This gene is a tumor suppressor and encodes a protein that binds to the eukaryotic translation initiation factor 4A1 and inhibits its function by preventing RNA binding. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010] See more...

Aliases for PDCD4 Gene

Aliases for PDCD4 Gene

  • Programmed Cell Death 4 2 3 5
  • Programmed Cell Death 4 (Neoplastic Transformation Inhibitor) 2 3
  • Neoplastic Transformation Inhibitor Protein 3 4
  • Programmed Cell Death Protein 4 3 4
  • Nuclear Antigen H731 2 3
  • Protein 197/15a 3 4
  • H731 3 4
  • Nuclear Antigen H731-Like 4

External Ids for PDCD4 Gene

Previous GeneCards Identifiers for PDCD4 Gene

  • GC10P111524
  • GC10P111865
  • GC10P112762
  • GC10P112296
  • GC10P112618
  • GC10P106260

Summaries for PDCD4 Gene

Entrez Gene Summary for PDCD4 Gene

  • This gene is a tumor suppressor and encodes a protein that binds to the eukaryotic translation initiation factor 4A1 and inhibits its function by preventing RNA binding. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

CIViC Summary for PDCD4 Gene

GeneCards Summary for PDCD4 Gene

PDCD4 (Programmed Cell Death 4) is a Protein Coding gene. Diseases associated with PDCD4 include Colorectal Cancer and Tongue Cancer. Among its related pathways are MAPK Signaling: Mitogen Stimulation Pathway and mTOR signaling pathway (Pathway Interaction Database). Gene Ontology (GO) annotations related to this gene include RNA binding and binding.

UniProtKB/Swiss-Prot Summary for PDCD4 Gene

  • 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).

Gene Wiki entry for PDCD4 Gene

Additional gene information for PDCD4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PDCD4 Gene

Genomics for PDCD4 Gene

GeneHancer (GH) Regulatory Elements for PDCD4 Gene

Promoters and enhancers for PDCD4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PDCD4 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PDCD4

Top Transcription factor binding sites by QIAGEN in the PDCD4 gene promoter:
  • AP-1
  • ATF-2
  • c-Jun
  • HNF-4alpha1
  • HNF-4alpha2

Genomic Locations for PDCD4 Gene

Genomic Locations for PDCD4 Gene
chr10:110,871,795-110,900,006
(GRCh38/hg38)
Size:
28,212 bases
Orientation:
Plus strand
chr10:112,631,553-112,659,764
(GRCh37/hg19)
Size:
28,212 bases
Orientation:
Plus strand

Genomic View for PDCD4 Gene

Genes around PDCD4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PDCD4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PDCD4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PDCD4 Gene

Proteins for PDCD4 Gene

  • Protein details for PDCD4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q53EL6-PDCD4_HUMAN
    Recommended name:
    Programmed cell death protein 4
    Protein Accession:
    Q53EL6
    Secondary Accessions:
    • B2RCV4
    • B5ME91
    • O15501
    • Q5VZS6
    • Q6PJI5
    • Q8TAR5
    • Q99834

    Protein attributes for PDCD4 Gene

    Size:
    469 amino acids
    Molecular mass:
    51735 Da
    Quaternary structure:
    • 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.
    SequenceCaution:
    • Sequence=AAB42218.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=AAH15036.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for PDCD4 Gene

    Alternative splice isoforms for PDCD4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PDCD4 Gene

Post-translational modifications for PDCD4 Gene

  • Polyubiquitinated, leading to its proteasomal degradation. Rapidly degraded in response to mitogens. Phosphorylation of the phosphodegron promotes interaction with BTRC and proteasomal degradation.
  • Phosphorylated at Ser-67 by RPS6KB1 in response to mitogens; phosphorylation promotes proteasomal degradation of PDCD4.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for PDCD4 Gene

Antibody Products

  • Abcam antibodies for PDCD4

No data available for DME Specific Peptides for PDCD4 Gene

Domains & Families for PDCD4 Gene

Gene Families for PDCD4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for PDCD4 Gene

Suggested Antigen Peptide Sequences for PDCD4 Gene

GenScript: Design optimal peptide antigens:
  • Protein 197/15a (PDCD4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q53EL6

UniProtKB/Swiss-Prot:

PDCD4_HUMAN :
  • Binds EIF4A1 via both MI domains.
  • Belongs to the PDCD4 family.
Domain:
  • Binds EIF4A1 via both MI domains.
Family:
  • Belongs to the PDCD4 family.
genes like me logo Genes that share domains with PDCD4: view

Function for PDCD4 Gene

Molecular function for PDCD4 Gene

UniProtKB/Swiss-Prot 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).
UniProtKB/Swiss-Prot Induction:
IL2/interleukin-2 stimulation inhibits expression, while IL12/interleukin-12 increases expression.
GENATLAS Biochemistry:
programmed cell death (apoptosis),inhibited by topoisomerase inhibitors (TIS)

