What is the complete designation for the protein commonly referred to as NPC1L1?

The complete designation for the protein commonly referred to as NPC1L1 is Niemann-Pick C1-Like 1.

Could you describe the primary locations within the human body where the NPC1L1 protein is expressed?

The NPC1L1 protein is primarily found on the epithelial cells of the gastrointestinal tract and also within hepatocytes, which are the main functional cells of the liver.

What role does the NPC1L1 protein play in the biological process of cholesterol absorption?

NPC1L1 protein appears to bind to a critical mediator that is essential for the absorption of cholesterol from the digestive system into the body.

How does the medication ezetimibe interact with the NPC1L1 protein?

The medication ezetimibe functions by inhibiting the NPC1L1 protein.

What are the quantitative effects on blood cholesterol levels when NPC1L1 is inhibited by ezetimibe?

When ezetimibe inhibits NPC1L1, it leads to a reduction in cholesterol absorption, consequently causing a decrease in blood cholesterol levels by approximately 15% to 20%.

What is the potential impact of genetic variations within the NPC1L1 gene on an individual's response to ezetimibe therapy?

Polymorphic variations, or differences in the DNA sequence, within the NPC1L1 gene could be associated with individuals not responding effectively to ezetimibe treatment.

Beyond cholesterol levels, what significant health risks appear to be reduced in individuals with inactivating mutations of the NPC1L1 gene?

Individuals possessing inactivating mutations in the NPC1L1 gene have been observed to have lower levels of LDL cholesterol and approximately a 50% reduction in their risk of developing coronary heart disease.

What concern was raised regarding a potential link between NPC1L1 inhibition and cancer risk, and on what basis?

A concern was raised that NPC1L1 inhibition by ezetimibe might be associated with an increased risk of cancer. This hypothesis stemmed from observations in one clinical trial where cancer incidence appeared higher in patients receiving a combination therapy of simvastatin and ezetimibe.

Following initial concerns, what did a comprehensive meta-analysis reveal about the association between ezetimibe treatment and cancer incidence?

A meta-analysis that reviewed clinical data related to ezetimibe treatment concluded that there was no observed increase in the risk of cancer associated with using the drug.

Beyond its primary designation, what other names or symbols are used to refer to NPC1L1?

Other names and symbols used for NPC1L1 include NPC11L1, NPC1 like intracellular cholesterol transporter 1, SLC65A2, and LDLCQ7.

What are some of the key external databases that provide unique identifiers for the NPC1L1 gene or protein?

Key external databases that provide identifiers for NPC1L1 include OMIM (Online Mendelian Inheritance in Man), MGI (Mouse Genome Informatics), HomoloGene, GeneCards, and OMA (Orthologous Matrix).

Could you specify the chromosomal location, including the band, of the NPC1L1 gene in humans?

In humans, the NPC1L1 gene is located on Chromosome 7, specifically within the 7p13 band.

What are the precise genomic coordinates (start and end base pairs) for the NPC1L1 gene on human Chromosome 7?

The NPC1L1 gene on human Chromosome 7 spans from base pair 44,512,535 to 44,541,330.

How does the chromosomal location of the NPC1L1 gene differ between humans and mice?

In humans, the NPC1L1 gene is found on Chromosome 7 at band 7p13, whereas in mice, it is located on Chromosome 11 at band 11A1.

What are the genomic coordinates for the NPC1L1 gene in mice, corresponding to its location on Chromosome 11?

The NPC1L1 gene in mice is situated on Chromosome 11 between base pair 6,161,013 and 6,180,143.

According to expression data from Bgee, in which human tissues does NPC1L1 exhibit the highest levels of RNA expression?

According to Bgee data, NPC1L1 RNA shows high expression in human tissues including the jejunal mucosa, duodenum, right lobe of the liver, testicles, islet of Langerhans, gallbladder, muscle layer of the sigmoid colon, right coronary artery, descending thoracic aorta, and popliteal artery.

Based on Bgee data, what are the primary mouse tissues demonstrating significant NPC1L1 RNA expression?

Bgee data indicates that NPC1L1 RNA is highly expressed in mouse tissues such as the epithelium of the small intestine, jejunum, ileum, duodenum, migratory enteric neural crest cells, embryos, Paneth cells, morulae, blastocysts, and the yolk sac.

