title: PHR1 encodes an abundant, pleckstrin homology domain-containing integral membrane protein in the photoreceptor outer segments.
abstract: We cloned human and murine cDNAs of a gene (designated PHR1), expressed preferentially in retina and brain. In both species, PHR1 utilizes two promoters and alternative splicing to produce four PHR1 transcripts, encoding isoforms of 243, 224, 208, and 189 amino acids, each with a pleckstrin homology domain at their N terminus and a transmembrane domain at their C terminus. Transcript 1 originates from a 5'-photoreceptor-specific promoter with at least three Crx elements ((C/T)TAATCC). Transcript 2 originates from the same promoter but lacks exon 7, which encodes 35 amino acids immediately C-terminal to the pleckstrin homology domain. Transcripts 3 and 4 originate from an internal promoter in intron 2 and either include or lack exon 7, respectively. In situ hybridization shows that PHR1 is highly expressed in photoreceptors, with lower expression in retinal ganglion cells. Immunohistochemistry localizes the PHR1 protein to photoreceptor outer segments where chemical extraction studies confirm it is an integral membrane protein. Using a series of PHR1 glutathione S-transferase fusion proteins to perform in vitro binding assays, we found PHR1 binds transducin betagamma subunits but not inositol phosphates. This activity and subcellular location suggests that PHR1 may function as a previously unrecognized modulator of the phototransduction pathway.
authors.affiliation: Predoctoral Training Program in Human Genetics, Department of Pediatrics, Baltimore, Maryland 21205, USA.
authors.forename: S
authors.initials: S
authors.lastname: Xu
authors.forename: R
authors.initials: R
authors.lastname: Ladak
authors.forename: D A
authors.initials: DA
authors.lastname: Swanson
authors.forename: A
authors.initials: A
authors.lastname: Soltyk
authors.forename: H
authors.initials: H
authors.lastname: Sun
authors.forename: L
authors.initials: L
authors.lastname: Ploder
authors.forename: D
authors.initials: D
authors.lastname: Vidgen
authors.forename: A M
authors.initials: AM
authors.lastname: Duncan
authors.forename: E
authors.initials: E
authors.lastname: Garami
authors.forename: D
authors.initials: D
authors.lastname: Valle
authors.forename: R R
authors.initials: RR
authors.lastname: McInnes
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001051:Apoenzymes / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism*; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000737:chemistry / Q000235:genetics*; D005091:Exons; D005656:Fungal Proteins; D005796:Genes; D006801:Humans; D007438:Introns; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D012160:Retina / Q000378:metabolism; D012374:Rod Cell Outer Segment / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D018909:src Homology Domains
chemical_list: D001051:Apoenzymes; D005656:Fungal Proteins; D008562:Membrane Glycoproteins; C091515:PHR1 protein, Candida albicans; D004255:Deoxyribodipyrimidine Photo-Lyase