SORL1 encodes sortilin-related receptor, a large type I membrane receptor of the VPS10P/LDLR family that cycles through the trans-Golgi network, endosomes, recycling endosomes, and the plasma membrane. It binds and sorts cargo proteins and peptides, including amyloid precursor protein, amyloid-beta peptides, lipoprotein-related ligands, neurotrophic factors and receptors, insulin receptor, and cytokine-receptor complexes. In neurons, SORL1 retains and retrieves APP-containing complexes through Golgi/endosomal routes and can direct amyloid-beta toward lysosomal degradation, thereby reducing amyloidogenic APP processing. Other cargo-specific roles in lipid metabolism, trophic signaling, cytokine signaling, vascular smooth muscle behavior, and receptor recycling reflect the same receptor-mediated sorting biology in different cell contexts.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005794 Golgi apparatus | IBA GO_REF:0000033 | ACCEPT | Summary: SorLA resides in the Golgi where, with AP-1, it executes TGN-endosome sorting; a major steady-state pool of the receptor is Golgi-associated. Reason: Golgi is a core compartment for SorLA's cargo-sorting cycle (UniProt subcellular location). |
| GO:0006892 post-Golgi vesicle-mediated transport | IBA GO_REF:0000033 | ACCEPT | Summary: SorLA participates in vesicular transport from the TGN onward, dispatching itself and cargo to endosomes and the cell surface. Reason: Core trafficking step in SorLA's sorting itinerary (IBA/IDA). |
| GO:0016020 membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Generic membrane association reflects SorLA's nature as an integral single-pass type I membrane protein distributed across the secretory/endosomal system. Reason: Correct but generic; consistent with the transmembrane receptor. |
| GO:0006622 protein targeting to lysosome | IBA GO_REF:0000033 | ACCEPT | Summary: SorLA routes select cargo (LPL, GDNF, IL6, APOA5, amyloid-beta) to lysosomes for degradation, a defined branch of its sorting output. Reason: Core degradative sorting branch of the receptor (IBA/IDA). |
| GO:0045053 protein retention in Golgi apparatus | IBA GO_REF:0000033 | ACCEPT | Summary: SorLA retains APP (and other cargo) in the TGN, the key event that limits APP's transit to amyloidogenic late-endosomal processing. Reason: Defining sorting outcome that links SorLA to reduced amyloidogenesis (IBA/IDA). |
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | ACCEPT | Summary: As a single-pass type I membrane protein, SorLA sits in the Golgi/TGN membrane where it engages adaptors (GGA, AP-1) and retains cargo such as APP. Reason: Correct membrane sub-localization for a transmembrane Golgi sorting receptor. |
| GO:0005041 low-density lipoprotein particle receptor activity | IEA GO_REF:0000117 | ACCEPT | Summary: SorLA functions as an LDL-receptor-family member with complement-type ligand-binding repeats that bind lipoprotein and LRPAP1/RAP ligands. Reason: Core receptor activity defining SorLA's LDLR-family identity. |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: ADAM17-mediated shedding releases the soluble SorLA ectodomain (sLR11) into the extracellular space, where it acts as a secreted ligand-binding fragment. Reason: Reflects shed soluble ectodomain, a secondary product of the membrane receptor. |
| GO:0005764 lysosome | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: SorLA routes select cargo (LPL, GDNF, APOA5, amyloid-beta) toward lysosomes for catabolism; the lysosome is a destination of its degradative sorting branch. Reason: Terminal destination compartment downstream of SorLA's sorting decisions. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: ER-membrane residence reflects the newly synthesized receptor before propeptide cleavage and export; not where SorLA performs cargo sorting. Reason: Biosynthetic localization, peripheral to the endosome/TGN sorting role. |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | ACCEPT | Summary: SorLA resides in the Golgi where, with AP-1, it executes TGN-endosome sorting; a major steady-state pool of the receptor is Golgi-associated. Reason: Golgi is a core compartment for SorLA's cargo-sorting cycle (UniProt subcellular location). |
| GO:0005829 cytosol | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: SorLA is a single-pass type I membrane protein; only a small RIP-released C-terminal fragment is cytosolic, so a bulk cytosol annotation overstates its distribution. Reason: IEA cytosol overstates localization of an integral membrane protein. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: A minor surface pool of SorLA captures extracellular ligands and undergoes AP-2-dependent endocytosis; surface levels are low but functionally important. Reason: Cell-surface localization is the entry point for SorLA's endocytic sorting cycle. |
| GO:0010008 endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: The transmembrane receptor is embedded in the endosomal limiting membrane, where its cytosolic tail binds retromer/GGA adaptors for sorting. Reason: Membrane localization underpins SorLA's endosomal sorting function. |
| GO:0016020 membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Generic membrane association reflects SorLA's nature as an integral single-pass type I membrane protein distributed across the secretory/endosomal system. Reason: Correct but generic; consistent with the transmembrane receptor. |
| GO:0030658 transport vesicle membrane | IEA GO_REF:0000044 | ACCEPT | Summary: SorLA is carried in transport/secretory and endosome-to-TGN retrograde vesicles that shuttle it and its cargo between compartments. Reason: Vesicle-membrane localization matches its trafficking itinerary (UniProt: retrograde vesicles). |
| GO:0031901 early endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: SorLA occupies the early-endosome membrane where its cytoplasmic domain recruits sorting adaptors for cargo retrieval. Reason: Membrane sub-localization supporting endosomal cargo sorting. |
| GO:0032585 multivesicular body membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: MVB-membrane localization is consistent with SorLA delivering cargo to the lysosomal degradation pathway. Reason: Late-endosomal membrane, secondary to the core TGN/endosome retrieval role. |
| GO:0055038 recycling endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Membrane localization to recycling endosomes is consistent with SorLA promoting endocytic recycling of internalized receptors. Reason: Membrane sub-localization for SorLA's recycling function. |
| GO:0005515 protein binding | IPI PMID:11821067 The sorLA cytoplasmic domain interacts with GGA1 and -2 and ... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' (n=21 IPI) records many partner interactions but conveys no specific molecular function for this cargo receptor. Reason: Uninformative generic MF; specific ligand-binding terms already capture SorLA's activity. |
| GO:0005515 protein binding | IPI PMID:16174740 Neuronal sorting protein-related receptor sorLA/LR11 regulat... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' (n=21 IPI) records many partner interactions but conveys no specific molecular function for this cargo receptor. Reason: Uninformative generic MF; specific ligand-binding terms already capture SorLA's activity. |
| GO:0005515 protein binding | IPI PMID:16407538 Interaction of the cytosolic domains of sorLA/LR11 with the ... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' (n=21 IPI) records many partner interactions but conveys no specific molecular function for this cargo receptor. Reason: Uninformative generic MF; specific ligand-binding terms already capture SorLA's activity. |
| GO:0005515 protein binding | IPI PMID:17326667 Apolipoprotein A-V interaction with members of the low densi... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' (n=21 IPI) records many partner interactions but conveys no specific molecular function for this cargo receptor. Reason: Uninformative generic MF; specific ligand-binding terms already capture SorLA's activity. |
