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MUTYH (mutY homolog (E. coli))

Identity

Other namesMYH
MYHbeta
MutY homolog (hMYH)
mutY (E. coli) homolog
mutY homolog
HGNC (Hugo) MUTYH
LocusID (NCBI) 4595
Location 1p34.1
Location_base_pair Starts at 45794914 and ends at 45806142 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

 
  Mutyh AUG 1, 2 and 3 are alternative codons for translation initiation; cDNA not drawn to scale (adapted from Parker et al., 2003).
Description The MUTYH gene contains 16 exons spanning a region of 11147 bp.
Transcription The transcribed mRNA is 1854 bp long. There are three major classes of human MUTYH mRNAs: a, b and g. Each of these undergoes alternative splicing, suggesting a total of 10 possible mature transcripts. However, their distribution and abundance in different normal tissues have yet to be determined. The reference isoform is MutYa3.

Protein

 
  Diagram of the MUTYH protein in scale. Filled boxes represent known functional domains (adapted from Sampson et al, 2005).
Description Aminoacids: 535. Molecular Weight: 52 kDa. MUTYH is a protein involved in base excision repair (BER). It contains a DNA binding domain, an adenine binding motif and several interaction domains for APE1, PCNA, RPA and MSH6, located in different regions of the gene.
Expression Ubiquitous.
Localisation Nuclear and mithocondrial.
Function MUTYH is involved in oxidative DNA damage repair. Human MutY is responsible for recognition and removal of inappropriately inserted adenine in Ao8-oxoG mispairs. If unrepaired, the Ao8-oxoG mispairs can result in C:G to A:T transversions. MUTYH functions in a postreplication repair pathway and is targeted to the newly synthesized daughter strand of DNA for removal of the adenine base.
Homology MUTYH is homologous to the bacterial MutY gene, and MUTYH homologues are also present in eukaryote.

Mutations

Germinal Biallelic germline mutations of MUTYH are associated with colorectal polyposis. The most common mutations in Caucasians are the missense substitutions Y165C (494A>G) and G382D (1145G>A). Functional analysis of C165 and D382 proteins has shown a severe decrease of catalytic activity. E466X and Y90X are the common mutations reported in Indian and Pakistani cases. Several other missense, nonsense, in-frame, frameshift and splicing mutations have been found in patients with colorectal polyposis.
Somatic To date, no MUTYH somatic mutation has been described.

Implicated in

Entity MAP (MUTYH-associated polyposis).
Disease Biallelic MUTYH mutations are responsible for the autosomal recessive form of intestinal adenomatous polyposis.
Oncogenesis Defective BER function associated with MUTYH mutations determines an increase in the somatic mutation rate, namely of G>T transversions at guanine residues that are potential targets of oxidative damage. Tumors from biallelic MUTYH mutation carriers display an excess of somatic G>T mutations in the APC and KRAS genes
  

