dbPTM

PDCD4_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	PDCD4_HUMAN
UniProt AC	Q53EL6
Protein Name	Programmed cell death protein 4
Gene Name	PDCD4
Organism	Homo sapiens (Human).
Sequence Length	469
Subcellular Localization	Nucleus . Cytoplasm . Shuttles between the nucleus and cytoplasm (By similarity). Predominantly nuclear under normal growth conditions, and when phosphorylated at Ser-457 (PubMed:16357133).
Protein Description	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)..
Protein Sequence	MDVENEQILNVNPADPDNLSDSLFSGDEENAGTEEIKNEINGNWISASSINEARINAKAKRRLRKNSSRDSGRGDSVSDSGSDALRSGLTVPTSPKGRLLDRRSRSGKGRGLPKKGGAGGKGVWGTPGQVYDVEEVDVKDPNYDDDQENCVYETVVLPLDERAFEKTLTPIIQEYFEHGDTNEVAEMLRDLNLGEMKSGVPVLAVSLALEGKASHREMTSKLLSDLCGTVMSTTDVEKSFDKLLKDLPELALDTPRAPQLVGQFIARAVGDGILCNTYIDSYKGTVDCVQARAALDKATVLLSMSKGGKRKDSVWGSGGGQQSVNHLVKEIDMLLKEYLLSGDISEAEHCLKELEVPHFHHELVYEAIIMVLESTGESTFKMILDLLKSLWKSSTITVDQMKRGYERIYNEIPDINLDVPHSYSVLERFVEECFQAGIISKQLRDLCPSRGRKRFVSEGDGGRLKPESY

