Cloning and characterization of a novel human phosphatidylinositol transfer protein, rdgBbeta.
The various PITP, retinal degeneration B (rdgB), and amino-terminal domain interacting receptor (Nir) phosphatidylinositol transfer proteins can be divided into two structural families. The small, soluble PITP isoforms contain only a phosphatidylinositol transfer domain and have been implicated in phosphoinositide signaling and vesicle trafficking. In contrast, the rdgB proteins, which include Nir2 and Nir3, contain an amino-terminal PITP-like domain, an acidic, Ca(2+)-binding domain, six putative transmembrane domains, and a conserved carboxyl-terminal domain. However, the biological function of rdgB proteins is unclear. Here, we report the isolation of a cDNA encoding a novel rdgB protein, mammalian rdgBbeta (MrdgBbeta). The 38-kDa MrdgBbeta protein contains an amino-terminal PITP-like domain and a short carboxyl-terminal domain. In contrast to other rdgB-like proteins, MrdgBbeta contains no transmembrane motifs or the conserved carboxyl-terminal domain. Using Northern and reverse transcription-polymerase chain reaction analysis, we demonstrate that MrdgBbeta mRNA is ubiquitously expressed. Immunofluorescence analysis of ectopic MrdgBbeta showed cytoplasmic staining, and the ability of recombinant MrdgBbeta to transfer phosphatidylinositol in vitro was similar to other PITP-like domains. Although early reports found functional degeneracy in vitro, the identification of a fifth mammalian PITP-like protein with a unique domain organization and widespread expression supports more recent results that suggest that different PITP-like domains have distinct functions in vivo.
Fullwood
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Y
Ludwig Institute for Cancer Research, Courtauld Building, 91 Riding House St., London W1P 8BT, United Kingdom.
dos Santos
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M
Hsuan
J J
JJ
D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002451:Cell Compartmentation; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000737:chemistry; D019143:Evolution, Molecular; D006801:Humans; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D010716:Phosphatidylinositols / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D002352:Carrier Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C107847:PITPNC1 protein, human; D010716:Phosphatidylinositols