CIDeRplusGeneral Information:
| Id: | 7,527 |
| Diseases: |
Cardiovascular disease
Diabetes mellitus, type II - [OMIM] Insulin resistance |
| Mammalia | |
| review | |
| Reference: | Kjolby M et al.(2015) Sortilin, encoded by the cardiovascular risk gene SORT1, and its suggested functions in cardiovascular disease Curr Atheroscler Rep 17: 496 [PMID: 25702058] |
Interaction Information:
| Comment | SORT1 encodes sortilin, a type I sorting receptor that has recently been implicated in LDL-cholesterol metabolism, VLDL secretion, PCSK9 secretion, and development of atherosclerotic lesions. Sortilin also seems to be involved in the development of atherosclerosis, by mechanisms not directly involving LDL-cholesterol, but possibly resulting from the attenuated secretion of proinflammatory cytokines, such as IL6 and TNFalpha, which accompanies lack of sortilin in immune cells. |
|
Formal Description Interaction-ID: 74242 |
|
| Comment | SORT1 encodes sortilin, a type I sorting receptor that has recently been implicated in LDL-cholesterol metabolism, VLDL secretion, PCSK9 secretion, and development of atherosclerotic lesions. Sortilin also seems to be involved in the development of atherosclerosis, by mechanisms not directly involving LDL-cholesterol, but possibly resulting from the attenuated secretion of proinflammatory cytokines, such as IL6 and TNFalpha, which accompanies lack of sortilin in immune cells. |
|
Formal Description Interaction-ID: 74317 |
|
| Comment | SORT1 encodes sortilin, a type I sorting receptor that has recently been implicated in LDL-cholesterol metabolism, VLDL secretion, PCSK9 secretion, and development of atherosclerotic lesions. Sortilin also seems to be involved in the development of atherosclerosis, by mechanisms not directly involving LDL-cholesterol, but possibly resulting from the attenuated secretion of proinflammatory cytokines, such as IL6 and TNFalpha, which accompanies lack of sortilin in immune cells. |
|
Formal Description Interaction-ID: 74318 |
|
| Comment | SORT1 encodes sortilin, a type I sorting receptor that has recently been implicated in LDL-cholesterol metabolism, VLDL secretion, PCSK9 secretion, and development of atherosclerotic lesions. Sortilin also seems to be involved in the development of atherosclerosis, by mechanisms not directly involving LDL-cholesterol, but possibly resulting from the attenuated secretion of proinflammatory cytokines, such as IL6 and TNFalpha, which accompanies lack of sortilin in immune cells. |
|
Formal Description Interaction-ID: 74319 |
|
| Comment | SORT1 encodes sortilin, a type I sorting receptor that has recently been implicated in LDL-cholesterol metabolism, VLDL secretion, PCSK9 secretion, and development of atherosclerotic lesions. Sortilin also seems to be involved in the development of atherosclerosis, by mechanisms not directly involving LDL-cholesterol, but possibly resulting from the attenuated secretion of proinflammatory cytokines, such as IL6 and TNFalpha, which accompanies lack of sortilin in immune cells. |
|
Formal Description Interaction-ID: 74320 |
|
| Drugbank entries | Show/Hide entries for IL6 |
| Comment | SORT1 encodes sortilin, a type I sorting receptor that has recently been implicated in LDL-cholesterol metabolism, VLDL secretion, PCSK9 secretion, and development of atherosclerotic lesions. Sortilin also seems to be involved in the development of atherosclerosis, by mechanisms not directly involving LDL-cholesterol, but possibly resulting from the attenuated secretion of proinflammatory cytokines, such as IL6 and TNFalpha, which accompanies lack of sortilin in immune cells. |
|
Formal Description Interaction-ID: 74321 |
|
| Drugbank entries | Show/Hide entries for TNF |
| Comment | SORT1 encodes sortilin, a type I sorting receptor that has recently been implicated in LDL-cholesterol metabolism, VLDL secretion, PCSK9 secretion, and development of atherosclerotic lesions. Sortilin also seems to be involved in the development of atherosclerosis, by mechanisms not directly involving LDL-cholesterol, but possibly resulting from the attenuated secretion of proinflammatory cytokines, such as IL6 and TNFalpha, which accompanies lack of sortilin in immune cells. |
|
Formal Description Interaction-ID: 74322 |
|
| Comment | A number of monogenic disorders, e.g., mutations in LDLR, PCSK9, APOB, and APOE, are known to influence lipid traits resulting in elevated LDL-cholesterol (LDL-C) and subsequent disease. |
|
Formal Description Interaction-ID: 74323 |
|
| Drugbank entries | Show/Hide entries for LDLR |
| Comment | A number of monogenic disorders, e.g., mutations in LDLR, PCSK9, APOB, and APOE, are known to influence lipid traits resulting in elevated LDL-cholesterol (LDL-C) and subsequent disease. |
|
Formal Description Interaction-ID: 74324 |
|
| Comment | A number of monogenic disorders, e.g., mutations in LDLR, PCSK9, APOB, and APOE, are known to influence lipid traits resulting in elevated LDL-cholesterol (LDL-C) and subsequent disease. |
|
Formal Description Interaction-ID: 74325 |
|
| Comment | A number of monogenic disorders, e.g., mutations in LDLR, PCSK9, APOB, and APOE, are known to influence lipid traits resulting in elevated LDL-cholesterol (LDL-C) and subsequent disease. |
|
Formal Description Interaction-ID: 74326 |
|
| Drugbank entries | Show/Hide entries for APOE |
