SORL1

  • Official Full Name

    sortilin-related receptor, L(DLR class) A repeats containing

  • Overview

    This gene encodes a mosaic protein that belongs to at least two families: the vacuolar protein sorting 10 (VPS10);domain-containing receptor family, and the low density lipoprotein receptor (LDLR) family. The encoded protein also;contains fibronectin type III repeats and an epidermal growth factor repeat. The encoded protein is translated as a;preproprotein and likely plays roles in endocytosis and sorting. There may be an association between expression of;this locus and Alzheimers Disease.
  • Synonyms

    SORL1; sortilin-related receptor, L(DLR class) A repeats containing; C11orf32, chromosome 11 open reading frame 32 , sortilin related receptor, L(DLR class) A repeats containing; sortilin-related receptor; gp250; LR11; LRP9; SorLA; SorLA 1; C11orf32; FLJ21930; FLJ39258; LDLR relative with 11 ligand binding repeats; LDLR relative with 11 ligand-binding repeats; Low density lipoprotein receptor relative with 11 ligand binding repeats; Low-density lipoprotein receptor relative with 11 ligand-binding repeats; LR 11; LRP 9; Mosaic protein LR11; SORL 1; SORL_HUMAN; SorLA-1; Sortilin related receptor; Sortilin related receptor L(DLR class) A repeats containing; Sorting protein related receptor containing LDLR class A repeats; Sorting protein-related receptor containing LDLR class A repeats; OTTHUMP00000231797; sortilin-related receptor, L(DLR class) A repeats-containing; low-density lipopro;

  • Recombinant Proteins
  • Protein Pre-coupled Magnetic Beads
  • Human
  • Mouse
  • E.coli
  • HEK293
  • Mammalian Cell
  • Wheat Germ
  • His
  • His (Fc)
  • Avi
  • N/A
Species Cat.# Product name Source (Host) Tag Protein Length Price
Human SORL1-29617TH Recombinant Human SORL1 Wheat Germ N/A 100 amino acids
Human SORL1-01H Active Recombinant Human SORL1 Protein, His-tagged HEK293 His 82-753
Human SORL1-801H Recombinant Human SORL1 protein, His-tagged E.coli His 1865-2214 aa
Mouse SORL1-15763M Recombinant Mouse SORL1 Protein Mammalian Cell His
Mouse SORL1-8576M-B Recombinant Mouse SORL1 Protein Pre-coupled Magnetic Beads HEK293
Mouse SORL1-8576M Recombinant Mouse SORL1 Protein, His (Fc)-Avi-tagged HEK293 His (Fc)-Avi
  • Background
  • Quality Guarantee
  • Case Study
  • Involved Pathway
  • Protein Function
  • Interacting Protein
  • Other Resource

What is SORL1 protein?

SORL1 (sortilin related receptor 1) gene is a protein coding gene which situated on the long arm of chromosome 11 at locus 11q24. It is a large, multi-domain containing, membrane-bound receptor that plays a significant role in endosomal sorting of proteins between the trans-Golgi network, endosomes, and the plasma membrane. SORL1 is composed of several distinct domains and belongs to both the low-density lipoprotein receptor (LDLR) family and the vacuolar protein sorting 10 (VPS10) domain receptor family. The level of SORL1 was found to be decreased in the AD brain, which positively correlated with β-amyloid (Aβ) accumulation. SORL1 protein is consisted of 2214 amino acids and its molecular mass is approximately 248.4 kDa.

What is the function of SORL1 protein?

SORL1 is involved in the sorting of proteins within the endosomal system, helping to direct proteins to either the lysosomal degradation pathway or back to the cell surface. SORL1 plays a crucial role in the trafficking and processing of APP. It helps to regulate the transport of APP away from the endosome, thereby influencing the production of amyloid-beta (Aβ) peptides, which are implicated in Alzheimer's disease. SORL1 works together with the retromer trafficking complex to regulate the recycling of APP out of the endosome, contributing to endosomal swelling and APP misprocessing when SORL1 function is compromised. SORL1's expression can significantly impact the neuronal recycling pathway, with loss of SORL1 causing endosomal traffic jams and enlargement of early and recycling endosomes.

