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Q00987 (MDM2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 186. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase Mdm2

EC=6.3.2.-
Alternative name(s):
Double minute 2 protein
Short name=Hdm2
Oncoprotein Mdm2
p53-binding protein Mdm2
Gene names
Name:MDM2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length491 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as a ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and SNAI1 and promotes them to proteasomal degradation. Ref.23 Ref.27 Ref.28 Ref.31 Ref.32 Ref.36 Ref.44 Ref.47 Ref.50 Ref.51 Ref.52 Ref.53 Ref.55

Subunit structure

Binds p53/TP53, TP73/p73, ARF/P14, PML, RBL5 and RP11, and specifically to RNA. Can interact with RB1, E1A-associated protein EP300 and the E2F1 transcription factor. Forms a ternary complex with p53/TP53 and WWOX. Interacts with CDKN2AIP, MTBP, RFWD3, TBRG1, USP7, PYHIN1, UBXN6, and RBBP6. Isoform Mdm2-F does not interact with p53/TP53. Interacts with and ubiquitinates HIV-1 Tat. Interacts with ARRB1 and ARRB2. Interacts (isoform 2)with PSMA3. Found in a trimeric complex with MDM2, MDM4 and UPB2. Interacts with USP2 (via N-terminus and C-terminus). Interacts with MDM4. Part of a complex with MDM2, DAXX, RASSF1 and USP7. Part of a complex with DAXX, MDM2 and USP7. Interacts directly with DAXX and USP7. Interacts (via C-terminus) with RASSF1 isoform A(via N-terminus); the interaction is independent of TP53. Interacts with APEX1; leading to its ubiquitination and degradation. Interacts with RYBP; this inhibits ubiquitination of TP53. Identified in a complex with RYBP and p53/TP53. Also component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in regulating p53/TP53 stabilization and activity. Binds directly both p53/TP53 and TRIM28. Component of the TRIM28/KAP1-ERBB4-MDM2 complex involved in connecting growth factor responses with DNA damage. Interacts directly with both TRIM28 and ERBB4 in the complex. Interacts with DYRK2. Interacts with IGF1R. Interacts with TRIM13; the interaction ubiquitinates MDM2 leading to its proteasomal degradation. Interacts with SNAI1; this interaction promotes SNAI1 ubiquitination. Interacts with NOTCH1 (via intracellular domain). Interacts with FHIT. Interacts with RFFL. Interacts with herpes virus 8 protein v-IRF4. Ref.4 Ref.14 Ref.22 Ref.23 Ref.24 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.36 Ref.38 Ref.39 Ref.40 Ref.41 Ref.42 Ref.44 Ref.46 Ref.47 Ref.50 Ref.51 Ref.52 Ref.53 Ref.54 Ref.55 Ref.56 Ref.57 Ref.59 Ref.60

Subcellular location

Nucleusnucleoplasm. Cytoplasm. Nucleusnucleolus. Note: Expressed predominantly in the nucleoplasm. Interaction with ARF(P14) results in the localization of both proteins to the nucleolus. The nucleolar localization signals in both ARF(P14) and MDM2 may be necessary to allow efficient nucleolar localization of both proteins. Colocalizes with RASSF1 isoform Ain the nucleus. Ref.14 Ref.28 Ref.34 Ref.41 Ref.52 Ref.57

Tissue specificity

Ubiquitous. Isoform Mdm2-A, isoform Mdm2-B, isoform Mdm2-C, isoform Mdm2-D, isoform Mdm2-E, isoform Mdm2-F and isoform Mdm2-G are observed in a range of cancers but absent in normal tissues.

Induction

By DNA damage.

Domain

Region I is sufficient for binding p53 and inhibiting its G1 arrest and apoptosis functions. It also binds p73 and E2F1. Region II contains most of a central acidic region required for interaction with ribosomal protein L5 and a putative C4-type zinc finger. The RING finger domain which coordinates two molecules of zinc interacts specifically with RNA whether or not zinc is present and mediates the heterooligomerization with MDM4. It is also essential for its ubiquitin ligase E3 activity toward p53 and itself.

Post-translational modification

Phosphorylation on Ser-166 by SGK1 activates ubiquitination of p53/TP53. Phosphorylated at multiple sites near the RING domain by ATM upon DNA damage; this prevents oligomerization and E3 ligase processivity and impedes constitutive p53/TP53 degradation. Ref.17 Ref.21 Ref.43 Ref.45

Autoubiquitination leads to proteasomal degradation; resulting in p53/TP53 activation it may be regulated by SFN. Also ubiquitinated by TRIM13. Deubiquitinated by USP2 leads to its accumulation and increases deubiquitination and degradation of p53/TP53. Deubiquitinated by USP7 leading to its stabilization.

Polymorphism

A polymorphism in the MDM2 promoter is associated with susceptibility to accelerated tumor formation in both hereditary and sporadic cancers [MIM:614401]. It also contributes to susceptibility to Li-Fraumeni syndrome, in patients carrying a TP53 germline mutation.

Involvement in disease

Seems to be amplified in certain tumors (including soft tissue sarcomas, osteosarcomas and gliomas). A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding.

Miscellaneous

MDM2 RING finger mutations that failed to ubiquitinate p53 in vitro did not target p53 for degradation when expressed in cells.

Sequence similarities

Belongs to the MDM2/MDM4 family.

Contains 1 RanBP2-type zinc finger.

Contains 1 RING-type zinc finger.

Contains 1 SWIB domain.

Caution

A report observed N-glycosylation at Asn-349 (Ref.48). However, as the protein is not extracellular, additional evidences are required to confirm this result.

