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Description:
N-glycosylase/DNA lyase [Includes: 8-oxoguanine DNA glycosylase(EC 3.2.2.-); DNA-(apurinic or apyrimidinic site) lyase (EC 4.2.99.18)(AP lyase)].
Molecular weight: 38782
View which proteins in this organism that is involved with DNA Repair;
classified after biological processes (using data from the GOA project):
DNA repair( GO:0006281 ) base-excision repair( GO:0006284 )
Important dates:
01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
01-DEC-2000, sequence version 2.
07-FEB-2006, entry version 61.
Phylogenetic order:
Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Catarrhini Hominidae Homo.
To calculate the pI (Isoelectric point - the pH where a protein has a neutral charge),
go to this page and enter the protein ID (e.g 3MG_ECOLI): http://us.expasy.org/tools/pi_tool.html
Links to references in other databases for protein OGG1_HUMAN:
| Database | Pointer | Add. info#1 | Add. info#2 |
| EMBL | U96710 | AAB81132.1 | - |
| EMBL | Y11838 | CAA72536.1 | - |
| EMBL | Y11731 | CAA72414.1 | - |
| EMBL | AB000410 | BAA19103.1 | - |
| EMBL | AF003595 | AAB61340.1 | - |
| EMBL | U88527 | AAB68614.1 | - |
| EMBL | U88620 | AAB68615.1 | - |
| EMBL | Y13277 | CAA73726.1 | - |
| EMBL | AF026691 | AAB84013.1 | - |
| EMBL | AJ131341 | CAA10351.1 | - |
| EMBL | AF088282 | AAD41680.1 | - |
| EMBL | AF088282 | AAD41681.1 | - |
| EMBL | AF088282 | AAD41682.1 | - |
| EMBL | AB019528 | BAA76635.1 | - |
| EMBL | AB019529 | BAA76636.1 | - |
| EMBL | AB019530 | BAA76637.1 | - |
| EMBL | AB019531 | BAA76638.1 | - |
| EMBL | AB019532 | BAA76639.1 | - |
| EMBL | AF521807 | AAM74236.1 | - |
| PIR | T45069 | T45069. | |
| PDB | 1EBM | X-ray | A=12-325. |
| PDB | 1FN7 | X-ray | A=12-325. |
| PDB | 1HU0 | X-ray | A=12-327. |
| PDB | 1KO9 | X-ray | A=1-345. |
| PDB | 1LWV | X-ray | A=12-327. |
| PDB | 1LWW | X-ray | A=12-327. |
| PDB | 1LWY | X-ray | A=12-327. |
| PDB | 1M3H | X-ray | A=12-325. |
| PDB | 1M3Q | X-ray | A=12-325. |
| PDB | 1N39 | X-ray | A=12-325. |
| PDB | 1N3A | X-ray | A=12-325. |
| PDB | 1N3C | X-ray | A=12-325. |
| Ensembl | ENSG00000114026 | Homo sapiens.1 | |
| H-InvDB | HIX0003031 | -.1 | |
| HGNC | HGNC:8125 | OGG1.1 | |
| MIM | 144700 | phenotype. | |
| MIM | 601982 | gene. | |
| Reactome | O15527 | -.1 | |
| GO | GO:0005654 | C:nucleoplasm | TAS. |
| GO | GO:0003684 | F:damaged DNA binding | TAS. |
| GO | GO:0004519 | F:endonuclease activity | TAS. |
| GO | GO:0008534 | F:purine-specific oxidized base lesion DNA N-... | TAS. |
| GO | GO:0006284 | P:base-excision repair | TAS. |
| InterPro | IPR003265 | Endo_3c. | |
| InterPro | IPR000445 | HhH. | |
| InterPro | IPR004577 | Ogg. | |
| InterPro | IPR012904 | OGG_N. | |
| InterPro | IPR012294 | TFIID_C/glycos_N. | |
| Pfam | PF00633 | HHH | 1. |
| Pfam | PF00730 | HhH-GPD | 1. |
| Pfam | PF07934 | OGG_N | 1. |
| SMART | SM00478 | ENDO3c | 1. |
| TIGRFAMs | TIGR00588 | ogg | 1. |
Keywords:
3D-structure; Alternative splicing; DNA damage; DNA repair; Glycosidase; Hydrolase; Lyase; Mitochondrion; Multifunctional enzyme; Nuclear protein; Polymorphism.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE, AND ALTERNATIVE SPLICING.
