Gene/Proteome Database (LMPD)
LMPD ID
LMP001283
Gene ID
Species
Homo sapiens (Human)
Gene Name
NPC1-like 1
Gene Symbol
Synonyms
NPC11L1
Chromosome
7
Map Location
7p13
Summary
The protein encoded by this gene is a multi-pass membrane protein. It contains a conserved N-terminal Niemann-Pick C1 (NPC1) domain and a putative sterol-sensing domain (SSD) which includes a YQRL motif functioning as a plasma membrane to trans-Golgi network transport signal in other proteins. This protein takes up free cholesterol into cells through vesicular endocytosis and plays a critical role in the absorption of intestinal cholesterol. It also has the ability to transport alpha-tocopherol (vitamin E). The drug ezetimibe targets this protein and inhibits the absorption of intestinal cholesterol and alpha-tocopherol. In addition, this protein may play a critical role in regulating lipid metabolism. Polymorphic variations in this gene are associated with plasma total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels and coronary heart disease (CHD) risk. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
Orthologs
Proteins
| Niemann-Pick C1-like protein 1 isoform 1 precursor | |
|---|---|
| Refseq ID | NP_037521 |
| Protein GI | 156231351 |
| UniProt ID | Q9UHC9 |
| mRNA ID | NM_013389 |
| Length | 1359 |
| RefSeq Status | REVIEWED |
| MAEAGLRGWLLWALLLRLAQSEPYTTIHQPGYCAFYDECGKNPELSGSLMTLSNVSCLSNTPARKITGDHLILLQKICPRLYTGPNTQACCSAKQLVSLEASLSITKALLTRCPACSDNFVNLHCHNTCSPNQSLFINVTRVAQLGAGQLPAVVAYEAFYQHSFAEQSYDSCSRVRVPAAATLAVGTMCGVYGSALCNAQRWLNFQGDTGNGLAPLDITFHLLEPGQAVGSGIQPLNEGVARCNESQGDDVATCSCQDCAASCPAIARPQALDSTFYLGQMPGSLVLIIILCSVFAVVTILLVGFRVAPARDKSKMVDPKKGTSLSDKLSFSTHTLLGQFFQGWGTWVASWPLTILVLSVIPVVALAAGLVFTELTTDPVELWSAPNSQARSEKAFHDQHFGPFFRTNQVILTAPNRSSYRYDSLLLGPKNFSGILDLDLLLELLELQERLRHLQVWSPEAQRNISLQDICYAPLNPDNTSLYDCCINSLLQYFQNNRTLLLLTANQTLMGQTSQVDWKDHFLYCANAPLTFKDGTALALSCMADYGAPVFPFLAIGGYKGKDYSEAEALIMTFSLNNYPAGDPRLAQAKLWEEAFLEEMRAFQRRMAGMFQVTFMAERSLEDEINRTTAEDLPIFATSYIVIFLYISLALGSYSSWSRVMVDSKATLGLGGVAVVLGAVMAAMGFFSYLGIRSSLVILQVVPFLVLSVGADNIFIFVLEYQRLPRRPGEPREVHIGRALGRVAPSMLLCSLSEAICFFLGALTPMPAVRTFALTSGLAVILDFLLQMSAFVALLSLDSKRQEASRLDVCCCVKPQELPPPGQGEGLLLGFFQKAYAPFLLHWITRGVVLLLFLALFGVSLYSMCHISVGLDQELALPKDSYLLDYFLFLNRYFEVGAPVYFVTTLGYNFSSEAGMNAICSSAGCNNFSFTQKIQYATEFPEQSYLAIPASSWVDDFIDWLTPSSCCRLYISGPNKDKFCPSTVNSLNCLKNCMSITMGSVRPSVEQFHKYLPWFLNDRPNIKCPKGGLAAYSTSVNLTSDGQVLDTVAILSPRLEYSGTISAHCNLYLLDSTSRFMAYHKPLKNSQDYTEALRAARELAANITADLRKVPGTDPAFEVFPYTITNVFYEQYLTILPEGLFMLSLCLVPTFAVSCLLLGLDLRSGLLNLLSIVMILVDTVGFMALWGISYNAVSLINLVSAVGMSVEFVSHITRSFAISTKPTWLERAKEATISMGSAVFAGVAMTNLPGILVLGLAKAQLIQIFFFRLNLLITLLGLLHGLVFLPVILSYVGPDVNPALALEQKRAEEAVAAVMVASCPNHPSRVSTADNIYVNHSFEGSIKGAGAISNFLPNNGRQF | |
| sig_peptide: 1..21 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 2369 peptide sequence: MAEAGLRGWLLWALLLRLAQS mat_peptide: 22..1332 product: Niemann-Pick C1-like protein 1 isoform 2 calculated_mol_wt: 143414 peptide sequence: EPYTTIHQPGYCAFYDECGKNPELSGSLMTLSNVSCLSNTPARKITGDHLILLQKICPRLYTGPNTQACCSAKQLVSLEASLSITKALLTRCPACSDNFVNLHCHNTCSPNQSLFINVTRVAQLGAGQLPAVVAYEAFYQHSFAEQSYDSCSRVRVPAAATLAVGTMCGVYGSALCNAQRWLNFQGDTGNGLAPLDITFHLLEPGQAVGSGIQPLNEGVARCNESQGDDVATCSCQDCAASCPAIARPQALDSTFYLGQMPGSLVLIIILCSVFAVVTILLVGFRVAPARDKSKMVDPKKGTSLSDKLSFSTHTLLGQFFQGWGTWVASWPLTILVLSVIPVVALAAGLVFTELTTDPVELWSAPNSQARSEKAFHDQHFGPFFRTNQVILTAPNRSSYRYDSLLLGPKNFSGILDLDLLLELLELQERLRHLQVWSPEAQRNISLQDICYAPLNPDNTSLYDCCINSLLQYFQNNRTLLLLTANQTLMGQTSQVDWKDHFLYCANAPLTFKDGTALALSCMADYGAPVFPFLAIGGYKGKDYSEAEALIMTFSLNNYPAGDPRLAQAKLWEEAFLEEMRAFQRRMAGMFQVTFMAERSLEDEINRTTAEDLPIFATSYIVIFLYISLALGSYSSWSRVMVDSKATLGLGGVAVVLGAVMAAMGFFSYLGIRSSLVILQVVPFLVLSVGADNIFIFVLEYQRLPRRPGEPREVHIGRALGRVAPSMLLCSLSEAICFFLGALTPMPAVRTFALTSGLAVILDFLLQMSAFVALLSLDSKRQEASRLDVCCCVKPQELPPPGQGEGLLLGFFQKAYAPFLLHWITRGVVLLLFLALFGVSLYSMCHISVGLDQELALPKDSYLLDYFLFLNRYFEVGAPVYFVTTLGYNFSSEAGMNAICSSAGCNNFSFTQKIQYATEFPEQSYLAIPASSWVDDFIDWLTPSSCCRLYISGPNKDKFCPSTVNSLNCLKNCMSITMGSVRPSVEQFHKYLPWFLNDRPNIKCPKGGLAAYSTSVNLTSDGQVLASRFMAYHKPLKNSQDYTEALRAARELAANITADLRKVPGTDPAFEVFPYTITNVFYEQYLTILPEGLFMLSLCLVPTFAVSCLLLGLDLRSGLLNLLSIVMILVDTVGFMALWGISYNAVSLINLVSAVGMSVEFVSHITRSFAISTKPTWLERAKEATISMGSAVFAGVAMTNLPGILVLGLAKAQLIQIFFFRLNLLITLLGLLHGLVFLPVILSYVGPDVNPALALEQKRAEEAVAAVMVASCPNHPSRVSTADNIYVNHSFEGSIKGAGAISNFLPNNGRQF sig_peptide: 1..21 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 2369 peptide sequence: MAEAGLRGWLLWALLLRLAQS sig_peptide: 1..21 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 2369 peptide sequence: MAEAGLRGWLLWALLLRLAQS mat_peptide: 22..1359 product: Niemann-Pick C1-like protein 1 experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (Q9UHC9.2) calculated_mol_wt: 146378 peptide