title: Functional similarities between the dictyostelium protein AprA and the human protein dipeptidyl-peptidase IV.
abstract: Autocrine proliferation repressor protein A (AprA) is a protein secreted by Dictyostelium discoideum cells. Although there is very little sequence similarity between AprA and any human protein, AprA has a predicted structural similarity to the human protein dipeptidyl peptidase IV (DPPIV). AprA is a chemorepellent for Dictyostelium cells, and DPPIV is a chemorepellent for neutrophils. This led us to investigate if AprA and DPPIV have additional functional similarities. We find that like AprA, DPPIV is a chemorepellent for, and inhibits the proliferation of, D. discoideum cells, and that AprA binds some DPPIV binding partners such as fibronectin. Conversely, rAprA has DPPIV-like protease activity. These results indicate a functional similarity between two eukaryotic chemorepellent proteins with very little sequence similarity, and emphasize the usefulness of using a predicted protein structure to search a protein structure database, in addition to searching for proteins with similar sequences.
authors.affiliation: Department of Biology, Texas A&M University, College Station, Texas.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Herlihy
authors.affiliation: Department of Biology, Texas A&M University, College Station, Texas.
authors.forename: Yu
authors.identifier: 0000-0002-1100-1338
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Biology, Texas A&M University, College Station, Texas.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Phillips
authors.affiliation: Department of Biology, Texas A&M University, College Station, Texas.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Gomer
mesh_terms: D004023:Dictyostelium / Q000201:enzymology*; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry*; D005353:Fibronectins / Q000737:chemistry; D006801:Humans; D011485:Protein Binding; D015800:Protozoan Proteins / Q000737:chemistry*; D040681:Structural Homology, Protein
chemical_list: D005353:Fibronectins; D015800:Protozoan Proteins; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4
keywords: AprA; DPPIV; chemorepellent; functional similarity; protease; structure similarity