MDM2
entrez
4193
canonical
uniprot
Q00987
canonical
ensembl
ENSG00000135679
resolver
ensp
ENSP00000258148
resolver
ensp
ENSP00000258149
resolver
ensp
ENSP00000299252
resolver
ensp
ENSP00000377064
resolver
ensp
ENSP00000377067
resolver
ensp
ENSP00000444430
resolver
ensp
ENSP00000621865
resolver
enst
ENST00000258148
resolver
enst
ENST00000393415
resolver
genesymbol
MDM2
resolver
genesymbol
mdm2
resolver
hgnc
HGNC:6973
resolver
uniprot
A0A0A6YYM9
resolver
uniprot
A0A0A8KB75
resolver
uniprot
A0A0K0K1B6
resolver
uniprot
A0ACM8QE14
resolver
uniprot
A6NL51
resolver
uniprot
A7UKX7
resolver
uniprot
A7UKX8
resolver
uniprot
A7UKX9
resolver
uniprot
A8K2S6
resolver
uniprot
E7EPE3
resolver
uniprot
F6RKA8
resolver
uniprot
G3XA89
resolver
uniprot
Q13226
resolver
uniprot
Q13297
resolver
uniprot
Q13298
resolver
uniprot
Q13299
resolver
uniprot
Q13300
resolver
uniprot
Q13301
resolver
uniprot
Q53XW0
resolver
uniprot
Q71TW9
resolver
uniprot
Q8WYJ1
resolver
uniprot
Q8WYJ2
resolver
uniprot
Q96DS0
resolver
uniprot
Q9UGI3
resolver
uniprot
Q9UMT8
resolver
uniprot_entry
A0A0A8KB75_HUMAN
resolver
uniprot_entry
A0ACM8QE14_HUMAN
resolver
uniprot_entry
A7UKX7_HUMAN
resolver
uniprot_entry
A7UKX8_HUMAN
resolver
uniprot_entry
A7UKX9_HUMAN
resolver
uniprot_entry
G3XA89_HUMAN
resolver
uniprot_entry
MDM2_HUMAN
resolver
uniprot_entry
Q96DS0_HUMAN
resolver
uniprot_sec
A0A0A6YYM9
resolver
uniprot_sec
A0A0K0K1B6
resolver
uniprot_sec
A6NL51
resolver
uniprot_sec
A8K2S6
resolver
uniprot_sec
E7EPE3
resolver
uniprot_sec
F6RKA8
resolver
uniprot_sec
Q13226
resolver
uniprot_sec
Q13297
resolver
uniprot_sec
Q13298
resolver
uniprot_sec
Q13299
resolver
uniprot_sec
Q13300
resolver
uniprot_sec
Q13301
resolver
uniprot_sec
Q53XW0
resolver
uniprot_sec
Q71TW9
resolver
uniprot_sec
Q8WYJ1
resolver
uniprot_sec
Q8WYJ2
resolver
uniprot_sec
Q9UGI3
resolver
uniprot_sec
Q9UMT8
resolver
amino_acid_sequence
MCNTNMSVPTDGAVTTSQIPASEQETLVRPKPLLLKLLKSVGAQKDTYTMKEVLFYLGQYIMTKRLYDEKQQHIVYCSNDLLGDLFGVPSFSVKEHRKIYTMIYRNLVVVNQQESSDSGTSVSENRCHLEGGSDQKDLVQELQEEKPSSSHLVSRPSTSSRRRAISETEENSDELSGERQRKRHKSDSISLSFDESLALCVIREICCERSSSSESTGTPSNPDLDAGVSEHSGDWLDQDSVSDQFSVEFEVESLDSEDYSLSEEGQELSDEDDEVYQVTVYQAGESDTDSFEEDPEISLADYWKCTSCNEMNPPLPSHCNRCWALRENWLPEDKGKDKGEISEKAKLENSTQAEEGFDVPDCKKTIVNDSRESCVEENDDKITQASQSQESEDYSQPSTSSSIIYSSQEDVKEFEREETQDKEESVESSLPLNAIEPCVICQGRPKNGCIVHGKTGHLMACFTCAKKLKKRNKPCPVCRQPIQMIVLTYFP
uniprot
proteins
disease_involvement
DISEASE: Note=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.; DISEASE: Lessel-Kubisch syndrome (LSKB) [MIM:618681]: An autosomal recessive progeroid syndrome characterized by short stature, pinched facial features, prematurely gray hair, scleroderma-like skin changes, small kidneys and consecutive kidney failure, followed by severe arterial hypertension. {ECO:0000269|PubMed:28846075}. Note=The disease may be caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.3.2.27
uniprot
proteins
function
FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome (PubMed:29681526, PubMed:21317885). 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 a 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). Negatively regulates NDUFS1, leading to decreased mitochondrial respiration, marked oxidative stress, and commitment to the mitochondrial pathway of apoptosis (PubMed:30879903). Binds NDUFS1 leading to its cytosolic retention rather than mitochondrial localization resulting in decreased supercomplex assembly (interactions between complex I and complex III), decreased complex I activity, ROS production, and apoptosis (PubMed:30879903). {ECO:0000250|UniProtKB:P23804, ECO:0000269|PubMed:12821780, ECO:0000269|PubMed:15053880, ECO:0000269|PubMed:15195100, ECO:0000269|PubMed:15632057, ECO:0000269|PubMed:16337594, ECO:0000269|PubMed:17290220, ECO:0000269|PubMed:19098711, ECO:0000269|PubMed:19219073, ECO:0000269|PubMed:19837670, ECO:0000269|PubMed:19965871, ECO:0000269|PubMed:20173098, ECO:0000269|PubMed:20385133, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:21317885, ECO:0000269|PubMed:22128911, ECO:0000269|PubMed:29681526, ECO:0000269|PubMed:30879903}.
