NPC1-like intracellular cholesterol transporter 1
Details
- Name
- NPC1-like intracellular cholesterol transporter 1
- Kind
- protein
- Synonyms
- Niemann-Pick C1-like protein 1
- NPC1L1
- Gene Name
- NPC1L1
- UniProtKB Entry
- Q9UHC9Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0037079|NPC1-like intracellular cholesterol transporter 1 MAEAGLRGWLLWALLLRLAQSEPYTTIHQPGYCAFYDECGKNPELSGSLMTLSNVSCLSN TPARKITGDHLILLQKICPRLYTGPNTQACCSAKQLVSLEASLSITKALLTRCPACSDNF VNLHCHNTCSPNQSLFINVTRVAQLGAGQLPAVVAYEAFYQHSFAEQSYDSCSRVRVPAA ATLAVGTMCGVYGSALCNAQRWLNFQGDTGNGLAPLDITFHLLEPGQAVGSGIQPLNEGV ARCNESQGDDVATCSCQDCAASCPAIARPQALDSTFYLGQMPGSLVLIIILCSVFAVVTI LLVGFRVAPARDKSKMVDPKKGTSLSDKLSFSTHTLLGQFFQGWGTWVASWPLTILVLSV IPVVALAAGLVFTELTTDPVELWSAPNSQARSEKAFHDQHFGPFFRTNQVILTAPNRSSY RYDSLLLGPKNFSGILDLDLLLELLELQERLRHLQVWSPEAQRNISLQDICYAPLNPDNT SLYDCCINSLLQYFQNNRTLLLLTANQTLMGQTSQVDWKDHFLYCANAPLTFKDGTALAL SCMADYGAPVFPFLAIGGYKGKDYSEAEALIMTFSLNNYPAGDPRLAQAKLWEEAFLEEM RAFQRRMAGMFQVTFMAERSLEDEINRTTAEDLPIFATSYIVIFLYISLALGSYSSWSRV MVDSKATLGLGGVAVVLGAVMAAMGFFSYLGIRSSLVILQVVPFLVLSVGADNIFIFVLE YQRLPRRPGEPREVHIGRALGRVAPSMLLCSLSEAICFFLGALTPMPAVRTFALTSGLAV ILDFLLQMSAFVALLSLDSKRQEASRLDVCCCVKPQELPPPGQGEGLLLGFFQKAYAPFL LHWITRGVVLLLFLALFGVSLYSMCHISVGLDQELALPKDSYLLDYFLFLNRYFEVGAPV YFVTTLGYNFSSEAGMNAICSSAGCNNFSFTQKIQYATEFPEQSYLAIPASSWVDDFIDW LTPSSCCRLYISGPNKDKFCPSTVNSLNCLKNCMSITMGSVRPSVEQFHKYLPWFLNDRP NIKCPKGGLAAYSTSVNLTSDGQVLDTVAILSPRLEYSGTISAHCNLYLLDSTSRFMAYH KPLKNSQDYTEALRAARELAANITADLRKVPGTDPAFEVFPYTITNVFYEQYLTILPEGL FMLSLCLVPTFAVSCLLLGLDLRSGLLNLLSIVMILVDTVGFMALWGISYNAVSLINLVS AVGMSVEFVSHITRSFAISTKPTWLERAKEATISMGSAVFAGVAMTNLPGILVLGLAKAQ LIQIFFFRLNLLITLLGLLHGLVFLPVILSYVGPDVNPALALEQKRAEEAVAAVMVASCP NHPSRVSTADNIYVNHSFEGSIKGAGAISNFLPNNGRQF
- Number of residues
- 1359
- Molecular Weight
- 148726.52
- Theoretical pI
- 6.31
- GO Classification
- Functionsmyosin V bindingProcessescholesterol biosynthetic process / cholesterol homeostasis / cholesterol transport / intestinal cholesterol absorption / lipoprotein metabolic processComponentsapical plasma membrane / cytoplasmic vesicle membrane / plasma membrane
- General Function
