Full text data of TP53I3
TP53I3
(PIG3)
[Confidence: low (only semi-automatic identification from reviews)]
Quinone oxidoreductase PIG3; 1.-.-.- (Tumor protein p53-inducible protein 3; p53-induced gene 3 protein)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Quinone oxidoreductase PIG3; 1.-.-.- (Tumor protein p53-inducible protein 3; p53-induced gene 3 protein)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q53FA7
ID QORX_HUMAN Reviewed; 332 AA.
AC Q53FA7; D6W533; O14679; O14685; Q38G78; Q6JLE7; Q9BWB8;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 27-SEP-2005, sequence version 2.
DT 22-JAN-2014, entry version 86.
DE RecName: Full=Quinone oxidoreductase PIG3;
DE EC=1.-.-.-;
DE AltName: Full=Tumor protein p53-inducible protein 3;
DE AltName: Full=p53-induced gene 3 protein;
GN Name=TP53I3; Synonyms=PIG3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND INDUCTION BY
RP TP53.
RC TISSUE=Colon cancer;
RX PubMed=9305847; DOI=10.1038/38525;
RA Polyak K., Xia Y., Zweier J.L., Kinzler K.W., Vogelstein B.;
RT "A model for p53-induced apoptosis.";
RL Nature 389:300-306(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Mammary tumor;
RX PubMed=15067011; DOI=10.1074/jbc.M401049200;
RA Nicholls C.D., Shields M.A., Lee P.W.K., Robbins S.M., Beattie T.L.;
RT "UV-dependent alternative splicing uncouples p53 activity and PIG3
RT gene function through rapid proteolytic degradation.";
RL J. Biol. Chem. 279:24171-24178(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Gastric mucosa;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 1-33; 163-176; 184-203; 259-267; 297-303 AND
RP 326-332, ACETYLATION AT MET-1, AND MASS SPECTROMETRY.
RC TISSUE=Lung carcinoma;
RA Bienvenut W.V., Vousden K.H., Lukashchuk N.;
RL Submitted (MAR-2008) to UniProtKB.
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH NADP, FUNCTION,
RP SUBUNIT, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF TYR-51 AND SER-151.
RX PubMed=19349281; DOI=10.1074/jbc.M109.001800;
RA Porte S., Valencia E., Yakovtseva E.A., Borras E., Shafqat N.,
RA Debreczeny J.E., Pike A.C.W., Oppermann U., Farres J., Fita I.,
RA Pares X.;
RT "Three-dimensional structure and enzymatic function of proapoptotic
RT human p53-inducible quinone oxidoreductase PIG3.";
RL J. Biol. Chem. 284:17194-17205(2009).
RN [12]
RP VARIANT LYS-180.
RX PubMed=17224074; DOI=10.1186/bcr1637;
RA Chanock S.J., Burdett L., Yeager M., Llaca V., Langeroed A.,
RA Presswalla S., Kaaresen R., Strausberg R.L., Gerhard D.S.,
RA Kristensen V., Perou C.M., Boerresen-Dale A.-L.;
RT "Somatic sequence alterations in twenty-one genes selected by
RT expression profile analysis of breast carcinomas.";
RL Breast Cancer Res. 9:R5-R5(2007).
CC -!- FUNCTION: May be involved in the generation of reactive oxygen
CC species (ROS). Has low NADPH-dependent beta-naphthoquinone
CC reductase activity, with a preference for 1,2-beta-naphthoquinone
CC over 1,4-beta-naphthoquinone. Has low NADPH-dependent diamine
CC reductase activity (in vitro).
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=215 uM for 1,2-naphthoquinone;
CC -!- SUBUNIT: Homodimer.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=UV radiation favors the production of isoform 2;
CC Name=1;
CC IsoId=Q53FA7-1; Sequence=Displayed;
CC Note=Major isoform under normal light conditions;
CC Name=2; Synonyms=PIG3AS;
CC IsoId=Q53FA7-2; Sequence=VSP_015783, VSP_015784;
CC Note=Major isoform under UV light exposure. Undergoes rapid
CC proteolytic degradation by the proteasome;
CC -!- INDUCTION: Isoform 1 and isoform 2 are both activated by p53/TP53,
CC doxorubicin, etoposide and ionizing radiation. Isoform 2 is highly
CC activated by UV radiation.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. Quinone oxidoreductase subfamily.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC39535.1; Type=Erroneous gene model prediction;
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/tp53i3/";
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DR EMBL; AF010309; AAC39528.1; -; mRNA.
