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Q9UHC9 (NPCL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 84. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
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to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Niemann-Pick C1-like protein 1
Gene names
Name:NPC1L1
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length1359 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.6

Subunit structure

Interacts with RAB11A, MYO5B and RAB11FIP2. Interaction with RAB11A, MYO5B and RAB11FIP2 is required for proper transport to the plasma membrane upon cholesterol depletion. Ref.7

Subcellular location

Apical cell membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein By similarity. Cytoplasmic vesicle membrane; Multi-pass membrane protein. Note: Subfractionation of brush border membranes from proximal enterocytes suggests considerable association with the apical membrane fraction. Exists as a predominantly cell surface membrane expressed protein By similarity. According to Ref.4, localizes in a subcellular vesicular compartment rich in RAB5. Ref.4

Tissue specificity

Widely expressed. Expressed in liver. Also expressed in small intestine, pancreas, kidney, lung, pancreas, spleen, heart, gall bladder, brain, testis, stomach and muscle. Ref.1 Ref.2 Ref.4

Induction

Expression is decreased in Caco-2 cells upon PPARD activation. Ref.5

Post-translational modification

Highly glycosylated By similarity.

Polymorphism

Variations in NPC1L1 gene could be associated with non-response to ezetimibe treatment.

Sequence similarities

Belongs to the patched family.

Contains 1 SSD (sterol-sensing) domain.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UHC9-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9UHC9-2)

Also known as: NPC1L1DELTAE15;

The sequence of this isoform differs from the canonical sequence as follows:
     1046-1072: Missing.
Isoform 3 (identifier: Q9UHC9-3)

Also known as: NPCL1T;

The sequence of this isoform differs from the canonical sequence as follows:
     723-724: RL → GP
     725-1359: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 13591338Niemann-Pick C1-like protein 1
PRO_0000023266

Regions

Topological domain22 – 284263Extracellular Potential
Transmembrane285 – 30521Helical; Name=1; Potential
Topological domain306 – 35146Cytoplasmic Potential
Transmembrane352 – 37221Helical; Name=2; Potential
Topological domain373 – 632260Extracellular Potential
Transmembrane633 – 65321Helical; Name=3; Potential
Topological domain654 – 66613Cytoplasmic Potential
Transmembrane667 – 68721Helical; Name=4; Potential
Topological domain688 – 6969Extracellular Potential
Transmembrane697 – 71721Helical; Name=5; Potential
Topological domain718 – 74225Cytoplasmic Potential
Transmembrane743 – 76321Helical; Name=6; Potential
Topological domain764 – 77613Extracellular Potential
Transmembrane777 – 79721Helical; Name=7; Potential
Topological domain798 – 84649Cytoplasmic Potential
Transmembrane847 – 86721Helical; Name=8; Potential
Topological domain868 – 88215Extracellular Potential
Transmembrane883 – 90321Helical; Name=9; Potential
Topological domain904 – 1139236Cytoplasmic Potential
Transmembrane1140 – 116021Helical; Name=10; Potential
Topological domain1161 – 11688Extracellular Potential
Transmembrane1169 – 118921Helical; Name=11; Potential
Topological domain1190 – 11912Cytoplasmic Potential
Transmembrane1192 – 121221Helical; Name=12; Potential
Topological domain1213 – 123624Extracellular Potential
Transmembrane1237 – 125721Helical; Name=13; Potential
Topological domain1258 – 1359102Cytoplasmic Potential
Domain632 – 797166SSD
Compositional bias500 – 5034Poly-Leu

Amino acid modifications

Glycosylation541N-linked (GlcNAc...) Potential
Glycosylation1321N-linked (GlcNAc...) Potential
Glycosylation1381N-linked (GlcNAc...) Potential
Glycosylation2441N-linked (GlcNAc...) Potential
Glycosylation4161N-linked (GlcNAc...) Potential
Glycosylation4311N-linked (GlcNAc...) Potential
Glycosylation4641N-linked (GlcNAc...) Potential
Glycosylation4791N-linked (GlcNAc...) Potential
Glycosylation4971N-linked (GlcNAc...) Potential
Glycosylation5061N-linked (GlcNAc...) Potential
Glycosylation6261N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence723 – 7242RL → GP in isoform 3.
VSP_015312
Alternative sequence725 – 1359635Missing in isoform 3.
VSP_015313
Alternative sequence1046 – 107227Missing in isoform 2.
VSP_015314
Natural variant551V → L Non-response to ezetimibe treatment. Ref.8
VAR_023369
Natural variant5101M → I.
Corresponds to variant rs1468384 [ dbSNP | Ensembl ].
VAR_056659
Natural variant12331I → N. Ref.8
Corresponds to variant rs52815063 [ dbSNP | Ensembl ].
VAR_023370
Natural variant13081E → K.
Corresponds to variant rs217435 [ dbSNP | Ensembl ].
VAR_056660

Secondary structure

1 ............................... 1359
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 3225D53D93B768B6

FASTA1,359148,698
        10         20         30         40         50         60 
MAEAGLRGWL LWALLLRLAQ SEPYTTIHQP GYCAFYDECG KNPELSGSLM TLSNVSCLSN 