What specific molecular functions has the Gene Ontology assigned to the NPC1L1 protein?

The Gene Ontology has assigned the molecular functions of myosin V binding and protein binding to the NPC1L1 protein.

In terms of cellular localization, what components does the Gene Ontology identify as being associated with NPC1L1?

The Gene Ontology identifies NPC1L1 as being associated with the membrane, plasma membrane, brush border membrane, apical plasma membrane, cytoplasmic vesicle membrane, cytoplasmic vesicle, integral component of membrane, and spanning component of plasma membrane.

What key biological processes is NPC1L1 involved in, as categorized by the Gene Ontology?

Gene Ontology categorizes NPC1L1 as being involved in biological processes such as lipoprotein metabolic process, steroid metabolic process, lipid metabolism, cholesterol transport, cholesterol metabolic process, intestinal cholesterol absorption, cholesterol biosynthetic process, intestinal lipid absorption, and cellular response to sterol depletion.

What are the respective UniProt accession numbers for the NPC1L1 protein in humans and mice?

The UniProt accession number for human NPC1L1 is Q9UHC9, and for mouse NPC1L1, it is Q6T3U4.

Can you provide the Ensembl gene identifiers for NPC1L1 in both human and mouse genomes?

The Ensembl gene identifier for human NPC1L1 is ENSG00000015520, and for mouse NPC1L1, it is ENSMUSG00000020447.

What are the Entrez gene identification numbers for NPC1L1 in humans and mice?

The Entrez gene ID for human NPC1L1 is 29881, and for mouse NPC1L1, it is 237636.

What are the various RefSeq mRNA accession numbers associated with the human NPC1L1 gene?

The human NPC1L1 gene is associated with the RefSeq mRNA accession numbers NM_001101648, NM_001300967, and NM_013389.

What are the RefSeq protein accession numbers corresponding to the human NPC1L1 gene?

The RefSeq protein accession numbers for the human NPC1L1 gene are NP_001095118, NP_001287896, and NP_037521.

Does the provided text include a RefSeq protein identifier for the mouse NPC1L1?

No, the provided text indicates that there is no RefSeq protein identifier listed for mouse NPC1L1 (marked as n/a).

What specific identifier is referenced in the context of Protein Data Bank (PDB) structures related to NPC1L1?

The identifier 3QNT is referenced in the context of Protein Data Bank (PDB) structures related to NPC1L1.

Beyond standard gene and protein databases, what other external resources offer information or related media for NPC1L1?

External resources offering information on NPC1L1 include the U.S. National Library of Medicine's Medical Subject Headings (MeSH), the PDBe-KB database, Wikidata, and Wikimedia Commons, which hosts related media.

What is the significance of the NPC1L1 protein's presence on the brush border membrane?

The Gene Ontology lists NPC1L1 as being associated with the brush border membrane, which is a characteristic feature of cells lining the small intestine, suggesting a role in absorption processes occurring there.

What does the term 'Niemann-Pick C1-Like 1' suggest about the protein's relationship to other known conditions or proteins?

The name 'Niemann-Pick C1-Like 1' suggests that this protein shares similarities or a functional relationship with the protein involved in Niemann-Pick disease type C1, indicating a potential role in lipid metabolism or transport.

How does the location of NPC1L1 in hepatocytes relate to its function?

The presence of NPC1L1 in hepatocytes, the main cells of the liver, is significant because the liver plays a crucial role in cholesterol metabolism and processing absorbed cholesterol from the gastrointestinal tract.

What is the potential therapeutic implication of NPC1L1's role as an entry factor for Hepatitis C Virus?

Since NPC1L1 acts as an accessory receptor for Hepatitis C Virus entry, inhibiting NPC1L1, potentially with drugs like ezetimibe, could be explored as a therapeutic strategy to combat HCV infection.

What does the reference to 'myosin V binding' in the Gene Ontology imply about NPC1L1's cellular activity?

The association with myosin V binding suggests that NPC1L1 may be involved in intracellular transport processes, as myosin V is a motor protein known to move cargo along actin filaments within cells.

What is the functional relevance of NPC1L1 being an 'integral component of membrane'?

Being an integral component of the membrane means that NPC1L1 is embedded within the cell's lipid bilayer, which is essential for its function as a receptor or transporter that interacts with molecules across the membrane boundary.

