P01106 (MYC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Myc proto-oncogene protein

Alternative name(s):
Class E basic helix-loop-helix protein 39
Short name=bHLHe39
Proto-oncogene c-Myc
Transcription factor p64

Gene names

Name:	MYC
Synonyms:	BHLHE39

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

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 and SPAG9. Interacts with PARP10. Interacts with KDM5A and KDM5B. Interacts (when phosphorylated at Thr-58 and Ser-62) with FBXW7. Interacts with PIM2 By similarity. Interacts with NO66. Ref.23 Ref.25 Ref.26 Ref.29 Ref.30 Ref.31 Ref.32
Subcellular location	Nucleus › nucleoplasm. Nucleus › nucleolus Ref.32.
Post-translational modification	Phosphorylated by PRKDC. Phosphorylation at Ser-329 by PIM2 leads to the stabilization of MYC By similarity. Phosphorylation at Ser-62 by CDK2 prevents Ras-induced senescence. 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. Ref.18 Ref.20 Ref.22 Ref.23 Ref.32 Ref.35 Ref.36 Ref.40 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 isoform 1 of FBXW7 (FBW7alpha), leading to its deubiquitination and preventing degradation. In the nucleolus, however, ubiquitination is not counteracted by USP28, due to the lack of interaction between isoform 4 of FBXW7 (FBW7gamma) and USP28, explaining the selective MYC degradation in the nucleolus. Also polyubiquitinated by the DCX(TRUSS) complex. Ref.18 Ref.20 Ref.22 Ref.23 Ref.32 Ref.35 Ref.36 Ref.40
Involvement in disease	Overexpression of MYC is implicated in the etiology of a variety of hematopoietic tumors. A chromosomal aberration involving MYC may be a cause of a form of B-cell chronic lymphocytic leukemia. Translocation t(8;12)(q24;q22) with BTG1. Burkitt lymphoma (BL) [MIM:113970]: A form of undifferentiated malignant lymphoma commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. Note: The gene represented in this entry is involved in disease pathogenesis. Chromosomal aberrations involving MYC are usually found in Burkitt lymphoma. Translocations t(8;14), t(8;22) or t(2;8) which juxtapose MYC to one of the heavy or light chain immunoglobulin gene loci.
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.28
Sequence similarities	Contains 1 bHLH (basic helix-loop-helix) domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Proto-oncogene
Ligand	DNA-binding
Molecular function	Activator
PTM	Acetylation Glycoprotein Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MAPK cascade Inferred from mutant phenotype Ref.29. Source: UniProtKB Notch signaling pathway Traceable author statement. Source: Reactome branching involved in ureteric bud morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB canonical Wnt receptor signaling pathway Inferred from direct assay PubMed 21533051. Source: UniProtKB cell cycle arrest Inferred from direct assay PubMed 10962037. Source: UniProtKB cellular iron ion homeostasis Inferred from direct assay PubMed 9924025. Source: UniProtKB cellular response to UV Inferred from expression pattern Ref.29. Source: UniProtKB cellular response to drug Inferred from direct assay Ref.29PubMed 19179467. Source: UniProtKB chromatin remodeling Inferred from direct assay PubMed 21533051. Source: UniProtKB energy reserve metabolic process Non-traceable author statement PubMed 9924025. Source: UniProtKB fibroblast apoptotic process Traceable