Q00987 (MDM2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

MDM2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	491 AA.
Sequence status	Complete.
Protein existence	Evidence 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 an 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.43 Ref.45 Ref.47 Ref.48 Ref.49 Ref.50 Ref.52
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. 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.43 Ref.45 Ref.47 Ref.48 Ref.49 Ref.50 Ref.51 Ref.52 Ref.53 Ref.54 Ref.56 Ref.57
Subcellular location	Nucleus › nucleoplasm. Cytoplasm. Nucleus › nucleolus. 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. Ref.14 Ref.28 Ref.34 Ref.40 Ref.49 Ref.54
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. Auto-ubiquitinated; which leads to proteasomal degradation. 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.

Ontologies

Keywords
Biological process	Host-virus interaction Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Disease	Proto-oncogene
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Inferred from mutant phenotype PubMed 21726810. Source: UniProtKB cellular response to UV-C Inferred from electronic annotation. Source: Compara cellular response to acid Inferred from electronic annotation. Source: Compara cellular response to alkaloid Inferred from electronic annotation. Source: Compara cellular response to antibiotic Inferred from electronic annotation. Source: Compara cellular response to estrogen stimulus Inferred from electronic annotation. Source: Compara cellular response to hydrogen peroxide Inferred from electronic annotation. Source: Compara cellular response to hypoxia Inferred from expression pattern PubMed 20810912. Source: UniProtKB cellular response to peptide hormone stimulus Inferred from electronic annotation. Source: Compara cellular response to vitamin B1 Inferred from electronic annotation. Source: Compara 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: Compara 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: Compara negative regulation of protein processing Inferred from electronic annotation. Source: Compara 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: Compara 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: Compara 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 stimulus Inferred from electronic annotation. Source: Compara response to cocaine Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to ether Inferred from electronic annotation. Source: Compara response to iron ion Inferred from electronic annotation. Source: Compara response to magnesium ion Inferred from electronic annotation. Source: Compara response to morphine Inferred from electronic annotation. Source: Compara synaptic transmission Traceable author statement. Source: Reactome traversing start control point of mitotic cell cycle Inferred from electronic annotation. Source: Compara virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome endocytic vesicle membrane Traceable author statement. Source: Reactome nucleolus Inferred from direct assay Ref.19Ref.54. 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: Compara
Molecular_function	ubiquitin-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
itself		2	EBI-389668,EBI-389668
AR	P10275	2	EBI-389668,EBI-608057
BTRC	Q9Y297	9	EBI-389668,EBI-307461
CDKN2A	Q8N726	3	EBI-389668,EBI-625922
CSNK1A1	P48729	3	EBI-389668,EBI-1383726
CSNK1A1	P48729-2	3	EBI-389668,EBI-2040168
CSNK1D	P48730	6	EBI-389668,EBI-751621
Csnk1d	Q06486	2	EBI-389668,EBI-2910316	From a different organism.
CSNK1E	P49674	3	EBI-389668,EBI-749343
CUL1	Q13616	3	EBI-389668,EBI-359390
DAXX	Q9UER7	14	EBI-389668,EBI-77321
EEF1A1	P68104	6	EBI-389668,EBI-352162
ESR1	P03372	2	EBI-389668,EBI-78473
EZR	P15311	3	EBI-389668,EBI-1056902
FBXW11	Q9UKB1	4	EBI-389668,EBI-355189
GNL3	Q9BVP2	3	EBI-389668,EBI-641642
GNL3L	Q9NVN8	8	EBI-389668,EBI-746682
JMY	Q8N9B5	2	EBI-389668,EBI-866435
JUN	P05412	3	EBI-389668,EBI-852823
JUND	P17535	3	EBI-389668,EBI-2682803
MDM4	O15151	6	EBI-389668,EBI-398437
NCL	P19338	2	EBI-389668,EBI-346967
NPM1	P06748	3	EBI-389668,EBI-78579
Npm1	Q61937	2	EBI-389668,EBI-626362	From a different organism.
PML	P29590	6	EBI-389668,EBI-295890
PML	P29590-5	6	EBI-389668,EBI-304008
PPM1D	O15297	4	EBI-389668,EBI-1551512
RB1	P06400	3	EBI-389668,EBI-491274
RPL11	P62913	6	EBI-389668,EBI-354380
RPS27	P42677	5	EBI-389668,EBI-356336
RPS27L	Q71UM5	6	EBI-389668,EBI-355126
RPS7	P62081	15	EBI-389668,EBI-354360
RYR2	Q92736	2	EBI-389668,EBI-1170425
SET	Q01105	2	EBI-389668,EBI-1053182
TP53	P04637	29	EBI-389668,EBI-366083
USP7	Q93009	13	EBI-389668,EBI-302474