Ontologies

Keywords
   Biological processHost-virus interaction
Ubl conjugation pathway
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   DiseaseProto-oncogene
   DomainZinc-finger
   LigandMetal-binding
Zinc
   Molecular functionLigase
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest

Inferred from mutant phenotype PubMed 21726810. Source: UniProtKB

Fc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

cellular response to UV-C

Inferred from electronic annotation. Source: Ensembl

cellular response to acid

Inferred from electronic annotation. Source: Ensembl

cellular response to alkaloid

Inferred from electronic annotation. Source: Ensembl

cellular response to antibiotic

Inferred from electronic annotation. Source: Ensembl

cellular response to estrogen stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to hydrogen peroxide

Inferred from electronic annotation. Source: Ensembl

cellular response to hypoxia

Inferred from expression pattern PubMed 20810912. Source: UniProtKB

cellular response to peptide hormone stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to vitamin B1

Inferred from electronic annotation. Source: Ensembl

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

establishment of protein localization

Inferred from direct assay PubMed 10360174. Source: BHF-UCL

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

innate immune response

Traceable author statement. Source: Reactome

negative regulation of DNA damage response, signal transduction by p53 class mediator

Inferred from direct assay PubMed 10360174PubMed 9529249. Source: BHF-UCL

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell cycle arrest

Inferred from direct assay PubMed 9529249. Source: BHF-UCL

negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein processing

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 9271120. Source: UniProtKB

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

peptidyl-lysine modification

Inferred from mutant phenotype PubMed 19372219. Source: BHF-UCL

phosphatidylinositol-mediated signaling

Traceable author statement. Source: Reactome

positive regulation of cell proliferation

Traceable author statement PubMed 7791904. Source: BHF-UCL

positive regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

positive regulation of mitotic cell cycle

Inferred from mutant phenotype Ref.36. Source: UniProtKB

positive regulation of proteasomal ubiquitin-dependent protein catabolic process

Inferred from direct assay PubMed 11278372. Source: BHF-UCL

positive regulation of protein export from nucleus

Inferred from electronic annotation. Source: Ensembl

protein complex assembly

Inferred from direct assay Ref.16PubMed 12915590. Source: UniProtKB

protein destabilization

Inferred from direct assay PubMed 10360174PubMed 9529249. Source: BHF-UCL

protein localization to nucleus

Inferred from direct assay PubMed 10360174. Source: BHF-UCL

protein ubiquitination involved in ubiquitin-dependent protein catabolic process

Inferred from direct assay PubMed 11278372. Source: BHF-UCL

response to antibiotic

Inferred from expression pattern PubMed 20810912. Source: UniProtKB

response to carbohydrate

Inferred from electronic annotation. Source: Ensembl

response to cocaine

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to ether

Inferred from electronic annotation. Source: Ensembl

response to iron ion

Inferred from electronic annotation. Source: Ensembl

response to magnesium ion

Inferred from electronic annotation. Source: Ensembl

response to morphine

Inferred from electronic annotation. Source: Ensembl

synaptic transmission

Traceable author statement. Source: Reactome

traversing start control point of mitotic cell cycle

Inferred from electronic annotation. Source: Ensembl

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

endocytic vesicle membrane

Traceable author statement. Source: Reactome

nucleolus

Inferred from direct assay Ref.19Ref.57. Source: UniProtKB

nucleoplasm

Inferred from direct assay Ref.19PubMed 12915590. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

protein complex

Inferred from direct assay PubMed 9529249. Source: BHF-UCL

synapse

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionubiquitin-protein ligase activity

Inferred from direct assay Ref.15. Source: UniProtKB

zinc ion binding

Inferred from direct assay Ref.18. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself4EBI-389668,EBI-389668
ADRBK1P250984EBI-389668,EBI-3904795
AKT1P317493EBI-389668,EBI-296087
ARP102752EBI-389668,EBI-608057
BTRCQ9Y2979EBI-389668,EBI-307461
CDKN2AQ8N7264EBI-389668,EBI-625922
CSNK1A1P487293EBI-389668,EBI-1383726
CSNK1A1P48729-23EBI-389668,EBI-2040168
CSNK1DP487306EBI-389668,EBI-751621
Csnk1dQ064862EBI-389668,EBI-2910316From a different organism.
CSNK1EP496743EBI-389668,EBI-749343
CUL1Q136163EBI-389668,EBI-359390
DAXXQ9UER718EBI-389668,EBI-77321
DLG4P783523EBI-389668,EBI-80389
EEF1A1P681049EBI-389668,EBI-352162
ESR1P033722EBI-389668,EBI-78473
EZRP153113EBI-389668,EBI-1056902
FBXW11Q9UKB14EBI-389668,EBI-355189
FKBP3Q006882EBI-389668,EBI-1044081
Fkbp3Q624464EBI-389668,EBI-8313562From a different organism.
GNL3Q9BVP23EBI-389668,EBI-641642
GNL3LQ9NVN88EBI-389668,EBI-746682
GORABQ5T7V86EBI-389668,EBI-3917143
HNRNPKP619782EBI-389668,EBI-304185
JMYQ8N9B52EBI-389668,EBI-866435
JUNP054123EBI-389668,EBI-852823
JUNDP175353EBI-389668,EBI-2682803
MDM4O151518EBI-389668,EBI-398437
NCLP193388EBI-389668,EBI-346967
NPM1P067485EBI-389668,EBI-78579
Npm1Q619372EBI-389668,EBI-626362From a different organism.
NR0B2Q154664EBI-389668,EBI-3910729
OTUB1Q96FW15EBI-389668,EBI-1058491
PLK1P533507EBI-389668,EBI-476768
PMLP295906EBI-389668,EBI-295890
PMLP29590-56EBI-389668,EBI-304008
PPM1DO152974EBI-389668,EBI-1551512
PPP2R5CQ133625EBI-389668,EBI-1266156
PSMA3P257882EBI-389668,EBI-348380
PSME3P612898EBI-389668,EBI-355546
RASSF1Q9NS235EBI-389668,EBI-367363
RB1P064004EBI-389668,EBI-491274
RPL11P6291311EBI-389668,EBI-354380
RPL23P628293EBI-389668,EBI-353303
RPL5P467775EBI-389668,EBI-358018
RPS27P426775EBI-389668,EBI-356336
RPS27LQ71UM56EBI-389668,EBI-355126
RPS7P6208115EBI-389668,EBI-354360
RYBPQ8N48811EBI-389668,EBI-752324
RYR2Q927362EBI-389668,EBI-1170425
S100A1P232972EBI-389668,EBI-743686
S100A2P290342EBI-389668,EBI-752230
S100A4P264473EBI-389668,EBI-717058
S100A6P067032EBI-389668,EBI-352877
S100BP042712EBI-389668,EBI-458391
SETQ011052EBI-389668,EBI-1053182
TP53P0463760EBI-389668,EBI-366083
UBCP0CG486EBI-389668,EBI-3390054
USP2O756044EBI-389668,EBI-743272
USP7Q9300918EBI-389668,EBI-302474
vIRF-4Q2HR732EBI-389668,EBI-9001898From a different organism.

