General information | DisProt: | DP00336 | Name: | Cyclin-dependent kinase inhibitor 2A [Isoform 4] | Synonym(s): | CD2A2_HUMAN
p14ARF
p19ARF
| First appeared in release: | Release 3.1 (03/31/2006) | UniProt: | Q8N726-1 | UniGene: | Hs.512599 | SwissProt: | CD2A2_HUMAN | TrEMBL: | | NCBI (GI): | 74751077 | Source organism: | Homo sapiens (Human) | Sequence length: | 173 | Percent disordered: | 21% | Homologues: | |
Native sequence |
10 20 30 40 50 60 | | | | | | MGRGRCVGPS LQLRGQEWRC SPLVPKGGAA AAELGPGGGE NMVRRFLVTL RIRRACGPPR - 60 VRVFVVHIPR LTGEWAAPGA PAAVALVLML LRSQRLGQQP LPRRPGHDDG QRPSGGAAAA - 120 PRRGAQLRRP RHSHPTRARR CPGGLPGHAG GAAPGRGAAG RARCLGPSAR GPG
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Functional narrative |
Capable of inducing cell cycle arrest in G1 and G2 phases. Acts as a tumor suppressor. Binds to MDM2 and blocks its nucleocytoplasmic shuttling by sequestering it in the nucleolus. This inhibits the oncogenic action of MDM2 by blocking MDM2-induced degradation of p53 and enhancing p53-dependent transactivation and apoptosis. Also induces G2 arrest and apoptosis in a p53-independent manner by preventing the activation of cyclin B1/CDC2 complexes. Binds to BCL6 and down-regulates BCL6-induced transcriptional repression. Binds to E2F1 and MYC and blocks their transcriptional activator activity but has no effect on MYC transcriptional repression. Binds to TOP1/TOPOI and stimulates its activity. This complex binds to rRNA gene promoters and may play a role in rRNA transcription and/or maturation. Interacts with NPM1/B23 and promotes its polyubiquitination and degradation, thus inhibiting rRNA processing. Interacts with UBE2I/UBC9 and enhances sumoylation of a number of its binding partners including MDM2 and E2F1. Binds to HUWE1 and represses its ubiquitin ligase activity. May play a role in controlling cell proliferation and apoptosis during mammary gland development.
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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: | 1 - 37 | Length: | 37 | Region sequence: |
MGRGRCVGPSLQLRGQEWRCSPLVPKGGAAAAELGPG | 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, 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
- 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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