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 491

491

E3 ubiquitin-protein ligase Mdm2

PRO_0000157332

Regions

Domain

27 – 107

81

SWIB

Zinc finger

299 – 328

30

RanBP2-type

Zinc finger

438 – 479

42

RING-type

Region

1 – 110

110

Necessary for interaction with USP2

Region

150 – 230

81

Interaction with PYHIN1

Region

170 – 306

137

Interaction with MTBP By similarity

Region

210 – 304

95

ARF-binding

Region

223 – 232

10

Interaction with USP7

Region

242 – 331

90

Region II

Region

276 – 491

216

Necessary for interaction with USP2

Motif

179 – 185

7

Nuclear localization signal Potential

Motif

190 – 202

13

Nuclear export signal

Motif

466 – 473

8

Nucleolar localization signal Potential

Compositional bias

210 – 215

6

Poly-Ser

Compositional bias

243 – 301

59

Asp/Glu-rich (acidic)

Amino acid modifications

Modified residue

166

1

Phosphoserine; by SGK1 Ref.44 Ref.46

Modified residue

240

1

Phosphoserine Ref.21

Modified residue

242

1

Phosphoserine Ref.21

Modified residue

246

1

Phosphoserine Ref.21

Modified residue

260

1

Phosphoserine Ref.21

Modified residue

262

1

Phosphoserine Ref.21

Modified residue

386

1

Phosphoserine; by ATM

Modified residue

395

1

Phosphoserine; by ATM

Modified residue

407

1

Phosphoserine; by ATM

Modified residue

419

1

Phosphothreonine; by ATM

Modified residue

425

1

Phosphoserine; by ATM

Modified residue

429

1

Phosphoserine; by ATM

Natural variations

Alternative sequence

1 – 61

61

Missing in isoform Mdm2-alpha.

VSP_003207

Alternative sequence

1

1

M → MVRSRQM in isoform 11.

VSP_037997

Alternative sequence

28 – 300

273

Missing in isoform Mdm2-B.

VSP_003209

Alternative sequence

28 – 222

195

Missing in isoform Mdm2-A and isoform Mdm2-A1.

VSP_003208

Alternative sequence

30 – 388

359

Missing in isoform Mdm2-D.

VSP_003210

Alternative sequence

53 – 222

170

Missing in isoform Mdm2-C.

VSP_003211

Alternative sequence

53 – 97

45

Missing in isoform Mdm2-F.

VSP_022578

Alternative sequence

76 – 102

27

YCSND…KIYTM → NDCANLFPLVDLSIRELYIS NYITLGI in isoform Mdm2-E.

VSP_003212

Alternative sequence

103 – 491

389

Missing in isoform Mdm2-E.

VSP_003213

Alternative sequence

115 – 169

55

Missing in isoform Mdm2-G.

VSP_022579

Alternative sequence

275 – 300

26

Missing in isoform Mdm2-A1.

VSP_003214

Experimental info

Mutagenesis

305

1

C → S: No loss of ubiquitin ligase E3 activity.

Mutagenesis

374

1

C → T: No loss of ubiquitin ligase E3 activity.

