ID   PDCD4_MOUSE             Reviewed;         469 AA.
AC   Q61823; P97296; Q3T9A9;
DT   31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   15-JAN-2008, entry version 60.
DE   Programmed cell death protein 4 (Topoisomerase-inhibitor suppressed
DE   protein) (Protein MA-3).
GN   Name=Pdcd4; Synonyms=Ma3, Tis;
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], AND TISSUE SPECIFICITY.
RC   STRAIN=ICR; TISSUE=Thymus;
RX   MEDLINE=96125207; PubMed=8543179; DOI=10.1016/0378-1119(95)00607-9;
RA   Shibahara K., Asano M., Ishida Y., Aoki T., Koike T., Honjo T.;
RT   "Isolation of a novel mouse gene MA-3 that is induced upon programmed
RT   cell death.";
RL   Gene 166:297-301(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Lymphoma;
RX   MEDLINE=97069646; PubMed=8912629; DOI=10.1006/bbrc.1996.1609;
RA   Onishi Y., Kizaki H.;
RT   "Molecular cloning of the genes suppressed in RVC lymphoma cells by
RT   topoisomerase inhibitors.";
RL   Biochem. Biophys. Res. Commun. 228:7-13(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX   MEDLINE=98382539; PubMed=9714845; DOI=10.1016/S0378-1119(98)00313-8;
RA   Onishi Y., Hashimoto S., Kizaki H.;
RT   "Cloning of the TIS gene suppressed by topoisomerase inhibitors.";
RL   Gene 215:453-459(1998).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=BTBR T+ tf/J;
RX   PubMed=16682971; DOI=10.1038/ng1796;
RA   Clee S.M., Yandell B.S., Schueler K.M., Rabaglia M.E., Richards O.C.,
RA   Raines S.M., Kabara E.A., Klass D.M., Mui E.T.-K., Stapleton D.S.,
RA   Gray-Keller M.P., Young M.B., Stoehr J.P., Lan H., Boronenkov I.,
RA   Raess P.W., Flowers M.T., Attie A.D.;
RT   "Positional cloning of Sorcs1, a type 2 diabetes quantitative trait
RT   locus.";
RL   Nat. Genet. 38:688-693(2006).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J, and NOD; TISSUE=Spleen, and Testis;
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   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Ebert L., Muenstermann E., Schatten R., Henze S., Bohn E.,
RA   Mollenhauer J., Wiemann S., Schick M., Korn B.;
RT   "Cloning of mouse full open reading frames in Gateway(R) system entry
RT   vector (pDONR201).";
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6; TISSUE=Brain;
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   [8]
RP   FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH EIF4A1 AND
RP   EIF4A2.
RX   PubMed=12482958; DOI=10.1128/MCB.23.1.26-37.2003;
RA   Yang H.-S., Jansen A.P., Komar A.A., Zheng X., Merrick W.C.,
RA   Costes S., Lockett S.J., Sonenberg N., Colburn N.H.;
RT   "The transformation suppressor Pdcd4 is a novel eukaryotic translation
RT   initiation factor 4A binding protein that inhibits translation.";
RL   Mol. Cell. Biol. 23:26-37(2003).
RN   [9]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=12894233; DOI=10.1038/sj.onc.1206710;
RA   Boehm M., Sawicka K., Siebrasse J.P., Brehmer-Fastnacht A., Peters R.,
RA   Klempnauer K.-H.;
RT   "The transformation suppressor protein Pdcd4 shuttles between nucleus
RT   and cytoplasm and binds RNA.";
RL   Oncogene 22:4905-4910(2003).
RN   [10]
RP   FUNCTION.
RX   PubMed=16024603; DOI=10.1158/0008-5472.CAN-04-2119;
RA   Jansen A.P., Camalier C.E., Colburn N.H.;
RT   "Epidermal expression of the translation inhibitor programmed cell
RT   death 4 suppresses tumorigenesis.";
RL   Cancer Res. 65:6034-6041(2005).
RN   [11]
RP   X-RAY CRYSTALLOGRAPHY (1.15 ANGSTROMS) OF 320-469.
RX   PubMed=17060447; DOI=10.1128/MCB.00867-06;
RA   Laronde-Leblanc N., Santhanam A.N., Baker A.R., Wlodawer A.,
RA   Colburn N.H.;
RT   "Structural basis for inhibition of translation by the tumor
RT   suppressor pdcd4.";
RL   Mol. Cell. Biol. 27:147-156(2007).
CC   -!- FUNCTION: Tumor suppressor. Inhibits tumor promoter-induced
CC       neoplastic transformation. Down-regulates the expression of
CC       MAP4K1, thus inhibiting events important in driving invasion,
CC       namely, MAPK85 activation and consequent JUN-dependent
CC       transcription. May play a role in apoptosis. Inhibits the helicase
CC       activity of EIF4A and cap-dependent translation. Binds RNA.
CC   -!- SUBUNIT: Interacts with EIF4A1 and EIF4A2.
CC   -!- INTERACTION:
CC       Q61655:Ddx19a; NbExp=1; IntAct=EBI-296473, EBI-296479;
CC       Q62448:Eif4g2; NbExp=1; IntAct=EBI-296473, EBI-296494;
CC   -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Shuttles between
CC       nucleus and cytoplasm. Predominantly nuclear under normal growth
CC       conditions. Exported from the nucleus in the absence of serum.
