NPCL1_HUMAN
ID NPCL1_HUMAN Reviewed; 1359 AA.
AC Q9UHC9; A4D2J7; B7ZLE6; D3DVK9; Q17RV5; Q6R3Q4; Q9UHC8;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2012, sequence version 2.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=NPC1-like intracellular cholesterol transporter 1 {ECO:0000312|HGNC:HGNC:7898};
DE Short=NPC1L1 {ECO:0000303|PubMed:15928087};
DE AltName: Full=Niemann-Pick C1-like protein 1 {ECO:0000303|PubMed:10783261};
DE Flags: Precursor;
GN Name=NPC1L1 {ECO:0000312|HGNC:HGNC:7898};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), AND TISSUE SPECIFICITY.
RX PubMed=10783261; DOI=10.1006/geno.2000.6151;
RA Davies J.P., Levy B., Ioannou Y.A.;
RT "Evidence for a Niemann-Pick C (NPC) gene family: identification and
RT characterization of NPC1L1.";
RL Genomics 65:137-145(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RX PubMed=14976318; DOI=10.1126/science.1093131;
RA Altmann S.W., Davis H.R. Jr., Zhu L.-J., Yao X., Hoos L.M., Tetzloff G.,
RA Iyer S.P.N., Maguire M., Golovko A., Zeng M., Wang L., Murgolo N.,
RA Graziano M.P.;
RT "Niemann-Pick C1 like 1 protein is critical for intestinal cholesterol
RT absorption.";
RL Science 303:1201-1204(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TOPOLOGY.
RX PubMed=19325169; DOI=10.1194/jlr.m800669-jlr200;
RA Wang J., Chu B.-B., Ge L., Li B.-L., Yan Y., Song B.L.;
RT "Membrane topology of human NPC1L1, a key protein in enterohepatic
RT cholesterol absorption.";
RL J. Lipid Res. 50:1653-1662(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4).
RC TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15671032; DOI=10.1074/jbc.m409110200;
RA Davies J.P., Scott C., Oishi K., Liapis A., Ioannou Y.A.;
RT "Inactivation of NPC1L1 causes multiple lipid transport defects and
RT protects against diet-induced hypercholesterolemia.";
RL J. Biol. Chem. 280:12710-12720(2005).
RN [9]
RP INDUCTION.
RX PubMed=15604518; DOI=10.1194/jlr.m400400-jlr200;
RA van der Veen J.N., Kruit J.K., Havinga R., Baller J.F.W., Chimini G.,
RA Lestavel S., Staels B., Groot P.H.E., Groen A.K., Kuipers F.;
RT "Reduced cholesterol absorption upon PPARdelta activation coincides with
RT decreased intestinal expression of NPC1L1.";
RL J. Lipid Res. 46:526-534(2005).
RN [10]
RP FUNCTION.
RX PubMed=15928087; DOI=10.1073/pnas.0500269102;
RA Garcia-Calvo M., Lisnock J., Bull H.G., Hawes B.E., Burnett D.A.,
RA Braun M.P., Crona J.H., Davis H.R. Jr., Dean D.C., Detmers P.A.,
RA Graziano M.P., Hughes M., MacIntyre D.E., Ogawa A., O'neill K.A.,
RA Iyer S.P.N., Shevell D.E., Smith M.M., Tang Y.S., Makarewicz A.M.,
RA Ujjainwalla F., Altmann S.W., Chapman K.T., Thornberry N.A.;
RT "The target of ezetimibe is Niemann-Pick C1-like 1 (NPC1L1).";
RL Proc. Natl. Acad. Sci. U.S.A. 102:8132-8137(2005).
RN [11]
RP INTERACTION WITH RAB11A; MYO5B AND RAB11FIP2.
RX PubMed=19542231; DOI=10.1074/jbc.m109.034355;
RA Chu B.-B., Ge L., Xie C., Zhao Y., Miao H.-H., Wang J., Li B.-L.,
RA Song B.-L.;
RT "Requirement of myosin Vb.Rab11a.Rab11-FIP2 complex in cholesterol-
RT regulated translocation of NPC1L1 to the cell surface.";
RL J. Biol. Chem. 284:22481-22490(2009).