External links

Nomenclature
HGNC (Hugo)MUTYH   7527
Cards
AtlasMUTYHID41464ch1p34
Entrez_Gene (NCBI)MUTYH  4595  mutY homolog
GeneCards (Weizmann)MUTYH
Ensembl hg19 (Hinxton)ENSG00000132781 [Gene_View]  chr1:45794914-45806142 [Contig_View]  MUTYH [Vega]
Ensembl hg38 (Hinxton)ENSG00000132781 [Gene_View]  chr1:45794914-45806142 [Contig_View]  MUTYH [Vega]
ICGC DataPortalENSG00000132781
cBioPortalMUTYH
AceView (NCBI)MUTYH
Genatlas (Paris)MUTYH
WikiGenes4595
SOURCE (Princeton)MUTYH
Genomic and cartography
GoldenPath hg19 (UCSC)MUTYH  -     chr1:45794914-45806142 -  1p34.1   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)MUTYH  -     1p34.1   [Description]    (hg38-Dec_2013)
EnsemblMUTYH - 1p34.1 [CytoView hg19]  MUTYH - 1p34.1 [CytoView hg38]
Mapping of homologs : NCBIMUTYH [Mapview hg19]  MUTYH [Mapview hg38]
OMIM132600   604933   608456   613659   
Gene and transcription
Genbank (Entrez)AB025227 AB032920 AB032921 AB032922 AB032923
RefSeq transcript (Entrez)NM_001048171 NM_001048172 NM_001048173 NM_001048174 NM_001128425 NM_001293190 NM_001293191 NM_001293192 NM_001293195 NM_001293196 NM_012222
RefSeq genomic (Entrez)AC_000133 NC_000001 NC_018912 NG_008189 NT_032977 NW_001838578 NW_004929290
Consensus coding sequences : CCDS (NCBI)MUTYH
Cluster EST : UnigeneHs.271353 [ NCBI ]
CGAP (NCI)Hs.271353
Alternative Splicing : Fast-db (Paris)GSHG0002054
Alternative Splicing GalleryENSG00000132781
Gene ExpressionMUTYH [ NCBI-GEO ]     MUTYH [ SEEK ]   MUTYH [ MEM ]
SOURCE (Princeton)Expression in : [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9UIF7 (Uniprot)
NextProtQ9UIF7  [Medical]
With graphics : InterProQ9UIF7
Splice isoforms : SwissVarQ9UIF7 (Swissvar)
Catalytic activity : Enzyme3.2.2.- [ Enzyme-Expasy ]   3.2.2.-3.2.2.- [ IntEnz-EBI ]   3.2.2.- [ BRENDA ]   3.2.2.- [ KEGG ]   
Domaine pattern : Prosite (Expaxy)ENDONUCLEASE_III_1 (PS00764)    ENDONUCLEASE_III_2 (PS01155)    NUDIX (PS51462)   
Domains : Interpro (EBI)DNA_glycosylase    Endonuclease-III-like_CS2    Endouclease-III_FeS-bd_BS    Endouclease3_FeS-loop_motif    HhH-GPD_domain    HTH_base_excis_C    MutY_C    NUDIX_hydrolase_dom    NUDIX_hydrolase_dom-like   
Related proteins : CluSTrQ9UIF7
Domain families : Pfam (Sanger)HhH-GPD (PF00730)    NUDIX_4 (PF14815)   
Domain families : Pfam (NCBI)pfam00730    pfam14815   
Domain families : Smart (EMBL)ENDO3c (SM00478)  FES (SM00525)  
DMDM Disease mutations4595
Blocks (Seattle)Q9UIF7
PDB (SRS)1X51    3N5N   
PDB (PDBSum)1X51    3N5N   
PDB (IMB)1X51    3N5N   
PDB (RSDB)1X51    3N5N   
Human Protein AtlasENSG00000132781
Peptide AtlasQ9UIF7
HPRD05380
IPIIPI00844241   IPI00414235   IPI00746950   IPI00456700   IPI00414237   IPI00973054   IPI00414236   IPI00647822   IPI00975588   IPI00979216   IPI00984533   IPI00979273   IPI00978469   IPI00983218   IPI00977847   IPI00982209   IPI00982612   IPI00980898   IPI01012578   IPI00979243   IPI00980305   
Protein Interaction databases
DIP (DOE-UCLA)Q9UIF7
IntAct (EBI)Q9UIF7
FunCoupENSG00000132781
BioGRIDMUTYH
IntegromeDBMUTYH
STRING (EMBL)MUTYH
Ontologies - Pathways
QuickGOQ9UIF7
Ontology : AmiGOprotein binding  nucleus  nucleoplasm  mitochondrion  DNA repair  base-excision repair  base-excision repair, AP site formation  mismatch repair  hydrolase activity, acting on glycosyl bonds  MutLalpha complex binding  MutLbeta complex binding  MutSalpha complex binding  MutSbeta complex binding  depurination  metal ion binding  4 iron, 4 sulfur cluster binding  
Ontology : EGO-EBIprotein binding  nucleus  nucleoplasm  mitochondrion  DNA repair  base-excision repair  base-excision repair, AP site formation  mismatch repair  hydrolase activity, acting on glycosyl bonds  MutLalpha complex binding  MutLbeta complex binding  MutSalpha complex binding  MutSbeta complex binding  depurination  metal ion binding  4 iron, 4 sulfur cluster binding  
Pathways : KEGGBase excision repair   
REACTOMEQ9UIF7 [protein]
REACTOME PathwaysREACT_216 DNA Repair [pathway]
Protein Interaction DatabaseMUTYH
DoCM (Curated mutations)MUTYH
Wikipedia pathwaysMUTYH
Gene fusion - rearrangements
Polymorphisms : SNP, variants
NCBI Variation ViewerMUTYH [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MUTYH
dbVarMUTYH
ClinVarMUTYH
1000_GenomesMUTYH 
Exome Variant ServerMUTYH
SNP (GeneSNP Utah)MUTYH
SNP : HGBaseMUTYH
Genetic variants : HAPMAPMUTYH
Genomic VariantsMUTYH  MUTYH [DGVbeta]
Mutations
ICGC Data PortalENSG00000132781 
Cancer Gene: CensusMUTYH 
Somatic Mutations in Cancer : COSMICMUTYH 
CONAN: Copy Number AnalysisMUTYH 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)Colon cancer gene variant databases
LOVD (Leiden Open Variation Database)MSeqDR-LSDB Mitochondrial Disease Locus Specific Database
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)1:45794914-45806142
Mutations and Diseases : HGMDMUTYH
OMIM132600    604933    608456    613659   
MedgenMUTYH
NextProtQ9UIF7 [Medical]
GENETestsMUTYH
Disease Genetic AssociationMUTYH
Huge Navigator MUTYH [HugePedia]  MUTYH [HugeCancerGEM]
snp3D : Map Gene to Disease4595
DGIdb (Drug Gene Interaction db)MUTYH
General knowledge
Homologs : HomoloGeneMUTYH
Homology/Alignments : Family Browser (UCSC)MUTYH
Phylogenetic Trees/Animal Genes : TreeFamMUTYH
Chemical/Protein Interactions : CTD4595
Chemical/Pharm GKB GenePA31328
Clinical trialMUTYH
Cancer Resource (Charite)ENSG00000132781
Other databases
Probes
Litterature
PubMed209 Pubmed reference(s) in Entrez
CoreMineMUTYH
GoPubMedMUTYH
iHOPMUTYH

