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MYC (MYC proto-oncogene, bHLH transcription factor)

Written2000-08Niels B Atkin
Department of Cancer Research, Mount Vernon Hospital, Northwood, Middlesex, UK
Updated2017-08Anwar N Mohamed
Cytogenetics Laboratory, Pathology Department, Detroit Medical Center, Wayne State University School of Medicine, Detroit, MI USA; amohamed@dmc.org

Abstract Review the structure, function, and role of CMYC gene in tumorigenesis

Keywords MYC; CMYC; MYC signature; transcription factor; Burkitt lymphoma; diffuse large B-cell lymphoma; follicular lymphoma; mantle cell lymphoma; multiple myeloma; lung cancer; breast cancer; colon cancer ; prostate cancer

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)c-Myc
bHLHe39
MYCC
Other aliasCMYC
MYC proto-oncogene
V-MYC avian myelocytomatosis viral oncogene homolog
Class E Basic Helix-Loop-Helix Protein 39
Transcription Factor P64
BHLHe39
HGNC (Hugo)
LocusID (NCBI) 4609
Atlas_Id 27
Location 8q24.21  [Link to chromosome band 8q24]
Location_base_pair Starts at 127736069 and ends at 127741434 bp from pter ( according to hg19-Feb_2009)  [Mapping MYC.png]
 
  MYC (8q24) in normal cells: PAC 944B18 (top) and PAC 968N11 (below) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
 
  FISH using MYC/IGH/CEP8 triple color dual fusion DNA probe set, showing dual fusion pattern, consistent with t(8;14)(q24;q32) [left] in a case with Burkitt lymphoma; MYC amplification in acute myeloid leukemia [right] - Anwar N. Mohamed.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
BCL3 (19q13.32) / MYC (8q24.21)BCL6 (3q27.3) / MYC (8q24.21)BCL7A (12q24.31) / MYC (8q24.21)
BTG1 (12q21.33) / MYC (8q24.21)C2CD5 (12p12.1) / MYC (8q24.21)CLPSL1 (6p21.31) / MYC (8q24.21)
COL26A1 (7q22.1) / MYC (8q24.21)CSMD3 (8q23.3) / MYC (8q24.21)CTTN (11q13.3) / MYC (8q24.21)
GID4 (17p11.2) / MYC (8q24.21)HFE2 (1q21.1) / MYC (8q24.21)HMGN2P46 (15q21.1) / MYC (8q24.21)
JCHAIN (4q13.3) / MYC (8q24.21)LRMP (12p12.1) / MYC (8q24.21)MIR142 (17q22) / MYC (8q24.21)
MYC (8q24.21) / AP5M1 (14q22.3)MYC (8q24.21) / ARHGEF17 (11q13.4)MYC (8q24.21) / BCL6 (3q27.3)
MYC (8q24.21) / BCL7A (12q24.31)MYC (8q24.21) / BTG1 (12q21.33)MYC (8q24.21) / MYC (8q24.21)
MYC (8q24.21) / MYCL (1p34.2)MYC (8q24.21) / RCC1 (1p35.3)MYC (8q24.21) / SUPT3H (6p21.1)
MYC (8q24.21) / ZBTB5 (9p13.2)MYC (8q24.21) / ZCCHC7 (9p13.2)MYC (8q24.21) / ZFP36 (19q13.2)
PVT1 (8q24.21) / MYC (8q24.21)RARRES3 (11q12.3) / MYC (8q24.21)RCC1 (1p35.3) / MYC (8q24.21)
RNF213 (17q25.3) / MYC (8q24.21)SDF4 (1p36.33) / MYC (8q24.21)SPATA48 (7p12.2) / MYC (8q24.21)
STPG1 (1p36.11) / MYC (8q24.21)UBC (12q24.31) / MYC (8q24.21)
Note MYC gene encodes a multifunctional, nuclear phosphoprotein that controls a variety of cellular functions, including cell cycle, cell growth, apoptosis, cellular metabolism and biosynthesis, adhesion, and mitochondrial biogenesis. MYC has been shown to be an essential global transcription factor capable of either promoting or repressing the expression of a massive array of genes, accounting for >15% of the human genome, commonly referred to as the "MYC signature" (Knoepfler 2007). MYC is among the most frequently affected gene in human cancers, overexpressed in most human cancers and contributes to the cause of at least 40% of tumors. Dysregulation of MYC expression results through various types of genetic alterations leading to a constitutive activity of MYC in various cancers (Dang et al, 2006).

