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Protein

Programmed cell death protein 4

Gene

PDCD4

Organism
Homo sapiens (Human)
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 (By similarity).By similarity6 Publications

GO - Molecular functioni

GO - Biological processi

  • apoptotic process Source: UniProtKB
  • cell aging Source: UniProtKB
  • negative regulation of apoptotic process Source: Ensembl
  • negative regulation of cell cycle Source: UniProtKB
  • negative regulation of JUN kinase activity Source: UniProtKB
  • negative regulation of myofibroblast differentiation Source: BHF-UCL
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of smooth muscle cell apoptotic process Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Apoptosis

Keywords - Ligandi

RNA-binding

Enzyme and pathway databases

SIGNORiQ53EL6.

Names & Taxonomyi

Protein namesi
Recommended name:
Programmed cell death protein 4
Alternative name(s):
Neoplastic transformation inhibitor protein
Nuclear antigen H731-like
Protein 197/15a
Gene namesi
Name:PDCD4
Synonyms:H731
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:8763. PDCD4.

Subcellular locationi

  • Nucleus By similarity
  • Cytoplasm By similarity

  • Note: Shuttles between the nucleus and cytoplasm (By similarity). Predominantly nuclear under normal growth conditions, and when phosphorylated at Ser-457 (PubMed:16357133).1 Publication

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi67S → A: Loss of phosphorylation site. Reduces interaction with BTRC. Abolishes phosphorylation by PKB; when associated with A-457. 2 Publications1
Mutagenesisi71S → A: Strongly reduced interaction with BTRC. Strongly reduced ubiquitination. 1 Publication1
Mutagenesisi76S → A: Strongly reduced interaction with BTRC. Strongly reduced ubiquitination. 1 Publication1
Mutagenesisi174E → A: Reduced inhibition of EIF4A1 helicase activity. 1 Publication1
Mutagenesisi210E → A: Reduced inhibition of EIF4A1 helicase activity. Strongly reduced inhibition of translation. 1 Publication1
Mutagenesisi249E → A: Reduced interaction with EIF4A1. 1 Publication1
Mutagenesisi252L → A: Strongly reduced interaction with EIF4A1. Reduced inhibition of EIF4A1 helicase activity. Strongly reduced inhibition of translation. 1 Publication1
Mutagenesisi253D → A: Strongly reduced interaction with EIF4A1. Strongly reduced inhibition of translation. Reduced inhibition of EIF4A1 helicase activity. 2 Publications1
Mutagenesisi255P → A: Reduced inhibition of EIF4A1 helicase activity. Strongly reduced inhibition of translation. 1 Publication1
Mutagenesisi333M → A: No effect on inhibition of EIF4A1 and on inhibition of translation; when associated with A-340. 1 Publication1
Mutagenesisi337E → A: No effect on inhibition of EIF4A1 and on inhibition of translation. 1 Publication1
Mutagenesisi340L → A: No effect on inhibition of EIF4A1 and on inhibition of translation; when associated with A-333. 1 Publication1
Mutagenesisi358H → A: Strongly reduced interaction with EIF4A1. 1 Publication1
Mutagenesisi359F → A: Strongly reduced inhibition of EIF4A1. Strongly reduced inhibition of translation. 1 Publication1
Mutagenesisi361H → A: Strongly reduced inhibition of EIF4A1. Strongly reduced inhibition of translation. 1 Publication1
Mutagenesisi414D → A: Strongly reduced interaction with EIF4A1. Strongly reduced inhibition of translation. 1 Publication1
Mutagenesisi418D → A: Reduced interaction with EIF4A1. Strongly reduced inhibition of translation. 1 Publication1
Mutagenesisi420P → A: Strongly reduced interaction with EIF4A1. Strongly reduced inhibition of translation. 1 Publication1
Mutagenesisi457S → A: Loss of phosphorylation site, and loss of nuclear accumulation. Abolishes phosphorylation by PKB; when associated with A-67. 1 Publication1

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

DisGeNETi27250.
OpenTargetsiENSG00000150593.
PharmGKBiPA33113.