author statement PubMed 10962037. Source: UniProtKB negative regulation of apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell division Inferred from direct assay PubMed 10962037. Source: UniProtKB negative regulation of fibroblast proliferation Inferred from direct assay PubMed 10962037. Source: UniProtKB negative regulation of monocyte differentiation Inferred from mutant phenotype PubMed 9924025. Source: UniProtKB negative regulation of stress-activated MAPK cascade Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 9924025. Source: UniProtKB oxygen transport Non-traceable author statement PubMed 9924025. Source: UniProtKB positive regulation of DNA biosynthetic process Inferred from mutant phenotype PubMed 9924025. Source: UniProtKB positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from direct assay PubMed 19179467. Source: UniProtKB positive regulation of epithelial cell proliferation Inferred from direct assay PubMed 18987311. Source: UniProtKB positive regulation of fibroblast proliferation Inferred from direct assay PubMed 18987311PubMed 9924025. Source: UniProtKB positive regulation of metanephric cap mesenchymal cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of response to DNA damage stimulus Inferred from direct assay PubMed 19179467. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 9924025. Source: UniProtKB regulation of telomere maintenance Inferred from mutant phenotype PubMed 17765874. Source: BHF-UCL response to DNA damage stimulus Inferred from direct assay Ref.29. Source: UniProtKB response to gamma radiation Inferred from direct assay PubMed 19179467. Source: UniProtKB transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome transforming growth factor beta receptor signaling pathway Traceable author statement. Source: Reactome
Cellular_component	nucleolus Inferred from direct assay Ref.32. Source: UniProtKB nucleoplasm Inferred from direct assay Ref.32. Source: UniProtKB protein complex Inferred from direct assay Ref.29. Source: UniProtKB spindle Inferred from electronic annotation. Source: Compara
Molecular_function	E-box binding Inferred from direct assay PubMed 18818310. Source: UniProtKB protein complex binding Inferred from direct assay PubMed 18987311. Source: UniProtKB sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 9924025. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
	P03070	2	EBI-447544,EBI-617698	From a different organism.
BRD3	Q15059	3	EBI-447544,EBI-1383460
CDK4	P11802	2	EBI-447544,EBI-295644
CEP57	Q86XR8	3	EBI-447544,EBI-308614
CHD4	Q14839	2	EBI-447544,EBI-372916
CHUK	O15111	3	EBI-447544,EBI-81249
EFTUD2	Q15029	5	EBI-447544,EBI-357897
FBXW7	Q969H0	2	EBI-447544,EBI-359574
FBXW8	Q8N3Y1	3	EBI-447544,EBI-914770
HDAC2	Q92769	2	EBI-447544,EBI-301821
HDAC3	O15379	6	EBI-447544,EBI-607682
KIAA1524	Q8TCG1	2	EBI-447544,EBI-1379376
KIAA1967	Q8N163	8	EBI-447544,EBI-355410
MAX	P61244	21	EBI-447544,EBI-751711
Max	P52164	4	EBI-447544,EBI-1184963	From a different organism.
MCM7	P33993	6	EBI-447544,EBI-355924
PIAS2	O75928	4	EBI-447544,EBI-348555
SIRT1	Q96EB6	4	EBI-447544,EBI-1802965
SKP2	Q13309	2	EBI-447544,EBI-456291
SNIP1	Q8TAD8	9	EBI-447544,EBI-749336
SP1	P08047	4	EBI-447544,EBI-298336
TOP1	P11387	2	EBI-447544,EBI-876302
TRRAP	Q9Y4A5	4	EBI-447544,EBI-399128
UBTF	P17480	2	EBI-447544,EBI-396235
ZBTB17	Q13105	2	EBI-447544,EBI-372156