What is the significance of NPC1L1's involvement in 'intestinal cholesterol absorption' as indicated by its Gene Ontology classification?

The classification of NPC1L1 in processes like 'intestinal cholesterol absorption' directly links it to the mechanism by which the body takes up dietary cholesterol from the digestive system, highlighting its importance in lipid homeostasis.

What does the presence of multiple RefSeq mRNA identifiers for human NPC1L1 suggest?

The existence of multiple RefSeq mRNA identifiers for human NPC1L1 suggests that there might be different transcript variants or isoforms of the gene, potentially leading to proteins with slightly different functions or expression patterns.

What is the general classification of NPC1L1 mentioned in the short description of the article?

The short description classifies NPC1L1 as a mammalian protein found in Homo sapiens.

Which external links provide access to structural information for NPC1L1?

The PDBe-KB database provides access to structural information for human NPC1L1 (UniProt Q9UHC9).

What is the relationship between NPC1L1 and the drug ezetimibe regarding cholesterol reduction?

Ezetimibe inhibits NPC1L1, which in turn reduces cholesterol absorption in the intestine, leading to lower blood cholesterol levels.

What specific gene nomenclature resources are referenced for NPC1L1?

The text references GeneCards and HGNC (via Genenames.org) as resources for NPC1L1 gene nomenclature.

How is NPC1L1 related to lipid metabolism according to its Gene Ontology classification?

According to Gene Ontology, NPC1L1 is involved in several lipid metabolism-related processes, including lipoprotein metabolic process, steroid metabolic process, lipid metabolism, cholesterol transport, cholesterol metabolic process, and cholesterol biosynthetic process.

What does the presence of NPC1L1 in the testicle suggest about its potential roles?

The expression of NPC1L1 RNA in the testicle, as indicated by Bgee data, suggests potential roles beyond cholesterol absorption, possibly related to testicular function or development.

What is the significance of NPC1L1 being located on the plasma membrane?

NPC1L1's presence on the plasma membrane, the outer boundary of the cell, is crucial for its function in interacting with substances from the extracellular environment, such as cholesterol or viruses.

Npc1l1 Wiki: NPC1L1: The Cholesterol Gatekeeper

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Introduction to NPC1L1

Protein Identity

Niemann-Pick C1-Like 1 (NPC1L1) is a protein primarily found on the surface of epithelial cells lining the gastrointestinal tract and within hepatocytes (liver cells). It plays a crucial role in the body's management of lipids.

Cellular Localization

NPC1L1 is embedded within the plasma membrane, specifically localizing to the brush border membrane of intestinal epithelial cells and the apical plasma membrane of hepatocytes. It is also found associated with cytoplasmic vesicles, indicating dynamic cellular trafficking.

Gene and Aliases

The gene encoding this protein is known as NPC1L1. It is also referred to by aliases such as NPC11L1, NPC1 like intracellular cholesterol transporter 1, and SLC65A2.

Core Function: Cholesterol Transport

Mediating Absorption

NPC1L1 functions as a critical mediator for the absorption of dietary cholesterol from the small intestine into the bloodstream. It is also involved in the reabsorption of biliary cholesterol.

Target for Ezetimibe

The widely used cholesterol-lowering drug ezetimibe specifically targets and inhibits the NPC1L1 protein. By blocking NPC1L1, ezetimibe effectively reduces intestinal cholesterol absorption.

Impact on Blood Lipids

The inhibition of NPC1L1 by ezetimibe leads to a significant reduction in circulating blood cholesterol levels, typically by 15-20%. This mechanism makes NPC1L1 a key player in managing hyperlipidemia.

Genetic Insights

Gene Location

The NPC1L1 gene is located on chromosome 7p13 in humans and chromosome 11 A1 in mice. Specific base pair coordinates define its genomic position.

Species	Chromosome	Band	Start (bp)	End (bp)
Human	7	7p13	44,512,535	44,541,330
Human
Mouse	11	11 A1	6,161,013	6,180,143
Mouse

Orthologs and Identifiers

NPC1L1 orthologs are found across various species, including humans and mice. Numerous identifiers link NPC1L1 to various biological databases.