| GO:0005515 protein binding | IPI PMID:23333276 SorLA controls neurotrophic activity by sorting of GDNF and ... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' (n=21 IPI) records many partner interactions but conveys no specific molecular function for this cargo receptor. Reason: Uninformative generic MF; specific ligand-binding terms already capture SorLA's activity. |
| GO:0005515 protein binding | IPI PMID:25643321 Structural basis for amyloidogenic peptide recognition by so... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' (n=21 IPI) records many partner interactions but conveys no specific molecular function for this cargo receptor. Reason: Uninformative generic MF; specific ligand-binding terms already capture SorLA's activity. |
| GO:0005515 protein binding | IPI PMID:26053850 The Golgi-Localized Ξ³-Ear-Containing ARF-Binding (GGA) Prote... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' (n=21 IPI) records many partner interactions but conveys no specific molecular function for this cargo receptor. Reason: Uninformative generic MF; specific ligand-binding terms already capture SorLA's activity. |
| GO:0005515 protein binding | IPI PMID:26858303 Cytokine-Like Factor 1, an Essential Facilitator of Cardiotr... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' (n=21 IPI) records many partner interactions but conveys no specific molecular function for this cargo receptor. Reason: Uninformative generic MF; specific ligand-binding terms already capture SorLA's activity. |
| GO:0005515 protein binding | IPI PMID:28265003 SorLA in Interleukin-6 Signaling and Turnover. | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' (n=21 IPI) records many partner interactions but conveys no specific molecular function for this cargo receptor. Reason: Uninformative generic MF; specific ligand-binding terms already capture SorLA's activity. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' (n=21 IPI) records many partner interactions but conveys no specific molecular function for this cargo receptor. Reason: Uninformative generic MF; specific ligand-binding terms already capture SorLA's activity. |
| GO:0005515 protein binding | IPI PMID:30679749 HSPA12A targets the cytoplasmic domain and affects the traff... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' (n=21 IPI) records many partner interactions but conveys no specific molecular function for this cargo receptor. Reason: Uninformative generic MF; specific ligand-binding terms already capture SorLA's activity. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' (n=21 IPI) records many partner interactions but conveys no specific molecular function for this cargo receptor. Reason: Uninformative generic MF; specific ligand-binding terms already capture SorLA's activity. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' (n=21 IPI) records many partner interactions but conveys no specific molecular function for this cargo receptor. Reason: Uninformative generic MF; specific ligand-binding terms already capture SorLA's activity. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' (n=21 IPI) records many partner interactions but conveys no specific molecular function for this cargo receptor. Reason: Uninformative generic MF; specific ligand-binding terms already capture SorLA's activity. |
| GO:0002024 diet induced thermogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SorLA's metabolic regulation of adipose energy expenditure extends to diet-induced thermogenesis, a systemic consequence of its ectodomain activity. Reason: Pleiotropic energy-balance phenotype, downstream of metabolic signaling roles. |
| GO:0005641 nuclear envelope lumen | IEA GO_REF:0000107 | UNDECIDED | Summary: RIP releases a SorLA C-terminal fragment that localizes to the nucleus, but a specific nuclear-envelope-lumen assignment is not clearly supported by the evidence reviewed. Reason: Cannot verify the nuclear-envelope-lumen call; nuclear targeting is only of a cleaved fragment. |
| GO:0005771 multivesicular body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SorLA is seen in MVBs/late endosomes as part of cargo routing toward lysosomal degradation (e.g. LPL, GDNF). Reason: Downstream late-endosomal station of the degradative arm of SorLA sorting. |
| GO:0006605 protein targeting | IEA GO_REF:0000107 | ACCEPT | Summary: SorLA directs bound client proteins to specific destinations (TGN retention, lysosomal degradation or surface recycling), the essence of its sorting role. Reason: Core process: directing proteins to their correct intracellular location. |
| GO:0010897 negative regulation of triglyceride catabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: By trafficking LPL to lysosomes and degrading it, SorLA reduces lipase activity and triglyceride catabolism; a metabolic consequence of degradative sorting. Reason: Lipid-metabolism effect downstream of SorLA-mediated LPL turnover. |
| GO:0016477 cell migration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SorLA modulates migration of smooth-muscle and myeloid cells through uPAR/PLAUR surface regulation, a pleiotropic consequence of its receptor trafficking. Reason: Generic pleiotropic migration role secondary to ligand trafficking. |
| GO:0019828 aspartic-type endopeptidase inhibitor activity | IEA GO_REF:0000107 | MODIFY | Summary: SorLA reduces BACE1-dependent APP cleavage by sequestering APP and interfering with BACE1-APP encounter; this is competitive cargo sorting, not direct aspartic-protease inhibition. Reason: Effect on BACE1 is indirect via trafficking; better captured as negative regulation of amyloid-beta formation. Proposed replacements: negative regulation of amyloid-beta formation |
| GO:0030514 negative regulation of BMP signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The SorLA N-terminal ectodomain inhibits BMP/Smad signaling in adipose tissue to restrain energy expenditure; a metabolic, ectodomain-mediated role. Reason: Pleiotropic metabolic signaling effect of the soluble ectodomain (IEA/ISS). |
| GO:0038020 insulin receptor recycling | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SorLA recycles internalized INSR via the Golgi to the surface, raising INSR surface levels in adipocytes; a tissue-specific instance of its recycling-sorting role. Reason: Cargo-specific recycling event downstream of SorLA's general recycling activity. |
| GO:0043025 neuronal cell body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SorLA is enriched in neuronal soma, consistent with its high brain expression and role in neuronal cargo (APP, TrkB, GDNF) trafficking. Reason: Cell-type-specific localization reflecting neuronal expression, not a distinct core compartment. |
| GO:0045053 protein retention in Golgi apparatus | IEA GO_REF:0000107 | ACCEPT | Summary: SorLA retains APP (and other cargo) in the TGN, the key event that limits APP's transit to amyloidogenic late-endosomal processing. Reason: Defining sorting outcome that links SorLA to reduced amyloidogenesis (IBA/IDA). |
| GO:0046628 positive regulation of insulin receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: By increasing INSR surface expression through recycling, SorLA strengthens insulin signaling in adipose tissue, a pleiotropic downstream consequence. Reason: Signaling effect secondary to SorLA-mediated INSR recycling. |
| GO:0050768 negative regulation of neurogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SorLA influences neuronal development consistent with its high brain expression and trafficking of neurotrophic cargo (BDNF/TrkB, GDNF). Reason: Developmental role downstream of neurotrophic-receptor sorting (IEA/ISS). |
| GO:0097356 perinucleolar compartment | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: No evidence places this transmembrane sorting receptor in the perinucleolar compartment; the IEA call is implausible for SorLA. Reason: Implausible nuclear sub-compartment for a membrane sorting receptor; electronic over-annotation. |