DNA/RNA

Description CMYC is composed of three exons spanning over 4 kb with the second and third exons encoding most MYC protein. These two exons have at least 70% sequence homology among species. However, exon1 is untranslated whose sequence is not as well conserved through evolution. The exon1 has been postulated to play a role in translational control and mRNA stability. There are four MYC transcriptional promoters. In normal cells, promoter P2 contributes to approximately 75% of total MYC transcripts while P1 accounts for most the remaining 25% transcripts (Dang CV 2012).
Transcription MYC mRNA contains an IRES (internal ribosome entry site) that allows the RNA to be translated into protein when 5' cap-dependent translation is inhibited, such as during viral infection.

Protein

Description 439 amino acids and 48 kDa in the p64; 454 amino acids in the p67 (15 additional amino acids in N-term; contains from N-term to C-term: a transactivation domain, an acidic domain, a nuclear localization signal, a basic domain, an helix-loop-helix motif, and a leucin zipper; DNA binding protein.
Expression Expressed in almost all proliferating cells in embryonic and adult tissues; in adult tissues, expression correlates with cell proliferation; abnormally high expression is found in a wide variety of human cancers.
Localisation located predominantly in the nucleus.
The myc protein contains an unstructured N-terminal transcriptional regulatory domain followed by a nuclear localization signal and a C-terminal region with a basic DNA-binding domain tied to a helix-loop-helix-leucine zipper (bHLHZip) dimerization motif. The bHLHzip motif of MYC dimerizes with the MAX, which is a prerequisite for specific binding to DNA at E-box sequences (5'-CA(C/T)G(T/C)G-3') (Dang 2012). Upon DNA binding the MYC/MAX heterodimer recruits co-factors, which mediate multiple effects of MYC on gene expression in a context-dependent manner. This dimerization process is essential for induction of cell cycle progression, apoptosis, and transformation suggesting that MYC exerts its oncogenic effects by transactivation of target genes via E-boxes (Amati B, Land H, 1994; Grandori C et al 2000). The coding exons of MYC encode for the N-terminal region which has a transcriptional regulatory domain, a region that contains conserved MYC Boxes I and II, followed by MYC Box III and IV, and a nuclear targeting sequence. The N-terminal region will bind with co-activator complexes, making MYC acts as the transcription or repression factor (Cowling et al 2006).
In normal cells, MYC is tightly regulated by mitotic and developmental signals, and in turn, it regulates the expression of downstream target genes. Both MYC mRNA and protein have very short half-lives in normal cells (20-30 minutes each). Without appropriate positive regulatory signals, MYC protein levels are low and insufficient to promote cellular proliferation. In addition, MYC protein is rapidly degraded by the ubiquitin-linked proteasome machinery. The short-life and instability of MYC protein and mRNA together would seem to be an effective safeguard mechanism of MYC regulation (Herrick and Ross et al, 1994). However, these controls are lost in cancer cells, resulting in aberrantly high levels of MYC protein. In its physiological role, MYC is broadly expressed during embryogenesis and in tissue with high proliferative capacity such as skin epidermis and gut. Its expression strongly correlates with cell proliferation.
Function MYC functions as a transcriptional regulator, capable to induce or repress the expression of a large number of genes, which are thought to mediate its biological functions (Adhikary and Eilers 2005). MYC protein cannot form homodimers, but it binds to MAX that is an obligate heterodimeric partner for MYC in mediating its functions. The MYC-MAX complex is a potent activator of transcription for a critical set of cellular target genes. Initially, two additional partners for Max had been identified, MXI1 and MXD1 (Mad1). Two more Max-interacting proteins, MXD3 (Mad3) and MXD4 (Mad4), which behave similarly to MXD1 have been reported. The transcription activation is mediated exclusively by MYC-MAX complexes, whereas MAX-MXD1 and MAX-MXI1 complexes mediate transcription repression through identical binding sites. Max expression is not highly regulated and its protein is very stable; in contrast, MXD1 protein appears to have a short half-life and to be highly regulated (Amati and Land, 1994). MXI1 protein is also regulated. MYC-MAX heterodimers activate transcription through interactions with transcriptional coactivators ( TRRAP, ACTL6A (BAF53)) and their associated histone acetyltransferases and/or ATPase/helicases, resulting in transition from the G0/1 phase to the S phase (Nilsson and Cleveland, 2003). Several studies have established that MAX is essential for MYC-mediated gene transactivation, transformation, cell cycle progression and apoptosis. On the other hand, overexpression of MXI1 and MXD1 can antagonize MYC activity in cellular transformation assays and proliferation and can diminish the malignant phenotype of tumor cells. MXD1 can also inhibit apoptosis and reverse the differentiation blocking effect of MYC in leukemia cells. (Dang 2012). These findings are consistent with the concept that MXD1 and MXI1 suppress MYC function. In addition to interacting with proteins involved in transcription regulation, MYC also interacts with enzymes controlling histone methylation.
