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Protein

E3 ubiquitin-protein ligase Mdm2

Gene

MDM2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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). Ubiquitinates DLG4, leading to proteasomal degradation of DLG4 which is required for AMPA receptor endocytosis (By similarity).By similarity14 Publications

Miscellaneous

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

Caution

Was reported to interact with UBXN6 but the corresponding article has been retracted (PubMed:18768758).
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

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.1 Publication

Regions

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processHost-virus interaction, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

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-3232142 SUMOylation of ubiquitinylation proteins
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
R-HSA-8941858 Regulation of RUNX3 expression and activity
SignaLinkiQ00987
SIGNORiQ00987

Protein family/group databases

MoonDBiQ00987 Predicted

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase Mdm2 (EC:2.3.2.271 Publication)
Alternative name(s):
Double minute 2 protein
Short name:
Hdm2
Oncoprotein Mdm2
RING-type E3 ubiquitin transferase Mdm2Curated
p53-binding protein Mdm2
Gene namesi
Name:MDM2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000135679.21
HGNCiHGNC:6973 MDM2
MIMi164785 gene
neXtProtiNX_Q00987

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

MaxQBiQ00987
PaxDbiQ00987
PeptideAtlasiQ00987
PRIDEiQ00987
ProteomicsDBi57889
57890 [Q00987-10]
57891 [Q00987-11]
57892 [Q00987-2]
57893 [Q00987-3]
57894 [Q00987-4]
57895 [Q00987-5]
57896 [Q00987-6]
57897 [Q00987-7]
57898 [Q00987-8]
57899 [Q00987-9]

PTM databases

iPTMnetiQ00987
PhosphoSitePlusiQ00987

Miscellaneous databases

PMAP-CutDBiQ00987

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 Expressed in 207 organ(s), highest expression level in oviduct epithelium
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, 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 TBRG1. Interacts with the 5S RNP which is composed of the 5S RNA, RPL5 and RPL11; the interaction is direct, occurs in the nucleoplasm and negatively regulates MDM2-mediated TP53 ubiquitination and degradation (PubMed:15195100, PubMed:24120868). Interacts with ADGRB1; the interaction results in inhibition of MDM2-mediated ubiquitination and degradation of DLG4/PSD95, promoting DLG4 stability and regulating synaptic plasticity (By similarity). Interacts with RPL23A; this interaction may promote p53/TP53 polyubiquitination (PubMed:26203195).By similarity36 Publications
(Microbial infection) Interacts with herpes virus 8 protein v-IRF4.1 Publication
(Microbial infection) Interacts with and ubiquitinates HIV-1 Tat.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
itself4EBI-389668,EBI-389668
AKT1P317494EBI-389668,EBI-296087
ARP102752EBI-389668,EBI-608057
ARRB1P494073EBI-389668,EBI-743313
Arrb2P290674EBI-389668,EBI-1636616From Rattus norvegicus.
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 Rattus norvegicus.
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 Mus musculus.
GNL3Q9BVP23EBI-389668,EBI-641642
GNL3LQ9NVN88EBI-389668,EBI-746682
GORABQ5T7V86EBI-389668,EBI-3917143
GRK2P250984EBI-389668,EBI-3904795
HNRNPKP619782EBI-389668,EBI-304185
IGF1RP080692EBI-389668,EBI-475981
JMYQ8N9B52EBI-389668,EBI-866435
JUNP054123EBI-389668,EBI-852823
JUNDP175353EBI-389668,EBI-2682803
MDM4O1515110EBI-389668,EBI-398437
NCLP193388EBI-389668,EBI-346967
NPM1P067485EBI-389668,EBI-78579
Npm1Q619372EBI-389668,EBI-626362From Mus musculus.
NR0B2Q154664EBI-389668,EBI-3910729
NUMBP497576EBI-389668,EBI-915016
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
RB1P064005EBI-389668,EBI-491274
RFWD3Q6PCD55EBI-5279149,EBI-2129159
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
RRM2BQ7LG562EBI-389668,EBI-9009083
RRM2BQ7LG56-12EBI-389668,EBI-15741413
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
TP53P0463791EBI-389668,EBI-366083
TP73O153504EBI-389668,EBI-389606
UBCP0CG486EBI-389668,EBI-3390054
USP2O756044EBI-389668,EBI-743272
USP7Q9300927EBI-389668,EBI-302474
vIRF-4Q2HR732EBI-389668,EBI-9001898From Human herpesvirus 8 type P (isolate GK18).
Xpo1Q6P5F94EBI-389668,EBI-2550236From Mus musculus.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110358, 474 interactors
CORUMiQ00987
DIPiDIP-392N
ELMiQ00987
IntActiQ00987, 188 interactors
MINTiQ00987
STRINGi9606.ENSP00000417281