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P01106-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P01106-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MDFFRVVENQQPPATM

Note: Initiates from CTG codon.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 439

439

Myc proto-oncogene protein

PRO_0000127293

Regions

Domain

354 – 406

53

bHLH

Region

413 – 434

22

Leucine-zipper

Compositional bias

33 – 37

5

Poly-Gln

Compositional bias

88 – 91

4

Poly-Gly

Amino acid modifications

Modified residue

6

1

Phosphoserine Ref.38

Modified residue

8

1

Phosphothreonine; by RAF; in vitro Ref.22

Modified residue

58

1

Phosphothreonine; by GSK3; alternate Ref.20 Ref.23 Ref.27 Ref.32 Ref.33 Ref.39

Modified residue

62

1

Phosphoserine; by DYRK2, GSK3 and CDK2 Ref.20 Ref.23 Ref.32 Ref.33 Ref.35 Ref.36 Ref.39 Ref.40

Modified residue

71

1

Phosphoserine Ref.33

Modified residue

143

1

N6-acetyllysine; by PCAF Ref.24

Modified residue

148

1

N6-acetyllysine Ref.34

Modified residue

157

1

N6-acetyllysine; by PCAF Ref.24

Modified residue

161

1

Phosphoserine Ref.38

Modified residue

275

1

N6-acetyllysine; by PCAF Ref.24

Modified residue

317

1

N6-acetyllysine; by PCAF Ref.24

Modified residue

323

1

N6-acetyllysine; by PCAF Ref.24

Modified residue

329

1

Phosphoserine; by PIM2; in vitro By similarity

Modified residue

371

1

N6-acetyllysine; by PCAF Ref.24

Glycosylation

58

1

O-linked (GlcNAc); alternate Ref.21

CAR_000033

Natural variations

Alternative sequence

1

1

M → MDFFRVVENQQPPATM in isoform 2.

VSP_037813

Natural variant

11

1

N → S. Ref.11
Corresponds to variant rs4645959 [ dbSNP | Ensembl ].

VAR_016327

Natural variant

39

1

E → D in a Burkitt lymphoma symple. Ref.5 Ref.19

VAR_063384

Natural variant

57

1

P → S in a Burkitt lymphoma sample. Ref.19

VAR_063385

Natural variant

59

1

P → A in a Burkitt lymphoma sample. Ref.19

VAR_063386

Natural variant

86

1

N → T in a Burkitt lymphoma sample. Ref.19

VAR_063387

Natural variant

160

1

G → C. Ref.11
Corresponds to variant rs4645960 [ dbSNP | Ensembl ].

VAR_016328

Natural variant

170

1

V → I. Ref.11
Corresponds to variant rs4645961 [ dbSNP | Ensembl ].

VAR_016329

Natural variant

322

1

A → V. Ref.11
Corresponds to variant rs4645968 [ dbSNP | Ensembl ].

VAR_016330

Experimental info

Mutagenesis

58

1

T → A: Impairs interaction with FBXW7 and subsequent degradation by the proteasome. Normal inhibition of Ras-induced senescence. Ref.23 Ref.32 Ref.35 Ref.36

Mutagenesis

62

1

S → A: Impairs interaction with FBXW7 and subsequent degradation by the proteasome. Impaired inhibition of Ras-induced senescence. Abolishes phosphorylation by DYRK2, and subsequent phosphorylation by GSK3B at Thr-58. Ref.23 Ref.32 Ref.35 Ref.36 Ref.40

Sequence conflict

6 – 7

2

SF → TI no nucleotide entry Ref.5

Sequence conflict

10

1

R → K no nucleotide entry Ref.5

Sequence conflict

56

1

L → LL no nucleotide entry Ref.5

Sequence conflict

62

1

S → P in CAA25288. Ref.7

Sequence conflict

88

1

G → D no nucleotide entry Ref.5

Sequence conflict

92

1

S → N no nucleotide entry Ref.5

Sequence conflict

114

1

S → N no nucleotide entry Ref.5

Sequence conflict

120

1

D → G no nucleotide entry Ref.5

Sequence conflict

171

1

C → S no nucleotide entry Ref.5

Sequence conflict

203

1

S → R no nucleotide entry Ref.5

Sequence conflict

230

1

S → A no nucleotide entry Ref.5

Sequence conflict

240

1

L → F no nucleotide entry Ref.5

Sequence conflict

245

1

P → S no nucleotide entry Ref.5

Isoform 2:

Sequence conflict

2

1

D → N in BAA01374. Ref.7

Sequence conflict

6

1

V → E in BAA01374. Ref.7

Secondary structure

1

.

.

.

.

.

.

.

439

Helix Strand Turn

Details...

