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Protein

Programmed cell death protein 4

Gene

Pdcd4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Complete GO annotation...

Keywords - Biological processi

Apoptosis

Keywords - Ligandi

RNA-binding

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:107490. Pdcd4.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Decreases benign tumor development and malignant progression.

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.

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.
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

WithEntry#Exp.IntActNotes
Eif4a1P608434EBI-296473,EBI-6665935
Eif4g2Q624482EBI-296473,EBI-296494

Protein-protein interaction databases

BioGridi202070. 2 interactors.
IntActiQ61823. 4 interactors.
MINTiMINT-7012023.
STRINGi10090.ENSMUSP00000025931.

Structurei

Secondary structure

1469
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi162 – 178Combined sources17
Helixi181 – 189Combined sources9
Turni190 – 192Combined sources3
Helixi195 – 199Combined sources5
Helixi200 – 208Combined sources9
Helixi213 – 224Combined sources12
Turni225 – 229Combined sources5
Helixi233 – 245Combined sources13
Helixi247 – 253Combined sources7
Helixi257 – 270Combined sources14
Helixi280 – 282Combined sources3
Helixi289 – 302Combined sources14
Beta strandi320 – 322Combined sources3
Helixi326 – 341Combined sources16
Helixi344 – 354Combined sources11
Helixi357 – 359Combined sources3
Helixi360 – 373Combined sources14
Beta strandi374 – 377Combined sources4
Helixi378 – 392Combined sources15
Helixi398 – 418Combined sources21
Helixi422 – 435Combined sources14
Helixi441 – 445Combined sources5

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...

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
Contains 2 MI domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

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

Family and domain databases

Gene3Di1.25.40.180. 2 hits.
InterProiIPR016024. ARM-type_fold.
IPR003891. Initiation_fac_eIF4g_MI.
IPR016021. MIF4-like.
[Graphical view]
PfamiPF02847. MA3. 2 hits.
[Graphical view]
SMARTiSM00544. MA3. 2 hits.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 2 hits.
PROSITEiPS51366. MI. 2 hits.
[Graphical view]

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.

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. 2 interactors.
IntActiQ61823. 4 interactors.
MINTiMINT-7012023.
STRINGi10090.ENSMUSP00000025931.

PTM databases

iPTMnetiQ61823.
PhosphoSitePlusiQ61823.

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.
OMAiDGYKGTV.
OrthoDBiEOG091G07EZ.
PhylomeDBiQ61823.
TreeFamiTF323207.

Miscellaneous databases

ChiTaRSiPdcd4. mouse.
EvolutionaryTraceiQ61823.
PROiQ61823.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000024975.
CleanExiMM_PDCD4.
GenevisibleiQ61823. MM.

Family and domain databases

Gene3Di1.25.40.180. 2 hits.
InterProiIPR016024. ARM-type_fold.
IPR003891. Initiation_fac_eIF4g_MI.
IPR016021. MIF4-like.
[Graphical view]
PfamiPF02847. MA3. 2 hits.
[Graphical view]
SMARTiSM00544. MA3. 2 hits.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 2 hits.
PROSITEiPS51366. MI. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPDCD4_MOUSE
AccessioniPrimary (citable) accession number: Q61823
Secondary accession number(s): P97296, Q3T9A9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: November 1, 1996
Last modified: November 2, 2016
This is version 142 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.