dbPTM

MDM4_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	MDM4_HUMAN
UniProt AC	O15151
Protein Name	Protein Mdm4
Gene Name	MDM4
Organism	Homo sapiens (Human).
Sequence Length	490
Subcellular Localization	Nucleus.
Protein Description	Inhibits p53/TP53- and TP73/p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Inhibits degradation of MDM2. Can reverse MDM2-targeted degradation of TP53 while maintaining suppression of TP53 transactivation and apoptotic functions..
Protein Sequence	MTSFSTSAQCSTSDSACRISPGQINQVRPKLPLLKILHAAGAQGEMFTVKEVMHYLGQYIMVKQLYDQQEQHMVYCGGDLLGELLGRQSFSVKDPSPLYDMLRKNLVTLATATTDAAQTLALAQDHSMDIPSQDQLKQSAEESSTSRKRTTEDDIPTLPTSEHKCIHSREDEDLIENLAQDETSRLDLGFEEWDVAGLPWWFLGNLRSNYTPRSNGSTDLQTNQDVGTAIVSDTTDDLWFLNESVSEQLGVGIKVEAADTEQTSEEVGKVSDKKVIEVGKNDDLEDSKSLSDDTDVEVTSEDEWQCTECKKFNSPSKRYCFRCWALRKDWYSDCSKLTHSLSTSDITAIPEKENEGNDVPDCRRTISAPVVRPKDAYIKKENSKLFDPCNSVEFLDLAHSSESQETISSMGEQLDNLSEQRTDTENMEDCQNLLKPCSLCEKRPRDGNIIHGRTGHLVTCFHCARRLKKAGASCPICKKEIQLVIKVFIA

