| General information | | DisProt: | DP00334 | | Name: | E3 ubiquitin-protein ligase Mdm2 [Isoform Mdm2] | | Synonym(s): | MDM2_HUMAN
p53-binding protein Mdm2
Oncoprotein Mdm2
Double minute 2 protein
Hdm2
| | First appeared in release: | Release 3.0 (02/17/2006) | | UniProt: | Q00987-1 | | UniGene: | Hs.484551 | | SwissProt: | MDM2_HUMAN | | TrEMBL: | | | NCBI (GI): | 266516 | | Source organism: | Homo sapiens (Human) | | Sequence length: | 491 | | Percent disordered: | 23% | | Homologues: | |
| Native sequence |
10 20 30 40 50 60
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MCNTNMSVPT DGAVTTSQIP ASEQETLVRP KPLLLKLLKS VGAQKDTYTM KEVLFYLGQY - 60
IMTKRLYDEK QQHIVYCSND LLGDLFGVPS FSVKEHRKIY TMIYRNLVVV NQQESSDSGT - 120
SVSENRCHLE GGSDQKDLVQ ELQEEKPSSS HLVSRPSTSS RRRAISETEE NSDELSGERQ - 180
RKRHKSDSIS LSFDESLALC VIREICCERS SSSESTGTPS NPDLDAGVSE HSGDWLDQDS - 240
VSDQFSVEFE VESLDSEDYS LSEEGQELSD EDDEVYQVTV YQAGESDTDS FEEDPEISLA - 300
DYWKCTSCNE MNPPLPSHCN RCWALRENWL PEDKGKDKGE ISEKAKLENS TQAEEGFDVP - 360
DCKKTIVNDS RESCVEENDD KITQASQSQE SEDYSQPSTS SSIIYSSQED VKEFEREETQ - 420
DKEESVESSL PLNAIEPCVI CQGRPKNGCI VHGKTGHLMA CFTCAKKLKK RNKPCPVCRQ - 480
PIQMIVLTYF P
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| Functional narrative |
Inhibits TP53/p53- and TP73/p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Functions as a ubiquitin ligase E3, in the presence of E1 and E2, toward p53 and itself. Permits the nuclear export of p53 and targets it for proteasome-mediated proteolysis. Functions as an ubiquitin ligase E3 toward ARRB1. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein.
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| Map of ordered and disordered regions |
Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.
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| Region 1 | | Type: | Disordered | | Name: | | | Location: | 210 - 304 | | Length: | 95 | | Region sequence: |
SSSSESTGTPSNPDLDAGVSEHSGDWLDQDSVSDQFSVEFEVESLDSEDYSLSEEGQELS
DEDDEVYQVTVYQAGESDTDSFEEDPEISLADYWK | | Modification type: | Fragment
| | PDB: | | | Structural/functional type: | Function arises via a disorder to order transition
| | Functional classes: | | | Functional subclasses: | Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (pH: 6; 2H2O (v/v) 5 %; potassium phosphate (buffer) 10 mM)
- Circular dichroism (CD) spectroscopy, far-UV (298 K; pH: 7; Tris-HCl 10 mM)
| References:
- Bothner B, Lewis WS, DiGiammarino EL, Weber JD, Bothner SJ, Kriwacki RW. "Defining the molecular basis of Arf and Hdm2 interactions." J Mol Biol. 2001; 314(2): 263-77. PubMed: 11718560
| Comments:
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| Region 2 | | Type: | Disordered | | Name: | | | Location: | 240 - 254 | | Length: | 15 | | Region sequence: |
SVSDQFSVEFEVESL | | Modification type: | Fragment
| | PDB: | | | Structural/functional type: | Function arises via a disorder to order transition
| | Functional classes: | | | Functional subclasses: | Protein-protein binding
| Detection methods:
- Circular dichroism (CD) spectroscopy, far-UV
| References:
- Bothner B, Aubin Y, Kriwacki RW. "Peptides derived from two dynamically disordered proteins self-assemble into amyloid-like fibrils." J Am Chem Soc. 2003; 125(11): 3200-1. PubMed: 12630860
| Comments:
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| Region 3 | | Type: | Disordered | | Name: | | | Location: | 1 - 17 | | Length: | 17 | | Region sequence: |
MCNTNMSVPTDGAVTTS | | Modification type: | Fragment
| | PDB: | | | Structural/functional type: | Relationship to function unknown
| | Functional classes: | Unknown
| | Functional subclasses: | Unknown
| Detection methods:
- Nuclear magnetic resonance (NMR) (288 K; 2H2O 99.9 %)
| References:
- Uhrinova S, Uhrin D, Powers H, Watt K, Zheleva D, Fischer P, McInnes C, Barlow PN. "Structure of free MDM2 N-terminal domain reveals conformational adjustments that accompany p53-binding." J Mol Biol. 2005; 350(3): 587-98. PubMed: 15953616
| Comments:
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