ID   PDCD4_HUMAN             Reviewed;         469 AA.
AC   Q53EL6; O15501; Q5VZS6; Q6PJI5; Q8TAR5; Q99834;
DT   31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT   24-MAY-2005, sequence version 1.
DT   02-OCT-2007, entry version 22.
DE   Programmed cell death protein 4 (Nuclear antigen H731-like)
DE   (Neoplastic transformation inhibitor protein) (Protein 197/15a).
GN   Name=PDCD4; Synonyms=H731;
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].
RC   TISSUE=Glial tumor;
RA   Matsuhashi S., Yoshinaga H., Yatsuki H., Tsugita A., Hori K.;
RT   "Isolation of a novel gene from a human cell line with Pr-28 MAb which
RT   recognizes a nuclear antigen involved in the cell cycle.";
RL   Res. Commun. Biochem. Cell Mol. Biol. 1:109-120(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION.
RC   TISSUE=Blood;
RX   MEDLINE=98430669; PubMed=9759869;
RA   Azzoni L., Zatsepina O., Abebe B., Bennett I.M., Kanakaraj P.,
RA   Perussia B.;
RT   "Differential transcriptional regulation of CD161 and a novel gene,
RT   197/15a, by IL-2, IL-15, and IL-12 in NK and T cells.";
RL   J. Immunol. 161:3493-3500(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Spleen;
RA   Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL   Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ILE-36.
RX   PubMed=15164054; DOI=10.1038/nature02462;
RA   Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA   Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA   Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA   Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA   Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA   Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA   Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA   Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA   Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA   Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA   Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA   Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA   Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA   Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA   Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA   Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA   Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA   Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA   Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA   Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA   Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA   Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA   Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA   Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 10.";
RL   Nature 429:375-381(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT TYR-48.
RC   TISSUE=Brain, and Skin;
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   [6]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=10632927; DOI=10.1046/j.1440-1827.1999.00995.x;
RA   Yoshinaga H., Matsuhashi S., Fujiyama C., Masaki Z.;
RT   "Novel human PDCD4 (H731) gene expressed in proliferative cells is
RT   expressed in the small duct epithelial cells of the breast as revealed
RT   by an anti-H731 antibody.";
RL   Pathol. Int. 49:1067-1077(1999).
RN   [7]
RP   REDUCED EXPRESSION IN LUNG CANCER.
RX   PubMed=12898601; DOI=10.1002/path.1378;
RA   Chen Y., Knosel T., Kristiansen G., Pietas A., Garber M.E.,
RA   Matsuhashi S., Ozaki I., Petersen I.;
RT   "Loss of PDCD4 expression in human lung cancer correlates with tumour
RT   progression and prognosis.";
RL   J. Pathol. 200:640-646(2003).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-152, AND MASS
RP   SPECTROMETRY.
RX   PubMed=15592455; DOI=10.1038/nbt1046;
RA   Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA   Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT   "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT   cells.";
RL   Nat. Biotechnol. 23:94-101(2005).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-76 AND SER-457, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Epithelium;
RX   PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA   Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA   Mann M.;
RT   "Global, in vivo, and site-specific phosphorylation dynamics in
RT   signaling networks.";
RL   Cell 127:635-648(2006).
RN   [10]
RP   FUNCTION, AND REDUCED EXPRESSION IN COLON CARCINOMA.
RX   PubMed=16449643; DOI=10.1128/MCB.26.4.1297-1306.2006;
RA   Yang H.-S., Matthews C.P., Clair T., Wang Q., Baker A.R., Li C.-C.,
RA   Tan T.-H., Colburn N.H.;
RT   "Tumorigenesis suppressor Pdcd4 down-regulates mitogen-activated
RT   protein kinase kinase kinase kinase 1 expression to suppress colon
RT   carcinoma cell invasion.";
RL   Mol. Cell. Biol. 26:1297-1306(2006).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-93 AND SER-457, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Epithelium;
RX   PubMed=16964243; DOI=10.1038/nbt1240;
RA   Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT   "A probability-based approach for high-throughput protein
RT   phosphorylation analysis and site localization.";
RL   Nat. Biotechnol. 24:1285-1292(2006).
RN   [12]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-457, AND MASS
RP   SPECTROMETRY.
RX   PubMed=17287340; DOI=10.1073/pnas.0611217104;
RA   Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A.;
RT   "Global proteomic profiling of phosphopeptides using electron transfer
RT   dissociation tandem mass spectrometry.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(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 (By
CC       similarity).
CC   -!- SUBUNIT: Interacts with EIF4A1 and EIF4A2 (By similarity).
CC   -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Shuttles between
CC       the nucleus and cytoplasm. Predominantly nuclear under normal
CC       growth conditions. Exported from the nucleus in the absence of
CC       serum.
CC   -!- TISSUE SPECIFICITY: Up-regulated in proliferative cells. Highly
CC       expressed in epithelial cells of the mammary gland.
CC   -!- INDUCTION: IL2 stimulation inhibits expression, while IL12
CC       increases expression.
CC   -!- DOMAIN: Binds EIF4A1 via the MA3 domains (By similarity).
CC   -!- DISEASE: Loss of expression correlated with tumor progression of
CC       lung and colon carcinoma.
