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Protein

E3 ubiquitin-protein ligase Mdm2

Gene

MDM2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (PubMed:12821780, PubMed:15053880, PubMed:15195100, PubMed:15632057, PubMed:16337594, PubMed:17290220, PubMed:19098711, PubMed:19219073, PubMed:19837670, PubMed:19965871, PubMed:20173098, PubMed:20385133, PubMed:20858735, PubMed:22128911). Ubiquitinates DCX, leading to DCX degradation and reduction of the dendritic spine density of olfactory bulb granule cells (By similarity).By similarity14 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri299 – 328RanBP2-typePROSITE-ProRule annotationAdd BLAST30
Zinc fingeri438 – 479RING-typePROSITE-ProRule annotationAdd BLAST42

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • ligase activity Source: UniProtKB
  • p53 binding Source: UniProtKB
  • SUMO transferase activity Source: Reactome
  • ubiquitin protein ligase activity Source: BHF-UCL
  • ubiquitin protein ligase binding Source: UniProtKB
  • ubiquitin-protein transferase activity Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Host-virus interaction, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000135679-MONOMER.
BRENDAi6.3.2.19. 2681.
ReactomeiR-HSA-198323. AKT phosphorylates targets in the cytosol.
R-HSA-2559580. Oxidative Stress Induced Senescence.
R-HSA-2559585. Oncogene Induced Senescence.
R-HSA-3232118. SUMOylation of transcription factors.
R-HSA-399719. Trafficking of AMPA receptors.
R-HSA-5674400. Constitutive Signaling by AKT1 E17K in Cancer.
R-HSA-5689880. Ub-specific processing proteases.
R-HSA-6804756. Regulation of TP53 Activity through Phosphorylation.
R-HSA-6804757. Regulation of TP53 Degradation.
R-HSA-6804760. Regulation of TP53 Activity through Methylation.
R-HSA-69541. Stabilization of p53.
SignaLinkiQ00987.
SIGNORiQ00987.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:MDM2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:6973. MDM2.

Subcellular locationi

  • 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 A in the nucleus.

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • endocytic vesicle membrane Source: Reactome
  • nucleolus Source: UniProtKB
  • nucleoplasm Source: UniProtKB
  • nucleus Source: UniProtKB
  • plasma membrane Source: Reactome
  • protein complex Source: BHF-UCL
  • synapse Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

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.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi305C → S: No loss of ubiquitin ligase E3 activity. 1 Publication1
Mutagenesisi374C → T: No loss of ubiquitin ligase E3 activity. 1 Publication1
Mutagenesisi438C → L: No loss of ubiquitin ligase E3 activity. 1 Publication1
Mutagenesisi441C → G: Fails to interact with MDM4. 1 Publication1
Mutagenesisi449C → A: Loss of ubiquitin ligase E3 activity. 1 Publication1
Mutagenesisi449C → S: No substantial decrease of ubiquitin ligase E3 activity. 1 Publication1
Mutagenesisi452H → A: Loss of ubiquitin ligase E3 activity. 1 Publication1
Mutagenesisi455T → A: Significant decrease of ubiquitin ligase E3 activity. 1 Publication1
Mutagenesisi457H → S: Loss of ubiquitin ligase E3 activity. 1 Publication1
Mutagenesisi461C → S: Loss of ubiquitin ligase E3 activity. 1 Publication1
Mutagenesisi464C → 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. 5 Publications1
Mutagenesisi475C → G: Loss of ubiquitin ligase E3 activity. 1 Publication1
Mutagenesisi478C → R: Fails to interact with MDM4. 1 Publication1
Mutagenesisi478C → S: Loss of ubiquitin ligase E3 activity. 1 Publication1

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi4193.
MalaCardsiMDM2.
MIMi614401. phenotype.
OpenTargetsiENSG00000135679.
Orphaneti99970. Dedifferentiated liposarcoma.
524. Li-Fraumeni syndrome.
99971. Well-differentiated liposarcoma.
PharmGKBiPA30718.

Chemistry databases

ChEMBLiCHEMBL5023.