sequence: EPYTTIHQPGYCAFYDECGKNPELSGSLMTLSNVSCLSNTPARKITGDHLILLQKICPRLYTGPNTQACCSAKQLVSLEASLSITKALLTRCPACSDNFVNLHCHNTCSPNQSLFINVTRVAQLGAGQLPAVVAYEAFYQHSFAEQSYDSCSRVRVPAAATLAVGTMCGVYGSALCNAQRWLNFQGDTGNGLAPLDITFHLLEPGQAVGSGIQPLNEGVARCNESQGDDVATCSCQDCAASCPAIARPQALDSTFYLGQMPGSLVLIIILCSVFAVVTILLVGFRVAPARDKSKMVDPKKGTSLSDKLSFSTHTLLGQFFQGWGTWVASWPLTILVLSVIPVVALAAGLVFTELTTDPVELWSAPNSQARSEKAFHDQHFGPFFRTNQVILTAPNRSSYRYDSLLLGPKNFSGILDLDLLLELLELQERLRHLQVWSPEAQRNISLQDICYAPLNPDNTSLYDCCINSLLQYFQNNRTLLLLTANQTLMGQTSQVDWKDHFLYCANAPLTFKDGTALALSCMADYGAPVFPFLAIGGYKGKDYSEAEALIMTFSLNNYPAGDPRLAQAKLWEEAFLEEMRAFQRRMAGMFQVTFMAERSLEDEINRTTAEDLPIFATSYIVIFLYISLALGSYSSWSRVMVDSKATLGLGGVAVVLGAVMAAMGFFSYLGIRSSLVILQVVPFLVLSVGADNIFIFVLEYQRLPRRPGEPREVHIGRALGRVAPSMLLCSLSEAICFFLGALTPMPAVRTFALTSGLAVILDFLLQMSAFVALLSLDSKRQEASRLDVCCCVKPQELPPPGQGEGLLLGFFQKAYAPFLLHWITRGVVLLLFLALFGVSLYSMCHISVGLDQELALPKDSYLLDYFLFLNRYFEVGAPVYFVTTLGYNFSSEAGMNAICSSAGCNNFSFTQKIQYATEFPEQSYLAIPASSWVDDFIDWLTPSSCCRLYISGPNKDKFCPSTVNSLNCLKNCMSITMGSVRPSVEQFHKYLPWFLNDRPNIKCPKGGLAAYSTSVNLTSDGQVLDTVAILSPRLEYSGTISAHCNLYLLDSTSRFMAYHKPLKNSQDYTEALRAARELAANITADLRKVPGTDPAFEVFPYTITNVFYEQYLTILPEGLFMLSLCLVPTFAVSCLLLGLDLRSGLLNLLSIVMILVDTVGFMALWGISYNAVSLINLVSAVGMSVEFVSHITRSFAISTKPTWLERAKEATISMGSAVFAGVAMTNLPGILVLGLAKAQLIQIFFFRLNLLITLLGLLHGLVFLPVILSYVGPDVNPALALEQKRAEEAVAAVMVASCPNHPSRVSTADNIYVNHSFEGSIKGAGAISNFLPNNGRQF | |
| Niemann-Pick C1-like protein 1 isoform 2 precursor | |
|---|---|
| Refseq ID | NP_001095118 |
| Protein GI | 156231353 |
| UniProt ID | Q9UHC9 |
| mRNA ID | NM_001101648 |
| Length | 1332 |
| RefSeq Status | REVIEWED |
| MAEAGLRGWLLWALLLRLAQSEPYTTIHQPGYCAFYDECGKNPELSGSLMTLSNVSCLSNTPARKITGDHLILLQKICPRLYTGPNTQACCSAKQLVSLEASLSITKALLTRCPACSDNFVNLHCHNTCSPNQSLFINVTRVAQLGAGQLPAVVAYEAFYQHSFAEQSYDSCSRVRVPAAATLAVGTMCGVYGSALCNAQRWLNFQGDTGNGLAPLDITFHLLEPGQAVGSGIQPLNEGVARCNESQGDDVATCSCQDCAASCPAIARPQALDSTFYLGQMPGSLVLIIILCSVFAVVTILLVGFRVAPARDKSKMVDPKKGTSLSDKLSFSTHTLLGQFFQGWGTWVASWPLTILVLSVIPVVALAAGLVFTELTTDPVELWSAPNSQARSEKAFHDQHFGPFFRTNQVILTAPNRSSYRYDSLLLGPKNFSGILDLDLLLELLELQERLRHLQVWSPEAQRNISLQDICYAPLNPDNTSLYDCCINSLLQYFQNNRTLLLLTANQTLMGQTSQVDWKDHFLYCANAPLTFKDGTALALSCMADYGAPVFPFLAIGGYKGKDYSEAEALIMTFSLNNYPAGDPRLAQAKLWEEAFLEEMRAFQRRMAGMFQVTFMAERSLEDEINRTTAEDLPIFATSYIVIFLYISLALGSYSSWSRVMVDSKATLGLGGVAVVLGAVMAAMGFFSYLGIRSSLVILQVVPFLVLSVGADNIFIFVLEYQRLPRRPGEPREVHIGRALGRVAPSMLLCSLSEAICFFLGALTPMPAVRTFALTSGLAVILDFLLQMSAFVALLSLDSKRQEASRLDVCCCVKPQELPPPGQGEGLLLGFFQKAYAPFLLHWITRGVVLLLFLALFGVSLYSMCHISVGLDQELALPKDSYLLDYFLFLNRYFEVGAPVYFVTTLGYNFSSEAGMNAICSSAGCNNFSFTQKIQYATEFPEQSYLAIPASSWVDDFIDWLTPSSCCRLYISGPNKDKFCPSTVNSLNCLKNCMSITMGSVRPSVEQFHKYLPWFLNDRPNIKCPKGGLAAYSTSVNLTSDGQVLASRFMAYHKPLKNSQDYTEALRAARELAANITADLRKVPGTDPAFEVFPYTITNVFYEQYLTILPEGLFMLSLCLVPTFAVSCLLLGLDLRSGLLNLLSIVMILVDTVGFMALWGISYNAVSLINLVSAVGMSVEFVSHITRSFAISTKPTWLERAKEATISMGSAVFAGVAMTNLPGILVLGLAKAQLIQIFFFRLNLLITLLGLLHGLVFLPVILSYVGPDVNPALALEQKRAEEAVAAVMVASCPNHPSRVSTADNIYVNHSFEGSIKGAGAISNFLPNNGRQF | |
| Niemann-Pick C1-like protein 1 isoform 3 precursor | |
|---|---|
| Refseq ID | NP_001287896 |
| Protein GI | 665821271 |
| UniProt ID | Q9UHC9 |
| mRNA ID | NM_001300967 |
| Length | 724 |
| RefSeq Status | REVIEWED |
| MAEAGLRGWLLWALLLRLAQSEPYTTIHQPGYCAFYDECGKNPELSGSLMTLSNVSCLSNTPARKITGDHLILLQKICPRLYTGPNTQACCSAKQLVSLEASLSITKALLTRCPACSDNFVNLHCHNTCSPNQSLFINVTRVAQLGAGQLPAVVAYEAFYQHSFAEQSYDSCSRVRVPAAATLAVGTMCGVYGSALCNAQRWLNFQGDTGNGLAPLDITFHLLEPGQAVGSGIQPLNEGVARCNESQGDDVATCSCQDCAASCPAIARPQALDSTFYLGQMPGSLVLIIILCSVFAVVTILLVGFRVAPARDKSKMVDPKKGTSLSDKLSFSTHTLLGQFFQGWGTWVASWPLTILVLSVIPVVALAAGLVFTELTTDPVELWSAPNSQARSEKAFHDQHFGPFFRTNQVILTAPNRSSYRYDSLLLGPKNFSGILDLDLLLELLELQERLRHLQVWSPEAQRNISLQDICYAPLNPDNTSLYDCCINSLLQYFQNNRTLLLLTANQTLMGQTSQVDWKDHFLYCANAPLTFKDGTALALSCMADYGAPVFPFLAIGGYKGKDYSEAEALIMTFSLNNYPAGDPRLAQAKLWEEAFLEEMRAFQRRMAGMFQVTFMAERSLEDEINRTTAEDLPIFATSYIVIFLYISLALGSYSSWSRVMVDSKATLGLGGVAVVLGAVMAAMGFFSYLGIRSSLVILQVVPFLVLSVGADNIFIFVLEYQGP | |
Gene Information
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0031526 | IEA:Ensembl | C | brush border membrane |
| GO:0031410 | IEA:UniProtKB-KW | C | cytoplasmic vesicle |
| GO:0016021 | IDA:UniProtKB | C | integral component of membrane |
| GO:0005886 | TAS:Reactome | C | plasma membrane |
| GO:0017137 | IPI:UniProtKB | F | Rab GTPase binding |
| GO:0008144 | IEA:Ensembl | F | drug binding |
| GO:0008158 | IEA:InterPro | F | hedgehog receptor activity |
| GO:0031489 | IPI:UniProtKB | F | myosin V binding |
| GO:0006695 | IMP:HGNC | P | cholesterol biosynthetic process |
| GO:0030301 | IMP:HGNC | P | cholesterol transport |
| GO:0030299 | IMP:HGNC | P | intestinal cholesterol absorption |
| GO:0042157 | IMP:HGNC | P | lipoprotein metabolic process |
