Molecular cloning and functional characterization of a human homologue of centaurin-alpha

Biochem Biophys Res Commun. 1999 Aug 19;262(1):237-44. doi: 10.1006/bbrc.1999.1065.


We report here the molecular cloning, expression, and characterisation of a human homologue of rat centaurin-alpha, which we have termed centaurin-alpha(1). The cDNA contains a single open reading frame, which encodes a 373-amino-acid protein with a calculated molecular weight of 43,429 Daltons. Centaurin-alpha(1) shows high identity at the amino acid level with the other centaurin-alpha homologues, p42(IP4) and PIP(3)BP. Northern analysis revealed that centaurin-alpha(1) expresses as a single 2.5-kb transcript, mainly in the brain. Recombinant centaurin-alpha(1) binds the inositol head group of PtdIns(3,4,5)P(3) and Ins(1,3,4, 5)P(4), with high affinity (K(d) 139.7 +/- 10.5 nM) and inositol phosphate specificity, consistent with it functioning as a putative PtdIns(3,4,5)P(3) receptor. In keeping with this conclusion, we have shown that GFP-tagged centaurin-alpha(1) recruits to the plasma membrane in a PI 3-kinase-dependent manner and the recruitment is inhibited by the PI 3-kinase inhibitor wortmannin. These results suggest that centaurin-alpha(1) can function as an in vivo PtdIns(3, 4,5)P(3) receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Androstadienes / pharmacology
  • Animals
  • Base Sequence
  • Binding Sites
  • Brain / metabolism
  • CHO Cells
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cloning, Molecular
  • Cricetinae
  • GTPase-Activating Proteins
  • Humans
  • Inositol Phosphates / metabolism
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Organ Specificity
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphatidylinositol Phosphates / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Wortmannin
  • Zinc Fingers


  • ADAP1 protein, human
  • Adap1 protein, rat
  • Adaptor Proteins, Signal Transducing
  • Androstadienes
  • Carrier Proteins
  • GTPase-Activating Proteins
  • Inositol Phosphates
  • Nerve Tissue Proteins
  • Phosphatidylinositol Phosphates
  • Phosphoinositide-3 Kinase Inhibitors
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • phosphatidylinositol 3,4,5-triphosphate
  • inositol-1,3,4,5-tetrakisphosphate
  • Wortmannin

Associated data

  • GENBANK/AJ006422