Target Genes Thousands of MYC target genes have been identified by following mRNA levels in experimentally controlled activation of the MYC gene (Menssen and Hermeking 2002). In general, genes targeted by MYC include mediators of metabolism, biosynthesis, and cell cycle progression, such that aberrant MYC expression is associated with uncontrolled cell growth, division, and metastasis, whereas loss or inhibition of MYC expression hinders growth, promotes differentiation, and sensitizes cells to DNA damage (Miller 2012; Hsieh 2015). Different target genes are regulated under specific conditions for specific cell types. Some of the most biologically important targets are CCND2 (cyclin D2), and cyclin-dependent kinases (CDKs), resulting in accelerated cell cycling; down-regulation of PTEN (phosphatase and tensin homolog deleted on chromosome ten) with consequent up-regulation of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/ MTOR) pathway; and stabilization of the proapoptotic protein and tumor suppressor TP53, (Hoffman and Liebermann 2008; Dang 2012) which can bypass the apoptotic BCL2 program. MYC, on the other hand, activates many ribosomal protein genes including RPL23, which binds to and retains NPM1 in the nucleolus, thereby inhibiting PIAS2 (Miz-1) activity (Wanzel, 2008). MYC itself is modulated by NPM1, which acts as a positive MYC coactivator (Schneider A 1997; Grandori C et al., 2005; Li Z, et al 2008).
MYC-targeted gene network also contains non-protein coding targets; among those are microRNAs (miRNAs). The miRNAs are 18- 22 nucleotides non-coding RNAs that negatively regulate gene expression at the post-transcriptional level via binding to 3'-UTRs of target mRNAs and mediate translational repression or mRNA degradation. Some miRNA function as an oncogene while others behave as tumor suppressor gene, in a cell-typed manner. Growing evidences have suggested that MYC regulates the expression of a number of miRNAs, resulting in widespread repression of miRNA and, at the same time, MYC being subjected to regulation by miRNAs, leading to sustained MYC activity and the corresponding MYC downstream pathways (Chang et al, 2008). Thus, these combined effects of MYC overexpression and downregulation of miRNAs play a central regulatory role in the MYC oncogenic pathways. For example, MYC upregulates expression of miR-17-92 clusters a set of oncogenic miRNAs, which contains six mature miRNAs. Recently, miR-19 was identified as the key oncogenic component of this cluster (Tao et al 2014; Koh 2016). Overexpression of miR-17-92 is observed in a large fraction of human cancers, including carcinomas of the breast, lung, and colon; medulloblastomas; neuroblastomas and B-cell lymphoma. The miR17-92 is commonly amplified at 13q31 in several subtypes of aggressive lymphomas. Its oncogenic function is reflected by down-regulation of PTEN, TP53 and E2F1, causing the activation of the PI3K/AKT pathway and inhibiting cellular apoptosis. The functional interaction between miR-17`92 and MYC is further emphasized by the finding that MYC is a potent transcriptional activator of miR-17-92 (O'Donnell et al. 2005), thus suggesting that miR-17-92 may contribute to the oncogenic properties of MYC. Another MYC-induced miRNA, MIR22, was recently shown to act as a potent proto-oncogenic miRNA by genome-wide deregulation of the epigenetic state through inhibition of methylcytosine dioxygenase TET proteins. In addition, MIR22 was characterized as a key regulator of self-renewal in the hematopoietic system. MYC also represses several miRNAs with tumor suppressor function such as MIR15A/ MIR16-1 and miR-34 that regulate apoptosis by targeting BCL2 and TP53 respectively. Likewise MYC is negatively regulated by several miRNAs such as miR-34 and MIR494. The auto functional interaction between MYC and miRNAs target genes maintains persistent expression of MYC, thus promoting the malignant phenotype (Tao et al 2014; Jackstadt 2015).
Furthermore, over expression of MYC can induce apoptosis. The apoptosis triggered or sensitized by MYC can be either TP53-dependent or TP53 independent, determined by the cell type and apoptotic trigger. The mechanisms of MYC-mediated apoptosis may involve several pathways. Overexpression of MYC increases DNA replication and possibly results in DNA damage that, in turn, triggers a TP53-mediated response leading to apoptosis, in some cell types (Hoffman and Libermann, 2008). As well, MYC expression seems to downregulate antiapoptotic proteins such as BCL2 or BCL2L1 (Bcl-XL) and upregulate pro-apoptotic elements such as BCL2L11 (BIM).
MYC also plays an important role in mitochondrial biogenesis. Large scale studies of gene expression in rat and human systems first suggested that MYC overexpression can induce nuclear encoded mitochondrial genes. In addition, MYC has been shown to bind to the promoters of genes encoding proteins involved in mitochondrial function. Using an inducible MYC-dependent human B cell model of cell proliferation it was shown that mitochondrial biogenesis is completely dependent on MYC expression. Moreover, the genes involved with mitochondrial biogenesis are among the MYC target genes most highly induced (Gao et al 2009).