RC TISSUE=Colon;
RX MEDLINE=97330655; PubMed=9187114;
RA Aburatani H., Hippo Y., Ishida T., Takashima R., Matsuba C.,
RA Kodama T., Takao M., Yasui A., Yamamoto K., Asano M., Fukasawa K.,
RA Yoshinari T., Inoue H., Otsuka E., Nishimura S.;
RT "Cloning and characterization of mammalian 8-hydroxyguanine-specific
RT DNA glycosylase/apurinic, apyrimidinic lyase, a functional mutM
RT homologue.";
RL Cancer Res. 57:2151-2156(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1A).
RX MEDLINE=97352815; PubMed=9207108; DOI=10.1073/pnas.94.14.7429;
RA Rosenquist T.A., Zharkov D.O., Grollman A.P.;
RT "Cloning and characterization of a mammalian 8-oxoguanine DNA
RT glycosylase.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:7429-7434(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE (ISOFORM 2).
RX MEDLINE=97368311; PubMed=9223306; DOI=10.1073/pnas.94.15.8016;
RA Roldan-Arjona T., Wei Y.-F., Carter K.C., Klungland A., Anselmino C.,
RA Wang R.-P., Augustus M., Lindahl T.;
RT "Molecular cloning and functional expression of a human cDNA encoding
RT the antimutator enzyme 8-hydroxyguanine-DNA glycosylase.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:8016-8020(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1A).
RX MEDLINE=97368310; PubMed=9223305; DOI=10.1073/pnas.94.15.8010;
RA Radicella J.P., Dherin C., Desmaze C., Fox M.S., Boiteux S.;
RT "Cloning and characterization of hOGG1, a human homolog of the OGG1
RT gene of Saccharomyces cerevisiae.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:8010-8015(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1A), ACTIVE SITE, AND MUTAGENESIS OF
RP LYS-249.
RX MEDLINE=97342862; PubMed=9197244; DOI=10.1016/S0960-9822(06)00187-4;
RA Lu R., Nash H.M., Verdine G.L.;
RT "A mammalian DNA repair enzyme that excises oxidatively damaged
RT guanines maps to a locus frequently lost in lung cancer.";
RL Curr. Biol. 7:397-407(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1A).
RX MEDLINE=97334205; PubMed=9190902; DOI=10.1038/sj.onc.1201139;
RA Arai K., Morishita K., Shinmura K., Kohno T., Taniwaki M., Ohwada S.,
RA Yokota J.;
RT "Cloning of a human homolog of the yeast OGG1 gene that is involved in
RT the repair of oxidative DNA damage.";
RL Oncogene 14:2857-2861(1997).
RN [7]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1A).
RX MEDLINE=98012228; PubMed=9348312; DOI=10.1084/jem.186.9.1547;
RA Kuo F.C., Sklar J.L.;
RT "Augmented expression of a human gene for 8-oxoguanine DNA glycosylase
RT (MutM) in B lymphocytes of the dark zone in lymph node germinal
RT centers.";
RL J. Exp. Med. 186:1547-1556(1997).
RN [8]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1A).
RX MEDLINE=98026907; PubMed=9321410; DOI=10.1093/emboj/16.20.6314;
RA Bjoras M., Luna L., Johnsen B.E., Hoff E., Haug T., Rognes T.,
RA Seeberg E.;
RT "Opposite base-dependent reactions of a human base excision repair
RT enzyme on DNA containing 7,8-dihydro-8-oxoguanine and abasic sites.";
RL EMBO J. 16:6314-6322(1997).
RN [9]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1A).
RA Dhenaut A., Boiteux S., Radicella J.;
RT "Genomic structure and promoter characterization of the human 8-OH-
RT guanine glycosylase gene (OGG1) gene.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE, AND ALTERNATIVE SPLICING.
RX MEDLINE=99380087; PubMed=10449904;
RA Ishida T., Hippo Y., Nakahori Y., Matsushita I., Kodama T.,
RA Nishimura S., Aburatani H.;
RT "Structure and chromosome location of human OGG1.";
RL Cytogenet. Cell Genet. 85:232-236(1999).
RN [11]
RP NUCLEOTIDE SEQUENCE, AND ALTERNATIVE SPLICING.
RX MEDLINE=99250167; PubMed=10233168;
RA Nishioka K., Ohtsubo T., Oda H., Fujiwara T., Kang D., Sugimachi K.,
RA Nakabeppu Y.;
RT "Expression and differential intracellular localization of two major
RT forms of human 8-Oxoguanine DNA glycosylase encoded by alternatively
RT spliced OGG1 mRNAs.";
RL Mol. Biol. Cell 10:1637-1652(1999).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLN-229; VAL-288;
RP ASN-322 AND CYS-326.