RN [12]
RP FUNCTION, AND INTERACTION WITH NPC2.
RX PubMed=22095670; DOI=10.1002/hep.24772;
RA Yamanashi Y., Takada T., Shoda J., Suzuki H.;
RT "Novel function of Niemann-Pick C1-like 1 as a negative regulator of
RT Niemann-Pick C2 protein.";
RL Hepatology 55:953-964(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.83 ANGSTROMS) OF 22-284, DISULFIDE BONDS, AND
RP GLYCOSYLATION AT ASN-54 AND ASN-138.
RX PubMed=21525977; DOI=10.1371/journal.pone.0018722;
RA Kwon H.J., Palnitkar M., Deisenhofer J.;
RT "The structure of the NPC1L1 N-terminal domain in a closed conformation.";
RL PLoS ONE 6:E18722-E18722(2011).
RN [14]
RP VARIANTS LEU-55 AND ASN-1233, AND POLYMORPHISM.
RX PubMed=15679830; DOI=10.1111/j.1399-0004.2004.00388.x;
RA Wang J., Williams C.M., Hegele R.A.;
RT "Compound heterozygosity for two non-synonymous polymorphisms in NPC1L1 in
RT a non-responder to ezetimibe.";
RL Clin. Genet. 67:175-177(2005).
RN [15]
RP VARIANTS 167-GLN--PHE-1359 DEL; 406-ARG--PHE-1359 DEL; 483-TYR--PHE-1359
RP DEL; 592-TRP--PHE-1359 DEL; 601-ARG--PHE-1359 DEL; 604-GLN--PHE-1359 DEL;
RP 738-ARG--PHE-1359 DEL; 803-GLU--PHE-1359 DEL; 967-CYS--PHE-1359 DEL AND
RP 1325-ARG--PHE-1359 DEL, POLYMORPHISM, AND INVOLVEMENT IN LDLCQ7.
RX PubMed=25390462; DOI=10.1056/nejmoa1405386;
RG Myocardial Infarction Genetics Consortium Investigators;
RA Stitziel N.O., Won H.H., Morrison A.C., Peloso G.M., Do R., Lange L.A.,
RA Fontanillas P., Gupta N., Duga S., Goel A., Farrall M., Saleheen D.,
RA Ferrario P., Koenig I., Asselta R., Merlini P.A., Marziliano N.,
RA Notarangelo M.F., Schick U., Auer P., Assimes T.L., Reilly M., Wilensky R.,
RA Rader D.J., Hovingh G.K., Meitinger T., Kessler T., Kastrati A.,
RA Laugwitz K.L., Siscovick D., Rotter J.I., Hazen S.L., Tracy R., Cresci S.,
RA Spertus J., Jackson R., Schwartz S.M., Natarajan P., Crosby J., Muzny D.,
RA Ballantyne C., Rich S.S., O'Donnell C.J., Abecasis G., Sunaev S.,
RA Nickerson D.A., Buring J.E., Ridker P.M., Chasman D.I., Austin E.,
RA Kullo I.J., Weeke P.E., Shaffer C.M., Bastarache L.A., Denny J.C.,
RA Roden D.M., Palmer C., Deloukas P., Lin D.Y., Tang Z.Z., Erdmann J.,
RA Schunkert H., Danesh J., Marrugat J., Elosua R., Ardissino D.,
RA McPherson R., Watkins H., Reiner A.P., Wilson J.G., Altshuler D.,
RA Gibbs R.A., Lander E.S., Boerwinkle E., Gabriel S., Kathiresan S.;
RT "Inactivating mutations in NPC1L1 and protection from coronary heart
RT disease.";
RL N. Engl. J. Med. 371:2072-2082(2014).
RN [16]
RP INTERACTION WITH LIMA1, AND MUTAGENESIS OF 1300-LEU--GLU-1303;
RP 1304-GLN--ARG-1306 AND 1308-GLU-GLU-1309.
RX PubMed=29880681; DOI=10.1126/science.aao6575;
RA Zhang Y.Y., Fu Z.Y., Wei J., Qi W., Baituola G., Luo J., Meng Y.J.,
RA Guo S.Y., Yin H., Jiang S.Y., Li Y.F., Miao H.H., Liu Y., Wang Y., Li B.L.,
RA Ma Y.T., Song B.L.;
RT "A LIMA1 variant promotes low plasma LDL cholesterol and decreases
RT intestinal cholesterol absorption.";
RL Science 360:1087-1092(2018).