Implicated in

Note MYC Deregulation
The expression of MYC is deregulated in cancer by several different mechanisms, including chromosomal translocations, amplifications, point mutations, epigenetic reprogramming, enhanced translation and increased protein stability. In most cases these alterations lead to a constitutive expression of intact MYC protein, which is normally only expressed during certain phases of the cell cycle. In Burkitt lymphoma (BL), the MYC oncogene is activated through a reciprocal t(8;14) or its variant which juxtaposes MYC/8q24 to enhancer of the immunoglobulin (Ig) heavy Chain (IGH) locus on chromosome 14q32 or the kappa or lambda light chain locus on chromosome 2 or 22. There are three main translocation breakpoints in MYC; class I breakpoints are within the exon 1 and first intron of MYC; class II breakpoints are located at the 5' end of the MYC, and usually within a few kilobases of exon 1; and the class III breakpoints are distant from MYC itself, and can be more than 100 kb away. Endemic BL typically shows class II translocation breakpoints in MYC while the sporadic BL often exhibits class I breakpoints of MYC. The t(8;14) or its variant is considered as an initiative event in BL. The MYC/8q24 translocations may also occur as secondary events in non-BL lymphomas such as diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and multiple myeloma (Cai et al, 2015; Nguyen L, et al 2017). Secondary MYC translocation is associated with a complex karyotype and most often confer aggressive clinical behavior and poor outcome. Recently, B-cell large cell lymphoma with MYC and BCL2 or/and BCL6 rearrangements so called double hit or triple hit lymphoma are recognized by the 2016 revision of WHO as a subset of a very aggressive lymphoma (Petrich 2014). >
Amplification of MYC gene has been shown in both hematopoietic and non-hematopoietic tumors, including lung, breast, colon, and prostate cancers. Insertional mutagenesis is seen in retrovirus-induced tumors, such as avian leucosis virus (ALV)-induced hematopoietic tumors, in which the proviral enhancer is integrated upstream of the MYC gene and leads to its overexpression. MYC overexpression may also occur because of post-translational modifications. MYC protein overexpression as a result of point mutations in N-terminal domain is also frequent. The most recurrently mutated residue is Thr-58, found in lymphoma. Normally, the phosphorylation of Thr-58 can control MYC degradation and mutation causing increase of MYC protein half-life in lymphoma (Cai et al 2017). Detection of MYC rearrangement is important in the diagnosis of BL and as a prognostic marker in other aggressive B-cell lymphomas. There are several techniques to detect MYC deregulation including conventional cytogenetics, fluorescence in situ hybridization (FISH), and immunohistochemistry. In clinical laboratory, FISH is being most frequently used approach (Figure 2) >
MYC as therapeutic target
MYC is documented to be involved broadly in many cancers, in which its expression is estimated to be elevated or deregulated in up to 70% of human cancers. Overexpression of MYC protein is not only to drive tumor initiation and progression, but is also essential for tumor maintenance. Furthermore, growth arrest, apoptosis and differentiation occur upon reduction in MYC levels. These features make MYC molecule a highly attractive target for cancer therapy. However, the lack of deep pocket in the structure of MYC protein makes the traditionally small molecule inhibitors are not feasible. For this reason, other alternative strategies are proposed. One approach suggests that the disruption of the MYC/MAX binding site can be a strategy for the inactivation of MYC function in neoplastic cells. Such an approach was already applied and different small molecule inhibitors that can specifically target MYC were already successfully produced. Other approach is based on the inhibition of MYC/MAX dimers binding to E-boxes in the promoters of different MYC target genes. Other groups have focused on transcriptional inhibition of the MYC gene. Preliminary evidence from experiments using MYC antisense oligonucleotides has been encouraging, but has not translated into effective clinical treatments ( Koh 2016).
  