Alternative products

This entry describes 11 isoforms produced by alternative splicing. [Align] [Select]
Isoform Mdm2 (identifier: Q00987-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Mdm2-A (identifier: Q00987-2)

The sequence of this isoform differs from the canonical sequence as follows:
     28-222: Missing.
Isoform Mdm2-A1 (identifier: Q00987-3)

The sequence of this isoform differs from the canonical sequence as follows:
     28-222: Missing.
     275-300: Missing.
Isoform Mdm2-B (identifier: Q00987-4)

The sequence of this isoform differs from the canonical sequence as follows:
     28-300: Missing.
Isoform Mdm2-C (identifier: Q00987-5)

The sequence of this isoform differs from the canonical sequence as follows:
     53-222: Missing.
Isoform Mdm2-D (identifier: Q00987-6)

The sequence of this isoform differs from the canonical sequence as follows:
     30-388: Missing.
Isoform Mdm2-E (identifier: Q00987-7)

The sequence of this isoform differs from the canonical sequence as follows:
     76-102: YCSNDLLGDLFGVPSFSVKEHRKIYTM → NDCANLFPLVDLSIRELYISNYITLGI
     103-491: Missing.
Isoform Mdm2-alpha (identifier: Q00987-8)

The sequence of this isoform differs from the canonical sequence as follows:
     1-61: Missing.
Isoform Mdm2-F (identifier: Q00987-9)

The sequence of this isoform differs from the canonical sequence as follows:
     53-97: Missing.
Isoform Mdm2-G (identifier: Q00987-10)

The sequence of this isoform differs from the canonical sequence as follows:
     115-169: Missing.
Isoform 11 (identifier: Q00987-11)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MVRSRQM

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 491491E3 ubiquitin-protein ligase Mdm2
PRO_0000157332

Regions

Domain27 – 10781SWIB
Zinc finger299 – 32830RanBP2-type
Zinc finger438 – 47942RING-type
Region1 – 110110Necessary for interaction with USP2
Region150 – 23081Interaction with PYHIN1 and necessary for interaction with RFFL
Region170 – 306137Interaction with MTBP By similarity
Region210 – 30495ARF-binding
Region223 – 23210Interaction with USP7
Region242 – 33190Region II
Region276 – 491216Necessary for interaction with USP2
Motif179 – 1857Nuclear localization signal Potential
Motif190 – 20213Nuclear export signal
Motif466 – 4738Nucleolar localization signal Potential
Compositional bias210 – 2156Poly-Ser
Compositional bias243 – 30159Asp/Glu-rich (acidic)

Amino acid modifications

Modified residue1661Phosphoserine; by SGK1 Ref.45 Ref.49
Modified residue2401Phosphoserine Ref.21
Modified residue2421Phosphoserine Ref.21
Modified residue2461Phosphoserine Ref.21
Modified residue2601Phosphoserine Ref.21
Modified residue2621Phosphoserine Ref.21
Modified residue3861Phosphoserine; by ATM Ref.43
Modified residue3951Phosphoserine; by ATM Ref.43
Modified residue4071Phosphoserine; by ATM Ref.43
Modified residue4191Phosphothreonine; by ATM Ref.43
Modified residue4251Phosphoserine; by ATM Ref.43
Modified residue4291Phosphoserine; by ATM Ref.43

Natural variations

Alternative sequence1 – 6161Missing in isoform Mdm2-alpha.
VSP_003207
Alternative sequence11M → MVRSRQM in isoform 11.
VSP_037997
Alternative sequence28 – 300273Missing in isoform Mdm2-B.
VSP_003209
Alternative sequence28 – 222195Missing in isoform Mdm2-A and isoform Mdm2-A1.
VSP_003208
Alternative sequence30 – 388359Missing in isoform Mdm2-D.
VSP_003210
Alternative sequence53 – 222170Missing in isoform Mdm2-C.
VSP_003211
Alternative sequence53 – 9745Missing in isoform Mdm2-F.
VSP_022578
Alternative sequence76 – 10227YCSND…KIYTM → NDCANLFPLVDLSIRELYIS NYITLGI in isoform Mdm2-E.
VSP_003212
Alternative sequence103 – 491389Missing in isoform Mdm2-E.
VSP_003213
Alternative sequence115 – 16955Missing in isoform Mdm2-G.
VSP_022579
Alternative sequence275 – 30026Missing in isoform Mdm2-A1.
VSP_003214

