|
|
Gene Symbol |
LDLR |
|
Aliases |
FH, FHC, FHCL1, LDLCQ2 |
|
Entrez Gene ID |
|
|
Gene Name |
Low density lipoprotein receptor |
|
Chromosomal Location |
19p13.2 |
|
HGNC ID |
|
|
Summary |
The low density lipoprotein receptor (LDLR) gene family consists of cell surface proteins involved in receptor-mediated endocytosis of specific ligands. Low density lipoprotein (LDL) is normally bound at the cell membrane and taken into the cell ending up in lysosomes where the protein is degraded and the cholesterol is made available for repression of microsomal enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting step in cholesterol synthesis. At the same time, a reciprocal stimulation of cholesterol ester synthesis takes place. Mutations in this gene cause the autosomal dominant disorder, familial hypercholesterolemia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Sep 2010]
|
|
RefSeq DNA |
|
|
RefSeq mRNA |
|
|
e!Ensembl
|
Gene Ontology (GO)
GO ID |
Ontology |
Function |
Evidence |
Reference |
GO:0006629 |
Biological process |
Lipid metabolic process |
TAS |
6299582, 10827173 |
GO:0006897 |
Biological process |
Endocytosis |
TAS |
12671190 |
GO:0006898 |
Biological process |
Receptor-mediated endocytosis |
TAS |
24825898 |
GO:0007616 |
Biological process |
Long-term memory |
IGI |
24412220 |
GO:0030299 |
Biological process |
Intestinal cholesterol absorption |
IMP |
17142622 |
GO:0030301 |
Biological process |
Cholesterol transport |
IMP |
17142622 |
GO:0030301 |
Biological process |
Cholesterol transport |
TAS |
20005821 |
GO:0034381 |
Biological process |
Plasma lipoprotein particle clearance |
TAS |
20005821 |
GO:0034383 |
Biological process |
Low-density lipoprotein particle clearance |
IMP |
6299582, 17142622 |
GO:0042632 |
Biological process |
Cholesterol homeostasis |
IGI |
24412220 |
GO:0042632 |
Biological process |
Cholesterol homeostasis |
IMP |
6299582, 17142622 |
GO:0042632 |
Biological process |
Cholesterol homeostasis |
TAS |
20005821 |
GO:0051246 |
Biological process |
Regulation of protein metabolic process |
IGI |
24412220 |
GO:0061771 |
Biological process |
Response to caloric restriction |
IGI |
24412220 |
GO:0070508 |
Biological process |
Cholesterol import |
IMP |
6299582 |
GO:0071404 |
Biological process |
Cellular response to low-density lipoprotein particle stimulus |
IMP |
6299582 |
GO:0090118 |
Biological process |
Receptor-mediated endocytosis involved in cholesterol transport |
IMP |
6299582 |
GO:0005764 |
Cellular component |
Lysosome |
IDA |
15166224, 17461796 |
GO:0005769 |
Cellular component |
Early endosome |
IDA |
15166224, 17461796 |
GO:0005770 |
Cellular component |
Late endosome |
IDA |
17461796 |
GO:0005794 |
Cellular component |
Golgi apparatus |
IDA |
17461796 |
GO:0005887 |
Cellular component |
Integral component of plasma membrane |
TAS |
6327078 |
GO:0005905 |
Cellular component |
Clathrin-coated pit |
IDA |
6091915, 15166224 |
GO:0009897 |
Cellular component |
External side of plasma membrane |
IDA |
15166224 |
GO:0009986 |
Cellular component |
Cell surface |
IDA |
17461796 |
GO:0016020 |
Cellular component |
Membrane |
HDA |
19946888 |
GO:0043235 |
Cellular component |
Receptor complex |
IDA |
23382219 |
GO:1990666 |
Cellular component |
PCSK9-LDLR complex |
IDA |
22081141, 22848640 |
GO:0002020 |
Molecular function |
Protease binding |
IPI |
22081141, 22848640 |
GO:0005041 |
Molecular function |
Low-density lipoprotein particle receptor activity |
IC |
22848640 |
GO:0005041 |
Molecular function |
Low-density lipoprotein particle receptor activity |
IDA |
6091915, 8626535 |
GO:0005041 |
Molecular function |
