SORT1 (sortilin 1)

Gene

• Entrez ID: 6272
• Gene name: Sortilin 1
• Gene symbol: SORT1
• Synonyms: Gp95, LDLCQ6, NT3, NTR3
• Chromosome: 1
• Chromosome location: 1p13.3|1p21.3-p13.1
• Summary: This gene encodes a member of the VPS10-related sortilin family of proteins. The encoded preproprotein is proteolytically processed by furin to generate the mature receptor. This receptor plays a role in the trafficking of different proteins to either the cell surface, or subcellular compartments such as lysosomes and endosomes. Expression levels of this gene may influence the risk of myocardial infarction in human patients. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT025550	hsa-miR-34a-5p	Proteomics	21566225
MIRT045915	hsa-miR-125b-5p	CLASH	23622248
MIRT046808	hsa-miR-222-3p	CLASH	23622248
MIRT439558	hsa-miR-1185-5p	HITS-CLIP	24374217
MIRT439560	hsa-miR-376a-3p	HITS-CLIP	24374217
MIRT439561	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT726471	hsa-miR-181c-5p	HITS-CLIP	22473208
MIRT726472	hsa-miR-181d-5p	HITS-CLIP	22473208
MIRT726473	hsa-miR-181b-5p	HITS-CLIP	22473208
MIRT726474	hsa-miR-181a-5p	HITS-CLIP	22473208

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001503	Process	Ossification	IEA
GO:0005515	Function	Protein binding	IPI	10085125, 11390366, 14985763, 16787399, 18687776, 19122660, 20584990, 20676133, 21092856, 21102451, 21949853, 22431521, 23236149, 24070898, 24128306, 25401472, 28541286, 32296183, 32814053
GO:0005764	Component	Lysosome	IDA	28541286
GO:0005765	Component	Lysosomal membrane	IEA
GO:0005769	Component	Early endosome	IDA	11331584
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005794	Component	Golgi apparatus	IBA	21873635
GO:0005794	Component	Golgi apparatus	IDA	11331584, 16787399, 18817523
GO:0005829	Component	Cytosol	IDA
GO:0005886	Component	Plasma membrane	IDA	11331584
GO:0005886	Component	Plasma membrane	NAS	14985763
GO:0005905	Component	Clathrin-coated pit	IDA	11331584
GO:0006622	Process	Protein targeting to lysosome	IEA
GO:0006892	Process	Post-Golgi vesicle-mediated transport	IBA	21873635
GO:0006895	Process	Golgi to endosome transport	IBA	21873635
GO:0006895	Process	Golgi to endosome transport	IDA	11331584
GO:0006897	Process	Endocytosis	IBA	21873635
GO:0006897	Process	Endocytosis	IDA	11331584, 21092856
GO:0007186	Process	G protein-coupled receptor signaling pathway	IMP	18258592
GO:0007218	Process	Neuropeptide signaling pathway	IDA	9756851
GO:0007275	Process	Multicellular organism development	IEA
GO:0008333	Process	Endosome to lysosome transport	IDA	11331584
GO:0008625	Process	Extrinsic apoptotic signaling pathway via death domain receptors	IDA	14985763
GO:0009986	Component	Cell surface	IDA	10085125
GO:0010008	Component	Endosome membrane	IDA	18817523
GO:0010465	Function	Nerve growth factor receptor activity	IDA	14985763
GO:0010468	Process	Regulation of gene expression	IMP	18258592
GO:0014902	Process	Myotube differentiation	IMP	18258592
GO:0016021	Component	Integral component of membrane	IBA	21873635
GO:0016021	Component	Integral component of membrane	IDA	15992544
GO:0016050	Process	Vesicle organization	IBA	21873635
GO:0016050	Process	Vesicle organization	IDA	15992544
GO:0019899	Function	Enzyme binding	IPI	10085125
GO:0030136	Component	Clathrin-coated vesicle	IDA	11331584
GO:0030140	Component	Trans-Golgi network transport vesicle	IEA
GO:0030379	Function	Neurotensin receptor activity, non-G protein-coupled	IDA	9756851
GO:0030425	Component	Dendrite	IEA
GO:0030659	Component	Cytoplasmic vesicle membrane	IEA
GO:0031410	Component	Cytoplasmic vesicle	IDA	9756851
GO:0031965	Component	Nuclear membrane	IEA
GO:0032509	Process	Endosome transport via multivesicular body sorting pathway	IDA	11331584
GO:0032580	Component	Golgi cisterna membrane	IEA
GO:0032868	Process	Response to insulin	IMP	15992544
GO:0038180	Process	Nerve growth factor signaling pathway	IEA
GO:0043025	Component	Neuronal cell body	IEA
GO:0045599	Process	Negative regulation of fat cell differentiation	IEA
GO:0046323	Process	Glucose import	IMP	15992544
GO:0048011	Process	Neurotrophin TRK receptor signaling pathway	IMP	14985763
GO:0048227	Process	Plasma membrane to endosome transport	IDA	11331584
GO:0048406	Function	Nerve growth factor binding	IPI	14985763
GO:0048471	Component	Perinuclear region of cytoplasm	IDA	11331584
GO:0051005	Process	Negative regulation of lipoprotein lipase activity	IDA	10085125
GO:0090160	Process	Golgi to lysosome transport	IDA	16787399
GO:1904037	Process	Positive regulation of epithelial cell apoptotic process	IEA
GO:1905394	Function	Retromer complex binding	IDA	18817523