CC -!- FUNCTION: Plays a major role in cholesterol homeostasis
CC (PubMed:22095670). Critical for the uptake of cholesterol across the
CC plasma membrane of the intestinal enterocyte (PubMed:22095670).
CC Involved in plant sterol absorption, it transports sitosterol, although
CC at lower rates than cholesterol (By similarity). Is the direct
CC molecular target of ezetimibe, a drug that inhibits cholesterol
CC absorption and is approved for the treatment of hypercholesterolemia
CC (PubMed:15928087). May have a function in the transport of multiple
CC lipids and their homeostasis, thereby influencing lipid metabolism
CC regulation (PubMed:15671032). May be involved in caveolin trafficking
CC from the plasma membrane (By similarity). In addition, acts as a
CC negative regulator of NPC2 and down-regulates its expression and
CC secretion by inhibiting its maturation and accelerating its degradation
CC (PubMed:22095670). {ECO:0000250|UniProtKB:Q6T3U3,
CC ECO:0000250|UniProtKB:Q6T3U4, ECO:0000269|PubMed:15928087,
CC ECO:0000269|PubMed:22095670, ECO:0000305|PubMed:15671032}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesterol(in) = cholesterol(out); Xref=Rhea:RHEA:39747,
CC ChEBI:CHEBI:16113; Evidence={ECO:0000305|PubMed:15671032,
CC ECO:0000305|PubMed:22095670};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=sitosterol(out) = sitosterol(in); Xref=Rhea:RHEA:70723,
CC ChEBI:CHEBI:27693; Evidence={ECO:0000250|UniProtKB:Q6T3U3};
CC -!- SUBUNIT: Interacts with RAB11A, MYO5B and RAB11FIP2. Interaction with
CC RAB11A, MYO5B and RAB11FIP2 is required for proper transport to the
CC plasma membrane upon cholesterol depletion. Interacts with NPC2.
CC Interacts with LIMA1 (PubMed:29880681). {ECO:0000269|PubMed:19542231,
CC ECO:0000269|PubMed:22095670, ECO:0000269|PubMed:29880681}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:15671032}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:15671032}. Cell membrane
CC {ECO:0000250|UniProtKB:Q6T3U3}; Multi-pass membrane protein
CC {ECO:0000250}. Cytoplasmic vesicle membrane
CC {ECO:0000269|PubMed:15671032}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:15671032}. Note=Subfractionation of brush border
CC membranes from proximal enterocytes suggests considerable association
CC with the apical membrane fraction. Exists as a predominantly cell
CC surface membrane expressed protein (By similarity). According to
CC PubMed:15671032, localizes in a subcellular vesicular compartment rich
CC in RAB5. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9UHC9-1; Sequence=Displayed;
CC Name=2; Synonyms=NPC1L1DELTAE15;
CC IsoId=Q9UHC9-2; Sequence=VSP_015314;
CC Name=3; Synonyms=NPCL1T;
CC IsoId=Q9UHC9-3; Sequence=VSP_015312, VSP_015313;
CC Name=4;
CC IsoId=Q9UHC9-4; Sequence=VSP_054503, VSP_015314;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in liver. Also
CC expressed in small intestine, pancreas, kidney, lung, pancreas, spleen,
CC heart, gall bladder, brain, testis, stomach and muscle.
CC {ECO:0000269|PubMed:10783261, ECO:0000269|PubMed:14976318,
CC ECO:0000269|PubMed:15671032}.
CC -!- INDUCTION: Expression is decreased in Caco-2 cells upon PPARD
CC activation. {ECO:0000269|PubMed:15604518}.
CC -!- PTM: Highly glycosylated. {ECO:0000250}.
CC -!- POLYMORPHISM: Genetic variations in NPC1L1 influence low density
CC lipoprotein cholesterol (LDL-C) content defining the low density
CC lipoprotein cholesterol level quantitative trait locus 7 (LDLCQ7)
CC [MIM:617966]. Inactivating variants may confer a lower risk of coronary
CC heart disease (PubMed:25390462). Rare NPC1L1 variants also influence
CC response to ezetimibe, a drug that reduces plasma LDL-C by blocking
CC sterol absorption in enterocytes (PubMed:15679830).
