Reviewed, UniProtKB/Swiss-Prot Q53EL6 (PDCD4_HUMAN)

Names and origin

Protein names

Recommended name:
    Programmed cell death protein 4
Alternative name(s):
    Nuclear antigen H731-like
    Neoplastic transformation inhibitor protein
    Protein 197/15a

Gene names

Name:	PDCD4
Synonyms:	H731

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	469 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Tumor suppressor. Inhibits tumor promoter-induced neoplastic transformation. 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. Inhibits the helicase activity of EIF4A and cap-dependent translation. Binds RNA By similarity.
Subunit structure	Interacts with EIF4A1 and EIF4A2 By similarity.
Subcellular location	Nucleus. Cytoplasm. Note: Shuttles between the nucleus and cytoplasm. Predominantly nuclear under normal growth conditions. Exported from the nucleus in the absence of serum. Ref.6
Tissue specificity	Up-regulated in proliferative cells. Highly expressed in epithelial cells of the mammary gland. Ref.6
Induction	IL2 stimulation inhibits expression, while IL12 increases expression. Ref.2
Domain	Binds EIF4A1 via the MA3 domains By similarity.
Involvement in disease	Loss of expression correlated with tumor progression of lung and colon carcinoma.
Sequence similarities	Belongs to the PDCD4 family. Contains 2 MI domains.
Sequence caution	The sequence AAB42218.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence AAH15036.1 differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Potential poly-A sequence.

Ontologies

Keywords
Biological process	Apoptosis Cell cycle
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	RNA-binding
Molecular function	Anti-oncogene
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	apoptosis Non-traceable author statement. Source: UniProtKB cell aging Inferred from direct assay. Source: UniProtKB cell cycle Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of JUN kinase activity Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell cycle Non-traceable author statement. Source: UniProtKB negative regulation of transcription Inferred from direct assay. Source: UniProtKB
Cellular component	cytosol Inferred from direct assay. Source: UniProtKB nucleus Inferred from mutant phenotype. Source: UniProtKB
Molecular function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EIF4A1	P60842	1	EBI-935824,EBI-73449
EIF4A2	Q14240	1	EBI-935824,EBI-73473
EIF4G1	Q04637	1	EBI-935824,EBI-73711
RPS13	P62277	1	EBI-935824,EBI-351850

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 469

469

Programmed cell death protein 4

PRO_0000256519

Regions

Domain

163 – 284

122

MI 1

Domain

326 – 449

124

MI 2

Motif

58 – 64

7

Nuclear localization signal Potential

Motif

241 – 250

10

Nuclear localization signal Potential

Amino acid modifications

Modified residue

76

1

Phosphoserine Ref.9 Ref.14

Modified residue

78

1

Phosphoserine Ref.14

Modified residue

80

1

Phosphoserine Ref.14

Modified residue

93

1

Phosphothreonine Ref.11 Ref.13

Modified residue

94

1

Phosphoserine Ref.14 Ref.13

Modified residue

152

1

Phosphotyrosine Ref.8

Modified residue

457

1

Phosphoserine Ref.9 Ref.14 Ref.11 Ref.13 Ref.12

Natural variations

Natural variant

36

1

V → I: dbSNP rs7081726. Ref.4

VAR_028901

Natural variant

48

1

S → Y: dbSNP rs11548765. Ref.5

VAR_028902

Natural variant

120

1

G → R in a breast cancer sample; somatic mutation. Ref.17

VAR_036375

Experimental info

Sequence conflict

79

1

D → E in AAB42218. Ref.1

Sequence conflict

102

1

R → G in AAB67706. Ref.2

Sequence conflict

130

1

V → G in AAB67706. Ref.2

Sequence conflict

220

1

S → T in AAB42218. Ref.1

Sequence conflict

222

1

L → F in AAB67706. Ref.2

Sequence conflict

440

1

S → W in AAB67706. Ref.2

Secondary structure

1

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469

Helix Strand Turn

Details...

