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FLASH GENE
Symbol PDCD4 contributors: mct/npt/pgu - updated : 20-08-2013
HGNC name programmed cell death 4 (neoplastic transformation inhibitor)
HGNC id 8763
Location 10q25.2      Physical location : 112.631.595 - 112.659.763
Synonym name
  • death upregulated gene
  • programmed cell death 4
  • nuclear antigen H731
  • Synonym symbol(s) H731, DUG, MGC33046, MGC33047
    DNA
    TYPE functioning gene
    STRUCTURE 28.21 kb     13 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (CAAT box)
    Binding site   transcription factor
    text structure
  • regulation of gene expression via Sp1/Sp3 (Leupold 2007)
  • transcriptional start sites of the promoter, is a functional CCAAT-box
  • ZNF148 is a regulator of PDCD4 by binding to the basal promoter either alone or by interacting with Sp family members
  • MAPPING cloned Y linked N status provisional
    Physical map
    LOC387711 10 LOC387711 LOC390001 10 similar to mitogen-activated protein kinase-activated protein kinase LOC390002 10 similar to B-cell receptor-associated protein 37; repressor of estrogen receptor activity XPNPEP1 10q25.3 X-prolyl aminopeptidase (aminopeptidase P) 1, soluble RNU4P5 10q25.2 RNA, U4 small nuclear pseudogene 5 ADD3 10q24.2-q24.3 adducin 3 (gamma) MXI1 10q25 MAX interacting protein 1 SMNDC1 10q23 survival motor neuron domain containing 1 DUSP5 10q25 dual specificity phosphatase 5 CSPG6 10q25 chondroitin sulfate proteoglycan 6 (bamacan) LOC340699 10q25.3 similar to 1110018J23Rik protein PDCD4 10q24 programmed cell death 4 (neoplastic transformation inhibitor) SHOC2 10q25 soc-2 suppressor of clear homolog (C. elegans) ADRA2A 10q25 adrenergic, alpha-2A-, receptor KIAA1560 10q25.3 glycerol 3-phosphate acyltransferase, mitochondrial TECTB 10q25-q26 tectorin beta LOC390003 10 similar to guanylyl cyclase with kinase-like domain, soluble FACL5 10q25.1-q25.2 fatty-acid-Coenzyme A ligase, long-chain 5 ZDHHC6 10q26.11 zinc finger, DHHC domain containing 6 VTI1A 10q26.11 vesicle transport through interaction with t-SNAREs homolog 1A (yeast) TCF7L2 10q25.3 transcription factor 7-like 2 (T-cell specific, HMG-box) FLJ23556 10q26.11 hypothetical protein FLJ23556 LOC390004 10 similar to peptidylprolyl isomerase E (cyclophilin E) HABP2 10q26.11 hyaluronan binding protein 2 NRAP 10q23-q26 nebulin-related anchoring protein CASP7 10q25.1-q25.2 caspase 7, apoptosis-related cysteine protease FLJ23537 10q26.11 hypothetical protein FLJ23537 DCLRE1A 10q25.1 DNA cross-link repair 1A (PSO2 homolog, S. cerevisiae) FLJ25621 10q26.11 FLJ25621 protein FLJ20147 10q26.11 hypothetical protein FLJ20147 ADRB1 10q24.3 adrenergic, beta-1-, receptor FLJ10188 10q26.11 CTCL tumor antigen L14-2 TDRD1 10q24.1-q25.3 tudor domain containing 1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 - 3591 51.6 469 - 2013 23578931
    13 - 3675 50.4 458 - 2013 23578931
  • including an alternate in-frame exon in the 5' coding region
  • using a downstream start codon compared to variant 1
  • isoform 2, PDCD4B
  • is a relevant target of MIR21 and protection of PDCD4B from MIR21 binding results in failure of atrioventricular valve development
  • 12 - 3602 - 455 - 2013 23578931
    PDCD4A
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivepancreas exocrineacinar gland  highly Homo sapiensAdult
     stomach    
    Endocrinepancreasislet of Langerhans  highly Homo sapiens
    Lymphoid/Immunethymus    
    Reproductivefemale systembreastmammary gland highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...) Homo sapiens
    Urinaryduct cell
    cell lineage
    cell lines highly expressed in bladder carcinoma and breast carcinoma
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES acid
    STRUCTURE
    motifs/domains
  • two putative nuclear localization signals
  • multiple phosphorylation sites for protein kinases
  • two C-terminal MA3 domains, which are thought to be responsible for its inhibitory function, and bind specifically to the eIF4A N-terminal domain