DR EMBL; AF010317; AAC39535.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AY371700; AAQ90166.1; -; mRNA.
DR EMBL; BT007149; AAP35813.1; -; mRNA.
DR EMBL; AK223382; BAD97102.1; -; mRNA.
DR EMBL; DQ232851; ABB02183.1; -; Genomic_DNA.
DR EMBL; AC008073; AAY14665.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00762.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00763.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00766.1; -; Genomic_DNA.
DR EMBL; BC000474; AAH00474.1; -; mRNA.
DR RefSeq; NP_001193731.1; NM_001206802.2.
DR RefSeq; NP_004872.2; NM_004881.4.
DR RefSeq; NP_671713.1; NM_147184.3.
DR UniGene; Hs.50649; -.
DR UniGene; Hs.733381; -.
DR PDB; 2J8Z; X-ray; 2.50 A; A=1-332.
DR PDB; 2OBY; X-ray; 3.00 A; A/B/C/D/E=1-332.
DR PDBsum; 2J8Z; -.
DR PDBsum; 2OBY; -.
DR ProteinModelPortal; Q53FA7; -.
DR SMR; Q53FA7; 1-332.
DR IntAct; Q53FA7; 4.
DR STRING; 9606.ENSP00000238721; -.
DR PhosphoSite; Q53FA7; -.
DR DMDM; 76789665; -.
DR PaxDb; Q53FA7; -.
DR PeptideAtlas; Q53FA7; -.
DR PRIDE; Q53FA7; -.
DR DNASU; 9540; -.
DR Ensembl; ENST00000238721; ENSP00000238721; ENSG00000115129.
DR Ensembl; ENST00000313482; ENSP00000322298; ENSG00000115129.
DR Ensembl; ENST00000335934; ENSP00000337834; ENSG00000115129.
DR Ensembl; ENST00000407482; ENSP00000384414; ENSG00000115129.
DR GeneID; 9540; -.
DR KEGG; hsa:9540; -.
DR UCSC; uc002rey.2; human.
DR CTD; 9540; -.
DR GeneCards; GC02M024300; -.
DR HGNC; HGNC:19373; TP53I3.
DR HPA; CAB017479; -.
DR HPA; HPA022012; -.
DR HPA; HPA028742; -.
DR MIM; 605171; gene.
DR neXtProt; NX_Q53FA7; -.
DR PharmGKB; PA134923704; -.
DR eggNOG; COG0604; -.
DR HOGENOM; HOG000294672; -.
DR HOVERGEN; HBG097584; -.
DR InParanoid; Q53FA7; -.
DR KO; K10133; -.
DR OMA; SSAHIGK; -.
DR OrthoDB; EOG7Z69CN; -.
DR PhylomeDB; Q53FA7; -.
DR EvolutionaryTrace; Q53FA7; -.
DR GeneWiki; TP53I3; -.
DR GenomeRNAi; 9540; -.
DR NextBio; 35770; -.
DR PRO; PR:Q53FA7; -.
DR ArrayExpress; Q53FA7; -.
DR Bgee; Q53FA7; -.
DR CleanEx; HS_TP53I3; -.
DR Genevestigator; Q53FA7; -.
DR GO; GO:0070402; F:NADPH binding; IDA:UniProtKB.
DR GO; GO:0003960; F:NADPH:quinone reductase activity; IDA:UniProtKB.
DR GO; GO:0048038; F:quinone binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; NAS:UniProtKB.
DR GO; GO:0006739; P:NADP metabolic process; IDA:UniProtKB.
DR Gene3D; 3.40.50.720; -; 1.
DR Gene3D; 3.90.180.10; -; 1.
DR InterPro; IPR013149; ADH_C.
DR InterPro; IPR013154; ADH_GroES-like.
DR InterPro; IPR002085; ADH_SF_Zn-type.
DR InterPro; IPR011032; GroES-like.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR014189; Quinone_OxRdtase_PIG3.
DR PANTHER; PTHR11695; PTHR11695; 1.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR TIGRFAMs; TIGR02824; quinone_pig3; 1.
DR PROSITE; PS01162; QOR_ZETA_CRYSTAL; FALSE_NEG.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Direct protein sequencing; NADP; Oxidoreductase; Polymorphism;
KW Reference proteome.
FT CHAIN 1 332 Quinone oxidoreductase PIG3.