Low-density lipoprotein particle receptor activity |
IMP |
6299582 |
GO:0005041 |
Molecular function |
Low-density lipoprotein particle receptor activity |
TAS |
20005821 |
GO:0005515 |
Molecular function |
Protein binding |
IPI |
10571240, 12221107, 17452316, 17461796, 18250299, 18753623, 20223219, 22081141, 22509010, 23589850, 24447298, 25613181 |
GO:0030169 |
Molecular function |
Low-density lipoprotein particle binding |
IMP |
6299582 |
GO:0030229 |
Molecular function |
Very-low-density lipoprotein particle receptor activity |
IDA |
8626535 |
GO:0032050 |
Molecular function |
Clathrin heavy chain binding |
TAS |
12121421 |
GO:0042802 |
Molecular function |
Identical protein binding |
IPI |
26526611 |
|
Protein Information |
|
Protein Name |
Low-density lipoprotein receptor, LDL receptor, low-density lipoprotein receptor class A domain-containing protein 3 |
|
Function |
Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. .; (Microbial infection) Acts as a receptor for hepatitis C virus in hepatocytes, but not through a direct interaction with viral proteins. .; (Microbial infection) Acts as a receptor for Vesicular stomatitis virus. .; (Microbial infection) In case of HIV-1 infection, may function as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells. |
|
|
|
|
|
UniProt |
|
|
PDB |
2FCW, 2KRI, 1AJJ, 1D2J, 1F5Y, 1F8Z, 1HJ7, 1HZ8, 1I0U, 1IJQ, 1LDL, 1LDR, 1LRX, 1N7D, 1XFE, 2LGP, 2M7P, 2MG9, 2W2M, 2W2N, 2W2O, 2W2P, 2W2Q, 3BPS, 3GCW, 3GCX, 3M0C, 3P5B, 3P5C, 3SO6, 4NE9, 5OY9, 5OYL |
|
|
|
Interactions |
| |
STRING |
MINT |
IntAct |
ENSP00000394560 |
P45984 |
P45984 |
|
| |
View interactions
|
|
| |
Associated Diseases
Disease group | Disease Name | References |
Cardiovascular Diseases |
Ischemic Cardiomyopathy |
|
Aortic Aneurysm |
|
Arteriosclerosis |
|
Atherosclerosis |
|
Coronary heart disease |
|
Myocardial Infarction |
|
Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
Genetic Diseases |
23651751, 21600525, 23956253, 1933004, 16020744, 22698793, 25769531, 24585268, 21600530, 2088165, 12732381, 15241806, 22398274, 9484998, 22881376, 9714107 |
Digestive System Diseases |
Fatty Liver |
|
Non-alcoholic Fatty Liver Disease |
|
Pyloric Stenosis |
|
Endocrine System Diseases |
PCOS |
|
Neoplasms |
Lung Cancer |
|
Nervous System Diseases |
Lateral Sclerosis |
|
Nutritional and Metabolic Diseases |
Hypercholesterolemia |
11295843, 9698020, 17935672, 8829662, 17347910, 12673584, 11641914, 1352322, 1301940, 7979249, 11810272, 9889019, 23375686, 11462246, 12436241, 12009418, 26020417, 20019594, 9727746, 11933210, 9409298, 21865347, 17335829, 1057090, 23680767, 7903864, 12227864, 16159606, 11139254, 7649, 26875785, 22884763, 18450471, 20530721 |
Hyperlipoproteinemia |
12673584, 11600564, 9430375, 10952765, 12522687, 12009418, 1867200, 8168830, 22160468, 17347910, 10447263, 8664907, 25378237, 7635461, 8740918, 7649549, 10532689, 8462973, 10660340, 7649546, 9654205, 7635482, 7573037, 9254862, 3955657, 7550239, 2569482, 7583548, 2726768, 10206683, 945 |
Dyslipidemias |
|
Hyperlipidemia |
|
Obesity |
|
|
References |
|
|
Dastorani Majid, Aghadavod Esmat, Mirhosseini Naghmeh, Foroozanfard Fatemeh, Zadeh Modarres Shahrzad, Amiri Siavashani Mehrnush, Asemi Zatollah |
Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, I.R, Iran.| Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, I.R, Iran. aghadavod_m@yahoo.com.| School of Public Health, University of Saskatchewan, Saskatoon, SK, Canada.| Department of Gynecology and Obstetrics, School of Medicine, Kashan University of Medical Sciences, Kashan, I.R, Iran.| Laser Application in Medical Science Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.| Taleghani Educational Hospital, IVF Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.| Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, I.R, Iran. asemi_r@yahoo.com. |
