APR_MOUSE
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 03-AUG-2022, entry version 150.
DE RecName: Full=Phorbol-12-myristate-13-acetate-induced protein 1;
DE AltName: Full=Protein Noxa;
GN Name=Pmaip1; Synonyms=Noxa;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH MCL1, SUBCELLULAR LOCATION,
RP FUNCTION, AND MUTAGENESIS OF LEU-27 AND LEU-78.
RX 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 p53-
RT 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., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., 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., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., 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 project:
RT 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, until
RT 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-only
RT 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 neural
RT 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, INTERACTION WITH
RP MCL1, AND IDENTIFICATION BY MASS SPECTROMETRY.
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 from
CC the mitochondria. Contributes to p53/TP53-dependent apoptosis after
CC radiation exposure. Promotes proteasomal degradation of MCL1. Competes
CC with BIM/BCL2L11 for binding to MCL1 and can displace BIM/BCL2L11 from
CC its binding site on MCL1 (By similarity). Competes with BAK1 for
CC binding to MCL1 and can displace BAK1 from its binding site on MCL1.
CC {ECO:0000250, ECO:0000269|PubMed:10807576, ECO:0000269|PubMed:15694340,
CC ECO:0000269|PubMed:15901672, ECO:0000269|PubMed:16822983,
CC ECO:0000269|PubMed:17389404}.
CC -!- SUBUNIT: Interacts with MCL1 (PubMed:10807576, PubMed:15901672,
CC PubMed:15694340, PubMed:17389404). Interacts with BCL2A1 (By
CC similarity). Interacts with BAX (By similarity). Interacts with BCL2L10
CC (By similarity). {ECO:0000250|UniProtKB:Q13794,
CC ECO:0000269|PubMed:10807576, ECO:0000269|PubMed:15694340,
CC ECO:0000269|PubMed:15901672, ECO:0000269|PubMed:17389404}.
CC -!- INTERACTION:
CC Q9JM54; P97287: Mcl1; NbExp=14; IntAct=EBI-709183, EBI-707292;
CC Q9JM54; Q07820: MCL1; Xeno; NbExp=2; IntAct=EBI-709183, EBI-1003422;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:10807576}.
CC -!- TISSUE SPECIFICITY: Detected in thymocytes after irradiation with X-
CC 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, thymus,
CC spleen, lung and kidney. {ECO:0000269|PubMed:16822983}.
CC -!- INDUCTION: Up-regulated after exposure to ionizing radiation and other
CC genotoxic agents. Up-regulation is mediated by p53.
CC {ECO:0000269|PubMed:16822983}.
CC -!- DOMAIN: The BH3 motif is essential for pro-apoptotic activity.
CC -!- SIMILARITY: Belongs to the PMAIP1 family. {ECO:0000305}.
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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 CCDS; CCDS29315.1; -.
DR RefSeq; NP_067426.1; NM_021451.2.
DR PDB; 2JM6; NMR; -; A=68-93.
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 AlphaFoldDB; Q9JM54; -.
DR SMR; Q9JM54; -.
DR BioGRID; 208439; 2.
DR ComplexPortal; CPX-305; MCL1:PMAIP1 complex.
DR DIP; DIP-45232N; -.
DR ELM; Q9JM54; -.
DR IntAct; Q9JM54; 4.
DR MINT; Q9JM54; -.
DR STRING; 10090.ENSMUSP00000025399; -.
DR iPTMnet; Q9JM54; -.
DR PhosphoSitePlus; Q9JM54; -.
DR PaxDb; Q9JM54; -.
DR PRIDE; Q9JM54; -.
DR DNASU; 58801; -.
DR Ensembl; ENSMUST00000025399; ENSMUSP00000025399; ENSMUSG00000024521.
DR GeneID; 58801; -.
DR KEGG; mmu:58801; -.
DR UCSC; uc008fft.1; mouse.
DR CTD; 5366; -.
DR MGI; MGI:1930146; Pmaip1.
DR VEuPathDB; HostDB:ENSMUSG00000024521; -.
DR eggNOG; ENOG502SEAE; Eukaryota.
DR GeneTree; ENSGT00530000065105; -.