- Plays a major role in cholesterol homeostasis (PubMed:22095670). Critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte (PubMed:22095670). Involved in plant sterol absorption, it transports sitosterol, although at lower rates than cholesterol (By similarity). Is the direct molecular target of ezetimibe, a drug that inhibits cholesterol absorption and is approved for the treatment of hypercholesterolemia (PubMed:15928087). May have a function in the transport of multiple lipids and their homeostasis, thereby influencing lipid metabolism regulation (PubMed:15671032). May be involved in caveolin trafficking from the plasma membrane (By similarity). In addition, acts as a negative regulator of NPC2 and down-regulates its expression and secretion by inhibiting its maturation and accelerating its degradation (PubMed:22095670)
- Specific Function
- cholesterol binding
- Pfam Domain Function
- Signal Regions
- 1-21
- Transmembrane Regions
- 285-305 352-372 633-653 667-687 697-717 743-763 777-797 847-867 1140-1160 1169-1189 1192-1212 1237-1257 1269-1289
- Cellular Location
- Apical cell membrane
- Gene sequence
>lcl|BSEQ0021278|Niemann-Pick C1-like protein 1 (NPC1L1) ATGGCGGAGGCCGGCCTGAGGGGCTGGCTGCTGTGGGCCCTGCTCCTGCGCTTGGCCCAG AGTGAGCCTTACACAACCATCCACCAGCCTGGCTACTGCGCCTTCTATGACGAATGTGGG AAGAACCCAGAGCTGTCTGGAAGCCTCATGACACTCTCCAACGTGTCCTGCCTGTCCAAC ACGCCGGCCCGCAAGATCACAGGTGATCACCTGATCCTATTACAGAAGATCTGCCCCCGC CTCTACACCGGCCCCAACACCCAAGCCTGCTGCTCCGCCAAGCAGCTGGTATCACTGGAA GCGAGTCTGTCGATCACCAAGGCCCTCCTCACCCGCTGCCCAGCCTGCTCTGACAATTTT GTGAACCTGCACTGCCACAACACGTGCAGCCCCAATCAGAGCCTCTTCATCAATGTGACC CGCGTGGCCCAGCTAGGGGCTGGACAACTCCCAGCTGTGGTGGCCTATGAGGCCTTCTAC CAGCATAGCTTTGCCGAGCAGAGCTATGACTCCTGCAGCCGTGTGCGCGTCCCTGCAGCT GCCACGCTGGCTGTGGGCACCATGTGTGGCGTGTATGGCTCTGCCCTTTGCAATGCCCAG CGCTGGCTCAACTTCCAGGGAGACACAGGCAATGGTCTGGCCCCACTGGACATCACCTTC CACCTCTTGGAGCCTGGCCAGGCCGTGGGGAGTGGGATTCAGCCTCTGAATGAGGGGGTT GCACGTTGCAATGAGTCCCAAGGTGACGACGTGGCGACCTGCTCCTGCCAAGACTGTGCT GCATCCTGTCCTGCCATAGCCCGCCCCCAGGCCCTCGACTCCACCTTCTACCTGGGCCAG ATGCCGGGCAGTCTGGTCCTCATCATCATCCTCTGCTCTGTCTTCGCTGTGGTCACCATC CTGCTTGTGGGATTCCGTGTGGCCCCCGCCAGGGACAAAAGCAAGATGGTGGACCCCAAG AAGGGCACCAGCCTCTCTGACAAGCTCAGCTTCTCCACCCACACCCTCCTTGGCCAGTTC TTCCAGGGCTGGGGCACGTGGGTGGCTTCGTGGCCTCTGACCATCTTGGTGCTATCTGTC ATCCCGGTGGTGGCCTTGGCAGCGGGCCTGGTCTTTACAGAACTCACTACGGACCCCGTG GAGCTGTGGTCGGCCCCCAACAGCCAAGCCCGGAGTGAGAAAGCTTTCCATGACCAGCAT TTCGGCCCCTTCTTCCGAACCAACCAGGTGATCCTGACGGCTCCTAACCGGTCCAGCTAC