Chemistry databases

ChEMBLiCHEMBL1781868.

Polymorphism and mutation databases

BioMutaiPDCD4.
DMDMi317373317.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002565191 – 469Programmed cell death protein 4Add BLAST469

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei25PhosphoserineBy similarity1
Modified residuei67Phosphoserine; by PKB and RPS6KB1Combined sources2 Publications1
Modified residuei68PhosphoserineCombined sources1
Modified residuei71PhosphoserineCombined sources1
Modified residuei76PhosphoserineCombined sources1
Modified residuei78PhosphoserineCombined sources1
Modified residuei80PhosphoserineCombined sources1
Modified residuei94PhosphoserineCombined sources1
Modified residuei152PhosphotyrosineCombined sources1
Modified residuei313PhosphoserineCombined sources1
Modified residuei317PhosphoserineCombined sources1
Modified residuei457Phosphoserine; by PKBCombined sources1 Publication1

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.1 Publication
Phosphorylated at Ser-67 by RPS6KB1 in response to mitogens; phosphorylation promotes proteasomal degradation of PDCD4.2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ53EL6.
MaxQBiQ53EL6.
PaxDbiQ53EL6.
PeptideAtlasiQ53EL6.
PRIDEiQ53EL6.

PTM databases

iPTMnetiQ53EL6.
PhosphoSitePlusiQ53EL6.
SwissPalmiQ53EL6.

Expressioni

Tissue specificityi

Up-regulated in proliferative cells. Highly expressed in epithelial cells of the mammary gland. Reduced expression in lung cancer and colon carcinoma.3 Publications

Inductioni

IL2/interleukin-2 stimulation inhibits expression, while IL12/interleukin-12 increases expression.1 Publication

Gene expression databases

BgeeiENSG00000150593.
CleanExiHS_PDCD4.
ExpressionAtlasiQ53EL6. baseline and differential.
GenevisibleiQ53EL6. HS.

Organism-specific databases

HPAiCAB037024.
HPA001032.
HPA027214.

Interactioni

Subunit structurei

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.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
APOEP026493EBI-935824,EBI-1222467
EIF4A1P608422EBI-935824,EBI-73449
EIF4A2Q142405EBI-935824,EBI-73473
EIF4A3P389193EBI-935824,EBI-299104
PSEN2P498103EBI-935824,EBI-2010251
RELAQ042066EBI-935824,EBI-73886
RPS13P622772EBI-935824,EBI-351850

Protein-protein interaction databases

BioGridi118098. 51 interactors.
DIPiDIP-29756N.
IntActiQ53EL6. 18 interactors.
STRINGi9606.ENSP00000280154.

Chemistry databases

BindingDBiQ53EL6.

Structurei

Secondary structure

1469
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi161 – 178Combined sources18
Helixi181 – 191Combined sources11
Helixi195 – 198Combined sources4
Helixi199 – 209Combined sources11
Helixi213 – 226Combined sources14
Turni227 – 229Combined sources3
Helixi233 – 253Combined sources21
Helixi257 – 270Combined sources14
Helixi278 – 281Combined sources4
Turni282 – 284Combined sources3
Helixi289 – 303Combined sources15
Beta strandi308 – 313Combined sources6
Helixi324 – 341Combined sources18
Helixi344 – 354Combined sources11
Helixi357 – 359Combined sources3
Helixi360 – 372Combined sources13
Helixi378 – 393Combined sources16
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
2GGFNMR-A327-450[»]
2KZTNMR-A157-318[»]
2RG8X-ray1.80A/B157-320[»]
2ZU6X-ray2.80B/E163-469[»]
3EIJX-ray2.80A/B157-469[»]
ProteinModelPortaliQ53EL6.
SMRiQ53EL6.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ53EL6.

