Crystal structure of the catalytic domain of an adenosine deaminase that acts on RNA (hADAR2) bound to inositol hexakisphosphate (IHP)Crystal structure of the catalytic domain of an adenosine deaminase that acts on RNA (hADAR2) bound to inositol hexakisphosphate (IHP)
Structural highlights
1zy7 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
RED1_HUMAN Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing. This may affect gene expression and function in a number of ways that include mRNA translation by changing codons and hence the amino acid sequence of proteins; pre-mRNA splicing by altering splice site recognition sequences; RNA stability by changing sequences involved in nuclease recognition; genetic stability in the case of RNA virus genomes by changing sequences during viral RNA replication; and RNA structure-dependent activities such as microRNA production or targeting or protein-RNA interactions. Can edit both viral and cellular RNAs and can edit RNAs at multiple sites (hyper-editing) or at specific sites (site-specific editing). Its cellular RNA substrates include: bladder cancer-associated protein (BLCAP), neurotransmitter receptors for glutamate (GRIA2 and GRIK2) and serotonin (HTR2C), GABA receptor (GABRA3) and potassium voltage-gated channel (KCNA1). Site-specific RNA editing of transcripts encoding these proteins results in amino acid substitutions which consequently alter their functional activities. Edits GRIA2 at both the Q/R and R/G sites efficiently but converts the adenosine in hotspot1 much less efficiently. Can exert a proviral effect towards human immunodeficiency virus type 1 (HIV-1) and enhances its replication via both an editing-dependent and editing-independent mechanism. The former involves editing of adenosines in the 5'UTR while the latter occurs via suppression of EIF2AK2/PKR activation and function. Can inhibit cell proliferation and migration and can stimulate exocytosis.[1][2][3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
↑Cenci C, Barzotti R, Galeano F, Corbelli S, Rota R, Massimi L, Di Rocco C, O'Connell MA, Gallo A. Down-regulation of RNA editing in pediatric astrocytomas: ADAR2 editing activity inhibits cell migration and proliferation. J Biol Chem. 2008 Mar 14;283(11):7251-60. doi: 10.1074/jbc.M708316200. Epub 2008 , Jan 4. PMID:18178553 doi:http://dx.doi.org/10.1074/jbc.M708316200
↑Galeano F, Leroy A, Rossetti C, Gromova I, Gautier P, Keegan LP, Massimi L, Di Rocco C, O'Connell MA, Gallo A. Human BLCAP transcript: new editing events in normal and cancerous tissues. Int J Cancer. 2010 Jul 1;127(1):127-37. doi: 10.1002/ijc.25022. PMID:19908260 doi:10.1002/ijc.25022
↑Doria M, Tomaselli S, Neri F, Ciafre SA, Farace MG, Michienzi A, Gallo A. ADAR2 editing enzyme is a novel human immunodeficiency virus-1 proviral factor. J Gen Virol. 2011 May;92(Pt 5):1228-32. doi: 10.1099/vir.0.028043-0. Epub 2011, Feb 2. PMID:21289159 doi:10.1099/vir.0.028043-0