CC   -!- TISSUE SPECIFICITY: Expressed ubiquitously. Highyly expressed in
CC       thymus and liver. Moderately expressed in brain, kidney and
CC       spleen; weakly in lung and heart. Expression is up- or down-
CC       regulated in response to apoptosis inducers. Regulated by many
CC       programmed cell death-inducing stimuli.
CC   -!- DOMAIN: Binds EIF4A1 via the MA3 domains (By similarity).
CC   -!- DISEASE: Decreases benign tumor development and malignant
CC       progression.
CC   -!- SIMILARITY: Belongs to the PDCD4 family.
CC   -!- SIMILARITY: Contains 2 MA3 domains.
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DR   EMBL; D50465; BAA09056.1; -; mRNA.
DR   EMBL; D86344; BAA13072.1; -; mRNA.
DR   EMBL; AB010139; BAA32356.1; -; Genomic_DNA.
DR   EMBL; DQ479921; ABF51670.1; -; Genomic_DNA.
DR   EMBL; CT010188; CAJ18396.1; -; mRNA.
DR   EMBL; AK134366; BAE22118.1; -; mRNA.
DR   EMBL; AK172654; BAE43115.1; -; mRNA.
DR   EMBL; BC055739; AAH55739.1; -; mRNA.
DR   PIR; JC4523; JC4523.
DR   RefSeq; NP_035180.2; -.
DR   UniGene; Mm.1605; -.
DR   PDB; 2HM8; NMR; -; A=319-449.
DR   PDB; 2IOL; X-ray; 2.00 A; A/B=320-469.
DR   PDB; 2ION; X-ray; 1.57 A; A=320-469.
DR   PDB; 2IOS; X-ray; 1.76 A; A=320-469.
DR   PDB; 2NSZ; X-ray; 1.15 A; A=320-469.
DR   PDBsum; 2HM8; -.
DR   PDBsum; 2IOL; -.
DR   PDBsum; 2ION; -.
DR   PDBsum; 2IOS; -.
DR   PDBsum; 2NSZ; -.
DR   SMR; Q61823; 322-450.
DR   IntAct; Q61823; -.
DR   Ensembl; ENSMUSG00000024975; Mus musculus.
DR   GeneID; 18569; -.
DR   KEGG; mmu:18569; -.
DR   MGI; MGI:107490; Pdcd4.
DR   ArrayExpress; Q61823; -.
DR   CleanEx; MM_PDCD4; -.
DR   GermOnline; ENSMUSG00000024975; Mus musculus.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0005515; F:protein binding; IPI:UniProtKB.
DR   GO; GO:0007569; P:cell aging; ISS:UniProtKB.
DR   GO; GO:0043508; P:negative regulation of JNK activity; ISS:UniProtKB.
DR   GO; GO:0016481; P:negative regulation of transcription; ISS:UniProtKB.
DR   InterPro; IPR003891; IF_eIF4G_MA3.
DR   Pfam; PF02847; MA3; 2.
DR   SMART; SM00544; MA3; 2.
PE   1: Evidence at protein level;
KW   3D-structure; Anti-oncogene; Apoptosis; Cell cycle; Cytoplasm;
KW   Nucleus; Phosphoprotein; Repeat; RNA-binding.
FT   CHAIN         1    469       Programmed cell death protein 4.
FT                                /FTId=PRO_0000256520.
FT   DOMAIN      164    275       MA3 1.
FT   DOMAIN      327    440       MA3 2.
FT   MOTIF        58     64       Nuclear localization signal (Potential).
FT   MOTIF       448    454       Nuclear localization signal (Potential).
FT   MOD_RES      76     76       Phosphoserine (By similarity).
FT   MOD_RES      93     93       Phosphothreonine (By similarity).
FT   MOD_RES     457    457       Phosphoserine (By similarity).
FT   CONFLICT    232    232       S -> I (in Ref. 2; BAA32356 and 3;
FT                                BAA13072).
FT   CONFLICT    369    369       V -> I (in Ref. 2; BAA32356 and 3;
FT                                BAA13072).
FT   CONFLICT    414    414       D -> G (in Ref. 5; BAE43115).
SQ   SEQUENCE   469 AA;  51702 MW;  6883BCE5011692F1 CRC64;
     MDIENEQTLN VNPTDPDNLS DSLFSGDEEN AGTEEIKNEI NGNWISASTI NEARINAKAK
     RRLRKNSSRD SGRGDSVSDN GSEAVRSGVA VPTSPKGRLL DRRSRSGKGR GLPKKGGAGG
     KGVWGTPGQV YDVEEVDVKD PNYDDDQENC VYETVVLPLD ETAFEKTLTP IIQEYFEHGD
     TNEVAEMLRD LNLGEMKSGV PVLAVSLALE GKASHREMTS KLLSDLCGTV MSTNDVEKSF
     DKLLKDLPEL ALDTPRAPQL VGQFIARAVG DGILCNTYID SYKGTVDCVQ ARAALDKATV
     LLSMSKGGKR KDSVWGSGGG QQPVNHLVKE IDMLLKEYLL SGDISEAEHC LKELEVPHFH
     HELVYEAIVM VLESTGESAF KMILDLLKSL WKSSTITIDQ MKRGYERIYN EIPDINLDVP
     HSYSVLERFV EECFQAGIIS KQLRDLCPSR GRKRFVSEGD GGRLKPESY
//