| GO:0099638 endosome to plasma membrane protein transport | IEA GO_REF:0000107 | ACCEPT | Summary: SorLA promotes return of internalized receptors (INSR, HER2) from endosomes to the plasma membrane, a recycling arm of its sorting activity. Reason: Core recycling route mediated by SorLA (UniProt: HER2/INSR recycling). |
| GO:1900168 positive regulation of glial cell-derived neurotrophic factor production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: SorLA controls regulated (vs constitutive) GDNF secretion by sorting GDNF and its receptors, influencing GDNF availability; a neurotrophic-specific role. Reason: Cargo-specific neurotrophic effect downstream of GDNF sorting. |
| GO:1902430 negative regulation of amyloid-beta formation | IEA GO_REF:0000107 | ACCEPT | Summary: SorLA lowers Abeta40/Abeta42 generation by sequestering APP from amyloidogenic processing and routing Abeta to lysosomes, the basis of its AD-protective role. Reason: Central disease-relevant output directly downstream of SorLA APP sorting (IDA/IMP). |
| GO:1902992 negative regulation of amyloid precursor protein catabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: By retaining APP in the TGN and limiting its access to secretases, SorLA reduces amyloidogenic APP catabolism, the best-characterized physiological output of its sorting. Reason: Hallmark functional consequence of SorLA's APP retention (IDA/IMP). |
| GO:1902997 negative regulation of neurofibrillary tangle assembly | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: SorLA's primary action is on APP/Abeta trafficking; an effect on tau neurofibrillary-tangle assembly is at best indirect and rests only on electronic/ISS inference. Reason: Tau-tangle effect is speculative and indirect; electronic over-annotation. |
| GO:1904179 positive regulation of adipose tissue development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Through its metabolic actions (INSR recycling, BMP inhibition, LPL turnover) SorLA influences adipose tissue development; a pleiotropic systemic role. Reason: Systemic metabolic/developmental role secondary to its trafficking functions. |
| GO:1990845 adaptive thermogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Soluble SorLA represses adipose thermogenesis via BMP/Smad inhibition, shifting energy balance toward storage; a metabolic role of the ectodomain. Reason: Pleiotropic metabolic phenotype of the shed ectodomain (IEA/ISS). |
| GO:0038024 cargo receptor activity | IDA PMID:17855360 SorLA/LR11 regulates processing of amyloid precursor protein... | ACCEPT | Summary: This is SorLA's defining activity: a VPS10P-domain cargo receptor that binds and sorts client proteins (APP, LPL, INSR, HER2, GDNF) among the TGN, endosomes and surface. Reason: Core defining molecular function of SorLA as an intracellular sorting receptor. |
| GO:0038024 cargo receptor activity | IDA PMID:11294867 Activation and functional characterization of the mosaic rec... | ACCEPT | Summary: This is SorLA's defining activity: a VPS10P-domain cargo receptor that binds and sorts client proteins (APP, LPL, INSR, HER2, GDNF) among the TGN, endosomes and surface. Reason: Core defining molecular function of SorLA as an intracellular sorting receptor. |
| GO:0038024 cargo receptor activity | TAS PMID:9157966 A novel mosaic protein containing LDL receptor elements is h... | ACCEPT | Summary: This is SorLA's defining activity: a VPS10P-domain cargo receptor that binds and sorts client proteins (APP, LPL, INSR, HER2, GDNF) among the TGN, endosomes and surface. Reason: Core defining molecular function of SorLA as an intracellular sorting receptor. |
| GO:0000139 Golgi membrane | EXP PMID:11294867 Activation and functional characterization of the mosaic rec... | ACCEPT | Summary: As a single-pass type I membrane protein, SorLA sits in the Golgi/TGN membrane where it engages adaptors (GGA, AP-1) and retains cargo such as APP. Reason: Correct membrane sub-localization for a transmembrane Golgi sorting receptor. |
| GO:0000139 Golgi membrane | EXP PMID:16174740 Neuronal sorting protein-related receptor sorLA/LR11 regulat... | ACCEPT | Summary: As a single-pass type I membrane protein, SorLA sits in the Golgi/TGN membrane where it engages adaptors (GGA, AP-1) and retains cargo such as APP. Reason: Correct membrane sub-localization for a transmembrane Golgi sorting receptor. |
| GO:0000139 Golgi membrane | EXP PMID:17855360 SorLA/LR11 regulates processing of amyloid precursor protein... | ACCEPT | Summary: As a single-pass type I membrane protein, SorLA sits in the Golgi/TGN membrane where it engages adaptors (GGA, AP-1) and retains cargo such as APP. Reason: Correct membrane sub-localization for a transmembrane Golgi sorting receptor. |
| GO:0000139 Golgi membrane | EXP PMID:21385844 SorLA regulates the activity of lipoprotein lipase by intrac... | ACCEPT | Summary: As a single-pass type I membrane protein, SorLA sits in the Golgi/TGN membrane where it engages adaptors (GGA, AP-1) and retains cargo such as APP. Reason: Correct membrane sub-localization for a transmembrane Golgi sorting receptor. |
| GO:0000139 Golgi membrane | EXP PMID:21994944 Sorting protein-related receptor SorLA controls regulated se... | ACCEPT | Summary: As a single-pass type I membrane protein, SorLA sits in the Golgi/TGN membrane where it engages adaptors (GGA, AP-1) and retains cargo such as APP. Reason: Correct membrane sub-localization for a transmembrane Golgi sorting receptor. |
| GO:0005576 extracellular region | EXP PMID:11082041 Ectodomain shedding, translocation and synthesis of SorLA ar... | KEEP AS NON CORE | Summary: ADAM17-mediated shedding releases the soluble SorLA ectodomain (sLR11) into the extracellular space, where it acts as a secreted ligand-binding fragment. Reason: Reflects shed soluble ectodomain, a secondary product of the membrane receptor. |
| GO:0005576 extracellular region | EXP PMID:15053742 The mosaic receptor sorLA/LR11 binds components of the plasm... | KEEP AS NON CORE | Summary: ADAM17-mediated shedding releases the soluble SorLA ectodomain (sLR11) into the extracellular space, where it acts as a secreted ligand-binding fragment. Reason: Reflects shed soluble ectodomain, a secondary product of the membrane receptor. |
| GO:0005576 extracellular region | EXP PMID:16393139 Tumour necrosis factor alpha-converting enzyme mediates ecto... | KEEP AS NON CORE | Summary: ADAM17-mediated shedding releases the soluble SorLA ectodomain (sLR11) into the extracellular space, where it acts as a secreted ligand-binding fragment. Reason: Reflects shed soluble ectodomain, a secondary product of the membrane receptor. |
| GO:0005576 extracellular region | EXP PMID:16531402 SorLA signaling by regulated intramembrane proteolysis. | KEEP AS NON CORE | Summary: ADAM17-mediated shedding releases the soluble SorLA ectodomain (sLR11) into the extracellular space, where it acts as a secreted ligand-binding fragment. Reason: Reflects shed soluble ectodomain, a secondary product of the membrane receptor. |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:17855360 SorLA/LR11 regulates processing of amyloid precursor protein... | KEEP AS NON CORE | Summary: ER-membrane residence reflects the newly synthesized receptor before propeptide cleavage and export; not where SorLA performs cargo sorting. Reason: Biosynthetic localization, peripheral to the endosome/TGN sorting role. |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:21385844 SorLA regulates the activity of lipoprotein lipase by intrac... | KEEP AS NON CORE | Summary: ER-membrane residence reflects the newly synthesized receptor before propeptide cleavage and export; not where SorLA performs cargo sorting. Reason: Biosynthetic localization, peripheral to the endosome/TGN sorting role. |
