Human Metabolome Database: Showing Protein Niemann-Pick C1-like protein 1 (HMDBP02773)

Identification Biological properties Gene properties Protein properties External links References XML Show 1 metabolite

Identification

HMDB Protein ID

HMDBP02773

Secondary Accession Numbers

8279

Name

Niemann-Pick C1-like protein 1

Synonyms

Not Available

Gene Name

NPC1L1

Protein Type

Enzyme

Biological Properties

General Function

Involved in cholesterol transport

Specific Function

Play 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 absorbtion. 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

Pathways

Not Available

Reactions

Not Available

GO Classification

Component
cell part
membrane
membrane part
intrinsic to membrane
integral to membrane
Function
molecular transducer activity
signal transducer activity
receptor activity
transmembrane receptor activity
hedgehog receptor activity
Process
establishment of localization
transport
lipid transport
sterol transport
cholesterol transport

Cellular Location

Cell membrane
Multi-pass membrane protein
Multi-pass membrane protein
Multi-pass membrane protein
Apical cell membrane
Cytoplasmic vesicle membrane

Gene Properties

Chromosome Location

Chromosome:7

Locus

7p13

SNPs

NPC1L1

Gene Sequence

>4080 bp
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
GATGGCCAGGTTTTAGACACAGTTGCCATTCTGTCACCCAGGCTGGAGTACAGTGGCACA
ATCTCGGCTCACTGCAACCTCTACCTCCTGGATTCAGCCTCCAGGTTCATGGCCTATCAC
AAGCCCCTGAAAAACTCACAGGATTACACAGAAGCTCTGCGGGCAGCTCGAGAGCTGGCA
GCCAACATCACTGCTGACCTGCGGAAAGTGCCTGGAACAGACCCGGCTTTTGAGGTCTTC
CCCTACACGATCACCAATGTGTTTTATGAGCAGTACCTGACCATCCTCCCTGAGGGGCTC
TTCATGCTCAGCCTCTGCCTTGTGCCCACCTTCGCTGTCTCCTGCCTCCTGCTGGGCCTG
GACCTGCGCTCCGGCCTCCTCAACCTGCTCTCCATTGTCATGATCCTCGTGGACACTGTC
GGCTTCATGGCCCTGTGGGGCATCAGTTACAATGCTGTGTCCCTCATCAACCTGGTCTCG
GCGGTGGGCATGTCTGTGGAGTTTGTGTCCCACATTACCCGCTCCTTTGCCATCAGCACC
AAGCCCACCTGGCTGGAGAGGGCCAAAGAGGCCACCATCTCTATGGGAAGTGCGGTGTTT
GCAGGTGTGGCCATGACCAACCTGCCTGGCATCCTTGTCCTGGGCCTCGCCAAGGCCCAG
CTCATTCAGATCTTCTTCTTCCGCCTCAACCTCCTGATCACTCTGCTGGGCCTGCTGCAT
GGCTTGGTCTTCCTGCCCGTCATCCTCAGCTACGTGGGGCCTGACGTTAACCCGGCTCTG
GCACTGGAGCAGAAGCGGGCTGAGGAGGCGGTGGCAGCAGTCATGGTGGCCTCTTGCCCA
AATCACCCCTCCCGAGTCTCCACAGCTGACAACATCTATGTCAACCACAGCTTTGAAGGT
TCTATCAAAGGTGCTGGTGCCATCAGCAACTTCTTGCCCAACAATGGGCGGCAGTTCTGA

Protein Properties

Number of Residues

1359

Molecular Weight

148696.5

Theoretical pI

6.31

Pfam Domain Function

Patched (PF02460 )

Signals

1-21

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

Protein Sequence

>Niemann-Pick C1-like protein 1
MAEAGLRGWLLWALLLRLAQSEPYTTIHQPGYCAFYDECGKNPELSGSLMTLSNVSCLSN
TPARKITGDHLILLQKICPRLYTGPNTQACCSAKQLVSLEASLSITKALLTRCPACSDNF
VNLHCHNTCSPNQSLFINVTRVAQLGAGQLPAVVAYEAFYQHSFAEQSYDSCSRVRVPAA
ATLAVGTMCGVYGSALCNAQRWLNFQGDTGNGLAPLDITFHLLEPGQAVGSGIQPLNEGV
ARCNESQGDDVATCSCQDCAASCPAIARPQALDSTFYLGQMPGSLVLIIILCSVFAVVTI
LLVGFRVAPARDKSKMVDPKKGTSLSDKLSFSTHTLLGQFFQGWGTWVASWPLTILVLSV
IPVVALAAGLVFTELTTDPVELWSAPNSQARSEKAFHDQHFGPFFRTNQVILTAPNRSSY
RYDSLLLGPKNFSGILDLDLLLELLELQERLRHLQVWSPEAQRNISLQDICYAPLNPDNT
SLYDCCINSLLQYFQNNRTLLLLTANQTLMGQTSQVDWKDHFLYCANAPLTFKDGTALAL
SCMADYGAPVFPFLAIGGYKGKDYSEAEALIMTFSLNNYPAGDPRLAQAKLWEEAFLEEM
RAFQRRMAGMFQVTFMAERSLEDEINRTTAEDLPIFATSYIVIFLYISLALGSYSSWSRV
MVDSKATLGLGGVAVVLGAVMAAMGFFSYLGIRSSLVILQVVPFLVLSVGADNIFIFVLE
YQRLPRRPGEPREVHIGRALGRVAPSMLLCSLSEAICFFLGALTPMPAVRTFALTSGLAV
ILDFLLQMSAFVALLSLDSKRQEASRLDVCCCVKPQELPPPGQGEGLLLGFFQKAYAPFL
LHWITRGVVLLLFLALFGVSLYSMCHISVGLDQELALPKDSYLLDYFLFLNRYFEVGAPV
YFVTTLGYNFSSEAGMNAICSSAGCNNFSFTQKIQYATEFPEQSYLAIPASSWVDDFIDW
LTPSSCCRLYISGPNKDKFCPSTVNSLNCLKNCMSITMGSVRPSVEQFHKYLPWFLNDRP
NIKCPKGGLAAYSTSVNLTSDGQVLDTVAILSPRLEYSGTISAHCNLYLLDSASRFMAYH
KPLKNSQDYTEALRAARELAANITADLRKVPGTDPAFEVFPYTITNVFYEQYLTILPEGL
FMLSLCLVPTFAVSCLLLGLDLRSGLLNLLSIVMILVDTVGFMALWGISYNAVSLINLVS
AVGMSVEFVSHITRSFAISTKPTWLERAKEATISMGSAVFAGVAMTNLPGILVLGLAKAQ
LIQIFFFRLNLLITLLGLLHGLVFLPVILSYVGPDVNPALALEQKRAEEAVAAVMVASCP
NHPSRVSTADNIYVNHSFEGSIKGAGAISNFLPNNGRQF

External Links

GenBank ID Protein

6643036

UniProtKB/Swiss-Prot ID

Q9UHC9

UniProtKB/Swiss-Prot Entry Name

NPCL1_HUMAN

PDB IDs

Not Available

GenBank Gene ID

GeneCard ID

GenAtlas ID

HGNC ID

References

General References

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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]