| General information | | DisProt: | DP00335 | | Name: | Cyclin-dependent kinase inhibitor 2A [Isoform 3] | | Synonym(s): | CD2A2_MOUSE
p19ARF
| | First appeared in release: | Release 3.0 (02/17/2006) | | UniProt: | Q64364-1 | | UniGene: | Mm.4733 | | SwissProt: | CD2A2_MOUSE | | TrEMBL: | | | NCBI (GI): | 77416386 | | Source organism: | Mus musculus (Mouse) | | Sequence length: | 169 | | Percent disordered: | 22% | | Homologues: | |
| Native sequence |
10 20 30 40 50 60
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MGRRFLVTVR IQRAGRPLQE RVFLVKFVRS RRPRTASCAL AFVNMLLRLE RILRRGPHRN - 60
PGPGDDDGQR SRSSSSAQLR CRFELRGPHY LLPPGARRSA GRLPGHAGGA ARVRGSAGCA - 120
RCLGSPAARL GPRAGTSRHR AIFAFRWVLF VFRWVVFVYR WERRPDRRA
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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: |
MGRRFLVTVRIQRAGRPLQERVFLVKFVRSRRPRTAS | | Modification type: | Fragment
| | PDB: | 1HN3:A | | 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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