Polymorphism and mutation databases

DMDMi266516.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001573321 – 491E3 ubiquitin-protein ligase Mdm2Add BLAST491

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei166Phosphoserine; by SGK1Combined sources1 Publication1
Modified residuei190PhosphoserineBy similarity1
Modified residuei240Phosphoserine1 Publication1
Modified residuei242Phosphoserine1 Publication1
Modified residuei246Phosphoserine1 Publication1
Modified residuei260Phosphoserine1 Publication1
Modified residuei262Phosphoserine1 Publication1
Modified residuei386Phosphoserine; by ATM1 Publication1
Modified residuei395Phosphoserine; by ATM1 Publication1
Modified residuei407Phosphoserine; by ATM1 Publication1
Modified residuei419Phosphothreonine; by ATM1 Publication1
Modified residuei425Phosphoserine; by ATM1 Publication1
Modified residuei429Phosphoserine; by ATM1 Publication1

Post-translational modificationi

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.5 Publications
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.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ00987.
MaxQBiQ00987.
PaxDbiQ00987.
PeptideAtlasiQ00987.
PRIDEiQ00987.

PTM databases

iPTMnetiQ00987.
PhosphoSitePlusiQ00987.

Miscellaneous databases

PMAP-CutDBQ00987.

Expressioni

Tissue specificityi

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.

Inductioni

By DNA damage.

Gene expression databases

BgeeiENSG00000135679.
ExpressionAtlasiQ00987. baseline and differential.
GenevisibleiQ00987. HS.

Organism-specific databases

HPAiCAB000086.
CAB016303.

Interactioni

Subunit structurei

Interacts with p53/TP53, TP73/p73, RBL5 and RP11. Binds 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, RFWD3, USP7, PYHIN1, UBXN6, and RBBP6. Interacts with ARRB1 and ARRB2. Interacts with PSMA3. Found in a trimeric complex with MDM2, MDM4 and USP2. 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 and RNF34; the interaction stabilizes MDM2. Interacts with CDK5RAP3 and CDKN2A/ARF; form a ternary complex involved in regulation of p53/TP53 (PubMed:16173922). Interacts with MTA1. Interacts with AARB2. Interacts with MTBP. Interacts with PML. Interacts with RPL11. Interacts with TBRG1. Interacts with herpes virus 8 protein v-IRF4. Interacts with and ubiquitinates HIV-1 Tat.37 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself4EBI-389668,EBI-389668
ADRBK1P250984EBI-389668,EBI-3904795
AKT1P317494EBI-389668,EBI-296087
ARP102752EBI-389668,EBI-608057
BTRCQ9Y2979EBI-389668,EBI-307461
CASP3P425742EBI-389668,EBI-524064
CDKN2AQ8N7265EBI-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
IGF1RP080692EBI-389668,EBI-475981
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
RPS3P233968EBI-389668,EBI-351193
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
TP53P0463765EBI-389668,EBI-366083
UBCP0CG486EBI-389668,EBI-3390054
USP2O756044EBI-389668,EBI-743272
USP7Q9300918EBI-389668,EBI-302474
vIRF-4Q2HR732EBI-389668,EBI-9001898From a different organism.

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • p53 binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110358. 426 interactors.
DIPiDIP-392N.
IntActiQ00987. 182 interactors.
MINTiMINT-101583.
STRINGi9606.ENSP00000417281.

Chemistry databases

BindingDBiQ00987.