AGGTATGACTCTCTGCTGCTGGGGCCCAAGAACTTCAGCGGAATCCTGGACCTGGACTTG CTGCTGGAGCTGCTAGAGCTGCAGGAGAGGCTGCGGCACCTCCAGGTATGGTCGCCCGAA GCACAGCGCAACATCTCCCTGCAGGACATCTGCTACGCCCCCCTCAATCCGGACAATACC AGTCTCTACGACTGCTGCATCAACAGCCTCCTGCAGTATTTCCAGAACAACCGCACGCTC CTGCTGCTCACAGCCAACCAGACACTGATGGGGCAGACCTCCCAAGTCGACTGGAAGGAC CATTTTCTGTACTGTGCCAATGCCCCGCTCACCTTCAAGGATGGCACAGCCCTGGCCCTG AGCTGCATGGCTGACTACGGGGCCCCTGTCTTCCCCTTCCTTGCCATTGGGGGGTACAAA GGAAAGGACTATTCTGAGGCAGAGGCCCTGATCATGACGTTCTCCCTCAACAATTACCCT GCCGGGGACCCCCGTCTGGCCCAGGCCAAGCTGTGGGAGGAGGCCTTCTTAGAGGAAATG CGAGCCTTCCAGCGTCGGATGGCTGGCATGTTCCAGGTCACGTTCATGGCTGAGCGCTCT CTGGAAGACGAGATCAATCGCACCACAGCTGAAGACCTGCCCATCTTTGCCACCAGCTAC ATTGTCATATTCCTGTACATCTCTCTGGCCCTGGGCAGCTATTCCAGCTGGAGCCGAGTG ATGGTGGACTCCAAGGCCACGCTGGGCCTCGGCGGGGTGGCCGTGGTCCTGGGAGCAGTC ATGGCTGCCATGGGCTTCTTCTCCTACTTGGGTATCCGCTCCTCCCTGGTCATCCTGCAA GTGGTTCCTTTCCTGGTGCTGTCCGTGGGGGCTGATAACATCTTCATCTTTGTTCTCGAG TACCAGAGGCTGCCCCGGAGGCCTGGGGAGCCACGAGAGGTCCACATTGGGCGAGCCCTA GGCAGGGTGGCTCCCAGCATGCTGTTGTGCAGCCTCTCTGAGGCCATCTGCTTCTTCCTA GGGGCCCTGACCCCCATGCCAGCTGTGCGGACCTTTGCCCTGACCTCTGGCCTTGCAGTG ATCCTTGACTTCCTCCTGCAGATGTCAGCCTTTGTGGCCCTGCTCTCCCTGGACAGCAAG AGGCAGGAGGCCTCCCGGTTGGACGTCTGCTGCTGTGTCAAGCCCCAGGAGCTGCCCCCG CCTGGCCAGGGAGAGGGGCTCCTGCTTGGCTTCTTCCAAAAGGCTTATGCCCCCTTCCTG CTGCACTGGATCACTCGAGGTGTTGTGCTGCTGCTGTTTCTCGCCCTGTTCGGAGTGAGC CTCTACTCCATGTGCCACATCAGCGTGGGACTGGACCAGGAGCTGGCCCTGCCCAAGGAC TCGTACCTGCTTGACTATTTCCTCTTTCTGAACCGCTACTTCGAGGTGGGGGCCCCGGTG TACTTTGTTACCACCTTGGGCTACAACTTCTCCAGCGAGGCTGGGATGAATGCCATCTGC TCCAGTGCAGGCTGCAACAACTTCTCCTTCACCCAGAAGATCCAGTATGCCACAGAGTTC CCTGAGCAGTCTTACCTGGCCATCCCTGCCTCCTCCTGGGTGGATGACTTCATTGACTGG CTGACCCCGTCCTCCTGCTGCCGCCTTTATATATCTGGCCCCAATAAGGACAAGTTCTGC CCCTCGACCGTCAACTCTCTGAACTGCCTAAAGAACTGCATGAGCATCACGATGGGCTCT GTGAGGCCCTCGGTGGAGCAGTTCCATAAGTATCTTCCCTGGTTCCTGAACGACCGGCCC AACATCAAATGTCCCAAAGGCGGCCTGGCAGCATACAGCACCTCTGTGAACTTGACTTCA GATGGCCAGGTTTTAGCCTCCAGGTTCATGGCCTATCACAAGCCCCTGAAAAACTCACAG GATTACACAGAAGCTCTGCGGGCAGCTCGAGAGCTGGCAGCCAACATCACTGCTGACCTG CGGAAAGTGCCTGGAACAGACCCGGCTTTTGAGGTCTTCCCCTACACGATCACCAATGTG TTTTATGAGCAGTACCTGACCATCCTCCCTGAGGGGCTCTTCATGCTCAGCCTCTGCCTT GTGCCCACCTTCGCTGTCTCCTGCCTCCTGCTGGGCCTGGACCTGCGCTCCGGCCTCCTC AACCTGCTCTCCATTGTCATGATCCTCGTGGACACTGTCGGCTTCATGGCCCTGTGGGGC