FT /FTId=PRO_0000160917.
FT NP_BIND 148 154 NADP.
FT NP_BIND 173 177 NADP.
FT NP_BIND 264 266 NADP.
FT BINDING 41 41 NADP.
FT BINDING 192 192 NADP.
FT BINDING 322 322 NADP.
FT MOD_RES 1 1 N-acetylmethionine.
FT VAR_SEQ 207 248 GAGVNLILDCIGGSYWEKNVNCLALDGRWVLYGLMGGGDIN
FT G -> VQANAGECFHGANSASLLHGGPPTSAAGSGQNLPSD
FT RNPGGP (in isoform 2).
FT /FTId=VSP_015783.
FT VAR_SEQ 249 332 Missing (in isoform 2).
FT /FTId=VSP_015784.
FT VARIANT 180 180 M -> K (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_033032.
FT VARIANT 223 223 E -> K (in dbSNP:rs35176319).
FT /FTId=VAR_048201.
FT MUTAGEN 51 51 Y->A: Loss of enzyme activity.
FT MUTAGEN 51 51 Y->F: Increased enzyme activity.
FT MUTAGEN 151 151 S->V: Loss of enzyme activity.
FT CONFLICT 36 36 A -> AA (in Ref. 1; AAC39535).
FT CONFLICT 263 263 T -> A (in Ref. 4; BAD97102).
FT CONFLICT 315 332 KYMEANKNIGKIVLELPQ -> STWRPTRT (in Ref.
FT 1; AAC39528).
FT STRAND 1 8
FT HELIX 12 14
FT STRAND 15 21
FT STRAND 29 38
FT HELIX 41 47
FT STRAND 59 61
FT STRAND 63 72
FT STRAND 78 80
FT STRAND 85 89
FT STRAND 95 102
FT HELIX 103 105
FT STRAND 106 108
FT HELIX 115 118
FT HELIX 122 132
FT TURN 133 135
FT STRAND 143 148
FT HELIX 152 163
FT STRAND 167 173
FT HELIX 175 184
FT STRAND 187 191
FT TURN 192 194
FT HELIX 197 204
FT TURN 205 207
FT STRAND 210 217
FT HELIX 219 221
FT HELIX 222 228
FT STRAND 229 237
FT STRAND 246 248
FT HELIX 250 256
FT STRAND 260 263
FT HELIX 271 284
FT HELIX 286 289
FT STRAND 301 306
FT HELIX 307 309
FT HELIX 310 318
FT STRAND 323 329
SQ SEQUENCE 332 AA; 35536 MW; C5A33C46B3F96473 CRC64;
MLAVHFDKPG GPENLYVKEV AKPSPGEGEV LLKVAASALN RADLMQRQGQ YDPPPGASNI
LGLEASGHVA ELGPGCQGHW KIGDTAMALL PGGGQAQYVT VPEGLLMPIP EGLTLTQAAA
IPEAWLTAFQ LLHLVGNVQA GDYVLIHAGL SGVGTAAIQL TRMAGAIPLV TAGSQKKLQM
AEKLGAAAGF NYKKEDFSEA TLKFTKGAGV NLILDCIGGS YWEKNVNCLA LDGRWVLYGL
MGGGDINGPL FSKLLFKRGS LITSLLRSRD NKYKQMLVNA FTEQILPHFS TEGPQRLLPV
LDRIYPVTEI QEAHKYMEAN KNIGKIVLEL PQ
//
ID QORX_HUMAN Reviewed; 332 AA.
AC Q53FA7; D6W533; O14679; O14685; Q38G78; Q6JLE7; Q9BWB8;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 27-SEP-2005, sequence version 2.
DT 22-JAN-2014, entry version 86.
DE RecName: Full=Quinone oxidoreductase PIG3;
DE EC=1.-.-.-;
DE AltName: Full=Tumor protein p53-inducible protein 3;
DE AltName: Full=p53-induced gene 3 protein;
GN Name=TP53I3; Synonyms=PIG3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND INDUCTION BY
RP TP53.