Structurei

Secondary structure

1491
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi7 – 10Combined sources4
Beta strandi13 – 15Combined sources3
Beta strandi17 – 19Combined sources3
Helixi23 – 25Combined sources3
Beta strandi27 – 30Combined sources4
Helixi32 – 41Combined sources10
Beta strandi46 – 49Combined sources4
Helixi50 – 64Combined sources15
Beta strandi71 – 76Combined sources6
Beta strandi78 – 80Combined sources3
Helixi81 – 86Combined sources6
Beta strandi88 – 92Combined sources5
Helixi96 – 104Combined sources9
Beta strandi107 – 109Combined sources3
Beta strandi295 – 297Combined sources3
Helixi299 – 301Combined sources3
Turni306 – 308Combined sources3
Beta strandi314 – 318Combined sources5
Turni320 – 322Combined sources3
Helixi433 – 435Combined sources3
Turni439 – 441Combined sources3
Beta strandi442 – 444Combined sources3
Beta strandi448 – 452Combined sources5
Beta strandi455 – 460Combined sources6
Helixi462 – 470Combined sources9
Turni476 – 478Combined sources3
Beta strandi484 – 489Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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-ray1.70A224-232[»]
2FOPX-ray2.10B145-150[»]
2GV2X-ray1.80A17-125[»]
2HDPNMR-A/B429-491[»]
2LZGNMR-A1-125[»]
2M86NMR-B17-125[»]
2MPSNMR-A3-109[»]
2RUHNMR-A6-102[»]
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[»]
3MQSX-ray2.40D394-403[»]
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[»]
4OASX-ray1.70A/C/E17-111[»]
4OBAX-ray1.60A/B/C17-111[»]
4OCCX-ray1.80A/C/E17-111[»]
4ODEX-ray1.80A6-110[»]
4ODFX-ray2.20A6-110[»]
4OGNX-ray1.38A6-110[»]
4OGTX-ray1.54A6-110[»]
4OGVX-ray2.20A/B/C17-111[»]
4OQ3X-ray2.30A/B/C/D17-111[»]
4QO4X-ray1.70A17-111[»]
4QOCX-ray1.70A/C/E/G/I/K17-111[»]
4UD7X-ray1.60A/B/C/D17-125[»]
4UE1X-ray1.45A/B/C/D17-125[»]
4UMNX-ray1.99A/B6-125[»]
4WT2X-ray1.42A6-110[»]
4XXBX-ray2.40B290-437[»]
4ZFIX-ray2.00A/B/C/D18-113[»]
4ZGKX-ray2.00A/B18-114[»]
4ZYCX-ray1.95A/B/C17-111[»]
4ZYFX-ray1.80A17-111[»]
4ZYIX-ray1.67A17-111[»]
5AFGX-ray1.90A17-108[»]
5C5AX-ray1.15A/B20-111[»]
5HMHX-ray1.79A/B21-116[»]
5HMIX-ray1.74A/B18-116[»]
5HMKX-ray2.17A/B17-125[»]
5LN2X-ray1.58A17-111[»]
DisProtiDP00334.
ProteinModelPortaliQ00987.
SMRiQ00987.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ00987.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 107SWIBAdd BLAST81

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 110Necessary for interaction with USP2Add BLAST110
Regioni150 – 230Interaction with PYHIN1 and necessary for interaction with RFFL and RNF342 PublicationsAdd BLAST81
Regioni170 – 306Interaction with MTBPBy similarityAdd BLAST137
Regioni210 – 304ARF-bindingAdd BLAST95
Regioni223 – 232Interaction with USP710
Regioni242 – 331Region IIAdd BLAST90
Regioni276 – 491Necessary for interaction with USP2Add BLAST216

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi179 – 185Nuclear localization signalSequence analysis7
Motifi190 – 202Nuclear export signalAdd BLAST13
Motifi466 – 473Nucleolar localization signalSequence analysis8

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi210 – 215Poly-Ser6
Compositional biasi243 – 301Asp/Glu-rich (acidic)Add BLAST59

Domaini

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.

Sequence similaritiesi

Belongs to the MDM2/MDM4 family.Curated
Contains 1 RanBP2-type zinc finger.PROSITE-ProRule annotation
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation
Contains 1 SWIB domain.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri299 – 328RanBP2-typePROSITE-ProRule annotationAdd BLAST30
Zinc fingeri438 – 479RING-typePROSITE-ProRule annotationAdd BLAST42

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IGXG. Eukaryota.
ENOG41125MP. LUCA.
GeneTreeiENSGT00530000063539.
HOVERGENiHBG013472.
InParanoidiQ00987.
KOiK06643.
OMAiGELPCKL.
OrthoDBiEOG091G0FYK.
PhylomeDBiQ00987.
TreeFamiTF105306.

Family and domain databases

Gene3Di1.10.245.10. 1 hit.
3.30.40.10. 1 hit.
InterProiIPR028340. 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]
PANTHERiPTHR13844:SF15. PTHR13844:SF15. 1 hit.
PfamiPF02201. SWIB. 1 hit.
PF00641. zf-RanBP. 1 hit.
[Graphical view]
PIRSFiPIRSF500700. MDM2. 1 hit.
PIRSF006748. p53_MDM_2/4. 1 hit.
SUPFAMiSSF47592. SSF47592. 2 hits.
SSF90209. SSF90209. 1 hit.
PROSITEiPS01358. ZF_RANBP2_1. 1 hit.
PS50199. ZF_RANBP2_2. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequences (11)i

Sequence statusi: Complete.