Helix

161 – 178

18

Helix

181 – 191

11

Helix

195 – 198

4

Helix

199 – 209

11

Helix

213 – 226

14

Turn

227 – 229

3

Helix

233 – 253

21

Helix

257 – 270

14

Helix

278 – 281

4

Turn

282 – 284

3

Helix

289 – 303

15

Helix

328 – 341

14

Helix

344 – 353

10

Helix

357 – 359

3

Helix

360 – 373

14

Helix

377 – 392

16

Helix

398 – 418

21

Helix

422 – 436

15

Helix

441 – 446

6

Sequences

	Sequence		Length	Mass (Da)
	Q53EL6-1 [UniParc]. Last modified May 24, 2005. Version 1. Checksum: 123B994FC6D71548	FASTA	469	51,721
	10 20 30 40 50 60 MDVENEQILN VNPADPDNLS DSLFSGDEEN AGTEEVKNEI NGNWISASSI NEARINAKAK 70 80 90 100 110 120 RRLRKNSSRD SGRGDSVSDS GSDALRSGLT VPTSPKGRLL DRRSRSGKGR GLPKKGGAGG 130 140 150 160 170 180 KGVWGTPGQV YDVEEVDVKD PNYDDDQENC VYETVVLPLD ERAFEKTLTP IIQEYFEHGD 190 200 210 220 230 240 TNEVAEMLRD LNLGEMKSGV PVLAVSLALE GKASHREMTS KLLSDLCGTV MSTTDVEKSF 250 260 270 280 290 300 DKLLKDLPEL ALDTPRAPQL VGQFIARAVG DGILCNTYID SYKGTVDCVQ ARAALDKATV 310 320 330 340 350 360 LLSMSKGGKR KDSVWGSGGG QQSVNHLVKE IDMLLKEYLL SGDISEAEHC LKELEVPHFH 370 380 390 400 410 420 HELVYEAIIM VLESTGESTF KMILDLLKSL WKSSTITVDQ MKRGYERIYN EIPDINLDVP 430 440 450 460 HSYSVLERFV EECFQAGIIS KQLRDLCPSR GRKRFVSEGD GGRLKPESY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of a novel gene from a human cell line with Pr-28 MAb which recognizes a nuclear antigen involved in the cell cycle." Matsuhashi S., Yoshinaga H., Yatsuki H., Tsugita A., Hori K. Res. Commun. Biochem. Cell Mol. Biol. 1:109-120(1997) Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Glial tumor.
[2]	"Differential transcriptional regulation of CD161 and a novel gene, 197/15a, by IL-2, IL-15, and IL-12 in NK and T cells." Azzoni L., Zatsepina O., Abebe B., Bennett I.M., Kanakaraj P., Perussia B. J. Immunol. 161:3493-3500(1998) [PubMed: 9759869] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION. Tissue: Blood.
[3]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Spleen.
[4]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ILE-36.
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT TYR-48. Tissue: Brain and Skin.
[6]	"Novel human PDCD4 (H731) gene expressed in proliferative cells is expressed in the small duct epithelial cells of the breast as revealed by an anti-H731 antibody." Yoshinaga H., Matsuhashi S., Fujiyama C., Masaki Z. Pathol. Int. 49:1067-1077(1999) [PubMed: 10632927] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[7]	"Loss of PDCD4 expression in human lung cancer correlates with tumour progression and prognosis." Chen Y., Knosel T., Kristiansen G., Pietas A., Garber M.E., Matsuhashi S., Ozaki I., Petersen I. J. Pathol. 200:640-646(2003) [PubMed: 12898601] [Abstract] Cited for: REDUCED EXPRESSION IN LUNG CANCER.
[8]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-152, MASS SPECTROMETRY.
[9]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-76 AND SER-457, MASS SPECTROMETRY. Tissue: Epithelium.
[10]	"Tumorigenesis suppressor Pdcd4 down-regulates mitogen-activated protein kinase kinase kinase kinase 1 expression to suppress colon carcinoma cell invasion." Yang H.-S., Matthews C.P., Clair T., Wang Q., Baker A.R., Li C.-C., Tan T.-H., Colburn N.H. Mol. Cell. Biol. 26:1297-1306(2006) [PubMed: 16449643] [Abstract] Cited for: FUNCTION, REDUCED EXPRESSION IN COLON CARCINOMA.
[11]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-93 AND SER-457, MASS SPECTROMETRY. Tissue: Epithelium.
[12]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-457, MASS SPECTROMETRY.
[13]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-93; SER-94 AND SER-457, MASS SPECTROMETRY.
[14]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-76; SER-78; SER-80; SER-94 AND SER-457, MASS SPECTROMETRY.
[15]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[16]	"Solution structure of the MA3 domain of human programmed cell death 4." RIKEN structural genomics initiative (RSGI) Submitted (APR-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 320-450.
[17]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-120.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

U83908 Genomic DNA. Translation: AAB42218.1. Sequence problems.
U96628 mRNA. Translation: AAB67706.1.
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.

IPI

IPI00290110.

PIR

JC5193.

RefSeq

NP_055271.2.
NP_663314.1.

UniGene

Hs.711490

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2GGF	NMR	-	A	327-450	[»]
2RG8	X-ray	1.80	A/B	157-320	[»]
2ZU6	X-ray	2.80	B/E	163-469	[»]
3EIJ	X-ray	2.80	A/B	157-469	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q53EL6. 6 interactions.

PTM databases

PhosphoSite

Q53EL6.

Genome annotation databases

Ensembl

ENSG00000150593. Homo sapiens. [Contig view]

GeneID

27250.

KEGG

hsa:27250.

Organism-specific databases

GeneCards

GC10P112618.

HGNC

HGNC:8763. PDCD4.

HPA

HPA001032.

MIM

608610. gene.

PharmGKB

PA33113.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q53EL6.

Gene expression databases

ArrayExpress

Q53EL6.

Bgee

Q53EL6.

CleanEx

HS_PDCD4.

GermOnline

ENSG00000150593. Homo sapiens.

Family and domain databases

InterPro

IPR003891. Initiation_fac_eIF4g_MI.
[Graphical view]

Pfam

PF02847. MA3. 2 hits.
[Graphical view]

SMART

SM00544. MA3. 2 hits.
[Graphical view]

PROSITE

PS51366. MI. 2 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

50179.

SOURCE

Search...

Entry information

Entry name

PDCD4_HUMAN

Accession

Primary (citable) accession number: Q53EL6
Secondary accession number(s): O15501 , Q5VZS6, Q6PJI5, Q8TAR5, Q99834

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2006
Last sequence update:	May 24, 2005
Last modified:	June 16, 2009
This is version 42 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)