Mutagenesis

438

1

C → L: No loss of ubiquitin ligase E3 activity.

Mutagenesis

441

1

C → G: Fails to interact with MDM4. Ref.16

Mutagenesis

449

1

C → A: Loss of ubiquitin ligase E3 activity. Ref.20

Mutagenesis

449

1

C → S: No substantial decrease of ubiquitin ligase E3 activity. Ref.20

Mutagenesis

452

1

H → A: Loss of ubiquitin ligase E3 activity.

Mutagenesis

455

1

T → A: Significant decrease of ubiquitin ligase E3 activity.

Mutagenesis

457

1

H → S: Loss of ubiquitin ligase E3 activity.

Mutagenesis

461

1

C → S: Loss of ubiquitin ligase E3 activity.

Mutagenesis

464

1

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. Ref.15 Ref.32 Ref.33 Ref.45 Ref.50

Mutagenesis

475

1

C → G: Loss of ubiquitin ligase E3 activity.

Mutagenesis

478

1

C → R: Fails to interact with MDM4. Ref.16

Mutagenesis

478

1

C → S: Loss of ubiquitin ligase E3 activity. Ref.16

Sequence conflict

17

1

S → P in AAA82237. Ref.10

Secondary structure

1

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491

Helix Strand Turn

Details...