uniprot
proteins
mass_dalton
55233
uniprot
proteins
mutagenesis
MUTAGEN 58; /note="G->A: No effect on its ability to induce apoptosis."; /evidence="ECO:0000269|PubMed:30879903"; MUTAGEN 305; /note="C->S: No loss of ubiquitin ligase E3 activity."; /evidence="ECO:0000269|PubMed:10722742"; MUTAGEN 374; /note="C->T: No loss of ubiquitin ligase E3 activity."; /evidence="ECO:0000269|PubMed:10722742"; MUTAGEN 386; /note="S->A: In MDM2-6A mutant; abolished phosphorylation by ATM and ubiquitination by the SCF(FBXO31) complex; when associated with A-395, A-407, A-419, A-425 and A-429."; /evidence="ECO:0000269|PubMed:19816404"; MUTAGEN 395; /note="S->A: In MDM2-6A mutant; abolished phosphorylation by ATM and ubiquitination by the SCF(FBXO31) complex; when associated with A-386, A-407, A-419, A-425 and A-429."; /evidence="ECO:0000269|PubMed:19816404"; MUTAGEN 407; /note="S->A: In MDM2-6A mutant; abolished phosphorylation by ATM and ubiquitination by the SCF(FBXO31) complex; when associated with A-386, A-395, A-419, A-425 and A-429."; /evidence="ECO:0000269|PubMed:19816404"; MUTAGEN 419; /note="T->A: In MDM2-6A mutant; abolished phosphorylation by ATM and ubiquitination by the SCF(FBXO31) complex; when associated with A-386, A-395, A-407, A-425 and A-429."; /evidence="ECO:0000269|PubMed:19816404"; MUTAGEN 425; /note="S->A: In MDM2-6A mutant; abolished phosphorylation by ATM and ubiquitination by the SCF(FBXO31) complex; when associated with A-386, A-395, A-407, A-419 and A-429."; /evidence="ECO:0000269|PubMed:19816404"; MUTAGEN 429; /note="S->A: In MDM2-6A mutant; abolished phosphorylation by ATM and ubiquitination by the SCF(FBXO31) complex; when associated with A-386, A-395, A-407, A-419 and A-425."; /evidence="ECO:0000269|PubMed:19816404"; MUTAGEN 438; /note="C->L: No loss of ubiquitin ligase E3 activity."; /evidence="ECO:0000269|PubMed:10722742"; MUTAGEN 441; /note="C->G: Fails to interact with MDM4."; /evidence="ECO:0000269|PubMed:10608892"; MUTAGEN 449; /note="C->A: Loss of ubiquitin ligase E3 activity."; /evidence="ECO:0000269|PubMed:10723139"; MUTAGEN 449; /note="C->S: No substantial decrease of ubiquitin ligase E3 activity."; /evidence="ECO:0000269|PubMed:10723139"; MUTAGEN 452; /note="H->A: Loss of ubiquitin ligase E3 activity."; /evidence="ECO:0000269|PubMed:10722742"; MUTAGEN 455; /note="T->A: Significant decrease of ubiquitin ligase E3 activity."; /evidence="ECO:0000269|PubMed:10722742"; MUTAGEN 457; /note="H->S: Loss of ubiquitin ligase E3 activity."; /evidence="ECO:0000269|PubMed:10722742"; MUTAGEN 461; /note="C->S: Loss of ubiquitin ligase E3 activity."; /evidence="ECO:0000269|PubMed:10722742"; MUTAGEN 464; /note="C->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. No effect on its ability to induce apoptosis."; /evidence="ECO:0000269|PubMed:15632057, ECO:0000269|PubMed:16479015, ECO:0000269|PubMed:19219073, ECO:0000269|PubMed:20173098, ECO:0000269|PubMed:30879903, ECO:0000269|PubMed:9450543"; MUTAGEN 475; /note="C->G: Loss of ubiquitin ligase E3 activity."; /evidence="ECO:0000269|PubMed:10722742"; MUTAGEN 478; /note="C->R: Fails to interact with MDM4."; /evidence="ECO:0000269|PubMed:10608892"; MUTAGEN 478; /note="C->S: Loss of ubiquitin ligase E3 activity."; /evidence="ECO:0000269|PubMed:10608892
uniprot
proteins
post_translational_modification