Helix

353 – 378

26

Helix

382 – 384

3

Helix

392 – 434

43

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 13, 1987. Version 1. Checksum: ED5C028029A4C5D1	FASTA	439	48,804
	10 20 30 40 50 60 MPLNVSFTNR NYDLDYDSVQ PYFYCDEEEN FYQQQQQSEL QPPAPSEDIW KKFELLPTPP 70 80 90 100 110 120 LSPSRRSGLC SPSYVAVTPF SLRGDNDGGG GSFSTADQLE MVTELLGGDM VNQSFICDPD 130 140 150 160 170 180 DETFIKNIII QDCMWSGFSA AAKLVSEKLA SYQAARKDSG SPNPARGHSV CSTSSLYLQD 190 200 210 220 230 240 LSAAASECID PSVVFPYPLN DSSSPKSCAS QDSSAFSPSS DSLLSSTESS PQGSPEPLVL 250 260 270 280 290 300 HEETPPTTSS DSEEEQEDEE EIDVVSVEKR QAPGKRSESG SPSAGGHSKP PHSPLVLKRC 310 320 330 340 350 360 HVSTHQHNYA APPSTRKDYP AAKRVKLDSV RVLRQISNNR KCTSPRSSDT EENVKRRTHN 370 380 390 400 410 420 VLERQRRNEL KRSFFALRDQ IPELENNEKA PKVVILKKAT AYILSVQAEE QKLISEEDLL 430 RKRREQLKHK LEQLRNSCA
	Isoform 2 [UniParc]. Checksum: 8B4107BB740689E5	FASTA	454	50,565
	10 20 30 40 50 60 MDFFRVVENQ QPPATMPLNV SFTNRNYDLD YDSVQPYFYC DEEENFYQQQ QQSELQPPAP 70 80 90 100 110 120 SEDIWKKFEL LPTPPLSPSR RSGLCSPSYV AVTPFSLRGD NDGGGGSFST ADQLEMVTEL 130 140 150 160 170 180 LGGDMVNQSF ICDPDDETFI KNIIIQDCMW SGFSAAAKLV SEKLASYQAA RKDSGSPNPA 190 200 210 220 230 240 RGHSVCSTSS LYLQDLSAAA SECIDPSVVF PYPLNDSSSP KSCASQDSSA FSPSSDSLLS 250 260 270 280 290 300 STESSPQGSP EPLVLHEETP PTTSSDSEEE QEDEEEIDVV SVEKRQAPGK RSESGSPSAG 310 320 330 340 350 360 GHSKPPHSPL VLKRCHVSTH QHNYAAPPST RKDYPAAKRV KLDSVRVLRQ ISNNRKCTSP 370 380 390 400 410 420 RSSDTEENVK RRTHNVLERQ RRNELKRSFF ALRDQIPELE NNEKAPKVVI LKKATAYILS 430 440 450 VQAEEQKLIS EEDLLRKRRE QLKHKLEQLR NSCA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human c-myc oncogene: structural consequences of translocation into the IgH locus in Burkitt lymphoma." Battey J., Moulding C., Taub R., Murphy W., Stewart T., Potter H., Lenoir G., Leder P. Cell 34:779-787(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 1).
[2]	"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], ALTERNATIVE SPLICING (ISOFORM 1).
[3]	"Identification and nucleotide sequence of a human locus homologous to the v-myc oncogene of avian myelocytomatosis virus MC29." Colby W.W., Chen E.Y., Smith D.H., Levinson A.D. Nature 301:722-725(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 1).
[4]	"Nucleotide sequence of cloned cDNA of human c-myc oncogene." Watt R., Stanton L.W., Marcu K.B., Gallo R.C., Croce C.M., Rovera G. Nature 303:725-728(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]	"Altered nucleotide sequences of a translocated c-myc gene in Burkitt lymphoma." Rabbitts T.H., Hamlyn P.H., Baer R. Nature 306:760-765(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ASP-39.
[6]	"Nucleotide sequence analysis of human c-myc locus, chicken homologue, and myelocytomatosis virus MC29 transforming gene reveals a highly conserved gene product." Watson D.K., Psallidopoulos M.C., Samuel K.P., Dalla-Favera R., Papas T.S. Proc. Natl. Acad. Sci. U.S.A. 80:3642-3645(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 1).
[7]	"Effect of somatic mutation within translocated c-myc genes in Burkitt's lymphoma." Rabbitts T.H., Forster A., Hamlyn P., Baer R. Nature 309:592-597(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-252.
[8]	"Nucleotide sequence of the human c-myc locus: provocative open reading frame within the first exon." Gazin C., Dupont S., de Dinechin D., Hampe A., Masson J.-M., Martin P., Stehelin D., Galibert F. EMBO J. 3:383-387(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 1).
