Home

MDM2 (human)

Overview MDM2 a ubiquitin ligase for p53, plays a central role in regulation of the stability of p53 via Akt-mediated MDM2 phosphorylation. Phosphorylation of MDM2 increases its interaction with p300, providing a platform to allow the assembly of the protein complex necessary for MDM2-mediated ubiquitination and degradation of p53. Phosphorylation of MDM2 also blocks its binding to p19ARF, increasing the degradation of p53. Facilitates the nuclear export of p53 and targets it for proteasome-mediated proteolysis. Eight alternatively spliced isoforms have been reported. Note: This description may include information from UniProtKB. Protein type: Ubiquitin conjugating system; Ubiquitin ligase; Inhibitor protein; Ligase; EC 6.3.2.19; EC 6.3.2.- Cellular Component: nucleoplasm; nuclear body; protein complex; cytoplasm; plasma membrane; nucleolus; cytosol; nucleus Molecular Function: identical protein binding; protein binding; enzyme binding; zinc ion binding; p53 binding; ubiquitin-protein ligase activity Biological Process: epidermal growth factor receptor signaling pathway; traversing start control point of mitotic cell cycle; fibroblast growth factor receptor signaling pathway; phosphoinositide-mediated signaling; nerve growth factor receptor signaling pathway; protein destabilization; protein ubiquitination during ubiquitin-dependent protein catabolic process; protein ubiquitination; negative regulation of transcription from RNA polymerase II promoter; positive regulation of mitotic cell cycle; DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; response to antibiotic; synaptic transmission; negative regulation of DNA damage response, signal transduction by p53 class mediator; establishment of protein localization; peptidyl-lysine modification; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; virus-host interaction; positive regulation of cell proliferation; protein complex assembly; regulation of protein catabolic process; negative regulation of transcription, DNA-dependent; cell cycle checkpoint; negative regulation of apoptosis Reference #:  Q00987 (UniProtKB) Alt. Names/Synonyms: Double minute 2 protein; double minute 2, human homolog of; E3 ubiquitin-protein ligase Mdm2; Hdm2; HDMX; MDM2; Mdm2 p53 binding protein homolog (mouse); Mdm2, transformed 3T3 cell double minute 2, p53 binding protein; MGC5370; MGC71221; Oncoprotein Mdm2; p53-binding protein; p53-binding protein Mdm2; ubiquitin-protein ligase E3 Mdm2 Gene Symbols: MDM2 Molecular weight: 55,233 Da Basal Isoelectric point: 4.6  Predict pI for various phosphorylation states CST Pathways:  Cell Cycle: G2/M DNA Damage Checkpoint  |  Crosstalk between PTMs  |  ErbB/HER Signaling  |  PI3K/Akt Signaling

Select Structure to View Below MDM2 1RV1 - A/B/C=25-109 (human) 1T4E - A/B=17-111 (human) 1T4F - M=17-125 (human) 1YCR - A=17-125 (human) 1Z1M - A=1-118 (human) 2AXI - A=17-125 (human) 2C6A - A=290-335 (human) 2C6B - A=290-335 (human) 2F1Y - A=- (human) 2FOP - B=145-150 (human) 2GV2 - A=17-125 (human) 2HDP - A/B=429-491 (human) 2LZG - A=1-125 (human) 2VJE - A/C=383-446 (human) 2VJF - A/C=383-446 (human) 3EQS - A=25-109 (human) 3G03 - A/C=18-125 (human) 3IUX - A/C=25-109 (human) 3IWY - A/C=25-109 (human) 3JZK - A=17-111 (human) 3JZR - A=17-125 (human) 3JZS - A=24-109 (human) 3LBK - A=18-111 (human) 3LBL - A/C/E=18-111 (human) 3LNJ - A/C/E=25-109 (human) 3LNZ - A/O/M/C/K/I/G/E=25-109 (human) 3TJ2 - A/C=18-111 (human) 3TPX - A/C/E=25-109 (human) 3TU1 - A=18-125 (human) 3V3B - A/B=24-110 (human) 3VBG - A/D/C/B=25-109 (human) 3VZV - A/B=25-109 (human) 4DIJ - A/B=17-111 (human) 4ERE - A/B=17-111 (human) 4ERF - A/C/E=17-111 (human) 4HBM - F/A/E/B/H/C/D/G=6-125 (human) 4JV7 - A=18-111 (human) 4JV9 - A=18-111 (human) 4JVE - A=18-111 (human) 4JVR - A/C/E=18-111 (human) 4JWR - A/C/B=17-111 (human)