Identifier Type	Human	Mouse
Entrez Gene ID	29881	237636
Ensembl ID	ENSG00000015520	ENSMUSG00000020447
UniProt ID	Q9UHC9	Q6T3U4
RefSeq mRNA	NM_001101648, NM_001300967, NM_013389	NM_207242
RefSeq Protein	NP_001095118, NP_001287896, NP_037521	N/A
UCSC Location	chr7: 44.51 – 44.54 Mb	chr11: 6.16 – 6.18 Mb

Polymorphisms and Response

Variations within the NPC1L1 gene, known as polymorphisms, can influence an individual's response to ezetimibe treatment. Certain genetic profiles may be associated with reduced efficacy of the drug.

Health Implications

Cardiovascular Protection

Remarkably, individuals with inactivating mutations in the NPC1L1 gene exhibit significantly lower levels of low-density lipoprotein (LDL) cholesterol. This genetic trait is associated with a substantial reduction, approximately 50%, in the risk of developing coronary heart disease.

Viral Interactions

Beyond its role in lipid metabolism, NPC1L1 has been identified as an accessory receptor that facilitates the entry of the Hepatitis C virus (HCV) into host cells. This discovery opens potential avenues for therapeutic strategies targeting viral infection.

Research & Clinical Considerations

Cancer Risk Hypothesis

Early clinical observations from trials combining simvastatin and ezetimibe led to a hypothesis suggesting a potential association between NPC1L1 inhibition and an increased risk of cancer. This warranted further investigation.

Evidence-Based Review

Subsequent comprehensive meta-analyses of extensive clinical trial data involving ezetimibe have conclusively demonstrated that treatment with this drug does not elevate the risk of developing cancer. The initial hypothesis has been refuted by robust evidence.

Functional Annotations

The NPC1L1 protein is characterized by specific molecular functions, cellular components, and biological processes.

Molecular Function

Myosin V binding
Protein binding

Cellular Component

Membrane
Plasma membrane
Brush border membrane
Apical plasma membrane
Cytoplasmic vesicle membrane
Cytoplasmic vesicle
Integral component of membrane
Spanning component of plasma membrane

Biological Process

Lipoprotein metabolic process
Steroid metabolic process
Lipid metabolism
Cholesterol transport
Cholesterol metabolic process
Intestinal cholesterol absorption
Cholesterol biosynthetic process
Intestinal lipid absorption
Cellular response to sterol depletion

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References

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This is not medical advice. The information provided on this website is not a substitute for professional medical consultation, diagnosis, or treatment. Always seek the advice of a qualified healthcare provider with any questions you may have regarding a medical condition or treatment. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

The creators of this page are not responsible for any errors or omissions, or for any actions taken based on the information provided herein.

NPC1L1: The Cholesterol Gatekeeper

💡 Dive in with Flashcard Learning! 💡

Introduction to NPC1L1 ℹ️

🧬 Protein Identity

📍 Cellular Localization

🏷️ Gene and Aliases

Core Function: Cholesterol Transport 🧪

📥 Mediating Absorption

💊 Target for Ezetimibe

📉 Impact on Blood Lipids

Genetic Insights 📜

🔢 Gene Location

🔗 Orthologs and Identifiers

💡 Polymorphisms and Response

Health Implications ❤️

🛡️ Cardiovascular Protection

🦠 Viral Interactions

Research & Clinical Considerations 🔬

⚠️ Cancer Risk Hypothesis

📊 Evidence-Based Review

🏷️ Functional Annotations

Molecular Function

Cellular Component

Biological Process

Teacher's Corner 🧑‍🏫

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References

📜 References

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Disclaimer ⚠️

📜 Important Notice

Dive in with Flashcard Learning!

Introduction to NPC1L1

Protein Identity

Cellular Localization

Gene and Aliases

Core Function: Cholesterol Transport

Mediating Absorption

Target for Ezetimibe

Impact on Blood Lipids

Genetic Insights

Gene Location

Orthologs and Identifiers

Polymorphisms and Response

Health Implications

Cardiovascular Protection

Viral Interactions

Research & Clinical Considerations

Cancer Risk Hypothesis

Evidence-Based Review

Functional Annotations

Teacher's Corner

True or False?

Test Your Knowledge!

Gamer's Corner

Discover other topics to study!

References

Feedback & Support

Disclaimer

Important Notice