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Protein Page:
MDM2 (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

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: Inhibitor protein; EC 6.3.2.19; Ligase; Ubiquitin conjugating system; Ubiquitin ligase; EC 6.3.2.-; Nucleolus
Chromosomal Location of Human Ortholog: 12q14.3-q15
Cellular Component: nucleoplasm; nuclear body; protein complex; cytoplasm; nucleolus; plasma membrane; synapse; cytosol; nucleus
Molecular Function: identical protein binding; peroxisome proliferator activated receptor binding; protein binding; enzyme binding; zinc ion binding; p53 binding; ubiquitin protein ligase binding; ubiquitin-protein ligase activity; ligase activity
Biological Process: nerve growth factor receptor signaling pathway; viral reproduction; protein ubiquitination during ubiquitin-dependent protein catabolic process; response to morphine; protein ubiquitination; negative regulation of transcription from RNA polymerase II promoter; negative regulation of caspase activity; positive regulation of mitotic cell cycle; DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; response to carbohydrate stimulus; positive regulation of protein export from nucleus; response to antibiotic; synaptic transmission; negative regulation of DNA damage response, signal transduction by p53 class mediator; response to magnesium ion; establishment of protein localization; peptidyl-lysine modification; positive regulation of cell proliferation; protein complex assembly; response to iron ion; response to drug; epidermal growth factor receptor signaling pathway; traversing start control point of mitotic cell cycle; fibroblast growth factor receptor signaling pathway; phosphoinositide-mediated signaling; protein destabilization; response to cocaine; response to ether; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; innate immune response; regulation of protein catabolic process; negative regulation of transcription, DNA-dependent; 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:  Crosstalk between PTMs  |  ErbB/HER Signaling  |  G2/M DNA Damage Checkpoint  |  PI3K/Akt Signaling
Select Structure to View Below

MDM2

Protein Structure Not Found.


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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
activity, induced: 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
 

Show Multiple Sequence Alignment


 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-ub RPKPLLLkLLkSVGA
0 2 K39-ub PLLLkLLkSVGAQkD
0 8 K45-ub LkSVGAQkDTYTMKE
0 1 K51 QkDTYTMKEVLFYLG
0 2 Y60-p VLFYLGQyIMTKRLY
0 2 K70-ub TKRLYDEkQQHIVYC
0 1 K94-ub GVPSFSVkEHRkIYT
0 3 K98-ub FSVkEHRkIYTMIYR
1 0 S118-p NQQESSDsGTsVSEN
1 0 S121-p ESSDsGTsVSENRCH
0 1 S148-p ELQEEKPsSSHLVSR
1 0 S157-p SHLVSRPstSsRRRA
1 0 T158-p HLVSRPstSsRRRAI
0 1 S160-p VSRPstSsRRRAIsE
0 2 A164 stSsRRRAIsEtEEN
31 13 S166-p SsRRRAIsEtEENsD
0 6 T168-p RRRAIsEtEENsDEL
1 3 S172-p IsEtEENsDELsGER
1 1 S176-p EENsDELsGERQRKR
9 7 S186-p RQRKRHKsDsIsLsF
2 2 S188-p RKRHKsDsIsLsFDE
0 1 S190-p RHKsDsIsLsFDEsL
0 3 S192-p KsDsIsLsFDEsLAL
0 1 S196-p IsLsFDEsLALCVIR
3 0 T218-p 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 2 S286-p tVYQAGEsDtDsFEE
0 1 T288-p YQAGEsDtDsFEEDP
1 1 S290-p AGEsDtDsFEEDPEI
0 1 T306-p LADYWKCtsCNEMNP
0 1 S307-p ADYWKCtsCNEMNPP
0 2 K334-ub ENWLPEDkGkDkGEI
0 3 K336-ub WLPEDkGkDkGEIsE
0 2 K338-ub PEDkGkDkGEIsEkA
1 0 S342-p GkDkGEIsEkAkLEN
0 3 K344-ub DkGEIsEkAkLENst
0 1 K346-ub GEIsEkAkLENstQA
1 0 S350-p EkAkLENstQAEEGF
1 0 T351-p kAkLENstQAEEGFD
0 8 K363-ub GFDVPDCkktIVNDS
0 6 K364-ub 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
6 2 S395-p sQESEDysQPSTSSS
1 0 Y405-p STSSSIIyssQEDVK
0 1 S406-p TSSSIIyssQEDVKE
2 3 S407-p SSSIIyssQEDVKEF
2 1 T419-p KEFEREEtQDKEEsV
1 2 S425-p EtQDKEEsVESsLPL
2 1 S429-p KEEsVESsLPLNAIE
0 2 K446-ub VICQGRPkNGCIVHG
1 0 K446-sm VICQGRPkNGCIVHG
0 1 K454-ub NGCIVHGkTGHLMAC
0 1 K466-ub MACFTCAkkLKKRNK
0 1 K467-ub ACFTCAkkLKKRNKP
3521 : Phospho-MDM2 (Ser166) Antibody
  MDM2 iso12  
S17 TDGAVTTSQIPASEQ
K36 RPKPLLLKLLKSVGA
K39 PLLLKLLKSVGAQKD
K45 LKSVGAQKDTYTMKE
K51 QKDTYTMKEVLFYLG
Y60 VLFYLGQYIMTKRLY
K70 TKRLYDEKQQHIVYC
K94 GVPSFSVKEHRKIYT
K98 FSVKEHRKIYTMIYR
R118 PLVDLSIR_______
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- gap
  mouse

