ID   APR_HUMAN               Reviewed;          54 AA.
AC   Q13794; B2R4T7;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   07-JUL-2009, entry version 59.
DE   RecName: Full=Phorbol-12-myristate-13-acetate-induced protein 1;
DE            Short=PMA-induced protein 1;
DE   AltName: Full=Immediate-early-response protein APR;
DE   AltName: Full=NOXA;
GN   Name=PMAIP1; Synonyms=NOXA;
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 [MRNA].
RX   MEDLINE=90376412; PubMed=2398525;
RA   Hijikata M., Kato N., Sato T., Kagami Y., Shimotohno K.;
RT   "Molecular cloning and characterization of a cDNA for a novel phorbol-
RT   12-myristate-13-acetate-responsive gene that is highly expressed in an
RT   adult T-cell leukemia cell line.";
RL   J. Virol. 64:4632-4639(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Ovary;
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 INDUCTION.
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   [5]
RP   FUNCTION, INDUCTION, SUBCELLULAR LOCATION, INTERACTION WITH BAX, AND
RP   MUTAGENESIS OF LEU-29.
RX   PubMed=15705586; DOI=10.1074/jbc.M412630200;
RA   Sun Y., Leaman D.W.;
RT   "Involvement of Noxa in cellular apoptotic responses to interferon,
RT   double-stranded RNA, and virus infection.";
RL   J. Biol. Chem. 280:15561-15568(2005).
RN   [6]
RP   FUNCTION, MASS SPECTROMETRY, MUTAGENESIS OF PHE-32 AND LYS-35, AND
RP   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   [7]
RP   FUNCTION, INTERACTION WITH MCL1, INDUCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=17374615; DOI=10.1074/jbc.M611186200;
RA   Han J., Goldstein L.A., Hou W., Rabinowich H.;
RT   "Functional linkage between NOXA and Bim in mitochondrial apoptotic
RT   events.";
RL   J. Biol. Chem. 282:16223-16231(2007).
RN   [8]
RP   FUNCTION, MUTAGENESIS OF LEU-29; PHE-32 AND LEU-36, AND INTERACTION
RP   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 BAK1 for binding to MCL1 and can displace BAK1
CC       from its binding site on MCL1 (By similarity). Competes with
CC       BIM/BCL2L11 for binding to MCL1 and can displace BIM/BCL2L11 from
CC       its binding site on MCL1.
CC   -!- SUBUNIT: Interacts with MCL1 and BAX.
CC   -!- INTERACTION:
CC       Q07440:Bcl2a1 (xeno); NbExp=1; IntAct=EBI-707392, EBI-707754;
CC       Q07820:MCL1; NbExp=1; IntAct=EBI-707392, EBI-1003422;
CC       P97287:Mcl1 (xeno); NbExp=1; IntAct=EBI-707392, EBI-707292;
CC   -!- SUBCELLULAR LOCATION: Mitochondrion.
CC   -!- TISSUE SPECIFICITY: Highly expressed in adult T-cell leukemia cell
CC       line.
CC   -!- INDUCTION: Up-regulated by p53, phorbol esters, double-stranded
CC       RNA, interferon-beta, and virus.
CC   -!- DOMAIN: The BH3 motif is essential for pro-apoptotic activity.
CC   -!- SIMILARITY: Belongs to the PMAIP1 family.
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DR   EMBL; D90070; BAA14111.1; -; mRNA.
DR   EMBL; AK311943; BAG34884.1; -; mRNA.
DR   EMBL; BC013120; AAH13120.1; -; mRNA.
DR   IPI; IPI00015177; -.
DR   PIR; I37018; I37018.
DR   RefSeq; NP_066950.1; -.
DR   UniGene; Hs.96; -.
DR   IntAct; Q13794; 7.
DR   Ensembl; ENSG00000141682; Homo sapiens.
DR   GeneID; 5366; -.
DR   KEGG; hsa:5366; -.
DR   UCSC; uc002lic.2; human.
DR   GeneCards; GC18P055718; -.
DR   H-InvDB; HIX0014485; -.
DR   HGNC; HGNC:9108; PMAIP1.
DR   MIM; 604959; gene.
DR   PharmGKB; PA33434; -.
DR   HOVERGEN; Q13794; -.
DR   Reactome; REACT_578; Apoptosis.
DR   NextBio; 20800; -.
DR   ArrayExpress; Q13794; -.
DR   Bgee; Q13794; -.
DR   CleanEx; HS_PMAIP1; -.
DR   GermOnline; ENSG00000141682; Homo sapiens.
DR   GO; GO:0005739; C:mitochondrion; IDA:HGNC.
DR   GO; GO:0005515; F:protein binding; IPI:IntAct.
DR   GO; GO:0006919; P:activation of caspase activity; IDA:HGNC.
DR   GO; GO:0006921; P:cell structure disassembly during apoptosis; IDA:HGNC.
DR   GO; GO:0006917; P:induction of apoptosis; IDA:HGNC.
DR   GO; GO:0001836; P:release of cytochrome c from mitochondria; IDA:HGNC.
DR   GO; GO:0043331; P:response to dsRNA; IDA:HGNC.
DR   GO; GO:0006926; P:virus-infected cell apoptosis; IDA:HGNC.
DR   InterPro; IPR000712; Bcl2_BH.
DR   PROSITE; PS01259; BH3; FALSE_NEG.
PE   1: Evidence at protein level;
KW   Apoptosis; Complete proteome; Mitochondrion.
FT   CHAIN         1     54       Phorbol-12-myristate-13-acetate-induced
FT                                protein 1.
FT                                /FTId=PRO_0000064644.
FT   REGION       41     50       Required for mitochondrial location.
FT   MOTIF        29     37       BH3.
FT   MUTAGEN      29     29       L->A: Reduced interaction with BAX.
FT   MUTAGEN      29     29       L->E: Loss of interaction with MCL1 and
FT                                of increased MCL1 degradation; when
FT                                associated with E-32 and E-32.
FT   MUTAGEN      32     32       F->E: Loss of interaction with MCL1 and
FT                                of increased MCL1 degradation; when
FT                                associated with E-29 and E-36.
FT   MUTAGEN      32     32       F->I: Alters specificity of protein
FT                                interaction and enhances pro-apoptotic
FT                                activity; when associated with E-35.
FT   MUTAGEN      35     35       K->E: Alters specificity of protein
FT                                interaction and enhances pro-apoptotic
FT                                activity; when associated with I-32.
FT   MUTAGEN      36     36       L->E: Loss of interaction with MCL1 and
FT                                of increased MCL1 degradation; when
FT                                associated with E-29 and E-32.
SQ   SEQUENCE   54 AA;  6030 MW;  291A142B27167E70 CRC64;
     MPGKKARKNA QPSPARAPAE LEVECATQLR RFGDKLNFRQ KLLNLISKLF CSGT
//