Reprod Biol Endocrinol. 2018 Oct 4;16(1):94. doi: 10.1186/s12958-018-0413-3. |
Abstract
BACKGROUND: Vitamin D deficiency in women diagnosed with polycystic ovary syndrome (PCOS) remarkably decreases the chance of pregnancy, which might be related to its impact on metabolic abnormalities in these patients. It is hypothesized that vitamin D supplementation influences metabolic profile of these patients and indirectly might affect fertility and the outcomes. Therefore, this study was conducted to determine the effects of vitamin D supplementation on the levels of anti-Mullerian hormone (AMH), metabolic profiles, and gene expression of insulin and lipid metabolism in infertile women with PCOS who were candidate for in vitro fertilization (IVF). METHODS: This study was a randomized, double-blinded, placebo-controlled trial conducted among 40 infertile women, aged 18-40 years, diagnosed with PCOS and was candidate for IVF. Participants were randomly assigned into two intervention groups for receiving either 50,000 IU vitamin D or placebo (n = 20 each group) every other week for 8 weeks. Gene expression for insulin and lipid metabolism was conducted using peripheral blood mononuclear cells (PBMCs) of women with PCOS, via RT-PCR method. RESULTS: Vitamin D supplementation led to a significant reduction in serum AMH (- 0.7 +/- 1.2 vs. - 0.1 +/- 0.5 ng/mL, P = 0.02), insulin levels (- 1.4 +/- 1.6 vs. -0.3 +/- 0.9 muIU/mL, P = 0.007), homeostatic model of assessment for insulin resistance (- 0.3 +/- 0.3 vs. -0.1 +/- 0.2, P = 0.008), and a significant increase in quantitative insulin sensitivity check index (+ 0.009 +/- 0.01 vs. + 0.001 +/- 0.004, P = 0.04), compared with the placebo. Moreover, following vitamin D supplementation there was a significant decrease in serum total- (- 5.1 +/- 12.6 vs. + 2.9 +/- 10.9 mg/dL, P = 0.03) and LDL-cholesterol levels (- 4.5 +/- 10.3 vs. + 2.5 +/- 10.6 mg/dL, P = 0.04) compared with the placebo. CONCLUSION: Overall, the findings of this trial supported that 50,000 IU vitamin D supplementation every other week for 8 weeks had beneficial effects on insulin metabolism, and lipid profile of infertile women with PCOS who are candidate for IVF. These benefits might not be evident upon having sufficient vitamin D levels. TRIAL REGISTRATION: This study was retrospectively registered in the Iranian website ( www.irct.ir ) for clinical trials registration ( http://www.irct.ir : IRCT20170513033941N27). |
|
|
Nasri Khadijeh, Hantoushzadeh Sedigheh, Aghadavod Esmat, Taghizadeh Mohsen, Asemi Zatollah |
Maternal-Fetal & Neonatal Research Center and Breast Feeding Research Center, Tehran University of Medical Sciences, Tehran, Iran.| Department of Gynecology and Obstetrics, Endocrinology and Metabolism Research Center, School of Medicine, Arak University of Medical Sciences, Arak, Iran.| Maternal-Fetal & Neonatal Research Center and Breast Feeding Research Center, Tehran University of Medical Sciences, Tehran, Iran.| Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran.| Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran.| Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran. |
Horm Metab Res. 2017 Jun;49(6):446-451. doi: 10.1055/s-0042-122782. Epub 2017 Feb |
Abstract
