The evolutionary strata of DARPP-32 tail implicates hierarchical functional expansion in higher vertebrates.
DARPP-32 (dopamine and adenosine 3', 5'-monophosphate-regulated phosphoprotein of 32 kDa), which belongs to PPP1R1 gene family, is known to act as an important integrator in dopamine-mediated neurotransmission via the inhibition of protein phosphatase-1 (PP1). Besides its neuronal roles, this protein also behaves as a key player in pathological and pharmacological aspects. Use of bioinformatics and phylogenetics approaches to further characterize the molecular features of DARPP-32 can guide future works. Predicted phosphorylation sites on DARPP-32 show conservation across vertebrates. Phylogenetics analysis indicates evolutionary strata of phosphorylation site acquisition at the C-terminus, suggesting functional expansion of DARPP-32, where more diverse signalling cues may involve in regulating DARPP-32 in inhibiting PP1 activity. Moreover, both phylogenetics and synteny analyses suggest de novo origination of PPP1R1 gene family via chromosomal rearrangement and exonization.
Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Choong Yong
CY
Ung
Teow Chong
TC
Teoh
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019295:Computational Biology; D017124:Conserved Sequence; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000737:chemistry*; D019143:Evolution, Molecular; D006801:Humans; D010766:Phosphorylation; D010802:Phylogeny; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D026801:Synteny; D014714:Vertebrates
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32