Experimental info

Mutagenesis3051C → S: No loss of ubiquitin ligase E3 activity.
Mutagenesis3741C → T: No loss of ubiquitin ligase E3 activity.
Mutagenesis4381C → L: No loss of ubiquitin ligase E3 activity.
Mutagenesis4411C → G: Fails to interact with MDM4. Ref.16
Mutagenesis4491C → A: Loss of ubiquitin ligase E3 activity. Ref.20
Mutagenesis4491C → S: No substantial decrease of ubiquitin ligase E3 activity. Ref.20
Mutagenesis4521H → A: Loss of ubiquitin ligase E3 activity.
Mutagenesis4551T → A: Significant decrease of ubiquitin ligase E3 activity.
Mutagenesis4571H → S: Loss of ubiquitin ligase E3 activity.
Mutagenesis4611C → S: Loss of ubiquitin ligase E3 activity.
Mutagenesis4641C → A: Loss of ubiquitin ligase E3 activity, enhances protein stability. Does not inhibit interaction with APEX1, but inhibits its ubiquitin ligase E3 activity on APEX1. Ref.15 Ref.32 Ref.33 Ref.47 Ref.53
Mutagenesis4751C → G: Loss of ubiquitin ligase E3 activity.
Mutagenesis4781C → R: Fails to interact with MDM4. Ref.16
Mutagenesis4781C → S: Loss of ubiquitin ligase E3 activity. Ref.16
Sequence conflict171S → P in AAA82237. Ref.10

Secondary structure

................................................ 491
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Mdm2 [UniParc].

Last modified April 1, 1993. Version 1.
Checksum: F37CE163876BC983

FASTA49155,233
        10         20         30         40         50         60 
MCNTNMSVPT DGAVTTSQIP ASEQETLVRP KPLLLKLLKS VGAQKDTYTM KEVLFYLGQY 

        70         80         90        100        110        120 
IMTKRLYDEK QQHIVYCSND LLGDLFGVPS FSVKEHRKIY TMIYRNLVVV NQQESSDSGT 

       130        140        150        160        170        180 
SVSENRCHLE GGSDQKDLVQ ELQEEKPSSS HLVSRPSTSS RRRAISETEE NSDELSGERQ 

       190        200        210        220        230        240 
RKRHKSDSIS LSFDESLALC VIREICCERS SSSESTGTPS NPDLDAGVSE HSGDWLDQDS 

       250        260        270        280        290        300 
VSDQFSVEFE VESLDSEDYS LSEEGQELSD EDDEVYQVTV YQAGESDTDS FEEDPEISLA 

       310        320        330        340        350        360 
DYWKCTSCNE MNPPLPSHCN RCWALRENWL PEDKGKDKGE ISEKAKLENS TQAEEGFDVP 

       370        380        390        400        410        420 
DCKKTIVNDS RESCVEENDD KITQASQSQE SEDYSQPSTS SSIIYSSQED VKEFEREETQ 

       430        440        450        460        470        480 
DKEESVESSL PLNAIEPCVI CQGRPKNGCI VHGKTGHLMA CFTCAKKLKK RNKPCPVCRQ 

       490 
PIQMIVLTYF P 

« Hide

Isoform Mdm2-A [UniParc].

Checksum: 9772439D74A4448B
Show »

FASTA29633,140
Isoform Mdm2-A1 [UniParc].

Checksum: A3ED7CCFF670634E
Show »

FASTA27030,265
Isoform Mdm2-B [UniParc].

Checksum: BB9C602F589EEC41
Show »

FASTA21824,467
Isoform Mdm2-C [UniParc].

Checksum: 4BD6213CA39D15C0
Show »

FASTA32135,980
Isoform Mdm2-D [UniParc].

Checksum: 770E9B66362CA97E
Show »

FASTA13214,689
Isoform Mdm2-E [UniParc].

Checksum: 75E2B91B94C786C1
Show »

FASTA10211,587
Isoform Mdm2-alpha [UniParc].

Checksum: C84E1F63E39E655D
Show »

FASTA43048,488
Isoform Mdm2-F [UniParc].

Checksum: 4B630B50750EADFE
Show »

FASTA44649,899
Isoform Mdm2-G [UniParc].

Checksum: 3C8F55E98BC4203A
Show »

FASTA43649,249
Isoform 11 [UniParc].

Checksum: CFEC32F36132D8FA
Show »

