PDCD4_RAT
ID PDCD4_RAT Reviewed; 469 AA.
AC Q9JID1;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Programmed cell death protein 4;
DE AltName: Full=Death up-regulated gene protein;
GN Name=Pdcd4; Synonyms=Dug;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, INTERACTION WITH
RP EIF4A1, INDUCTION, AND ALTERNATIVE SPLICING.
RX PubMed=12220511; DOI=10.1016/s0006-291x(02)02129-0;
RA Goeke A., Goeke R., Knolle A., Trusheim H., Schmidt H., Wilmen A.,
RA Carmody R., Goeke B., Chen Y.H.;
RT "DUG is a novel homologue of translation initiation factor 4G that binds
RT eIF4A.";
RL Biochem. Biophys. Res. Commun. 297:78-82(2002).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25; SER-76 AND SER-457, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Inhibits translation initiation and cap-dependent
CC translation. May excert its function by hindering the interaction
CC between EIF4A1 and EIF4G. Inhibits the helicase activity of EIF4A.
CC Modulates the activation of JUN kinase. Down-regulates the expression
CC of MAP4K1, thus inhibiting events important in driving invasion,
CC namely, MAPK85 activation and consequent JUN-dependent transcription.
CC May play a role in apoptosis. Tumor suppressor. Inhibits tumor
CC promoter-induced neoplastic transformation. Binds RNA (By similarity).
CC {ECO:0000250, ECO:0000269|PubMed:12220511}.
CC -!- SUBUNIT: Interacts (via MI domains) with EIF4A2 (By similarity).
CC Interacts (via MI domains) with EIF4A1 (via N-terminal domain).
CC Heterotrimer with EIF4A1; one molecule of PDCD4 binds two molecules of
CC EIF4A1. Interacts with EIF4G1. May form a complex with EIF4A1 and
CC EIF4G1. The interaction between PDCD4 and EIF4A1 interferes with the
CC interaction between EIF4A1 and EIF4G. When phosphorylated, interacts
CC with BTRC and FBXW11 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}.
CC Note=Shuttles between the nucleus and cytoplasm. Predominantly nuclear
CC under normal growth conditions, and when phosphorylated at Ser-457 (By
CC similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9JID1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9JID1-2; Sequence=VSP_021356;
CC -!- INDUCTION: Up-regulated by apoptotic inducers.
CC {ECO:0000269|PubMed:12220511}.
CC -!- DOMAIN: Binds EIF4A1 via both MI domains.
CC -!- PTM: Polyubiquitinated, leading to its proteasomal degradation. Rapidly
CC degraded in response to mitogens. Phosphorylation of the phosphodegron
CC promotes interaction with BTRC and proteasomal degradation (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated at Ser-67 by RPS6KB1 in response to mitogens;
CC phosphorylation promotes proteasomal degradation of PDCD4.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the PDCD4 family. {ECO:0000305}.
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DR EMBL; AF239739; AAF73961.2; -; mRNA.
DR RefSeq; NP_071601.2; NM_022265.2. [Q9JID1-1]
DR RefSeq; XP_006231675.1; XM_006231613.3. [Q9JID1-1]
DR RefSeq; XP_006231676.1; XM_006231614.3. [Q9JID1-1]
DR RefSeq; XP_006231677.1; XM_006231615.3. [Q9JID1-1]
DR RefSeq; XP_006231678.1; XM_006231616.3. [Q9JID1-1]
DR RefSeq; XP_017445137.1; XM_017589648.1. [Q9JID1-1]
DR AlphaFoldDB; Q9JID1; -.
DR BMRB; Q9JID1; -.
DR SMR; Q9JID1; -.
DR IntAct; Q9JID1; 1.
DR MINT; Q9JID1; -.
DR STRING; 10116.ENSRNOP00000020155; -.
DR iPTMnet; Q9JID1; -.
DR PhosphoSitePlus; Q9JID1; -.
DR PaxDb; Q9JID1; -.
DR Ensembl; ENSRNOT00000097657; ENSRNOP00000091790; ENSRNOG00000014779. [Q9JID1-2]
DR Ensembl; ENSRNOT00000119971; ENSRNOP00000076366; ENSRNOG00000014779. [Q9JID1-1]
DR GeneID; 64031; -.
DR KEGG; rno:64031; -.
DR UCSC; RGD:620816; rat. [Q9JID1-1]
DR CTD; 27250; -.