Chemistry databases

BindingDBiQ00987

Structurei

Secondary structure

1491
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

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
InterProiView protein in InterPro
IPR028340 Mdm2
IPR015459 MDM2_E3_ligase
IPR016495 p53_neg-reg_MDM_2/4
IPR036885 SWIB_MDM2_dom_sf
IPR003121 SWIB_MDM2_domain
IPR001876 Znf_RanBP2
IPR036443 Znf_RanBP2_sf
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
PANTHERiPTHR13844:SF15 PTHR13844:SF15, 1 hit
PfamiView protein in Pfam
PF02201 SWIB, 1 hit
PF00641 zf-RanBP, 1 hit
PIRSFiPIRSF500700 MDM2, 1 hit
PIRSF006748 p53_MDM_2/4, 1 hit
SUPFAMiSSF47592 SSF47592, 2 hits
SSF90209 SSF90209, 1 hit
PROSITEiView protein in PROSITE
PS01358 ZF_RANBP2_1, 1 hit
PS50199 ZF_RANBP2_2, 1 hit
PS50089 ZF_RING_2, 1 hit

Sequences (11+)i

Sequence statusi: Complete.

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

This entry has 11 described isoforms and 21 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 21 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
J3KN53J3KN53_HUMAN
E3 ubiquitin-protein ligase Mdm2
MDM2
466Annotation score:
A7UKY0A7UKY0_HUMAN
E3 ubiquitin-protein ligase Mdm2
MDM2 mdm2
257Annotation score:
A7UKX8A7UKX8_HUMAN
E3 ubiquitin-protein ligase Mdm2
MDM2 mdm2
256Annotation score:
G3XA89G3XA89_HUMAN
E3 ubiquitin-protein ligase Mdm2
MDM2 hCG_2014981
442Annotation score:
E7EPE2E7EPE2_HUMAN
E3 ubiquitin-protein ligase Mdm2
MDM2
229Annotation score:
Q9H4C5Q9H4C5_HUMAN
E3 ubiquitin-protein ligase Mdm2
MDM2
243Annotation score:
Q8TE47Q8TE47_HUMAN
E3 ubiquitin-protein ligase Mdm2
MDM2 MDM2 isoform KB9
243Annotation score:
A0A0C4DFR5A0A0C4DFR5_HUMAN
E3 ubiquitin-protein ligase Mdm2
MDM2
265Annotation score:
Q9H4C3Q9H4C3_HUMAN
E3 ubiquitin-protein ligase Mdm2
MDM2
130Annotation score:
F5H4Q8F5H4Q8_HUMAN
E3 ubiquitin-protein ligase Mdm2
MDM2
170Annotation score:
There are more potential isoformsShow all

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]
ENST00000539479; ENSP00000444430; ENSG00000135679 [Q00987-1]
GeneIDi4193
KEGGihsa:4193
UCSCiuc001sui.6 human [Q00987-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