FASTA49755,991

References

« Hide 'large scale' references
[1]"Amplification of a gene encoding a p53-associated protein in human sarcomas."
Oliner J.D., Kinzler K.W., Meltzer P.S., George D.L., Vogelstein B.
Nature 358:80-83(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MDM2).
Tissue: Colon.
[2]"Alternatively spliced mdm2 transcripts with loss of p53 binding domain sequences: transforming ability and frequent detection in human cancer."
Sigalas I., Calvert A.H., Anderson J.J., Neal D.E., Lunec J.
Nat. Med. 2:912-917(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS MDM2-A; MDM2-B; MDM2-C; MDM2-D AND MDM2-E).
Tissue: Ovarian carcinoma.
[3]"A novel exon within the mdm2 gene modulates translation initiation in vitro and disrupts the p53-binding domain of mdm2 protein."
Veldhoen N., Metcalfe S., Milner J.
Oncogene 18:7026-7033(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MDM2-ALPHA).
[4]"Analysis of the molecular species generated by MDM2 gene amplification in liposarcomas."
Tamborini E., Della Torre G., Lavarino C., Azzarelli A., Carpinelli P., Pierotti M.A., Pilotti S.
Int. J. Cancer 92:790-796(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS MDM2-F AND MDM2-G), INTERACTION WITH TP53.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM MDM2).
Tissue: Tongue.
[6]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM MDM2).
[7]NIEHS SNPs program
Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]"The finished DNA sequence of human chromosome 12."
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. expand/collapse author list , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 11).
Tissue: Rhabdomyosarcoma.
[10]"A functional p53-responsive intronic promoter is contained within the human mdm2 gene."
Zauberman A., Flusberg D., Haupt Y., Barak Y., Oren M.
Nucleic Acids Res. 23:2584-2592(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-24.
[11]"Translational enhancement of mdm2 oncogene expression in human tumor cells containing a stabilized wild-type p53 protein."
Landers J.E., Cassel S.L., George D.L.
Cancer Res. 57:3562-3568(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-9.
[12]"Genomic organisation of the human MDM2 oncogene and relationship to its alternatively spliced mRNAs."
Liang H., Atkins H., Abdel-Fattah R., Jones S.N., Lunec J.
Gene 338:217-223(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-491 (ISOFORM MDM2-A1).
[13]"A MboII polymorphism in exon 11 of the human MDM2 gene occurring in normal blood donors and in soft tissue sarcoma patients: an indication for an increased cancer susceptibility?"
Taubert H., Kappler M., Meye A., Bartel F., Schlott T., Lautenschlaeger C., Bache M., Schmidt H., Wuerl P.
Mutat. Res. 456:39-44(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 301-481.
[14]"Identification and characterization of multiple mdm-2 proteins and mdm-2-p53 protein complexes."
Olson D.C., Marechal V., Momand J., Chen J., Romocki C., Levine A.J.
Oncogene 8:2353-2360(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH TP53.
[15]"Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53."
Honda R., Tanaka H., Yasuda H.
FEBS Lett. 420:25-27(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF CYS-464.
[16]"Stabilization of the MDM2 oncoprotein by interaction with the structurally related MDMX protein."
Sharp D.A., Kratowicz S.A., Sank M.J., George D.L.
J. Biol. Chem. 274:38189-38196(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF CYS-441 AND CYS-478.
[17]"Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage."
Khosravi R., Maya R., Gottlieb T., Oren M., Shiloh Y., Shkedy D.
Proc. Natl. Acad. Sci. U.S.A. 96:14973-14977(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY ATM.
[18]"Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53."
Fang S., Jensen J.P., Ludwig R.L., Vousden K.H., Weissman A.M.
J. Biol. Chem. 275:8945-8951(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS.
[19]"Identification of a cryptic nucleolar-localization signal in MDM2."
Lohrum M.A.E., Ashcroft M., Kubbutat M.H.G., Vousden K.H.
Nat. Cell Biol. 2:179-181(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOLAR LOCALIZATION SIGNAL.
[20]"Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger domain of the ligase."
Honda R., Yasuda H.
Oncogene 19:1473-1476(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF CYS-449.
[21]"Hypophosphorylation of Mdm2 augments p53 stability."
Blattner C., Hay T., Meek D.W., Lane D.P.
Mol. Cell. Biol. 22:6170-6182(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-240; SER-242; SER-246; SER-260 AND SER-262.
[22]"A non-proteolytic role for ubiquitin in Tat-mediated transactivation of the HIV-1 promoter."
Bres V., Kiernan R.E., Linares L.K., Chable-Bessia C., Plechakova O., Treand C., Emiliani S., Peloponese J.-M., Jeang K.-T., Coux O., Scheffner M., Benkirane M.
Nat. Cell Biol. 5:754-761(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIV-1 TAT.
[23]"Mdm2-dependent ubiquitination and degradation of the insulin-like growth factor 1 receptor."
Girnita L., Girnita A., Larsson O.
Proc. Natl. Acad. Sci. U.S.A. 100:8247-8252(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN UBIQUITINATION OF IGF1R, INTERACTION WITH IGF1R.
[24]"Synergistic tumor suppression by coexpression of FHIT and p53 coincides with FHIT-mediated MDM2 inactivation and p53 stabilization in human non-small cell lung cancer cells."
Nishizaki M., Sasaki J., Fang B., Atkinson E.N., Minna J.D., Roth J.A., Ji L.
Cancer Res. 64:5745-5752(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FHIT.
[25]"A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans."
Bond G.L., Hu W., Bond E.E., Robins H., Lutzker S.G., Arva N.C., Bargonetti J., Bartel F., Taubert H., Wuerl P., Onel K., Yip L., Hwang S.J., Strong L.C., Lozano G., Levine A.J.
Cell 119:591-602(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO ACCELERATED TUMOR FORMATION.
[26]"Negative regulation of p53 functions by Daxx and the involvement of MDM2."
