Q9UHC9 (NPCL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Niemann-Pick C1-like protein 1

Gene names

Name:

NPC1L1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1359 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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 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. Acts as a negative regulator of NPC2 and down-regulates its expression and secretion by inhibiting its maturation and accelerating its degradation. Ref.10 Ref.12
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. Interacts with NPC2. Ref.11 Ref.12
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.8, localizes in a subcellular vesicular compartment rich in RAB5. Ref.8
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.8
Induction	Expression is decreased in Caco-2 cells upon PPARD activation. Ref.9
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.

Ontologies

Keywords
Biological process	Cholesterol metabolism Lipid metabolism Steroid metabolism Sterol metabolism
Cellular component	Cell membrane Cytoplasmic vesicle Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cholesterol biosynthetic process Inferred from mutant phenotype PubMed 17140581. Source: HGNC intestinal cholesterol absorption Inferred from mutant phenotype PubMed 17140581. Source: HGNC lipoprotein metabolic process Inferred from mutant phenotype PubMed 17140581. Source: HGNC
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasmic vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from direct assay Ref.3. Source: UniProtKB plasma membrane Traceable author statement. Source: Reactome
Molecular_function	hedgehog receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Potential

Chain

22 – 1359

1338

Niemann-Pick C1-like protein 1

PRO_0000023266

Regions

Topological domain

22 – 284

263

Extracellular Potential

Transmembrane

285 – 305

21

Helical; Name=1; Potential

Topological domain

306 – 351

46

Cytoplasmic Potential

Transmembrane

352 – 372

21

Helical; Name=2; Potential

Topological domain

373 – 632

260

Extracellular Potential

Transmembrane

633 – 653

21

Helical; Name=3; Potential

Topological domain

654 – 666

13

Cytoplasmic Potential

Transmembrane

667 – 687

21

Helical; Name=4; Potential

Topological domain

688 – 696

9

Extracellular Potential

Transmembrane

697 – 717

21

Helical; Name=5; Potential

Topological domain

718 – 742

25

Cytoplasmic Potential

Transmembrane

743 – 763

21

Helical; Name=6; Potential

Topological domain

764 – 776

13

Extracellular Potential

Transmembrane

777 – 797

21

Helical; Name=7; Potential

Topological domain

798 – 846

49

Cytoplasmic Potential

Transmembrane

847 – 867

21

Helical; Name=8; Potential

Topological domain

868 – 882

15

Extracellular Potential

Transmembrane

883 – 903

21

Helical; Name=9; Potential

Topological domain

904 – 1139

236

Cytoplasmic Potential

Transmembrane

1140 – 1160

21

Helical; Name=10; Potential

Topological domain

1161 – 1168

8

Extracellular Potential

Transmembrane

1169 – 1189

21

Helical; Name=11; Potential

Topological domain

1190 – 1191

2

Cytoplasmic Potential

Transmembrane

1192 – 1212

21

Helical; Name=12; Potential

Topological domain

1213 – 1236

24

Extracellular Potential

Transmembrane

1237 – 1257

21

Helical; Name=13; Potential

Topological domain

1258 – 1359

102

Cytoplasmic Potential

Domain

632 – 797

166

SSD

Compositional bias

500 – 503

4

Poly-Leu

Amino acid modifications

Glycosylation

54

1

N-linked (GlcNAc...) Potential

Glycosylation

132

1

N-linked (GlcNAc...) Potential

Glycosylation

138

1

N-linked (GlcNAc...) Potential

Glycosylation

244

1

N-linked (GlcNAc...) Potential

Glycosylation

416

1

N-linked (GlcNAc...) Potential

Glycosylation

431

1

N-linked (GlcNAc...) Potential

Glycosylation

464

1

N-linked (GlcNAc...) Potential

Glycosylation

479

1

N-linked (GlcNAc...) Potential

Glycosylation

497

1

N-linked (GlcNAc...) Potential

Glycosylation

506

1

N-linked (GlcNAc...) Potential

Glycosylation

626

1

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

723 – 724

2

RL → GP in isoform 3.

VSP_015312

Alternative sequence

725 – 1359

635

Missing in isoform 3.

VSP_015313

Alternative sequence

1046 – 1072

27

Missing in isoform 2.

VSP_015314

Natural variant

55

1

V → L Non-response to ezetimibe treatment. Ref.13

VAR_023369

Natural variant

510

1

M → I.
Corresponds to variant rs1468384 [ dbSNP | Ensembl ].

VAR_056659

Natural variant

1233

1

I → N. Ref.13
Corresponds to variant rs52815063 [ dbSNP | Ensembl ].

VAR_023370

Natural variant

1308

1

E → K.
Corresponds to variant rs217435 [ dbSNP | Ensembl ].

VAR_056660

Experimental info

Sequence conflict

1073

1

T → A in AAF20396. Ref.1

Secondary structure

1

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1359

Helix Strand Turn

Details...