[9]	"Allele-specific activation of the c-myc gene in an atypical Burkitt's lymphoma carrying the t(2;8) chromosomal translocation 250 kb downstream from c-myc." Tachibana K., Takayama N., Matsuo K., Kato S., Yamamoto K., Ohyama K., Umezawa A., Takano T. Gene 124:231-237(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORMS 1 AND 2).
[10]	"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] (ISOFORM 1).
[11]	NIEHS SNPs program Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-11; CYS-160; ILE-170 AND VAL-322.
[12]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Uterus.
[13]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[14]	Mural R.J., Istrail S., Sutton G.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. , 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].
[15]	"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] (ISOFORM 2). Tissue: Cervix, Placenta and Testis.
[16]	"Novel promoter upstream of the human c-myc gene and regulation of c-myc expression in B-cell lymphomas." Bentley D.L., Groudine M. Mol. Cell. Biol. 6:3481-3489(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-170 (ISOFORM 1). Tissue: Promyelocytic leukemia.
[17]	"The pathogenesis of Burkitt's lymphoma." Magrath I. Adv. Cancer Res. 55:133-270(1990) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN BURKITT LYMPHOMA.
[18]	"DNA-activated protein kinase in Raji Burkitt's lymphoma cells. Phosphorylation of c-Myc oncoprotein." Iijima S., Teraoka H., Date T., Tsukada K. Eur. J. Biochem. 206:595-603(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION.
[19]	"Point mutations in the c-Myc transactivation domain are common in Burkitt's lymphoma and mouse plasmacytomas." Bhatia K., Huppi K., Spangler G., Siwarski D., Iyer R., Magrath I. Nat. Genet. 5:56-61(1993) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN BURKITT LYMPHOMA, VARIANTS ASP-39; SER-57; ALA-59 AND THR-86.
[20]	"Transactivation of gene expression by Myc is inhibited by mutation at the phosphorylation sites Thr-58 and Ser-62." Gupta S., Seth A., Davis R.J. Proc. Natl. Acad. Sci. U.S.A. 90:3216-3220(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-58 AND SER-62.
[21]	"c-Myc is glycosylated at threonine 58, a known phosphorylation site and a mutational hot spot in lymphomas." Chou T.-Y., Hart G.W., Dang C.V. J. Biol. Chem. 270:18961-18965(1995) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT THR-58.
[22]	"c-Raf kinase binds to N-terminal domain of c-Myc." Alexandrov I., Shlyakhova L., Vartanian A., Zajac-Kaye M., Alexandrova N. FEBS Lett. 414:465-470(1997) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-8.
[23]	"Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7." Yada M., Hatakeyama S., Kamura T., Nishiyama M., Tsunematsu R., Imaki H., Ishida N., Okumura F., Nakayama K., Nakayama K.I. EMBO J. 23:2116-2125(2004) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION, INTERACTION WITH FBXW7, PHOSPHORYLATION AT THR-58 AND SER-62, MUTAGENESIS OF THR-58 AND SER-62.
[24]	"Six lysine residues on c-Myc are direct substrates for acetylation by p300." Zhang K., Faiola F., Martinez E. Biochem. Biophys. Res. Commun. 336:274-280(2005) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION AT LYS-143; LYS-157; LYS-275; LYS-317; LYS-323 AND LYS-371, MASS SPECTROMETRY.
[25]	"c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I." Grandori C., Gomez-Roman N., Felton-Edkins Z.A., Ngouenet C., Galloway D.A., Eisenman R.N., White R.J. Nat. Cell Biol. 7:311-318(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TAF1C.
[26]	"PARP-10, a novel Myc-interacting protein with poly(ADP-ribose) polymerase activity, inhibits transformation." Yu M., Schreek S., Cerni C., Schamberger C., Lesniewicz K., Poreba E., Vervoorts J., Walsemann G., Groetzinger J., Kremmer E., Mehraein Y., Mertsching J., Kraft R., Austen M., Luescher-Firzlaff J., Luescher B. Oncogene 24:1982-1993(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PARP10.