| Comment | Cardiovascular disease (CVD) is generally characterized as a polygenic disorder involving several different cell types including vascular smooth muscle cells (SMC), macrophages, T lymphocytes, endothelial cells, and hepatocytes, and it is commonly associated with risk factors such as lifestyle, e.g., smoking and physical inactivity, or potentially causative conditions like diabetes, high cholesterol levels, and hypertension. In each case, one of the most prominent risk factors is elevated levels of circulating low-density lipoprotein particles (LDL-C). |
|
Formal Description Interaction-ID: 74327 |
increases_activity of disease Cardiovascular disease |
| Comment | At 1p13.3, five SNPs, namely, rs599839, rs646776, rs12740374, rs629301, and rs4970834, are positioned between genes, i.e., downstream of SORT1, and near PSRC1 and CELSR2. In several independent studies, these SNPs have shown association to interconnected cardiovascular phenotypes encompassing LDL-C, coronary artery disease, myocardial infarction, abdominal aortic aneurysm, coronary artery calcification, and coronary artery stenosis. In particular, the association between 1p13.3 and LDL-C has been replicated in various populations. The five SNPs are in high linkage disequilibrium and constitute a major and minor haplotype, with allele frequencies 0.76 and 0.24, respectively. |
|
Formal Description Interaction-ID: 74328 |
|
| Comment | At 1p13.3, five SNPs, namely, rs599839, rs646776, rs12740374, rs629301, and rs4970834, are positioned between genes, i.e., downstream of SORT1, and near PSRC1 and CELSR2. In several independent studies, these SNPs have shown association to interconnected cardiovascular phenotypes encompassing LDL-C, coronary artery disease, myocardial infarction, abdominal aortic aneurysm, coronary artery calcification, and coronary artery stenosis. In particular, the association between 1p13.3 and LDL-C has been replicated in various populations. The five SNPs are in high linkage disequilibrium and constitute a major and minor haplotype, with allele frequencies 0.76 and 0.24, respectively. |
|
Formal Description Interaction-ID: 74329 |
|
| Comment | At 1p13.3, five SNPs, namely, rs599839, rs646776, rs12740374, rs629301, and rs4970834, are positioned between genes, i.e., downstream of SORT1, and near PSRC1 and CELSR2. In several independent studies, these SNPs have shown association to interconnected cardiovascular phenotypes encompassing LDL-C, coronary artery disease, myocardial infarction, abdominal aortic aneurysm, coronary artery calcification, and coronary artery stenosis. In particular, the association between 1p13.3 and LDL-C has been replicated in various populations. The five SNPs are in high linkage disequilibrium and constitute a major and minor haplotype, with allele frequencies 0.76 and 0.24, respectively. |
|
Formal Description Interaction-ID: 74330 |
|
| Comment | At 1p13.3, five SNPs, namely, rs599839, rs646776, rs12740374, rs629301, and rs4970834, are positioned between genes, i.e., downstream of SORT1, and near PSRC1 and CELSR2. In several independent studies, these SNPs have shown association to interconnected cardiovascular phenotypes encompassing LDL-C, coronary artery disease, myocardial infarction, abdominal aortic aneurysm, coronary artery calcification, and coronary artery stenosis. In particular, the association between 1p13.3 and LDL-C has been replicated in various populations. The five SNPs are in high linkage disequilibrium and constitute a major and minor haplotype, with allele frequencies 0.76 and 0.24, respectively. |
|
Formal Description Interaction-ID: 74331 |
|
| Comment | At 1p13.3, five SNPs, namely, rs599839, rs646776, rs12740374, rs629301, and rs4970834, are positioned between genes, i.e., downstream of SORT1, and near PSRC1 and CELSR2. In several independent studies, these SNPs have shown association to interconnected cardiovascular phenotypes encompassing LDL-C, coronary artery disease, myocardial infarction, abdominal aortic aneurysm, coronary artery calcification, and coronary artery stenosis. In particular, the association between 1p13.3 and LDL-C has been replicated in various populations. The five SNPs are in high linkage disequilibrium and constitute a major and minor haplotype, with allele frequencies 0.76 and 0.24, respectively. |
|
Formal Description Interaction-ID: 74332 |
|
| Comment | The major allele for the SNP, rs646776, was associated with lower mRNA levels for all three genes (SORT1, PSRC1, CELSR2). The total number of samples was limited to 60 human livers resulting in only 2 samples for the homozygous minor allele. In other words, evidence suggested that the minor allele conferred increased expression of SORT1, PSRC1, CELSR2 mRNA, and that expression of mRNA was inversely correlated to the level of LDL-C. |
|
Formal Description Interaction-ID: 74333 |
SNP increases_expression of gene/protein |
| Comment | The major allele for the SNP, rs646776, was associated with lower mRNA levels for all three genes (SORT1, PSRC1, CELSR2). The total number of samples was limited to 60 human livers resulting in only 2 samples for the homozygous minor allele. In other words, evidence suggested that the minor allele conferred increased expression of SORT1, PSRC1, CELSR2 mRNA, and that expression of mRNA was inversely correlated to the level of LDL-C. |
