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Protein

Programmed cell death protein 4

Gene

Pdcd4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.4 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionRNA-binding
Biological processApoptosis

Names & Taxonomyi

Protein namesi
Recommended name:
Programmed cell death protein 4
Alternative name(s):
Protein MA-3
Topoisomerase-inhibitor suppressed protein
Gene namesi
Name:Pdcd4
Synonyms:Ma3, Tis
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:107490 Pdcd4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Decreases benign tumor development and malignant progression.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi414D → A: Strongly reduced interaction with EIF4A1. 1 Publication1
Mutagenesisi418D → A: Strongly reduced interaction with EIF4A1. 1 Publication1
Mutagenesisi457S → A or D: No effect on interaction with EIF4A1. 1 Publication1

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002565201 – 469Programmed cell death protein 4Add BLAST469

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei25PhosphoserineBy similarity1
Modified residuei67Phosphoserine; by PKB and RPS6KB1By similarity1
Modified residuei68PhosphoserineBy similarity1
Modified residuei71PhosphoserineBy similarity1
Modified residuei76PhosphoserineCombined sources1
Modified residuei78PhosphoserineBy similarity1
Modified residuei94PhosphoserineBy similarity1
Modified residuei152PhosphotyrosineBy similarity1
Modified residuei313PhosphoserineCombined sources1
Modified residuei317PhosphoserineBy similarity1
Modified residuei457Phosphoserine; by PKBBy similarity1

Post-translational modificationi

Polyubiquitinated, leading to its proteasomal degradation. Rapidly degraded in response to mitogens. Phosphorylation of the phosphodegron promotes interaction with BTRC and proteasomal degradation (By similarity).By similarity
Phosphorylated at Ser-67 by RPS6KB1 in response to mitogens; phosphorylation promotes proteasomal degradation of PDCD4.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ61823
MaxQBiQ61823
PaxDbiQ61823
PeptideAtlasiQ61823
PRIDEiQ61823

PTM databases

iPTMnetiQ61823
PhosphoSitePlusiQ61823
SwissPalmiQ61823

Expressioni

Tissue specificityi

Expressed ubiquitously. Highyly expressed in thymus and liver. Moderately expressed in brain, kidney and spleen; weakly in lung and heart. Expression is up- or down-regulated in response to apoptosis inducers. Regulated by many programmed cell death-inducing stimuli.2 Publications

Gene expression databases

BgeeiENSMUSG00000024975 Expressed in 304 organ(s), highest expression level in pituitary gland
CleanExiMM_PDCD4
GenevisibleiQ61823 MM

Interactioni

Subunit structurei

Interacts (via MI domains) with EIF4A1 and EIF4A2 (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 (By similarity).By similarity

Binary interactionsi

Protein-protein interaction databases

BioGridi202070, 3 interactors
IntActiQ61823, 6 interactors
MINTiQ61823
STRINGi10090.ENSMUSP00000025931

Structurei

Secondary structure

1469
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ61823
SMRiQ61823
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ61823

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini163 – 284MI 1PROSITE-ProRule annotationAdd BLAST122
Domaini326 – 449MI 2PROSITE-ProRule annotationAdd BLAST124

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi58 – 64Nuclear localization signalSequence analysis7
Motifi70 – 76PhosphodegronBy similarity7
Motifi448 – 454Nuclear localization signalSequence analysis7

Domaini

Binds EIF4A1 via both MI domains.1 Publication

Sequence similaritiesi

Belongs to the PDCD4 family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0403 Eukaryota
ENOG410XQZZ LUCA
GeneTreeiENSGT00390000015948
HOGENOMiHOG000261612
HOVERGENiHBG052841
InParanoidiQ61823
KOiK16865
OMAiEAPIMLG
OrthoDBiEOG091G07EZ
PhylomeDBiQ61823
TreeFamiTF323207

Family and domain databases

Gene3Di1.25.40.180, 2 hits
InterProiView protein in InterPro
IPR016024 ARM-type_fold
IPR003891 Initiation_fac_eIF4g_MI
IPR016021 MIF4-like_sf
IPR039778 PDCD4
PANTHERiPTHR12626 PTHR12626, 1 hit
PfamiView protein in Pfam
PF02847 MA3, 2 hits
SMARTiView protein in SMART
SM00544 MA3, 2 hits
SUPFAMiSSF48371 SSF48371, 2 hits
PROSITEiView protein in PROSITE
PS51366 MI, 2 hits

Sequencei

Sequence statusi: Complete.