| GO:0042493 | IEA:Ensembl | P | response to drug |
| GO:0044281 | TAS:Reactome | P | small molecule metabolic process |
| GO:0015918 | TAS:Reactome | P | sterol transport |
KEGG Pathway Links
| KEGG Pathway ID | Description |
|---|---|
| hsa04975 | Fat digestion and absorption |
REACTOME Pathway Links
| REACTOME Pathway ID | Description |
|---|---|
| REACT_13781 | Trafficking of dietary sterols |
Domain Information
UniProt Annotations
Entry Information
Comments
| Comment Type | Description |
|---|---|
| Alternative Products | Event=Alternative splicing; Named isoforms=4; Name=1; IsoId=Q9UHC9-1; Sequence=Displayed; Name=2; Synonyms=NPC1L1DELTAE15; IsoId=Q9UHC9-2; Sequence=VSP_015314; Name=3; Synonyms=NPCL1T; IsoId=Q9UHC9-3; Sequence=VSP_015312, VSP_015313; Name=4; IsoId=Q9UHC9-4; Sequence=VSP_054503, VSP_015314; Note=No experimental confirmation available.; |
| 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. |
| Induction | Expression is decreased in Caco-2 cells upon PPARD activation. |
| Polymorphism | Variations in NPC1L1 gene could be associated with non-response to ezetimibe treatment. |
| Ptm | Highly glycosylated. |
| Similarity | Belongs to the patched family. |
| Similarity | Contains 1 SSD (sterol-sensing) domain. |
| Subcellular Location | Apical cell membrane ; Multi-pass membrane protein {ECO |
| Subunit | 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. |
| 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. {ECO |
Identical and Related Proteins
Unique RefSeq proteins for LMP001283 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 156231351 | RefSeq | NP_037521 | 1359 | Niemann-Pick C1-like protein 1 isoform 1 precursor |
| 156231353 | RefSeq | NP_001095118 | 1332 | Niemann-Pick C1-like protein 1 isoform 2 precursor |
| 665821271 | RefSeq | NP_001287896 | 724 | Niemann-Pick C1-like protein 1 isoform 3 precursor |
Identical Sequences to LMP001283 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:665821271 | GenBank | AAF20397.1 | 724 | truncated Niemann-Pick C1-like protein 1 [Homo sapiens] |
| GI:156231353 | GenBank | AAS56939.1 | 1332 | NPC1L1 splice variant [Homo sapiens] |
| GI:156231353 | GenBank | AAI17179.1 | 1332 | NPC1L1 protein [Homo sapiens] |
| GI:156231351 | GenBank | EAW61096.1 | 1359 | NPC1 (Niemann-Pick disease, type C1, gene)-like 1, isoform CRA_a [Homo sapiens] |
