MUTYH
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| MutY homolog (E. coli)
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| Image:PBB Protein MUTYH image.jpg | ||||||||||||||||||||||||||||||||||||||
| PDB rendering based on 1x51. | ||||||||||||||||||||||||||||||||||||||
| Available structures: For the file format that describes the 3D structures of molecules found in the Protein Data Bank, see Protein Data Bank (file format).
The Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. These data, typically obtained by X-ray crystallography or NMR spectroscopy, are submitted by biologists and biochemists from around the world, are released into the public domain, and can be accessed for free. HistoryFounded in 1971 by Drs. Edgar Meyer and Walter Hamilton Brookhaven National Laboratory, management of the Protein Data Bank was transferred in 1998 to members of the Research Collaboratory for Structural Bioinformatics (RCSB). The Worldwide Protein Data Bank (wwPDB) consists of organizations that act as deposition, data processing and distribution centers for PDB data. The founding members are RCSB PDB (USA), MSD-EBI (Europe) and PDBj (Japan). The BMRB (USA) group joined the wwPDB in 2006. The mission of the wwPDB is to maintain a single Protein Data Bank Archive of macromolecular structural data that is freely and publicly available to the global community. The PDB is a key resource in structural biology and is critical to more recent work in structural genomics. Countless derived databases and projects have been developed to integrate and classify the PDB in terms of protein structure, protein function and protein evolution. GrowthWhen the PDB was originally founded it contained just 7 protein structures. Since then it has undergone an approximate exponential growth in the number of structures, which does not show any sign of falling off. The growth rate of the PDB has been the subject of fairly extensive analysis. ContentsAs of 26 September, 2006, the database contained 39,051 released atomic coordinate entries (or "structures"), 35,767 of that proteins, the rest being nucleic acids, nucleic acid-protein complexes, and a few other molecules. About 5,000 new structures are released each year. Data are stored in the mmCIF format specifically developed for the purpose. Note that the database stores information about the exact location of all atoms in a large biomolecule (although, usually without the hydrogen atoms, as their positions are more of a statistical estimate); if one is only interested in sequence data, i.e. the list of amino acids making up a particular protein or the list of nucleotides making up a particular nucleic acid, the much larger databases from Swiss-Prot and the International Nucleotide Sequence Database Collaboration should be used. StatisticsAs of 11 September, 2007, the "PDB Holdings List" at RCSB reported the following statistics:
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| Symbol(s) | MUTYH; MGC4416; MYH | |||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 604933 MGI: 1917853 Homologene: 8156 | |||||||||||||||||||||||||||||||||||||
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| Human | Mouse | |||||||||||||||||||||||||||||||||||||
| Entrez | 4595 | 70603 | ||||||||||||||||||||||||||||||||||||
| Ensembl | ENSG00000132781 | ENSMUSG00000028687 | ||||||||||||||||||||||||||||||||||||
| Uniprot | Q9UIF7 | Q762C9 | ||||||||||||||||||||||||||||||||||||
| Refseq | NM_001048171 (mRNA) NP_001041636 (protein) | NM_133250 (mRNA) NP_573513 (protein) | ||||||||||||||||||||||||||||||||||||
| Location | Chr 1: 45.57 - 45.58 Mb | Chr 4: 116.31 - 116.32 Mb | ||||||||||||||||||||||||||||||||||||
| Pubmed search | [5] | [6] | ||||||||||||||||||||||||||||||||||||
MUTYH (mutY Homolog (E. coli)) is a human gene [1] that carries the instructions for cells to make an enzyme that is involved in the repair of DNA. This enzyme, MUTYH glycosylase, corrects particular mistakes that are made when DNA is copied (replicated) in preparation for cell division. The building blocks of DNA (base pairs) have specific partners. Normally, adenine pairs with thymine (written as A-T) and guanine pairs with cytosine (G-C). During the normal cellular activities, guanine sometimes becomes altered by oxygen, which causes it to pair with adenine instead of cytosine. MYH glycosylase fixes these mistakes so mutations don't accumulate in the DNA and lead to tumor formation and possibly cancer. This type of repair is known as base excision repair (BER).
The MUTYH gene is located on the short (p) arm of chromosome 1 between positions 34.3 and 32.1, from base pair 45,464,007 to base pair 45,475,152.