Beta strand

8 – 16

9

Beta strand

17 – 19

3

Helix

21 – 25

5

Beta strand

27 – 30

4

Helix

32 – 40

9

Beta strand

45 – 49

5

Helix

50 – 64

15

Beta strand

71 – 76

6

Beta strand

78 – 80

3

Helix

81 – 86

6

Beta strand

87 – 92

6

Helix

96 – 104

9

Beta strand

107 – 109

3

Beta strand

295 – 297

3

Helix

299 – 301

3

Turn

306 – 308

3

Beta strand

314 – 318

5

Turn

320 – 322

3

Helix

433 – 435

3

Turn

439 – 441

3

Beta strand

442 – 444

3

Beta strand

448 – 452

5

Beta strand

455 – 460

6

Helix

462 – 470

9

Turn

476 – 478

3

Beta strand

484 – 489

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform Mdm2 [UniParc]. Last modified April 1, 1993. Version 1. Checksum: F37CE163876BC983	FASTA	491	55,233
	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
	Isoform Mdm2-A [UniParc]. Checksum: 9772439D74A4448B	FASTA	296	33,140
	10 20 30 40 50 60 MCNTNMSVPT DGAVTTSQIP ASEQETLDLD AGVSEHSGDW LDQDSVSDQF SVEFEVESLD 70 80 90 100 110 120 SEDYSLSEEG QELSDEDDEV YQVTVYQAGE SDTDSFEEDP EISLADYWKC TSCNEMNPPL 130 140 150 160 170 180 PSHCNRCWAL RENWLPEDKG KDKGEISEKA KLENSTQAEE GFDVPDCKKT IVNDSRESCV 190 200 210 220 230 240 EENDDKITQA SQSQESEDYS QPSTSSSIIY SSQEDVKEFE REETQDKEES VESSLPLNAI 250 260 270 280 290 EPCVICQGRP KNGCIVHGKT GHLMACFTCA KKLKKRNKPC PVCRQPIQMI VLTYFP
	Isoform Mdm2-A1 [UniParc]. Checksum: A3ED7CCFF670634E	FASTA	270	30,265
	10 20 30 40 50 60 MCNTNMSVPT DGAVTTSQIP ASEQETLDLD AGVSEHSGDW LDQDSVSDQF SVEFEVESLD 70 80 90 100 110 120 SEDYSLSEEG QELSDEDDED YWKCTSCNEM NPPLPSHCNR CWALRENWLP EDKGKDKGEI 130 140 150 160 170 180 SEKAKLENST QAEEGFDVPD CKKTIVNDSR ESCVEENDDK ITQASQSQES EDYSQPSTSS 190 200 210 220 230 240 SIIYSSQEDV KEFEREETQD KEESVESSLP LNAIEPCVIC QGRPKNGCIV HGKTGHLMAC 250 260 270 FTCAKKLKKR NKPCPVCRQP IQMIVLTYFP
	Isoform Mdm2-B [UniParc]. Checksum: BB9C602F589EEC41	FASTA	218	24,467
	10 20 30 40 50 60 MCNTNMSVPT DGAVTTSQIP ASEQETLDYW KCTSCNEMNP PLPSHCNRCW ALRENWLPED 70 80 90 100 110 120 KGKDKGEISE KAKLENSTQA EEGFDVPDCK KTIVNDSRES CVEENDDKIT QASQSQESED 130 140 150 160 170 180 YSQPSTSSSI IYSSQEDVKE FEREETQDKE ESVESSLPLN AIEPCVICQG RPKNGCIVHG 190 200 210 KTGHLMACFT CAKKLKKRNK PCPVCRQPIQ MIVLTYFP
	Isoform Mdm2-C [UniParc]. Checksum: 4BD6213CA39D15C0	FASTA	321	35,980
	10 20 30 40 50 60 MCNTNMSVPT DGAVTTSQIP ASEQETLVRP KPLLLKLLKS VGAQKDTYTM KEDLDAGVSE 70 80 90 100 110 120 HSGDWLDQDS VSDQFSVEFE VESLDSEDYS LSEEGQELSD EDDEVYQVTV YQAGESDTDS 130 140 150 160 170 180 FEEDPEISLA DYWKCTSCNE MNPPLPSHCN RCWALRENWL PEDKGKDKGE ISEKAKLENS 190 200 210 220 230 240 TQAEEGFDVP DCKKTIVNDS RESCVEENDD KITQASQSQE SEDYSQPSTS SSIIYSSQED 250 260 270 280 290 300 VKEFEREETQ DKEESVESSL PLNAIEPCVI CQGRPKNGCI VHGKTGHLMA CFTCAKKLKK 310 320 RNKPCPVCRQ PIQMIVLTYF P
	Isoform Mdm2-D [UniParc]. Checksum: 770E9B66362CA97E	FASTA	132	14,689
	10 20 30 40 50 60 MCNTNMSVPT DGAVTTSQIP ASEQETLVRQ ESEDYSQPST SSSIIYSSQE DVKEFEREET 70 80 90 100 110 120 QDKEESVESS LPLNAIEPCV ICQGRPKNGC IVHGKTGHLM ACFTCAKKLK KRNKPCPVCR 130 QPIQMIVLTY FP
	Isoform Mdm2-E [UniParc]. Checksum: 75E2B91B94C786C1	FASTA	102	11,587