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
1	Acetylation	-------MDVENEQI -------CCCCCCCC	13.54	20068231
2 (in isoform 2)	Phosphorylation	-	57.34	28348404
4 (in isoform 2)	Phosphorylation	-	51.27	28348404
14	Phosphorylation	QILNVNPADPDNLSD CCCCCCCCCCCCCCC	35.45	27251275
14 (in isoform 2)	Phosphorylation	-	35.45	28348404
20	Phosphorylation	PADPDNLSDSLFSGD CCCCCCCCCCCCCCC	31.26	20363803
22	Phosphorylation	DPDNLSDSLFSGDEE CCCCCCCCCCCCCCC	28.12	20068231
22 (in isoform 2)	Phosphorylation	-	28.12	27174698
25	Phosphorylation	NLSDSLFSGDEENAG CCCCCCCCCCCCCCC	51.10	20363803
46	Phosphorylation	EINGNWISASSINEA HHCCCEECHHHHCHH	17.45	25159151
48	Phosphorylation	NGNWISASSINEARI CCCEECHHHHCHHHH	25.59	20068231
49	Phosphorylation	GNWISASSINEARIN CCEECHHHHCHHHHH	29.20	20068231
58	Ubiquitination	NEARINAKAKRRLRK CHHHHHHHHHHHHHH	50.37	-
60	Ubiquitination	ARINAKAKRRLRKNS HHHHHHHHHHHHHCC	37.03	-
67	Phosphorylation	KRRLRKNSSRDSGRG HHHHHHCCCCCCCCC	29.77	23401153
68	Phosphorylation	RRLRKNSSRDSGRGD HHHHHCCCCCCCCCC	49.88	27273156
71	Phosphorylation	RKNSSRDSGRGDSVS HHCCCCCCCCCCCCC	29.31	25159151
73	Methylation	NSSRDSGRGDSVSDS CCCCCCCCCCCCCCC	50.09	115386825
76	Phosphorylation	RDSGRGDSVSDSGSD CCCCCCCCCCCCCHH	26.75	29255136
78	Phosphorylation	SGRGDSVSDSGSDAL CCCCCCCCCCCHHHH	29.97	29255136
80	Phosphorylation	RGDSVSDSGSDALRS CCCCCCCCCHHHHHC	32.46	29255136
82	Phosphorylation	DSVSDSGSDALRSGL CCCCCCCHHHHHCCC	24.54	27273156
87	Phosphorylation	SGSDALRSGLTVPTS CCHHHHHCCCCCCCC	38.72	23927012
90	Phosphorylation	DALRSGLTVPTSPKG HHHHCCCCCCCCCCC	28.15	23927012
93	Phosphorylation	RSGLTVPTSPKGRLL HCCCCCCCCCCCCCC	54.01	29255136
94	Phosphorylation	SGLTVPTSPKGRLLD CCCCCCCCCCCCCCC	20.67	19664994
96	Ubiquitination	LTVPTSPKGRLLDRR CCCCCCCCCCCCCCC	57.33	-
121	Ubiquitination	KKGGAGGKGVWGTPG CCCCCCCCCCCCCCC	49.74	-
126	Phosphorylation	GGKGVWGTPGQVYDV CCCCCCCCCCCEEEE	14.45	21815630
131	Phosphorylation	WGTPGQVYDVEEVDV CCCCCCEEEEEEECC	13.34	22210691
143	Phosphorylation	VDVKDPNYDDDQENC ECCCCCCCCCCCCCC	26.57	22817900
152	Phosphorylation	DDQENCVYETVVLPL CCCCCCEEEEEEEEC	14.21	25159151
166	Ubiquitination	LDERAFEKTLTPIIQ CCHHHHHHHCHHHHH	42.24	21906983
175	Phosphorylation	LTPIIQEYFEHGDTN CHHHHHHHHHCCCHH	9.63	27642862
197	Ubiquitination	DLNLGEMKSGVPVLA HCCCCCCCCCCCEEE	39.49	-
212	Ubiquitination	VSLALEGKASHREMT HHHHHCCCHHHHHHH	37.02	-
224	Phosphorylation	EMTSKLLSDLCGTVM HHHHHHHHHHHCCHH	38.69	29449344
229	Phosphorylation	LLSDLCGTVMSTTDV HHHHHHCCHHCCHHH	16.43	29449344
231	Ubiquitination	SDLCGTVMSTTDVEK HHHHCCHHCCHHHHH	2.71	21890473
232	Phosphorylation	DLCGTVMSTTDVEKS HHHCCHHCCHHHHHH	24.66	29449344
233	Phosphorylation	LCGTVMSTTDVEKSF HHCCHHCCHHHHHHH	14.66	29449344
234	Phosphorylation	CGTVMSTTDVEKSFD HCCHHCCHHHHHHHH	30.64	29449344
238	Ubiquitination	MSTTDVEKSFDKLLK HCCHHHHHHHHHHHH	57.16	-
239	Phosphorylation	STTDVEKSFDKLLKD CCHHHHHHHHHHHHH	25.77	29449344
242	Ubiquitination	DVEKSFDKLLKDLPE HHHHHHHHHHHHCHH	54.42	21890473
242	Ubiquitination	DVEKSFDKLLKDLPE HHHHHHHHHHHHCHH	54.42	21890473
245	Ubiquitination	KSFDKLLKDLPELAL HHHHHHHHHCHHHHC	68.60	21906983
254	Phosphorylation	LPELALDTPRAPQLV CHHHHCCCCCHHHHH	18.61	-
267	Methylation	LVGQFIARAVGDGIL HHHHHHHHHHCCCEE	25.62	115486721
283	Ubiquitination	NTYIDSYKGTVDCVQ CEEECCCCCCHHHHH	52.65	2190698
297	Acetylation	QARAALDKATVLLSM HHHHHHHHHHHEEEC	46.97	25953088
297	Ubiquitination	QARAALDKATVLLSM HHHHHHHHHHHEEEC	46.97	-
299	Phosphorylation	RAALDKATVLLSMSK HHHHHHHHHEEECCC	19.89	20068231
303	Phosphorylation	DKATVLLSMSKGGKR HHHHHEEECCCCCCC	19.49	20068231
305	Phosphorylation	ATVLLSMSKGGKRKD HHHEEECCCCCCCCC	25.44	27251275
306	Acetylation	TVLLSMSKGGKRKDS HHEEECCCCCCCCCC	64.14	25953088
306	Ubiquitination	TVLLSMSKGGKRKDS HHEEECCCCCCCCCC	64.14	-
311	Ubiquitination	MSKGGKRKDSVWGSG CCCCCCCCCCCCCCC	58.82	-
313	Phosphorylation	KGGKRKDSVWGSGGG CCCCCCCCCCCCCCH	23.86	20044836
317	Phosphorylation	RKDSVWGSGGGQQSV CCCCCCCCCCHHHHH	20.67	23401153
323	Phosphorylation	GSGGGQQSVNHLVKE CCCCHHHHHHHHHHH	19.59	23401153
333	Sulfoxidation	HLVKEIDMLLKEYLL HHHHHHHHHHHHHHH	6.08	21406390
345	Phosphorylation	YLLSGDISEAEHCLK HHHHCCHHHHHHHHH	35.18	25159151
392	Ubiquitination	DLLKSLWKSSTITVD HHHHHHHHCCCCCHH	39.56	-
393	Phosphorylation	LLKSLWKSSTITVDQ HHHHHHHCCCCCHHH	22.57	20068231
394	Phosphorylation	LKSLWKSSTITVDQM HHHHHHCCCCCHHHH	21.80	20068231
395	Phosphorylation	KSLWKSSTITVDQMK HHHHHCCCCCHHHHH	27.97	20068231
397	Phosphorylation	LWKSSTITVDQMKRG HHHCCCCCHHHHHHH	20.37	20068231
402	Ubiquitination	TITVDQMKRGYERIY CCCHHHHHHHHHHHH	36.72	-
402	2-Hydroxyisobutyrylation	TITVDQMKRGYERIY CCCHHHHHHHHHHHH	36.72	-
405	Phosphorylation	VDQMKRGYERIYNEI HHHHHHHHHHHHHHC	13.18	22817900
440	Phosphorylation	CFQAGIISKQLRDLC HHHHCHHHHHHHHHC	16.66	24719451
457	Phosphorylation	RGRKRFVSEGDGGRL CCCCCCCCCCCCCCC	32.90	29255136
465	Sumoylation	EGDGGRLKPESY--- CCCCCCCCCCCC---	45.43	-
465	Sumoylation	EGDGGRLKPESY--- CCCCCCCCCCCC---	45.43	-
468	Phosphorylation	GGRLKPESY------ CCCCCCCCC------	44.67	21815630
469	Phosphorylation	GRLKPESY------- CCCCCCCC-------	22.40	23186163