Related conditions
Mutations in the MUTYH gene cause an autosomal recessive form of familial adenomatous polyposis (also called MUTYH-associated polyposis). Mutations in this gene affect the ability of cells to correct mistakes made during DNA replication. Both copies of the MUTYH gene are mutated in individuals who have autosomal recessive familial adenomatous polyposis. Most reported mutations in this gene cause production of a nonfunctional or low functioning glycosylase enzyme. When base excision repair in the cell is compromised, mutations in other genes build up, leading to cell overgrowth and possibly tumor formation. The two most common mutations in Caucasian Europeans are exchanges of amino acids (the building blocks of proteins) in the enzyme. One mutation replaces the amino acid tyrosine with cysteine at position 165 (also written as Tyr165Cys or Y165C). The other common mutation switches the amino acid glycine with aspartic acid at position 382 (also written as Gly382Asp or G382D).
References
Further reading
- Cheadle JP, Sampson JR (2003). "Exposing the MYtH about base excision repair and human inherited disease". Hum Mol Genet 12 Spec No 2: R159-65. PMID 12915454.
- Croitoru ME, Cleary SP, Di Nicola N, Manno M, Selander T, Aronson M, Redston M, Cotterchio M, Knight J, Gryfe R, Gallinger S (2004). "Association between biallelic and monoallelic germline MYH gene mutations and colorectal cancer risk". J Natl Cancer Inst 96 (21): 1631-4. PMID 15523092.
- Fleischmann C, Peto J, Cheadle J, Shah B, Sampson J, Houlston RS (2004). "Comprehensive analysis of the contribution of germline MYH variation to early-onset colorectal cancer". Int J Cancer 109 (4): 554-8. PMID 14991577.
- Jones S, Emmerson P, Maynard J, Best JM, Jordan S, Williams GT, Sampson JR, Cheadle JP (2002). "Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C-->T:A mutations". Hum Mol Genet 11 (23): 2961-7. PMID 12393807.
- Jones S, Lambert S, Williams GT, Best JM, Sampson JR, Cheadle JP (2004). "Increased frequency of the k-ras G12C mutation in MYH polyposis colorectal adenomas". Br J Cancer 90 (8): 1591-3. PMID 15083190.
- Kambara T, Whitehall VL, Spring KJ, Barker MA, Arnold S, Wynter CV, Matsubara N, Tanaka N, Young JP, Leggett BA, Jass JR (2004). "Role of inherited defects of MYH in the development of sporadic colorectal cancer". Genes Chromosomes Cancer 40 (1): 1-9. PMID 15034862.
- Lipton L, Halford SE, Johnson V, Novelli MR, Jones A, Cummings C, Barclay E, Sieber O, Sadat A, Bisgaard ML, Hodgson SV, Aaltonen LA, Thomas HJ, Tomlinson IP (2003). "Carcinogenesis in MYH-associated polyposis follows a distinct genetic pathway". Cancer Res 63 (22): 7595-9. PMID 14633673.
- Sampson JR, Dolwani S, Jones S, Eccles D, Ellis A, Evans DG, Frayling I, Jordan S, Maher ER, Mak T, Maynard J, Pigatto F, Shaw J, Cheadle JP (2003). "Autosomal recessive colorectal adenomatous polyposis due to inherited mutations of MYH". Lancet 362 (9377): 39-41. PMID 12853198.
- Sieber OM, Lipton L, Crabtree M, Heinimann K, Fidalgo P, Phillips RK, Bisgaard ML, Orntoft TF, Aaltonen LA, Hodgson SV, Thomas HJ, Tomlinson IP (2003). "Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH". N Engl J Med 348 (9): 791-9. PMID 12606733.
- Venesio T, Molatore S, Cattaneo F, Arrigoni A, Risio M, Ranzani GN (2004). "High frequency of MYH gene mutations in a subset of patients with familial adenomatous polyposis". Gastroenterology 126 (7): 1681-5. PMID 15188161.
- Wang L, Baudhuin LM, Boardman LA, Steenblock KJ, Petersen GM, Halling KC, French AJ, Johnson RA, Burgart LJ, Rabe K, Lindor NM, Thibodeau SN (2004). "MYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps". Gastroenterology 127 (1): 9-16. PMID 15236166.
External links
Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