PTM: Phosphorylation on Ser-166 by SGK1 activates ubiquitination of p53/TP53 (PubMed:19756449). Phosphorylated at multiple sites near the RING domain by ATM upon DNA damage; this promotes its ubiquitination and degradation, preventing p53/TP53 degradation (PubMed:10611322, PubMed:12167711, PubMed:18382127, PubMed:19816404, PubMed:26124108). {ECO:0000269|PubMed:10611322, ECO:0000269|PubMed:12167711, ECO:0000269|PubMed:18382127, ECO:0000269|PubMed:19756449, ECO:0000269|PubMed:19816404, ECO:0000269|PubMed:26124108}.; PTM: Autoubiquitination leads to proteasomal degradation; resulting in p53/TP53 activation it may be regulated by SFN (PubMed:18382127, PubMed:30879903). Also ubiquitinated by TRIM13 (PubMed:21333377). ATM-phosphorylated MDM2 is ubiquitinated by the SCF(FBXO31) complex in response to genotoxic stress, promoting its degradation and p53/TP53-mediated DNA damage response (PubMed:26124108). Deubiquitinated by USP2 leads to its accumulation and increases deubiquitination and degradation of p53/TP53 (PubMed:17290220). Deubiquitinated by USP7 leading to its stabilization (PubMed:15053880). {ECO:0000269|PubMed:15053880, ECO:0000269|PubMed:17290220, ECO:0000269|PubMed:18382127, ECO:0000269|PubMed:21333377, ECO:0000269|PubMed:26124108, ECO:0000269|PubMed:30879903}.
uniprot
proteins
protein_family
MDM2/MDM4 family
uniprot
proteins
pubmed
10597303
uniprot
proteins
pubmed
10608892
uniprot
proteins
pubmed
10611322
uniprot
proteins
pubmed
10707090
uniprot
proteins
pubmed
10722742
uniprot
proteins
pubmed
10723139
uniprot
proteins
pubmed
11087894
uniprot
proteins
pubmed
11351297
uniprot
proteins
pubmed
12167711
uniprot
proteins
pubmed
12821780
uniprot
proteins
pubmed
12883554
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15053880
uniprot
proteins
pubmed
15195100
uniprot
proteins
pubmed
15313915
uniprot
proteins
pubmed
15315825
uniprot
proteins
pubmed
15364927
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15550242
uniprot
proteins
pubmed
15632057
uniprot
proteins
pubmed
15878855
uniprot
proteins
pubmed
1614537
uniprot
proteins
pubmed
16173922
uniprot
proteins
pubmed
16219768
uniprot
proteins
pubmed
16337594
uniprot
proteins
pubmed
16402859
uniprot
proteins
pubmed
16474402
uniprot
proteins
pubmed
16479015
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
16845383
uniprot
proteins
pubmed
17003841
uniprot
proteins
pubmed
17110379
uniprot
proteins
pubmed
17290220
uniprot
proteins
pubmed
17460193
uniprot
proteins
pubmed
17470788
uniprot
proteins
pubmed
18382127
uniprot
proteins
pubmed
18566590
uniprot
proteins
pubmed
19098711
uniprot
proteins
pubmed
19139490
uniprot
proteins
pubmed
19219073
uniprot
proteins
pubmed
19369353
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19756449
uniprot
proteins
pubmed
19816404
uniprot
proteins
pubmed
19837670
uniprot
proteins
pubmed
19838211
uniprot
proteins
pubmed
19965871
uniprot
proteins
pubmed
20173098
uniprot
proteins
pubmed
20385133
uniprot
proteins
pubmed
20858735
uniprot
proteins
pubmed
21317885
uniprot
proteins
pubmed
21333377
uniprot
proteins
pubmed
22128911
uniprot
proteins
pubmed
22869143
uniprot
proteins
pubmed
22914926
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24120868
uniprot
proteins
pubmed
25384516
uniprot
proteins
pubmed
26124108
uniprot
proteins
pubmed
26203195
uniprot
proteins
pubmed
28846075
uniprot
proteins
pubmed
29681526
uniprot
proteins
pubmed
30879903
uniprot
proteins
pubmed
36897777
uniprot
proteins
pubmed
37291423
uniprot
proteins
pubmed
7651818
uniprot
proteins
pubmed
7689721
uniprot
proteins
pubmed
8705862
uniprot
proteins
pubmed
8875929
uniprot
proteins
pubmed
9270029
uniprot
proteins
pubmed
9450543
uniprot
proteins
sequence_length
491
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus, nucleoplasm {ECO:0000269|PubMed:10707090}. Cytoplasm {ECO:0000269|PubMed:30879903, ECO:0000269|PubMed:36897777}. Nucleus, nucleolus {ECO:0000269|PubMed:10707090}. Nucleus {ECO:0000269|PubMed:30879903, ECO:0000269|PubMed:36897777}. 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.
uniprot
proteins