|
Formal Description Interaction-ID: 74334 |
SNP increases_expression of gene/protein |
| Comment | The major allele for the SNP, rs646776, was associated with lower mRNA levels for all three genes (SORT1, PSRC1, CELSR2). The total number of samples was limited to 60 human livers resulting in only 2 samples for the homozygous minor allele. In other words, evidence suggested that the minor allele conferred increased expression of SORT1, PSRC1, CELSR2 mRNA, and that expression of mRNA was inversely correlated to the level of LDL-C. |
|
Formal Description Interaction-ID: 74335 |
SNP increases_expression of gene/protein |
| Comment | A study characterized the relationship between more than 39,000 transcripts and 782,476 SNPs in more than 400 human livers and found that out of seven SNPs associated with coronary artery disease, only rs599839 (1p13.3) appeared to be associated with expression traits. In humans, the major allele rs599839 was associated with low expression of SORT1, PSRC1, and CELSR2 and an elevated LDL cholesterol level. |
|
Formal Description Interaction-ID: 74336 |
SNP decreases_expression of gene/protein |
| Comment | A study characterized the relationship between more than 39,000 transcripts and 782,476 SNPs in more than 400 human livers and found that out of seven SNPs associated with coronary artery disease, only rs599839 (1p13.3) appeared to be associated with expression traits. In humans, the major allele rs599839 was associated with low expression of SORT1, PSRC1, and CELSR2 and an elevated LDL cholesterol level. |
|
Formal Description Interaction-ID: 74337 |
SNP decreases_expression of gene/protein |
| Comment | A study characterized the relationship between more than 39,000 transcripts and 782,476 SNPs in more than 400 human livers and found that out of seven SNPs associated with coronary artery disease, only rs599839 (1p13.3) appeared to be associated with expression traits. In humans, the major allele rs599839 was associated with low expression of SORT1, PSRC1, and CELSR2 and an elevated LDL cholesterol level. |
|
Formal Description Interaction-ID: 74338 |
SNP decreases_expression of gene/protein |
| Comment | A study characterized the relationship between more than 39,000 transcripts and 782,476 SNPs in more than 400 human livers and found that out of seven SNPs associated with coronary artery disease, only rs599839 (1p13.3) appeared to be associated with expression traits. In humans, the major allele rs599839 was associated with low expression of SORT1, PSRC1, and CELSR2 and an elevated LDL cholesterol level. |
|
Formal Description Interaction-ID: 74339 |
SNP increases_activity of |
| Comment | The major allele for the SNP, rs646776, was associated with lower mRNA levels for all three genes (SORT1, PSRC1, CELSR2). The total number of samples was limited to 60 human livers resulting in only 2 samples for the homozygous minor allele. In other words, evidence suggested that the minor allele conferred increased expression of SORT1, PSRC1, CELSR2 mRNA, and that expression of mRNA was inversely correlated to the level of LDL-C. |
|
Formal Description Interaction-ID: 74340 |
SNP decreases_activity of |
| Comment | SORT1 has been genetically associated to cardiovascular phenotypes, such as myocardial infarction, abdominal aortic aneurysm, coronary artery calcification, and coronary artery stenosis. |
|
Formal Description Interaction-ID: 74341 |
|
| Comment | SORT1 has been genetically associated to cardiovascular phenotypes, such as myocardial infarction, abdominal aortic aneurysm, coronary artery calcification, and coronary artery stenosis. |
|
Formal Description Interaction-ID: 74342 |
|
| Comment | SORT1 has been genetically associated to cardiovascular phenotypes, such as myocardial infarction, abdominal aortic aneurysm, coronary artery calcification, and coronary artery stenosis. |
|
Formal Description Interaction-ID: 74343 |
|
| Comment | SORT1 has been genetically associated to cardiovascular phenotypes, such as myocardial infarction, abdominal aortic aneurysm, coronary artery calcification, and coronary artery stenosis. |
|
Formal Description Interaction-ID: 74344 |
|
| Comment | Increased levels of sortilin protein and mRNA (but not for PSRC1 or CELSR2) were detected originating from vascular smooth muscle cells (SMCs) and inflammatory cells in aortic aneurysm tissue compared to normal aorta (control). |
|
Formal Description Interaction-ID: 74345 |
|
| Comment | Macrophages, T-cells, and SMCs express sortilin. |
|
Formal Description Interaction-ID: 74346 |
|
| Comment | Macrophages, T-cells, and SMCs express sortilin. |
|
Formal Description Interaction-ID: 74347 |
|
| Comment | Macrophages, T-cells, and SMCs express sortilin. |
|
Formal Description Interaction-ID: 74348 |
|
| Comment | Coronary artery calcification and myocardial infarction were associated to both rs599839 and rs6657811. |
|
Formal Description Interaction-ID: 74349 |
|
| Comment | Coronary artery calcification and myocardial infarction were associated to both rs599839 and rs6657811. |
|
Formal Description Interaction-ID: 74350 |
|
| Comment | Coronary artery calcification and myocardial infarction were associated to both rs599839 and rs6657811. |
|
Formal Description Interaction-ID: 74351 |
|