	10 20 30 40 50 60 MCNTNMSVPT DGAVTTSQIP ASEQETLVRP KPLLLKLLKS VGAQKDTYTM KEVLFYLGQY 70 80 90 100 IMTKRLYDEK QQHIVNDCAN LFPLVDLSIR ELYISNYITL GI
	Isoform Mdm2-alpha [UniParc]. Checksum: C84E1F63E39E655D	FASTA	430	48,488
	10 20 30 40 50 60 MTKRLYDEKQ QHIVYCSNDL LGDLFGVPSF SVKEHRKIYT MIYRNLVVVN QQESSDSGTS 70 80 90 100 110 120 VSENRCHLEG GSDQKDLVQE LQEEKPSSSH LVSRPSTSSR RRAISETEEN SDELSGERQR 130 140 150 160 170 180 KRHKSDSISL SFDESLALCV IREICCERSS SSESTGTPSN PDLDAGVSEH SGDWLDQDSV 190 200 210 220 230 240 SDQFSVEFEV ESLDSEDYSL SEEGQELSDE DDEVYQVTVY QAGESDTDSF EEDPEISLAD 250 260 270 280 290 300 YWKCTSCNEM NPPLPSHCNR CWALRENWLP EDKGKDKGEI SEKAKLENST QAEEGFDVPD 310 320 330 340 350 360 CKKTIVNDSR ESCVEENDDK ITQASQSQES EDYSQPSTSS SIIYSSQEDV KEFEREETQD 370 380 390 400 410 420 KEESVESSLP LNAIEPCVIC QGRPKNGCIV HGKTGHLMAC FTCAKKLKKR NKPCPVCRQP 430 IQMIVLTYFP
	Isoform Mdm2-F [UniParc]. Checksum: 4B630B50750EADFE	FASTA	446	49,899
	10 20 30 40 50 60 MCNTNMSVPT DGAVTTSQIP ASEQETLVRP KPLLLKLLKS VGAQKDTYTM KEKIYTMIYR 70 80 90 100 110 120 NLVVVNQQES SDSGTSVSEN RCHLEGGSDQ KDLVQELQEE KPSSSHLVSR PSTSSRRRAI 130 140 150 160 170 180 SETEENSDEL SGERQRKRHK SDSISLSFDE SLALCVIREI CCERSSSSES TGTPSNPDLD 190 200 210 220 230 240 AGVSEHSGDW LDQDSVSDQF SVEFEVESLD SEDYSLSEEG QELSDEDDEV YQVTVYQAGE 250 260 270 280 290 300 SDTDSFEEDP EISLADYWKC TSCNEMNPPL PSHCNRCWAL RENWLPEDKG KDKGEISEKA 310 320 330 340 350 360 KLENSTQAEE GFDVPDCKKT IVNDSRESCV EENDDKITQA SQSQESEDYS QPSTSSSIIY 370 380 390 400 410 420 SSQEDVKEFE REETQDKEES VESSLPLNAI EPCVICQGRP KNGCIVHGKT GHLMACFTCA 430 440 KKLKKRNKPC PVCRQPIQMI VLTYFP
	Isoform Mdm2-G [UniParc]. Checksum: 3C8F55E98BC4203A	FASTA	436	49,249
	10 20 30 40 50 60 MCNTNMSVPT DGAVTTSQIP ASEQETLVRP KPLLLKLLKS VGAQKDTYTM KEVLFYLGQY 70 80 90 100 110 120 IMTKRLYDEK QQHIVYCSND LLGDLFGVPS FSVKEHRKIY TMIYRNLVVV NQQEENSDEL 130 140 150 160 170 180 SGERQRKRHK SDSISLSFDE SLALCVIREI CCERSSSSES TGTPSNPDLD AGVSEHSGDW 190 200 210 220 230 240 LDQDSVSDQF SVEFEVESLD SEDYSLSEEG QELSDEDDEV YQVTVYQAGE SDTDSFEEDP 250 260 270 280 290 300 EISLADYWKC TSCNEMNPPL PSHCNRCWAL RENWLPEDKG KDKGEISEKA KLENSTQAEE 310 320 330 340 350 360 GFDVPDCKKT IVNDSRESCV EENDDKITQA SQSQESEDYS QPSTSSSIIY SSQEDVKEFE 370 380 390 400 410 420 REETQDKEES VESSLPLNAI EPCVICQGRP KNGCIVHGKT GHLMACFTCA KKLKKRNKPC 430 PVCRQPIQMI VLTYFP
	Isoform 11 [UniParc]. Checksum: CFEC32F36132D8FA	FASTA	497	55,991
	10 20 30 40 50 60 MVRSRQMCNT NMSVPTDGAV TTSQIPASEQ ETLVRPKPLL LKLLKSVGAQ KDTYTMKEVL 70 80 90 100 110 120 FYLGQYIMTK RLYDEKQQHI VYCSNDLLGD LFGVPSFSVK EHRKIYTMIY RNLVVVNQQE 130 140 150 160 170 180 SSDSGTSVSE NRCHLEGGSD QKDLVQELQE EKPSSSHLVS RPSTSSRRRA ISETEENSDE 190 200 210 220 230 240 LSGERQRKRH KSDSISLSFD ESLALCVIRE ICCERSSSSE STGTPSNPDL DAGVSEHSGD 250 260 270 280 290 300 WLDQDSVSDQ FSVEFEVESL DSEDYSLSEE GQELSDEDDE VYQVTVYQAG ESDTDSFEED 310 320 330 340 350 360 PEISLADYWK CTSCNEMNPP LPSHCNRCWA LRENWLPEDK GKDKGEISEK AKLENSTQAE 370 380 390 400 410 420 EGFDVPDCKK TIVNDSRESC VEENDDKITQ ASQSQESEDY SQPSTSSSII YSSQEDVKEF 430 440 450 460 470 480 EREETQDKEE SVESSLPLNA IEPCVICQGR PKNGCIVHGK TGHLMACFTC AKKLKKRNKP 490 CPVCRQPIQM IVLTYFP

