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Q61823 (PDCD4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Programmed cell death protein 4
Alternative name(s):
Protein MA-3
Topoisomerase-inhibitor suppressed protein
Gene names
Name:Pdcd4
Synonyms:Ma3, Tis
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length469 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8 Ref.9 Ref.10 Ref.11

Subunit structure

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. Ref.8 Ref.11 Ref.12 Ref.13

Subcellular location

Nucleus. Cytoplasm. Note: Shuttles between the nucleus and cytoplasm. Predominantly nuclear under normal growth conditions, and when phosphorylated at Ser-457 By similarity. Exported from the nucleus in the absence of serum. Ref.8 Ref.9

Tissue specificity

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. Ref.1 Ref.3

Domain

Binds EIF4A1 via both MI domains. Ref.13

Post-translational modification

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.

Phosphorylated at Ser-67 by RPS6KB1 in response to mitogens; phosphorylation promotes proteasomal degradation of PDCD4 By similarity.

Involvement in disease

Decreases benign tumor development and malignant progression.

Sequence similarities

Belongs to the PDCD4 family.

Contains 2 MI domains.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Eif4a1P608434EBI-296473,EBI-6665935
Eif4g2Q624482EBI-296473,EBI-296494

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 469469Programmed cell death protein 4
PRO_0000256520

Regions

Domain163 – 284122MI 1
Domain326 – 449124MI 2
Motif58 – 647Nuclear localization signal Potential
Motif70 – 767Phosphodegron By similarity
Motif448 – 4547Nuclear localization signal Potential

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue671Phosphoserine; by PKB and RPS6KB1 By similarity
Modified residue761Phosphoserine By similarity
Modified residue781Phosphoserine By similarity
Modified residue941Phosphoserine By similarity
Modified residue1521Phosphotyrosine By similarity
Modified residue4571Phosphoserine; by PKB By similarity

Experimental info

Mutagenesis4141D → A: Strongly reduced interaction with EIF4A1. Ref.11
Mutagenesis4181D → A: Strongly reduced interaction with EIF4A1. Ref.11
Mutagenesis4571S → A or D: No effect on interaction with EIF4A1. Ref.11
Sequence conflict2321S → I in BAA32356. Ref.2
Sequence conflict2321S → I in BAA13072. Ref.3
Sequence conflict3691V → I in BAA32356. Ref.2
Sequence conflict3691V → I in BAA13072. Ref.3
Sequence conflict4141D → G in BAE43115. Ref.5

Secondary structure

....................................... 469
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q61823 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 6883BCE5011692F1

FASTA46951,702
        10         20         30         40         50         60 
MDIENEQTLN VNPTDPDNLS DSLFSGDEEN AGTEEIKNEI NGNWISASTI NEARINAKAK 

        70         80         90        100        110        120 
RRLRKNSSRD SGRGDSVSDN GSEAVRSGVA VPTSPKGRLL DRRSRSGKGR GLPKKGGAGG 

       130        140        150        160        170        180 
KGVWGTPGQV YDVEEVDVKD PNYDDDQENC VYETVVLPLD ETAFEKTLTP IIQEYFEHGD 

       190        200        210        220        230        240 
TNEVAEMLRD LNLGEMKSGV PVLAVSLALE GKASHREMTS KLLSDLCGTV MSTNDVEKSF 

       250        260        270        280        290        300 
DKLLKDLPEL ALDTPRAPQL VGQFIARAVG DGILCNTYID SYKGTVDCVQ ARAALDKATV 

       310        320        330        340        350        360 
LLSMSKGGKR KDSVWGSGGG QQPVNHLVKE IDMLLKEYLL SGDISEAEHC LKELEVPHFH 

       370        380        390        400        410        420 
HELVYEAIVM VLESTGESAF KMILDLLKSL WKSSTITIDQ MKRGYERIYN EIPDINLDVP 

