ID   APR_MOUSE               Reviewed;         103 AA.
AC   Q9JM54;
DT   20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   04-NOV-2008, entry version 55.
DE   RecName: Full=Phorbol-12-myristate-13-acetate-induced protein 1;
DE   AltName: Full=Noxa;
GN   Name=Pmaip1; Synonyms=Noxa;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC   Muroidea; Muridae; Murinae; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH MCL1, SUBCELLULAR
RP   LOCATION, FUNCTION, AND MUTAGENESIS OF LEU-27 AND LEU-78.
RX   MEDLINE=20268001; PubMed=10807576; DOI=10.1126/science.288.5468.1053;
RA   Oda E., Ohki R., Murasawa H., Nemoto J., Shibue T., Yamashita T.,
RA   Tokino T., Taniguchi T., Tanaka N.;
RT   "Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of
RT   p53-induced apoptosis.";
RL   Science 288:1053-1058(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J, and NOD;
RC   TISSUE=Brain cortex, Dendritic cell, Kidney, and Thymus;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M.,
RA   Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
RA   Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
RA   Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
RA   Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
RA   Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
RA   di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
RA   Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
RA   Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
RA   Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
RA   Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
RA   Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
RA   Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
RA   Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
RA   Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
RA   Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
RA   Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
RA   Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
RA   Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
RA   Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B.,
RA   Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
RA   Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
RA   Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
RA   Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
RA   Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
RA   Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
RA   Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
RA   Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
RA   Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
RA   Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
RA   Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
RA   Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Limb;
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   [4]
RP   FUNCTION, AND INTERACTION WITH MCL1.
RX   PubMed=15901672; DOI=10.1101/gad.1304105;
RA   Willis S.N., Chen L., Dewson G., Wei A., Naik E., Fletcher J.I.,
RA   Adams J.M., Huang D.C.S.;
RT   "Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2,
RT   until displaced by BH3-only proteins.";
RL   Genes Dev. 19:1294-1305(2005).
RN   [5]
RP   FUNCTION, AND INTERACTION WITH MCL1.
RX   PubMed=15694340; DOI=10.1016/j.molcel.2004.12.030;
RA   Chen L., Willis S.N., Wei A., Smith B.J., Fletcher J.I., Hinds M.G.,
RA   Colman P.M., Day C.L., Adams J.M., Huang D.C.S.;
RT   "Differential targeting of prosurvival Bcl-2 proteins by their BH3-
RT   only ligands allows complementary apoptotic function.";
RL   Mol. Cell 17:393-403(2005).
RN   [6]
RP   FUNCTION, INDUCTION, AND TISSUE SPECIFICITY.
RX   PubMed=16822983; DOI=10.1523/JNEUROSCI.0196-06.2006;
RA   Akhtar R.S., Geng Y., Klocke B.J., Latham C.B., Villunger A.,
RA   Michalak E.M., Strasser A., Carroll S.L., Roth K.A.;
RT   "BH3-only proapoptotic Bcl-2 family members Noxa and Puma mediate
RT   neural precursor cell death.";
RL   J. Neurosci. 26:7257-7264(2006).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 68-93 IN COMPLEX WITH MCL1,
RP   STRUCTURE BY NMR OF 68-94 IN COMPLEX WITH MCL1, FUNCTION, MASS
RP   SPECTROMETRY, AND INTERACTION WITH MCL1.
RX   PubMed=17389404; DOI=10.1073/pnas.0701297104;
RA   Czabotar P.E., Lee E.F., van Delft M.F., Day C.L., Smith B.J.,
RA   Huang D.C.S., Fairlie W.D., Hinds M.G., Colman P.M.;
RT   "Structural insights into the degradation of Mcl-1 induced by BH3
RT   domains.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:6217-6222(2007).
CC   -!- FUNCTION: Promotes activation of caspases and apoptosis. Promotes
CC       mitochondrial membrane changes and efflux of apoptogenic proteins
CC       from the mitochondria. Contributes to p53-dependent apoptosis
CC       after radiation exposure. Promotes proteasomal degradation of
CC       MCL1. Competes with BIM/BCL2L11 for binding to MCL1 and can
CC       displace BIM/BCL2L11 from its binding site on MCL1 (By
CC       similarity). Competes with BAK1 for binding to MCL1 and can
CC       displace BAK1 from its binding site on MCL1.
CC   -!- SUBUNIT: Interacts with MCL1 and BAX (By similarity).