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
20	Phosphorylation	SDSACRISPGQINQV CCCCCCCCCHHHCCC	12.02	25159151
55	Phosphorylation	TVKEVMHYLGQYIMV EHHHHHHHHHHHHHH	8.40	19075013
93	Ubiquitination	GRQSFSVKDPSPLYD CCCCCCCCCCCHHHH	63.82	-
96	Phosphorylation	SFSVKDPSPLYDMLR CCCCCCCCHHHHHHH	37.36	22817900
99	Phosphorylation	VKDPSPLYDMLRKNL CCCCCHHHHHHHHCC	11.59	19075013
108	Phosphorylation	MLRKNLVTLATATTD HHHHCCCHHHHCCCC	17.53	25332170
113	Phosphorylation	LVTLATATTDAAQTL CCHHHHCCCCHHHHH	22.36	28348404
114	Phosphorylation	VTLATATTDAAQTLA CHHHHCCCCHHHHHH	22.60	28348404
119	Phosphorylation	ATTDAAQTLALAQDH CCCCHHHHHHHHHHC	14.85	27251275
127	Phosphorylation	LALAQDHSMDIPSQD HHHHHHCCCCCCCHH	26.83	28348404
150	Phosphorylation	SSTSRKRTTEDDIPT HCCCCCCCCCCCCCC	37.26	23186163
151	Phosphorylation	STSRKRTTEDDIPTL CCCCCCCCCCCCCCC	41.26	23186163
157	Phosphorylation	TTEDDIPTLPTSEHK CCCCCCCCCCCCCCC	45.78	23186163
160	Phosphorylation	DDIPTLPTSEHKCIH CCCCCCCCCCCCCCC	50.27	28450419
161	Phosphorylation	DIPTLPTSEHKCIHS CCCCCCCCCCCCCCC	35.45	28450419
222 (in isoform 5)	Phosphorylation	-	41.99	24114839
254	Sumoylation	EQLGVGIKVEAADTE HHHCCCEEEEECCCC	28.26	-
254	Sumoylation	EQLGVGIKVEAADTE HHHCCCEEEEECCCC	28.26	-
263	Phosphorylation	EAADTEQTSEEVGKV EECCCCCCHHHHHCC	31.69	-
264	Phosphorylation	AADTEQTSEEVGKVS ECCCCCCHHHHHCCC	31.30	-
289	Phosphorylation	DDLEDSKSLSDDTDV CCHHHHCCCCCCCCC	36.74	22817900
291	Phosphorylation	LEDSKSLSDDTDVEV HHHHCCCCCCCCCEE	40.30	27251275
314	Phosphorylation	TECKKFNSPSKRYCF CCCCCCCCCCCHHHH	33.41	25849741
316	Phosphorylation	CKKFNSPSKRYCFRC CCCCCCCCCHHHHHH	29.59	30576142
328	Ubiquitination	FRCWALRKDWYSDCS HHHHHHCCHHHHHHH	54.16	-
336	Ubiquitination	DWYSDCSKLTHSLST HHHHHHHHHHHCCCH	64.83	-
338	Phosphorylation	YSDCSKLTHSLSTSD HHHHHHHHHCCCHHC	17.10	28464451
340	Phosphorylation	DCSKLTHSLSTSDIT HHHHHHHCCCHHCCC	20.84	25159151
342	Phosphorylation	SKLTHSLSTSDITAI HHHHHCCCHHCCCCC	28.96	23401153
343	Phosphorylation	KLTHSLSTSDITAIP HHHHCCCHHCCCCCC	35.39	25159151
344	Phosphorylation	LTHSLSTSDITAIPE HHHCCCHHCCCCCCC	24.52	25159151
347	Phosphorylation	SLSTSDITAIPEKEN CCCHHCCCCCCCCCC	24.43	26552605
365	Phosphorylation	DVPDCRRTISAPVVR CCCCHHHHCCCCCCC	10.42	15788536
367	Phosphorylation	PDCRRTISAPVVRPK CCHHHHCCCCCCCCH	26.38	16163388
374	Ubiquitination	SAPVVRPKDAYIKKE CCCCCCCHHHCCCCC	44.41	-
379	Sumoylation	RPKDAYIKKENSKLF CCHHHCCCCCCCCCC	41.16	-
379	Sumoylation	RPKDAYIKKENSKLF CCHHHCCCCCCCCCC	41.16	-
384	Ubiquitination	YIKKENSKLFDPCNS CCCCCCCCCCCCCCC	65.83	-
391	Phosphorylation	KLFDPCNSVEFLDLA CCCCCCCCEEHHHCC	29.73	16163388
403	Phosphorylation	DLAHSSESQETISSM HCCCCCCCHHHHHHH	34.95	15788536

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
55	Y	Phosphorylation	Kinase	ABL1	P00519	GPS
55	Y	Phosphorylation	Kinase	ABL-FAMILY	-	GPS
96	S	Phosphorylation	Kinase	CDK1	P06493	PSP
99	Y	Phosphorylation	Kinase	ABL1	P00519	GPS
99	Y	Phosphorylation	Kinase	ABL-FAMILY	-	GPS
289	S	Phosphorylation	Kinase	CSNK1A1	P48729	GPS
314	S	Phosphorylation	Kinase	CDK4	P11802	PSP
314	S	Phosphorylation	Kinase	MAPK14	Q16539	GPS
342	S	Phosphorylation	Kinase	PRKAA1	P54645	GPS
342	S	Phosphorylation	Kinase	CHEK1	O14757	GPS
342	S	Phosphorylation	Kinase	CHK2	O96017	PSP
367	S	Phosphorylation	Kinase	AKT1	P31749	PSP
367	S	Phosphorylation	Kinase	CHK1	O14757	PSP
367	S	Phosphorylation	Kinase	CHK2	O96017	PSP
403	S	Phosphorylation	Kinase	ATM	Q13315	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	MDM2	Q00987	PMID:10218570

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
342	S	Phosphorylation	16163388
Phosphorylation at Ser-342 also induces ubiquitination and degradation but to a lower extent.
342	S	ubiquitylation	16163388
Phosphorylation at Ser-342 also induces ubiquitination and degradation but to a lower extent.
367	S	Phosphorylation	16163388
Phosphorylation at Ser-367 promotes interaction with YWHAG and subsequent ubiquitination and degradation.
367	S	ubiquitylation	16163388
Phosphorylation at Ser-367 promotes interaction with YWHAG and subsequent ubiquitination and degradation.