| GI:156231351 | GenBank | EAW61097.1 | 1359 | NPC1 (Niemann-Pick disease, type C1, gene)-like 1, isoform CRA_a [Homo sapiens] |
| GI:156231353 | GenBank | EAW61098.1 | 1332 | NPC1 (Niemann-Pick disease, type C1, gene)-like 1, isoform CRA_b [Homo sapiens] |
| GI:156231353 | GenBank | ACL18055.1 | 1332 | NPC1-like 1 protein [Homo sapiens] |
| GI:156231353 | GenBank | AED75203.1 | 1332 | Sequence 25 from patent US 7910698 |
| GI:156231353 | GenBank | AFO16160.1 | 1332 | Sequence 25 from patent US 8212016 |
| GI:156231351 | SwissProt | Q9UHC9.2 | 1359 | RecName: Full=Niemann-Pick C1-like protein 1; Flags: Precursor [Homo sapiens] |
Related Sequences to LMP001283 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:156231353 | EMBL | CCB07359.1 | 1332 | unnamed protein product [Homo sapiens] |
| GI:156231351 | EMBL | CCB07361.1 | 1359 | unnamed protein product [Homo sapiens] |
| GI:665821271 | EMBL | CCB07361.1 | 1359 | unnamed protein product [Homo sapiens] |
| GI:156231353 | EMBL | CDM55518.1 | 1332 | unnamed protein product [Homo sapiens] |
| GI:156231351 | EMBL | CDM55520.1 | 1359 | unnamed protein product [Homo sapiens] |
| GI:665821271 | EMBL | CDM55520.1 | 1359 | unnamed protein product [Homo sapiens] |
| GI:156231353 | EMBL | CDM63607.1 | 1332 | unnamed protein product [Homo sapiens] |
| GI:156231351 | EMBL | CDM63609.1 | 1359 | unnamed protein product [Homo sapiens] |
| GI:156231351 | GenBank | AAF20396.1 | 1359 | Niemann-Pick C1-like protein 1 [Homo sapiens] |
| GI:665821271 | GenBank | AAF20396.1 | 1359 | Niemann-Pick C1-like protein 1 [Homo sapiens] |
| GI:156231351 | GenBank | EAL23753.1 | 1359 | NPC1 (Niemann-Pick disease, type C1, gene)-like 1 [Homo sapiens] |
| GI:665821271 | GenBank | EAL23753.1 | 1359 | NPC1 (Niemann-Pick disease, type C1, gene)-like 1 [Homo sapiens] |
| GI:156231353 | GenBank | ABL47819.1 | 1332 | Sequence 4 from patent US 7135556 |
| GI:665821271 | GenBank | ABL47827.1 | 1359 | Sequence 44 from patent US 7135556 |
| GI:156231353 | GenBank | AED59493.1 | 1332 | Sequence 4 from patent US 7901893 |
| GI:156231351 | GenBank | AED59501.1 | 1359 | Sequence 44 from patent US 7901893 |
| GI:156231353 | GenBank | AFO16161.1 | 1332 | Sequence 26 from patent US 8212016 |
| GI:665821271 | GenBank | AHE02289.1 | 1359 | Sequence 60643 from patent US 8586006 |