CC {ECO:0000269|PubMed:15679830, ECO:0000269|PubMed:25390462}.
CC -!- MISCELLANEOUS: Target of cholesterol lowering drugs.
CC {ECO:0000269|PubMed:21525977}.
CC -!- SIMILARITY: Belongs to the patched family. {ECO:0000305}.
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DR EMBL; AF192522; AAF20396.1; -; mRNA.
DR EMBL; AF192523; AAF20397.1; -; mRNA.
DR EMBL; AY515256; AAS56939.1; -; mRNA.
DR EMBL; AY437865; AAR97886.1; -; mRNA.
DR EMBL; FJ481111; ACL18055.1; -; mRNA.
DR EMBL; AC004938; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH236960; EAL23753.1; -; Genomic_DNA.
DR EMBL; CH471128; EAW61096.1; -; Genomic_DNA.
DR EMBL; CH471128; EAW61097.1; -; Genomic_DNA.
DR EMBL; CH471128; EAW61098.1; -; Genomic_DNA.
DR EMBL; BC117178; AAI17179.1; -; mRNA.
DR EMBL; BC143756; AAI43757.1; -; mRNA.
DR CCDS; CCDS43575.1; -. [Q9UHC9-2]
DR CCDS; CCDS5491.1; -. [Q9UHC9-1]
DR CCDS; CCDS75587.1; -. [Q9UHC9-3]
DR RefSeq; NP_001095118.1; NM_001101648.1.
DR RefSeq; NP_001287896.1; NM_001300967.1. [Q9UHC9-3]
DR RefSeq; NP_037521.2; NM_013389.2. [Q9UHC9-1]
DR PDB; 3QNT; X-ray; 2.83 A; A=22-284.
DR PDB; 7DF8; EM; 3.03 A; A=1-1301.
DR PDB; 7DFW; EM; 2.69 A; A=1-1315.
DR PDB; 7DFZ; EM; 3.58 A; A=1-1300.
DR PDB; 7N4U; EM; 3.34 A; A/B=1-1359.
DR PDB; 7N4V; EM; 3.58 A; A/B=1-1359.
DR PDB; 7N4X; EM; 3.33 A; A=1-1359.
DR PDBsum; 3QNT; -.
DR PDBsum; 7DF8; -.
DR PDBsum; 7DFW; -.
DR PDBsum; 7DFZ; -.
DR PDBsum; 7N4U; -.
DR PDBsum; 7N4V; -.
DR PDBsum; 7N4X; -.
DR AlphaFoldDB; Q9UHC9; -.
DR SMR; Q9UHC9; -.
DR BioGRID; 118936; 1.
DR IntAct; Q9UHC9; 1.
DR STRING; 9606.ENSP00000289547; -.
DR BindingDB; Q9UHC9; -.
DR ChEMBL; CHEMBL2027; -.
DR DrugBank; DB00973; Ezetimibe.
DR DrugBank; DB11635; Tocofersolan.
DR DrugBank; DB00163; Vitamin E.
DR DrugCentral; Q9UHC9; -.
DR GuidetoPHARMACOLOGY; 2629; -.
DR SwissLipids; SLP:000001532; -.
DR TCDB; 2.A.6.6.6; the resistance-nodulation-cell division (rnd) superfamily.
DR GlyGen; Q9UHC9; 11 sites.
DR iPTMnet; Q9UHC9; -.
DR PhosphoSitePlus; Q9UHC9; -.
DR BioMuta; NPC1L1; -.
DR DMDM; 425906049; -.
DR jPOST; Q9UHC9; -.
DR MassIVE; Q9UHC9; -.
DR PaxDb; Q9UHC9; -.
DR PeptideAtlas; Q9UHC9; -.
DR PRIDE; Q9UHC9; -.
DR ProteomicsDB; 7220; -.
DR ProteomicsDB; 84317; -. [Q9UHC9-1]
DR ProteomicsDB; 84318; -. [Q9UHC9-2]
DR ProteomicsDB; 84319; -. [Q9UHC9-3]
DR Antibodypedia; 13403; 206 antibodies from 22 providers.