RC TISSUE=Colon cancer;
RX PubMed=9305847; DOI=10.1038/38525;
RA Polyak K., Xia Y., Zweier J.L., Kinzler K.W., Vogelstein B.;
RT "A model for p53-induced apoptosis.";
RL Nature 389:300-306(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Mammary tumor;
RX PubMed=15067011; DOI=10.1074/jbc.M401049200;
RA Nicholls C.D., Shields M.A., Lee P.W.K., Robbins S.M., Beattie T.L.;
RT "UV-dependent alternative splicing uncouples p53 activity and PIG3
RT gene function through rapid proteolytic degradation.";
RL J. Biol. Chem. 279:24171-24178(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Gastric mucosa;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 1-33; 163-176; 184-203; 259-267; 297-303 AND
RP 326-332, ACETYLATION AT MET-1, AND MASS SPECTROMETRY.
RC TISSUE=Lung carcinoma;
RA Bienvenut W.V., Vousden K.H., Lukashchuk N.;
RL Submitted (MAR-2008) to UniProtKB.
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH NADP, FUNCTION,
RP SUBUNIT, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF TYR-51 AND SER-151.
RX PubMed=19349281; DOI=10.1074/jbc.M109.001800;
RA Porte S., Valencia E., Yakovtseva E.A., Borras E., Shafqat N.,
RA Debreczeny J.E., Pike A.C.W., Oppermann U., Farres J., Fita I.,
RA Pares X.;
RT "Three-dimensional structure and enzymatic function of proapoptotic
RT human p53-inducible quinone oxidoreductase PIG3.";
RL J. Biol. Chem. 284:17194-17205(2009).
RN [12]
RP VARIANT LYS-180.
RX PubMed=17224074; DOI=10.1186/bcr1637;
RA Chanock S.J., Burdett L., Yeager M., Llaca V., Langeroed A.,
RA Presswalla S., Kaaresen R., Strausberg R.L., Gerhard D.S.,
RA Kristensen V., Perou C.M., Boerresen-Dale A.-L.;
RT "Somatic sequence alterations in twenty-one genes selected by
RT expression profile analysis of breast carcinomas.";
RL Breast Cancer Res. 9:R5-R5(2007).
CC -!- FUNCTION: May be involved in the generation of reactive oxygen
CC species (ROS). Has low NADPH-dependent beta-naphthoquinone
CC reductase activity, with a preference for 1,2-beta-naphthoquinone
CC over 1,4-beta-naphthoquinone. Has low NADPH-dependent diamine
CC reductase activity (in vitro).
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=215 uM for 1,2-naphthoquinone;
CC -!- SUBUNIT: Homodimer.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=UV radiation favors the production of isoform 2;
CC Name=1;
CC IsoId=Q53FA7-1; Sequence=Displayed;
CC Note=Major isoform under normal light conditions;
CC Name=2; Synonyms=PIG3AS;
CC IsoId=Q53FA7-2; Sequence=VSP_015783, VSP_015784;
CC Note=Major isoform under UV light exposure. Undergoes rapid
CC proteolytic degradation by the proteasome;
CC -!- INDUCTION: Isoform 1 and isoform 2 are both activated by p53/TP53,
CC doxorubicin, etoposide and ionizing radiation. Isoform 2 is highly
CC activated by UV radiation.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. Quinone oxidoreductase subfamily.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC39535.1; Type=Erroneous gene model prediction;
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/tp53i3/";
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DR EMBL; AF010309; AAC39528.1; -; mRNA.
DR EMBL; AF010317; AAC39535.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AY371700; AAQ90166.1; -; mRNA.
DR EMBL; BT007149; AAP35813.1; -; mRNA.
DR EMBL; AK223382; BAD97102.1; -; mRNA.
DR EMBL; DQ232851; ABB02183.1; -; Genomic_DNA.
DR EMBL; AC008073; AAY14665.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00762.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00763.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00766.1; -; Genomic_DNA.
DR EMBL; BC000474; AAH00474.1; -; mRNA.
DR RefSeq; NP_001193731.1; NM_001206802.2.
DR RefSeq; NP_004872.2; NM_004881.4.
DR RefSeq; NP_671713.1; NM_147184.3.
DR UniGene; Hs.50649; -.
DR UniGene; Hs.733381; -.
DR PDB; 2J8Z; X-ray; 2.50 A; A=1-332.
DR PDB; 2OBY; X-ray; 3.00 A; A/B/C/D/E=1-332.
DR PDBsum; 2J8Z; -.
DR PDBsum; 2OBY; -.
DR ProteinModelPortal; Q53FA7; -.
DR SMR; Q53FA7; 1-332.
DR IntAct; Q53FA7; 4.
DR STRING; 9606.ENSP00000238721; -.