        70         80         90        100        110        120 
TPARKITGDH LILLQKICPR LYTGPNTQAC CSAKQLVSLE ASLSITKALL TRCPACSDNF 

       130        140        150        160        170        180 
VNLHCHNTCS PNQSLFINVT RVAQLGAGQL PAVVAYEAFY QHSFAEQSYD SCSRVRVPAA 

       190        200        210        220        230        240 
ATLAVGTMCG VYGSALCNAQ RWLNFQGDTG NGLAPLDITF HLLEPGQAVG SGIQPLNEGV 

       250        260        270        280        290        300 
ARCNESQGDD VATCSCQDCA ASCPAIARPQ ALDSTFYLGQ MPGSLVLIII LCSVFAVVTI 

       310        320        330        340        350        360 
LLVGFRVAPA RDKSKMVDPK KGTSLSDKLS FSTHTLLGQF FQGWGTWVAS WPLTILVLSV 

       370        380        390        400        410        420 
IPVVALAAGL VFTELTTDPV ELWSAPNSQA RSEKAFHDQH FGPFFRTNQV ILTAPNRSSY 

       430        440        450        460        470        480 
RYDSLLLGPK NFSGILDLDL LLELLELQER LRHLQVWSPE AQRNISLQDI CYAPLNPDNT 

       490        500        510        520        530        540 
SLYDCCINSL LQYFQNNRTL LLLTANQTLM GQTSQVDWKD HFLYCANAPL TFKDGTALAL 

       550        560        570        580        590        600 
SCMADYGAPV FPFLAIGGYK GKDYSEAEAL IMTFSLNNYP AGDPRLAQAK LWEEAFLEEM 

       610        620        630        640        650        660 
RAFQRRMAGM FQVTFMAERS LEDEINRTTA EDLPIFATSY IVIFLYISLA LGSYSSWSRV 

       670        680        690        700        710        720 
MVDSKATLGL GGVAVVLGAV MAAMGFFSYL GIRSSLVILQ VVPFLVLSVG ADNIFIFVLE 

       730        740        750        760        770        780 
YQRLPRRPGE PREVHIGRAL GRVAPSMLLC SLSEAICFFL GALTPMPAVR TFALTSGLAV 

       790        800        810        820        830        840 
ILDFLLQMSA FVALLSLDSK RQEASRLDVC CCVKPQELPP PGQGEGLLLG FFQKAYAPFL 

       850        860        870        880        890        900 
LHWITRGVVL LLFLALFGVS LYSMCHISVG LDQELALPKD SYLLDYFLFL NRYFEVGAPV 

       910        920        930        940        950        960 
YFVTTLGYNF SSEAGMNAIC SSAGCNNFSF TQKIQYATEF PEQSYLAIPA SSWVDDFIDW 

       970        980        990       1000       1010       1020 
LTPSSCCRLY ISGPNKDKFC PSTVNSLNCL KNCMSITMGS VRPSVEQFHK YLPWFLNDRP 

      1030       1040       1050       1060       1070       1080 
NIKCPKGGLA AYSTSVNLTS DGQVLDTVAI LSPRLEYSGT ISAHCNLYLL DSASRFMAYH 

      1090       1100       1110       1120       1130       1140 
KPLKNSQDYT EALRAARELA ANITADLRKV PGTDPAFEVF PYTITNVFYE QYLTILPEGL 

      1150       1160       1170       1180       1190       1200 
FMLSLCLVPT FAVSCLLLGL DLRSGLLNLL SIVMILVDTV GFMALWGISY NAVSLINLVS 

      1210       1220       1230       1240       1250       1260 
AVGMSVEFVS HITRSFAIST KPTWLERAKE ATISMGSAVF AGVAMTNLPG ILVLGLAKAQ 

      1270       1280       1290       1300       1310       1320 
LIQIFFFRLN LLITLLGLLH GLVFLPVILS YVGPDVNPAL ALEQKRAEEA VAAVMVASCP 

      1330       1340       1350 
NHPSRVSTAD NIYVNHSFEG SIKGAGAISN FLPNNGRQF

« Hide

Isoform 2 (NPC1L1DELTAE15) [UniParc].

Checksum: EFE94F80309C3BF2
Show »

FASTA1,332145,764
Isoform 3 (NPCL1T) [UniParc].