| Comment | Coronary artery calcification and myocardial infarction were associated to both rs599839 and rs6657811. |
|
Formal Description Interaction-ID: 74352 |
|
| Comment | SORT1 encodes sortilin, a multiligand type 1 receptor that is expressed in many cell and tissue types including brain, heart, bone, fat, liver and neurons, hepatocytes, adipocytes, smooth muscle cells, blood lymphocytes, and macrophages. The extracellular part of sortilin is dominated by a small N-terminal propeptide followed by a large ligand binding 10-bladed beta-propeller. The propeptide prevents ligands from interacting with (pro)sortilin in the biosynthetic pathway until it is removed by cleavage in or after passage of the trans-Golgi network (TGN). The mature receptor binds a variety of ligands encompassing nerve growth factors and peptides, as well as cytokines and ligands associatedwith lipid metabolism, e.g., lipoprotein lipase, APOA-V, DLK1 and has, accordingly, been implicated in alternate tissue dependent functions. Sortilin is expressed on the cell surface in low abundance but predominates in Golgi and paranuclear compartments, and its short cytoplasmic domain contains functional motifs for endocytosis as well as Golgi-endosome sorting. |
|
Formal Description Interaction-ID: 74353 |
|
| Drugbank entries | Show/Hide entries for LPL |
| Comment | SORT1 encodes sortilin, a multiligand type 1 receptor that is expressed in many cell and tissue types including brain, heart, bone, fat, liver and neurons, hepatocytes, adipocytes, smooth muscle cells, blood lymphocytes, and macrophages. The extracellular part of sortilin is dominated by a small N-terminal propeptide followed by a large ligand binding 10-bladed beta-propeller. The propeptide prevents ligands from interacting with (pro)sortilin in the biosynthetic pathway until it is removed by cleavage in or after passage of the trans-Golgi network (TGN). The mature receptor binds a variety of ligands encompassing nerve growth factors and peptides, as well as cytokines and ligands associatedwith lipid metabolism, e.g., lipoprotein lipase, APOA-V, DLK1 and has, accordingly, been implicated in alternate tissue dependent functions. Sortilin is expressed on the cell surface in low abundance but predominates in Golgi and paranuclear compartments, and its short cytoplasmic domain contains functional motifs for endocytosis as well as Golgi-endosome sorting. |
|
Formal Description Interaction-ID: 74354 |
|
| Comment | SORT1 encodes sortilin, a multiligand type 1 receptor that is expressed in many cell and tissue types including brain, heart, bone, fat, liver and neurons, hepatocytes, adipocytes, smooth muscle cells, blood lymphocytes, and macrophages. The extracellular part of sortilin is dominated by a small N-terminal propeptide followed by a large ligand binding 10-bladed beta-propeller. The propeptide prevents ligands from interacting with (pro)sortilin in the biosynthetic pathway until it is removed by cleavage in or after passage of the trans-Golgi network (TGN). The mature receptor binds a variety of ligands encompassing nerve growth factors and peptides, as well as cytokines and ligands associatedwith lipid metabolism, e.g., lipoprotein lipase, APOA-V, DLK1 and has, accordingly, been implicated in alternate tissue dependent functions. Sortilin is expressed on the cell surface in low abundance but predominates in Golgi and paranuclear compartments, and its short cytoplasmic domain contains functional motifs for endocytosis as well as Golgi-endosome sorting. |
|
Formal Description Interaction-ID: 74355 |
|
| Comment | SORT1 encodes sortilin, a multiligand type 1 receptor that is expressed in many cell and tissue types including brain, heart, bone, fat, liver and neurons, hepatocytes, adipocytes, smooth muscle cells, blood lymphocytes, and macrophages. The extracellular part of sortilin is dominated by a small N-terminal propeptide followed by a large ligand binding 10-bladed beta-propeller. The propeptide prevents ligands from interacting with (pro)sortilin in the biosynthetic pathway until it is removed by cleavage in or after passage of the trans-Golgi network (TGN). The mature receptor binds a variety of ligands encompassing nerve growth factors and peptides, as well as cytokines and ligands associatedwith lipid metabolism, e.g., lipoprotein lipase, APOA-V, DLK1 and has, accordingly, been implicated in alternate tissue dependent functions. Sortilin is expressed on the cell surface in low abundance but predominates in Golgi and paranuclear compartments, and its short cytoplasmic domain contains functional motifs for endocytosis as well as Golgi-endosome sorting. |
|
Formal Description Interaction-ID: 74356 |
|
| Comment | SORT1 encodes sortilin, a multiligand type 1 receptor that is expressed in many cell and tissue types including brain, heart, bone, fat, liver and neurons, hepatocytes, adipocytes, smooth muscle cells, blood lymphocytes, and macrophages. The extracellular part of sortilin is dominated by a small N-terminal propeptide followed by a large ligand binding 10-bladed beta-propeller. The propeptide prevents ligands from interacting with (pro)sortilin in the biosynthetic pathway until it is removed by cleavage in or after passage of the trans-Golgi network (TGN). The mature receptor binds a variety of ligands encompassing nerve growth factors and peptides, as well as cytokines and ligands associatedwith lipid metabolism, e.g., lipoprotein lipase, APOA-V, DLK1 and has, accordingly, been implicated in alternate tissue dependent functions. Sortilin is expressed on the cell surface in low abundance but predominates in Golgi and paranuclear compartments, and its short cytoplasmic domain contains functional motifs for endocytosis as well as Golgi-endosome sorting. |