DR DNASU; 29881; -.
DR Ensembl; ENST00000289547.8; ENSP00000289547.4; ENSG00000015520.15. [Q9UHC9-1]
DR Ensembl; ENST00000423141.1; ENSP00000404670.1; ENSG00000015520.15. [Q9UHC9-3]
DR GeneID; 29881; -.
DR KEGG; hsa:29881; -.
DR UCSC; uc003tlb.4; human. [Q9UHC9-1]
DR CTD; 29881; -.
DR DisGeNET; 29881; -.
DR GeneCards; NPC1L1; -.
DR HGNC; HGNC:7898; NPC1L1.
DR HPA; ENSG00000015520; Group enriched (intestine, liver).
DR MalaCards; NPC1L1; -.
DR MIM; 608010; gene.
DR MIM; 617966; phenotype.
DR neXtProt; NX_Q9UHC9; -.
DR OpenTargets; ENSG00000015520; -.
DR Orphanet; 426; NON RARE IN EUROPE: Familial hypobetalipoproteinemia.
DR PharmGKB; PA31699; -.
DR VEuPathDB; HostDB:ENSG00000015520; -.
DR eggNOG; KOG1933; Eukaryota.
DR GeneTree; ENSGT00940000159904; -.
DR HOGENOM; CLU_002359_6_0_1; -.
DR InParanoid; Q9UHC9; -.
DR OrthoDB; 731120at2759; -.
DR PhylomeDB; Q9UHC9; -.
DR TreeFam; TF300416; -.
DR PathwayCommons; Q9UHC9; -.
DR Reactome; R-HSA-8963678; Intestinal lipid absorption. [Q9UHC9-2]
DR SignaLink; Q9UHC9; -.
DR SIGNOR; Q9UHC9; -.
DR BioGRID-ORCS; 29881; 21 hits in 1070 CRISPR screens.
DR ChiTaRS; NPC1L1; human.
DR GenomeRNAi; 29881; -.
DR Pharos; Q9UHC9; Tclin.
DR PRO; PR:Q9UHC9; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9UHC9; protein.
DR Bgee; ENSG00000015520; Expressed in jejunal mucosa and 99 other tissues.
DR ExpressionAtlas; Q9UHC9; baseline and differential.
DR Genevisible; Q9UHC9; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0044214; C:spanning component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0015485; F:cholesterol binding; IDA:UniProtKB.
DR GO; GO:0031489; F:myosin V binding; IPI:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IPI:UniProtKB.
DR GO; GO:0032934; F:sterol binding; IBA:GO_Central.
DR GO; GO:0008431; F:vitamin E binding; IDA:UniProtKB.
DR GO; GO:0071501; P:cellular response to sterol depletion; IDA:UniProtKB.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IMP:HGNC-UCL.
DR GO; GO:0042632; P:cholesterol homeostasis; IBA:GO_Central.
DR GO; GO:0030301; P:cholesterol transport; IMP:UniProtKB.
DR GO; GO:0030299; P:intestinal cholesterol absorption; IMP:HGNC-UCL.
DR GO; GO:0042157; P:lipoprotein metabolic process; IMP:HGNC-UCL.
DR GO; GO:0015918; P:sterol transport; IBA:GO_Central.
DR GO; GO:0042360; P:vitamin E metabolic process; IDA:UniProtKB.
DR GO; GO:0051180; P:vitamin transport; IDA:UniProtKB.
DR InterPro; IPR032190; NPC1_N.
DR InterPro; IPR003392; Ptc/Disp.
DR InterPro; IPR000731; SSD.
DR Pfam; PF16414; NPC1_N; 1.
DR Pfam; PF02460; Patched; 1.
DR Pfam; PF12349; Sterol-sensing; 1.
