Niemann-Pick C1-like protein 1

Details

Name
Niemann-Pick C1-like protein 1
Synonyms
  • Niemann-Pick C1-like protein 1 precursor
Gene Name
NPC1L1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0037079|Niemann-Pick C1-like protein 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
Functions
drug binding / hedgehog receptor activity / myosin V binding / Rab GTPase binding
Processes
cholesterol biosynthetic process / cholesterol homeostasis / cholesterol transport / intestinal cholesterol absorption / lipoprotein metabolic process / response to drug / small molecule metabolic process / sterol transport
Components
apical plasma membrane / brush border membrane / cytoplasmic vesicle membrane / integral component of membrane / plasma membrane
General Function
Rab gtpase binding
Specific Function
Plays a major role in cholesterol homeostasis. Is critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte. Is the direct molecular target of ezetimibe, a drug that inhibits cholesterol absorption. Lack of activity leads to multiple lipid transport defects. The protein may have a function in the transport of multiple lipids and their homeostasis, and may play a critical role in regulating lipid metabolism. Acts as a negative regulator of NPC2 and down-regulates its expression and secretion by inhibiting its maturation and accelerating its degradation.
Pfam Domain Function
Transmembrane Regions
285-305 352-372 633-653 667-687 697-717 743-763 777-797 847-867 883-903 1140-1160 1169-1189 1192-1212 1237-1257
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
ResourceLink
UniProtKB IDQ9UHC9
UniProtKB Entry NameNPCL1_HUMAN
GenBank Protein ID6643036
GenBank Gene IDAF192522
GenAtlas IDNPC1L1
HGNC IDHGNC:7898
General References
  1. 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. [PubMed:10783261]
  2. 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. [PubMed:14976318]
  3. 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. [PubMed:19325169]
  4. 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. [PubMed:12853948]
  5. 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. [PubMed:12690205]
  6. 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. [PubMed:15489334]
  7. 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. [PubMed:15671032]
  8. 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. [PubMed:15604518]
  9. 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. [PubMed:15928087]
  10. 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. [PubMed:19542231]
  11. 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. [PubMed:22095670]
  12. 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. [PubMed:21525977]
  13. 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. [PubMed:15679830]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00973EzetimibeapprovedyesinhibitorDetails
DB11635TocofersolanapprovednosubstrateDetails
DB00163Vitamin Eapproved, nutraceutical, vet_approvedunknownDetails