Q96PQ0 · SORC2_HUMAN
- ProteinVPS10 domain-containing receptor SorCS2
- GeneSORCS2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1159 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
The heterodimer formed by NGFR and SORCS2 functions as receptor for the precursor forms of NGF (proNGF) and BDNF (proBDNF) (PubMed:22155786, PubMed:24908487).
ProNGF and proBDNF binding both promote axon growth cone collapse (in vitro) (PubMed:22155786, PubMed:24908487).
Plays a role in the regulation of dendritic spine density in hippocampus neurons (By similarity).
Required for normal neurite branching and extension in response to BDNF (PubMed:27457814).
Plays a role in BDNF-dependent hippocampal synaptic plasticity. Together with NGFR and NTRK2, is required both for BDNF-mediated synaptic long-term depression and long-term potentiation (PubMed:27457814).
ProNGF binding promotes dissociation of TRIO from the heterodimer, which leads to inactivation of RAC1 and/or RAC2 and subsequent reorganization of the actin cytoskeleton (PubMed:22155786).
Together with the retromer complex subunit VPS35, required for normal expression of GRIN2A at synapses and dendritic cell membranes. Required for normal expression of the amino acid transporter SLC1A1 at the cell membrane, and thereby contributes to protect cells against oxidative stress (By similarity).
ProNGF and proBDNF binding both promote axon growth cone collapse (in vitro) (PubMed:22155786, PubMed:24908487).
Plays a role in the regulation of dendritic spine density in hippocampus neurons (By similarity).
Required for normal neurite branching and extension in response to BDNF (PubMed:27457814).
Plays a role in BDNF-dependent hippocampal synaptic plasticity. Together with NGFR and NTRK2, is required both for BDNF-mediated synaptic long-term depression and long-term potentiation (PubMed:27457814).
ProNGF binding promotes dissociation of TRIO from the heterodimer, which leads to inactivation of RAC1 and/or RAC2 and subsequent reorganization of the actin cytoskeleton (PubMed:22155786).
Together with the retromer complex subunit VPS35, required for normal expression of GRIN2A at synapses and dendritic cell membranes. Required for normal expression of the amino acid transporter SLC1A1 at the cell membrane, and thereby contributes to protect cells against oxidative stress (By similarity).
SorCS2 122 kDa chain
Does not promote Schwann cell apoptosis in response to proBDNF.
SorCS2 104 kDa chain and SorCS2 18 kDa chain together promote Schwann cell apoptosis in response to proBDNF.
Miscellaneous
Expression is decreased in the brains of Huntington disease (HD) patients after the onset of symptoms.
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 69-70 | Cleavage | ||||
Sequence: RS | ||||||
Site | 119-120 | Cleavage | ||||
Sequence: RA | ||||||
Site | 1030-1031 | Cleavage | ||||
Sequence: RS |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | dendritic spine | |
Cellular Component | early endosome membrane | |
Cellular Component | intracellular membrane-bounded organelle | |
Cellular Component | membrane | |
Cellular Component | perikaryon | |
Cellular Component | postsynaptic density membrane | |
Cellular Component | recycling endosome membrane | |
Molecular Function | neuropeptide receptor activity | |
Biological Process | intracellular protein transport | |
Biological Process | long-term synaptic depression | |