Intracellular trafficking path for SORLA.jpg

Fig1. Intracellular trafficking path for SORLA. (Vanessa Schmidt, 2017)

SORL1 Related Signaling Pathway

SORL1 is involved in the occurrence and development of late-onset Alzheimer's disease by interacting with different cytoplasmic adapters to affect the transport and metabolism of β-amyloid precursor proteins in cells. The interaction between SORL1 and brain-derived neurotrophic factor may affect the survival and function of neurons, and thus the progression of AD. SORL1 may be involved in regulating the expression and function of receptors on the cell surface, affecting the signaling of neurotransmitters. SORL1 may affect APP processing and Aβ production through Rho kinase signaling pathway. SORL1's interaction with GGA protein may affect its transport and recycling in the cellular endosome.

SORL1 Related Diseases

SORL1 gene is closely related to the pathogenesis of late-onset Alzheimer's disease (AD) and is a high-risk susceptibility gene whose expression is significantly reduced in AD patients. Studies have shown that SORL1 mainly plays a role in the early endosome and trans-Golgi, and affects the transport and metabolism of β-amyloid precursor protein by interacting with different cytoplasmic adapters, and then participates in the occurrence and development of AD. In addition, SORL1 gene knockout resulted in learning and memory impairment, abnormal distribution of n-methyl-D-aspartate receptor expression, and decreased expression of brain-derived neurotrophic factor and synaptic related proteins. It is suggested that SORL1 is involved in the pathogenesis of AD by regulating the signal axis of N-methyl-D-aspartate receptor-adenosine cyclophosphate-effecting-element binding protein (CREB) -brain-derived neurotrophic factor.

Bioapplications of SORL1

Recombinant SORL1 protein can be used to study its functions in intracellular material transport, immune response, cell adhesion and cell migration, especially in the study of Alzheimer's disease (AD), to explore how SORL1 affects the transport and metabolism of β-amyloid precursor protein (APP) and its role in the development of the disease. The development of drugs or antibodies that target SORL1 may provide new strategies for the treatment of certain diseases, especially in the field of AD therapy.

High Purity

SDS PAGE (SORL1-01H).jpg

Fig1. SDS-PAGE (SORL1-01H)

.

SDS PAGE (SORL1-801H).jpg

Fig2. SDS-PAGE (SORL1-801H)

Case Study 1: Bao-Yu Li, 2019

SORL1, the gene encoding the large multidomain SORLA protein, has emerged as only the fourth gene that when mutated can by itself cause Alzheimer's disease (AD), and as a gene reliably linked to both the early- and late-onset forms of the disease. SORLA is known to interact with the endosomal trafficking regulatory complex called retromer in regulating the recycling of endosomal cargo, including the amyloid precursor protein (APP) and the glutamate receptor GluA1. Nevertheless, SORLA's precise structural-functional relationship in endosomal recycling tubules remains unknown. Here, the researchers address these outstanding questions by relying on crystallographic and artificial-intelligence evidence to generate a structural model for how SORLA folds and fits into retromer-positive endosomal tubules, where it is found to dimerize via both SORLA's fibronectin-type-III (3Fn)- and VPS10p-domains. Moreover, they identify a SORLA fragment comprising the 3Fn-, transmembrane, and cytoplasmic domains that has the capacity to form a dimer, and to enhance retromer-dependent recycling of APP by decreasing its amyloidogenic processing.

GFP-trap immunoprecipitation analysis of lysates from HEK293 cells.jpg

Fig1. GFP-trap immunoprecipitation analysis of lysates from HEK293 cells.

Schematics representing domain architectures and predicted folding of the full SORLA luminal domain.jpg

Fig2. Schematics representing domain architectures and predicted folding of the full SORLA luminal domain.