[27]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-58, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[28]	"Induction of pluripotent stem cells from adult human fibroblasts by defined factors." Takahashi K., Tanabe K., Ohnuki M., Narita M., Ichisaka T., Tomoda K., Yamanaka S. Cell 131:861-872(2007) [PubMed] [Europe PMC] [Abstract] Cited for: BIOTECHNOLOGY.
[29]	"Fbw7 and Usp28 regulate myc protein stability in response to DNA damage." Popov N., Herold S., Llamazares M., Schulein C., Eilers M. Cell Cycle 6:2327-2331(2007) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP28, INTERACTION WITH FBXW7.
[30]	"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.
[31]	"Identification of Myc-associated protein with JmjC domain as a novel therapeutic target oncogene for lung cancer." Suzuki C., Takahashi K., Hayama S., Ishikawa N., Kato T., Ito T., Tsuchiya E., Nakamura Y., Daigo Y. Mol. Cancer Ther. 6:542-551(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NO66.
[32]	"The ubiquitin-specific protease USP28 is required for MYC stability." Popov N., Wanzel M., Madiredjo M., Zhang D., Beijersbergen R., Bernards R., Moll R., Elledge S.J., Eilers M. Nat. Cell Biol. 9:765-774(2007) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP28, INTERACTION WITH FBXW7, SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-58 AND SER-62, MUTAGENESIS OF THR-58 AND SER-62.
[33]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-58; SER-62 AND SER-71, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[34]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-148, MASS SPECTROMETRY.
[35]	"Tipping the balance: Cdk2 enables Myc to suppress senescence." Hydbring P., Larsson L.-G. Cancer Res. 70:6687-6691(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON SENESCENCE, PHOSPHORYLATION AT SER-62 BY CDK2, MUTAGENESIS OF THR-58 AND SER-62.
[36]	"Phosphorylation by Cdk2 is required for Myc to repress Ras-induced senescence in cotransformation." Hydbring P., Bahram F., Su Y., Tronnersjoe S., Hoegstrand K., von der Lehr N., Sharifi H.R., Lilischkis R., Hein N., Wu S., Vervoorts J., Henriksson M., Grandien A., Luescher B., Larsson L.-G. Proc. Natl. Acad. Sci. U.S.A. 107:58-63(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-62 BY CDK2, MUTAGENESIS OF THR-58 AND SER-62.
[37]	"Myc protein is stabilized by suppression of a novel E3 ligase complex in cancer cells." Choi S.H., Wright J.B., Gerber S.A., Cole M.D. Genes Dev. 24:1236-1241(2010) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION.
[38]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-6 AND SER-161, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[39]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-58 AND SER-62, MASS SPECTROMETRY.
[40]	"DYRK2 priming phosphorylation of c-Jun and c-Myc modulates cell cycle progression in human cancer cells." Taira N., Mimoto R., Kurata M., Yamaguchi T., Kitagawa M., Miki Y., Yoshida K. J. Clin. Invest. 122:859-872(2012) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-62, MUTAGENESIS OF SER-62.
[41]	"Insights into the mechanism of heterodimerization from the 1H-NMR solution structure of the c-Myc-Max heterodimeric leucine zipper." Lavigne P., Crump M.P., Gagne S.M., Hodges R.S., Kay C.M., Sykes B.D. J. Mol. Biol. 281:165-181(1998) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 402-434 IN COMPLEX WITH MAX.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