| GO:0005886 plasma membrane | EXP PMID:11294867 Activation and functional characterization of the mosaic rec... | ACCEPT | Summary: A minor surface pool of SorLA captures extracellular ligands and undergoes AP-2-dependent endocytosis; surface levels are low but functionally important. Reason: Cell-surface localization is the entry point for SorLA's endocytic sorting cycle. |
| GO:0005886 plasma membrane | EXP PMID:14764453 LR11, an LDL receptor gene family member, is a novel regulat... | ACCEPT | Summary: A minor surface pool of SorLA captures extracellular ligands and undergoes AP-2-dependent endocytosis; surface levels are low but functionally important. Reason: Cell-surface localization is the entry point for SorLA's endocytic sorting cycle. |
| GO:0005886 plasma membrane | EXP PMID:15053742 The mosaic receptor sorLA/LR11 binds components of the plasm... | ACCEPT | Summary: A minor surface pool of SorLA captures extracellular ligands and undergoes AP-2-dependent endocytosis; surface levels are low but functionally important. Reason: Cell-surface localization is the entry point for SorLA's endocytic sorting cycle. |
| GO:0005886 plasma membrane | EXP PMID:17855360 SorLA/LR11 regulates processing of amyloid precursor protein... | ACCEPT | Summary: A minor surface pool of SorLA captures extracellular ligands and undergoes AP-2-dependent endocytosis; surface levels are low but functionally important. Reason: Cell-surface localization is the entry point for SorLA's endocytic sorting cycle. |
| GO:0005886 plasma membrane | EXP PMID:31138794 SORLA regulates endosomal trafficking and oncogenic fitness ... | ACCEPT | Summary: A minor surface pool of SorLA captures extracellular ligands and undergoes AP-2-dependent endocytosis; surface levels are low but functionally important. Reason: Cell-surface localization is the entry point for SorLA's endocytic sorting cycle. |
| GO:0010008 endosome membrane | EXP PMID:21385844 SorLA regulates the activity of lipoprotein lipase by intrac... | ACCEPT | Summary: The transmembrane receptor is embedded in the endosomal limiting membrane, where its cytosolic tail binds retromer/GGA adaptors for sorting. Reason: Membrane localization underpins SorLA's endosomal sorting function. |
| GO:0010008 endosome membrane | EXP PMID:23333276 SorLA controls neurotrophic activity by sorting of GDNF and ... | ACCEPT | Summary: The transmembrane receptor is embedded in the endosomal limiting membrane, where its cytosolic tail binds retromer/GGA adaptors for sorting. Reason: Membrane localization underpins SorLA's endosomal sorting function. |
| GO:0031901 early endosome membrane | EXP PMID:17646382 Sorting by the cytoplasmic domain of the amyloid precursor p... | ACCEPT | Summary: SorLA occupies the early-endosome membrane where its cytoplasmic domain recruits sorting adaptors for cargo retrieval. Reason: Membrane sub-localization supporting endosomal cargo sorting. |
| GO:0031901 early endosome membrane | EXP PMID:21385844 SorLA regulates the activity of lipoprotein lipase by intrac... | ACCEPT | Summary: SorLA occupies the early-endosome membrane where its cytoplasmic domain recruits sorting adaptors for cargo retrieval. Reason: Membrane sub-localization supporting endosomal cargo sorting. |
| GO:0031901 early endosome membrane | EXP PMID:31138794 SORLA regulates endosomal trafficking and oncogenic fitness ... | ACCEPT | Summary: SorLA occupies the early-endosome membrane where its cytoplasmic domain recruits sorting adaptors for cargo retrieval. Reason: Membrane sub-localization supporting endosomal cargo sorting. |
| GO:0055038 recycling endosome membrane | EXP PMID:17855360 SorLA/LR11 regulates processing of amyloid precursor protein... | ACCEPT | Summary: Membrane localization to recycling endosomes is consistent with SorLA promoting endocytic recycling of internalized receptors. Reason: Membrane sub-localization for SorLA's recycling function. |
| GO:0055038 recycling endosome membrane | EXP PMID:31138794 SORLA regulates endosomal trafficking and oncogenic fitness ... | ACCEPT | Summary: Membrane localization to recycling endosomes is consistent with SorLA promoting endocytic recycling of internalized receptors. Reason: Membrane sub-localization for SorLA's recycling function. |
| GO:0001960 negative regulation of cytokine-mediated signaling pathway | IDA PMID:26858303 Cytokine-Like Factor 1, an Essential Facilitator of Cardiotr... | KEEP AS NON CORE | Summary: SorLA dampens cytokine signaling by internalizing and degrading IL6/CLCF1-CRLF1-CNTFR complexes, a downstream effect of its endocytic-degradative sorting. Reason: Signaling modulation secondary to SorLA cargo internalization and turnover. |
| GO:0005886 plasma membrane | IDA PMID:26858303 Cytokine-Like Factor 1, an Essential Facilitator of Cardiotr... | ACCEPT | Summary: A minor surface pool of SorLA captures extracellular ligands and undergoes AP-2-dependent endocytosis; surface levels are low but functionally important. Reason: Cell-surface localization is the entry point for SorLA's endocytic sorting cycle. |
| GO:0038024 cargo receptor activity | IDA PMID:26858303 Cytokine-Like Factor 1, an Essential Facilitator of Cardiotr... | ACCEPT | Summary: This is SorLA's defining activity: a VPS10P-domain cargo receptor that binds and sorts client proteins (APP, LPL, INSR, HER2, GDNF) among the TGN, endosomes and surface. Reason: Core defining molecular function of SorLA as an intracellular sorting receptor. |
| GO:1905146 lysosomal protein catabolic process | IDA PMID:26858303 Cytokine-Like Factor 1, an Essential Facilitator of Cardiotr... | KEEP AS NON CORE | Summary: Lysosomal degradation of SorLA-delivered cargo is a downstream consequence of its degradative sorting branch rather than the proximal sorting activity itself. Reason: Downstream catabolic outcome of SorLA's lysosomal targeting. |
| GO:0031901 early endosome membrane | IDA PMID:16174740 Neuronal sorting protein-related receptor sorLA/LR11 regulat... | ACCEPT | Summary: SorLA occupies the early-endosome membrane where its cytoplasmic domain recruits sorting adaptors for cargo retrieval. Reason: Membrane sub-localization supporting endosomal cargo sorting. |
| GO:0042147 retrograde transport, endosome to Golgi | IDA PMID:16174740 Neuronal sorting protein-related receptor sorLA/LR11 regulat... | ACCEPT | Summary: SorLA's cytosolic tail engages retromer (VPS29) and GGA adaptors to retrieve itself and cargo from endosomes back to the TGN. Reason: Central retrieval route defining SorLA's sorting behaviour (IDA). |
| GO:0140318 protein transporter activity | IDA PMID:16174740 Neuronal sorting protein-related receptor sorLA/LR11 regulat... | ACCEPT | Summary: SorLA physically carries bound cargo proteins between compartments, consistent with its cargo-receptor role in directing protein localization. Reason: Captures the cargo-carrying activity central to SorLA's sorting function (IDA). |
| GO:1902430 negative regulation of amyloid-beta formation | IDA PMID:16174740 Neuronal sorting protein-related receptor sorLA/LR11 regulat... | ACCEPT | Summary: SorLA lowers Abeta40/Abeta42 generation by sequestering APP from amyloidogenic processing and routing Abeta to lysosomes, the basis of its AD-protective role. Reason: Central disease-relevant output directly downstream of SorLA APP sorting (IDA/IMP). |
| GO:0019828 aspartic-type endopeptidase inhibitor activity | IDA PMID:16407538 Interaction of the cytosolic domains of sorLA/LR11 with the ... | MODIFY | Summary: SorLA reduces BACE1-dependent APP cleavage by sequestering APP and interfering with BACE1-APP encounter; this is competitive cargo sorting, not direct aspartic-protease inhibition. Reason: Effect on BACE1 is indirect via trafficking; better captured as negative regulation of amyloid-beta formation. Proposed replacements: negative regulation of amyloid-beta formation |
