NPC1 Membrane Protein Introduction

Introduction of NPC1

NPC intracellular cholesterol transporter 1 (NPC1) is a protein that in humans is encoded by the NPC1 gene (chromosome location 18q11). It is a membrane protein consisting of 1278 amino acids and containing 13 transmembrane helices. Mutations in the NPC1 gene lead to the development of a variety of diseases, particularly cholesterol translocation disorders in mammalian cells.

Basic Information of NPC1
Protein Name	NPC intracellular cholesterol transporter 1
Gene Name	NPC1
Aliases	NPC, NPC intracellular cholesterol transporter 1, SLC65A1, POGZ
Organism	Homo sapiens (Human)
UniProt ID	O15118
Transmembrane Times	13
Length (aa)	1278
Sequence	MTARGLALGLLLLLLCPAQVFSQSCVWYGECGIAYGDKRYNCEYSGPPKPLPKDGYDLVQELCPGFFFGNVSLCCDVRQLQTLKDNLQLPLQFLSRCPSCFYNLLNLFCELTCSPRQSQFLNVTATEDYVDPVTNQTKTNVKELQYYVGQSFANAMYNACRDVEAPSSNDKALGLLCGKDADACNATNWIEYMFNKDNGQAPFTITPVFSDFPVHGMEPMNNATKGCDESVDEVTAPCSCQDCSIVCGPKPQPPPPPAPWTILGLDAMYVIMWITYMAFLLVFFGAFFAVWCYRKRYFVSEYTPIDSNIAFSVNASDKGEASCCDPVSAAFEGCLRRLFTRWGSFCVRNPGCVIFFSLVFITACSSGLVFVRVTTNPVDLWSAPSSQARLEKEYFDQHFGPFFRTEQLIIRAPLTDKHIYQPYPSGADVPFGPPLDIQILHQVLDLQIAIENITASYDNETVTLQDICLAPLSPYNTNCTILSVLNYFQNSHSVLDHKKGDDFFVYADYHTHFLYCVRAPASLNDTSLLHDPCLGTFGGPVFPWLVLGGYDDQNYNNATALVITFPVNNYYNDTEKLQRAQAWEKEFINFVKNYKNPNLTISFTAERSIEDELNRESDSDVFTVVISYAIMFLYISLALGHMKSCRRLLVDSKVSLGIAGILIVLSSVACSLGVFSYIGLPLTLIVIEVIPFLVLAVGVDNIFILVQAYQRDERLQGETLDQQLGRVLGEVAPSMFLSSFSETVAFFLGALSVMPAVHTFSLFAGLAVFIDFLLQITCFVSLLGLDIKRQEKNRLDIFCCVRGAEDGTSVQASESCLFRFFKNSYSPLLLKDWMRPIVIAIFVGVLSFSIAVLNKVDIGLDQSLSMPDDSYMVDYFKSISQYLHAGPPVYFVLEEGHDYTSSKGQNMVCGGMGCNNDSLVQQIFNAAQLDNYTRIGFAPSSWIDDYFDWVKPQSSCCRVDNITDQFCNASVVDPACVRCRPLTPEGKQRPQGGDFMRFLPMFLSDNPNPKCGKGGHAAYSSAVNILLGHGTRVGATYFMTYHTVLQTSADFIDALKKARLIASNVTETMGINGSAYRVFPYSVFYVFYEQYLTIIDDTIFNLGVSLGAIFLVTMVLLGCELWSAVIMCATIAMVLVNMFGVMWLWGISLNAVSLVNLVMSCGISVEFCSHITRAFTVSMKGSRVERAEEALAHMGSSVFSGITLTKFGGIVVLAFAKSQIFQIFYFRMYLAMVLLGATHGLIFLPVLLSYIGPSVNKAKSCATEERYKGTERERLLNF

Function of NPC1 Membrane Protein

NPC1 abnormalities are the main cause of C-type Niemann-Pick disease. NPC1 is an indispensable transporter of cholesterol in human cells. It plays an important role in the transport of cholesterol with NPC1 binding to cholesterol transporter to promote cholesterol transport. Cholesterol binds to NPC1, in which the hydroxyl group is buried in the binding pocket and is exported from the lysosome restriction membrane to the ER and plasma membrane by an unknown mechanism. Mutations in NPC1 gene cause abnormal accumulation of cholesterol in lysosomes, resulting in excessive accumulation of lipids in the liver, kidney, spleen and even brain of patients, causing lesions in these organs. NPC1 is also an Ebola receptor in human cells and plays an irreplaceable role in the invasion of Ebola. In addition, NPC1 may play a role in vesicle trafficking in glial cells, a process that may be critical to maintaining the structural and functional integrity of nerve endings.

NPC1 Membrane Protein Introduction Fig.1 NPC1/2 TTD trafficking patterns of cholesterol. (Subramanian, 2008)

Application of NPC1 Membrane Protein in Literature

Ebrahimifakhari D., et al. Reduction of TMEM97 increases NPC1 protein levels and restores cholesterol trafficking in Niemann-pick type C1 disease cells. Human Molecular Genetics. 2016, 25(16):3588-3599. PubMed ID: 27378690

This paper showed that a reduction of TMEM97 increased NPC1 levels in cells through a post-transcriptional mechanism and proposed TMEM97 inhibition as a novel strategy to increase residual NPC1 levels in cells and a potential therapeutic target for NP-C.
Kuroda M., et al. Interaction between TIM-1 and NPC1 is important for cellular entry of Ebola virus. Journal of Virology. 2015, 89(12):6481. PubMed ID: 25855742

This article found that TIM-1 and NPC1 colocalized and interacted in the intracellular vesicles where EBOV glycoprotein (GP)-mediated membrane fusion occurred，suggesting a novel mechanism underlying filovirus membrane fusion and providing a potential cellular target for antiviral compounds.
Li J., et al. Glycosylation inhibition reduces cholesterol accumulation in NPC1 protein-deficient cells. Proceedings of the National Academy of Sciences of the United States of America. 2015, 112(48):14876-81. PubMed ID: 26578804

The article concluded that NPC1 protein transfers cholesterol during cholesterol transfer.
Yu X.H., et al. NPC1, intracellular cholesterol trafficking and atherosclerosis. Clinica chimica acta; international journal of clinical chemistry. 2014, 429(3):69. PubMed ID: 24296264

This review summarized the role of NPC1 in regulating intracellular cholesterol trafficking and atherosclerosis.
Vanier M.T. and Suzuki K. Recent advances in elucidating Niemann-Pick C disease. Brain Pathology. 2010, 8(1):163-174. PubMed ID: 9458174

The article described that homologies of the NPC1 protein were in line with its putative involvement in cellular cholesterol traffic and occurrence of neurofibrillary tangles in the brain of patients with a slowly progressive course.

NPC1 Preparation Options

To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Besides, we also provide customized anti-NPC1 antibody development services based on our versatile Magic™ anti-membrane protein antibody discovery platform.

Creative Biolabs offers high-quality membrane protein preparation services to facilitate the projects of worldwide customers. For more detailed information, please feel free to contact us for more details.

Reference

Subramanian K and Balch W E. (2008). NPC1/NPC2 function as a tag team duo to mobilize cholesterol. Proceedings of the National Academy of Sciences of the United States of America. 105(40),15223-15224.

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