Wikipedia

Myc entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L00058, L00057 Genomic DNA. Translation: AAA59882.1.
K00535, K00534 Genomic DNA. Translation: AAA59880.1.
K00535, K00534 Genomic DNA. Translation: ABW69847.1.
X00196, X00198 Genomic DNA. Translation: CAA25015.2.
X00364 Genomic DNA. Translation: CAA25106.1.
V00568 mRNA. Translation: CAA23831.1.
K01906, K01905 Genomic DNA. Translation: AAA59881.1.
K02276 mRNA. Translation: AAA36340.1.
X00676 Genomic DNA. Translation: CAA25288.1.
D10493 Genomic DNA. Translation: BAA01374.2.
D10493 Genomic DNA. Translation: BAA01375.1.
BT019768 mRNA. Translation: AAV38573.1.
AY214166 Genomic DNA. Translation: AAO21131.1.
AK312883 mRNA. Translation: BAG35731.1.
AC103819 Genomic DNA. No translation available.
CH471060 Genomic DNA. Translation: EAW92098.1.
BC000141 mRNA. Translation: AAH00141.2.
BC000917 mRNA. Translation: AAH00917.2.
BC058901 mRNA. Translation: AAH58901.2.
M13929 mRNA. Translation: AAA88092.1.

IPI

IPI00033016.
IPI00935431.

PIR

TVHUM. A01349.
TVHUT. A01350.

RefSeq

NP_002458.2. NM_002467.4.

UniGene

Hs.202453.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A93	NMR	-	A	406-434	[»]
1EE4	X-ray	2.10	C/D/E/F	320-328	[»]
1MV0	NMR	-	A	55-68	[»]
1NKP	X-ray	1.80	A/D	353-434	[»]
2A93	NMR	-	A	406-434	[»]

DisProt

DP00260.

ProteinModelPortal

P01106.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-28143N.

IntAct

P01106. 655 interactions.

MINT

MINT-257327.

STRING

9606.ENSP00000367207.

PTM databases

GlycoSuiteDB

P01106.

PhosphoSite

P01106.

Polymorphism databases

DMDM

127619.

2D gel databases

SWISS-2DPAGE

P01106.

Proteomic databases

PaxDb

P01106.

PRIDE

P01106.

Protocols and materials databases

DNASU

4609.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000377970; ENSP00000367207; ENSG00000136997.

GeneID

4609.

KEGG

hsa:4609.

UCSC

uc003ysi.3. human.
uc022bbe.1. human.

Organism-specific databases

CTD

4609.

GeneCards

GC08P128748.

H-InvDB

HIX0007784.

HGNC

HGNC:7553. MYC.

HPA

CAB000084.
CAB010307.

MIM

113970. phenotype.
190080. gene.

neXtProt

NX_P01106.

Orphanet

543. Burkitt lymphoma.

PharmGKB

PA31353.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG42590.

HOGENOM

HOG000043075.

HOVERGEN

HBG000472.

InParanoid

P01106.

KO

K04377.

PhylomeDB

P01106.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000136997-MONOMER.

Pathway_Interaction_DB

wnt_canonical_pathway. Canonical Wnt signaling pathway.
ceramidepathway. Ceramide signaling pathway.
foxm1pathway. FOXM1 transcription factor network.
il2_pi3kpathway. IL2 signaling events mediated by PI3K.
il2_stat5pathway. IL2 signaling events mediated by STAT5.
il2_1pathway. IL2-mediated signaling events.
il6_7pathway. IL6-mediated signaling events.
pdgfrbpathway. PDGFR-beta signaling pathway.
ps1pathway. Presenilin action in Notch and Wnt signaling.
smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.
telomerasepathway. Regulation of Telomerase.

Reactome

REACT_111102. Signal Transduction.
REACT_71. Gene Expression.

SignaLink

P01106.

Gene expression databases

ArrayExpress

P01106.

Bgee

P01106.

CleanEx

HS_MYC.

Genevestigator

P01106.

GermOnline

ENSG00000136997. Homo sapiens.

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

BindingDB

P01106.

ChEMBL

CHEMBL1250348.

ChiTaRS

MYC. human.

EvolutionaryTrace

P01106.

GenomeRNAi

4609.

NextBio

17740.

SOURCE

Search...

Entry information

Entry name

MYC_HUMAN

Accession

Primary (citable) accession number: P01106
Secondary accession number(s): A8WFE7, P01107, Q14026

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	August 13, 1987
Last modified:	May 29, 2013
This is version 180 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.