DR PROSITE; PS50156; SSD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cholesterol metabolism;
KW Cytoplasmic vesicle; Disulfide bond; Glycoprotein; Lipid metabolism;
KW Membrane; Reference proteome; Signal; Steroid metabolism;
KW Sterol metabolism; Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..1359
FT /note="NPC1-like intracellular cholesterol transporter 1"
FT /id="PRO_0000023266"
FT TOPO_DOM 22..284
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 285..305
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 306..351
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 352..372
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 373..632
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 633..653
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 654..666
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 667..687
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 688..696
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 697..717
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 718..742
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 743..763
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 764..776
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 777..797
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 798..846
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 847..867
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 868..1139
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1140..1160
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1161..1168
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1169..1189
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1190..1191
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1192..1212
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1213..1236
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1237..1257
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1258..1268
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1269..1289
FT /note="Helical; Name=13"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1290..1359
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 632..797
FT /note="SSD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT CARBOHYD 54
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21525977"
FT CARBOHYD 132
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21525977"
FT CARBOHYD 244
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 416
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 431
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 464
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 479
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 497
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 506
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 626
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 33..90
FT /evidence="ECO:0000269|PubMed:21525977"
FT DISULFID 39..57
FT /evidence="ECO:0000269|PubMed:21525977"
FT DISULFID 78..125
FT /evidence="ECO:0000269|PubMed:21525977"
FT DISULFID 91..129
FT /evidence="ECO:0000269|PubMed:21525977"
FT DISULFID 113..254
FT /evidence="ECO:0000269|PubMed:21525977"
FT DISULFID 116..172
FT /evidence="ECO:0000269|PubMed:21525977"
FT DISULFID 189..197
FT /evidence="ECO:0000269|PubMed:21525977"
FT DISULFID 243..259
FT /evidence="ECO:0000269|PubMed:21525977"
FT DISULFID 256..263
FT /evidence="ECO:0000269|PubMed:21525977"
FT DISULFID 471..485
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 525..542
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 920..925
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 966..1024
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 980..989
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT VAR_SEQ 723..724
FT /note="RL -> GP (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10783261"
FT /id="VSP_015312"
FT VAR_SEQ 725..1359
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10783261"
FT /id="VSP_015313"
FT VAR_SEQ 850..895
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054503"
FT VAR_SEQ 1046..1072
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:10783261,
FT ECO:0000303|PubMed:14976318, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:19325169"
FT /id="VSP_015314"
FT VARIANT 55
FT /note="V -> L (found in a non-responder to ezetimibe
FT treatment; dbSNP:rs119457968)"
FT /evidence="ECO:0000269|PubMed:15679830"
FT /id="VAR_023369"
FT VARIANT 167..1359
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:25390462"
FT /id="VAR_080844"
FT VARIANT 406..1359
FT /note="Missing (associated with low LDL-C content and
FT protection against coronary heart disease)"
FT /evidence="ECO:0000269|PubMed:25390462"
FT /id="VAR_080845"
FT VARIANT 483..1359
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:25390462"
FT /id="VAR_080846"
FT VARIANT 510
FT /note="M -> I (in dbSNP:rs1468384)"
FT /id="VAR_056659"
FT VARIANT 592..1359
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:25390462"
FT /id="VAR_080847"
FT VARIANT 601..1359
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:25390462"
FT /id="VAR_080848"
FT VARIANT 604..1359
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:25390462"
FT /id="VAR_080849"
FT VARIANT 738..1359
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:25390462"
FT /id="VAR_080850"
FT VARIANT 803..1359
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:25390462"
FT /id="VAR_080851"
FT VARIANT 967..1359
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:25390462"
FT /id="VAR_080852"
FT VARIANT 1233
FT /note="I -> N (found in a non-responder to ezetimibe
FT treatment; dbSNP:rs52815063)"
FT /evidence="ECO:0000269|PubMed:15679830"
FT /id="VAR_023370"
FT VARIANT 1308
FT /note="E -> K (in dbSNP:rs217435)"
FT /id="VAR_056660"
FT VARIANT 1325..1359
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:25390462"
FT /id="VAR_080853"
FT MUTAGEN 1300..1303
FT /note="LALE->AAAA: Does not affect interaction with LIMA1."
FT /evidence="ECO:0000269|PubMed:29880681"
FT MUTAGEN 1304..1306
FT /note="QKR->AAA: Abolishes interaction with LIMA1."
FT /evidence="ECO:0000269|PubMed:29880681"
FT MUTAGEN 1308..1309
FT /note="EE->AA: Does not affect interaction with LIMA1."