Bibliography

Characterization of a mammalian homolog of the Escherichia coli MutY mismatch repair protein.
McGoldrick JP, Yeh YC, Solomon M, Essigmann JM, Lu AL
Molecular and cellular biology. 1995 ; 15 (2) : 989-996.
PMID 7823963
 
Identification of human MutY homolog (hMYH) as a repair enzyme for 2-hydroxyadenine in DNA and detection of multiple forms of hMYH located in nuclei and mitochondria.
Ohtsubo T, Nishioka K, Imaiso Y, Iwai S, Shimokawa H, Oda H, Fujiwara T, Nakabeppu Y
Nucleic acids research. 2000 ; 28 (6) : 1355-1364.
PMID 10684930
 
Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors.
Al-Tassan N, Chmiel NH, Maynard J, Fleming N, Livingston AL, Williams GT, Hodges AK, Davies DR, David SS, Sampson JR, Cheadle JP
Nature genetics. 2002 ; 30 (2) : 227-232.
PMID 11818965
 
Human MutY homolog, a DNA glycosylase involved in base excision repair, physically and functionally interacts with mismatch repair proteins human MutS homolog 2/human MutS homolog 6.
Gu Y, Parker A, Wilson TM, Bai H, Chang DY, Lu AL
The Journal of biological chemistry. 2002 ; 277 (13) : 11135-11142.
PMID 11801590
 
Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C-->T:A mutations.
Jones S, Emmerson P, Maynard J, Best JM, Jordan S, Williams GT, Sampson JR, Cheadle JP
Human molecular genetics. 2002 ; 11 (23) : 2961-2967.
PMID 12393807
 
Germline mutations but not somatic changes at the MYH locus contribute to the pathogenesis of unselected colorectal cancers.
Halford SE, Rowan AJ, Lipton L, Sieber OM, Pack K, Thomas HJ, Hodgson SV, Bodmer WF, Tomlinson IP
The American journal of pathology. 2003 ; 162 (5) : 1545-1548.
PMID 12707038
 
Carcinogenesis in MYH-associated polyposis follows a distinct genetic pathway.
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
Cancer research. 2003 ; 63 (22) : 7595-7599.
PMID 14633673
 
Human MutY: gene structure, protein functions and interactions, and role in carcinogenesis.
Parker AR, Eshleman JR
Cellular and molecular life sciences : CMLS. 2003 ; 60 (10) : 2064-2083.
PMID 14618256
 