| GO:0019828 aspartic-type endopeptidase inhibitor activity | IMP PMID:17855360 SorLA/LR11 regulates processing of amyloid precursor protein... | MODIFY | Summary: SorLA reduces BACE1-dependent APP cleavage by sequestering APP and interfering with BACE1-APP encounter; this is competitive cargo sorting, not direct aspartic-protease inhibition. Reason: Effect on BACE1 is indirect via trafficking; better captured as negative regulation of amyloid-beta formation. Proposed replacements: negative regulation of amyloid-beta formation |
| GO:0019828 aspartic-type endopeptidase inhibitor activity | IMP PMID:21989385 Quantitative modelling of amyloidogenic processing and its i... | MODIFY | Summary: SorLA reduces BACE1-dependent APP cleavage by sequestering APP and interfering with BACE1-APP encounter; this is competitive cargo sorting, not direct aspartic-protease inhibition. Reason: Effect on BACE1 is indirect via trafficking; better captured as negative regulation of amyloid-beta formation. Proposed replacements: negative regulation of amyloid-beta formation |
| GO:1902992 negative regulation of amyloid precursor protein catabolic process | IDA PMID:16407538 Interaction of the cytosolic domains of sorLA/LR11 with the ... | ACCEPT | Summary: By retaining APP in the TGN and limiting its access to secretases, SorLA reduces amyloidogenic APP catabolism, the best-characterized physiological output of its sorting. Reason: Hallmark functional consequence of SorLA's APP retention (IDA/IMP). |
| GO:1902992 negative regulation of amyloid precursor protein catabolic process | IMP PMID:17855360 SorLA/LR11 regulates processing of amyloid precursor protein... | ACCEPT | Summary: By retaining APP in the TGN and limiting its access to secretases, SorLA reduces amyloidogenic APP catabolism, the best-characterized physiological output of its sorting. Reason: Hallmark functional consequence of SorLA's APP retention (IDA/IMP). |
| GO:1902992 negative regulation of amyloid precursor protein catabolic process | IMP PMID:21989385 Quantitative modelling of amyloidogenic processing and its i... | ACCEPT | Summary: By retaining APP in the TGN and limiting its access to secretases, SorLA reduces amyloidogenic APP catabolism, the best-characterized physiological output of its sorting. Reason: Hallmark functional consequence of SorLA's APP retention (IDA/IMP). |
| GO:0005515 protein binding | IPI PMID:11294867 Activation and functional characterization of the mosaic rec... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' (n=21 IPI) records many partner interactions but conveys no specific molecular function for this cargo receptor. Reason: Uninformative generic MF; specific ligand-binding terms already capture SorLA's activity. |
| GO:0005794 Golgi apparatus | IDA PMID:11294867 Activation and functional characterization of the mosaic rec... | ACCEPT | Summary: SorLA resides in the Golgi where, with AP-1, it executes TGN-endosome sorting; a major steady-state pool of the receptor is Golgi-associated. Reason: Golgi is a core compartment for SorLA's cargo-sorting cycle (UniProt subcellular location). |
| GO:0006898 receptor-mediated endocytosis | IDA PMID:11294867 Activation and functional characterization of the mosaic rec... | ACCEPT | Summary: SorLA mediates AP-2/clathrin-dependent internalization of surface ligands (uPA-PAI1, APOA5, IL6, HER2), feeding them into its endosomal sorting itinerary. Reason: Core uptake step of SorLA's cargo-sorting cycle (IDA/TAS). |
| GO:0007218 neuropeptide signaling pathway | IDA PMID:11294867 Activation and functional characterization of the mosaic rec... | KEEP AS NON CORE | Summary: SorLA's interaction with neuropeptides (HA) links it to neuropeptide signaling, a downstream context of its ligand-binding capacity. Reason: Signaling context downstream of SorLA neuropeptide binding. |
| GO:0009986 cell surface | IDA PMID:11294867 Activation and functional characterization of the mosaic rec... | ACCEPT | Summary: Surface-exposed SorLA binds ligands (e.g. APP, IL6, uPAR) and mediates their internalization; the surface pool also undergoes ectodomain shedding. Reason: Cell-surface presence is required for SorLA receptor-mediated endocytosis (IDA). |
| GO:0042923 neuropeptide binding | IPI PMID:11082041 Ectodomain shedding, translocation and synthesis of SorLA ar... | KEEP AS NON CORE | Summary: The VPS10P domain binds neuropeptides such as head activator (HA) and neurotensin; a specific partner-binding activity peripheral to the core sorting role. Reason: Partner-specific ligand binding; ancillary to the defining cargo-receptor activity. |
| GO:0042923 neuropeptide binding | IPI PMID:11294867 Activation and functional characterization of the mosaic rec... | KEEP AS NON CORE | Summary: The VPS10P domain binds neuropeptides such as head activator (HA) and neurotensin; a specific partner-binding activity peripheral to the core sorting role. Reason: Partner-specific ligand binding; ancillary to the defining cargo-receptor activity. |
| GO:0031333 negative regulation of protein-containing complex assembly | IMP PMID:21989385 Quantitative modelling of amyloidogenic processing and its i... | KEEP AS NON CORE | Summary: By sequestering APP and modulating BACE1 access, SorLA can limit assembly of processing complexes; an indirect effect of its cargo-binding behaviour. Reason: Indirect complex-assembly effect downstream of SorLA ligand sequestration (IMP). |
| GO:0005515 protein binding | IPI PMID:21994944 Sorting protein-related receptor SorLA controls regulated se... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' (n=21 IPI) records many partner interactions but conveys no specific molecular function for this cargo receptor. Reason: Uninformative generic MF; specific ligand-binding terms already capture SorLA's activity. |
| GO:0005794 Golgi apparatus | IDA PMID:21994944 Sorting protein-related receptor SorLA controls regulated se... | ACCEPT | Summary: SorLA resides in the Golgi where, with AP-1, it executes TGN-endosome sorting; a major steady-state pool of the receptor is Golgi-associated. Reason: Golgi is a core compartment for SorLA's cargo-sorting cycle (UniProt subcellular location). |
| GO:0005886 plasma membrane | IDA PMID:21994944 Sorting protein-related receptor SorLA controls regulated se... | ACCEPT | Summary: A minor surface pool of SorLA captures extracellular ligands and undergoes AP-2-dependent endocytosis; surface levels are low but functionally important. Reason: Cell-surface localization is the entry point for SorLA's endocytic sorting cycle. |
| GO:1900168 positive regulation of glial cell-derived neurotrophic factor production | IDA PMID:21994944 Sorting protein-related receptor SorLA controls regulated se... | KEEP AS NON CORE | Summary: SorLA controls regulated (vs constitutive) GDNF secretion by sorting GDNF and its receptors, influencing GDNF availability; a neurotrophic-specific role. Reason: Cargo-specific neurotrophic effect downstream of GDNF sorting. |
| GO:0005515 protein binding | IPI PMID:30448281 Soluble LR11 competes with amyloid Ξ² in binding to cerebrosp... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' (n=21 IPI) records many partner interactions but conveys no specific molecular function for this cargo receptor. Reason: Uninformative generic MF; specific ligand-binding terms already capture SorLA's activity. |
| GO:0006605 protein targeting | IDA PMID:27322061 SORLA facilitates insulin receptor signaling in adipocytes a... | ACCEPT | Summary: SorLA directs bound client proteins to specific destinations (TGN retention, lysosomal degradation or surface recycling), the essence of its sorting role. Reason: Core process: directing proteins to their correct intracellular location. |
| GO:0010897 negative regulation of triglyceride catabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: By trafficking LPL to lysosomes and degrading it, SorLA reduces lipase activity and triglyceride catabolism; a metabolic consequence of degradative sorting. Reason: Lipid-metabolism effect downstream of SorLA-mediated LPL turnover. |