Other IDs

• MIM: 602458
• HGNC: 11186
• e!Ensembl: ENSG00000134243

Protein

• UniProt ID: Q99523
• Protein name: Sortilin (100 kDa NT receptor) (Glycoprotein 95) (Gp95) (Neurotensin receptor 3) (NT3) (NTR3)
• Protein 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). Lysosomal proteins bind specifically to the receptor in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelysosomal compartment where the low pH mediates the dissociation of the complex (PubMed:16787399). The receptor is then recycled back to the Golgi for another round of trafficking through its binding to the retromer. 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.
• PDB: 3F6K, 3G2U, 3G2V, 4MSL, 4N7E, 4PO7, 5MRH, 5MRI, 6EHO, 6X3L, 6X48, 6X4H
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF15902	Sortilin-Vps10	142 → 572	Sortilin, neurotensin receptor 3,	Domain
  PF15901	Sortilin_C	574 → 740	Sortilin, neurotensin receptor 3, C-terminal	Domain

• Sequence:

  MERPWGAADGLSRWPHGLGLLLLLQLLPPSTLSQDRLDAPPPPAAPLPRWSGPIGVSWGL
  RAAAAGGAFPRGGRWRRSAPGEDEECGRVRDFVAKLANNTHQHVFDDLRGSVSLSWVGDS
  TGVILVLTTFHVPLVIMTFGQSKLYRSEDYGKNFKDITDLINNTFIRTEFGMAIGPENSG
  KVVLTAEVSGGSRGGRIFRSSDFAKNFVQTDLPFHPLTQMMYSPQNSDYLLALSTENGLW
  VSKNFGGKWEEIHKAVCLAKWGSDNTIFFTTYANGSCKADLGALELWRTSDLGKSFKTIG
  VKIYSFGLGGRFLFASVMADKDTTRRIHVSTDQGDTWSMAQLPSVGQEQFYSILAANDDM
  VFMHVDEPGDTGFGTIFTSDDRGIVYSKSLDRHLYTTTGGETDFTNVTSLRGVYITSVLS
  EDNSIQTMITFDQGGRWTHLRKPENSECDATAKNKNECSLHIHASYSISQKLNVPMAPLS
  EPNAVGIVIAHGSVGDAISVMVPDVYISDDGGYSWTKMLEGPHYYTILDSGGIIVAIEHS
  SRPINVIKFSTDEGQCWQTYTFTRDPIYFTGLASEPGARSMNISIWGFTESFLTSQWVSY
  TIDFKDILERNCEEKDYTIWLAHSTDPEDYEDGCILGYKEQFLRLRKSSVCQNGRDYVVT
  KQPSICLCSLEDFLCDFGYYRPENDSKCVEQPELKGHDLEFCLYGREEHLTTNGYRKIPG
  DKCQGGVNPVREVKDLKKKCTSNFLSPEKQNSKSNSVPIILAIVGLMLVTVVAGVLIVKK
  YVCGGRFLVHRYSVLQQHAEANGVDGVDALDTASHTNKSGYHDDSDEDLLE

• Sequence length: 831

Pathways

KEGG:

Lysosome
Neurotrophin signaling pathway
Cholesterol metabolism

Reactome:

Golgi Associated Vesicle Biogenesis

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Coronary artery disease	Coronary Artery Disease	rs137852988, rs121918313, rs-1, rs121918529, rs121918531, rs137852340, rs405509, rs1555800701, rs1215189537	21378990
Cholestasis	Cholestasis	rs121909103, rs751511532, rs376368459, rs762702807, rs1578490102, rs1578499691, rs1578504946, rs1317656688, rs199791850, rs1452792080, rs1578491039	28453831

Unknown
Disease name	Disease term	dbSNP ID	References
Cardiovascular diseases	Cardiovascular Diseases		25805502
Coronary arteriosclerosis	Coronary Arteriosclerosis		21378990