Zhao L.Y., Liu J., Sidhu G.S., Niu Y., Liu Y., Wang R., Liao D.
J. Biol. Chem. 279:50566-50579(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DAXX.
[27]"A dynamic role of HAUSP in the p53-Mdm2 pathway."
Li M., Brooks C.L., Kon N., Gu W.
Mol. Cell 13:879-886(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH USP7, DEUBIQUITINATION BY USP7.
[28]"PML regulates p53 stability by sequestering Mdm2 to the nucleolus."
Bernardi R., Scaglioni P.P., Bergmann S., Horn H.F., Vousden K.H., Pandolfi P.P.
Nat. Cell Biol. 6:665-672(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PML AND RPL11, SUBCELLULAR LOCATION.
[29]"{beta}-Arrestin is crucial for ubiquitination and down-regulation of the insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3 ligase."
Girnita L., Shenoy S.K., Sehat B., Vasilcanu R., Girnita A., Lefkowitz R.J., Larsson O.
J. Biol. Chem. 280:24412-24419(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ARRB1 AND ARRB2.
[30]"WOX1 is essential for tumor necrosis factor-, UV light-, staurosporine-, and p53-mediated cell death, and its tyrosine 33-phosphorylated form binds and stabilizes serine 46-phosphorylated p53."
Chang N.-S., Doherty J., Ensign A., Schultz L., Hsu L.-J., Hong Q.
J. Biol. Chem. 280:43100-43108(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH WWOX AND TP53.
[31]"MDM2 promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma protein."
Sdek P., Ying H., Chang D.L., Qiu W., Zheng H., Touitou R., Allday M.J., Xiao Z.X.
Mol. Cell 20:699-708(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PSMA3.
[32]"Regulation of p53 and MDM2 activity by MTBP."
Brady M., Vlatkovic N., Boyd M.T.
Mol. Cell. Biol. 25:545-553(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MTBP, MUTAGENESIS OF CYS-464.
[33]"Interferon-inducible protein IFIXalpha1 functions as a negative regulator of HDM2."
Ding Y., Lee J.-F., Lu H., Lee M.-H., Yan D.-H.
Mol. Cell. Biol. 26:1979-1996(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, INTERACTION WITH PYHIN1, MUTAGENESIS OF CYS-464.
[34]"Critical role for Daxx in regulating Mdm2."
Tang J., Qu L.K., Zhang J., Wang W., Michaelson J.S., Degenhardt Y.Y., El-Deiry W.S., Yang X.
Nat. Cell Biol. 8:855-862(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH DAXX AND USP7, INTERACTION WITH DAXX, SUBCELLULAR LOCATION.
[35]"CARF binds to three members (ARF, p53, and HDM2) of the p53 tumor-suppressor pathway."
Kamrul H.M., Wadhwa R., Kaul S.C.
Ann. N. Y. Acad. Sci. 1100:312-315(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CDKN2AIP.
[36]"The deubiquitinating enzyme USP2a regulates the p53 pathway by targeting Mdm2."
Stevenson L.F., Sparks A., Allende-Vega N., Xirodimas D.P., Lane D.P., Saville M.K.
EMBO J. 26:976-986(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH USP2, UBIQUITINATION, DEUBIQUITINATION BY USP2.
[37]"The single-nucleotide polymorphism 309 in the MDM2 gene contributes to the Li-Fraumeni syndrome and related phenotypes."
Ruijs M.W., Schmidt M.K., Nevanlinna H., Tommiska J., Aittomaki K., Pruntel R., Verhoef S., Van't Veer L.J.
Eur. J. Hum. Genet. 15:110-114(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO ACCELERATED TUMOR FORMATION AND LI-FRAUMENI SYNDROME.
[38]"A novel nuclear interactor of ARF and MDM2 (NIAM) that maintains chromosomal stability."
Tompkins V.S., Hagen J., Frazier A.A., Lushnikova T., Fitzgerald M.P., di Tommaso A.D., Ladeveze V., Domann F.E., Eischen C.M., Quelle D.E.
J. Biol. Chem. 282:1322-1333(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TBRG1.
[39]"PACT is a negative regulator of p53 and essential for cell growth and embryonic development."
Li L., Deng B., Xing G., Teng Y., Tian C., Cheng X., Yin X., Yang J., Gao X., Zhu Y., Sun Q., Zhang L., Yang X., He F.
Proc. Natl. Acad. Sci. U.S.A. 104:7951-7956(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RBBP6.
[40]"CARPs enhance p53 turnover by degrading 14-3-3sigma and stabilizing MDM2."
Yang W., Dicker D.T., Chen J., El-Deiry W.S.
Cell Cycle 7:670-682(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RFFL, AUTOUBIQUITINATION.
[41]"The tumour suppressor RASSF1A promotes MDM2 self-ubiquitination by disrupting the MDM2-DAXX-HAUSP complex."
Song M.S., Song S.J., Kim S.Y., Oh H.J., Lim D.S.
EMBO J. 27:1863-1874(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH DAXX; RASSF1 AND USP7, INTERACTION WITH RASSF1; USP7 AND DAXX, SUBCELLULAR LOCATION.
[42]"AAA ATPase p97 and adaptor UBXD1 suppress MDM2 ubiquitination and degradation and promote constitutive p53 turnover."
Zweitzig D.R., Shcherbik N., Haines D.S.
Mol. Biol. Cell 19:5029-5029(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UBXN6.
[43]"ATM activates p53 by regulating MDM2 oligomerization and E3 processivity."
Cheng Q., Chen L., Li Z., Lane W.S., Chen J.
EMBO J. 28:3857-3867(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-386; SER-395; SER-407; THR-419; SER-425 AND SER-429.
[44]"RYBP stabilizes p53 by modulating MDM2."
Chen D., Zhang J., Li M., Rayburn E.R., Wang H., Zhang R.
EMBO Rep. 10:166-172(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RYBP, IDENTIFICATION IN A COMPLEX WITH RYBP AND TP53.
[45]"Sgk1 activates MDM2-dependent p53 degradation and affects cell proliferation, survival, and differentiation."
Amato R., D'Antona L., Porciatti G., Agosti V., Menniti M., Rinaldo C., Costa N., Bellacchio E., Mattarocci S., Fuiano G., Soddu S., Paggi M.G., Lang F., Perrotti N.
J. Mol. Med. 87:1221-1239(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-166 BY SGK1.
[46]"Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 4 targets MDM2 to deregulate the p53 tumor suppressor pathway."
Lee H.R., Toth Z., Shin Y.C., Lee J.S., Chang H., Gu W., Oh T.K., Kim M.H., Jung J.U.
J. Virol. 83:6739-6747(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HHV-8 PROTEIN VIRF4.
[47]"Ubiquitination of mammalian AP endonuclease (APE1) regulated by the p53-MDM2 signaling pathway."
Busso C.S., Iwakuma T., Izumi T.