Limited data are available evaluating the effects of omega-3 fatty acids supplementation on gene expression involved in the insulin and lipid-signaling pathway in women with polycystic ovary syndrome (PCOS). This study was conducted to evaluate the effects of omega-3 fatty acids supplementation on gene expression involved in the insulin and lipid signaling pathway in women with PCOS. This randomized double blind, placebo-controlled trial was done among 60 women aged 18-40 years old and diagnosed with PCOS according to the Rotterdam criteria. Participants were randomly assigned into 2 groups to receive either 1 000 mg omega-3 fatty acids from flaxseed oil containing 400 mg alpha-linolenic acid (n=30) or placebo (n=30) twice a day for 12 weeks. Gene expressions involved in the insulin and lipid-signaling pathway were quantified in blood samples of PCOS women with RT-PCR method. Quantitative results of RT-PCR demonstrated that compared with the placebo, omega-3 fatty acids supplementation upregulated peroxisome proliferator-activated receptor gamma (PPAR-gamma) mRNA (p=0.005) in peripheral blood mononuclear cells of women with PCOS. In addition, compared to the placebo, omega-3 fatty acids supplementation downregulated expressed levels of oxidized low-density lipoprotein receptor (LDLR) mRNA (p=0.002) in peripheral blood mononuclear cells of women with PCOS. We did not observe any significant effect of omega-3 fatty acids supplementation on expressed levels of glucose transporter 1 (GLUT-1) and lipoprotein(a) [Lp(a)] genes in peripheral blood mononuclear cells. Overall, omega-3 fatty acids supplementation for 12 weeks in PCOS women significantly improved gene expression of PPAR-gamma and LDLR. |
|
|
Mondal Kalyani, Chakraborty Pratip, Kabir Syed N |
Reproductive Biology Research, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, 700032, WB, India.| Institute of Reproductive Medicine, Salt Lake City, Kolkata, 700106, WB, India.| Reproductive Biology Research, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, 700032, WB, India. Electronic address: snkabir@atgcdiagnostics.com. |
Biochem Biophys Res Commun. 2018 Sep 3;503(1):8-13. doi: |
Abstract
Women with polycystic ovary syndrome (PCOS) are at increased risk of cardiovascular diseases (CVD); however, the independent role of PCOS in the incident CVD remains unknown. There are reports that hyperhomocysteinemia (HHcy), a potential cause of CVD, is frequently associated with PCOS. The present study investigates the independent attributes of hyperandrogenemia (HA), the integral associate of PCOS, and HHcy in causing atherogenic dyslipidemia. Twenty-five-day old rats were treated with homocysteine (Hcy) at 50mg/kg/day dose level for 12 weeks. The HepG2 cell lines transfected with siRNA directed to PCSK9 were challenged with Hcy, homocysteine thiolactone (HTL), testosterone, 5alpha-dihydroxytestosterone (5alpha-DHT), or estradiol for 24h. Rats administered with Hcy developed HHcy and displayed PCOS-like phenotypes with adversely altered lipid homeostasis and attenuated PI3K-AKT and Wnt signalling cascade. Overexpression of steroidogenic acute regulatory protein (StAR) and down-regulated expression of Aromatase together with elevated testosterone level marked the state of HA. In culture, the HepG2 cells responded independently to Hcy, HTL, testosterone, and 5alpha-DHT by an overt expression of PCSK9 and down-regulated expression of LDLR. The effect was magnified under the combined influence of Hcy and androgen(s). Estradiol, by contrast, exhibited the reverse effect. The findings suggest that HA may independently attribute to an increased cardiovascular risk in PCOS; however, the coexistence of HHcy catalyzes the risk further. |
|
|
|