This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.

Uniprot Accession Number: P01106

Protein Sequence

>gi|71774083|ref|NP_002458.2| myc proto-oncogene protein [Homo sapiens]
MDFFRVVENQQPPATMPLNVSFTNRNYDLDYDSVQPYFYCDEEENFYQQQQQSELQPPAPSEDIWKKFEL
LPTPPLSPSRRSGLCSPSYVAVTPFSLRGDNDGGGGSFSTADQLEMVTELLGGDMVNQSFICDPDDETFI
KNIIIQDCMWSGFSAAAKLVSEKLASYQAARKDSGSPNPARGHSVCSTSSLYLQDLSAAASECIDPSVVF
PYPLNDSSSPKSCASQDSSAFSPSSDSLLSSTESSPQGSPEPLVLHEETPPTTSSDSEEEQEDEEEIDVV
SVEKRQAPGKRSESGSPSAGGHSKPPHSPLVLKRCHVSTHQHNYAAPPSTRKDYPAAKRVKLDSVRVLRQ
ISNNRKCTSPRSSDTEENVKRRTHNVLERQRRNELKRSFFALRDQIPELENNEKAPKVVILKKATAYILS
VQAEEQKLISEEDLLRKRREQLKHKLEQLRNSCA

The protein sequence was obtained from Entrez and is in the FASTA format.(6)

The above image is of the MYC-MAX heterodimer leucine zipper. The zipper is linked through a disulfide bond that is present at the N-termini of the protein.(5)

Protein Domain

Within the protein sequence of MYC, a helix-loop-helix (HLH-red in figure to left) domain was found to be present along with the amino terminal region (green) and a leucine zipper (yellow).(2) The HLH domain is contained between the 375 amino acid residue and the 427 residue. HLH domains consist mainly of basic residues which enables them to interact with negatively charged DNA. The HLH domain is found in eukaryotes and functions as a transcription factor in developmental pathways. The specific actions of these transcription factors is to cause a dimerization of inactive monomoers to a complex that acts in trans and enables development to continue in a highly regulated manner.(1) The presence of a leucine zipper domain is also indicative of MYC's ability to recognize and intreract with DNA. More specifically, MYC forms a heterodimer with the MAX protein. The formation of the MYC-MAX heterodimer is used to control cell growth and apoptosis and does so by interacting directly with genes that govern cell replication.(2)

MYC Inhibitor

The image to the left is the structure of a chemical compound that inhibits the interaction between the MYC and MAX complex. The compound is a thiazolidinone that is capable of permeating the cell membrane and prevents the "transactivation of c-MYC target gene expression". C-myc inhibitor is capable of inhibiting MYC directed tumor cell growth. It has been shown to work both in vitro and in vivo and makes it a useful compound for studying the functions of myc and the resulting phenotypes. (3)(4) For another example of a compound that influences MYC, please visit the Scientific Article Review page.

Comparison of Protein Structures

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Above are the protein domains for human (top), rat (middle), and mouse (bottom). The blue represents the N-terminal domain common in the MYC family. The green segment represents the helix-loop-helix domain and the orange represents the leucine zipper domain. As indicated by the phylogeny tree on the Gene Sequence page, the rat and the human are very closely related in mRNA sequence. This similarity can be seen in the protein structure of both the human and the rat. While the rat shows very close similarities in the domains it is 453 amino acids in length whereas both the human and mouse proteins are 454 amino acids in length. In evaluating the proteins domains, the differences in the mouse and the human protein seemed odd. To further investigate the gap inbetween the two N-terminal domains on the mouse protein, both the mouse and the human sequences were blasted. Below are the results that were found. (8) The query sequence is the mouse protein sequence and the subject is the human sequence. Looking at homologene, the gap between the two N-terminal domains occurred inbetween approximately 217 and 310 amino acid. (7)(8) This span of sequence (217 residue to 310 residue) was closely scrutinized. Looking at this portion of the sequence there are approximately 10 differences in amino acid residues which may be sufficient to differ the domains between the two organisms. With the rat N-terminal extending all the way through, it may be an ideal model organism to study Burkitt Lymphoma in the future.
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References:
1SMART
2Pfam
3NCBI-PubChem
4CalbioChem
5Protein Database
6Entrez
7Blast
8Homologene

Contact Info: Deeter Neumann, [email protected], May 14, 2009