FT /evidence="ECO:0000269|PubMed:29880681"
FT CONFLICT 1073
FT /note="T -> A (in Ref. 1; AAF20396 and 7; AAI43757)"
FT /evidence="ECO:0000305"
FT STRAND 34..40
FT /evidence="ECO:0007829|PDB:3QNT"
FT STRAND 47..49
FT /evidence="ECO:0007829|PDB:3QNT"
FT STRAND 55..58
FT /evidence="ECO:0007829|PDB:3QNT"
FT HELIX 68..77
FT /evidence="ECO:0007829|PDB:3QNT"
FT HELIX 79..81
FT /evidence="ECO:0007829|PDB:3QNT"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:3QNT"
FT STRAND 88..90
FT /evidence="ECO:0007829|PDB:3QNT"
FT HELIX 93..109
FT /evidence="ECO:0007829|PDB:3QNT"
FT TURN 110..112
FT /evidence="ECO:0007829|PDB:3QNT"
FT HELIX 114..129
FT /evidence="ECO:0007829|PDB:3QNT"
FT HELIX 133..135
FT /evidence="ECO:0007829|PDB:3QNT"
FT STRAND 137..143
FT /evidence="ECO:0007829|PDB:3QNT"
FT STRAND 146..149
FT /evidence="ECO:0007829|PDB:3QNT"
FT STRAND 152..161
FT /evidence="ECO:0007829|PDB:3QNT"
FT HELIX 162..172
FT /evidence="ECO:0007829|PDB:3QNT"
FT HELIX 186..188
FT /evidence="ECO:0007829|PDB:3QNT"
FT STRAND 194..196
FT /evidence="ECO:0007829|PDB:3QNT"
FT HELIX 199..206
FT /evidence="ECO:0007829|PDB:3QNT"
FT TURN 209..212
FT /evidence="ECO:0007829|PDB:3QNT"
FT STRAND 215..223
FT /evidence="ECO:0007829|PDB:3QNT"
FT HELIX 225..228
FT /evidence="ECO:0007829|PDB:3QNT"
FT TURN 248..250
FT /evidence="ECO:0007829|PDB:3QNT"
FT TURN 256..258
FT /evidence="ECO:0007829|PDB:3QNT"
FT HELIX 260..262
FT /evidence="ECO:0007829|PDB:3QNT"
FT HELIX 334..350
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 352..367
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 368..372
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 379..383
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 389..400
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 406..412
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 420..423
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 425..427
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 429..432
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 434..436
FT /evidence="ECO:0007829|PDB:7N4U"
FT HELIX 438..452
FT /evidence="ECO:0007829|PDB:7N4X"
FT TURN 459..461
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 463..465
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 467..469
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 474..476
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 477..479
FT /evidence="ECO:0007829|PDB:7N4U"
FT HELIX 482..484
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 487..489
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 490..492
FT /evidence="ECO:0007829|PDB:7N4X"
FT TURN 493..496
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 498..501
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 505..509
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 512..516
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 518..527
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 535..537
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 545..548
FT /evidence="ECO:0007829|PDB:7N4U"
FT HELIX 552..555
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 556..558
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 564..566
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 569..576
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 586..606
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 608..610
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 614..616
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 620..629
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 633..648
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 655..659
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 660..663
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 666..689
FT /evidence="ECO:0007829|PDB:7N4X"
FT TURN 696..701
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 702..723
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 732..761
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 767..803
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 808..810