|
Formal Description Interaction-ID: 74357 |
|
| Comment | SORT1 encodes sortilin, a multiligand type 1 receptor that is expressed in many cell and tissue types including brain, heart, bone, fat, liver and neurons, hepatocytes, adipocytes, smooth muscle cells, blood lymphocytes, and macrophages. The extracellular part of sortilin is dominated by a small N-terminal propeptide followed by a large ligand binding 10-bladed beta-propeller. The propeptide prevents ligands from interacting with (pro)sortilin in the biosynthetic pathway until it is removed by cleavage in or after passage of the trans-Golgi network (TGN). The mature receptor binds a variety of ligands encompassing nerve growth factors and peptides, as well as cytokines and ligands associatedwith lipid metabolism, e.g., lipoprotein lipase, APOA-V, DLK1 and has, accordingly, been implicated in alternate tissue dependent functions. Sortilin is expressed on the cell surface in low abundance but predominates in Golgi and paranuclear compartments, and its short cytoplasmic domain contains functional motifs for endocytosis as well as Golgi-endosome sorting. |
|
Formal Description Interaction-ID: 74358 |
|
| Comment | SORT1 encodes sortilin, a multiligand type 1 receptor that is expressed in many cell and tissue types including brain, heart, bone, fat, liver and neurons, hepatocytes, adipocytes, smooth muscle cells, blood lymphocytes, and macrophages. The extracellular part of sortilin is dominated by a small N-terminal propeptide followed by a large ligand binding 10-bladed beta-propeller. The propeptide prevents ligands from interacting with (pro)sortilin in the biosynthetic pathway until it is removed by cleavage in or after passage of the trans-Golgi network (TGN). The mature receptor binds a variety of ligands encompassing nerve growth factors and peptides, as well as cytokines and ligands associatedwith lipid metabolism, e.g., lipoprotein lipase, APOA-V, DLK1 and has, accordingly, been implicated in alternate tissue dependent functions. Sortilin is expressed on the cell surface in low abundance but predominates in Golgi and paranuclear compartments, and its short cytoplasmic domain contains functional motifs for endocytosis as well as Golgi-endosome sorting. |
|
Formal Description Interaction-ID: 74359 |
|
| Comment | SORT1 encodes sortilin, a multiligand type 1 receptor that is expressed in many cell and tissue types including brain, heart, bone, fat, liver and neurons, hepatocytes, adipocytes, smooth muscle cells, blood lymphocytes, and macrophages. The extracellular part of sortilin is dominated by a small N-terminal propeptide followed by a large ligand binding 10-bladed beta-propeller. The propeptide prevents ligands from interacting with (pro)sortilin in the biosynthetic pathway until it is removed by cleavage in or after passage of the trans-Golgi network (TGN). The mature receptor binds a variety of ligands encompassing nerve growth factors and peptides, as well as cytokines and ligands associatedwith lipid metabolism, e.g., lipoprotein lipase, APOA-V, DLK1 and has, accordingly, been implicated in alternate tissue dependent functions. Sortilin is expressed on the cell surface in low abundance but predominates in Golgi and paranuclear compartments, and its short cytoplasmic domain contains functional motifs for endocytosis as well as Golgi-endosome sorting. |
|
Formal Description Interaction-ID: 74360 |
|
| Comment | SORT1 encodes sortilin, a multiligand type 1 receptor that is expressed in many cell and tissue types including brain, heart, bone, fat, liver and neurons, hepatocytes, adipocytes, smooth muscle cells, blood lymphocytes, and macrophages. The extracellular part of sortilin is dominated by a small N-terminal propeptide followed by a large ligand binding 10-bladed beta-propeller. The propeptide prevents ligands from interacting with (pro)sortilin in the biosynthetic pathway until it is removed by cleavage in or after passage of the trans-Golgi network (TGN). The mature receptor binds a variety of ligands encompassing nerve growth factors and peptides, as well as cytokines and ligands associatedwith lipid metabolism, e.g., lipoprotein lipase, APOA-V, DLK1 and has, accordingly, been implicated in alternate tissue dependent functions. Sortilin is expressed on the cell surface in low abundance but predominates in Golgi and paranuclear compartments, and its short cytoplasmic domain contains functional motifs for endocytosis as well as Golgi-endosome sorting. |
|
Formal Description Interaction-ID: 74361 |
|
| Drugbank entries | Show/Hide entries for IFNG |