This entry describes 11 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Mdm2 (identifier: Q00987-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MCNTNMSVPT DGAVTTSQIP ASEQETLVRP KPLLLKLLKS VGAQKDTYTM
60 70 80 90 100
KEVLFYLGQY IMTKRLYDEK QQHIVYCSND LLGDLFGVPS FSVKEHRKIY
110 120 130 140 150
TMIYRNLVVV NQQESSDSGT SVSENRCHLE GGSDQKDLVQ ELQEEKPSSS
160 170 180 190 200
HLVSRPSTSS RRRAISETEE NSDELSGERQ RKRHKSDSIS LSFDESLALC
210 220 230 240 250
VIREICCERS SSSESTGTPS NPDLDAGVSE HSGDWLDQDS VSDQFSVEFE
260 270 280 290 300
VESLDSEDYS LSEEGQELSD EDDEVYQVTV YQAGESDTDS FEEDPEISLA
310 320 330 340 350
DYWKCTSCNE MNPPLPSHCN RCWALRENWL PEDKGKDKGE ISEKAKLENS
360 370 380 390 400
TQAEEGFDVP DCKKTIVNDS RESCVEENDD KITQASQSQE SEDYSQPSTS
410 420 430 440 450
SSIIYSSQED VKEFEREETQ DKEESVESSL PLNAIEPCVI CQGRPKNGCI
460 470 480 490
VHGKTGHLMA CFTCAKKLKK RNKPCPVCRQ PIQMIVLTYF P
Length:491
Mass (Da):55,233
Last modified:April 1, 1993 - v1
Checksum:iF37CE163876BC983
GO
Isoform Mdm2-A (identifier: Q00987-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     28-222: Missing.

Show »
Length:296
Mass (Da):33,140
Checksum:i9772439D74A4448B
GO
Isoform Mdm2-A1 (identifier: Q00987-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     28-222: Missing.
     275-300: Missing.

Show »
Length:270
Mass (Da):30,265
Checksum:iA3ED7CCFF670634E
GO
Isoform Mdm2-B (identifier: Q00987-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     28-300: Missing.

Show »
Length:218
Mass (Da):24,467
Checksum:iBB9C602F589EEC41
GO
Isoform Mdm2-C (identifier: Q00987-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     53-222: Missing.

Show »
Length:321
Mass (Da):35,980
Checksum:i4BD6213CA39D15C0
GO
Isoform Mdm2-D (identifier: Q00987-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     30-388: Missing.

Show »
Length:132
Mass (Da):14,689
Checksum:i770E9B66362CA97E
GO
Isoform Mdm2-E (identifier: Q00987-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     76-102: YCSNDLLGDLFGVPSFSVKEHRKIYTM → NDCANLFPLVDLSIRELYISNYITLGI
     103-491: Missing.

Show »
Length:102
Mass (Da):11,587
Checksum:i75E2B91B94C786C1
GO
Isoform Mdm2-alpha (identifier: Q00987-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-61: Missing.

Show »
Length:430
Mass (Da):48,488
Checksum:iC84E1F63E39E655D
GO
Isoform Mdm2-F (identifier: Q00987-9) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     53-97: Missing.

Note: Does not interact with p53/TP53.
Show »
Length:446
Mass (Da):49,899
Checksum:i4B630B50750EADFE
GO
Isoform Mdm2-G (identifier: Q00987-10) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     115-169: Missing.

Show »
Length:436
Mass (Da):49,249
Checksum:i3C8F55E98BC4203A
GO
Isoform 11 (identifier: Q00987-11) [UniParc]FASTAAdd to basket

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

Show »
Length:497
Mass (Da):55,991
Checksum:iCFEC32F36132D8FA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti17S → P in AAA82237 (PubMed:7651818).Curated1