RA Rieder M.J., Livingston R.J., Braun A.C., Montoya M.A., Chung M.-W.,
RA Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D.,
RA Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A.;
RT "NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department
RT of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP REVIEW.
RX MEDLINE=20239648; PubMed=10775435; DOI=10.1006/abbi.2000.1773;
RA Boiteux S., Radicella J.P.;
RT "The human OGG1 gene: structure, functions, and its implication in the
RT process of carcinogenesis.";
RL Arch. Biochem. Biophys. 377:1-8(2000).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 12-327 OF MUTANT GLN-247 IN
RP COMPLEX WITH DNA, AND CHARACTERIZATION OF VARIANT HIS-154.
RX PubMed=10706276; DOI=10.1038/35002510;
RA Bruner S.D., Norman D.P.G., Verdine G.L.;
RT "Structural basis for recognition and repair of the endogenous mutagen
RT 8-oxoguanine in DNA.";
RL Nature 403:859-866(2000).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH DNA AND
RP 8-OXO-GUANINE.
RX MEDLINE=21901651; PubMed=11902834; DOI=10.1006/jmbi.2002.5400;
RA Bjoras M., Seeberg E., Luna L., Pearl L.H., Barrett T.E.;
RT "Reciprocal 'flipping'; underlies substrate recognition and catalytic
RT activation by the human 8-oxo-guanine DNA glycosylase.";
RL J. Mol. Biol. 317:171-177(2002).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 12-327 OF MUTANTS ASN-268;
RP GLU-268 AND GLN-268 IN COMPLEX WITH DNA, AND MUTAGENESIS OF ASP-268.
RX PubMed=12578369; DOI=10.1021/bi026823d;
RA Norman D.P.G., Chung S.J., Verdine G.L.;
RT "Structural and biochemical exploration of a critical amino acid in
RT human 8-oxoguanine glycosylase.";
RL Biochemistry 42:1564-1572(2003).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 12-327 IN COMPLEX WITH DNA
RP AND 8-OXO-GUANINE.
RX PubMed=12592398; DOI=10.1038/nsb902;
RA Fromme J.C., Bruner S.D., Yang W., Karplus M., Verdine G.L.;
RT "Product-assisted catalysis in base-excision DNA repair.";
RL Nat. Struct. Biol. 10:204-211(2003).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 12-325 OF MUTANT GLU-268 IN
RP COMPLEX WITH DNA.
RX PubMed=15610848; DOI=10.1016/j.chembiol.2004.09.014;
RA Chung S.J., Verdine G.L.;
RT "Structures of end products resulting from lesion processing by a DNA
RT glycosylase/lyase.";
RL Chem. Biol. 11:1643-1649(2004).
RN [19]
RP VARIANT HIS-154.
RX MEDLINE=98438755; PubMed=9765618;
RA Shinmura K., Kohno T., Kasai H., Koda K., Sugimura H., Yokota J.;
RT "Infrequent mutations of the hOGG1 gene, that is involved in the
RT excision of 8-hydroxyguanine in damaged DNA, in human gastric
RT cancer.";
RL Jpn. J. Cancer Res. 89:825-828(1998).
RN [20]
RP VARIANTS SER-85; GLN-131 AND THR-232, AND CHARACTERIZATION OF VARIANT
RP GLN-131.
RX MEDLINE=98324718; PubMed=9662341; DOI=10.1038/sj.onc.1202096;
RA Chevillard S., Radicella J.P., Levalois C., Lebeau J., Poupon M.-F.,
RA Oudard S., Dutrillaux B., Boiteux S.;
RT "Mutations in OGG1, a gene involved in the repair of oxidative DNA
RT damage, are found in human lung and kidney tumours.";
RL Oncogene 16:3083-3086(1998).
RN [21]
RP CHARACTERIZATION OF VARIANT CYS-326.
RX MEDLINE=99428653; PubMed=10497264; DOI=10.1093/nar/27.20.4001;
RA Dherin C., Radicella J.P., Dizdaroglu M., Boiteux S.;
RT "Excision of oxidatively damaged DNA bases by the human alpha-hOgg1
RT protein and the polymorphic alpha-hOgg1(Ser326Cys) protein which is
RT frequently found in human populations.";
RL Nucleic Acids Res. 27:4001-4007(1999).
RN [22]
RP CHARACTERIZATION OF VARIANTS GLN-46 AND HIS-154.
