TY - JOUR
T1 - Evidence for a niemann-pick C (NPC) gene family
T2 - Identification and characterization of NPC1L1
AU - Davies, Joanna P.
AU - Levy, Brynn
AU - Ioannou, Yiannis A.
N1 - Funding Information:
This work was supported in part by a grant from the Ara Parseg-hian Research Foundation and by a grant from the March of Dimes Foundation.
PY - 2000/4/15
Y1 - 2000/4/15
N2 - Niemann-Pick type C1 (NPC1) disease is caused by defects in the NPC1 protein, which result in perturbation of subcellular cholesterol transport. To identify related proteins that may be involved in subcellular cholesterol trafficking, the expressed sequence tag (EST) database was searched to find homologues of human NPCL. A short, weakly similar EST was identified and used to obtain a full-length human cDNA of about 5 kb and two alternatively spliced transcripts. The gene, named NPC1L1, was mapped to chromosome 7p13, contained 26 exons, including an unusually large 1526-bp exon 2, and spanned approximately 29 kb. In contrast to NPC1, the NPC1L1 putative promoter region contained a sterol-regulatory element. The predicted protein shared 42% identity and 51% similarity with NPC1. Interestingly, NPC1L1 contains the conserved amino-terminal 'NPC1 domain' and the putative sterol-sensing domain, providing strong evidence that it is related to human NPC1 and suggesting that these may comprise a new family of NPC1-related proteins. However, the two differ with respect to their putative intracellular targeting signals. Collectively, these data suggest that NPC1L1 and NPC1 form part of a family of related proteins that may have similar functions at different subcellular locations, perhaps at sequential steps of the same cholesterol transport pathway. (C) 2000 Academic Press.
AB - Niemann-Pick type C1 (NPC1) disease is caused by defects in the NPC1 protein, which result in perturbation of subcellular cholesterol transport. To identify related proteins that may be involved in subcellular cholesterol trafficking, the expressed sequence tag (EST) database was searched to find homologues of human NPCL. A short, weakly similar EST was identified and used to obtain a full-length human cDNA of about 5 kb and two alternatively spliced transcripts. The gene, named NPC1L1, was mapped to chromosome 7p13, contained 26 exons, including an unusually large 1526-bp exon 2, and spanned approximately 29 kb. In contrast to NPC1, the NPC1L1 putative promoter region contained a sterol-regulatory element. The predicted protein shared 42% identity and 51% similarity with NPC1. Interestingly, NPC1L1 contains the conserved amino-terminal 'NPC1 domain' and the putative sterol-sensing domain, providing strong evidence that it is related to human NPC1 and suggesting that these may comprise a new family of NPC1-related proteins. However, the two differ with respect to their putative intracellular targeting signals. Collectively, these data suggest that NPC1L1 and NPC1 form part of a family of related proteins that may have similar functions at different subcellular locations, perhaps at sequential steps of the same cholesterol transport pathway. (C) 2000 Academic Press.
UR - http://www.scopus.com/inward/record.url?scp=0034655917&partnerID=8YFLogxK
U2 - 10.1006/geno.2000.6151
DO - 10.1006/geno.2000.6151
M3 - Article
C2 - 10783261
AN - SCOPUS:0034655917
SN - 0888-7543
VL - 65
SP - 137
EP - 145
JO - Genomics
JF - Genomics
IS - 2
ER -