InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SORT1

Summary

InnateDB Protein

IDBP-100816.6

Last Modified

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

Gene Symbol

SORT1

Protein Name

sortilin 1

Synonyms

Gp95; LDLCQ6; NT3;

Species

Homo sapiens

Ensembl Protein

ENSP00000256637

InnateDB Gene

IDBG-100814 (SORT1)

Protein Structure

UniProt Annotation

Function

Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is independent of the mannose-6-phosphate receptor (M6PR). Also required for protein transport from the Golgi apparatus to the endosomes. Promotes neuronal apoptosis by mediating endocytosis of the proapoptotic precursor forms of BDNF (proBDNF) and NGFB (proNGFB). Also acts as a receptor for neurotensin. May promote mineralization of the extracellular matrix during osteogenic differentiation by scavenging extracellular LPL. Probably required in adipocytes for the formation of specialized storage vesicles containing the glucose transporter SLC2A4/GLUT4 (GLUT4 storage vesicles, or GSVs). These vesicles provide a stable pool of SLC2A4 and confer increased responsiveness to insulin. May also mediate transport from the endoplasmic reticulum to the Golgi. {ECO:0000269PubMed:10085125, ECO:0000269PubMed:11331584, ECO:0000269PubMed:11390366, ECO:0000269PubMed:12209882, ECO:0000269PubMed:12598608, ECO:0000269PubMed:14657016, ECO:0000269PubMed:14985763, ECO:0000269PubMed:15313463, ECO:0000269PubMed:15930396, ECO:0000269PubMed:15987945}.

Subcellular Localization

Membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Endosome membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Golgi apparatus, Golgi stack membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Nucleus membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Cell membrane; Single-pass type I membrane protein; Extracellular side. Lysosome membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Note=Localized to membranes of the endoplasmic reticulum, endosomes, Golgi stack, lysosomes and nucleus. A small fraction of the protein is also localized to the plasma membrane. May also be found in SLC2A4/GLUT4 storage vesicles (GSVs) in adipocytes. Localization to the plasma membrane in adipocytes may be enhanced by insulin.

Disease Associations

Note=A common polymorphism located in a non-coding region between CELSR2 and PSRC1 alters a CEBP transcription factor binding site and is responsible for changes in hepatic expression of SORT1. Altered SORT1 expression in liver affects low density lipoprotein cholesterol levels in plasma and is associated with susceptibility to myocardial infarction.

Tissue Specificity

Expressed in brain and prostate (at protein level). Expressed at high levels in brain, spinal cord, heart, skeletal muscle, thyroid, placenta and testis. Expressed at lower levels in lymphoid organs, kidney, colon and liver. {ECO:0000269PubMed:20048080, ECO:0000269PubMed:9013611}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 30 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.

Experimentally validated
Total	30 [view]
Protein-Protein	29 [view]
Protein-DNA	0
Protein-RNA	1 [view]
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	2 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding
GO:0010465	nerve growth factor receptor activity
GO:0019899	enzyme binding
GO:0030379	neurotensin receptor activity, non-G-protein coupled
GO:0048406	nerve growth factor binding

Biological Process

GO:0001503	ossification
GO:0006895	Golgi to endosome transport
GO:0006897	endocytosis
GO:0007186	G-protein coupled receptor signaling pathway
GO:0007218	neuropeptide signaling pathway
GO:0007275	multicellular organismal development
GO:0008333	endosome to lysosome transport
GO:0008625	extrinsic apoptotic signaling pathway via death domain receptors
GO:0010468	regulation of gene expression
GO:0014902	myotube differentiation
GO:0016050	vesicle organization
GO:0032509	endosome transport via multivesicular body sorting pathway
GO:0032868	response to insulin
GO:0038180	nerve growth factor signaling pathway
GO:0046323	glucose import
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048227	plasma membrane to endosome transport
GO:0051005	negative regulation of lipoprotein lipase activity

Cellular Component

GO:0005765	lysosomal membrane
GO:0005769	early endosome
GO:0005789	endoplasmic reticulum membrane
GO:0005794	Golgi apparatus
GO:0005886	plasma membrane
GO:0005905	coated pit
GO:0009986	cell surface
GO:0010008	endosome membrane
GO:0016021	integral component of membrane
GO:0016023	cytoplasmic membrane-bounded vesicle
GO:0030136	clathrin-coated vesicle
GO:0030140	trans-Golgi network transport vesicle
GO:0031965	nuclear membrane
GO:0032580	Golgi cisterna membrane
GO:0048471	perinuclear region of cytoplasm