RX MEDLINE=20368626; PubMed=10908322; DOI=10.1093/nar/28.14.2672;
RA Audebert M., Radicella J.P., Dizdaroglu M.;
RT "Effect of single mutations in the OGG1 gene found in human tumors on
RT the substrate specificity of the ogg1 protein.";
RL Nucleic Acids Res. 28:2672-2678(2000).
RN [23]
RP CHARACTERIZATION OF VARIANT GLU-12.
RX MEDLINE=22397562; PubMed=12509224; DOI=10.1016/S1568-7864(02)00034-4;
RA Audebert M., Charbonnier J.B., Boiteux S., Radicella J.P.;
RT "Mitochondrial targeting of human 8-oxoguanine DNA glycosylase hOGG1
RT is impaired by a somatic mutation found in kidney cancer.";
RL DNA Repair 1:497-505(2002).
Feature:
CHAIN 1 345 N-glycosylase/DNA lyase.
/FTId=PRO_0000058591.
ACT_SITE 249 249 Schiff-base intermediate with DNA.
BINDING 149 149 DNA.
BINDING 154 154 DNA.
BINDING 204 204 DNA.
BINDING 266 266 8-oxoguanine; via carbonyl oxygen.
BINDING 268 268 8-oxoguanine.
BINDING 270 270 DNA.
BINDING 287 287 DNA.
BINDING 315 315 8-oxoguanine.
BINDING 319 319 8-oxoguanine.
VARSPLIC 191 195 EVEAH -> PWQCI (in isoform 2C).
/FTId=VSP_003750.
VARSPLIC 196 345 Missing (in isoform 2C).
/FTId=VSP_003751.
VARSPLIC 250 345 VADCICLMALDKPQAVPVDVHMWHIAQRDYSWHPTTSQAKG
PSPQTNKELGNFFRSLWGPYAGWAQAVLFSADLRQSRHAQE
PPAKRRKGSKGPEG -> GLLGNAFDGHQLLRPLIFCQDHL
REGPPIGRGDSQGEELEPQLPSSLSSIPYGFCDHCWTKDVD
DPPLVTHPSPGSRDGHMTQAWPVKVVSPLATVIGHVMQASL
LAL (in isoform 2B).
/FTId=VSP_003749.
VARSPLIC 317 345 VLFSADLRQSRHAQEPPAKRRKGSKGPEG -> VSVPRCPP
(in isoform 1B).
/FTId=VSP_003746.
VARSPLIC 317 345 VLFSADLRQSRHAQEPPAKRRKGSKGPEG -> TPPSYRCC
SVPTCANPAMLRSHQQSAERVPKGRKARWGTLDKEIPQAPS
PPFPTSLSPSPPSLMLGRGLPVTTSKARHPQIKQSVCTTRW
GGGY (in isoform 1C).
/FTId=VSP_003747.
VARSPLIC 317 345 VLFSADLRQSRHAQEPPAKRRKGSKGPEG -> GLLGNAFD
GHQLLRPLIFCQDHLREGPPIGRGDSQGEELEPQLPSSLSS
IPYGFCDHCWTKDVDDPPLVTHPSPGSRDGHMTQAWPVKVV
SPLATVIGHVMQASLLAL (in isoform 2A).
/FTId=VSP_003748.
VARSPLIC 317 345 VLFSADLRQSRHAQEPPAKRRKGSKGPEG -> LCQVITTF
MTFLGPHRLDQMPPEELQTSSSRLG (in isoform
2D).
/FTId=VSP_003752.
VARSPLIC 317 345 VLFSADLRQSRHAQEPPAKRRKGSKGPEG -> AGSDAS
(in isoform 2E).
/FTId=VSP_003753.
VARIANT 12 12 G -> E (in kidney cancer; no effect on
activity. Abolishes mitochondrial
localization).
/FTId=VAR_024831.
VARIANT 46 46 R -> Q (in kidney cancer; diminished
activity).
/FTId=VAR_009519.
VARIANT 85 85 A -> S (in lung cancer; dbSNP:17050550).
/FTId=VAR_024832.
VARIANT 131 131 R -> Q (in lung cancer; loss of
activity).
/FTId=VAR_024833.
VARIANT 154 154 R -> H (in gastric cancer; No effect on
base-excision activity. Alters substrate
specificity and strongly increases
mutagenic mis-repair).
/FTId=VAR_009520.
VARIANT 229 229 R -> Q (in dbSNP:1805373).
/FTId=VAR_014487.
VARIANT 232 232 S -> T (in kidney cancer).
/FTId=VAR_024834.
VARIANT 288 288 A -> V (in dbSNP:3219012).