| GO:0038020 insulin receptor recycling | IDA PMID:27322061 SORLA facilitates insulin receptor signaling in adipocytes a... | KEEP AS NON CORE | Summary: SorLA recycles internalized INSR via the Golgi to the surface, raising INSR surface levels in adipocytes; a tissue-specific instance of its recycling-sorting role. Reason: Cargo-specific recycling event downstream of SorLA's general recycling activity. |
| GO:0046628 positive regulation of insulin receptor signaling pathway | IDA PMID:27322061 SORLA facilitates insulin receptor signaling in adipocytes a... | KEEP AS NON CORE | Summary: By increasing INSR surface expression through recycling, SorLA strengthens insulin signaling in adipose tissue, a pleiotropic downstream consequence. Reason: Signaling effect secondary to SorLA-mediated INSR recycling. |
| GO:1904179 positive regulation of adipose tissue development | IDA PMID:27322061 SORLA facilitates insulin receptor signaling in adipocytes a... | KEEP AS NON CORE | Summary: Through its metabolic actions (INSR recycling, BMP inhibition, LPL turnover) SorLA influences adipose tissue development; a pleiotropic systemic role. Reason: Systemic metabolic/developmental role secondary to its trafficking functions. |
| GO:0002024 diet induced thermogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SorLA's metabolic regulation of adipose energy expenditure extends to diet-induced thermogenesis, a systemic consequence of its ectodomain activity. Reason: Pleiotropic energy-balance phenotype, downstream of metabolic signaling roles. |
| GO:0005515 protein binding | IPI PMID:21385844 SorLA regulates the activity of lipoprotein lipase by intrac... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' (n=21 IPI) records many partner interactions but conveys no specific molecular function for this cargo receptor. Reason: Uninformative generic MF; specific ligand-binding terms already capture SorLA's activity. |
| GO:0005768 endosome | IDA PMID:21385844 SorLA regulates the activity of lipoprotein lipase by intrac... | ACCEPT | Summary: SorLA cycles through endosomes, capturing internalized cargo (APP, LPL, INSR, HER2) for retrieval to the TGN or routing to lysosomes. Reason: Endosome is a defining compartment of SorLA's retrieval/sorting itinerary. |
| GO:0005769 early endosome | IDA PMID:21385844 SorLA regulates the activity of lipoprotein lipase by intrac... | ACCEPT | Summary: SorLA reaches early endosomes after internalization and directs cargo such as APOA5 and APP toward retrieval or onward lysosomal routing. Reason: Early endosome is an early station of SorLA's sorting itinerary (IDA/IMP). |
| GO:0005771 multivesicular body | IDA PMID:21385844 SorLA regulates the activity of lipoprotein lipase by intrac... | KEEP AS NON CORE | Summary: SorLA is seen in MVBs/late endosomes as part of cargo routing toward lysosomal degradation (e.g. LPL, GDNF). Reason: Downstream late-endosomal station of the degradative arm of SorLA sorting. |
| GO:0005783 endoplasmic reticulum | IDA PMID:21385844 SorLA regulates the activity of lipoprotein lipase by intrac... | KEEP AS NON CORE | Summary: SorLA transits the ER during biosynthesis and maturation, but its sorting activity acts downstream in the TGN/endosomal system rather than in the ER. Reason: Biosynthetic transit compartment, upstream of and peripheral to the core sorting cycle. |
| GO:0005794 Golgi apparatus | IDA PMID:21385844 SorLA regulates the activity of lipoprotein lipase by intrac... | ACCEPT | Summary: SorLA resides in the Golgi where, with AP-1, it executes TGN-endosome sorting; a major steady-state pool of the receptor is Golgi-associated. Reason: Golgi is a core compartment for SorLA's cargo-sorting cycle (UniProt subcellular location). |
| GO:0005886 plasma membrane | IDA PMID:21385844 SorLA regulates the activity of lipoprotein lipase by intrac... | ACCEPT | Summary: A minor surface pool of SorLA captures extracellular ligands and undergoes AP-2-dependent endocytosis; surface levels are low but functionally important. Reason: Cell-surface localization is the entry point for SorLA's endocytic sorting cycle. |
| GO:0006605 protein targeting | IDA PMID:21385844 SorLA regulates the activity of lipoprotein lipase by intrac... | ACCEPT | Summary: SorLA directs bound client proteins to specific destinations (TGN retention, lysosomal degradation or surface recycling), the essence of its sorting role. Reason: Core process: directing proteins to their correct intracellular location. |
| GO:0030514 negative regulation of BMP signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The SorLA N-terminal ectodomain inhibits BMP/Smad signaling in adipose tissue to restrain energy expenditure; a metabolic, ectodomain-mediated role. Reason: Pleiotropic metabolic signaling effect of the soluble ectodomain (IEA/ISS). |
| GO:1990845 adaptive thermogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Soluble SorLA represses adipose thermogenesis via BMP/Smad inhibition, shifting energy balance toward storage; a metabolic role of the ectodomain. Reason: Pleiotropic metabolic phenotype of the shed ectodomain (IEA/ISS). |
| GO:0005041 low-density lipoprotein particle receptor activity | TAS PMID:20005821 Overexpression of low-density lipoprotein receptor in the br... | ACCEPT | Summary: SorLA functions as an LDL-receptor-family member with complement-type ligand-binding repeats that bind lipoprotein and LRPAP1/RAP ligands. Reason: Core receptor activity defining SorLA's LDLR-family identity. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-8871506 | ACCEPT | Summary: As a single-pass type I membrane protein, SorLA sits in the Golgi/TGN membrane where it engages adaptors (GGA, AP-1) and retains cargo such as APP. Reason: Correct membrane sub-localization for a transmembrane Golgi sorting receptor. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-8871494 | ACCEPT | Summary: The transmembrane receptor is embedded in the endosomal limiting membrane, where its cytosolic tail binds retromer/GGA adaptors for sorting. Reason: Membrane localization underpins SorLA's endosomal sorting function. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-8871506 | ACCEPT | Summary: The transmembrane receptor is embedded in the endosomal limiting membrane, where its cytosolic tail binds retromer/GGA adaptors for sorting. Reason: Membrane localization underpins SorLA's endosomal sorting function. |
| GO:0050768 negative regulation of neurogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: SorLA influences neuronal development consistent with its high brain expression and trafficking of neurotrophic cargo (BDNF/TrkB, GDNF). Reason: Developmental role downstream of neurotrophic-receptor sorting (IEA/ISS). |
| GO:1902997 negative regulation of neurofibrillary tangle assembly | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: SorLA's primary action is on APP/Abeta trafficking; an effect on tau neurofibrillary-tangle assembly is at best indirect and rests only on electronic/ISS inference. Reason: Tau-tangle effect is speculative and indirect; electronic over-annotation. |
| GO:1902953 positive regulation of ER to Golgi vesicle-mediated transport | IMP PMID:17855360 SorLA/LR11 regulates processing of amyloid precursor protein... | ACCEPT | Summary: SorLA promotes anterograde ER-to-Golgi transport of cargo, complementing its retrieval activity in establishing correct cargo localization. Reason: Trafficking-regulatory role consistent with its sorting function (IMP). |
| GO:1902966 positive regulation of protein localization to early endosome | IMP PMID:22621900 GGA1-mediated endocytic traffic of LR11/SorLA alters APP int... | ACCEPT | Summary: SorLA drives delivery of cargo into early endosomes en route to retrieval or degradation, an integral step of its sorting cycle. Reason: Direct manifestation of SorLA endosomal cargo sorting (IMP). |
| GO:0001540 amyloid-beta binding | IDA PMID:24523320 Lysosomal sorting of amyloid-Ξ² by the SORLA receptor is impa... | ACCEPT | Summary: SorLA directly binds amyloid-beta (and APP C99/Abeta40) via its ectodomain, enabling capture of newly produced Abeta for lysosomal clearance. Reason: Defining ligand interaction underlying SorLA's anti-amyloidogenic sorting (IDA/IPI). |