DR HOGENOM; CLU_2262862_0_0_1; -.
DR InParanoid; Q9JM54; -.
DR OMA; YCTWSAP; -.
DR OrthoDB; 1636703at2759; -.
DR TreeFam; TF339379; -.
DR Reactome; R-MMU-111448; Activation of NOXA and translocation to mitochondria.
DR Reactome; R-MMU-111453; BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members.
DR BioGRID-ORCS; 58801; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Pmaip1; mouse.
DR EvolutionaryTrace; Q9JM54; -.
DR PRO; PR:Q9JM54; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q9JM54; protein.
DR Bgee; ENSMUSG00000024521; Expressed in gastrula and 144 other tissues.
DR ExpressionAtlas; Q9JM54; baseline and differential.
DR Genevisible; Q9JM54; MM.
DR GO; GO:0097136; C:Bcl-2 family protein complex; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; ISO:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:MGI.
DR GO; GO:0042149; P:cellular response to glucose starvation; ISO:MGI.
DR GO; GO:0051607; P:defense response to virus; ISO:MGI.
DR GO; GO:0044346; P:fibroblast apoptotic process; IMP:MGI.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; ISO:MGI.
DR GO; GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; IMP:UniProtKB.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IMP:MGI.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IDA:MGI.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IMP:ParkinsonsUK-UCL.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IMP:MGI.
DR GO; GO:0010917; P:negative regulation of mitochondrial membrane potential; IDA:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0043517; P:positive regulation of DNA damage response, signal transduction by p53 class mediator; IMP:UniProtKB.
DR GO; GO:1902043; P:positive regulation of extrinsic apoptotic signaling pathway via death domain receptors; ISO:MGI.
DR GO; GO:2000271; P:positive regulation of fibroblast apoptotic process; IMP:MGI.
DR GO; GO:0010907; P:positive regulation of glucose metabolic process; ISO:MGI.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; ISO:MGI.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:MGI.
DR GO; GO:1900740; P:positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; IMP:MGI.
DR GO; GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; ISO:MGI.
DR GO; GO:0010498; P:proteasomal protein catabolic process; ISO:MGI.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; ISO:MGI.
DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; ISO:MGI.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IDA:UniProtKB.
DR GO; GO:0043331; P:response to dsRNA; ISO:MGI.
DR GO; GO:0009411; P:response to UV; IMP:MGI.
DR GO; GO:0010165; P:response to X-ray; IMP:MGI.
DR GO; GO:0043029; P:T cell homeostasis; IMP:UniProtKB.
DR DisProt; DP01281; -.
DR InterPro; IPR024140; Noxa.
DR PANTHER; PTHR14299; PTHR14299; 1.
DR Pfam; PF15150; PMAIP1; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Mitochondrion; Reference proteome; Repeat.
FT CHAIN 1..103
FT /note="Phorbol-12-myristate-13-acetate-induced protein 1"
FT /id="PRO_0000333230"
FT REGION 90..99
FT /note="Required for mitochondrial location"
FT /evidence="ECO:0000250"
FT MOTIF 27..35
FT /note="BH3 1"
FT MOTIF 78..86
FT /note="BH3 2"
FT MUTAGEN 27
FT /note="L->A: Loss of pro-apoptotic activity and of
FT targeting to mitochondria; when associated with A-78."
FT /evidence="ECO:0000269|PubMed:10807576"
FT MUTAGEN 78
FT /note="L->A: Loss of pro-apoptotic activity and of
FT targeting to mitochondria; when associated with A-27."
FT /evidence="ECO:0000269|PubMed:10807576"
FT HELIX 22..39
FT /evidence="ECO:0007829|PDB:2ROD"
FT HELIX 77..90
FT /evidence="ECO:0007829|PDB:2NLA"
SQ SEQUENCE 103 AA; 11566 MW; 9B9A5B04D5535E30 CRC64;
MPGRKARRNA PVNPTRAELP PEFAAQLRKI GDKVYCTWSA PDITVVLAQM PGKSQKSRMR
SPSPTRVPAD LKDECAQLRR IGDKVNLRQK LLNLISKLFN LVT
