Human Sortilin-related receptor(SORL1) ELISA kit

Sorting receptor that directs several proteins to their correct location within the cell. Along with AP-1 complex, involved Golgi apparatus - endosome sorting. Sorting receptor for APP, regulating its intracellular trafficking and processing into amyloidogenic-beta peptides. Retains APP in the trans-Golgi network, hence preventing its transit through late endosomes where amyloid beta peptides Abeta40 and Abeta42 are generated. May also sort newly produced amyloid-beta peptides to lysosomes for catabolism. Does not affect APP trafficking from the endoplasmic reticulum to Golgi compartments. Sorting receptor for the BDNF receptor NTRK2/TRKB that facilitates NTRK2 trafficking between synaptic plasma membranes, postsynaptic densities and cell soma, hence positively regulates BDNF signaling by controlling the intracellular location of its receptor. Sorting receptor for GDNF that promotes GDNF regulated, but not constitutive secretion. Sorting receptor for the GDNF-GFRA1 complex, directing it from the cell surface to endosomes. GDNF is then targeted to lysosomes and degraded, while its receptor GFRA1 recycles back to the cell membrane, resulting in a GDNF clearance pathway. The SORL1-GFRA1 complex further targets RET for endocytosis, but not for degradation, affecting GDNF-induced neurotrophic activities. Sorting receptor for ERBB2/HER2. Regulates ERBB2 subcellular distribution by promoting its recycling after internalization from endosomes back to the plasma membrane, hence stimulating phosphoinositide 3-kinase (PI3K)-dependent ERBB2 signaling. In ERBB2-dependent cancer cells, promotes cell proliferation. Sorting receptor for lipoprotein lipase LPL. Promotes LPL localization to endosomes and later to the lysosomes, leading to degradation of newly synthesized LPL. Potential sorting receptor for APOA5, inducing APOA5 internalization to early endosomes, then to late endosomes, wherefrom a portion is sent to lysosomes and degradation, another portion is sorted to the trans-Golgi network. Sorting receptor for the insulin receptor INSR. Promotes recycling of internalized INSR via the Golgi apparatus back to the cell surface, thereby preventing lysosomal INSR catabolism, increasing INSR cell surface expression and strengthening insulin signal reception in adipose tissue. Does not affect INSR internalization. Plays a role in renal ion homeostasis, controlling the phospho-regulation of SLC12A1/NKCC2 by STK39/SPAK kinase and PPP3CB/calcineurin A beta phosphatase, possibly through intracellular sorting of STK39 and PPP3CB. Stimulates, via the N-terminal ectodomain, the proliferation and migration of smooth muscle cells, possibly by increasing cell surface expression of the urokinase receptor uPAR/PLAUR. This may promote extracellular matrix proteolysis and hence facilitate cell migration. By acting on the migration of intimal smooth muscle cells, may accelerate intimal thickening following vascular injury. Promotes adhesion of monocytes. Stimulates proliferation and migration of monocytes/macrophages. Through its action on intimal smooth muscle cells and macrophages, may accelerate intimal thickening and macrophage foam cell formation in the process of atherosclerosis. Regulates hypoxia-enhanced adhesion of hematopoietic stem and progenitor cells to the bone marrow stromal cells via a PLAUR-mediated pathway. This function is mediated by the N-terminal ectodomain. Metabolic regulator, which functions to maintain the adequate balance between lipid storage and oxidation in response to changing environmental conditions, such as temperature and diet. The N-terminal ectodomain negatively regulates adipose tissue energy expenditure, acting through the inhibition the BMP/Smad pathway. May regulate signaling by the heterodimeric neurotrophic cytokine CLCF1-CRLF1 bound to the CNTFR receptor by promoting the endocytosis of the tripartite complex CLCF1-CRLF1-CNTFR and lysosomal degradation. May regulate IL6 signaling, decreasing cis signaling, possibly by interfering with IL6-binding to membrane-bound IL6R, while up-regulating trans signaling via soluble IL6R.