Polymorphismi

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

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0032071 – 61Missing in isoform Mdm2-alpha. 1 PublicationAdd BLAST61
Alternative sequenceiVSP_0379971M → MVRSRQM in isoform 11. 1 Publication1
Alternative sequenceiVSP_00320928 – 300Missing in isoform Mdm2-B. 1 PublicationAdd BLAST273
Alternative sequenceiVSP_00320828 – 222Missing in isoform Mdm2-A and isoform Mdm2-A1. 2 PublicationsAdd BLAST195
Alternative sequenceiVSP_00321030 – 388Missing in isoform Mdm2-D. 1 PublicationAdd BLAST359
Alternative sequenceiVSP_00321153 – 222Missing in isoform Mdm2-C. 1 PublicationAdd BLAST170
Alternative sequenceiVSP_02257853 – 97Missing in isoform Mdm2-F. 1 PublicationAdd BLAST45
Alternative sequenceiVSP_00321276 – 102YCSND…KIYTM → NDCANLFPLVDLSIRELYIS NYITLGI in isoform Mdm2-E. 1 PublicationAdd BLAST27
Alternative sequenceiVSP_003213103 – 491Missing in isoform Mdm2-E. 1 PublicationAdd BLAST389
Alternative sequenceiVSP_022579115 – 169Missing in isoform Mdm2-G. 1 PublicationAdd BLAST55
Alternative sequenceiVSP_003214275 – 300Missing in isoform Mdm2-A1. 1 PublicationAdd BLAST26

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS61189.1. [Q00987-5]
CCDS8986.2. [Q00987-11]
PIRiS24354.
RefSeqiNP_001138811.1. NM_001145339.2.
NP_001265391.1. NM_001278462.1. [Q00987-5]
NP_002383.2. NM_002392.5. [Q00987-11]
XP_005268929.1. XM_005268872.4. [Q00987-1]
XP_006719462.1. XM_006719399.3. [Q00987-8]
UniGeneiHs.484551.
Hs.733536.

Genome annotation databases

EnsembliENST00000258149; ENSP00000258149; ENSG00000135679. [Q00987-11]
ENST00000299252; ENSP00000299252; ENSG00000135679. [Q00987-5]
ENST00000360430; ENSP00000353611; ENSG00000135679. [Q00987-2]
ENST00000393413; ENSP00000377065; ENSG00000135679. [Q00987-4]
GeneIDi4193.
KEGGihsa:4193.
UCSCiuc001sui.6. human. [Q00987-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs
Wikipedia

Mdm2 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS61189.1. [Q00987-5]
CCDS8986.2. [Q00987-11]
PIRiS24354.
RefSeqiNP_001138811.1. NM_001145339.2.
NP_001265391.1. NM_001278462.1. [Q00987-5]
NP_002383.2. NM_002392.5. [Q00987-11]
XP_005268929.1. XM_005268872.4. [Q00987-1]
XP_006719462.1. XM_006719399.3. [Q00987-8]
UniGeneiHs.484551.
Hs.733536.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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-ray1.70A224-232[»]
2FOPX-ray2.10B145-150[»]
2GV2X-ray1.80A17-125[»]
2HDPNMR-A/B429-491[»]
2LZGNMR-A1-125[»]
2M86NMR-B17-125[»]
2MPSNMR-A3-109[»]
2RUHNMR-A6-102[»]
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[»]
3MQSX-ray2.40D394-403[»]
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[»]
4OASX-ray1.70A/C/E17-111[»]
4OBAX-ray1.60A/B/C17-111[»]
4OCCX-ray1.80A/C/E17-111[»]
4ODEX-ray1.80A6-110[»]
4ODFX-ray2.20A6-110[»]
4OGNX-ray1.38A6-110[»]
4OGTX-ray1.54A6-110[»]
4OGVX-ray2.20A/B/C17-111[»]
4OQ3X-ray2.30A/B/C/D17-111[»]
4QO4X-ray1.70A17-111[»]
4QOCX-ray1.70A/C/E/G/I/K17-111[»]
4UD7X-ray1.60A/B/C/D17-125[»]
4UE1X-ray1.45A/B/C/D17-125[»]
4UMNX-ray1.99A/B6-125[»]
4WT2X-ray1.42A6-110[»]
4XXBX-ray2.40B290-437[»]
4ZFIX-ray2.00A/B/C/D18-113[»]
4ZGKX-ray2.00A/B18-114[»]
4ZYCX-ray1.95A/B/C17-111[»]
4ZYFX-ray1.80A17-111[»]
4ZYIX-ray1.67A17-111[»]
5AFGX-ray1.90A17-108[»]
5C5AX-ray1.15A/B20-111[»]
5HMHX-ray1.79A/B21-116[»]
5HMIX-ray1.74A/B18-116[»]
5HMKX-ray2.17A/B17-125[»]
5LN2X-ray1.58A17-111[»]
DisProtiDP00334.
ProteinModelPortaliQ00987.
SMRiQ00987.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110358. 426 interactors.
DIPiDIP-392N.
IntActiQ00987. 182 interactors.
MINTiMINT-101583.
STRINGi9606.ENSP00000417281.

