MUTYH (mutY homolog (E. coli))

Identity

Other names	MYH
	MYHbeta
	MutY homolog (hMYH)
	mutY (E. coli) homolog
	mutY homolog
HGNC	MUTYH
Location	1p34.3-p32.1
Location_base_pair	Starts at 45567501 and ends at 45578729 bp from pter (hg18-Mar_2006).

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	MUTYH   7527
Entrez_Gene	MUTYH  4595  mutY homolog (E. coli)
	Cards
Atlas	MUTYHID41464ch1p34
GeneCards	MUTYH
Ensembl	MUTYH [Search_View]   ENSG00000132781 [Gene_View]
Genatlas	MUTYH
GeneLynx	MUTYH
eGenome	MUTYH
euGene	4595
	Genomic and cartography
GoldenPath	MUTYH  -     chr1:45567501-45578729 -  1p34.1   [Description]    (hg18-Mar_2006)
Ensembl	MUTYH - 1p34.1 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	MUTYH
	Gene and transcription
Genbank	AB025227 [ ENTREZ ]
Genbank	AB032920 [ ENTREZ ]
Genbank	AB032921 [ ENTREZ ]
Genbank	AB032922 [ ENTREZ ]
Genbank	AB032923 [ ENTREZ ]
RefSeq	NM_001048171 [ SRS ]    NM_001048171 [ ENTREZ ]
RefSeq	NM_001048172 [ SRS ]    NM_001048172 [ ENTREZ ]
RefSeq	NM_001048173 [ SRS ]    NM_001048173 [ ENTREZ ]
RefSeq	NM_001048174 [ SRS ]    NM_001048174 [ ENTREZ ]
RefSeq	NM_001128425 [ SRS ]    NM_001128425 [ ENTREZ ]
RefSeq	NM_012222 [ SRS ]    NM_012222 [ ENTREZ ]
RefSeq	AC_000044 [ SRS ]    AC_000044 [ ENTREZ ]
RefSeq	AC_000133 [ SRS ]    AC_000133 [ ENTREZ ]
RefSeq	NC_000001 [ SRS ]    NC_000001 [ ENTREZ ]
RefSeq	NG_008189 [ SRS ]    NG_008189 [ ENTREZ ]
RefSeq	NT_032977 [ SRS ]    NT_032977 [ ENTREZ ]
RefSeq	NW_001838578 [ SRS ]    NW_001838578 [ ENTREZ ]
RefSeq	NW_921351 [ SRS ]    NW_921351 [ ENTREZ ]
AceView	MUTYH AceView - NCBI
Unigene	Hs.271353 [ SRS ]    Hs.271353 [ NCBI ]     HS271353 [ spliceNest ]
	Protein : pattern, domain, 3D structure
SwissProt	Q5T411 [ SRS]    Q5T411 [ EXPASY ]     Q5T411 [ INTERPRO ]     Q5T411 [ UNIPROT ]
Prosite	PS00764 ENDONUCLEASE_III_1 [ SRS ]    PS00764 ENDONUCLEASE_III_1 [ Expasy ]
Prosite	PS01155 ENDONUCLEASE_III_2 [ SRS ]    PS01155 ENDONUCLEASE_III_2 [ Expasy ]
Interpro	IPR003265 Endo_3c [ SRS ]    IPR003265 Endo_3c [ EBI ]
Interpro	IPR004036 Endonuclease-III_CS2 [ SRS ]    IPR004036 Endonuclease-III_CS2 [ EBI ]
Interpro	IPR004035 Endouclease-III_FeS-bd_CS1 [ SRS ]    IPR004035 Endouclease-III_FeS-bd_CS1 [ EBI ]
Interpro	IPR003651 FeS_bd [ SRS ]    IPR003651 FeS_bd [ EBI ]
Interpro	IPR000445 HhH [ SRS ]    IPR000445 HhH [ EBI ]
Interpro	IPR000086 NUDIX_hydrolase_core [ SRS ]    IPR000086 NUDIX_hydrolase_core [ EBI ]
CluSTr	Q5T411
Pfam	PF00633 HHH [ SRS ]    PF00633 HHH [ Sanger ]    pfam00633 [ NCBI-CDD ]
Pfam	PF00730 HhH-GPD [ SRS ]    PF00730 HhH-GPD [ Sanger ]    pfam00730 [ NCBI-CDD ]
Pfam	PF00293 NUDIX [ SRS ]    PF00293 NUDIX [ Sanger ]    pfam00293 [ NCBI-CDD ]
Smart	SM00478 ENDO3c [EMBL]
Smart	SM00525 FES [EMBL]
Blocks	Q5T411
HPRD	05380
	Protein Interaction databases
DIP	Q5T411
IntAct	Q5T411
	Polymorphism : SNP, mutations, diseases
OMIM	132600;137215;604933;608456    [ map ]
GENECLINICS	132600;137215;604933;608456
SNP	MUTYH [dbSNP-NCBI]
SNP	NM_001048171 [SNP-NCI]
SNP	NM_001048172 [SNP-NCI]
SNP	NM_001048173 [SNP-NCI]
SNP	NM_001048174 [SNP-NCI]
SNP	NM_001128425 [SNP-NCI]
SNP	NM_012222 [SNP-NCI]
SNP	MUTYH [GeneSNPs - Utah]  MUTYH] [HGBASE - SRS]
HAPMAP	MUTYH [HAPMAP]
COSMIC	MUTYH [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	MUTYH
	General knowledge
Family Browser	MUTYH [UCSC Family Browser]
SOURCE	NM_001048171
SOURCE	NM_001048172
SOURCE	NM_001048173
SOURCE	NM_001048174
SOURCE	NM_001128425
SOURCE	NM_012222
SMD	Hs.271353
SAGE	Hs.271353
GO	DNA binding [Amigo]  DNA binding
GO	catalytic activity [Amigo]  catalytic activity
GO	endonuclease activity [Amigo]  endonuclease activity
GO	iron ion binding [Amigo]  iron ion binding
GO	protein binding [Amigo]  protein binding
GO	intracellular [Amigo]  intracellular
GO	nucleus [Amigo]  nucleus
GO	nucleoplasm [Amigo]  nucleoplasm
GO	base-excision repair [Amigo]  base-excision repair
GO	mismatch repair [Amigo]  mismatch repair
GO	metabolic process [Amigo]  metabolic process
GO	hydrolase activity [Amigo]  hydrolase activity
GO	hydrolase activity, acting on glycosyl bonds [Amigo]  hydrolase activity, acting on glycosyl bonds
GO	DNA N-glycosylase activity [Amigo]  DNA N-glycosylase activity
GO	MutLalpha complex binding [Amigo]  MutLalpha complex binding
GO	MutLbeta complex binding [Amigo]  MutLbeta complex binding
GO	MutSalpha complex binding [Amigo]  MutSalpha complex binding
GO	MutSbeta complex binding [Amigo]  MutSbeta complex binding
GO	depurination [Amigo]  depurination
GO	negative regulation of cell cycle [Amigo]  negative regulation of cell cycle
GO	metal ion binding [Amigo]  metal ion binding
GO	4 iron, 4 sulfur cluster binding [Amigo]  4 iron, 4 sulfur cluster binding
PubGene	MUTYH
TreeFam	MUTYH
CTD	4595 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	MUTYH Related clones (RZPD - Berlin)
	PubMed
PubMed	93 Pubmed reference(s) in Entrez

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

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Contributor(s)

Written	06-2006	Maurizio 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. June 2006 . URL : http://AtlasGeneticsOncology.org/Genes/MUTYHID41464ch1p34.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Sat Oct 11 12:54:07 2008