/FTId=VAR_018890.
VARIANT 320 320 S -> T (in dbSNP:1801128).
/FTId=VAR_014488.
VARIANT 322 322 D -> N (in dbSNP:3219014).
/FTId=VAR_018891.
VARIANT 326 326 S -> C (common polymorphism in the
Japanese population; dbSNP:1052133).
/FTId=VAR_009521.
MUTAGEN 249 249 K->Q: Loss of activity.
MUTAGEN 268 268 D->E,Q: No effect on activity.
MUTAGEN 268 268 D->N: Decreases activity about 65-fold.
CONFLICT 47 47 W -> WW (in Ref. 9).
CONFLICT 308 308 G -> E (in Ref. 9).
CONFLICT 316 316 A -> ATPPSLQ (in Ref. 2).
STRAND 11 13
TURN 16 18
HELIX 20 22
STRAND 24 27
TURN 30 32
HELIX 35 38
TURN 39 40
STRAND 41 43
STRAND 45 45
STRAND 48 51
TURN 52 53
STRAND 54 59
TURN 60 61
STRAND 62 68
STRAND 70 78
HELIX 90 99
TURN 100 103
STRAND 104 104
HELIX 106 116
HELIX 118 126
STRAND 127 127
TURN 128 129
HELIX 137 147
TURN 148 149
HELIX 152 166
STRAND 167 167
STRAND 169 173
TURN 174 175
STRAND 176 179
HELIX 184 187
TURN 188 188
STRAND 189 189
TURN 190 191
HELIX 192 198
TURN 199 200
TURN 202 203
HELIX 204 217
TURN 218 218
STRAND 219 219
STRAND 221 221
HELIX 222 227
TURN 228 230
STRAND 231 231
HELIX 233 240
TURN 241 242
STRAND 243 243
TURN 244 245
HELIX 248 258
STRAND 259 259
TURN 262 263
STRAND 268 268
HELIX 269 279
STRAND 284 287
STRAND 289 292
HELIX 293 307
TURN 309 310
HELIX 311 324
Comments:
-!- FUNCTION: DNA repair enzyme that incises DNA at 8-oxoG residues.
Excises 7,8-dihydro-8-oxoguanine and 2,6-diamino-4-hydroxy-5-N-
methylformamidopyrimidine (FAPY) from damaged DNA. Has a beta-
lyase activity that nicks DNA 3' to the lesion.
-!- CATALYTIC ACTIVITY: Endonucleolytic cleavage near apurinic or
apyrimidinic sites to products with 5'-phosphate.
-!- SUBCELLULAR LOCATION: Nuclear (isoform 1A) and mitochondrial
(isoform 2A).
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=8;
Name=1A; Synonyms=Alpha;
IsoId=O15527-1; Sequence=Displayed;
Name=1B;
IsoId=O15527-2; Sequence=VSP_003746;
Name=1C;
IsoId=O15527-3; Sequence=VSP_003747;
Name=2A; Synonyms=Beta;
IsoId=O15527-4; Sequence=VSP_003748;
Name=2B;
IsoId=O15527-5; Sequence=VSP_003749;
Name=2C;
IsoId=O15527-6; Sequence=VSP_003750, VSP_003751;
Name=2D;
IsoId=O15527-7; Sequence=VSP_003752;
Name=2E;
IsoId=O15527-8; Sequence=VSP_003753;
-!- TISSUE SPECIFICITY: Ubiquitous.
-!- DISEASE: Defects in OGG1 are associated with tumor formation.
-!- DISEASE: Defects in OGG1 are a cause of renal cell carcinoma
(RCC1) [MIM:144700].
-!- SIMILARITY: Belongs to the type-1 OGG1 family.
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Sequence length: 345
MPARALLPRR MGHRTLASTP ALWASIPCPR SELRLDLVLP SGQSFRWREQ SPAHWSGVLA
DQVWTLTQTE EQLHCTVYRG DKSQASRPTP DELEAVRKYF QLDVTLAQLY HHWGSVDSHF
QEVAQKFQGV RLLRQDPIEC LFSFICSSNN NIARITGMVE RLCQAFGPRL IQLDDVTYHG
FPSLQALAGP EVEAHLRKLG LGYRARYVSA SARAILEEQG GLAWLQQLRE SSYEEAHKAL
CILPGVGTKV ADCICLMALD KPQAVPVDVH MWHIAQRDYS WHPTTSQAKG PSPQTNKELG
NFFRSLWGPY AGWAQAVLFS ADLRQSRHAQ EPPAKRRKGS KGPEG