Phenotypes From GWAS Catalog for PDCD4 Gene

Gene Ontology (GO) - Molecular Function for PDCD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003723 RNA binding IEA --
GO:0005515 protein binding IPI 12054647
genes like me logo Genes that share ontologies with PDCD4: view
genes like me logo Genes that share phenotypes with PDCD4: view

Animal Models for PDCD4 Gene

MGI Knock Outs for PDCD4:

Animal Model Products

CRISPR Products

miRNA for PDCD4 Gene

miRTarBase miRNAs that target PDCD4

Clone Products

  • Addgene plasmids for PDCD4

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for PDCD4 Gene

Localization for PDCD4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for PDCD4 Gene

Nucleus. Cytoplasm. Note=Shuttles between the nucleus and cytoplasm (By similarity). Predominantly nuclear under normal growth conditions, and when phosphorylated at Ser-457 (PubMed:16357133). {ECO:0000269 PubMed:16357133}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PDCD4 gene
Compartment Confidence
nucleus 5
cytosol 5
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 2
endosome 2
peroxisome 1
endoplasmic reticulum 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for PDCD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IBA,ISS --
GO:0005737 cytoplasm IMP 16357133
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with PDCD4: view

Pathways & Interactions for PDCD4 Gene

genes like me logo Genes that share pathways with PDCD4: view

Pathways by source for PDCD4 Gene

2 Cell Signaling Technology pathways for PDCD4 Gene
1 GeneTex pathway for PDCD4 Gene

SIGNOR curated interactions for PDCD4 Gene

Is inactivated by:

Gene Ontology (GO) - Biological Process for PDCD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006915 apoptotic process TAS,NAS 12054647
GO:0007569 cell aging IDA 12054647
GO:0030509 BMP signaling pathway IDA 18548003
GO:0034393 positive regulation of smooth muscle cell apoptotic process IEA --
GO:0035722 interleukin-12-mediated signaling pathway TAS --
genes like me logo Genes that share ontologies with PDCD4: view

Drugs & Compounds for PDCD4 Gene

No Compound Related Data Available

Transcripts for PDCD4 Gene

mRNA/cDNA for PDCD4 Gene

3 REFSEQ mRNAs :
14 NCBI additional mRNA sequence :
11 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

  • Addgene plasmids for PDCD4

Alternative Splicing Database (ASD) splice patterns (SP) for PDCD4 Gene

ExUns: 1 ^ 2 ^ 3a · 3b · 3c · 3d ^ 4a · 4b ^ 5 ^ 6 ^ 7a · 7b · 7c · 7d ^ 8 ^ 9a · 9b · 9c ^ 10 ^ 11a · 11b · 11c ^ 12a · 12b · 12c · 12d ^
SP1: - - - - -
SP2: - - - -
SP3: - - - - - - -
SP4: - - - - - - - -
SP5: - - - - - -
SP6: - -
SP7: - - - - - -
SP8: - - -
SP9: -
SP10: - - - - - - -
SP11: - -
SP12:
SP13:
SP14: - - - -
SP15:
SP16:

ExUns: 13a · 13b ^ 14a · 14b · 14c ^ 15 ^ 16 ^ 17a · 17b · 17c ^ 18
SP1: - - -
SP2: - - - - -
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13: -
SP14:
SP15:
SP16:

Relevant External Links for PDCD4 Gene

GeneLoc Exon Structure for
PDCD4

Expression for PDCD4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PDCD4 Gene

mRNA differential expression in normal tissues according to GTEx for PDCD4 Gene

This gene is overexpressed in Pancreas (x8.8).

Protein differential expression in normal tissues from HIPED for PDCD4 Gene

This gene is overexpressed in Lymph node (8.1), Tlymphocyte (7.1), and Peripheral blood mononuclear cells (6.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for PDCD4 Gene



Protein tissue co-expression partners for PDCD4 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PDCD4

SOURCE GeneReport for Unigene cluster for PDCD4 Gene:

Hs.711490

mRNA Expression by UniProt/SwissProt for PDCD4 Gene:

Q53EL6-PDCD4_HUMAN
Tissue specificity: Up-regulated in proliferative cells. Highly expressed in epithelial cells of the mammary gland. Reduced expression in lung cancer and colon carcinoma.