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
67	S	Phosphorylation	Kinase	AKT1	P31749	PSP
67	S	Phosphorylation	Kinase	P70S6K	P23443	PSP
67	S	Phosphorylation	Kinase	AKT-FAMILY	-	GPS
67	S	Phosphorylation	Kinase	PKB_GROUP	-	PhosphoELM
76	S	Phosphorylation	Kinase	RPS6KA1	Q15418	GPS
457	S	Phosphorylation	Kinase	AKT1	P31749	PSP
457	S	Phosphorylation	Kinase	RPS6KA1	Q15418	GPS
457	S	Phosphorylation	Kinase	P70S6K	P23443	PSP
457	S	Phosphorylation	Kinase	AKT-FAMILY	-	GPS
457	S	Phosphorylation	Kinase	PKB_GROUP	-	PhosphoELM
-	K	Ubiquitination	E3 ubiquitin ligase	BTRC	Q9Y297	PMID:17053147
-	K	Ubiquitination	E3 ubiquitin ligase	FBXW11	Q9UKB1	PMID:24658274
-	K	Ubiquitination	E3 ubiquitin ligase	SKP2	Q13309	PMID:30760284
-	K	Ubiquitination	E3 ubiquitin ligase	DTL	Q9NZJ0	PMID:31409387

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
67	S	Phosphorylation		16357133
Phosphorylated at Ser-67 by RPS6KB1 in response to mitogens; phosphorylation promotes proteasomal degradation of PDCD4.