CC   -!- SIMILARITY: Belongs to the PDCD4 family.
CC   -!- SIMILARITY: Contains 2 MA3 domains.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB42218.1; Type=Erroneous gene model prediction;
CC       Sequence=AAH15036.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence;
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DR   EMBL; U83908; AAB42218.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; U96628; AAB67706.1; -; mRNA.
DR   EMBL; AK223623; BAD97343.1; -; mRNA.
DR   EMBL; AL158163; CAH72815.1; -; Genomic_DNA.
DR   EMBL; AL136368; CAH72815.1; JOINED; Genomic_DNA.
DR   EMBL; AL136368; CAI40095.1; -; Genomic_DNA.
DR   EMBL; AL158163; CAI40095.1; JOINED; Genomic_DNA.
DR   EMBL; BC015036; AAH15036.1; ALT_SEQ; mRNA.
DR   EMBL; BC026104; AAH26104.1; -; mRNA.
DR   EMBL; BC031049; AAH31049.1; -; mRNA.
DR   PIR; JC5193; JC5193.
DR   RefSeq; NP_055271.2; -.
DR   RefSeq; NP_663314.1; -.
DR   UniGene; Hs.232543; -.
DR   Ensembl; ENSG00000150593; Homo sapiens.
DR   GeneID; 27250; -.
DR   HGNC; HGNC:8763; PDCD4.
DR   HPA; HPA001032; -.
DR   MIM; 608610; gene.
DR   PharmGKB; PA33113; -.
DR   GermOnline; ENSG00000150593; Homo sapiens.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IMP:UniProtKB.
DR   GO; GO:0005515; F:protein binding; IPI:UniProtKB.
DR   GO; GO:0006915; P:apoptosis; NAS:UniProtKB.
DR   GO; GO:0007569; P:cell aging; IDA:UniProtKB.
DR   GO; GO:0043508; P:negative regulation of JNK activity; ISS:UniProtKB.
DR   GO; GO:0045786; P:negative regulation of progression through ...; NAS:UniProtKB.
DR   GO; GO:0016481; P:negative regulation of transcription; IDA:UniProtKB.
DR   InterPro; IPR003891; IF_eIF4G_MA3.
DR   Pfam; PF02847; MA3; 2.
DR   SMART; SM00544; MA3; 2.
PE   1: Evidence at protein level;
KW   Anti-oncogene; Apoptosis; Cell cycle; Cytoplasm; Nucleus;
KW   Phosphorylation; Polymorphism; Repeat; RNA-binding.
FT   CHAIN         1    469       Programmed cell death protein 4.
FT                                /FTId=PRO_0000256519.
FT   DOMAIN      164    275       MA3 1.
FT   DOMAIN      327    440       MA3 2.
FT   MOTIF        58     64       Nuclear localization signal (Potential).
FT   MOTIF       241    250       Nuclear localization signal (Potential).
FT   MOD_RES      76     76       Phosphoserine.
FT   MOD_RES      93     93       Phosphothreonine.
FT   MOD_RES     152    152       Phosphotyrosine.
FT   MOD_RES     457    457       Phosphoserine.
FT   VARIANT      36     36       V -> I (in dbSNP:rs7081726).
FT                                /FTId=VAR_028901.
FT   VARIANT      48     48       S -> Y (in dbSNP:rs11548765).
FT                                /FTId=VAR_028902.
FT   CONFLICT     79     79       D -> E (in Ref. 1; AAB42218).
FT   CONFLICT    102    102       R -> G (in Ref. 2; AAB67706).
FT   CONFLICT    130    130       V -> G (in Ref. 2; AAB67706).
FT   CONFLICT    220    220       S -> T (in Ref. 1; AAB42218).
FT   CONFLICT    222    222       L -> F (in Ref. 2; AAB67706).
FT   CONFLICT    440    440       S -> W (in Ref. 2; AAB67706).
SQ   SEQUENCE   469 AA;  51721 MW;  123B994FC6D71548 CRC64;
     MDVENEQILN VNPADPDNLS DSLFSGDEEN AGTEEVKNEI NGNWISASSI NEARINAKAK
     RRLRKNSSRD SGRGDSVSDS GSDALRSGLT VPTSPKGRLL DRRSRSGKGR GLPKKGGAGG
     KGVWGTPGQV YDVEEVDVKD PNYDDDQENC VYETVVLPLD ERAFEKTLTP IIQEYFEHGD
     TNEVAEMLRD LNLGEMKSGV PVLAVSLALE GKASHREMTS KLLSDLCGTV MSTTDVEKSF
     DKLLKDLPEL ALDTPRAPQL VGQFIARAVG DGILCNTYID SYKGTVDCVQ ARAALDKATV
     LLSMSKGGKR KDSVWGSGGG QQSVNHLVKE IDMLLKEYLL SGDISEAEHC LKELEVPHFH
     HELVYEAIIM VLESTGESTF KMILDLLKSL WKSSTITVDQ MKRGYERIYN EIPDINLDVP
     HSYSVLERFV EECFQAGIIS KQLRDLCPSR GRKRFVSEGD GGRLKPESY
//