Defective human MutY phosphorylation exists in colorectal cancer cell lines with wild-type MutY alleles.
Parker AR, O'Meally RN, Sahin F, Su GH, Racke FK, Nelson WG, DeWeese TL, Eshleman JR
The Journal of biological chemistry. 2003 ; 278 (48) : 47937-47945.
PMID 12966098
 
Autosomal recessive colorectal adenomatous polyposis due to inherited mutations of MYH.
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
Lancet. 2003 ; 362 (9377) : 39-41.
PMID 12853198
 
Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH.
Sieber OM, Lipton L, Crabtree M, Heinimann K, Fidalgo P, Phillips RK, Bisgaard ML, Orntoft TF, Aaltonen LA, Hodgson SV, Thomas HJ, Tomlinson IP
The New England journal of medicine. 2003 ; 348 (9) : 791-799.
PMID 12606733
 
Association between biallelic and monoallelic germline MYH gene mutations and colorectal cancer risk.
Croitoru ME, Cleary SP, Di Nicola N, Manno M, Selander T, Aronson M, Redston M, Cotterchio M, Knight J, Gryfe R, Gallinger S
Journal of the National Cancer Institute. 2004 ; 96 (21) : 1631-1634.
PMID 15523092
 
Prevalence of the Y165C, G382D and 1395delGGA germline mutations of the MYH gene in Italian patients with adenomatous polyposis coli and colorectal adenomas.
Gismondi V, Meta M, Bonelli L, Radice P, Sala P, Bertario L, Viel A, Fornasarig M, Arrigoni A, Gentile M, Ponz de Leon M, Anselmi L, Mareni C, Bruzzi P, Varesco L
International journal of cancer. Journal international du cancer. 2004 ; 109 (5) : 680-684.
PMID 14999774
 
The multiple colorectal adenoma phenotype and MYH, a base excision repair gene.
Lipton L, Tomlinson I
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2004 ; 2 (8) : 633-638.
PMID 15290654
 
Increased frequency of the k-ras G12C mutation in MYH polyposis colorectal adenomas.
Jones S, Lambert S, Williams GT, Best JM, Sampson JR, Cheadle JP
British journal of cancer. 2004 ; 90 (8) : 1591-1593.
PMID 15083190
 
High frequency of MYH gene mutations in a subset of patients with familial adenomatous polyposis.
Venesio T, Molatore S, Cattaneo F, Arrigoni A, Risio M, Ranzani GN
Gastroenterology. 2004 ; 126 (7) : 1681-1685.
PMID 15188161
 
The multiple colorectal adenoma phenotype and MYH, a base excision repair gene.
Lipton L, Tomlinson I
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2004 ; 2 (8) : 633-638.
PMID 15290654
 
Functional characterization of two human MutY homolog (hMYH) missense mutations (R227W and V232F) that lie within the putative hMSH6 binding domain and are associated with hMYH polyposis.
Bai H, Jones S, Guan X, Wilson TM, Sampson JR, Cheadle JP, Lu AL
Nucleic acids research. 2005 ; 33 (2) : 597-604.
PMID 15673720
 
Cells with pathogenic biallelic mutations in the human MUTYH gene are defective in DNA damage binding and repair.
Parker AR, Sieber OM, Shi C, Hua L, Takao M, Tomlinson IP, Eshleman JR
Carcinogenesis. 2005 ; 26 (11) : 2010-2018.
PMID 15987719
 
Insight into the functional consequences of hMYH variants associated with colorectal cancer: distinct differences in the adenine glycosylase activity and the response to AP endonucleases of Y150C and G365D murine MYH.
Pope MA, Chmiel NH, David SS
DNA repair. 2005 ; 4 (3) : 315-325.
PMID 15661655
 
MutYH (MYH) and colorectal cancer.
Sampson JR, Jones S, Dolwani S, Cheadle JP
Biochemical Society transactions. 2005 ; 33 (Pt 4) : 679-683.
PMID 16042573
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written06-2006Maurizio Genuardi, Rossella Tricarico
Department of Clinical Pathophysiology, University of Florence, Viale Gaetano Pieraccini 6, 50139 Firenze, Italy

Citation

This paper should be referenced as such :
Genuardi, M ; Tricarico, R. MUTYH (mutY homolog (E
coli))
Atlas Genet Cytogenet Oncol Haematol. 2006;10(4):236-238.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/MUTYHID41464ch1p34.html

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