1. Data show that amyloid precursor protein (APP) dimerization affects its interaction with LDL receptor related protein 1 (LRP1) and LDL-receptor related protein SorLA (SorLA), suggesting that APP dimerization modulates its interplay with sorting molecules and in turn its localization and processing. PMID: 28799085
2. The sorting-related receptor with A-type repeats (SorLA) is a well-studied pathogenic factor for Alzheimer's and belongs to the Vps10p domain receptor family, which also encompasses sortilin and SorCS1-3. PMID: 29499509
3. A meta-analysis identified empirical data assessing effects of a single nucleotide polymorphisms of SORL1 on Alzheimer's disease based on 14 studies involving 37941 cases and 49727 control studies; showed increased risk between single nucleotide polymorphisms (rs641120, rs1010159) and Alzheimer's disease susceptibility in Asian populations, single nucleotide polymorphisms rs641120 was detected as a decreased risk in both. PMID: 29036834
4. This study found one SORL1 RNA transcript strongly regulated by SORL1-BDNF interactions in elderly without pathological AD and showing stronger associations with diffuse than neuritic Abeta plaques. PMID: 28322202
5. The findings of this study suggested that three genetic variants rs2070045, rs1699102, and rs3824968 could significantly regulate SORL1 expression in human brain tissues. PMID: 28527213
6. We conclude that rs1784933 and rs1805192 minor alleles, gene- gene interaction between rs1784933 and rs1805192, gene- environment interaction between rs1784933 and alcohol drinking, and haplotype containing the rs1784933- A and rs689021- C alleles are all associated with increased LOAD risk. PMID: 28427149
7. Show reduced sortilin-related receptor (SORL1) expression only in neural stem cells of a patient carrying two copies of APOE4 allele with increased amyloid beta/SORL1 localization along the degenerated neurites. PMID: 28634550
8. This study shown rare Genetic Variant in SORL1 May Increase Penetrance of Alzheimer's Disease in a Family with Several Generations of APOE-varepsilon4 Homozygosity. PMID: 27911290
9. The C allele in SORL1 was found to be a protective factor for late-onset Alzheimer's disease in both Caucasian and Han Chinese. PMID: 26873856
10. Report altered hippocampal functional connectivity in carriers with risk APOE epsilon4 or SORL1 G-allele, which may predispose these risk-allele carriers to be susceptible for Alzheimer disease. PMID: 28229235
11. There was no significant association between single nucleotide polymorphisms (SNPS) of GAB2 rs2373115 (G > T) and PICALM rs541458 (C > T) and Alzheimer's disease (AD). The allele T of rs3851179 in PICALM was associated with a 13 % increase in the risk of AD. Seven SNPs on SORL1 were significantly associated with AD. PMID: 26611835
12. Its genetic variation contributes to pathogenesis of Alzheimer disease. PMID: 28789839
13. SORL1 variations influence the atrophy of specific Alzheimer disease-related brain structures, suggesting the potential role of SORL1 in the neurodegeneration of cognitive related regions. PMID: 27177090
14. These findings elucidate how the SORL1 variants shape the neural system to modulate age-related cognitive decline and support the hypothesis that SORL1 may represent a candidate gene for late-onset Alzheimer's disease. PMID: 27779372
15. Weight loss dieting in overweight and obese individuals with T2D resulted in a reduction in plasma sLR11 levels that was associated with improvements in lipid-profile and glycemic state PMID: 27697674
16. These results demonstrate a novel role for SORLA as a physiological and pathological EphA4 modulator. PMID: 29114064
17. Using three different patient cohorts of early onset Alzheimer disease (AD), study describes three SORL1 variants that segregate with disease in three families adding to the literature which supports SORL1 as a major player in AD pathoetiology. PMID: 28595629
18. SORL1 variant characteristics associated with variant pathogenicity were identified in Alzheimer disease cohort. PMID: 28537274
19. The results of this study support the effect of SORL1 gene on the disease risks and pathognomonic surrogates of Alzheimer's disease and mild cognitive impairment. PMID: 28034305
20. Study provides the first evidence that the sortilin-related receptor 1 gene is associated with brain functional connectivity density differences in healthy young adults. PMID: 26627482
21. Analysis of the molecular mechanism for the association of SORL1 with obesity: there is a genetic link between neurodegeneration and metabolism that converges on the receptor SORLA PMID: 27322061
22. This review will provide a comprehensive overview of the evidence implicating SORLA-mediated protein sorting in neurodegenerative processes, and how receptor gene variants in the human population impair functional receptor expression in sporadic but possibly also in autosomal-dominant forms of Alzheimer's disease. PMID: 27638701
23. SorLA ectodomain, released from the cell membrane upon enzymatic cleavage of full-length SorLA, may act as an IL-6 carrier protein that stabilizes IL-6 and its capacity for trans signaling. PMID: 28265003
24. observed a 1.5-fold enrichment of rare non-synonymous variants of sortilin-related receptor 1 in Alzheimer's disease patients PMID: 27026413