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[»]
5J7FX-ray2.00A/B/C/D1-125[»]
5J7GX-ray1.85A/B/C/D18-125[»]
5LAVX-ray1.73A19-111[»]
5LAWX-ray1.64A18-111[»]
5LAYX-ray2.71A/B/C/D/E/F17-111[»]
5LAZX-ray1.66A18-111[»]
5LN2X-ray1.58A17-111[»]
5MNJX-ray2.16C/G428-491[»]
5OC8X-ray1.56A17-111[»]
5SWKX-ray1.92A/B1-150[»]
5TRFX-ray2.10A/B/C/D/E10-118[»]
5UMMX-ray1.65A/C25-109[»]
5VK0X-ray1.80A/C/E/G/I/K/M/O/Q/S/U/W25-109[»]
5WTSX-ray3.00B6-125[»]
5XXKX-ray1.66A/B6-125[»]
5Z02X-ray1.35A24-112[»]
5ZXFX-ray1.25A24-110[»]
DisProtiDP00334
ProteinModelPortaliQ00987
SMRiQ00987
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110358, 474 interactors
CORUMiQ00987
DIPiDIP-392N
ELMiQ00987
IntActiQ00987, 188 interactors
MINTiQ00987
STRINGi9606.ENSP00000417281

Chemistry databases

BindingDBiQ00987
ChEMBLiCHEMBL5023

Protein family/group databases

MoonDBiQ00987 Predicted

PTM databases

iPTMnetiQ00987
PhosphoSitePlusiQ00987

Polymorphism and mutation databases

DMDMi266516

Proteomic databases

MaxQBiQ00987
PaxDbiQ00987
PeptideAtlasiQ00987
PRIDEiQ00987
ProteomicsDBi57889
57890 [Q00987-10]
57891 [Q00987-11]
57892 [Q00987-2]
57893 [Q00987-3]
57894 [Q00987-4]
57895 [Q00987-5]
57896 [Q00987-6]
57897 [Q00987-7]
57898 [Q00987-8]
57899 [Q00987-9]

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]
ENST00000539479; ENSP00000444430; ENSG00000135679 [Q00987-1]
GeneIDi4193
KEGGihsa:4193
UCSCiuc001sui.6 human [Q00987-1]

Organism-specific databases

CTDi4193
DisGeNETi4193
EuPathDBiHostDB:ENSG00000135679.21
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

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-3232142 SUMOylation of ubiquitinylation proteins
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
R-HSA-8941858 Regulation of RUNX3 expression and activity
SignaLinkiQ00987
SIGNORiQ00987

Miscellaneous databases

ChiTaRSiMDM2 human
EvolutionaryTraceiQ00987
GeneWikiiMdm2
GenomeRNAii4193
PMAP-CutDBiQ00987
PROiPR:Q00987
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000135679 Expressed in 207 organ(s), highest expression level in oviduct epithelium
ExpressionAtlasiQ00987 baseline and differential
GenevisibleiQ00987 HS

Family and domain databases

Gene3Di1.10.245.10, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR028340 Mdm2
IPR015459 MDM2_E3_ligase
IPR016495 p53_neg-reg_MDM_2/4
IPR036885 SWIB_MDM2_dom_sf
IPR003121 SWIB_MDM2_domain
IPR001876 Znf_RanBP2
IPR036443 Znf_RanBP2_sf
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
PANTHERiPTHR13844:SF15 PTHR13844:SF15, 1 hit
PfamiView protein in Pfam
PF02201 SWIB, 1 hit
PF00641 zf-RanBP, 1 hit
PIRSFiPIRSF500700 MDM2, 1 hit
PIRSF006748 p53_MDM_2/4, 1 hit
SUPFAMiSSF47592 SSF47592, 2 hits
SSF90209 SSF90209, 1 hit
PROSITEiView protein in PROSITE
PS01358 ZF_RANBP2_1, 1 hit
PS50199 ZF_RANBP2_2, 1 hit
PS50089 ZF_RING_2, 1 hit
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 historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: October 10, 2018
This is version 238 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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