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Protein

Programmed cell death protein 4

Gene

PDCD4

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionRNA-binding
Biological processApoptosis

Enzyme and pathway databases

ReactomeiR-HSA-8950505 Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
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

EuPathDBiHostDB:ENSG00000150593.15
HGNCiHGNC:8763 PDCD4
MIMi608610 gene
neXtProtiNX_Q53EL6

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

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
ProteomicsDBi62437

PTM databases

CarbonylDBiQ53EL6
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 Expressed in 231 organ(s), highest expression level in body of pancreas
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

Protein-protein interaction databases

BioGridi118098, 51 interactors
CORUMiQ53EL6
DIPiDIP-29756N
ELMiQ53EL6
IntActiQ53EL6, 18 interactors
STRINGi9606.ENSP00000280154

Chemistry databases

BindingDBiQ53EL6

Structurei

Secondary structure

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

3D structure databases

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0403 Eukaryota
ENOG410XQZZ LUCA
GeneTreeiENSGT00390000015948
HOGENOMiHOG000261612
HOVERGENiHBG052841
InParanoidiQ53EL6
KOiK16865
OMAiEAPIMLG
OrthoDBiEOG091G07EZ
PhylomeDBiQ53EL6
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

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5VZS7Q5VZS7_HUMAN
Programmed cell death protein 4
PDCD4
231Annotation score:

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 → VCombined sources5 PublicationsCorresponds to variant dbSNP:rs7081726Ensembl.1
Natural variantiVAR_02890248S → Y1 PublicationCorresponds to variant dbSNP:rs11548765Ensembl.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 Genomic DNA No translation available.
AL136368 Genomic DNA No translation available.
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

Similar proteinsi

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 Genomic DNA No translation available.
AL136368 Genomic DNA No translation available.
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
CORUMiQ53EL6
DIPiDIP-29756N
ELMiQ53EL6
IntActiQ53EL6, 18 interactors
STRINGi9606.ENSP00000280154

Chemistry databases

BindingDBiQ53EL6
ChEMBLiCHEMBL1781868

PTM databases

CarbonylDBiQ53EL6
iPTMnetiQ53EL6
PhosphoSitePlusiQ53EL6
SwissPalmiQ53EL6

Polymorphism and mutation databases

BioMutaiPDCD4
DMDMi317373317

Proteomic databases

EPDiQ53EL6
MaxQBiQ53EL6
PaxDbiQ53EL6
PeptideAtlasiQ53EL6
PRIDEiQ53EL6
ProteomicsDBi62437

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
EuPathDBiHostDB:ENSG00000150593.15
GeneCardsiPDCD4
H-InvDBiHIX0009201
HGNCiHGNC:8763 PDCD4
HPAiCAB037024
HPA001032
HPA027214
MIMi608610 gene
neXtProtiNX_Q53EL6
OpenTargetsiENSG00000150593
PharmGKBiPA33113
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-HSA-8950505 Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
SIGNORiQ53EL6

Miscellaneous databases

ChiTaRSiPDCD4 human
EvolutionaryTraceiQ53EL6
GeneWikiiPDCD4
GenomeRNAii27250
PROiPR:Q53EL6
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000150593 Expressed in 231 organ(s), highest expression level in body of pancreas
CleanExiHS_PDCD4
ExpressionAtlasiQ53EL6 baseline and differential
GenevisibleiQ53EL6 HS

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_HUMAN
AccessioniPrimary (citable) accession number: Q53EL6
Secondary accession number(s): B2RCV4
, B5ME91, O15501, Q5VZS6, Q6PJI5, Q8TAR5, Q99834
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: January 11, 2011
Last modified: November 7, 2018
This is version 131 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
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