NPC1L1

Protein identityUniProt · HPA

UniProt accession

Q9UHC9

Gene

NPC1L1

Ensembl

ENSG00000015520

Chromosome

7

Canonical length

1359 aa

Protein class

FDA approved drug targets, Metabolic proteins, Predicted membrane proteins, Transporters

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1359 residues, UniProt reviewed canonical sequence.

>Q9UHC9|NPC1L1
     1  MAEAGLRGWL LWALLLRLAQ SEPYTTIHQP GYCAFYDECG KNPELSGSLM TLSNVSCLSN
    61  TPARKITGDH LILLQKICPR LYTGPNTQAC CSAKQLVSLE ASLSITKALL TRCPACSDNF
   121  VNLHCHNTCS PNQSLFINVT RVAQLGAGQL PAVVAYEAFY QHSFAEQSYD SCSRVRVPAA
   181  ATLAVGTMCG VYGSALCNAQ RWLNFQGDTG NGLAPLDITF HLLEPGQAVG SGIQPLNEGV
   241  ARCNESQGDD VATCSCQDCA ASCPAIARPQ ALDSTFYLGQ MPGSLVLIII LCSVFAVVTI
   301  LLVGFRVAPA RDKSKMVDPK KGTSLSDKLS FSTHTLLGQF FQGWGTWVAS WPLTILVLSV
   361  IPVVALAAGL VFTELTTDPV ELWSAPNSQA RSEKAFHDQH FGPFFRTNQV ILTAPNRSSY
   421  RYDSLLLGPK NFSGILDLDL LLELLELQER LRHLQVWSPE AQRNISLQDI CYAPLNPDNT
   481  SLYDCCINSL LQYFQNNRTL LLLTANQTLM GQTSQVDWKD HFLYCANAPL TFKDGTALAL
   541  SCMADYGAPV FPFLAIGGYK GKDYSEAEAL IMTFSLNNYP AGDPRLAQAK LWEEAFLEEM
   601  RAFQRRMAGM FQVTFMAERS LEDEINRTTA EDLPIFATSY IVIFLYISLA LGSYSSWSRV
   661  MVDSKATLGL GGVAVVLGAV MAAMGFFSYL GIRSSLVILQ VVPFLVLSVG ADNIFIFVLE
   721  YQRLPRRPGE PREVHIGRAL GRVAPSMLLC SLSEAICFFL GALTPMPAVR TFALTSGLAV
   781  ILDFLLQMSA FVALLSLDSK RQEASRLDVC CCVKPQELPP PGQGEGLLLG FFQKAYAPFL
   841  LHWITRGVVL LLFLALFGVS LYSMCHISVG LDQELALPKD SYLLDYFLFL NRYFEVGAPV
   901  YFVTTLGYNF SSEAGMNAIC SSAGCNNFSF TQKIQYATEF PEQSYLAIPA SSWVDDFIDW
   961  LTPSSCCRLY ISGPNKDKFC PSTVNSLNCL KNCMSITMGS VRPSVEQFHK YLPWFLNDRP
  1021  NIKCPKGGLA AYSTSVNLTS DGQVLDTVAI LSPRLEYSGT ISAHCNLYLL DSTSRFMAYH
  1081  KPLKNSQDYT EALRAARELA ANITADLRKV PGTDPAFEVF PYTITNVFYE QYLTILPEGL
  1141  FMLSLCLVPT FAVSCLLLGL DLRSGLLNLL SIVMILVDTV GFMALWGISY NAVSLINLVS
  1201  AVGMSVEFVS HITRSFAIST KPTWLERAKE ATISMGSAVF AGVAMTNLPG ILVLGLAKAQ
  1261  LIQIFFFRLN LLITLLGLLH GLVFLPVILS YVGPDVNPAL ALEQKRAEEA VAAVMVASCP
  1321  NHPSRVSTAD NIYVNHSFEG SIKGAGAISN FLPNNGRQF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NPC1L1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

13

Mean surface accessibility (rSASA)

0.25

Highest tissue expression

51 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.94

gnomAD pLI

0

gnomAD missense Z

0.41

DepMap mean gene effect

-0.14

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cholesterol biosynthetic process
• cholesterol homeostasis
• cholesterol transport
• intestinal cholesterol absorption
• lipoprotein metabolic process
• sterol transport
• vitamin E metabolic process
• vitamin transport
• cellular response to sterol depletion

Molecular functions

• cholesterol binding
• myosin V binding
• protein homodimerization activity
• small GTPase binding
• vitamin E binding

Cellular components

• apical plasma membrane
• cytoplasmic vesicle membrane
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Sterol-sensing domain
• Niemann-Pick C1, N-terminal
• NPC1, middle luminal domain
• HMGCR/SNAP/NPC1-like, sterol-sensing domain
• Sterol-sensing domain of SREBP cleavage-activation
• Niemann-Pick C1 N terminus
• NPC1, middle luminal domain

KeywordsUniProt

• Cell membrane
• Cholesterol metabolism
• Cytoplasmic vesicle
• Disulfide bond
• Glycoprotein
• Lipid metabolism
• Membrane
• Signal
• Steroid metabolism
• Sterol metabolism
• Transmembrane
• Transmembrane helix
• Transport

InteractionsUniProt · HPA

Protein binding partners of NPC1L1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• LIMA1
• MYO5B
• NPC2
• RAB11A
• RAB11FIP2