| GO:0005515 protein binding | IPI PMID:24001769 SORLA-dependent and -independent functions for PACS1 in cont... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' (n=21 IPI) records many partner interactions but conveys no specific molecular function for this cargo receptor. Reason: Uninformative generic MF; specific ligand-binding terms already capture SorLA's activity. |
| GO:0005769 early endosome | IMP PMID:22621900 GGA1-mediated endocytic traffic of LR11/SorLA alters APP int... | ACCEPT | Summary: SorLA reaches early endosomes after internalization and directs cargo such as APOA5 and APP toward retrieval or onward lysosomal routing. Reason: Early endosome is an early station of SorLA's sorting itinerary (IDA/IMP). |
| GO:0005769 early endosome | IDA PMID:24001769 SORLA-dependent and -independent functions for PACS1 in cont... | ACCEPT | Summary: SorLA reaches early endosomes after internalization and directs cargo such as APOA5 and APP toward retrieval or onward lysosomal routing. Reason: Early endosome is an early station of SorLA's sorting itinerary (IDA/IMP). |
| GO:0005802 trans-Golgi network | IDA PMID:24001769 SORLA-dependent and -independent functions for PACS1 in cont... | ACCEPT | Summary: SorLA is predominantly localized to the TGN, the compartment where it retains APP and from which it dispatches cargo to endosomes. Reason: TGN is the principal steady-state site of this sorting receptor (UniProt: 'predominantly in the TGN'). |
| GO:0006622 protein targeting to lysosome | IDA PMID:24523320 Lysosomal sorting of amyloid-Ξ² by the SORLA receptor is impa... | ACCEPT | Summary: SorLA routes select cargo (LPL, GDNF, IL6, APOA5, amyloid-beta) to lysosomes for degradation, a defined branch of its sorting output. Reason: Core degradative sorting branch of the receptor (IBA/IDA). |
| GO:0045732 positive regulation of protein catabolic process | IDA PMID:24523320 Lysosomal sorting of amyloid-Ξ² by the SORLA receptor is impa... | ACCEPT | Summary: By routing clients (LPL, GDNF, IL6, amyloid-beta) to lysosomes, SorLA promotes their catabolism as a downstream output of degradative sorting. Reason: Direct outcome of SorLA's lysosomal targeting branch (IDA). |
| GO:0055037 recycling endosome | IMP PMID:22621900 GGA1-mediated endocytic traffic of LR11/SorLA alters APP int... | ACCEPT | Summary: SorLA traffics through recycling endosomes, enabling cargo such as INSR and HER2 to be returned to the cell surface. Reason: Recycling-endosome residence supports SorLA-mediated receptor recycling (IMP). |
| GO:1902430 negative regulation of amyloid-beta formation | IDA PMID:22621900 GGA1-mediated endocytic traffic of LR11/SorLA alters APP int... | ACCEPT | Summary: SorLA lowers Abeta40/Abeta42 generation by sequestering APP from amyloidogenic processing and routing Abeta to lysosomes, the basis of its AD-protective role. Reason: Central disease-relevant output directly downstream of SorLA APP sorting (IDA/IMP). |
| GO:1902430 negative regulation of amyloid-beta formation | IMP PMID:24001769 SORLA-dependent and -independent functions for PACS1 in cont... | ACCEPT | Summary: SorLA lowers Abeta40/Abeta42 generation by sequestering APP from amyloidogenic processing and routing Abeta to lysosomes, the basis of its AD-protective role. Reason: Central disease-relevant output directly downstream of SorLA APP sorting (IDA/IMP). |
| GO:1902430 negative regulation of amyloid-beta formation | IMP PMID:24523320 Lysosomal sorting of amyloid-Ξ² by the SORLA receptor is impa... | ACCEPT | Summary: SorLA lowers Abeta40/Abeta42 generation by sequestering APP from amyloidogenic processing and routing Abeta to lysosomes, the basis of its AD-protective role. Reason: Central disease-relevant output directly downstream of SorLA APP sorting (IDA/IMP). |
| GO:2001137 positive regulation of endocytic recycling | IMP PMID:22621900 GGA1-mediated endocytic traffic of LR11/SorLA alters APP int... | ACCEPT | Summary: SorLA enhances recycling of internalized cargo back to the surface, exemplified by HER2 recycling that sustains PI3K-dependent signaling. Reason: Core recycling-promoting activity of the sorting receptor (IMP). |
| GO:0001540 amyloid-beta binding | IPI PMID:16407538 Interaction of the cytosolic domains of sorLA/LR11 with the ... | ACCEPT | Summary: SorLA directly binds amyloid-beta (and APP C99/Abeta40) via its ectodomain, enabling capture of newly produced Abeta for lysosomal clearance. Reason: Defining ligand interaction underlying SorLA's anti-amyloidogenic sorting (IDA/IPI). |
| GO:0005515 protein binding | IPI PMID:17855360 SorLA/LR11 regulates processing of amyloid precursor protein... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' (n=21 IPI) records many partner interactions but conveys no specific molecular function for this cargo receptor. Reason: Uninformative generic MF; specific ligand-binding terms already capture SorLA's activity. |
| GO:0005641 nuclear envelope lumen | IDA PMID:17855360 SorLA/LR11 regulates processing of amyloid precursor protein... | UNDECIDED | Summary: RIP releases a SorLA C-terminal fragment that localizes to the nucleus, but a specific nuclear-envelope-lumen assignment is not clearly supported by the evidence reviewed. Reason: Cannot verify the nuclear-envelope-lumen call; nuclear targeting is only of a cleaved fragment. |
| GO:0005641 nuclear envelope lumen | IDA PMID:21989385 Quantitative modelling of amyloidogenic processing and its i... | UNDECIDED | Summary: RIP releases a SorLA C-terminal fragment that localizes to the nucleus, but a specific nuclear-envelope-lumen assignment is not clearly supported by the evidence reviewed. Reason: Cannot verify the nuclear-envelope-lumen call; nuclear targeting is only of a cleaved fragment. |
| GO:0005783 endoplasmic reticulum | IDA PMID:17855360 SorLA/LR11 regulates processing of amyloid precursor protein... | KEEP AS NON CORE | Summary: SorLA transits the ER during biosynthesis and maturation, but its sorting activity acts downstream in the TGN/endosomal system rather than in the ER. Reason: Biosynthetic transit compartment, upstream of and peripheral to the core sorting cycle. |
| GO:0006605 protein targeting | IDA PMID:16407538 Interaction of the cytosolic domains of sorLA/LR11 with the ... | ACCEPT | Summary: SorLA directs bound client proteins to specific destinations (TGN retention, lysosomal degradation or surface recycling), the essence of its sorting role. Reason: Core process: directing proteins to their correct intracellular location. |
| GO:0006892 post-Golgi vesicle-mediated transport | IDA PMID:17855360 SorLA/LR11 regulates processing of amyloid precursor protein... | ACCEPT | Summary: SorLA participates in vesicular transport from the TGN onward, dispatching itself and cargo to endosomes and the cell surface. Reason: Core trafficking step in SorLA's sorting itinerary (IBA/IDA). |
| GO:0031267 small GTPase binding | IPI PMID:17855360 SorLA/LR11 regulates processing of amyloid precursor protein... | KEEP AS NON CORE | Summary: Reported binding to a small GTPase (e.g. RHOH) is a specific partner interaction not central to SorLA's cargo-sorting mechanism. Reason: Specific partner binding, peripheral to the core sorting function (IPI). |
| GO:0031985 Golgi cisterna | IDA PMID:17855360 SorLA/LR11 regulates processing of amyloid precursor protein... | ACCEPT | Summary: IDA localization to Golgi cisternae is consistent with SorLA's residence in the Golgi stack during cargo sorting and retrieval. Reason: Cisternal localization refines the core Golgi pool of this sorting receptor. |
| GO:0034067 protein localization to Golgi apparatus | IDA PMID:17855360 SorLA/LR11 regulates processing of amyloid precursor protein... | ACCEPT | Summary: By capturing and retrieving cargo to the Golgi/TGN, SorLA establishes the Golgi localization of clients such as APP. Reason: Direct consequence of SorLA's retrieval/retention activity (IDA). |
| GO:0045053 protein retention in Golgi apparatus | IDA PMID:17855360 SorLA/LR11 regulates processing of amyloid precursor protein... | ACCEPT | Summary: SorLA retains APP (and other cargo) in the TGN, the key event that limits APP's transit to amyloidogenic late-endosomal processing. Reason: Defining sorting outcome that links SorLA to reduced amyloidogenesis (IBA/IDA). |
| GO:1902430 negative regulation of amyloid-beta formation | IDA PMID:16407538 Interaction of the cytosolic domains of sorLA/LR11 with the ... | ACCEPT | Summary: SorLA lowers Abeta40/Abeta42 generation by sequestering APP from amyloidogenic processing and routing Abeta to lysosomes, the basis of its AD-protective role. Reason: Central disease-relevant output directly downstream of SorLA APP sorting (IDA/IMP). |
| GO:1902430 negative regulation of amyloid-beta formation | IMP PMID:17855360 SorLA/LR11 regulates processing of amyloid precursor protein... | ACCEPT | Summary: SorLA lowers Abeta40/Abeta42 generation by sequestering APP from amyloidogenic processing and routing Abeta to lysosomes, the basis of its AD-protective role. Reason: Central disease-relevant output directly downstream of SorLA APP sorting (IDA/IMP). |
| GO:1902430 negative regulation of amyloid-beta formation | IMP PMID:21989385 Quantitative modelling of amyloidogenic processing and its i... | ACCEPT | Summary: SorLA lowers Abeta40/Abeta42 generation by sequestering APP from amyloidogenic processing and routing Abeta to lysosomes, the basis of its AD-protective role. Reason: Central disease-relevant output directly downstream of SorLA APP sorting (IDA/IMP). |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: HDA detection of SorLA in exosomes is consistent with proteomic surveys; it is incidental to the receptor's intracellular sorting function. Reason: High-throughput proteomic localization; not a core functional site. |
| GO:0005515 protein binding | IPI PMID:14764453 LR11, an LDL receptor gene family member, is a novel regulat... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' (n=21 IPI) records many partner interactions but conveys no specific molecular function for this cargo receptor. Reason: Uninformative generic MF; specific ligand-binding terms already capture SorLA's activity. |
| GO:0005576 extracellular region | IDA PMID:14764453 LR11, an LDL receptor gene family member, is a novel regulat... | KEEP AS NON CORE | Summary: ADAM17-mediated shedding releases the soluble SorLA ectodomain (sLR11) into the extracellular space, where it acts as a secreted ligand-binding fragment. Reason: Reflects shed soluble ectodomain, a secondary product of the membrane receptor. |
| GO:0014910 regulation of smooth muscle cell migration | IDA PMID:14764453 LR11, an LDL receptor gene family member, is a novel regulat... | KEEP AS NON CORE | Summary: The shed SorLA ectodomain promotes smooth-muscle migration via increased uPAR surface display, a pleiotropic vascular role of the soluble fragment. Reason: Vascular phenotype downstream of ectodomain/uPAR handling, not core sorting. |
| GO:0016020 membrane | IDA PMID:14764453 LR11, an LDL receptor gene family member, is a novel regulat... | ACCEPT | Summary: Generic membrane association reflects SorLA's nature as an integral single-pass type I membrane protein distributed across the secretory/endosomal system. Reason: Correct but generic; consistent with the transmembrane receptor. |
| GO:0005768 endosome | IDA PMID:16174740 Neuronal sorting protein-related receptor sorLA/LR11 regulat... | ACCEPT | Summary: SorLA cycles through endosomes, capturing internalized cargo (APP, LPL, INSR, HER2) for retrieval to the TGN or routing to lysosomes. Reason: Endosome is a defining compartment of SorLA's retrieval/sorting itinerary. |
| GO:0005794 Golgi apparatus | IDA PMID:16174740 Neuronal sorting protein-related receptor sorLA/LR11 regulat... | ACCEPT | Summary: SorLA resides in the Golgi where, with AP-1, it executes TGN-endosome sorting; a major steady-state pool of the receptor is Golgi-associated. Reason: Golgi is a core compartment for SorLA's cargo-sorting cycle (UniProt subcellular location). |
| GO:0006605 protein targeting | IMP PMID:16174740 Neuronal sorting protein-related receptor sorLA/LR11 regulat... | ACCEPT | Summary: SorLA directs bound client proteins to specific destinations (TGN retention, lysosomal degradation or surface recycling), the essence of its sorting role. Reason: Core process: directing proteins to their correct intracellular location. |
| GO:0030169 low-density lipoprotein particle binding | IPI PMID:17326667 Apolipoprotein A-V interaction with members of the low densi... | ACCEPT | Summary: Through its LDLR-class complement repeats SorLA binds LDL particles, reflecting its membership in the LDL-receptor gene family. Reason: Direct ligand-binding activity characteristic of this LDLR-family receptor (IPI). |
| GO:0005886 plasma membrane | TAS PMID:9157966 A novel mosaic protein containing LDL receptor elements is h... | ACCEPT | Summary: A minor surface pool of SorLA captures extracellular ligands and undergoes AP-2-dependent endocytosis; surface levels are low but functionally important. Reason: Cell-surface localization is the entry point for SorLA's endocytic sorting cycle. |
| GO:0006898 receptor-mediated endocytosis | TAS PMID:9157966 A novel mosaic protein containing LDL receptor elements is h... | ACCEPT | Summary: SorLA mediates AP-2/clathrin-dependent internalization of surface ligands (uPA-PAI1, APOA5, IL6, HER2), feeding them into its endosomal sorting itinerary. Reason: Core uptake step of SorLA's cargo-sorting cycle (IDA/TAS). |
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Download this section (compressed HTML)Q: Should GO add a more specific APP/amyloid-beta cargo sorting receptor activity term for SORL1-like receptor functions, or is cargo receptor activity plus cargo-specific binding/process annotations sufficient?
Suggested experts: GO receptor activity curators, Alzheimer trafficking experts
Q: Which SORL1 cargo-specific phenotypes, such as insulin receptor recycling, GDNF/GFRA1 turnover, IL6-family cytokine regulation, or HER2 recycling, should be retained as non-core versus represented only through generic cargo sorting?
Suggested experts: VPS10P-domain receptor experts, GO annotation curators
Q: Are nuclear-envelope or perinucleolar localization annotations for SORL1 supported by direct full-text evidence, or are they artifacts of perinuclear Golgi/endosomal localization descriptions?
Suggested experts: cellular trafficking curators, SORL1 cell biology experts
Experiment: Use endogenous SORL1 knock-in/knockout neurons to compare APP, BACE1, and nascent amyloid-beta routing across TGN, early endosome, recycling endosome, and lysosomal compartments.
Hypothesis: SORL1 lowers amyloidogenic processing primarily by retaining or retrieving APP/BACE1-containing cargo away from compartments that favor BACE cleavage and by routing nascent amyloid-beta to lysosomes.
Type: live-cell cargo trafficking and compartment-resolved APP processing assay
Experiment: Introduce Alzheimer-associated SORL1 variants into the endogenous locus and assay cargo binding, adaptor recruitment, endosome-to-Golgi retrieval, and A-beta lysosomal targeting.
Hypothesis: Pathogenic SORL1 variants impair specific cargo-binding or adaptor-dependent trafficking steps without eliminating the general sorting-receptor scaffold.
Type: endogenous variant knock-in functional rescue assay
Experiment: Compare APP/A-beta, insulin receptor, GDNF/GFRA1, IL6-family cytokine complexes, and HER2 as parallel cargoes in matched cellular systems.
Hypothesis: SORL1 uses a shared trafficking architecture for many cargoes, but Alzheimer-relevant APP/A-beta handling depends on cargo-specific binding and adaptor requirements.
Type: multi-cargo receptor sorting assay
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