  • HOMOLOGY
    interspecies homolog to murine Pdcd4 (96.8pc)
    homolog to rattus Pdcd4 (96.8pc)
    intraspecies homolog to EIF4G
    Homologene
    FAMILY
  • PDCD4 family
  • CATEGORY regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text overproduced and localized in the cytoplasm during the cell cycle in tumor cell lines
    basic FUNCTION
  • regulating EIF4G-dependent translation through direct interaction with EIF4G and RPS13 in senescent fibroblasts
  • inhibiting the translation initiation factor EIF4A
  • inhibiting tumor promoter-induced neoplastic transformation
  • down-regulating the expression of MAP4K1, thus inhibiting events important in driving invasion, namely, MAPK85 activation and consequent JUN-dependent transcription
  • inhibit invasion by activating activator protein-1 (AP-1)
  • inhibits invasion/intravasation and regulates urokinase receptor PLAUR gene expression via Sp-transcription factors
  • involved in TGFB1-induced apoptosis via the SMAD pathway
  • involved in the regulation of transcription and translation
  • directly involved in translational suppression of a natural mRNA, providing the first evidence for a key role of the RNA-binding domain in targeting PDCD4 to a specific mRNA
  • critical suppressor of apoptosis by inhibiting the translation of procaspase-3 mRNA
  • by affecting the translation and activity of TP53, is likely to exert pleiotropic effects on these biological processes and thereby influence the cellular homeostasis
  • may play a critical function in arresting cell cycle progression at key checkpoint, thus inhibiting cell proliferation, as well as suppressing tumour metastasis
  • CELLULAR PROCESS cell life, proliferation/growth
    cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • form a tighter and more stable complex with EIF4A, which explains the need for two tandem MA3 domains
  • NFKB&
  • 8722;MIR21&
    8722;PDCD4 axis plays a crucial role in Type 1 diabetes
    INTERACTION
    DNA
    RNA binding
    small molecule
    protein
  • binding to EIF4A presumably through MA3 domains and to EIF4G (PDCD4 MA3 domains compete with the eIF4G-MA3 and with RNA for binding to EIF4A)
  • associated with TP53 mRNA and suppresses its translation
  • negative correlation between the expression of FAT1 and PDCD4
  • MIR21 plays a necessary role in cardiac valvulogenesis, in large part due to an obligatory downregulation of PDCD4
  • cell & other
    REGULATION
    inhibited by IL2 stimulation
    Other phosphorylated by S6K1 in response to mitogens and subsequently degraded via the ubiquitin ligase SCF-beta, allowing efficient proteins synthesis and cell growth
    increased expression by IL12 stimulation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    loss of expression correlated with tumor progression of lung and colon carcinoma
    tumoral     --low  
    associated with the progression of serous cystadenocarcinomas and may serve as an important prognostic marker
    tumoral     --over  
    in bladder carcinoma and breast carcinoma
    constitutional       loss of function
    deficiency in pancreatic islet beta cells renders them resistant to death
    tumoral     --low  
    significantly lower in moderately or poorly differentiated digestive tract cancers than in well-differentiated cancers
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • might be a potentially valuable molecular target in diagnosis for human digestive tract cancers
  • Therapy target
    SystemTypeDisorderPubmed
    diabetetype 1 
    the NFkB−MIR21−PDCD4 axis plays a crucial role in T1D and represents a unique therapeutic target for treating the disease
    cancerdigestivepancreas
    might be a potentially valuable molecular target in therapy for human digestive tract cancers
    miscelleaneousvascular 
    may be a new therapeutic target in proliferative vascular diseases
    ANIMAL & CELL MODELS