| Comment | SORT1 encodes sortilin, a multiligand type 1 receptor that is expressed in many cell and tissue types including brain, heart, bone, fat, liver and neurons, hepatocytes, adipocytes, smooth muscle cells, blood lymphocytes, and macrophages. The extracellular part of sortilin is dominated by a small N-terminal propeptide followed by a large ligand binding 10-bladed beta-propeller. The propeptide prevents ligands from interacting with (pro)sortilin in the biosynthetic pathway until it is removed by cleavage in or after passage of the trans-Golgi network (TGN). The mature receptor binds a variety of ligands encompassing nerve growth factors and peptides, as well as cytokines and ligands associatedwith lipid metabolism, e.g., lipoprotein lipase, APOA-V, DLK1 and has, accordingly, been implicated in alternate tissue dependent functions. Sortilin is expressed on the cell surface in low abundance but predominates in Golgi and paranuclear compartments, and its short cytoplasmic domain contains functional motifs for endocytosis as well as Golgi-endosome sorting. |
|
Formal Description Interaction-ID: 74362 |
|
| Drugbank entries | Show/Hide entries for IL6 |
| Comment | SORT1 encodes sortilin, a multiligand type 1 receptor that is expressed in many cell and tissue types including brain, heart, bone, fat, liver and neurons, hepatocytes, adipocytes, smooth muscle cells, blood lymphocytes, and macrophages. The extracellular part of sortilin is dominated by a small N-terminal propeptide followed by a large ligand binding 10-bladed beta-propeller. The propeptide prevents ligands from interacting with (pro)sortilin in the biosynthetic pathway until it is removed by cleavage in or after passage of the trans-Golgi network (TGN). The mature receptor binds a variety of ligands encompassing nerve growth factors and peptides, as well as cytokines and ligands associatedwith lipid metabolism, e.g., lipoprotein lipase, APOA-V, DLK1 and has, accordingly, been implicated in alternate tissue dependent functions. Sortilin is expressed on the cell surface in low abundance but predominates in Golgi and paranuclear compartments, and its short cytoplasmic domain contains functional motifs for endocytosis as well as Golgi-endosome sorting. |
|
Formal Description Interaction-ID: 74363 |
|
| Comment | SORT1 encodes sortilin, a multiligand type 1 receptor that is expressed in many cell and tissue types including brain, heart, bone, fat, liver and neurons, hepatocytes, adipocytes, smooth muscle cells, blood lymphocytes, and macrophages. The extracellular part of sortilin is dominated by a small N-terminal propeptide followed by a large ligand binding 10-bladed beta-propeller. The propeptide prevents ligands from interacting with (pro)sortilin in the biosynthetic pathway until it is removed by cleavage in or after passage of the trans-Golgi network (TGN). The mature receptor binds a variety of ligands encompassing nerve growth factors and peptides, as well as cytokines and ligands associatedwith lipid metabolism, e.g., lipoprotein lipase, APOA-V, DLK1 and has, accordingly, been implicated in alternate tissue dependent functions. Sortilin is expressed on the cell surface in low abundance but predominates in Golgi and paranuclear compartments, and its short cytoplasmic domain contains functional motifs for endocytosis as well as Golgi-endosome sorting. |
|
Formal Description Interaction-ID: 74364 |
|
| Comment | SORT1 encodes sortilin, a multiligand type 1 receptor that is expressed in many cell and tissue types including brain, heart, bone, fat, liver and neurons, hepatocytes, adipocytes, smooth muscle cells, blood lymphocytes, and macrophages. The extracellular part of sortilin is dominated by a small N-terminal propeptide followed by a large ligand binding 10-bladed beta-propeller. The propeptide prevents ligands from interacting with (pro)sortilin in the biosynthetic pathway until it is removed by cleavage in or after passage of the trans-Golgi network (TGN). The mature receptor binds a variety of ligands encompassing nerve growth factors and peptides, as well as cytokines and ligands associatedwith lipid metabolism, e.g., lipoprotein lipase, APOA-V, DLK1 and has, accordingly, been implicated in alternate tissue dependent functions. Sortilin is expressed on the cell surface in low abundance but predominates in Golgi and paranuclear compartments, and its short cytoplasmic domain contains functional motifs for endocytosis as well as Golgi-endosome sorting. |
|
Formal Description Interaction-ID: 74365 |
|
| Comment | SORT1 encodes sortilin, a multiligand type 1 receptor that is expressed in many cell and tissue types including brain, heart, bone, fat, liver and neurons, hepatocytes, adipocytes, smooth muscle cells, blood lymphocytes, and macrophages. The extracellular part of sortilin is dominated by a small N-terminal propeptide followed by a large ligand binding 10-bladed beta-propeller. The propeptide prevents ligands from interacting with (pro)sortilin in the biosynthetic pathway until it is removed by cleavage in or after passage of the trans-Golgi network (TGN). The mature receptor binds a variety of ligands encompassing nerve growth factors and peptides, as well as cytokines and ligands associatedwith lipid metabolism, e.g., lipoprotein lipase, APOA-V, DLK1 and has, accordingly, been implicated in alternate tissue dependent functions. Sortilin is expressed on the cell surface in low abundance but predominates in Golgi and paranuclear compartments, and its short cytoplasmic domain contains functional motifs for endocytosis as well as Golgi-endosome sorting. |
|
Formal Description Interaction-ID: 74366 |