       430        440        450        460 
HSYSVLERFV EECFQAGIIS KQLRDLCPSR GRKRFVSEGD GGRLKPESY 

« Hide

References

« Hide 'large scale' references
[1]"Isolation of a novel mouse gene MA-3 that is induced upon programmed cell death."
Shibahara K., Asano M., Ishida Y., Aoki T., Koike T., Honjo T.
Gene 166:297-301(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Strain: ICR.
Tissue: Thymus.
[2]"Molecular cloning of the genes suppressed in RVC lymphoma cells by topoisomerase inhibitors."
Onishi Y., Kizaki H.
Biochem. Biophys. Res. Commun. 228:7-13(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Lymphoma.
[3]"Cloning of the TIS gene suppressed by topoisomerase inhibitors."
Onishi Y., Hashimoto S., Kizaki H.
Gene 215:453-459(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY.
[4]"Positional cloning of Sorcs1, a type 2 diabetes quantitative trait locus."
Clee S.M., Yandell B.S., Schueler K.M., Rabaglia M.E., Richards O.C., Raines S.M., Kabara E.A., Klass D.M., Mui E.T.-K., Stapleton D.S., Gray-Keller M.P., Young M.B., Stoehr J.P., Lan H., Boronenkov I., Raess P.W., Flowers M.T., Attie A.D.
Nat. Genet. 38:688-693(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: BTBR T+ tf/J.
[5]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J and NOD.
Tissue: Spleen and Testis.
[6]"Cloning of mouse full open reading frames in Gateway(R) system entry vector (pDONR201)."
Ebert L., Muenstermann E., Schatten R., Henze S., Bohn E., Mollenhauer J., Wiemann S., Schick M., Korn B.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6.
Tissue: Brain.
[8]"The transformation suppressor Pdcd4 is a novel eukaryotic translation initiation factor 4A binding protein that inhibits translation."
Yang H.-S., Jansen A.P., Komar A.A., Zheng X., Merrick W.C., Costes S., Lockett S.J., Sonenberg N., Colburn N.H.
Mol. Cell. Biol. 23:26-37(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH EIF4A1 AND EIF4A2.
[9]"The transformation suppressor protein Pdcd4 shuttles between nucleus and cytoplasm and binds RNA."
Boehm M., Sawicka K., Siebrasse J.P., Brehmer-Fastnacht A., Peters R., Klempnauer K.-H.
Oncogene 22:4905-4910(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[10]"Epidermal expression of the translation inhibitor programmed cell death 4 suppresses tumorigenesis."
Jansen A.P., Camalier C.E., Colburn N.H.
Cancer Res. 65:6034-6041(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Structural basis for inhibition of translation by the tumor suppressor pdcd4."
Laronde-Leblanc N., Santhanam A.N., Baker A.R., Wlodawer A., Colburn N.H.
Mol. Cell. Biol. 27:147-156(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.15 ANGSTROMS) OF 320-469, FUNCTION, INTERACTION WITH EIF4A AND EIF4G, SUBUNIT, MUTAGENESIS OF ASP-414; ASP-418 AND SER-457.
[12]"Structure of the C-terminal MA-3 domain of the tumour suppressor protein Pdcd4 and characterization of its interaction with eIF4A."
Waters L.C., Veverka V., Bohm M., Schmedt T., Choong P.T., Muskett F.W., Klempnauer K.H., Carr M.D.
Oncogene 26:4941-4950(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 319-449, INTERACTION WITH EIF4A1.
[13]"Structural basis for translational inhibition by the tumour suppressor Pdcd4."
Loh P.G., Yang H.S., Walsh M.A., Wang Q., Wang X., Cheng Z., Liu D., Song H.
EMBO J. 28:274-285(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 120-469 IN COMPLEX WITH EIF4A1, SUBUNIT, DOMAIN.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRJC4523.
RefSeqNP_001161963.1. NM_001168491.1.
NP_001161964.1. NM_001168492.1.
NP_035180.2. NM_011050.4.
XP_006526825.1. XM_006526762.1.
UniGeneMm.1605.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2HM8NMR-A319-449[»]
2IOLX-ray2.00A/B320-469[»]
2IONX-ray1.57A320-469[»]
2IOSX-ray1.76A320-469[»]
2KZTNMR-B319-449[»]
2NSZX-ray1.15A322-450[»]
3EIQX-ray3.50C120-469[»]
ProteinModelPortalQ61823.
SMRQ61823. Positions 157-450.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202070. 1 interaction.
IntActQ61823. 4 interactions.
MINTMINT-7012023.

PTM databases

PhosphoSiteQ61823.

Proteomic databases

PaxDbQ61823.
PRIDEQ61823.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000025931; ENSMUSP00000025931; ENSMUSG00000024975.
ENSMUST00000074371; ENSMUSP00000073975; ENSMUSG00000024975.
ENSMUST00000165617; ENSMUSP00000133135; ENSMUSG00000024975.
GeneID18569.
KEGGmmu:18569.
UCSCuc008hxb.2. mouse.

Organism-specific databases

CTD27250.
MGIMGI:107490. Pdcd4.

Phylogenomic databases

eggNOGNOG249108.
GeneTreeENSGT00390000015948.
HOGENOMHOG000261612.
HOVERGENHBG052841.
InParanoidQ61823.
KOK16865.
OMALSMSKGG.
OrthoDBEOG7X9G6X.
PhylomeDBQ61823.
TreeFamTF323207.

Gene expression databases

BgeeQ61823.
CleanExMM_PDCD4.
GenevestigatorQ61823.

Family and domain databases

Gene3D1.25.40.180. 2 hits.
InterProIPR016024. ARM-type_fold.
IPR003891. Initiation_fac_eIF4g_MI.
IPR016021. MIF4-like_typ_1/2/3.
[Graphical view]
PfamPF02847. MA3. 2 hits.
[Graphical view]
SMARTSM00544. MA3. 2 hits.
[Graphical view]
SUPFAMSSF48371. SSF48371. 2 hits.
PROSITEPS51366. MI. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPDCD4. mouse.
EvolutionaryTraceQ61823.
NextBio294400.
PROQ61823.
SOURCESearch...

Entry information

Entry namePDCD4_MOUSE
AccessionPrimary (citable) accession number: Q61823
Secondary accession number(s): P97296, Q3T9A9
Entry history
Integrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot