Mammalian homologues of yeast vacuolar protein sorting (vps) genes implicated in Golgi-to-lysosome trafficking.
Sec1p, Vps33p, Vps45p and Sly1p constitute a family of proteins implicated in vesicle trafficking at distinct stages of the yeast secretory pathway. Several mammalian homologues of Sec1p have been described, including n-sec1 which has been implicated in the regulation of synaptic vesicle docking at the nerve terminal. We have characterized cDNA clones encoding three additional mammalian homologues belonging to this family: r-vps33a and r-vps33b from rat, which are 30 and 26% identical to yeast Vps33p, respectively, and h-vps45 from human which is 38% identical to yeast Vps45p at the amino acid (aa) level. Phylogenetic analysis of 16 Sec1p-related proteins from several species is consistent with the hypothesis that the evolution of this gene family parallels the specialization of vesicle trafficking to distinct intracellular compartments. By Northern analysis, each of these genes is expressed in all tissues examined (brain, spleen, lung, liver, skeletal muscle, kidney, testis). While n-sec1 binds syntaxin 1a, 2, and 3, r-vps33a, r-vps33b and h-vps45 do not bind any of the known syntaxins. We propose that the three proteins bind as yet unidentified syntaxin homologues involved in vesicle trafficking between the Golgi apparatus, prelysosomal compartment(s), and the lysosome.
Pevsner
J
J
Beckman Center, Stanford University Medical School, CA 94305, USA.
Hsu
S C
SC
Hyde
P S
PS
Scheller
R H
RH
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D010802:Phylogeny; D011485:Protein Binding; D050765:Qa-SNARE Proteins; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D050827:Syntaxin 1; D014617:Vacuoles; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D018076:DNA, Complementary; D005656:Fungal Proteins; D008565:Membrane Proteins; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; D012333:RNA, Messenger; C497931:SEC1 protein, S cerevisiae; C494212:STX1A protein, human; D029701:Saccharomyces cerevisiae Proteins; C494213:Stx1a protein, rat; D050827:Syntaxin 1; C065454:VPS33 protein, S cerevisiae; C092934:VPS45 protein, S cerevisiae; D033921:Vesicular Transport Proteins