 
S17 TEGAASTSQIPASEQ
K36 RPKPLLLKLLKSVGA
K39 PLLLKLLKSVGAQND
N45 LKSVGAQNDTYTMkE
K51-ac QNDTYTMkEIIFYIG
Y60 IIFYIGQYIMTKRLY
K70 TKRLYDEKQQHIVYC
K94 GVPSFSVKEHRKIYA
K98 FSVKEHRKIYAMIYR
S115 VAVSQQDSGTSLSES
S118 SQQDSGTSLSESRRQ
S145 APPEEKPSSSDLISR
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
S189 RsLsFDPSLGLCELR
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-ub GLDVPDGkkLTENDA
K362-ub 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
3521 : Phospho-MDM2 (Ser166) Antibody
  rat

 
S17 TEGAAGTSQIPASEQ
- gap
- gap
- gap
- gap
Y35 IIFYIGQYIMTKRLY
K45 TKRLYDEKQQHIVYC
K69 GVPSFSVKEHRKIYA
K73 FSVKEHRKIYAMIYR
S90 VVVSQQDSGTSPSES
S93 SQQDSGTSPSESRCQ
S120 ASQEEKPSSSDVVSR
S129 SDVVSRPSTSSRRRA
T130 DVVSRPSTSSRRRAI
S132 VSRPSTSSRRRAISE
A136 STSSRRRAISETEEN
S138 SSRRRAISETEENTD
T140 RRRAISETEENTDEL
T144 ISETEENTDELPGER
P148 EENTDELPGERQRKR
A158 RQRKRHRALSFDESL
- gap
- gap
S160 RKRHRALSFDESLGL
S164 RALSFDESLGLCVLR
T186 SSSEATDTPSHQDLD
S188 SEATDTPSHQDLDDG
S197 QDLDDGVSDHSADCL
S208 ADCLDQDSVSDQFSV
S210 CLDQDSVSDQFSVEF
S214 DSVSDQFSVEFEVES
S221 SVEFEVESLDSEDYS
S224 FEVESLDSEDYSLSD
S228 SLDSEDYSLSDEGHE
S230 DSEDYSLSDEGHELS
S237 SDEGHELSDEDDEVY
Y244 SDEDDEVYRVTVYQA
T247 DDEVYRVTVYQAGEs
Y249 EVYRVTVYQAGEsDA
S254-p TVYQAGEsDADsFEG
A256 YQAGEsDADsFEGDP
S258-p AGEsDADsFEGDPEI
T274 LADYWKCTSCNEMNP
S275 ADYWKCTSCNEMNPP
K302 ENWLPDDKGKDKVEI
K304 WLPDDKGKDKVEISE
K306 PDDKGKDKVEISEKA
S310 GKDKVEISEKAKLES
K312 DKVEISEKAKLESSD
K314 VEISEKAKLESSDQA
S318 EKAKLESSDQAEEGL
D319 KAKLESSDQAEEGLD
K331 GLDVPDGKKVTEDDA
K332 LDVPDGKKVTEDDAK
T334 VPDGKKVTEDDAKES
S341 TEDDAKESSAEDSEE
L354 EEKVAQMLLSQESDD
S356 KVAQMLLSQESDDYS
Y362 LSQESDDYSQPSTSS
S363 SQESDDYSQPSTSSS
Y373 STSSSIVYSSQESGK
S374 TSSSIVYSSQESGKE
S375 SSSIVYSSQESGKEL
T386 GKELKEDTQDKEESM
S392 DTQDKEESMESSFSL
S396 KEESMESSFSLNAIE
K413 VICQGRPKNGCIVHG
K413 VICQGRPKNGCIVHG
K421 NGCIVHGKTGHLMSC
K433 MSCFTCAKKLKKRNK
K434 SCFTCAKKLKKRNKP
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