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of PDCD4_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
RL5_HUMAN	RPL5	physical	12054647
RS13_HUMAN	RPS13	physical	12054647
IF4G1_HUMAN	EIF4G1	physical	12054647
FBW1A_HUMAN	BTRC	physical	18296647
FBW1A_HUMAN	BTRC	physical	17053147
FBW1A_HUMAN	BTRC	physical	23056346
DAXX_HUMAN	DAXX	physical	23536002
ARC1B_HUMAN	ARPC1B	physical	22863883
BTF3_HUMAN	BTF3	physical	22863883
PAIP1_HUMAN	PAIP1	physical	22863883
TPD52_HUMAN	TPD52	physical	22863883
UFD1_HUMAN	UFD1L	physical	22863883
IF4A2_HUMAN	EIF4A2	physical	26344197
IF6_HUMAN	EIF6	physical	26344197
ERF1_HUMAN	ETF1	physical	26344197
CNDD3_HUMAN	NCAPD3	physical	26344197
PCF11_HUMAN	PCF11	physical	26344197
PRS4_HUMAN	PSMC1	physical	26344197
SMD1_HUMAN	SNRPD1	physical	26344197
UBE2S_HUMAN	UBE2S	physical	25928036
IBTK_HUMAN	IBTK	physical	25882842

Drug and Disease Associations

Kegg Disease
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of PDCD4_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Quantitative phosphoproteomic analysis of T cell receptor signalingreveals system-wide modulation of protein-protein interactions."; Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,Rodionov V., Han D.K.; Sci. Signal. 2:RA46-RA46(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94, AND MASSSPECTROMETRY.	19690332 [Abstract]
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach."; Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.; Anal. Chem. 81:4493-4501(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-78 AND SER-94, AND MASSSPECTROMETRY.	19413330 [Abstract]
"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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-76; SER-78; SER-80;SER-94 AND SER-457, AND MASS SPECTROMETRY.	18669648 [Abstract]
"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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-93; SER-94 AND SER-457,AND MASS SPECTROMETRY.	18187866 [Abstract]
"Evaluation of the low-specificity protease elastase for large-scalephosphoproteome analysis."; Wang B., Malik R., Nigg E.A., Korner R.; Anal. Chem. 80:9526-9533(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-76, AND MASSSPECTROMETRY.	19007248 [Abstract]
"Global proteomic profiling of phosphopeptides using electron transferdissociation 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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-457, AND MASSSPECTROMETRY.	17287340 [Abstract]
"S6K1- and betaTRCP-mediated degradation of PDCD4 promotes proteintranslation and cell growth."; Dorrello N.V., Peschiaroli A., Guardavaccaro D., Colburn N.H.,Sherman N.E., Pagano M.; Science 314:467-471(2006). Cited for: FUNCTION, PHOSPHORYLATION AT SER-67 BY RPS6KB1, PHOSPHODEGRON MOTIF,INTERACTION WITH BTRC AND FBXW11, UBIQUITINATION, MASS SPECTROMETRY,AND MUTAGENESIS OF SER-67; SER-71 AND SER-76.	17053147 [Abstract]
"A probability-based approach for high-throughput proteinphosphorylation analysis and site localization."; Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; Nat. Biotechnol. 24:1285-1292(2006). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-93 AND SER-457, AND MASSSPECTROMETRY.	16964243 [Abstract]
"Global, in vivo, and site-specific phosphorylation dynamics insignaling networks."; Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.; Cell 127:635-648(2006). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-76 AND SER-457, AND MASSSPECTROMETRY.	17081983 [Abstract]
"Akt phosphorylates and regulates Pdcd4 tumor suppressor protein."; Palamarchuk A., Efanov A., Maximov V., Aqeilan R.I., Croce C.M.,Pekarsky Y.; Cancer Res. 65:11282-11286(2005). Cited for: PHOSPHORYLATION AT SER-67 AND SER-457 BY PKB, FUNCTION, MUTAGENESIS OFSER-67 AND SER-457, AND SUBCELLULAR LOCATION.	16357133 [Abstract]
"Immunoaffinity profiling of tyrosine phosphorylation in cancercells."; 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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-152, AND MASSSPECTROMETRY.	15592455 [Abstract]

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