Oncogene 28:1616-1625(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH APEX1, MUTAGENESIS OF CYS-464.
[48]"A strategy for precise and large scale identification of core fucosylated glycoproteins."
Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.
Mol. Cell. Proteomics 8:913-923(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION.
[49]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals 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) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[50]"p53 inhibits tumor cell invasion via the degradation of snail protein in hepatocellular carcinoma."
Lim S.O., Kim H., Jung G.
FEBS Lett. 584:2231-2236(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SNAI1.
[51]"ATM augments nuclear stabilization of DYRK2 by inhibiting MDM2 in the apoptotic response to DNA damage."
Taira N., Yamamoto H., Yamaguchi T., Miki Y., Yoshida K.
J. Biol. Chem. 285:4909-4919(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DYRK2 UBIQUITINATION, INTERACTION WITH DYRK2.
[52]"Interactions of ErbB4 and Kap1 connect the growth factor and DNA damage response pathways."
Gilmore-Hebert M., Ramabhadran R., Stern D.F.
Mol. Cancer Res. 8:1388-1398(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRIM28 IN THE TRIM28/KAP1-ERBB4-MDM2 COMPLEX AND WITH TP53 IN THE TRIM28/KAP1-MDM2-P53/TP53 COMPLEX, FUNCTION, SUBCELLULAR LOCATION.
[53]"RFWD3-Mdm2 ubiquitin ligase complex positively regulates p53 stability in response to DNA damage."
Fu X., Yucer N., Liu S., Li M., Yi P., Mu J.J., Yang T., Chu J., Jung S.Y., O'Malley B.W., Gu W., Qin J., Wang Y.
Proc. Natl. Acad. Sci. U.S.A. 107:4579-4584(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TP53 AND RFWD3, MUTAGENESIS OF CYS-464.
[54]"MdmX is a substrate for the deubiquitinating enzyme USP2a."
Allende-Vega N., Sparks A., Lane D.P., Saville M.K.
Oncogene 29:432-441(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH USP2 AND MDM4.
[55]"Notch1 binds and induces degradation of Snail in hepatocellular carcinoma."
Lim S.O., Kim H.S., Quan X., Ahn S.M., Kim H., Hsieh D., Seong J.K., Jung G.
BMC Biol. 9:83-83(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SNAI1 AND NOTCH1.
[56]"Ret finger protein 2 enhances ionizing radiation-induced apoptosis via degradation of AKT and MDM2."
Joo H.M., Kim J.Y., Jeong J.B., Seong K.M., Nam S.Y., Yang K.H., Kim C.S., Kim H.S., Jeong M., An S., Jin Y.W.
Eur. J. Cell Biol. 90:420-431(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRIM13, UBIQUITINATION.
[57]"BMK1 is involved in the regulation of p53 through disrupting the PML-MDM2 interaction."
Yang Q., Liao L., Deng X., Chen R., Gray N.S., Yates J.R. III, Lee J.D.
Oncogene 32:3156-3164(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PML.
[58]"Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain."
Kussie P.H., Gorina S., Marechal V., Elenbaas B., Moreau J., Levine A.J., Pavletich N.P.
Science 274:948-953(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 25-109 IN COMPLEX WITH P53.
[59]"Structural basis of competitive recognition of p53 and MDM2 by HAUSP/USP7: implications for the regulation of the p53-MDM2 pathway."
Hu M., Gu L., Li M., Jeffrey P.D., Gu W., Shi Y.
PLoS Biol. 4:228-239(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 224-232 IN COMPLEX WITH USP7, INTERACTION WITH USP7.
[60]"Molecular recognition of p53 and MDM2 by USP7/HAUSP."
Sheng Y., Saridakis V., Sarkari F., Duan S., Wu T., Arrowsmith C.H., Frappier L.
Nat. Struct. Mol. Biol. 13:285-291(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 145-150 IN COMPLEX WITH USP7, INTERACTION WITH USP7.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M92424 mRNA. Translation: AAA60568.1.
Z12020 mRNA. Translation: CAA78055.1.
U33199 mRNA. Translation: AAA75514.1.
U33200 mRNA. Translation: AAA75515.1.
U33201 mRNA. Translation: AAA75516.1.
U33202 mRNA. Translation: AAA75517.1.
U33203 mRNA. Translation: AAA75518.1.
AF092844 mRNA. Translation: AAL40179.1.
AF092845 mRNA. Translation: AAL40180.1.
AK290341 mRNA. Translation: BAF83030.1.
BT007258 mRNA. Translation: AAP35922.1.
AF527840 Genomic DNA. Translation: AAM78554.1.
AC025423 Genomic DNA. No translation available.
BC009893 mRNA. No translation available.
U28935 Genomic DNA. Translation: AAA82237.1.
U39736 Genomic DNA. Translation: AAA82061.1.
AF201370 mRNA. Translation: AAF42995.1.
AJ251943 Genomic DNA. Translation: CAB64448.1.
PIRS24354.
RefSeqNP_001138811.1. NM_001145339.2.
NP_001265391.1. NM_001278462.1.
NP_002383.2. NM_002392.5.
XP_005268929.1. XM_005268872.1.
UniGeneHs.484551.
Hs.733536.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1RV1X-ray2.30A/B/C25-109[»]
1T4EX-ray2.60A/B17-111[»]
1T4FX-ray1.90M17-125[»]
1YCRX-ray2.60A17-125[»]
1Z1MNMR-A1-118[»]
2AXIX-ray1.40A17-125[»]
2C6ANMR-A290-335[»]
2C6BNMR-A290-335[»]
2F1YX-ray1.70A-[»]
2FOPX-ray2.10B145-150[»]
2GV2X-ray1.80A17-125[»]
2HDPNMR-A/B429-491[»]
2LZGNMR-A1-125[»]
2M86NMR-B17-125[»]
2VJEX-ray2.20A/C428-491[»]
2VJFX-ray2.30A/C428-491[»]
3EQSX-ray1.65A25-109[»]
3G03X-ray1.80A/C18-125[»]
3IUXX-ray1.65A/C25-109[»]
3IWYX-ray1.93A/C25-109[»]
3JZKX-ray2.10A17-111[»]
3JZRX-ray2.10A17-125[»]
3JZSX-ray1.78A24-109[»]
3LBKX-ray2.30A18-111[»]
3LBLX-ray1.60A/C/E18-111[»]
3LNJX-ray2.40A/C/E25-109[»]
3LNZX-ray1.95A/C/E/G/I/K/M/O25-109[»]
3TJ2X-ray2.10A/C18-111[»]
3TPXX-ray1.80A/C/E25-109[»]
3TU1X-ray1.60A18-125[»]
3V3BX-ray2.00A/B24-110[»]
3VBGX-ray2.80A/B/C/D25-109[»]
3VZVX-ray2.80A/B25-109[»]
3W69X-ray1.90A/B25-109[»]
4DIJX-ray1.90A/B17-111[»]
4EREX-ray1.80A/B17-111[»]
4ERFX-ray2.00A/C/E17-111[»]
4HBMX-ray1.90A/B/C/D/E/F/G/H6-125[»]
4HFZX-ray2.69A/C17-125[»]
4HG7X-ray1.60A17-108[»]
4JV7X-ray2.20A18-111[»]
4JV9X-ray2.50A18-111[»]
4JVEX-ray2.30A18-111[»]
4JVRX-ray1.70A/C/E18-111[»]
4JWRX-ray2.35A/B/C17-111[»]
4MDNX-ray1.90A18-110[»]
4MDQX-ray2.12A25-110[»]
DisProtDP00334.
ProteinModelPortalQ00987.
SMRQ00987. Positions 6-111, 290-335, 432-491.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110358. 299 interactions.
DIPDIP-392N.
IntActQ00987. 179 interactions.
MINTMINT-101583.