Breakpoints

 

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Citation

This paper should be referenced as such :
Mohamed AN
MYC (MYC proto-oncogene, bHLH transcription factor);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/MYCID27.html
History of this paper:
Atkin, NB. MYC (v-myc myelocytomatosis viral oncogene homolog (avian)). Atlas Genet Cytogenet Oncol Haematol. 2000;4(4):181-182.
http://documents.irevues.inist.fr/bitstream/handle/2042/37661/08-2000-MYCID27.pdf


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 44 ]
  3q27 rearrangements (BCL6) in non Hodgkin lymphoma::t(3;Var)(q27;Var) in non Hodgkin lymphoma
Classification of B-cell non-Hodgkin lymphomas (NHL)
B-cell prolymphocytic leukemia (B-PLL)
Burkitt's lymphoma (BL)
Classical Hodgkin lymphoma
Chronic myelogenous leukaemia (CML)
dic(9;12)(p13;p13) PAX5/ETV6
Double Hit Lymphoma (DHL)::Triple Hit Lymphoma (THL)
Hodgkin lymphoma
B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma
t(7;14)(q35;q32.1) TRB/TCL1A::inv(14)(q11q32.1) TRA-TRD/TCL1A::t(14;14)(q11;q32.1) TRA-TRD/TCL1A
HIV-associated lymphomas
MLL amplification in leukemia
Monomorphic PTLD (B- and T/NK-cell types)
Multiple Myeloma
Nodular lymphocyte-predominant Hodgkin lymphoma
Pediatric-type Follicular Lymphoma
Plasmablastic lymphoma (PBL)
Plasma cell leukemia (PCL)
r(8)
t(1;8)(p11-13;q24)
t(1;8)(p21-22;q24)
t(2;8)(p15;q24) BCL11A/MYC
t(3;6)(q27;p21) PIM1/BCL6
t(3;8)(q26;q24) PVT1/MECOM
t(3;8)(q27;q24) BCL6/MYC
t(3;12)(q27;p12) LRMP/BCL6
t(5;11)(q33;p13) CAPRIN1/PDGFRB
t(6;20)(q15;q11.2) BACH2/BCL2L1
t(7;8)(p12;q24) /MYC
t(8;9)(q24;p13) ?/MYC
t(8;12)(q24;p12) LRMP/MYC
t(8;12)(q24;q22) BTG1/MYC
t(8;14)(q24;q32) IGH/MYC::t(2;8)(p12;q24) IGK/MYC::t(8;22)(q24;q11) IGL/MYC
t(8;14)(q24;q11) TRA/MYC
t(8;17)(q24;q22) ???BCL3/MYC
t(9;10)(q34;q22) ZMIZ1/ABL1
der(X)t(X;8)(q28;q11.2)
t(14;15)(q32;q11) IGH/NBEAP1
t(14;19)(q32;p13) IGH/EPOR::t(14;19)(q32;p13) IGH/BRD4 ?
t(17;20)(q21;q11)
t(3;11)(q13.13;q23) KMT2A/KIAA1524
T-cell/histiocyte rich large B-cell lymphoma
Histiocyte-rich B-cell lymphoma


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 34 ]
  Bone: Aneurysmal bone cysts
Nervous system: Astrocytic tumors
Esophagus: Barrett's esophagus, dysplasia and adenocarcinoma
Bladder: Urothelial carcinomas
Bone: Angiosarcoma
Bone tumors: an overview
Breast tumors : an overview
Bone: Chondrosarcoma
Colon: Colorectal adenocarcinoma
Bone: Conventional Osteosarcoma
Breast: Ductal carcinoma
Fallopian tube tumors: an overview
Gastric Tumors: an overview
Liver: Hepatocellular carcinoma
Head and Neck: Laryngeal squamous cell carcinoma
Liver tumors: an overview
Lung: Non-small cell carcinoma
Lung: small cell cancer
Male breast cancer
Testis: Germ cell tumors
Head and Neck: Oral squamous cell carcinoma
Bone: Osteosarcoma
Ovarian tumours : an overview
Ovary: Sex cord-stromal tumors
Ovary: Choriocarcinoma
Ovary: Epithelial tumors
Prostate tumors: an overview
Skin: Melanoma
Soft tissue tumors: an overview
Bone: Aneurysmal bone cyst with t(3;17)(q21;p13) CNBP/USP6
Lung: Translocations in Small Cell Carcinoma
Uterus Tumours: an Overview
Eye: Posterior uveal melanoma
Bone: Vascular Tumors