Beta strand

34 – 40

7

Beta strand

47 – 49

3

Beta strand

55 – 58

4

Helix

68 – 77

10

Helix

79 – 81

3

Beta strand

84 – 86

3

Beta strand

88 – 90

3

Helix

93 – 109

17

Turn

110 – 112

3

Helix

114 – 129

16

Helix

133 – 135

3

Beta strand

137 – 143

7

Beta strand

146 – 149

4

Beta strand

152 – 161

10

Helix

162 – 172

11

Helix

186 – 188

3

Beta strand

194 – 196

3

Helix

199 – 206

8

Turn

209 – 212

4

Beta strand

215 – 223

9

Helix

225 – 228

4

Turn

248 – 250

3

Turn

256 – 258

3

Helix

260 – 262

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 28, 2012. Version 2. Checksum: 594F698B48D66DE7	FASTA	1,359	148,728
	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 DSTSRFMAYH 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
	Isoform 2 (NPC1L1DELTAE15) [UniParc]. Checksum: 8483F336EBFD3EA3	FASTA	1,332	145,794
	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 DGQVLTSRFM AYHKPLKNSQ DYTEALRAAR ELAANITADL 1090 1100 1110 1120 1130 1140 RKVPGTDPAF EVFPYTITNV FYEQYLTILP EGLFMLSLCL VPTFAVSCLL LGLDLRSGLL 1150 1160 1170 1180 1190 1200 NLLSIVMILV DTVGFMALWG ISYNAVSLIN LVSAVGMSVE FVSHITRSFA ISTKPTWLER 1210 1220 1230 1240 1250 1260 AKEATISMGS AVFAGVAMTN LPGILVLGLA KAQLIQIFFF RLNLLITLLG LLHGLVFLPV 1270 1280 1290 1300 1310 1320 ILSYVGPDVN PALALEQKRA EEAVAAVMVA SCPNHPSRVS TADNIYVNHS FEGSIKGAGA 1330 ISNFLPNNGR QF
	Isoform 3 (NPCL1T) [UniParc]. Checksum: 15564FF42565270F	FASTA	724	79,138
	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 YQGP

References

	« Hide 'large scale' referencesShow '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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
[3]	"Membrane topology of human NPC1L1, a key protein in enterohepatic cholesterol absorption." Wang J., Chu B.-B., Ge L., Li B.-L., Yan Y., Song B.L. J. Lipid Res. 50:1653-1662(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TOPOLOGY.
[4]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., 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 C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., 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 W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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. , 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Liver.
[8]	"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] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[9]	"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] [Europe PMC] [Abstract] Cited for: INDUCTION.
[10]	"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. , 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] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RAB11A; MYO5B AND RAB11FIP2.
[12]	"Novel function of Niemann-Pick C1-like 1 as a negative regulator of Niemann-Pick C2 protein." Yamanashi Y., Takada T., Shoda J., Suzuki H. Hepatology 55:953-964(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH NPC2.
[13]	"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] [Europe PMC] [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.
FJ481111 mRNA. Translation: ACL18055.1.
AC004938 Genomic DNA. No translation available.
CH236960 Genomic DNA. Translation: EAL23753.1.
CH471128 Genomic DNA. Translation: EAW61096.1.
CH471128 Genomic DNA. Translation: EAW61097.1.
CH471128 Genomic DNA. Translation: EAW61098.1.
BC117178 mRNA. Translation: AAI17179.1.

IPI

IPI00002984.
IPI00640209.
IPI00641846.

RefSeq

NP_001095118.1. NM_001101648.1.
NP_037521.2. NM_013389.2.

UniGene

Hs.567486.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3QNT	X-ray	2.83	A	22-284	[»]

ProteinModelPortal

Q9UHC9.

SMR

Q9UHC9. Positions 22-265.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UHC9. 1 interaction.

STRING

9606.ENSP00000289547.

Protein family/group databases

TCDB

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

PTM databases

PhosphoSite

Q9UHC9.

Polymorphism databases

DMDM

73921245.

Proteomic databases

PaxDb

Q9UHC9.

PRIDE

Q9UHC9.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000289547; ENSP00000289547; ENSG00000015520.
ENST00000381160; ENSP00000370552; ENSG00000015520.
ENST00000423141; ENSP00000404670; ENSG00000015520.

GeneID

29881.

KEGG

hsa:29881.

UCSC

uc003tld.3. human.

Organism-specific databases

CTD

29881.

GeneCards

GC07M044552.

H-InvDB

HIX0201184.

HGNC

HGNC:7898. NPC1L1.

HPA

HPA018105.

MIM

608010. gene+phenotype.

neXtProt

NX_Q9UHC9.

PharmGKB

PA31699.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG149152.

HOGENOM

HOG000036674.

HOVERGEN

HBG003913.

InParanoid

Q9UHC9.

KO

K14461.

OMA

FMAERSL.

OrthoDB

EOG490787.

PhylomeDB

Q9UHC9.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

Q9UHC9.

Bgee

Q9UHC9.

CleanEx

HS_NPC1L1.

Genevestigator

Q9UHC9.

GermOnline

ENSG00000015520. Homo sapiens.

Family and domain databases

InterPro

IPR003392. Patched.
IPR000731. SSD.
[Graphical view]

Pfam

PF02460. Patched. 1 hit.
[Graphical view]

PROSITE

PS50156. SSD. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q9UHC9.

ChEMBL

CHEMBL2027.

DrugBank

DB00973. Ezetimibe.

GenomeRNAi

29881.

NextBio

52405.

SOURCE

Search...

Entry information

Entry name

NPCL1_HUMAN

Accession

Primary (citable) accession number: Q9UHC9
Secondary accession number(s): A4D2J7 , D3DVK9, Q17RV5, Q6R3Q4, Q9UHC8

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 30, 2005
Last sequence update:	November 28, 2012
Last modified:	May 1, 2013
This is version 97 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.