InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SORL1

Summary

InnateDB Protein

IDBP-74759.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

SORL1

Protein Name

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

Synonyms

C11orf32; gp250; LR11; LRP9; SORLA; SorLA-1;

Species

Homo sapiens

Ensembl Protein

ENSP00000260197

InnateDB Gene

IDBG-74757 (SORL1)

Protein Structure

UniProt Annotation

Function

Likely to be a multifunctional endocytic receptor, that may be implicated in the uptake of lipoproteins and of proteases. Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. Binds the receptor- associated protein (RAP). Could play a role in cell-cell interaction. Involved in APP trafficking to and from the Golgi apparatus. It probably acts as a sorting receptor that protects APP from trafficking to late endosome and from processing into amyloid beta, thereby reducing the burden of amyloidogenic peptide formation. Involved in the regulation of smooth muscle cells migration, probably through PLAUR binding and decreased internalization. {ECO:0000269PubMed:14764453, ECO:0000269PubMed:16174740}.

Subcellular Localization

Membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Golgi apparatus. Endosome. Secreted.

Disease Associations

Alzheimer disease (AD) [MIM:104300]: Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta- APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death. {ECO:0000269PubMed:21220680, ECO:0000269PubMed:22472873, ECO:0000269PubMed:23565137}. Note=The gene represented in this entry is involved in disease pathogenesis.

Tissue Specificity

Expressed mainly in brain, where it is most abundant in the cerebellum, cerebral cortex and the occipital pole; low expression in the putamen and the thalamus. Expression is significantly reduced in the frontal cortex of patients suffering from Alzheimer disease. According to PubMed:9157966, found in spinal cord, testis, liver, kidney and pancreas with detectable levels in placenta, lung and heart. According to PubMed:8940146, expressed in the prostate, ovary, thyroid and spleen, but not found in kidney, liver, lung, skeletal muscle, bone marrow and adrenals. {ECO:0000269PubMed:16174740}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 18 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.

Experimentally validated
Total	18 [view]
Protein-Protein	17 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	2 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001540	beta-amyloid binding
GO:0004888	transmembrane signaling receptor activity
GO:0005515	protein binding
GO:0030169	low-density lipoprotein particle binding
GO:0030306	ADP-ribosylation factor binding

Biological Process

GO:0000042	protein targeting to Golgi
GO:0006605	protein targeting
GO:0006622	protein targeting to lysosome
GO:0006869	lipid transport
GO:0006892	post-Golgi vesicle-mediated transport
GO:0006898	receptor-mediated endocytosis
GO:0007165	signal transduction
GO:0008203	cholesterol metabolic process
GO:0008219	cell death
GO:0008283	cell proliferation
GO:0014910	regulation of smooth muscle cell migration
GO:0016477	cell migration
GO:0032091	negative regulation of protein binding
GO:0032460	negative regulation of protein oligomerization
GO:0043407	negative regulation of MAP kinase activity
GO:0045053	protein retention in Golgi apparatus
GO:0045732	positive regulation of protein catabolic process
GO:0050768	negative regulation of neurogenesis
GO:0051604	protein maturation
GO:0070863	positive regulation of protein exit from endoplasmic reticulum
GO:1901215	negative regulation of neuron death
GO:1902430	negative regulation of beta-amyloid formation
GO:1902771	positive regulation of choline O-acetyltransferase activity
GO:1902948	negative regulation of tau-protein kinase activity
GO:1902953	positive regulation of ER to Golgi vesicle-mediated transport
GO:1902955	positive regulation of early endosome to recycling endosome transport
GO:1902960	negative regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process
GO:1902963	negative regulation of metalloendopeptidase activity involved in amyloid precursor protein catabolic process
GO:1902966	positive regulation of protein localization to early endosome
GO:1902997	negative regulation of neurofibrillary tangle assembly
GO:2001137	positive regulation of endocytic recycling

Cellular Component

GO:0005615	extracellular space
GO:0005641	nuclear envelope lumen
GO:0005768	endosome
GO:0005769	early endosome
GO:0005771	multivesicular body
GO:0005783	endoplasmic reticulum
GO:0005794	Golgi apparatus
GO:0005802	trans-Golgi network
GO:0005887	integral component of plasma membrane
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0031985	Golgi cisterna
GO:0034362	low-density lipoprotein particle
GO:0043025	neuronal cell body
GO:0055037	recycling endosome
GO:0070062	extracellular vesicular exosome