Q61823-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MDIENEQTLN VNPTDPDNLS DSLFSGDEEN AGTEEIKNEI NGNWISASTI
60 70 80 90 100
NEARINAKAK RRLRKNSSRD SGRGDSVSDN GSEAVRSGVA VPTSPKGRLL
110 120 130 140 150
DRRSRSGKGR GLPKKGGAGG KGVWGTPGQV YDVEEVDVKD PNYDDDQENC
160 170 180 190 200
VYETVVLPLD ETAFEKTLTP IIQEYFEHGD TNEVAEMLRD LNLGEMKSGV
210 220 230 240 250
PVLAVSLALE GKASHREMTS KLLSDLCGTV MSTNDVEKSF DKLLKDLPEL
260 270 280 290 300
ALDTPRAPQL VGQFIARAVG DGILCNTYID SYKGTVDCVQ ARAALDKATV
310 320 330 340 350
LLSMSKGGKR KDSVWGSGGG QQPVNHLVKE IDMLLKEYLL SGDISEAEHC
360 370 380 390 400
LKELEVPHFH HELVYEAIVM VLESTGESAF KMILDLLKSL WKSSTITIDQ
410 420 430 440 450
MKRGYERIYN EIPDINLDVP HSYSVLERFV EECFQAGIIS KQLRDLCPSR
460
GRKRFVSEGD GGRLKPESY
Length:469
Mass (Da):51,702
Last modified:November 1, 1996 - v1
Checksum:i6883BCE5011692F1
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti232S → I in BAA32356 (PubMed:8912629).Curated1
Sequence conflicti232S → I in BAA13072 (PubMed:9714845).Curated1
Sequence conflicti369V → I in BAA32356 (PubMed:8912629).Curated1
Sequence conflicti369V → I in BAA13072 (PubMed:9714845).Curated1
Sequence conflicti414D → G in BAE43115 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D50465 mRNA Translation: BAA09056.1
D86344 mRNA Translation: BAA13072.1
AB010139 Genomic DNA Translation: BAA32356.1
DQ479921 Genomic DNA Translation: ABF51670.1
CT010188 mRNA Translation: CAJ18396.1
AK134366 mRNA Translation: BAE22118.1
AK172654 mRNA Translation: BAE43115.1
BC055739 mRNA Translation: AAH55739.1
CCDSiCCDS29903.1
PIRiJC4523
RefSeqiNP_001161963.1, NM_001168491.1
NP_001161964.1, NM_001168492.1
NP_035180.2, NM_011050.4
XP_006526825.1, XM_006526762.3
UniGeneiMm.1605

Genome annotation databases

EnsembliENSMUST00000025931; ENSMUSP00000025931; ENSMUSG00000024975
ENSMUST00000074371; ENSMUSP00000073975; ENSMUSG00000024975
ENSMUST00000165617; ENSMUSP00000133135; ENSMUSG00000024975
GeneIDi18569
KEGGimmu:18569
UCSCiuc008hxb.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D50465 mRNA Translation: BAA09056.1
D86344 mRNA Translation: BAA13072.1
AB010139 Genomic DNA Translation: BAA32356.1
DQ479921 Genomic DNA Translation: ABF51670.1
CT010188 mRNA Translation: CAJ18396.1
AK134366 mRNA Translation: BAE22118.1
AK172654 mRNA Translation: BAE43115.1
BC055739 mRNA Translation: AAH55739.1
CCDSiCCDS29903.1
PIRiJC4523
RefSeqiNP_001161963.1, NM_001168491.1
NP_001161964.1, NM_001168492.1
NP_035180.2, NM_011050.4
XP_006526825.1, XM_006526762.3
UniGeneiMm.1605

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2HM8NMR-A319-449[»]
2IOLX-ray2.00A/B320-469[»]
2IONX-ray1.57A320-467[»]
2IOSX-ray1.76A320-469[»]
2KZTNMR-B319-449[»]
2NSZX-ray1.15A322-450[»]
3EIQX-ray3.50C120-469[»]
ProteinModelPortaliQ61823
SMRiQ61823
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202070, 3 interactors
IntActiQ61823, 6 interactors
MINTiQ61823
STRINGi10090.ENSMUSP00000025931

PTM databases

iPTMnetiQ61823
PhosphoSitePlusiQ61823
SwissPalmiQ61823

Proteomic databases

EPDiQ61823
MaxQBiQ61823
PaxDbiQ61823
PeptideAtlasiQ61823
PRIDEiQ61823

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000025931; ENSMUSP00000025931; ENSMUSG00000024975
ENSMUST00000074371; ENSMUSP00000073975; ENSMUSG00000024975
ENSMUST00000165617; ENSMUSP00000133135; ENSMUSG00000024975
GeneIDi18569
KEGGimmu:18569
UCSCiuc008hxb.2 mouse

Organism-specific databases

CTDi27250
MGIiMGI:107490 Pdcd4

Phylogenomic databases

eggNOGiKOG0403 Eukaryota
ENOG410XQZZ LUCA
GeneTreeiENSGT00390000015948
HOGENOMiHOG000261612
HOVERGENiHBG052841
InParanoidiQ61823
KOiK16865
OMAiEAPIMLG
OrthoDBiEOG091G07EZ
PhylomeDBiQ61823
TreeFamiTF323207

Miscellaneous databases

ChiTaRSiPdcd4 mouse
EvolutionaryTraceiQ61823
PROiPR:Q61823
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000024975 Expressed in 304 organ(s), highest expression level in pituitary gland
CleanExiMM_PDCD4
GenevisibleiQ61823 MM

Family and domain databases

Gene3Di1.25.40.180, 2 hits
InterProiView protein in InterPro
IPR016024 ARM-type_fold
IPR003891 Initiation_fac_eIF4g_MI
IPR016021 MIF4-like_sf
IPR039778 PDCD4
PANTHERiPTHR12626 PTHR12626, 1 hit
PfamiView protein in Pfam
PF02847 MA3, 2 hits
SMARTiView protein in SMART
SM00544 MA3, 2 hits
SUPFAMiSSF48371 SSF48371, 2 hits
PROSITEiView protein in PROSITE
PS51366 MI, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiPDCD4_MOUSE
AccessioniPrimary (citable) accession number: Q61823
Secondary accession number(s): P97296, Q3T9A9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: November 1, 1996
Last modified: November 7, 2018
This is version 155 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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