P24528 (MGMT_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Methylated-DNA--protein-cysteine methyltransferase
EC=2.1.1.63

Alternative name(s):
6-O-methylguanine-DNA methyltransferase
Short name=MGMT
O-6-methylguanine-DNA-alkyltransferase

Gene names

Name:

Mgmt

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	209 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) in DNA. Repairs alkylated guanine in DNA by stoichiometrically transferring the alkyl group at the O-6 position to a cysteine residue in the enzyme. This is a suicide reaction: the enzyme is irreversibly inactivated.
Catalytic activity	DNA (containing 6-O-methylguanine) + protein L-cysteine = DNA (without 6-O-methylguanine) + protein S-methyl-L-cysteine.
Cofactor	Binds 1 zinc ion By similarity.
Subcellular location	Nucleus Probable.
Miscellaneous	This enzyme catalyzes only one turnover and therefore is not strictly catalytic. According to one definition, an enzyme is a biocatalyst that acts repeatedly and over many reaction cycles.
Sequence similarities	Belongs to the MGMT family.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Nucleus
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Methyltransferase Transferase
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	DNA dealkylation involved in DNA repair Inferred from direct assay PubMed 15025514. Source: RGD cellular response to ionizing radiation Inferred from expression pattern PubMed 9780001. Source: RGD cellular response to organic cyclic compound Inferred from expression pattern PubMed 19549930. Source: RGD cellular response to oxidative stress Inferred from expression pattern PubMed 11133343. Source: RGD mammary gland epithelial cell differentiation Inferred from expression pattern PubMed 16086375. Source: RGD negative regulation of cell death Inferred from direct assay Ref.4. Source: RGD positive regulation of DNA repair Inferred from direct assay Ref.4. Source: RGD regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from electronic annotation. Source: Compara response to drug Inferred from expression pattern PubMed 19860839. Source: RGD response to ethanol Inferred from expression pattern PubMed 11524300. Source: RGD response to folic acid Inferred from expression pattern PubMed 20051376. Source: RGD response to toxin Inferred from expression pattern PubMed 20011461. Source: RGD
Cellular_component	nucleus Inferred from direct assay PubMed 11524300. Source: RGD
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW calcium ion binding Inferred from direct assay PubMed 12479403. Source: RGD methylated-DNA-[protein]-cysteine S-methyltransferase activity Inferred from direct assay PubMed 15025514. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 209	209	Methylated-DNA--protein-cysteine methyltransferase		PRO_0000139361
Sites
	Active site	149	1	Nucleophile; methyl group acceptor By similarity
	Metal binding	5	1	Zinc By similarity
	Metal binding	24	1	Zinc By similarity
	Metal binding	29	1	Zinc By similarity
	Metal binding	89	1	Zinc By similarity
	Binding site	99	1	DNA; via amide nitrogen By similarity
	Binding site	118	1	DNA By similarity
	Binding site	119	1	DNA; via amide nitrogen By similarity
	Binding site	127	1	DNA By similarity
	Binding site	132	1	DNA By similarity
	Binding site	155	1	DNA; via amide nitrogen By similarity

Sequences

	Sequence		Length	Mass (Da)
	P24528 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 61F8F51C8937D4A7	FASTA	209	22,244
	10 20 30 40 50 60 MAEICKMKYT VLDSPLGKIE LSGCERGLHG IRFLSGKTPN TDPTEAPACP EVLGGPEGVP 70 80 90 100 110 120 EPLVQCTAWL EAYFHEPAAT EGLPLPALHH PVFQQDSFTR QVLWKLLKVV KFGEMVSYQQ 130 140 150 160 170 180 LAALAGNPKA ARAVGGAMRS NPVPILIPCH RVIRSDGAIG NYSGGGQTVK EWLLAHEGIP 190 200 TGQPASKGLG LIGSWLKPSF ESSSPKPSG

References

[1]	"cDNA cloning of the rat O6-methylguanine-DNA-methyltransferase." Rahden-Staron I., Laval F. Biochem. Biophys. Res. Commun. 177:597-602(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Isolation and cDNA cloning of a rat O6-alkylguanine-DNA-alkyltransferase gene, molecular analysis of expression in rat liver." Potter P.M., Rafferty J.A., Cawkwell L., Wilkinson M.C., Cooper D.P., O'Connor P.J., Margison G.P. Carcinogenesis 12:727-733(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[3]	"Ribozyme-mediated modulation of human O6-methylguanine-DNA methyltransferase expression." Potter P.M., Harris L.C., Remack J.S., Edwards C.C., Brent T.P. Cancer Res. 53:1731-1734(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Cloning and expresion of cDNA for rat O6-methylguanine-DNA methyltransferase." Sakumi K., Shiraishi A., Hayakawa H., Sekiguchi M. Nucleic Acids Res. 19:5597-5601(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Specificities of human, rat and E. coli O6-methylguanine-DNA methyltransferases towards the repair of O6-methyl and O6-ethylguanine in DNA." Liem L.-K., Lim A., Li B.F.L. Nucleic Acids Res. 22:1613-1619(1994) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION, PARTIAL PROTEIN SEQUENCE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	S61804 mRNA. Translation: AAB20187.1. M76704 mRNA. Translation: AAA42052.1. X54862 mRNA. Translation: CAA38648.1.
IPI	IPI00231869.
PIR	XURTMC. JN0071.
RefSeq	NP_036993.1. NM_012861.1.
UniGene	Rn.9836.
3D structure databases
ProteinModelPortal	P24528.
SMR	P24528. Positions 5-185.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000021537.
PTM databases
PhosphoSite	P24528.
Proteomic databases
PaxDb	P24528.
PRIDE	P24528.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000021537; ENSRNOP00000021537; ENSRNOG00000016038.
GeneID	25332.
KEGG	rno:25332.
Organism-specific databases
CTD	4255.
RGD	3087. Mgmt.
Phylogenomic databases
eggNOG	COG0350.
GeneTree	ENSGT00390000015799.
HOGENOM	HOG000244137.
HOVERGEN	HBG001146.
InParanoid	P24528.
KO	K00567.
OMA	HLKQWLL.
Gene expression databases
ArrayExpress	P24528.
Genevestigator	P24528.
GermOnline	ENSRNOG00000016038. Rattus norvegicus.
Family and domain databases
Gene3D	1.10.10.10. 1 hit.
InterPro	IPR001497. MethylDNA_cys_MeTrfase_AS. IPR014048. MethylDNA_cys_MeTrfase_DNA-bd. IPR008332. MethylG_MeTrfase. IPR011991. WHTH_DNA-bd_dom. [Graphical view]
Pfam	PF01035. DNA_binding_1. 1 hit. PF02870. Methyltransf_1N. 1 hit. [Graphical view]
SUPFAM	SSF46767. MethylDNA_cys_mtrans_DNA_bd. 1 hit.
TIGRFAMs	TIGR00589. ogt. 1 hit.
PROSITE	PS00374. MGMT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	606215.

Entry information

Entry name

MGMT_RAT

Accession

Primary (citable) accession number: P24528

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 100 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program