Checksum: 15564FF42565270F
Show »

FASTA72479,138

References

« Hide 'large scale' references
[1]"Evidence for a Niemann-Pick C (NPC) gene family: identification and characterization of NPC1L1."
Davies J.P., Levy B., Ioannou Y.A.
Genomics 65:137-145(2000) [PubMed: 10783261] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), TISSUE SPECIFICITY.
[2]"Niemann-Pick C1 like 1 protein is critical for intestinal cholesterol absorption."
Altmann S.W., Davis H.R. Jr., Zhu L.-J., Yao X., Hoos L.M., Tetzloff G., Iyer S.P.N., Maguire M., Golovko A., Zeng M., Wang L., Murgolo N., Graziano M.P.
Science 303:1201-1204(2004) [PubMed: 14976318] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
[3]"Human chromosome 7: DNA sequence and biology."
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. expand/collapse author list , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
Science 300:767-772(2003) [PubMed: 12690205] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Inactivation of NPC1L1 causes multiple lipid transport defects and protects against diet-induced hypercholesterolemia."
Davies J.P., Scott C., Oishi K., Liapis A., Ioannou Y.A.
J. Biol. Chem. 280:12710-12720(2005) [PubMed: 15671032] [Abstract]
Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[5]"Reduced cholesterol absorption upon PPARdelta activation coincides with decreased intestinal expression of NPC1L1."
van der Veen J.N., Kruit J.K., Havinga R., Baller J.F.W., Chimini G., Lestavel S., Staels B., Groot P.H.E., Groen A.K., Kuipers F.
J. Lipid Res. 46:526-534(2005) [PubMed: 15604518] [Abstract]
Cited for: INDUCTION.
[6]"The target of ezetimibe is Niemann-Pick C1-like 1 (NPC1L1)."
Garcia-Calvo M., Lisnock J., Bull H.G., Hawes B.E., Burnett D.A., Braun M.P., Crona J.H., Davis H.R. Jr., Dean D.C., Detmers P.A., Graziano M.P., Hughes M., MacIntyre D.E., Ogawa A., O'neill K.A., Iyer S.P.N., Shevell D.E., Smith M.M. expand/collapse author list , Tang Y.S., Makarewicz A.M., Ujjainwalla F., Altmann S.W., Chapman K.T., Thornberry N.A.
Proc. Natl. Acad. Sci. U.S.A. 102:8132-8137(2005) [PubMed: 15928087] [Abstract]
Cited for: FUNCTION.
[7]"Requirement of myosin Vb.Rab11a.Rab11-FIP2 complex in cholesterol-regulated translocation of NPC1L1 to the cell surface."
Chu B.-B., Ge L., Xie C., Zhao Y., Miao H.-H., Wang J., Li B.-L., Song B.-L.
J. Biol. Chem. 284:22481-22490(2009) [PubMed: 19542231] [Abstract]
Cited for: INTERACTION WITH RAB11A; MYO5B AND RAB11FIP2.
[8]"Compound heterozygosity for two non-synonymous polymorphisms in NPC1L1 in a non-responder to ezetimibe."
Wang J., Williams C.M., Hegele R.A.
Clin. Genet. 67:175-177(2005) [PubMed: 15679830] [Abstract]
Cited for: VARIANTS LEU-55 AND ASN-1233.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AF192522 mRNA. Translation: AAF20396.1.
AF192523 mRNA. Translation: AAF20397.1.
AY515256 mRNA. Translation: AAS56939.1.
AY437865 mRNA. Translation: AAR97886.1.
CH236960 Genomic DNA. Translation: EAL23753.1.
IPIIPI00002984.
IPI00640209.
IPI00641846.
RefSeqNP_001095118.1. NM_001101648.1.
NP_037521.2. NM_013389.2.
UniGeneHs.567486.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3QNTX-ray2.83A22-284[»]
ProteinModelPortalQ9UHC9.
SMRQ9UHC9. Positions 22-265, 1121-1194.
ModBaseSearch...

Protein-protein interaction databases

STRINGQ9UHC9.

Protein family/group databases

TCDB2.A.6.6.6. resistance-nodulation-cell division (RND) superfamily.

Polymorphism databases

DMDM73921245.

Proteomic databases

PRIDEQ9UHC9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000289547; ENSP00000289547; ENSG00000015520.
GeneID29881.
KEGGhsa:29881.
UCSCuc003tlc.1. human.
uc003tld.2. human.

Organism-specific databases

CTD29881.
GeneCardsGC07M044552.
H-InvDBHIX0201184.
HGNCHGNC:7898. NPC1L1.
HPAHPA018105.
MIM608010. gene+phenotype.
neXtProtNX_Q9UHC9.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG19100.
GeneTreeENSGT00550000074234.
HOGENOMHBG326129.
HOVERGENHBG003913.
InParanoidQ9UHC9.
OrthoDBEOG490787.
PhylomeDBQ9UHC9.

Enzyme and pathway databases

ReactomeREACT_22258. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpressQ9UHC9.
BgeeQ9UHC9.
CleanExHS_NPC1L1.
GenevestigatorQ9UHC9.
GermOnlineENSG00000015520. Homo sapiens.

Family and domain databases

InterProIPR003392. Patched.
IPR000731. SSD.
[Graphical view]
KOK14461.
PfamPF02460. Patched. 1 hit.
[Graphical view]
PROSITEPS50156. SSD. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

DrugBankDB00973. Ezetimibe.
NextBio52405.
SOURCESearch...

Entry information

Entry nameNPCL1_HUMAN
AccessionPrimary (citable) accession number: Q9UHC9
Secondary accession number(s): A4D2J7, Q6R3Q4, Q9UHC8
Entry history
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: May 1, 2000
Last modified: January 25, 2012
This is version 84 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

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