References

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[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.
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[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].
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[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]	"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.
[41]	"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.
[42]	"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.
[43]	"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.
[44]	"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.
[45]	"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.
[46]	"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, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[47]	"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.
[48]	"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.
[49]	"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.
[50]	"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.
[51]	"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.
[52]	"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.
[53]	"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.
[54]	"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 0:0-0(2012) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PML.
[55]	"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.
[56]	"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.
[57]	"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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

Wikipedia

Mdm2 entry

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.

IPI

IPI00103723.
IPI00103724.
IPI00218551.
IPI00218552.
IPI00218553.
IPI00295694.
IPI00410597.
IPI00472971.
IPI00789663.
IPI00944540.
IPI00981581.

PIR

S24354.

RefSeq

NP_002383.2. NM_002392.4.

UniGene

Hs.484551.
Hs.733536.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1RV1	X-ray	2.30	A/B/C	25-109	[»]
1T4E	X-ray	2.60	A/B	17-111	[»]
1T4F	X-ray	1.90	M	17-125	[»]
1YCR	X-ray	2.60	A	17-125	[»]
1Z1M	NMR	-	A	1-118	[»]
2AXI	X-ray	1.40	A	17-125	[»]
2C6A	NMR	-	A	290-335	[»]
2C6B	NMR	-	A	290-335	[»]
2F1Y	X-ray	1.70	A	-	[»]
2FOP	X-ray	2.10	B	145-150	[»]
2GV2	X-ray	1.80	A	17-125	[»]
2HDP	NMR	-	A/B	429-491	[»]
2LZG	NMR	-	A	1-125	[»]
2VJE	X-ray	2.20	A/C	428-491	[»]
2VJF	X-ray	2.30	A/C	428-491	[»]
3EQS	X-ray	1.65	A	25-109	[»]
3G03	X-ray	1.80	A/C	18-125	[»]
3IUX	X-ray	1.65	A/C	25-109	[»]
3IWY	X-ray	1.93	A/C	25-109	[»]
3JZK	X-ray	2.10	A	17-111	[»]
3JZR	X-ray	2.10	A	17-125	[»]
3JZS	X-ray	1.78	A	24-109	[»]
3LBK	X-ray	2.30	A	18-111	[»]
3LBL	X-ray	1.60	A/C/E	18-111	[»]
3LNJ	X-ray	2.40	A/C/E	25-109	[»]
3LNZ	X-ray	1.95	A/C/E/G/I/K/M/O	25-109	[»]
3TJ2	X-ray	2.10	A/C	18-111	[»]
3TPX	X-ray	1.80	A/C/E	25-109	[»]
3TU1	X-ray	1.60	A	18-125	[»]
3V3B	X-ray	2.00	A/B	24-110	[»]
3VBG	X-ray	2.80	A/B/C/D	25-109	[»]
3VZV	X-ray	2.80	A/B	25-109	[»]
4DIJ	X-ray	1.90	A/B	17-111	[»]
4ERE	X-ray	1.80	A/B	17-111	[»]
4ERF	X-ray	2.00	A/C/E	17-111	[»]
4HBM	X-ray	1.90	A/B/C/D/E/F/G/H	6-125	[»]

DisProt

DP00334.