STRING  |  Scansite  |  Phospho.ELM  |  NetworKIN  |  Pfam  |  RCSB PDB 1RV1 1T4E 1T4F 1YCR 1Z1M 2AXI 2C6A 2C6B 2F1Y 2FOP 2GV2 2HDP 2LZG 2VJE 2VJF 3EQS 3G03 3IUX 3IWY 3JZK 3JZR 3JZS 3LBK 3LBL 3LNJ 3LNZ 3TJ2 3TPX 3TU1 3V3B 3VBG 3VZV 4DIJ 4ERE 4ERF 4HBM 4JV7 4JV9 4JVE 4JVR 4JWR  |  ENZYME  |  Phospho3D  |  DISEASE  |  Source  |  UCSD-Nature  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene

	Sites Implicated In
apoptosis, altered: S157‑p, S166‑p, S186‑p apoptosis, induced: Y394‑p cell cycle regulation: S157‑p, S166‑p cell growth, altered: S269‑p transcription, altered: Y394‑p translation, altered: S166‑p activation: S166‑p, S186‑p, S240‑p, S242‑p, S246‑p, S253‑p, S256‑p, S260‑p, S262‑p enzymatic activity, induced: S17‑p, S157‑p, S166‑p, S260‑p intracellular localization: S166‑p, S186‑p, Y276‑p molecular association, regulation: S17‑p, S118‑p, S121‑p, S166‑p, S186‑p, S260‑p, S269‑p, Y276‑p, S386‑p, S429‑p protein degradation: S118‑p, S121‑p, S260‑p, S395‑p protein stabilization: S166‑p, S186‑p, S188‑p ubiquitination: S17‑p, S118‑p, S121‑p, S166‑p, S186‑p, S260‑p, S386‑p, S429‑p

	Modification Sites and Domains	Show Modification Legend
Click here to view phosphorylation modifications only

	Modification Sites in Parent Protein, Orthologs, and Isoforms	Show Modification Legend

SS  SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.	MS  MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.			human ► Hide Isoforms
3	0		S17-p	TDGAVTTsQIPASEQ
0	1		K36-u	RPKPLLLkLLkSVGA
0	2		K39-u	PLLLkLLkSVGAQkD
0	8		K45-u	LkSVGAQkDTYTMKE
0	1		K51	QkDTYTMKEVLFYLG
0	2		Y60-p	VLFYLGQyIMTKRLY
0	2		K70-u	TKRLYDEkQQHIVYC
0	1		K94-u	GVPSFSVkEHRkIYT
0	3		K98-u	FSVkEHRkIYTMIYR
1	0		S118-p	NQQESSDsGTsVSEN
1	0		S121-p	ESSDsGTsVSENRCH
1	0		S157-p	SHLVSRPstSsRRRA
1	0		T158-p	HLVSRPstSsRRRAI
0	1		S160-p	VSRPstSsRRRAIsE
0	2		A164	stSsRRRAIsEtEEN
30	10		S166-p	SsRRRAIsEtEENsD
0	5		T168-p	RRRAIsEtEENsDEL
1	3		S172-p	IsEtEENsDELsGER
1	1		S176-p	EENsDELsGERQRKR
10	5		S186-p	RQRKRHKsDsIsLsF
3	1		S188-p	RKRHKsDsIsLsFDE
0	1		S190-p	RHKsDsIsLsFDESL
0	2		S192-p	KsDsIsLsFDESLAL
2	0		T218	SSSESTGTPsNPDLD
1	1		S220-p	SESTGTPsNPDLDAG
1	0		S229-p	PDLDAGVsEHSGDWL
3	1		S240-p	GDWLDQDsVsDQFsV
3	1		S242-p	WLDQDsVsDQFsVEF
3	0		S246-p	DsVsDQFsVEFEVEs
2	1		S253-p	sVEFEVEsLDsEDYs
3	1		S256-p	FEVEsLDsEDYsLsE
6	1		S260-p	sLDsEDYsLsEEGQE
3	0		S262-p	DsEDYsLsEEGQELs
3	1		S269-p	sEEGQELsDEDDEVy
1	1		Y276-p	sDEDDEVyQVtVYQA
1	0		T279-p	DDEVyQVtVYQAGEs
0	1		Y281	EVyQVtVYQAGEsDt
0	1		S286-p	tVYQAGEsDtDsFEE
0	1		T288-p	YQAGEsDtDsFEEDP
1	0		S290-p	AGEsDtDsFEEDPEI
0	1		T306-p	LADYWKCtsCNEMNP
0	1		S307-p	ADYWKCtsCNEMNPP
0	2		K334-u	ENWLPEDkGkDkGEI
0	3		K336-u	WLPEDkGkDkGEIsE
0	2		K338-u	PEDkGkDkGEIsEkA
1	0		S342-p	GkDkGEIsEkAkLEN
0	3		K344-u	DkGEIsEkAkLENst
0	1		K346-u	GEIsEkAkLENstQA
1	0		S350-p	EkAkLENstQAEEGF
1	0		T351-p	kAkLENstQAEEGFD
0	8		K363-u	GFDVPDCkktIVNDS
0	6		K364-u	FDVPDCkktIVNDSR
1	0		T365-p	DVPDCkktIVNDSRE
1	1		S373-p	IVNDSREsCVEENDD
3	2		S386-p	DDKITQAsQsQESED
0	1		S388-p	KITQAsQsQESEDys
2	0		Y394-p	QsQESEDysQPSTSS
5	2		S395-p	sQESEDysQPSTSSS
1	0		Y405-p	STSSSIIyssQEDVK
0	1		S406-p	TSSSIIyssQEDVKE
2	2		S407-p	SSSIIyssQEDVKEF
2	1		T419-p	KEFEREEtQDKEEsV
1	2		S425-p	EtQDKEEsVESsLPL
2	1		S429-p	KEEsVESsLPLNAIE
0	2		K446-u	VICQGRPkNGCIVHG
1	0		K446-s	VICQGRPkNGCIVHG
0	1		K454-u	NGCIVHGkTGHLMAC
0	1		K466-u	MACFTCAkkLKKRNK
0	1		K467-u	ACFTCAkkLKKRNKP