Chemistry databases

BindingDBiQ00987.
ChEMBLiCHEMBL5023.

PTM databases

iPTMnetiQ00987.
PhosphoSitePlusiQ00987.

Polymorphism and mutation databases

DMDMi266516.

Proteomic databases

EPDiQ00987.
MaxQBiQ00987.
PaxDbiQ00987.
PeptideAtlasiQ00987.
PRIDEiQ00987.

Protocols and materials databases

DNASUi4193.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000258149; ENSP00000258149; ENSG00000135679. [Q00987-11]
ENST00000299252; ENSP00000299252; ENSG00000135679. [Q00987-5]
ENST00000360430; ENSP00000353611; ENSG00000135679. [Q00987-2]
ENST00000393413; ENSP00000377065; ENSG00000135679. [Q00987-4]
GeneIDi4193.
KEGGihsa:4193.
UCSCiuc001sui.6. human. [Q00987-1]

Organism-specific databases

CTDi4193.
DisGeNETi4193.
GeneCardsiMDM2.
HGNCiHGNC:6973. MDM2.
HPAiCAB000086.
CAB016303.
MalaCardsiMDM2.
MIMi164785. gene.
614401. phenotype.
neXtProtiNX_Q00987.
OpenTargetsiENSG00000135679.
Orphaneti99970. Dedifferentiated liposarcoma.
524. Li-Fraumeni syndrome.
99971. Well-differentiated liposarcoma.
PharmGKBiPA30718.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IGXG. Eukaryota.
ENOG41125MP. LUCA.
GeneTreeiENSGT00530000063539.
HOVERGENiHBG013472.
InParanoidiQ00987.
KOiK06643.
OMAiGELPCKL.
OrthoDBiEOG091G0FYK.
PhylomeDBiQ00987.
TreeFamiTF105306.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000135679-MONOMER.
BRENDAi6.3.2.19. 2681.
ReactomeiR-HSA-198323. AKT phosphorylates targets in the cytosol.
R-HSA-2559580. Oxidative Stress Induced Senescence.
R-HSA-2559585. Oncogene Induced Senescence.
R-HSA-3232118. SUMOylation of transcription factors.
R-HSA-399719. Trafficking of AMPA receptors.
R-HSA-5674400. Constitutive Signaling by AKT1 E17K in Cancer.
R-HSA-5689880. Ub-specific processing proteases.
R-HSA-6804756. Regulation of TP53 Activity through Phosphorylation.
R-HSA-6804757. Regulation of TP53 Degradation.
R-HSA-6804760. Regulation of TP53 Activity through Methylation.
R-HSA-69541. Stabilization of p53.
SignaLinkiQ00987.
SIGNORiQ00987.

Miscellaneous databases

ChiTaRSiMDM2. human.
EvolutionaryTraceiQ00987.
GeneWikiiMdm2.
GenomeRNAii4193.
PMAP-CutDBQ00987.
PROiQ00987.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000135679.
ExpressionAtlasiQ00987. baseline and differential.
GenevisibleiQ00987. HS.

Family and domain databases

Gene3Di1.10.245.10. 1 hit.
3.30.40.10. 1 hit.
InterProiIPR028340. 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]
PANTHERiPTHR13844:SF15. PTHR13844:SF15. 1 hit.
PfamiPF02201. SWIB. 1 hit.
PF00641. zf-RanBP. 1 hit.
[Graphical view]
PIRSFiPIRSF500700. MDM2. 1 hit.
PIRSF006748. p53_MDM_2/4. 1 hit.
SUPFAMiSSF47592. SSF47592. 2 hits.
SSF90209. SSF90209. 1 hit.
PROSITEiPS01358. ZF_RANBP2_1. 1 hit.
PS50199. ZF_RANBP2_2. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMDM2_HUMAN
AccessioniPrimary (citable) accession number: Q00987
Secondary accession number(s): A6NL51
, A8K2S6, Q13226, Q13297, Q13298, Q13299, Q13300, Q13301, Q53XW0, Q71TW9, Q8WYJ1, Q8WYJ2, Q9UGI3, Q9UMT8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: November 30, 2016
This is version 217 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Miscellaneous

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

Caution

A report observed N-glycosylation at Asn-349 (PubMed:19139490). However, as the protein is not extracellular, additional evidences are required to confirm this result.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.