DR PhosphoSite; Q53FA7; -.
DR DMDM; 76789665; -.
DR PaxDb; Q53FA7; -.
DR PeptideAtlas; Q53FA7; -.
DR PRIDE; Q53FA7; -.
DR DNASU; 9540; -.
DR Ensembl; ENST00000238721; ENSP00000238721; ENSG00000115129.
DR Ensembl; ENST00000313482; ENSP00000322298; ENSG00000115129.
DR Ensembl; ENST00000335934; ENSP00000337834; ENSG00000115129.
DR Ensembl; ENST00000407482; ENSP00000384414; ENSG00000115129.
DR GeneID; 9540; -.
DR KEGG; hsa:9540; -.
DR UCSC; uc002rey.2; human.
DR CTD; 9540; -.
DR GeneCards; GC02M024300; -.
DR HGNC; HGNC:19373; TP53I3.
DR HPA; CAB017479; -.
DR HPA; HPA022012; -.
DR HPA; HPA028742; -.
DR MIM; 605171; gene.
DR neXtProt; NX_Q53FA7; -.
DR PharmGKB; PA134923704; -.
DR eggNOG; COG0604; -.
DR HOGENOM; HOG000294672; -.
DR HOVERGEN; HBG097584; -.
DR InParanoid; Q53FA7; -.
DR KO; K10133; -.
DR OMA; SSAHIGK; -.
DR OrthoDB; EOG7Z69CN; -.
DR PhylomeDB; Q53FA7; -.
DR EvolutionaryTrace; Q53FA7; -.
DR GeneWiki; TP53I3; -.
DR GenomeRNAi; 9540; -.
DR NextBio; 35770; -.
DR PRO; PR:Q53FA7; -.
DR ArrayExpress; Q53FA7; -.
DR Bgee; Q53FA7; -.
DR CleanEx; HS_TP53I3; -.
DR Genevestigator; Q53FA7; -.
DR GO; GO:0070402; F:NADPH binding; IDA:UniProtKB.
DR GO; GO:0003960; F:NADPH:quinone reductase activity; IDA:UniProtKB.
DR GO; GO:0048038; F:quinone binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; NAS:UniProtKB.
DR GO; GO:0006739; P:NADP metabolic process; IDA:UniProtKB.
DR Gene3D; 3.40.50.720; -; 1.
DR Gene3D; 3.90.180.10; -; 1.
DR InterPro; IPR013149; ADH_C.
DR InterPro; IPR013154; ADH_GroES-like.
DR InterPro; IPR002085; ADH_SF_Zn-type.
DR InterPro; IPR011032; GroES-like.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR014189; Quinone_OxRdtase_PIG3.
DR PANTHER; PTHR11695; PTHR11695; 1.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR TIGRFAMs; TIGR02824; quinone_pig3; 1.
DR PROSITE; PS01162; QOR_ZETA_CRYSTAL; FALSE_NEG.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Direct protein sequencing; NADP; Oxidoreductase; Polymorphism;
KW Reference proteome.
FT CHAIN 1 332 Quinone oxidoreductase PIG3.
FT /FTId=PRO_0000160917.
FT NP_BIND 148 154 NADP.
FT NP_BIND 173 177 NADP.
FT NP_BIND 264 266 NADP.
FT BINDING 41 41 NADP.
FT BINDING 192 192 NADP.
FT BINDING 322 322 NADP.
FT MOD_RES 1 1 N-acetylmethionine.
FT VAR_SEQ 207 248 GAGVNLILDCIGGSYWEKNVNCLALDGRWVLYGLMGGGDIN
FT G -> VQANAGECFHGANSASLLHGGPPTSAAGSGQNLPSD
FT RNPGGP (in isoform 2).
FT /FTId=VSP_015783.
FT VAR_SEQ 249 332 Missing (in isoform 2).
FT /FTId=VSP_015784.
FT VARIANT 180 180 M -> K (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_033032.
FT VARIANT 223 223 E -> K (in dbSNP:rs35176319).
FT /FTId=VAR_048201.
FT MUTAGEN 51 51 Y->A: Loss of enzyme activity.
FT MUTAGEN 51 51 Y->F: Increased enzyme activity.
FT MUTAGEN 151 151 S->V: Loss of enzyme activity.
FT CONFLICT 36 36 A -> AA (in Ref. 1; AAC39535).
FT CONFLICT 263 263 T -> A (in Ref. 4; BAD97102).