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 MDM4_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SMAD3_HUMAN	SMAD3	physical	12483531
SMAD4_HUMAN	SMAD4	physical	12483531
EP300_HUMAN	EP300	physical	12483531
MDM2_HUMAN	MDM2	physical	12483531
MDM2_HUMAN	MDM2	physical	12393902
P53_HUMAN	TP53	physical	12393902
UB2D1_HUMAN	UBE2D1	physical	12393902
CDN2A_HUMAN	CDKN2A	physical	11297540
ARF_HUMAN	CDKN2A	physical	11297540
P53_HUMAN	TP53	physical	9226370
P53_HUMAN	TP53	physical	18485870
1433G_HUMAN	YWHAG	physical	16511572
1433E_HUMAN	YWHAE	physical	16227609
1433B_HUMAN	YWHAB	physical	16227609
KC1A_HUMAN	CSNK1A1	physical	16024788
P53_HUMAN	TP53	physical	16024788
MDM2_HUMAN	MDM2	physical	20473904
P53_HUMAN	TP53	physical	11223036
P73_HUMAN	TP73	physical	11223036
UBP7_HUMAN	USP7	physical	20713061
MDM4_HUMAN	MDM4	physical	17301054
CDN1A_HUMAN	CDKN1A	physical	18086887
PRS8_HUMAN	PSMC5	physical	18086887
PSMD2_HUMAN	PSMD2	physical	18086887
P63_HUMAN	TP63	physical	21088494
P53_HUMAN	TP53	physical	21088494
P73_HUMAN	TP73	physical	21088494
P53_HUMAN	TP53	physical	17301054
MDM2_HUMAN	MDM2	physical	19683495
UBP2_HUMAN	USP2	physical	19838211
MDM2_HUMAN	MDM2	physical	19838211
RFWD2_HUMAN	RFWD2	physical	20333547
ZN363_HUMAN	RCHY1	physical	20333547
MDM2_HUMAN	MDM2	physical	20484049
CDN1A_HUMAN	CDKN1A	physical	21148311
1433G_HUMAN	YWHAG	physical	21148311
P53_HUMAN	TP53	physical	21925390
KC1A_HUMAN	CSNK1A1	physical	21925390
1433B_HUMAN	YWHAB	physical	21925390
MDM2_HUMAN	MDM2	physical	21925390
P53_HUMAN	TP53	physical	21965653
P53_HUMAN	TP53	physical	12874296
MDM2_HUMAN	MDM2	physical	12874296
MDM2_HUMAN	MDM2	physical	22266850
P53_HUMAN	TP53	physical	22266850
MDM2_HUMAN	MDM2	physical	17159902
P53_HUMAN	TP53	physical	10827196
P53_HUMAN	TP53	physical	21075307
MDM2_HUMAN	MDM2	physical	16055726
UB2D2_HUMAN	UBE2D2	physical	20705607
ABL1_HUMAN	ABL1	physical	19075013
P53_HUMAN	TP53	physical	19305137
P53_HUMAN	TP53	physical	18677113
P53_HUMAN	TP53	physical	17875722
MDM2_HUMAN	MDM2	physical	10608892
P53_HUMAN	TP53	physical	10608892
1433T_HUMAN	YWHAQ	physical	18356162
1433E_HUMAN	YWHAE	physical	18356162
P53_HUMAN	TP53	physical	22374672
UB2D1_HUMAN	UBE2D1	physical	17301054
UB2D3_HUMAN	UBE2D3	physical	19683495
RB_HUMAN	RB1	physical	16510145
A4_HUMAN	APP	physical	21832049
PP1A_HUMAN	PPP1CA	physical	23277204
1433T_HUMAN	YWHAQ	physical	17110929
KC1A_HUMAN	CSNK1A1	physical	17110929
BCL2_HUMAN	BCL2	physical	19521340
P53_HUMAN	TP53	physical	19521340
KC1A_HUMAN	CSNK1A1	physical	23028042
P53_HUMAN	TP53	physical	23028042