External links

Nomenclature
HGNC (Hugo)MYC   7553
Cards
AtlasMYCID27
Entrez_Gene (NCBI)MYC  4609  MYC proto-oncogene, bHLH transcription factor
AliasesMRTL; MYCC; bHLHe39; c-Myc
GeneCards (Weizmann)MYC
Ensembl hg19 (Hinxton)ENSG00000136997 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000136997 [Gene_View]  chr8:127736069-127741434 [Contig_View]  MYC [Vega]
ICGC DataPortalENSG00000136997
TCGA cBioPortalMYC
AceView (NCBI)MYC
Genatlas (Paris)MYC
WikiGenes4609
SOURCE (Princeton)MYC
Genetics Home Reference (NIH)MYC
Genomic and cartography
GoldenPath hg38 (UCSC)MYC  -     chr8:127736069-127741434 +  8q24.21   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)MYC  -     8q24.21   [Description]    (hg19-Feb_2009)
EnsemblMYC - 8q24.21 [CytoView hg19]  MYC - 8q24.21 [CytoView hg38]
Mapping of homologs : NCBIMYC [Mapview hg19]  MYC [Mapview hg38]
OMIM113970   190080   
Gene and transcription
Genbank (Entrez)AA807892 AK303921 AK312883 BC000141 BC000917
RefSeq transcript (Entrez)NM_002467
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)MYC
Cluster EST : UnigeneHs.202453 [ NCBI ]
CGAP (NCI)Hs.202453
Alternative Splicing GalleryENSG00000136997
Gene ExpressionMYC [ NCBI-GEO ]   MYC [ EBI - ARRAY_EXPRESS ]   MYC [ SEEK ]   MYC [ MEM ]
Gene Expression Viewer (FireBrowse)MYC [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)4609
GTEX Portal (Tissue expression)MYC
Human Protein AtlasENSG00000136997-MYC [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP01106   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP01106  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP01106
Splice isoforms : SwissVarP01106
PhosPhoSitePlusP01106
Domaine pattern : Prosite (Expaxy)BHLH (PS50888)   
Domains : Interpro (EBI)bHLH_dom    Myc-LZ    Tscrpt_reg_Myc    Tscrpt_reg_Myc_N   
Domain families : Pfam (Sanger)HLH (PF00010)    Myc-LZ (PF02344)    Myc_N (PF01056)   
Domain families : Pfam (NCBI)pfam00010    pfam02344    pfam01056   
Domain families : Smart (EMBL)HLH (SM00353)  
Conserved Domain (NCBI)MYC
DMDM Disease mutations4609
Blocks (Seattle)MYC
PDB (SRS)1A93    1EE4    1MV0    1NKP    2A93    2OR9    4Y7R    5I4Z    5I50   
PDB (PDBSum)1A93    1EE4    1MV0    1NKP    2A93    2OR9    4Y7R    5I4Z    5I50   
PDB (IMB)1A93    1EE4    1MV0    1NKP    2A93    2OR9    4Y7R    5I4Z    5I50   
PDB (RSDB)1A93    1EE4    1MV0    1NKP    2A93    2OR9    4Y7R    5I4Z    5I50   
Structural Biology KnowledgeBase1A93    1EE4    1MV0    1NKP    2A93    2OR9    4Y7R    5I4Z    5I50   
SCOP (Structural Classification of Proteins)1A93    1EE4    1MV0    1NKP    2A93    2OR9    4Y7R    5I4Z    5I50   
CATH (Classification of proteins structures)1A93    1EE4    1MV0    1NKP    2A93    2OR9    4Y7R    5I4Z    5I50   
SuperfamilyP01106
Human Protein Atlas [tissue]ENSG00000136997-MYC [tissue]
Peptide AtlasP01106
HPRD01818
IPIIPI00935431   IPI00033016   IPI00816223   IPI00977922   IPI00026900   IPI00425663   IPI00796046   IPI00973947   
Protein Interaction databases
DIP (DOE-UCLA)P01106
IntAct (EBI)P01106
FunCoupENSG00000136997
BioGRIDMYC
STRING (EMBL)MYC
ZODIACMYC
Ontologies - Pathways
QuickGOP01106
Ontology : AmiGOG1/S transition of mitotic cell cycle  negative regulation of transcription from RNA polymerase II promoter  MAPK cascade  RNA polymerase II core promoter proximal region sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding  branching involved in ureteric bud morphogenesis  positive regulation of mesenchymal cell proliferation  DNA binding  DNA binding  transcription factor activity, sequence-specific DNA binding  protein binding  nucleus  nucleoplasm  nucleoplasm  nucleolus  cytosol  energy reserve metabolic process  chromatin remodeling  