Case Study 2: Christy Hung, 2021

Dysfunction of the endolysosomal-autophagy network is emerging as an important pathogenic process in Alzheimer's disease. Mutations in the sorting receptor-encoding gene SORL1 cause autosomal-dominant Alzheimer's disease, and SORL1 variants increase risk for late-onset AD. To understand the contribution of SORL1 mutations to AD pathogenesis, the researchers analyze the effects of a SORL1 truncating mutation on SORL1 protein levels and endolysosome function in human neurons. They find that truncating mutation results in SORL1 haploinsufficiency and enlarged endosomes in human neurons. Analysis of isogenic SORL1 wild-type, heterozygous, and homozygous null neurons demonstrates that, whereas SORL1 haploinsufficiency results in endosome dysfunction, complete loss of SORL1 leads to additional defects in lysosome function and autophagy. Neuronal endolysosomal dysfunction caused by loss of SORL1 is relieved by extracellular antisense oligonucleotide-mediated reduction of APP protein, demonstrating that PSEN1, APP, and SORL1 act in a common pathway regulating the endolysosome system, which becomes dysfunctional in AD.

Total full-length SORL1 levels are reduced.jpg

Fig3. Total full-length SORL1 levels are reduced by approximately 50% in SORL1 mutant neurons.

Representative western blots of SORL1 and neuron-specific β3-tubulin are shown.jpg

Fig4. Representative western blots of SORL1 and neuron-specific β3-tubulin are shown.

SORL1 interacts with two isoforms of VPS26.jpg

Fig1. SORL1 interacts with two isoforms of VPS26. (Swati Mishra, 2024)

SORLA-dependent sorting of APP and Aβ.jpg

Fig2. SORLA-dependent sorting of APP and Aβ. (Olav M Andersen, 2016)

SORL1 involved in several pathways and played different roles in them. We selected most pathways SORL1 participated on our site, such as , which may be useful for your reference. Also, other proteins which involved in the same pathway with SORL1 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

Pathway Name Pathway Related Protein

SORL1 has several biochemical functions, for example, ADP-ribosylation factor binding, beta-amyloid binding, low-density lipoprotein particle binding. Some of the functions are cooperated with other proteins, some of the functions could acted by SORL1 itself. We selected most functions SORL1 had, and list some proteins which have the same functions with SORL1. You can find most of the proteins on our site.

Function Related Protein
ADP-ribosylation factor bindingRAB11FIP4B;GGA2;ADCYAP1R1;RAB11FIP4;GGA3;SORL1;RAB11FIP4A;ZFP652;GRASP
beta-amyloid bindingAPBB1;TM2D1;APOE;APOEB;FBXO2;BCHE;BACE1;ITM2C;OLFM1
low-density lipoprotein particle bindingCOLEC12;SCARF1;SORL1;CRP;PCSK9;LDLR;CDH13;ANKRA2;THBS1
protein bindingCCNA2;HSF2;MRFAP1;FBXO3;CIC;XAGE2;ADAM22;FGFBP1;OPRM1
transmembrane signaling receptor activityPTH1RB;CD3G;FZD8B;GP1BB;TNFRSF11A;ANTXR1;Cd79a, Cd79b;NPC1;FCAMR

SORL1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with SORL1 here. Most of them are supplied by our site. Hope this information will be useful for your research of SORL1.

GGA2; GGA1; dimyristoylphosphatidyl choline; heparin; calcium(2+); DYRK3; APOE; LRPAP1; APOA5

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08/14/2022

    Whether I need assistance in experimental design, troubleshooting, or data interpretation, they provide prompt and personalized support, ensuring that my research progresses smoothly and efficiently.

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      This proactive approach not only aids in expanding my knowledge but also encourages continuous improvement and innovation in my experimental approach.

      10/15/2019

        The manufacturer's commitment to customer support and collaboration greatly enhances the overall research experience.

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