FT CONFLICT 315 332 KYMEANKNIGKIVLELPQ -> STWRPTRT (in Ref.
FT 1; AAC39528).
FT STRAND 1 8
FT HELIX 12 14
FT STRAND 15 21
FT STRAND 29 38
FT HELIX 41 47
FT STRAND 59 61
FT STRAND 63 72
FT STRAND 78 80
FT STRAND 85 89
FT STRAND 95 102
FT HELIX 103 105
FT STRAND 106 108
FT HELIX 115 118
FT HELIX 122 132
FT TURN 133 135
FT STRAND 143 148
FT HELIX 152 163
FT STRAND 167 173
FT HELIX 175 184
FT STRAND 187 191
FT TURN 192 194
FT HELIX 197 204
FT TURN 205 207
FT STRAND 210 217
FT HELIX 219 221
FT HELIX 222 228
FT STRAND 229 237
FT STRAND 246 248
FT HELIX 250 256
FT STRAND 260 263
FT HELIX 271 284
FT HELIX 286 289
FT STRAND 301 306
FT HELIX 307 309
FT HELIX 310 318
FT STRAND 323 329
SQ SEQUENCE 332 AA; 35536 MW; C5A33C46B3F96473 CRC64;
MLAVHFDKPG GPENLYVKEV AKPSPGEGEV LLKVAASALN RADLMQRQGQ YDPPPGASNI
LGLEASGHVA ELGPGCQGHW KIGDTAMALL PGGGQAQYVT VPEGLLMPIP EGLTLTQAAA
IPEAWLTAFQ LLHLVGNVQA GDYVLIHAGL SGVGTAAIQL TRMAGAIPLV TAGSQKKLQM
AEKLGAAAGF NYKKEDFSEA TLKFTKGAGV NLILDCIGGS YWEKNVNCLA LDGRWVLYGL
MGGGDINGPL FSKLLFKRGS LITSLLRSRD NKYKQMLVNA FTEQILPHFS TEGPQRLLPV
LDRIYPVTEI QEAHKYMEAN KNIGKIVLEL PQ
//
MIM
605171
*RECORD*
*FIELD* NO
605171
*FIELD* TI
*605171 TUMOR PROTEIN p53-INDUCIBLE PROTEIN 3; TP53I3
;;p53-INDUCED GENE 3; PIG3
*FIELD* TX
read more
CLONING
DNA damage and/or hyperproliferative signals activate wildtype p53 tumor
suppressor protein (TP53; 191170), inducing cell cycle arrest or
apoptosis. Mutations that inactivate p53 occur in 50% of all tumors.
Polyak et al. (1997) used serial analysis of gene expression (SAGE) to
evaluate cellular mRNA levels in a colorectal cancer cell line
transfected with p53. Of 7,202 transcripts identified, only 14 were
expressed at levels more than 10-fold higher in p53-expressing cells
than in control cells. Polyak et al. (1997) termed these genes
'p53-induced genes,' or PIGs, several of which were predicted to encode
redox-controlling proteins. They noted that reactive oxygen species
(ROS) are potent inducers of apoptosis. Flow cytometric analysis showed
that p53 expression induces ROS production, which increases as apoptosis
progresses under some conditions. The authors stated that the PIG3 gene
encodes a quinone oxidoreductase homolog (see 123691).
MAPPING
By analysis of a BAC clone, Polyak et al. (1997) mapped the PIG3 gene to
2p.
GENE FUNCTION
The gene PIG3 is induced by the tumor suppressor p53 but not by p53
mutants unable to induce apoptosis, suggesting its involvement in
p53-mediated cell death. Contente et al. (2002) showed that p53 directly
binds and activates the PIG3 promoter, but not through the DNA element
described by Polyak et al. (1997). Instead, p53 interacts with a
pentanucleotide microsatellite sequence within the PIG3 promoter
(TGYCC)n where Y = C or T. Despite its limited similarity to the
p53-binding consensus, this sequence is necessary and sufficient for
transcriptional activation of the PIG3 promoter by p53 and binds
specifically to p53 in vitro and in vivo. In a population of 117 healthy
donors from Germany, the microsatellite was found to be polymorphic, the
number of pentanucleotide repeats being 10, 15, 16, or 17, and the
frequency of alleles 5.1%, 62.0%, 21.4%, and 11.5%, respectively. The
number of repeats directly correlated with the extent of transcriptional
activation by p53. This was the first time that a microsatellite had
been shown to mediate the induction of a promoter through direct
interaction with a transcription factor. Moreover, this sequence of PIG3
was the first p53-responsive element found to be polymorphic. Contente
et al. (2002) suggested that inheritance of this microsatellite may
affect an individual's susceptibility to cancer.