regulation of transcription from RNA polymerase II promoter  transcription from RLA pomyeerase II promoter  cellular iron ion homeostasis  cellular response to DNA damage stimulus  cell cycle arrest  Notch signaling pathway  transcription factor binding  positive regulation of cell proliferation  response to gamma radiation  regulation of gene expression  positive regulation of gene expression  positive regulation of gene expression  oxygen transport  protein deubiquitination  regulation of telomere maintenance  protein complex binding  negative regulation of stress-activated MAPK cascade  protein-DNA complex disassembly  activating transcription factor binding  cellular response to UV  cellular response to drug  response to drug  negative regulation of apoptotic process  protein complex  positive regulation of cysteine-type endopeptidase activity involved in apoptotic process  fibroblast apoptotic process  negative regulation of monocyte differentiation  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  protein dimerization activity  positive regulation of fibroblast proliferation  positive regulation of fibroblast proliferation  negative regulation of fibroblast proliferation  positive regulation of epithelial cell proliferation  chromosome organization  negative regulation of cell division  positive regulation of telomerase activity  canonical Wnt signaling pathway  ERK1 and ERK2 cascade  repressing transcription factor binding  response to growth factor  E-box binding  cellular response to hypoxia  positive regulation of metanephric cap mesenchymal cell proliferation  beta-catenin-TCF complex assembly  positive regulation of DNA biosynthetic process  positive regulation of response to DNA damage stimulus  
Ontology : EGO-EBIG1/S transition of mitotic cell cycle  negative regulation of transcription from RNA polymerase II promoter  MAPK cascade  RNA polymerase II core promoter proximal region sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding  branching involved in ureteric bud morphogenesis  positive regulation of mesenchymal cell proliferation  DNA binding  DNA binding  transcription factor activity, sequence-specific DNA binding  protein binding  nucleus  nucleoplasm  nucleoplasm  nucleolus  cytosol  energy reserve metabolic process  chromatin remodeling  regulation of transcription from RNA polymerase II promoter  transcription from RNA polymerase II promoter  cellular iron ion homeostasis  cellular response to DNA damage stimulus  cell cycle arrest  Notch signaling pathway  transcription factor binding  positive regulation of cell proliferation  response to gamma radiation  regulation of gene expression  positive regulation of gene expression  positive regulation of gene expression  oxygen transport  protein deubiquitination  regulation of telomere maintenance  protein complex binding  negative regulation of stress-activated MAPK cascade  protein-DNA complex disassembly  activating transcription factor binding  cellular response to UV  cellular response to drug  response to drug  negative regulation of apoptotic process  protein complex  positive regulation of cysteine-type endopeptidase activity involved in apoptotic process  fibroblast apoptotic process  negative regulation of monocyte differentiation  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  protein dimerization activity  positive regulation of fibroblast proliferation  positive regulation of fibroblast proliferation  negative regulation of fibroblast proliferation  positive regulation of epithelial cell proliferation  chromosome organization  negative regulation of cell division  positive regulation of telomerase activity  canonical Wnt signaling pathway  ERK1 and ERK2 cascade  repressing transcription factor binding  response to growth factor  E-box binding  cellular response to hypoxia  positive regulation of metanephric cap mesenchymal cell proliferation  beta-catenin-TCF complex assembly  positive regulation of DNA biosynthetic process  positive regulation of response to DNA damage stimulus  
