title: An unsuspected ecdysteroid/steroid phosphatase activity in the key T-cell regulator, Sts-1: surprising relationship to insect ecdysteroid phosphate phosphatase.
abstract: The insect enzyme ecdysteroid phosphate phosphatase (EPP) mobilizes active ecdysteroids from an inactive phosphorylated pool. Previously assigned to a novel class, it is shown here that it resides in the large histidine phosphatase superfamily related to cofactor-dependent phosphoglycerate mutase, a superfamily housing notably diverse catalytic activities. Molecular modeling reveals a plausible substrate-binding mode for EPP. Analysis of genomic and transcript data for a number of insect species shows that EPP may exist in both the single domain form previously characterized and in a longer, multidomain form. This latter form bears a quite unexpected relationship in sequence and domain architecture to vertebrate proteins, including Sts-1, characterized as a key regulator of T-cell activity. Long form Drosophila melanogaster EPP, human Sts-1, and a related protein from Caenorhabditis elegans have all been cloned, assayed, and shown to catalyse the hydrolysis of ecdysteroid and steroid phosphates. The surprising relationship described and explored here between EPP and Sts-1 has implications for our understanding of the function(s) of both.
authors.affiliation: School of Biological Sciences, University of Liverpool, Biosciences Building, Liverpool L69 7ZB, United Kingdom.
authors.forename: Lyndsay
authors.initials: L
authors.lastname: Davies
authors.forename: Ian P
authors.initials: IP
authors.lastname: Anderson
authors.forename: Philip C
authors.initials: PC
authors.lastname: Turner
authors.forename: Alan D
authors.initials: AD
authors.lastname: Shirras
authors.forename: Huw H
authors.initials: HH
authors.lastname: Rees
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rigden
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D019295:Computational Biology; D030562:Databases, Protein; D019143:Evolution, Molecular; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases; D017386:Sequence Homology, Amino Acid; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D019476:Insect Proteins; C423262:UBASH3A protein, human; C476613:ecdysteroid-phosphate phosphatase; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases; C489397:UBASH3B protein, human