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 827..834
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 836..840
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 843..863
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 864..866
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 873..880
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 882..892
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 899..904
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 913..917
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 922..925
FT /evidence="ECO:0007829|PDB:7N4U"
FT HELIX 930..938
FT /evidence="ECO:0007829|PDB:7N4X"
FT TURN 941..943
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 948..951
FT /evidence="ECO:0007829|PDB:7N4U"
FT HELIX 953..960
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 961..973
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 978..980
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 987..989
FT /evidence="ECO:0007829|PDB:7N4U"
FT STRAND 991..995
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 998..1000
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 1005..1016
FT /evidence="ECO:0007829|PDB:7N4X"
FT TURN 1029..1032
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 1033..1038
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 1040..1042
FT /evidence="ECO:0007829|PDB:7N4U"
FT STRAND 1077..1079
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 1086..1107
FT /evidence="ECO:0007829|PDB:7N4X"
FT STRAND 1119..1122
FT /evidence="ECO:0007829|PDB:7N4X"
FT TURN 1124..1128
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 1131..1133
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 1136..1156
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 1162..1186
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 1192..1204
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 1206..1217
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 1224..1251
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 1254..1256
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 1260..1265
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 1268..1280
FT /evidence="ECO:0007829|PDB:7N4X"
FT TURN 1281..1283
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 1284..1292
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 1298..1302
FT /evidence="ECO:0007829|PDB:7N4X"
FT HELIX 1305..1308
FT /evidence="ECO:0007829|PDB:7N4X"
SQ SEQUENCE 1359 AA; 148728 MW; 594F698B48D66DE7 CRC64;
MAEAGLRGWL LWALLLRLAQ SEPYTTIHQP GYCAFYDECG KNPELSGSLM TLSNVSCLSN
TPARKITGDH LILLQKICPR LYTGPNTQAC CSAKQLVSLE ASLSITKALL TRCPACSDNF
VNLHCHNTCS PNQSLFINVT RVAQLGAGQL PAVVAYEAFY QHSFAEQSYD SCSRVRVPAA
ATLAVGTMCG VYGSALCNAQ RWLNFQGDTG NGLAPLDITF HLLEPGQAVG SGIQPLNEGV
ARCNESQGDD VATCSCQDCA ASCPAIARPQ ALDSTFYLGQ MPGSLVLIII LCSVFAVVTI
LLVGFRVAPA RDKSKMVDPK KGTSLSDKLS FSTHTLLGQF FQGWGTWVAS WPLTILVLSV
IPVVALAAGL VFTELTTDPV ELWSAPNSQA RSEKAFHDQH FGPFFRTNQV ILTAPNRSSY
RYDSLLLGPK NFSGILDLDL LLELLELQER LRHLQVWSPE AQRNISLQDI CYAPLNPDNT
SLYDCCINSL LQYFQNNRTL LLLTANQTLM GQTSQVDWKD HFLYCANAPL TFKDGTALAL
SCMADYGAPV FPFLAIGGYK GKDYSEAEAL IMTFSLNNYP AGDPRLAQAK LWEEAFLEEM
RAFQRRMAGM FQVTFMAERS LEDEINRTTA EDLPIFATSY IVIFLYISLA LGSYSSWSRV
MVDSKATLGL GGVAVVLGAV MAAMGFFSYL GIRSSLVILQ VVPFLVLSVG ADNIFIFVLE
YQRLPRRPGE PREVHIGRAL GRVAPSMLLC SLSEAICFFL GALTPMPAVR TFALTSGLAV
ILDFLLQMSA FVALLSLDSK RQEASRLDVC CCVKPQELPP PGQGEGLLLG FFQKAYAPFL
LHWITRGVVL LLFLALFGVS LYSMCHISVG LDQELALPKD SYLLDYFLFL NRYFEVGAPV
YFVTTLGYNF SSEAGMNAIC SSAGCNNFSF TQKIQYATEF PEQSYLAIPA SSWVDDFIDW
LTPSSCCRLY ISGPNKDKFC PSTVNSLNCL KNCMSITMGS VRPSVEQFHK YLPWFLNDRP
NIKCPKGGLA AYSTSVNLTS DGQVLDTVAI LSPRLEYSGT ISAHCNLYLL DSTSRFMAYH
KPLKNSQDYT EALRAARELA ANITADLRKV PGTDPAFEVF PYTITNVFYE QYLTILPEGL
FMLSLCLVPT FAVSCLLLGL DLRSGLLNLL SIVMILVDTV GFMALWGISY NAVSLINLVS
AVGMSVEFVS HITRSFAIST KPTWLERAKE ATISMGSAVF AGVAMTNLPG ILVLGLAKAQ
LIQIFFFRLN LLITLLGLLH GLVFLPVILS YVGPDVNPAL ALEQKRAEEA VAAVMVASCP
NHPSRVSTAD NIYVNHSFEG SIKGAGAISN FLPNNGRQF