Pathways : BIOCARTA [Genes]   
Pathways : KEGG   
REACTOMEP01106 [protein]
REACTOME PathwaysR-HSA-8866911 [pathway]   
NDEx NetworkMYC
Atlas of Cancer Signalling NetworkMYC
Wikipedia pathwaysMYC
Orthology - Evolution
OrthoDB4609
GeneTree (enSembl)ENSG00000136997
Phylogenetic Trees/Animal Genes : TreeFamMYC
HOVERGENP01106
HOGENOMP01106
Homologs : HomoloGeneMYC
Homology/Alignments : Family Browser (UCSC)MYC
Gene fusions - Rearrangements
Fusion : MitelmanBCL3/MYC [19q13.32/8q24.21]  [t(8;19)(q24;q13)]  
Fusion : MitelmanBTG1/MYC [12q21.33/8q24.21]  [t(8;12)(q24;q22)]  
Fusion : MitelmanCSMD3/MYC [8q23.3/8q24.21]  [t(8;8)(q23;q24)]  
Fusion : MitelmanHMGN2P46/MYC [15q21.1/8q24.21]  [t(8;15)(q24;q21)]  
Fusion : MitelmanIGH/MYC [14q32.33/8q24.21]  [t(6;8;14)(p21;q24;q32)]  [t(8;14)(q24;q32)]  
[t(8;14;18)(q24;q32;q21)]  
Fusion : MitelmanIGK/MYC [2p11.2/8q24.21]  [t(2;8)(p11;q24)]  
Fusion : MitelmanIGL/MYC [22q11.22/8q24.21]  [t(8;22)(q24;q11)]  
Fusion : MitelmanLRMP/MYC [12p12.1/8q24.21]  [t(8;12)(q24;p12)]  
Fusion : MitelmanMYC/ARHGEF17 [8q24.21/11q13.4]  [t(8;11)(q24;q13)]  
Fusion : MitelmanMYC/BCL7A [8q24.21/12q24.31]  [t(8;14;12)(q24;q32;q24)]  
Fusion : MitelmanMYC/ZBTB5 [8q24.21/9p13.2]  [t(8;9)(q24;p13)]  
Fusion : MitelmanMYC/ZCCHC7 [8q24.21/9p13.2]  [t(8;9)(q24;p13)]  
Fusion : MitelmanPVT1/MYC [8q24.21/8q24.21]  [t(8;8)(q24;q24)]  
Fusion : MitelmanRNF213/MYC [17q25.3/8q24.21]  [t(8;17)(q24;q25)]  
Fusion : MitelmanTRA/MYC [-/8q24.21]  [t(8;14)(q24;q11)]  
Fusion : TICdbIg [MYC]  -  8q24.21 []
Fusion : TICdbMIR142 [17q22]  -  MYC [8q24.21]
Fusion : TICdbMYC [8q24.21]  -  Ig []
Fusion Cancer (Beijing)ENSG00000211894 [MYC]  -  8q24.21 [FUSC000227]  [FUSC000227]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerMYC [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MYC
dbVarMYC
ClinVarMYC
1000_GenomesMYC 
Exome Variant ServerMYC
ExAC (Exome Aggregation Consortium)ENSG00000136997
GNOMAD BrowserENSG00000136997
Genetic variants : HAPMAP4609
Genomic Variants (DGV)MYC [DGVbeta]
DECIPHERMYC [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisMYC 
Mutations
ICGC Data PortalMYC 
TCGA Data PortalMYC 
Broad Tumor PortalMYC
OASIS PortalMYC [ Somatic mutations - Copy number]
Cancer Gene: CensusMYC 
Somatic Mutations in Cancer : COSMICMYC  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDMYC
intOGen PortalMYC
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch MYC
DgiDB (Drug Gene Interaction Database)MYC
DoCM (Curated mutations)MYC (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)MYC (select a term)
intoGenMYC
NCG5 (London)MYC
Cancer3DMYC(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM113970    190080   
Orphanet3747    14434   
MedgenMYC
Genetic Testing Registry MYC
NextProtP01106 [Medical]
TSGene4609
GENETestsMYC
Target ValidationMYC
Huge Navigator MYC [HugePedia]
snp3D : Map Gene to Disease4609
BioCentury BCIQMYC
ClinGenMYC
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD4609
Chemical/Pharm GKB GenePA31353
Drug Sensitivity MYC
Clinical trialMYC
Miscellaneous
canSAR (ICR)MYC (select the gene name)
Probes
Litterature
PubMed499 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineMYC
EVEXMYC
GoPubMedMYC
iHOPMYC
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Oct 12 16:28:18 CEST 2017

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