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low-density lipoprotein receptor relative with 11 ligand-binding repeats; sortilin-related receptor; sorting protein-related receptor containing LDLR class A repeats; LDLR relative with 11 ligand-binding repeats (SorLA, SorLA-1, LR11, SORL1)
Function:
1) multifunctional endocytic receptor
2) implicated in the uptake of lipoproteins & proteases
3) binds LDL & transports it into cells by endocytosis
4) binds the receptor-associated protein (p39RAP)
5) cell-cell interaction
6) propeptide removed in the N-terminus may be cleaved by furin
7) may be receptor for retromer complex [2]
Structure:
- belongs to the SORL1 family
- contains 5 BNR repeats
- contains 1 EGF-like domain
- contains 6 fibronectin F3 modules
- contains 11 LDL-receptor class A domains
- contains 5 LDL-receptor class B repeats
Compartment:
- membrane; single-pass type 1 membrane protein (putative)
Expression:
- expressed mainly in brain
- abundant in the cerebral cortex, entorhinal cortex, occipital pole, cerebellum
- low expression in the putamen, thalamus
- may be expressed at lower levels in spinal cord, testis, pancreas, placenta, heart, prostate, ovary, thyroid, spleen
Pathology:
- has been implicated in AD
- has putative APP-binding domain
General
VPS10 domain-containing protein (VPS10)
Properties
SIZE: MW = 248 kD
entity length = 2214 aa
COMPARTMENT: plasma membrane
MOTIF: N-glycosylation site {N99}
BNR {136-147}
N-glycosylation site {N158+}
BNR {232-243}
N-glycosylation site {N368+}
EGF domain {1026-1072}
MOTIF: N-glycosylation site {N1035}
N-glycosylation site {N1068}
N-glycosylation site {N1367+}
cysteine residue {C1426+}
MODIFICATION: cysteine residue {C1444+}
cysteine residue {C1438+}
MODIFICATION: cysteine residue {C1453+}
cysteine residue {C1444+}
MODIFICATION: cysteine residue {C1426+}
cysteine residue {C1453+}
MODIFICATION: cysteine residue {C1438+}
N-glycosylation site {N1458+}
transmembrane domain {2138-2158}
Database Correlations
OMIM 602005
UniProt Q92673
PFAM correlations
Entrez Gene 6653
Kegg hsa:6653
References
- UniProt :accession Q92673
- Small SA, Kent K, Pierce A, Leung C, Kang MS, Okada H,
Honig L, Vonsattel JP, Kim TW.
Model-guided microarray implicates the retromer complex in
Alzheimer's disease.
Ann Neurol. 2005 Dec;58(6):909-19.
PMID: 16315276