ATCAGTTACAATGCTGTGTCCCTCATCAACCTGGTCTCGGCGGTGGGCATGTCTGTGGAG TTTGTGTCCCACATTACCCGCTCCTTTGCCATCAGCACCAAGCCCACCTGGCTGGAGAGG GCCAAAGAGGCCACCATCTCTATGGGAAGTGCGGTGTTTGCAGGTGTGGCCATGACCAAC CTGCCTGGCATCCTTGTCCTGGGCCTCGCCAAGGCCCAGCTCATTCAGATCTTCTTCTTC CGCCTCAACCTCCTGATCACTCTGCTGGGCCTGCTGCATGGCTTGGTCTTCCTGCCCGTC ATCCTCAGCTACGTGGGGCCTGACGTTAACCCGGCTCTGGCACTGGAGCAGAAGCGGGCT GAGGAGGCGGTGGCAGCAGTCATGGTGGCCTCTTGCCCAAATCACCCCTCCCGAGTCTCC ACAGCTGACAACATCTATGTCAACCACAGCTTTGAAGGTTCTATCAAAGGTGCTGGTGCC ATCAGCAACTTCTTGCCCAACAATGGGCGGCAGTTCTGA
- Chromosome Location
- 7
- Locus
- 7p13
- External Identifiers
Resource Link UniProtKB ID Q9UHC9 UniProtKB Entry Name NPCL1_HUMAN GenBank Protein ID 6643036 GenBank Gene ID AF192522 GeneCard ID NPC1L1 GenAtlas ID NPC1L1 HGNC ID HGNC:7898 PDB ID(s) 3QNT, 7DF8, 7DFW, 7DFZ, 7N4U, 7N4V, 7N4X KEGG ID hsa:29881 IUPHAR/Guide To Pharmacology ID 2629 NCBI Gene ID 29881 - General References
- Davies JP, Levy B, Ioannou YA: Evidence for a Niemann-pick C (NPC) gene family: identification and characterization of NPC1L1. Genomics. 2000 Apr 15;65(2):137-45. [Article]
- Altmann SW, Davis HR Jr, Zhu LJ, Yao X, Hoos LM, Tetzloff G, Iyer SP, Maguire M, Golovko A, Zeng M, Wang L, Murgolo N, Graziano MP: Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science. 2004 Feb 20;303(5661):1201-4. [Article]
- Wang J, Chu BB, Ge L, Li BL, Yan Y, Song BL: Membrane topology of human NPC1L1, a key protein in enterohepatic cholesterol absorption. J Lipid Res. 2009 Aug;50(8):1653-62. doi: 10.1194/jlr.M800669-JLR200. Epub 2009 Mar 26. [Article]
- Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. [Article]
- Scherer SW, Cheung J, MacDonald JR, Osborne LR, Nakabayashi K, Herbrick JA, Carson AR, Parker-Katiraee L, Skaug J, Khaja R, Zhang J, Hudek AK, Li M, Haddad M, Duggan GE, Fernandez BA, Kanematsu E, Gentles S, Christopoulos CC, Choufani S, Kwasnicka D, Zheng XH, Lai Z, Nusskern D, Zhang Q, Gu Z, Lu F, Zeesman S, Nowaczyk MJ, Teshima I, Chitayat D, Shuman C, Weksberg R, Zackai EH, Grebe TA, Cox SR, Kirkpatrick SJ, Rahman N, Friedman JM, Heng HH, Pelicci PG, Lo-Coco F, Belloni E, Shaffer LG, Pober B, Morton CC, Gusella JF, Bruns GA, Korf BR, Quade BJ, Ligon AH, Ferguson H, Higgins AW, Leach NT, Herrick SR, Lemyre E, Farra CG, Kim HG, Summers