|
| Comment | SORT1 encodes sortilin, a multiligand type 1 receptor that is expressed in many cell and tissue types including brain, heart, bone, fat, liver and neurons, hepatocytes, adipocytes, smooth muscle cells, blood lymphocytes, and macrophages. The extracellular part of sortilin is dominated by a small N-terminal propeptide followed by a large ligand binding 10-bladed beta-propeller. The propeptide prevents ligands from interacting with (pro)sortilin in the biosynthetic pathway until it is removed by cleavage in or after passage of the trans-Golgi network (TGN). The mature receptor binds a variety of ligands encompassing nerve growth factors and peptides, as well as cytokines and ligands associatedwith lipid metabolism, e.g., lipoprotein lipase, APOA-V, DLK1 and has, accordingly, been implicated in alternate tissue dependent functions. Sortilin is expressed on the cell surface in low abundance but predominates in Golgi and paranuclear compartments, and its short cytoplasmic domain contains functional motifs for endocytosis as well as Golgi-endosome sorting. |
|
Formal Description Interaction-ID: 74367 |
|
| Comment | SORT1 encodes sortilin, a multiligand type 1 receptor that is expressed in many cell and tissue types including brain, heart, bone, fat, liver and neurons, hepatocytes, adipocytes, smooth muscle cells, blood lymphocytes, and macrophages. The extracellular part of sortilin is dominated by a small N-terminal propeptide followed by a large ligand binding 10-bladed beta-propeller. The propeptide prevents ligands from interacting with (pro)sortilin in the biosynthetic pathway until it is removed by cleavage in or after passage of the trans-Golgi network (TGN). The mature receptor binds a variety of ligands encompassing nerve growth factors and peptides, as well as cytokines and ligands associatedwith lipid metabolism, e.g., lipoprotein lipase, APOA-V, DLK1 and has, accordingly, been implicated in alternate tissue dependent functions. Sortilin is expressed on the cell surface in low abundance but predominates in Golgi and paranuclear compartments, and its short cytoplasmic domain contains functional motifs for endocytosis as well as Golgi-endosome sorting. |
|
Formal Description Interaction-ID: 74368 |
|
| Drugbank entries | Show/Hide entries for BACE1 |
| Comment | SORT1 encodes sortilin, a multiligand type 1 receptor that is expressed in many cell and tissue types including brain, heart, bone, fat, liver and neurons, hepatocytes, adipocytes, smooth muscle cells, blood lymphocytes, and macrophages. The extracellular part of sortilin is dominated by a small N-terminal propeptide followed by a large ligand binding 10-bladed beta-propeller. The propeptide prevents ligands from interacting with (pro)sortilin in the biosynthetic pathway until it is removed by cleavage in or after passage of the trans-Golgi network (TGN). The mature receptor binds a variety of ligands encompassing nerve growth factors and peptides, as well as cytokines and ligands associatedwith lipid metabolism, e.g., lipoprotein lipase, APOA-V, DLK1 and has, accordingly, been implicated in alternate tissue dependent functions. Sortilin is expressed on the cell surface in low abundance but predominates in Golgi and paranuclear compartments, and its short cytoplasmic domain contains functional motifs for endocytosis as well as Golgi-endosome sorting. |
|
Formal Description Interaction-ID: 74369 |
|
| Comment | SORT1 encodes sortilin, a multiligand type 1 receptor that is expressed in many cell and tissue types including brain, heart, bone, fat, liver and neurons, hepatocytes, adipocytes, smooth muscle cells, blood lymphocytes, and macrophages. The extracellular part of sortilin is dominated by a small N-terminal propeptide followed by a large ligand binding 10-bladed beta-propeller. The propeptide prevents ligands from interacting with (pro)sortilin in the biosynthetic pathway until it is removed by cleavage in or after passage of the trans-Golgi network (TGN). The mature receptor binds a variety of ligands encompassing nerve growth factors and peptides, as well as cytokines and ligands associatedwith lipid metabolism, e.g., lipoprotein lipase, APOA-V, DLK1 and has, accordingly, been implicated in alternate tissue dependent functions. Sortilin is expressed on the cell surface in low abundance but predominates in Golgi and paranuclear compartments, and its short cytoplasmic domain contains functional motifs for endocytosis as well as Golgi-endosome sorting. |
|
Formal Description Interaction-ID: 74370 |
|
| Comment | SORT1 encodes sortilin, a multiligand type 1 receptor that is expressed in many cell and tissue types including brain, heart, bone, fat, liver and neurons, hepatocytes, adipocytes, smooth muscle cells, blood lymphocytes, and macrophages. The extracellular part of sortilin is dominated by a small N-terminal propeptide followed by a large ligand binding 10-bladed beta-propeller. The propeptide prevents ligands from interacting with (pro)sortilin in the biosynthetic pathway until it is removed by cleavage in or after passage of the trans-Golgi network (TGN). The mature receptor binds a variety of ligands encompassing nerve growth factors and peptides, as well as cytokines and ligands associatedwith lipid metabolism, e.g., lipoprotein lipase, APOA-V, DLK1 and has, accordingly, been implicated in alternate tissue dependent functions. Sortilin is expressed on the cell surface in low abundance but predominates in Golgi and paranuclear compartments, and its short cytoplasmic domain contains functional motifs for endocytosis as well as Golgi-endosome sorting. |