DR RGD; 620816; Pdcd4.
DR eggNOG; KOG0403; Eukaryota.
DR GeneTree; ENSGT00390000015948; -.
DR HOGENOM; CLU_025354_1_0_1; -.
DR InParanoid; Q9JID1; -.
DR OMA; HHELIYE; -.
DR PhylomeDB; Q9JID1; -.
DR TreeFam; TF323207; -.
DR PRO; PR:Q9JID1; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000014779; Expressed in pancreas and 20 other tissues.
DR ExpressionAtlas; Q9JID1; baseline and differential.
DR Genevisible; Q9JID1; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0030509; P:BMP signaling pathway; ISO:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISO:RGD.
DR GO; GO:0060940; P:epithelial to mesenchymal transition involved in cardiac fibroblast development; IGI:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:RGD.
DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; ISO:RGD.
DR GO; GO:0043508; P:negative regulation of JUN kinase activity; ISS:UniProtKB.
DR GO; GO:1904761; P:negative regulation of myofibroblast differentiation; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:1905064; P:negative regulation of vascular associated smooth muscle cell differentiation; ISO:RGD.
DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; ISO:RGD.
DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; ISO:RGD.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISO:RGD.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO:RGD.
DR GO; GO:0034393; P:positive regulation of smooth muscle cell apoptotic process; IMP:RGD.
DR GO; GO:1905461; P:positive regulation of vascular associated smooth muscle cell apoptotic process; ISO:RGD.
DR GO; GO:0051246; P:regulation of protein metabolic process; IMP:RGD.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR003891; Initiation_fac_eIF4g_MI.
DR InterPro; IPR039778; PDCD4.
DR PANTHER; PTHR12626; PTHR12626; 1.
DR Pfam; PF02847; MA3; 2.
DR SMART; SM00544; MA3; 2.
DR SUPFAM; SSF48371; SSF48371; 2.
DR PROSITE; PS51366; MI; 2.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Apoptosis; Cytoplasm; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; RNA-binding; Tumor suppressor;
KW Ubl conjugation.
FT CHAIN 1..469
FT /note="Programmed cell death protein 4"
FT /id="PRO_0000256522"
FT DOMAIN 163..284
FT /note="MI 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00698"
FT DOMAIN 326..449
FT /note="MI 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00698"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 58..128
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 58..64
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 70..76
FT /note="Phosphodegron"
FT /evidence="ECO:0000250"
FT MOTIF 448..454
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 7..27
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q53EL6"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 67
FT /note="Phosphoserine; by PKB and RPS6KB1"
FT /evidence="ECO:0000250|UniProtKB:Q53EL6"
FT MOD_RES 68
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53EL6"
FT MOD_RES 71
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53EL6"
FT MOD_RES 76
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 78
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53EL6"
FT MOD_RES 94
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53EL6"
FT MOD_RES 152
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q53EL6"
FT MOD_RES 313
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53EL6"
FT MOD_RES 317
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q53EL6"
FT MOD_RES 457
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT VAR_SEQ 367..403
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12220511"
FT /id="VSP_021356"
SQ SEQUENCE 469 AA; 51736 MW; 16D712EA267F9EEC CRC64;
MDVENEQILN VNPTDPDNLS DSLFSGDEEN AGTEEIKNEI NGNWISASTI NEARINAKAK
RRLRKNSSRD SGRGDSVSDN GSEAVRSGVA VPTSPKGRLL DRRSRSGKGR GLPKKGGAGG
KGVWGTPGQV YDVEEVDVKD PNYDDDQENC VYETVVLPLD ETAFEKTLTP IIQEYFEHGD
TNEVAEMLRD LNLGEMKSGV PVLAVSLALE GKASHREMTS KLLSDLCGTV MSTNDVEKSF
DKLLKDLPEL ALDTPRAPQL VGQFIARAVG DGILCNTYID SYKGTVDCVQ ARAALDKATV
LLSMSKGGKR KDSVWGSGGG QQPVNHLVKE IDMLLKEYLL SGDMSEAEHC LKELEVPHFH
HELVYEAIVM VLESTGESAF KMMLDLLKSL WKSSTITIDQ MKRGYERIYN EIPDINLDVP
HSYSVLERFV EECFQAGIIS KQLRDLCPSR GRKRFVSEGD GGRLKPESY