*FIELD* RF
1. Contente, A.; Dittmer, A.; Koch, M. C.; Roth, J.; Dobbelstein,
M.: A polymorphic microsatellite that mediates induction of PIG3
by p53. Nature Genet. 30: 315-320, 2002.
2. Polyak, K.; Xia, Y.; Zweier, J. L.; Kinzler, K. W.; Vogelstein,
B.: A model for p53-induced apoptosis. Nature 389: 300-305, 1997.
*FIELD* CN
Victor A. McKusick - updated: 2/19/2002
*FIELD* CD
Paul J. Converse: 7/25/2000
*FIELD* ED
carol: 07/21/2006
alopez: 2/22/2002
terry: 2/19/2002
mgross: 7/25/2000
*RECORD*
*FIELD* NO
605171
*FIELD* TI
*605171 TUMOR PROTEIN p53-INDUCIBLE PROTEIN 3; TP53I3
;;p53-INDUCED GENE 3; PIG3
*FIELD* TX
read more
CLONING
DNA damage and/or hyperproliferative signals activate wildtype p53 tumor
suppressor protein (TP53; 191170), inducing cell cycle arrest or
apoptosis. Mutations that inactivate p53 occur in 50% of all tumors.
Polyak et al. (1997) used serial analysis of gene expression (SAGE) to
evaluate cellular mRNA levels in a colorectal cancer cell line
transfected with p53. Of 7,202 transcripts identified, only 14 were
expressed at levels more than 10-fold higher in p53-expressing cells
than in control cells. Polyak et al. (1997) termed these genes
'p53-induced genes,' or PIGs, several of which were predicted to encode
redox-controlling proteins. They noted that reactive oxygen species
(ROS) are potent inducers of apoptosis. Flow cytometric analysis showed
that p53 expression induces ROS production, which increases as apoptosis
progresses under some conditions. The authors stated that the PIG3 gene
encodes a quinone oxidoreductase homolog (see 123691).
MAPPING
By analysis of a BAC clone, Polyak et al. (1997) mapped the PIG3 gene to
2p.
GENE FUNCTION
The gene PIG3 is induced by the tumor suppressor p53 but not by p53
mutants unable to induce apoptosis, suggesting its involvement in
p53-mediated cell death. Contente et al. (2002) showed that p53 directly
binds and activates the PIG3 promoter, but not through the DNA element
described by Polyak et al. (1997). Instead, p53 interacts with a
pentanucleotide microsatellite sequence within the PIG3 promoter
(TGYCC)n where Y = C or T. Despite its limited similarity to the
p53-binding consensus, this sequence is necessary and sufficient for
transcriptional activation of the PIG3 promoter by p53 and binds
specifically to p53 in vitro and in vivo. In a population of 117 healthy
donors from Germany, the microsatellite was found to be polymorphic, the
number of pentanucleotide repeats being 10, 15, 16, or 17, and the
frequency of alleles 5.1%, 62.0%, 21.4%, and 11.5%, respectively. The
number of repeats directly correlated with the extent of transcriptional
activation by p53. This was the first time that a microsatellite had
been shown to mediate the induction of a promoter through direct
interaction with a transcription factor. Moreover, this sequence of PIG3
was the first p53-responsive element found to be polymorphic. Contente
et al. (2002) suggested that inheritance of this microsatellite may
affect an individual's susceptibility to cancer.
*FIELD* RF
1. Contente, A.; Dittmer, A.; Koch, M. C.; Roth, J.; Dobbelstein,
M.: A polymorphic microsatellite that mediates induction of PIG3
by p53. Nature Genet. 30: 315-320, 2002.
2. Polyak, K.; Xia, Y.; Zweier, J. L.; Kinzler, K. W.; Vogelstein,
B.: A model for p53-induced apoptosis. Nature 389: 300-305, 1997.
*FIELD* CN
Victor A. McKusick - updated: 2/19/2002
*FIELD* CD
Paul J. Converse: 7/25/2000
*FIELD* ED
carol: 07/21/2006
alopez: 2/22/2002
terry: 2/19/2002
mgross: 7/25/2000