ProteinModelPortal

Q00987.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-392N.

IntAct

Q00987. 145 interactions.

MINT

MINT-101583.

PTM databases

PhosphoSite

Q00987.

Polymorphism databases

DMDM

266516.

Proteomic databases

PaxDb

Q00987.

PRIDE

Q00987.

Protocols and materials databases

DNASU

4193.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000258149; ENSP00000258149; ENSG00000135679.
ENST00000299252; ENSP00000299252; ENSG00000135679.
ENST00000348801; ENSP00000335096; ENSG00000135679.
ENST00000356290; ENSP00000348637; ENSG00000135679.
ENST00000360430; ENSP00000353611; ENSG00000135679.
ENST00000393412; ENSP00000377064; ENSG00000135679.
ENST00000393413; ENSP00000377065; ENSG00000135679.
ENST00000428863; ENSP00000410694; ENSG00000135679.
ENST00000462284; ENSP00000417281; ENSG00000135679.
ENST00000540827; ENSP00000440932; ENSG00000135679.

GeneID

4193.

KEGG

hsa:4193.

UCSC

uc001sui.3. human.
uc001sun.4. human.
uc001suo.3. human.
uc009zqx.3. human.
uc009zqy.1. human.
uc009zrc.3. human.
uc009zrh.3. human.
uc021rah.1. human.

Organism-specific databases

CTD

4193.

GeneCards

GC12P069201.

HGNC

HGNC:6973. MDM2.

HPA

CAB000086.
CAB016303.

MIM

164785. gene.
614401. phenotype.

neXtProt

NX_Q00987.

Orphanet

99970. Dedifferentiated liposarcoma.
99971. Well-differentiated liposarcoma.

PharmGKB

PA30718.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG46328.

HOVERGEN

HBG013472.

InParanoid

Q00987.

KO

K06643.

OMA

LCVIREI.

OrthoDB

EOG4P8FK2.

PhylomeDB

Q00987.

Enzyme and pathway databases

Pathway_Interaction_DB

aurora_a_pathway. Aurora A signaling.
pi3kciaktpathway. Class I PI3K signaling events mediated by Akt.
ar_tf_pathway. Regulation of Androgen receptor activity.
ranbp2pathway. Sumoylation by RanBP2 regulates transcriptional repression.

Reactome

REACT_111102. Signal Transduction.
REACT_115566. Cell Cycle.
REACT_116125. Disease.
REACT_13685. Neuronal System.
REACT_6900. Immune System.

SignaLink

Q00987.

Gene expression databases

ArrayExpress

Q00987.

Bgee

Q00987.

Genevestigator

Q00987.

GermOnline

ENSG00000135679. Homo sapiens.

Family and domain databases

Gene3D

3.30.40.10. 1 hit.

InterPro

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]

PANTHER

PTHR10360:SF9. PTHR10360:SF9. 1 hit.

Pfam

PF02201. SWIB. 1 hit.
PF00641. zf-RanBP. 1 hit.
[Graphical view]

PIRSF

PIRSF006748. p53_MDM_2/4. 1 hit.

SMART

SM00184. RING. 1 hit.
[Graphical view]

SUPFAM

SSF47592. MDM2. 2 hits.

PROSITE

PS01358. ZF_RANBP2_1. 1 hit.
PS50199. ZF_RANBP2_2. 1 hit.
PS00518. ZF_RING_1. False negative.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q00987.

ChEMBL

CHEMBL5023.

EvolutionaryTrace

Q00987.

GenomeRNAi

4193.

NextBio

16526.

PMAP-CutDB

Q00987.

SOURCE

Search...

Entry information

Entry name

MDM2_HUMAN

Accession

Primary (citable) accession number: Q00987
Secondary accession number(s): A6NL51 , 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:	May 29, 2013
This is version 177 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.