AM, Gripp KW, Roberts W, Szatmari P, Winsor EJ, Grzeschik KH, Teebi A, Minassian BA, Kere J, Armengol L, Pujana MA, Estivill X, Wilson MD, Koop BF, Tosi S, Moore GE, Boright AP, Zlotorynski E, Kerem B, Kroisel PM, Petek E, Oscier DG, Mould SJ, Dohner H, Dohner K, Rommens JM, Vincent JB, Venter JC, Li PW, Mural RJ, Adams MD, Tsui LC: Human chromosome 7: DNA sequence and biology. Science. 2003 May 2;300(5620):767-72. Epub 2003 Apr 10. [Article]
- Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
- Davies JP, Scott C, Oishi K, Liapis A, Ioannou YA: Inactivation of NPC1L1 causes multiple lipid transport defects and protects against diet-induced hypercholesterolemia. J Biol Chem. 2005 Apr 1;280(13):12710-20. Epub 2005 Jan 25. [Article]
- van der Veen JN, Kruit JK, Havinga R, Baller JF, Chimini G, Lestavel S, Staels B, Groot PH, Groen AK, Kuipers F: Reduced cholesterol absorption upon PPARdelta activation coincides with decreased intestinal expression of NPC1L1. J Lipid Res. 2005 Mar;46(3):526-34. Epub 2004 Dec 16. [Article]
- Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, Crona JH, Davis HR Jr, Dean DC, Detmers PA, Graziano MP, Hughes M, Macintyre DE, Ogawa A, O'neill KA, Iyer SP, Shevell DE, Smith MM, Tang YS, Makarewicz AM, Ujjainwalla F, Altmann SW, Chapman KT, Thornberry NA: The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8132-7. Epub 2005 May 31. [Article]
- Chu BB, Ge L, Xie C, Zhao Y, Miao HH, Wang J, Li BL, Song BL: Requirement of myosin Vb.Rab11a.Rab11-FIP2 complex in cholesterol-regulated translocation of NPC1L1 to the cell surface. J Biol Chem. 2009 Aug 14;284(33):22481-90. doi: 10.1074/jbc.M109.034355. Epub 2009 Jun 19. [Article]
- Yamanashi Y, Takada T, Shoda J, Suzuki H: Novel function of Niemann-Pick C1-like 1 as a negative regulator of Niemann-Pick C2 protein. Hepatology. 2012 Mar;55(3):953-64. doi: 10.1002/hep.24772. Epub 2012 Jan 30. [Article]
- Kwon HJ, Palnitkar M, Deisenhofer J: The structure of the NPC1L1 N-terminal domain in a closed conformation. PLoS One. 2011 Apr 15;6(4):e18722. doi: 10.1371/journal.pone.0018722. [Article]
- Wang J, Williams CM, Hegele RA: Compound heterozygosity for two non-synonymous polymorphisms in NPC1L1 in a non-responder to ezetimibe. Clin Genet. 2005 Feb;67(2):175-7. [Article]