25. This review article discusses the molecular mechanisms that govern sorting of SORLA and its cargo in multiple cell types, and why genetic defects in this receptor results in devastating diseases. [review] PMID: 27832290
26. The presence of rare coding variants in SORL1 in three different European American cohorts: early-onset, late-onset AD (LOAD) and familial LOAD, was examined. PMID: 27650968
27. sLR11 levels in bile may be indicative of cancer cell conditions and may serve as potential novel biomarker in patients with BTC and PC PMID: 27079357
28. Increased sLR11 concentrations are highly associated with increased IMT as well as with FPG in middle-aged, non-obese patients with T2D. Circulating sLR11 may be a novel marker representing the pathophysiology of intimal SMCs in patients with T2D PMID: 27095609
29. SORL1 protein is involved with late onset Alzheimer's disease. [review] PMID: 27773727
30. The DNA methylation of the SORL1 5'-flanking region may significantly influence the manifestation of mild cognitive impairment in T2 Diabetes mellitus, and might be associated with its neurocognitive presentation. PMID: 27641082
31. Findings provide evidence that sortilin receptor 1 rs3824968 modulates regional gray matter volume and is associated with brain trajectory during the adult lifespan. PMID: 26996954
32. Serum LR11 reflects the development of vascular lesions in patients with serious coronary artery lesions. PMID: 26761773
33. Elevated sLR11 levels may increase the cardiovascular disease risk especially in subjects with delayed clearance of triglyceride-rich remnants, such as in familial hypercholesterolemia patients. PMID: 26520897
34. CLF-1, based on its binding site for CLC and on two additional and independent sites for CNTFRalpha and sorLA, is a key player in CLC and CNTFRalpha signaling and turnover. PMID: 26858303
35. Serum soluble LR11, a novel tumor derived biomarker associated with the outcome of patients with diffuse large B-cell lymphoma PMID: 25676033
36. sLR11 levels in humans are shown to positively correlate with body mass index and adiposity. PMID: 26584636
37. The findings of this study confirm that SORL1 is associated with Alzheimer's Disease and might be a potential tool for identifying Mild Cognitive Impairment subjects at high risk of conversion to lzheimer's Disease. PMID: 25881907
38. Study suggested a sex-moderated association of the SORL1 rs2070045 polymorphism and executive function in healthy elderly PMID: 25598427
39. Mutating recombinant human SORLA, disrupting retromer binding caused retrograde-sorting defect, endosomal accumulation, TGN, depletion, and enhanced APP processing. Disrupting the GGA interaction increased Abeta via defective anterograde lysosomal targeting. PMID: 26377460
40. genetic polymorphism controls protein expression, which directly regulates the amount of Abeta peptides implicated in Alzheimer's disease PMID: 25772071
41. SORL1 may be implicated in the downstream pathology in AD. PMID: 25659857
42. circulating sLR11 levels may be a potential marker for angiographic late loss in patients after coronary stenting PMID: 25443876
43. SORL1 risk variants influenced microstructure of white matter tracts with known susceptibility in Alzheimer's disease with consistent effect from childhood onward and predicted lower levels of mRNA expression PMID: 24166411
44. Mutants of metal binding site M1 in APP E2 show metal specific differences in binding of heparin but not of sorLA PMID: 25835329
45. SORL1 gene SNPs at rs689021 and rs3824966 loci show no relationship with LOAD onset in the Chinese Han population of the Hunan Changsha region. A SORL1 gene SNP at the rs1784933 locus is associated with LOAD onset, with the A allele being a risk factor. PMID: 25450149
46. SLR11 had a positive correlation with average ATT. PMID: 24859021
47. SORLA CR(5-8) cluster binds APP and is essential for the SorLA-dependent decrease in APP proteolysis. PMID: 25525276
48. Brain DNA methylation in SORL1 was associated with pathological Alzheimer disease. PMID: 25365775
49. Seventeen coding exonic variants were significantly associated with Alzheimer's disease. PMID: 25382023
50. human-apoE-isoform-dependent differences modulate the cellular uptake of Abeta mediated by LR11/SorLA PMID: 25482438

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Alzheimer disease (AD)

Golgi apparatus membrane; Single-pass type I membrane protein. Golgi apparatus, trans-Golgi network membrane; Single-pass type I membrane protein. Endosome membrane; Single-pass type I membrane protein. Early endosome membrane; Single-pass type I membrane protein. Recycling endosome membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein. Endosome, multivesicular body membrane; Single-pass type I membrane protein. Cell membrane; Single-pass type I membrane protein. Cytoplasmic vesicle, secretory vesicle membrane; Single-pass type I membrane protein. Secreted.

VPS10-related sortilin family, SORL1 subfamily

Highly expressed in brain (at protein level). Most abundant in the cerebellum, cerebral cortex and occipital pole; low levels in the putamen and thalamus. Expression is significantly reduced in the frontal cortex of patients suffering from Alzheimer disea

HGNC: 11185

OMIM: 104300

KEGG: hsa:6653

STRING: 9606.ENSP00000260197

UniGene: Hs.368592