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 – 76Phosphodegron7
Motifi241 – 250Nuclear localization signalSequence analysis10

Domaini

Binds EIF4A1 via both MI domains.2 Publications

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.
InParanoidiQ53EL6.
KOiK16865.
OMAiDGYKGTV.
OrthoDBiEOG091G07EZ.
PhylomeDBiQ53EL6.
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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q53EL6-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDVENEQILN VNPADPDNLS DSLFSGDEEN AGTEEIKNEI NGNWISASSI
60 70 80 90 100
NEARINAKAK RRLRKNSSRD SGRGDSVSDS GSDALRSGLT VPTSPKGRLL
110 120 130 140 150
DRRSRSGKGR GLPKKGGAGG KGVWGTPGQV YDVEEVDVKD PNYDDDQENC
160 170 180 190 200
VYETVVLPLD ERAFEKTLTP IIQEYFEHGD TNEVAEMLRD LNLGEMKSGV
210 220 230 240 250
PVLAVSLALE GKASHREMTS KLLSDLCGTV MSTTDVEKSF DKLLKDLPEL
260 270 280 290 300
ALDTPRAPQL VGQFIARAVG DGILCNTYID SYKGTVDCVQ ARAALDKATV
310 320 330 340 350
LLSMSKGGKR KDSVWGSGGG QQSVNHLVKE IDMLLKEYLL SGDISEAEHC
360 370 380 390 400
LKELEVPHFH HELVYEAIIM VLESTGESTF KMILDLLKSL WKSSTITVDQ
410 420 430 440 450
MKRGYERIYN EIPDINLDVP HSYSVLERFV EECFQAGIIS KQLRDLCPSR
460
GRKRFVSEGD GGRLKPESY
Length:469
Mass (Da):51,735
Last modified:January 11, 2011 - v2
Checksum:i2CAE1D2055491177
GO
Isoform 2 (identifier: Q53EL6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: MDVENEQILNVNPAD → MTKY

Note: No experimental confirmation available.
Show »
Length:458
Mass (Da):50,576
Checksum:iE887AA311F3EB4D4
GO

Sequence cautioni

The sequence AAB42218 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence AAH15036 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti79D → E in AAB42218 (Ref. 1) Curated1
Sequence conflicti102R → G in AAB67706 (PubMed:9759869).Curated1
Sequence conflicti130V → G in AAB67706 (PubMed:9759869).Curated1
Sequence conflicti220S → T in AAB42218 (Ref. 1) Curated1
Sequence conflicti222L → F in AAB67706 (PubMed:9759869).Curated1
Sequence conflicti309K → R in BAG37701 (PubMed:14702039).Curated1
Sequence conflicti314V → A in BAG37701 (PubMed:14702039).Curated1
Sequence conflicti440S → W in AAB67706 (PubMed:9759869).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02890136I → V.Combined sources5 PublicationsCorresponds to variant rs7081726dbSNPEnsembl.1
Natural variantiVAR_02890248S → Y.1 PublicationCorresponds to variant rs11548765dbSNPEnsembl.1
Natural variantiVAR_036375120G → R in a breast cancer sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0456221 – 15MDVEN…VNPAD → MTKY in isoform 2. 1 PublicationAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U83908 Genomic DNA. Translation: AAB42218.1. Sequence problems.
U96628 mRNA. Translation: AAB67706.1.
AK315295 mRNA. Translation: BAG37701.1.
AK223623 mRNA. Translation: BAD97343.1.
AL158163, AL136368 Genomic DNA. Translation: CAH72815.1.
AL136368, AL158163 Genomic DNA. Translation: CAI40095.1.
BC015036 mRNA. Translation: AAH15036.1. Sequence problems.
BC026104 mRNA. Translation: AAH26104.1.
BC031049 mRNA. Translation: AAH31049.1.
CCDSiCCDS44478.1. [Q53EL6-2]
CCDS7567.1. [Q53EL6-1]
PIRiJC5193.
RefSeqiNP_055271.2. NM_014456.4. [Q53EL6-1]
NP_663314.1. NM_145341.3. [Q53EL6-2]
UniGeneiHs.711490.