|
Formal Description Interaction-ID: 74371 |
|
| Comment | Cyp7a1 encodes the enzyme cholesterol 7alpha-hydroxylase which catalyzes the first step in the pathway that converts hepatic cholesterol into bile salts. Liver samples of Sort1-/- mice presented an increase in CYP7A1 enzyme. |
|
Formal Description Interaction-ID: 74372 |
|
| Comment | Cyp7a1 encodes the enzyme cholesterol 7alpha-hydroxylase which catalyzes the first step in the pathway that converts hepatic cholesterol into bile salts. Liver samples of Sort1-/- mice presented an increase in CYP7A1 enzyme. |
|
Formal Description Interaction-ID: 74373 |
|
| Comment | Sort1-/- mice (exon 14 targeted) fed high fat diet exhibit lower mRNA expression of the lipogenesis genes Fas and Scd, an increase in insulin resistance, and lower TG content in the livers. The involvement of Fas and Scd could also affect the VLDL secretion. |
|
Formal Description Interaction-ID: 74374 |
|
| Drugbank entries | Show/Hide entries for FASN |
| Comment | Sort1-/- mice (exon 14 targeted) fed high fat diet exhibit lower mRNA expression of the lipogenesis genes Fas and Scd, an increase in insulin resistance, and lower TG content in the livers. The involvement of Fas and Scd could also affect the VLDL secretion. |
|
Formal Description Interaction-ID: 74375 |
|
| Comment | Sort1-/- mice (exon 14 targeted) fed high fat diet exhibit lower mRNA expression of the lipogenesis genes Fas and Scd, an increase in insulin resistance, and lower TG content in the livers. The involvement of Fas and Scd could also affect the VLDL secretion. |
|
Formal Description Interaction-ID: 74376 |
|
| Comment | Overexpression of untagged human sortilin (adenovirus) in WT mice resulted in hypercholesterolemia, increased APOB100 (but unchanged APOB48), and accumulation of circulating LDL/IDL particles compared to corresponding levels in controls transfected with lacZ. |
|
Formal Description Interaction-ID: 74377 |
|
| Comment | Overexpression of untagged human sortilin (adenovirus) in WT mice resulted in hypercholesterolemia, increased APOB100 (but unchanged APOB48), and accumulation of circulating LDL/IDL particles compared to corresponding levels in controls transfected with lacZ. |
|
Formal Description Interaction-ID: 74378 |
|
| Comment | Sortilin confers cellular uptake of LDL-C if overexpressed. |
|
Formal Description Interaction-ID: 74379 |
|
| Comment | High-fat diet induces downregulation of Sort1 mRNA in mouse livers (using ob/ob, DIO, and Ldlr knockouts). |
|
Formal Description Interaction-ID: 74380 |
|
| Comment | ER stress represses sortilin expression (mRNA and protein) and is associated with increased VLDL secretion. ER stress was induced by obesity (ob/ob mice), high-fat diet (in C57BL6/j and Li-Tsc1KO), or by administration of tunicamycin. All resulted in reduction in sortilin expression, and concomitantly increased VLDL secretion (not shown in tunicamycin-treated animals, though). The effect of obesity and high-fat diet on sortilin was most convincing. |
|
Formal Description Interaction-ID: 74381 |
|
| Comment | Expression of sortilin was low in human steatotic livers, and palmitate and ceramide increase sortilin degradation without affecting Sort1/SORT1 mRNA and biosynthesis of sortilin in murine hepatocytes and HepG2 cells. In conclusion, obesity, steatosis, and free fatty acids seem to downregulate sortilin in the liver. |
|
Formal Description Interaction-ID: 74382 |
|
| Comment | Expression of sortilin was low in human steatotic livers, and palmitate and ceramide increase sortilin degradation without affecting Sort1/SORT1 mRNA and biosynthesis of sortilin in murine hepatocytes and HepG2 cells. In conclusion, obesity, steatosis, and free fatty acids seem to downregulate sortilin in the liver. |
|
Formal Description Interaction-ID: 74383 |
drug/chemical compound decreases_quantity of gene/protein |
| Drugbank entries | Show/Hide entries for Palmitic acid |
| Comment | Expression of sortilin was low in human steatotic livers, and palmitate and ceramide increase sortilin degradation without affecting Sort1/SORT1 mRNA and biosynthesis of sortilin in murine hepatocytes and HepG2 cells. In conclusion, obesity, steatosis, and free fatty acids seem to downregulate sortilin in the liver. |
|
Formal Description Interaction-ID: 74384 |
|
| Comment | Findings in separate strains of knockout mice strongly suggest that sortilin deficiency is "protective" and lowers the level of circulating LDL-C and cholesterol. In humans, however, low levels of sortilin (in carriers of the major haplotype/allele) are paralleled by an increased risk of developing hyperlipidemia and disease. This apparent paradox is further complicated by the conflicting results obtained by overexpression of sortilin in mice - results that are difficult to evaluate and compare due to differences in experimental approach (e.g., overexpression in the liver or whole body, and use of different types of genetically modified animals). |
|
Formal Description Interaction-ID: 74385 |
|