Evidence on tissue expression from TISSUES for PDCD4 Gene

  • Nervous system(4.8)
  • Blood(4.6)
  • Liver(4.5)
  • Skin(4.5)
  • Spleen(4.5)
  • Intestine(3.2)
  • Lung(2.9)
  • Pancreas(2.9)
  • Heart(2.8)
  • Lymph node(2.6)
  • Muscle(2.6)
  • Thyroid gland(2.2)
  • Stomach(2.1)
  • Bone marrow(2)
genes like me logo Genes that share expression patterns with PDCD4: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Phenotype-based relationships between genes and organs from Gene ORGANizer for PDCD4 Gene

Orthologs for PDCD4 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for PDCD4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PDCD4 31 30
  • 99.64 (n)
OneToOne
dog
(Canis familiaris)
Mammalia PDCD4 31 30
  • 95.17 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia PDCD4 31
  • 95 (a)
OneToOne
cow
(Bos Taurus)
Mammalia PDCD4 31 30
  • 93.89 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 93 (a)
OneToMany
-- 31
  • 92 (a)
OneToMany
mouse
(Mus musculus)
Mammalia Pdcd4 17 31 30
  • 89.55 (n)
rat
(Rattus norvegicus)
Mammalia Pdcd4 30
  • 88.7 (n)
chicken
(Gallus gallus)
Aves PDCD4 31 30
  • 80.23 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia PDCD4 31
  • 84 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia pdcd4 30
  • 70.97 (n)
Str.6786 30
African clawed frog
(Xenopus laevis)
Amphibia pdcd4-prov 30
zebrafish
(Danio rerio)
Actinopterygii pdcd4b 31 30
  • 66.31 (n)
OneToOne
pdcd4 30
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.1132 30
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000378 30
  • 49.82 (n)
fruit fly
(Drosophila melanogaster)
Insecta Pdcd4 31 30
  • 47.88 (n)
OneToOne
CG10990 32
  • 39 (a)
thale cress
(Arabidopsis thaliana)
eudicotyledons AT4G24800 30
  • 46.25 (n)
rice
(Oryza sativa)
Liliopsida Os08g0120500 30
  • 48.25 (n)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.2910 31
  • 40 (a)
OneToOne
Cin.4897 30
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.4897 30
Species where no ortholog for PDCD4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for PDCD4 Gene

ENSEMBL:
Gene Tree for PDCD4 (if available)
TreeFam:
Gene Tree for PDCD4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PDCD4: view image

Paralogs for PDCD4 Gene

No data available for Paralogs for PDCD4 Gene

Variants for PDCD4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PDCD4 Gene

SNP ID Clinical significance and condition Chr 10 pos Variation AA Info Type
710229 Benign: not provided 110,894,480(+) C/T SYNONYMOUS_VARIANT
747235 Benign: not provided 110,881,291(+) G/A SYNONYMOUS_VARIANT
VAR_036375 A breast cancer sample p.Gly120Arg
rs11548765 - p.Ser48Tyr
rs7081726 - p.Ile36Val

Additional dbSNP identifiers (rs#s) for PDCD4 Gene

Structural Variations from Database of Genomic Variants (DGV) for PDCD4 Gene

Variant ID Type Subtype PubMed ID
nsv1035602 CNV loss 25217958
nsv1069515 CNV deletion 25765185
nsv7211 OTHER inversion 18451855
nsv7548 CNV insertion 18451855
nsv831985 CNV gain+loss 17160897
nsv951847 CNV duplication 24416366

Variation tolerance for PDCD4 Gene

Residual Variation Intolerance Score: 13.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.25; 24.97% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PDCD4 Gene

Human Gene Mutation Database (HGMD)
PDCD4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
PDCD4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PDCD4 Gene

Disorders for PDCD4 Gene

MalaCards: The human disease database

(7) MalaCards diseases for PDCD4 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
colorectal cancer
  • crc
tongue cancer
  • malignant neoplasm of anterior 2/3 of tongue
tongue squamous cell carcinoma
  • squamous cell carcinoma of tongue
lung cancer
  • adenocarcinoma of lung
esophageal cancer
  • esophageal cancer, somatic
- elite association - COSMIC cancer census association via MalaCards
Search PDCD4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for PDCD4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with PDCD4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for PDCD4 Gene

Publications for PDCD4 Gene

  1. Structural basis for translational inhibition by the tumour suppressor Pdcd4. (PMID: 19153607) Loh PG … Song H (The EMBO journal 2009) 3 4 23 54
  2. Tumorigenesis suppressor Pdcd4 down-regulates mitogen-activated protein kinase kinase kinase kinase 1 expression to suppress colon carcinoma cell invasion. (PMID: 16449643) Yang HS … Colburn NH (Molecular and cellular biology 2006) 3 4 23 54
  3. Akt phosphorylates and regulates Pdcd4 tumor suppressor protein. (PMID: 16357133) Palamarchuk A … Pekarsky Y (Cancer research 2005) 3 4 23 54
  4. Novel human PDCD4 (H731) gene expressed in proliferative cells is expressed in the small duct epithelial cells of the breast as revealed by an anti-H731 antibody. (PMID: 10632927) Yoshinaga H … Masaki Z (Pathology international 1999) 3 4 23 54
  5. Differential transcriptional regulation of CD161 and a novel gene, 197/15a, by IL-2, IL-15, and IL-12 in NK and T cells. (PMID: 9759869) Azzoni L … Perussia B (Journal of immunology (Baltimore, Md. : 1950) 1998) 2 3 4 54

Products for PDCD4 Gene