Genome annotation databases

EnsembliENST00000280154; ENSP00000280154; ENSG00000150593. [Q53EL6-1]
ENST00000393104; ENSP00000376816; ENSG00000150593. [Q53EL6-2]
GeneIDi27250.
KEGGihsa:27250.
UCSCiuc001kzg.4. human. [Q53EL6-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U83908 Genomic DNA. Translation: AAB42218.1. Sequence problems.
U96628 mRNA. Translation: AAB67706.1.
AK315295 mRNA. Translation: BAG37701.1.
AK223623 mRNA. Translation: BAD97343.1.
AL158163, AL136368 Genomic DNA. Translation: CAH72815.1.
AL136368, AL158163 Genomic DNA. Translation: CAI40095.1.
BC015036 mRNA. Translation: AAH15036.1. Sequence problems.
BC026104 mRNA. Translation: AAH26104.1.
BC031049 mRNA. Translation: AAH31049.1.
CCDSiCCDS44478.1. [Q53EL6-2]
CCDS7567.1. [Q53EL6-1]
PIRiJC5193.
RefSeqiNP_055271.2. NM_014456.4. [Q53EL6-1]
NP_663314.1. NM_145341.3. [Q53EL6-2]
UniGeneiHs.711490.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2GGFNMR-A327-450[»]
2KZTNMR-A157-318[»]
2RG8X-ray1.80A/B157-320[»]
2ZU6X-ray2.80B/E163-469[»]
3EIJX-ray2.80A/B157-469[»]
ProteinModelPortaliQ53EL6.
SMRiQ53EL6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118098. 51 interactors.
DIPiDIP-29756N.
IntActiQ53EL6. 18 interactors.
STRINGi9606.ENSP00000280154.

Chemistry databases

BindingDBiQ53EL6.
ChEMBLiCHEMBL1781868.

PTM databases

iPTMnetiQ53EL6.
PhosphoSitePlusiQ53EL6.
SwissPalmiQ53EL6.

Polymorphism and mutation databases

BioMutaiPDCD4.
DMDMi317373317.

Proteomic databases

EPDiQ53EL6.
MaxQBiQ53EL6.
PaxDbiQ53EL6.
PeptideAtlasiQ53EL6.
PRIDEiQ53EL6.

Protocols and materials databases

DNASUi27250.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000280154; ENSP00000280154; ENSG00000150593. [Q53EL6-1]
ENST00000393104; ENSP00000376816; ENSG00000150593. [Q53EL6-2]
GeneIDi27250.
KEGGihsa:27250.
UCSCiuc001kzg.4. human. [Q53EL6-1]

Organism-specific databases

CTDi27250.
DisGeNETi27250.
GeneCardsiPDCD4.
H-InvDBHIX0009201.
HGNCiHGNC:8763. PDCD4.
HPAiCAB037024.
HPA001032.
HPA027214.
MIMi608610. gene.
neXtProtiNX_Q53EL6.
OpenTargetsiENSG00000150593.
PharmGKBiPA33113.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0403. Eukaryota.
ENOG410XQZZ. LUCA.
GeneTreeiENSGT00390000015948.
HOGENOMiHOG000261612.
HOVERGENiHBG052841.
InParanoidiQ53EL6.
KOiK16865.
OMAiDGYKGTV.
OrthoDBiEOG091G07EZ.
PhylomeDBiQ53EL6.
TreeFamiTF323207.

Enzyme and pathway databases

SIGNORiQ53EL6.

Miscellaneous databases

ChiTaRSiPDCD4. human.
EvolutionaryTraceiQ53EL6.
GeneWikiiPDCD4.
GenomeRNAii27250.
PROiQ53EL6.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000150593.
CleanExiHS_PDCD4.
ExpressionAtlasiQ53EL6. baseline and differential.
GenevisibleiQ53EL6. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: Q53EL6
Secondary accession number(s): B2RCV4
, B5ME91, O15501, Q5VZS6, Q6PJI5, Q8TAR5, Q99834
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: January 11, 2011
Last modified: November 2, 2016
This is version 116 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.