ID:PDCD4_HUMAN DESCRIPTION: RecName: Full=Programmed cell death protein 4; AltName: Full=Neoplastic transformation inhibitor protein; AltName: Full=Nuclear antigen H731-like; AltName: Full=Protein 197/15a; FUNCTION: Inhibits translation initiation and cap-dependent translation. May excert its function by hindering the interaction between EIF4A1 and EIF4G. Inhibits the helicase activity of EIF4A. Modulates the activation of JUN kinase. Down-regulates the expression of MAP4K1, thus inhibiting events important in driving invasion, namely, MAPK85 activation and consequent JUN-dependent transcription. May play a role in apoptosis. Tumor suppressor. Inhibits tumor promoter-induced neoplastic transformation. Binds RNA (By similarity). SUBUNIT: Interacts (via MI domains) with EIF4A2 (By similarity). Interacts (via MI domains) with EIF4A1 (via N-terminal domain). Heterotrimer with EIF4A1; one molecule of PDCD4 binds two molecules of EIF4A1. Interacts with EIF4G1. May form a complex with EIF4A1 and EIF4G1. The interaction between PDCD4 and EIF4A1 interferes with the interaction between EIF4A1 and EIF4G. When phosphorylated, interacts with BTRC and FBXW11. INTERACTION: P02649:APOE; NbExp=3; IntAct=EBI-935824, EBI-1222467; P49810:PSEN2; NbExp=3; IntAct=EBI-935824, EBI-2010251; P62277:RPS13; NbExp=2; IntAct=EBI-935824, EBI-351850; SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Shuttles between the nucleus and cytoplasm. Predominantly nuclear under normal growth conditions, and when phosphorylated at Ser-457. Exported from the nucleus in the absence of serum. TISSUE SPECIFICITY: Up-regulated in proliferative cells. Highly expressed in epithelial cells of the mammary gland. Reduced expression in lung cancer and colon carcinoma. INDUCTION: IL2/interleukin-2 stimulation inhibits expression, while IL12/interleukin-12 increases expression. DOMAIN: Binds EIF4A1 via both MI domains. PTM: Polyubiquitinated, leading to its proteasomal degradation. Rapidly degraded in response to mitogens. Phosphorylation of the phosphodegron promotes interaction with BTRC and proteasomal degradation. PTM: Phosphorylated at Ser-67 by RPS6KB1 in response to mitogens; phosphorylation promotes proteasomal degradation of PDCD4. SIMILARITY: Belongs to the PDCD4 family. SIMILARITY: Contains 2 MI domains. SEQUENCE CAUTION: Sequence=AAB42218.1; Type=Erroneous gene model prediction; Sequence=AAH15036.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/PDCD4ID41675ch10q24.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q53EL6
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006915 apoptotic process GO:0007569 cell aging GO:0030509 BMP signaling pathway GO:0034393 positive regulation of smooth muscle cell apoptotic process GO:0035722 interleukin-12-mediated signaling pathway GO:0043066 negative regulation of apoptotic process GO:0043508 negative regulation of JUN kinase activity GO:0045786 negative regulation of cell cycle GO:0045892 negative regulation of transcription, DNA-templated GO:0050729 positive regulation of inflammatory response GO:0051246 regulation of protein metabolic process GO:0060940 epithelial to mesenchymal transition involved in cardiac fibroblast development GO:0071222 cellular response to lipopolysaccharide GO:1900016 negative regulation of cytokine production involved in inflammatory response GO:1901224 positive regulation of NIK/NF-kappaB signaling GO:1904706 negative regulation of vascular smooth muscle cell proliferation GO:1904761 negative regulation of myofibroblast differentiation GO:1905064 negative regulation of vascular smooth muscle cell differentiation GO:1905461 positive regulation of vascular associated smooth muscle cell apoptotic process GO:2000353 positive regulation of endothelial cell apoptotic process
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