	MDM2 iso12
S17	TDGAVTTSQIPASEQ
K36	RPKPLLLKLLKSVGA
K39	PLLLKLLKSVGAQKD
K45	LKSVGAQKDTYTMKE
K51	QKDTYTMKEVLFYLG
Y60	VLFYLGQYIMTKRLY
K70	TKRLYDEKQQHIVYC
K94	GVPSFSVKEHRKIYT
K98	FSVKEHRKIYTMIYR
R118	PLVDLSIR_______
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap

	mouse
S17	TEGAASTSQIPASEQ
K36	RPKPLLLKLLKSVGA
K39	PLLLKLLKSVGAQND
N45	LKSVGAQNDTYTMkE
K51-a	QNDTYTMkEIIFYIG
Y60	IIFYIGQYIMTKRLY
K70	TKRLYDEKQQHIVYC
K94	GVPSFSVKEHRKIYA
K98	FSVKEHRKIYAMIYR
S115	VAVSQQDSGTSLSES
S118	SQQDSGTSLSESRRQ
S154	SDLISRLSTSSRRRs
T155	DLISRLSTSSRRRsI
S157	ISRLSTSSRRRsIsE
S161-p	STSSRRRsIsEtEEN
S163-p	SSRRRsIsEtEENTD
T165-p	RRRsIsEtEENTDEL
T169	IsEtEENTDELPGER
P173	EENTDELPGERHRKR
S183-p	RHRKRRRsLsFDPSL
-	gap
-	gap
S185-p	RKRRRsLsFDPSLGL
T216-p	SSSESTEtPSHQDLD
S218	SESTEtPSHQDLDDG
S227	QDLDDGVSEHSGDCL
S238-p	GDCLDQDsVsDQFsV
S240-p	CLDQDsVsDQFsVEF
S244-p	DsVsDQFsVEFEVES
S251	sVEFEVESLDsEDYs
S254-p	FEVESLDsEDYsLSD
S258-p	SLDsEDYsLSDEGHE
S260	DsEDYsLSDEGHELS
S267	SDEGHELSDEDDEVy
Y274-p	SDEDDEVyRVTVyQT
T277	DDEVyRVTVyQTGES
Y279-p	EVyRVTVyQTGESDT
S284	TVyQTGESDTDSFEG
T286	yQTGESDTDSFEGDP
S288	TGESDTDSFEGDPEI
T304	LADYWKCTSCNEMNP
S305	ADYWKCTSCNEMNPP
K332	ENWLPDDKGKDKVEI
K334	WLPDDKGKDKVEISE
K336	PDDKGKDKVEISEKA
S340	GKDKVEISEKAKLEN
K342	DKVEISEKAKLENSA
K344	VEISEKAKLENSAQA
S348	EKAKLENSAQAEEGL
A349	KAKLENSAQAEEGLD
K361-u	GLDVPDGkkLTENDA
K362-u	LDVPDGkkLTENDAK
T364	VPDGkkLTENDAKEP
P371	TENDAKEPCAEEDSE
P385	EEKAEQTPLSQESDD
S387	KAEQTPLSQESDDYS
Y393	LSQESDDYSQPSTSS
S394	SQESDDYSQPSTSSS
Y404	STSSSIVYSSQESVK
S405	TSSSIVYSSQESVKE
S406	SSSIVYSSQESVKEL
T417	VKELKEETQDKDESV
S423	ETQDKDESVESSFSL
S427	KDESVESSFSLNAIE
K444	VICQGRPKNGCIVHG
K444	VICQGRPKNGCIVHG
K452	NGCIVHGKTGHLMSC
K464	MSCFTCAKKLKKRNK
K465	SCFTCAKKLKKRNKP

Home  |  Curator Login With enhanced literature mining using Linguamatics I2E Produced by 3rd Millennium  |  Design by Digizyme ©2003-2013 Cell Signaling Technology, Inc.