Chemistry

BindingDBQ00987.
ChEMBLCHEMBL5023.

PTM databases

PhosphoSiteQ00987.

Polymorphism databases

DMDM266516.

Proteomic databases

PaxDbQ00987.
PRIDEQ00987.

Protocols and materials databases

DNASU4193.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000258149; ENSP00000258149; ENSG00000135679. [Q00987-10]
ENST00000299252; ENSP00000299252; ENSG00000135679. [Q00987-5]
ENST00000348801; ENSP00000335096; ENSG00000135679.
ENST00000356290; ENSP00000348637; ENSG00000135679. [Q00987-5]
ENST00000360430; ENSP00000353611; ENSG00000135679. [Q00987-2]
ENST00000393412; ENSP00000377064; ENSG00000135679. [Q00987-4]
ENST00000393413; ENSP00000377065; ENSG00000135679. [Q00987-4]
ENST00000428863; ENSP00000410694; ENSG00000135679. [Q00987-3]
ENST00000462284; ENSP00000417281; ENSG00000135679. [Q00987-11]
ENST00000540827; ENSP00000440932; ENSG00000135679. [Q00987-2]
GeneID4193.
KEGGhsa:4193.
UCSCuc001sui.4. human. [Q00987-11]
uc001sun.5. human. [Q00987-5]
uc001suo.4. human. [Q00987-2]
uc009zqy.1. human. [Q00987-1]
uc009zrc.4. human. [Q00987-4]
uc009zrh.4. human. [Q00987-3]

Organism-specific databases

CTD4193.
GeneCardsGC12P069201.
HGNCHGNC:6973. MDM2.
HPACAB000086.
CAB016303.
MIM164785. gene.
614401. phenotype.
neXtProtNX_Q00987.
Orphanet99970. Dedifferentiated liposarcoma.
99971. Well-differentiated liposarcoma.
PharmGKBPA30718.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG46328.
HOVERGENHBG013472.
InParanoidQ00987.
KOK06643.
OMALCVIREI.
OrthoDBEOG7RRF7T.
PhylomeDBQ00987.
TreeFamTF105306.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_115566. Cell Cycle.
REACT_116125. Disease.
REACT_120956. Cellular responses to stress.
REACT_13685. Neuronal System.
REACT_6900. Immune System.
SignaLinkQ00987.

Gene expression databases

ArrayExpressQ00987.
BgeeQ00987.
GenevestigatorQ00987.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
InterProIPR028340. Mdm2.
IPR015459. MDM2_E3_ligase.
IPR016495. p53_neg-reg_MDM_2/4.
IPR003121. SWIB_MDM2_domain.
IPR001876. Znf_RanBP2.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PANTHERPTHR10360:SF9. PTHR10360:SF9. 1 hit.
PfamPF02201. SWIB. 1 hit.
PF00641. zf-RanBP. 1 hit.
[Graphical view]
PIRSFPIRSF500700. MDM2. 1 hit.
PIRSF006748. p53_MDM_2/4. 1 hit.
SMARTSM00184. RING. 1 hit.
[Graphical view]
SUPFAMSSF47592. SSF47592. 2 hits.
PROSITEPS01358. ZF_RANBP2_1. 1 hit.
PS50199. ZF_RANBP2_2. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ00987.
GeneWikiMdm2.
GenomeRNAi4193.
NextBio16526.
PMAP-CutDBQ00987.
PROQ00987.
SOURCESearch...

Entry information

Entry nameMDM2_HUMAN
AccessionPrimary (citable) accession number: Q00987
Secondary accession number(s): A6NL51 expand/collapse secondary AC list , A8K2S6, Q13226, Q13297, Q13298, Q13299, Q13300, Q13301, Q53XW0, Q71TW9, Q8WYJ1, Q8WYJ2, Q9UGI3, Q9UMT8
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: March 19, 2014
This is version 186 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM