160009; ENSMUSP00000123852; ENSMUSG00000022346. ENSMUST00000161976; ENSMUSP00000123821; ENSMUSG00000022346.
GeneID	17869.
KEGG	mmu:17869.
Organism-specific databases
CTD	4609.
MGI	MGI:97250. Myc.
Phylogenomic databases
eggNOG	NOG42590.
GeneTree	ENSGT00510000046414.
HOVERGEN	HBG000472.
InParanoid	P01108.
KO	K04377.
OrthoDB	EOG42RD7N.
Gene expression databases
ArrayExpress	P01108.
Bgee	P01108.
CleanEx	MM_MYC.
Genevestigator	P01108.
GermOnline	ENSMUSG00000022346. Mus musculus.
Family and domain databases
Gene3D	4.10.280.10. 1 hit.
InterPro	IPR011598. bHLH_dom. IPR003327. Myc-LZ. IPR002418. Tscrpt_reg_Myc. IPR012682. Tscrpt_reg_Myc_N. [Graphical view]
Pfam	PF00010. HLH. 1 hit. PF02344. Myc-LZ. 1 hit. PF01056. Myc_N. 1 hit. [Graphical view]
PIRSF	PIRSF001705. Myc_protein. 1 hit.
PRINTS	PR00044. LEUZIPPRMYC.
SMART	SM00353. HLH. 1 hit. [Graphical view]
SUPFAM	SSF47459. HLH_basic. 1 hit.
PROSITE	PS50888. BHLH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	MYC. mouse.
NextBio	292641.
SOURCE	Search...

Entry information

Entry name

MYC_MOUSE

Accession

Primary (citable) accession number: P01108
Secondary accession number(s): P70247, Q3UM70, Q61422

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	May 1, 2013
This is version 143 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program