P53_HUMAN	TP53	physical	23671280
MDM4_HUMAN	MDM4	physical	24127580
P53_HUMAN	TP53	physical	24127580
UB2D2_HUMAN	UBE2D2	physical	24127580
UBP2_HUMAN	USP2	physical	24445145
P53_HUMAN	TP53	physical	24445145
BCL2_HUMAN	BCL2	physical	24445145
MDM4_HUMAN	MDM4	physical	24755078
UBC_HUMAN	UBC	physical	24755078
MDM2_HUMAN	MDM2	physical	24755078
P53_HUMAN	TP53	physical	10075736
MDM2_HUMAN	MDM2	physical	23946421
P53_HUMAN	TP53	physical	23946421
BY55_HUMAN	CD160	physical	25416956
CAN7_HUMAN	CAPN7	physical	25416956
RN115_HUMAN	RNF115	physical	25416956
FSBP_HUMAN	RAD54B	physical	25384516
RA54B_HUMAN	RAD54B	physical	25384516
SMCA2_HUMAN	SMARCA2	physical	25384516
MDM2_HUMAN	MDM2	physical	25384516
MDM2_HUMAN	MDM2	physical	11606419
MDM4_HUMAN	MDM4	physical	25888903
P53_HUMAN	TP53	physical	20515689
NBN_HUMAN	NBN	physical	24608433
MRE11_HUMAN	MRE11A	physical	24608433
RAD50_HUMAN	RAD50	physical	24608433
UBP22_HUMAN	USP22	physical	25547493
MDM2_HUMAN	MDM2	physical	25105592
MDM2_HUMAN	MDM2	physical	25659040
MDM2_HUMAN	MDM2	physical	25703327
RB_HUMAN	RB1	physical	25703327
KC1A_HUMAN	CSNK1A1	physical	25825738
P53_HUMAN	TP53	physical	25825738
MDM2_HUMAN	MDM2	physical	26359458
MDM2_HUMAN	MDM2	physical	27617579
P53_HUMAN	TP53	physical	28514442
KC1A_HUMAN	CSNK1A1	physical	28514442
F193A_HUMAN	FAM193A	physical	28514442
PELI1_HUMAN	PELI1	physical	28514442
CCDB1_HUMAN	CCNDBP1	physical	28514442
ASGL1_HUMAN	ASRGL1	physical	28514442
P73_HUMAN	TP73	physical	28514442
MDM2_HUMAN	MDM2	physical	28514442
1433Z_HUMAN	YWHAZ	physical	28514442
E2AK4_HUMAN	EIF2AK4	physical	28514442
HBB_HUMAN	HBB	physical	28514442
CDK1_HUMAN	CDK1	physical	15735705
MDM2_HUMAN	MDM2	physical	26720344
P53_HUMAN	TP53	physical	18316739

Drug and Disease Associations

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

Regulatory Network of MDM4_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"14-3-3gamma binds to MDMX that is phosphorylated by UV-activatedChk1, resulting in p53 activation."; Jin Y., Dai M.S., Lu S.Z., Xu Y., Luo Z., Zhao Y., Lu H.; EMBO J. 25:1207-1218(2006). Cited for: FUNCTION IN TP53 ACTIVATION, PHOSPHORYLATION AT SER-367 BY CHEK1, ANDINTERACTION WITH YWHAG.	16511572 [Abstract]
"ATM and Chk2-dependent phosphorylation of MDMX contribute to p53activation after DNA damage."; Chen L., Gilkes D.M., Pan Y., Lane W.S., Chen J.; EMBO J. 24:3411-3422(2005). Cited for: FUNCTION IN TP53 ACTIVATION, PHOSPHORYLATION AT SER-342 AND SER-367 BYCHEK2, UBIQUITINATION, AND INTERACTION WITH MDM2.	16163388 [Abstract]

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