CC   -!- INTERACTION:
CC       Q07820:MCL1 (xeno); NbExp=1; IntAct=EBI-709183, EBI-1003422;
CC       P97287:Mcl1; NbExp=1; IntAct=EBI-709183, EBI-707292;
CC   -!- SUBCELLULAR LOCATION: Mitochondrion.
CC   -!- TISSUE SPECIFICITY: Detected in thymocytes after irradiation with
CC       X-rays. Not detectable in untreated thymocytes (at protein level).
CC       Detected in embryonic neural precursor cells of the telencephalon
CC       Constitutively expressed at low levels in adult brain, testis,
CC       thymus, spleen, lung and kidney.
CC   -!- INDUCTION: Up-regulated after exposure to ionizing radiation and
CC       other genotoxic agents. Up-regulation is mediated by p53.
CC   -!- DOMAIN: The BH3 motif is essential for pro-apoptotic activity.
CC   -!- SIMILARITY: Belongs to the PMAIP1 family.
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DR   EMBL; AB041230; BAA95781.1; -; mRNA.
DR   EMBL; AK043856; BAC31682.1; -; mRNA.
DR   EMBL; AK088556; BAC40421.1; -; mRNA.
DR   EMBL; AK143990; BAE25650.1; -; mRNA.
DR   EMBL; AK169914; BAE41454.1; -; mRNA.
DR   EMBL; BC050821; AAH50821.1; -; mRNA.
DR   RefSeq; NP_067426.1; -.
DR   UniGene; Mm.271878; -.
DR   PDB; 2JM6; NMR; -; A=68-94.
DR   PDB; 2NLA; X-ray; 2.80 A; B=68-93.
DR   PDB; 2ROD; NMR; -; B=17-42.
DR   PDBsum; 2JM6; -.
DR   PDBsum; 2NLA; -.
DR   PDBsum; 2ROD; -.
DR   IntAct; Q9JM54; -.
DR   Ensembl; ENSMUSG00000024521; Mus musculus.
DR   GeneID; 58801; -.
DR   KEGG; mmu:58801; -.
DR   MGI; MGI:1930146; Pmaip1.
DR   HOGENOM; Q9JM54; -.
DR   HOVERGEN; Q9JM54; -.
DR   NextBio; 314374; -.
DR   ArrayExpress; Q9JM54; -.
DR   GO; GO:0005741; C:mitochondrial outer membrane; EXP:Reactome.
DR   GO; GO:0005515; F:protein binding; IPI:IntAct.
DR   GO; GO:0008629; P:induction of apoptosis by intracellular sig...; IMP:MGI.
DR   GO; GO:0048147; P:negative regulation of fibroblast prolifera...; IMP:MGI.
DR   GO; GO:0043525; P:positive regulation of neuron apoptosis; IMP:MGI.
DR   GO; GO:0001844; P:protein insertion into mitochondrial membra...; IMP:MGI.
DR   GO; GO:0001836; P:release of cytochrome c from mitochondria; IMP:MGI.
DR   GO; GO:0006974; P:response to DNA damage stimulus; IMP:MGI.
DR   GO; GO:0009411; P:response to UV; IMP:MGI.
DR   GO; GO:0010165; P:response to X-ray; IMP:MGI.
DR   PROSITE; PS01259; BH3; FALSE_NEG.
PE   1: Evidence at protein level;
KW   3D-structure; Apoptosis; Mitochondrion; Repeat.
FT   CHAIN         1    103       Phorbol-12-myristate-13-acetate-induced
FT                                protein 1.
FT                                /FTId=PRO_0000333230.
FT   REGION       90     99       Required for mitochondrial location (By
FT                                similarity).
FT   MOTIF        27     35       BH3 1.
FT   MOTIF        78     86       BH3 2.
FT   MUTAGEN      27     27       L->A: Loss of pro-apoptotic activity and
FT                                of targeting to mitochondria; when
FT                                associated with A-78.
FT   MUTAGEN      78     78       L->A: Loss of pro-apoptotic activity and
FT                                of targeting to mitochondria; when
FT                                associated with A-27.
FT   HELIX        71     93
SQ   SEQUENCE   103 AA;  11566 MW;  9B9A5B04D5535E30 CRC64;
     MPGRKARRNA PVNPTRAELP PEFAAQLRKI GDKVYCTWSA PDITVVLAQM PGKSQKSRMR
     SPSPTRVPAD LKDECAQLRR IGDKVNLRQK LLNLISKLFN LVT
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