Biological Process | neuropeptide signaling pathway |
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameVPS10 domain-containing receptor SorCS2
- Cleaved into 3 chains
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ96PQ0
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Single-pass type I membrane protein
Cytoplasmic vesicle membrane ; Single-pass type I membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 51-1078 | Extracellular | ||||
Sequence: RSPEPGRLGPHAQLTRVPRSPPAGRAEPGGGEDRQARGTEPGAPGPSPGPAPGPGEDGAPAAGYRRWERAAPLAGVASRAQVSLISTSFVLKGDATHNQAMVHWTGENSSVILILTKYYHADMGKVLESSLWRSSDFGTSYTKLTLQPGVTTVIDNFYICPTNKRKVILVSSSLSDRDQSLFLSADEGATFQKQPIPFFVETLIFHPKEEDKVLAYTKESKLYVSSDLGKKWTLLQERVTKDHVFWSVSGVDADPDLVHVEAQDLGGDFRYVTCAIHNCSEKMLTAPFAGPIDHGSLTVQDDYIFFKATSANQTKYYVSYRRNEFVLMKLPKYALPKDLQIISTDESQVFVAVQEWYQMDTYNLYQSDPRGVRYALVLQDVRSSRQAEESVLIDILEVRGVKGVFLANQKIDGKVMTLITYNKGRDWDYLRPPSMDMNGKPTNCKPPDCHLHLHLRWADNPYVSGTVHTKDTAPGLIMGAGNLGSQLVEYKEEMYITSDCGHTWRQVFEEEHHILYLDHGGVIVAIKDTSIPLKILKFSVDEGLTWSTHNFTSTSVFVDGLLSEPGDETLVMTVFGHISFRSDWELVKVDFRPSFSRQCGEEDYSSWELSNLQGDRCIMGQQRSFRKRKSTSWCIKGRSFTSALTSRVCECRDSDFLCDYGFERSSSSESSTNKCSANFWFNPLSPPDDCALGQTYTSSLGYRKVVSNVCEGGVDMQQSQVQLQCPLTPPRGLQVSIQGEAVAVRPGEDVLFVVRQEQGDVLTTKYQVDLGDGFKAMYVNLTLTGEPIRHRYESPGIYRVSVRAENTAGHDEAVLFVQVNSPLQALYLEVVPVIGLNQEVNLTAVLLPLNPNLTVFYWWIGHSLQPLLSLDNSVTTRFSDTGDVRVTVQAACGNSVLQDSRVLRVLDQFQVMPLQFSKELDAYNPNTPEWREDVGLVVTRLLSKETSVPQELLVTVVKPGLPTLADLYVLLPPPRPTRKRSLSSDKRLAAIQQVLNAQKISFLLRGGVRVLVALRDTGTGAEQLGGGG | ||||||
Transmembrane | 1079-1099 | Helical | ||||
Sequence: GYWAVVVLFVIGLFAAGAFIL | ||||||
Topological domain | 1100-1159 | Cytoplasmic | ||||
Sequence: YKFKRKRPGRTVYAQMHNEKEQEMTSPVSHSEDVQGAVQGNHSGVVLSINSREMHSYLVS |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 66-69 | Decreased proteolytic processing; when associated with 116-A--A-119. | ||||
Sequence: RVPR → AVPA | ||||||
Mutagenesis | 116-119 | Decreased proteolytic processing; when associated with 66-A--A-69. | ||||
Sequence: RWER → AWEA | ||||||
Natural variant | VAR_060109 | 345 | in dbSNP:rs34058821 | |||
Sequence: G → R | ||||||
Natural variant | VAR_060110 | 695 | in dbSNP:rs16840892 | |||
Sequence: T → M | ||||||
Natural variant | VAR_060111 | 745 | in dbSNP:rs16840899 | |||
Sequence: T → I | ||||||
Mutagenesis | 1027 | Strongly increases generation of the 104 kDa chain. | ||||
Sequence: T → R | ||||||
Mutagenesis | 1028-1030 | Abolishes generation of the 104 kDa chain. | ||||
Sequence: RKR → AKA |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,449 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, glycosylation, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-50 | |||||
Sequence: MAHRGPSRASKGPGPTARAPSPGAPPPPRSPRSRPLLLLLLLLGACGAAG | ||||||
Chain | PRO_0000033172 | 51-1159 | VPS10 domain-containing receptor SorCS2 | |||
Sequence: RSPEPGRLGPHAQLTRVPRSPPAGRAEPGGGEDRQARGTEPGAPGPSPGPAPGPGEDGAPAAGYRRWERAAPLAGVASRAQVSLISTSFVLKGDATHNQAMVHWTGENSSVILILTKYYHADMGKVLESSLWRSSDFGTSYTKLTLQPGVTTVIDNFYICPTNKRKVILVSSSLSDRDQSLFLSADEGATFQKQPIPFFVETLIFHPKEEDKVLAYTKESKLYVSSDLGKKWTLLQERVTKDHVFWSVSGVDADPDLVHVEAQDLGGDFRYVTCAIHNCSEKMLTAPFAGPIDHGSLTVQDDYIFFKATSANQTKYYVSYRRNEFVLMKLPKYALPKDLQIISTDESQVFVAVQEWYQMDTYNLYQSDPRGVRYALVLQDVRSSRQAEESVLIDILEVRGVKGVFLANQKIDGKVMTLITYNKGRDWDYLRPPSMDMNGKPTNCKPPDCHLHLHLRWADNPYVSGTVHTKDTAPGLIMGAGNLGSQLVEYKEEMYITSDCGHTWRQVFEEEHHILYLDHGGVIVAIKDTSIPLKILKFSVDEGLTWSTHNFTSTSVFVDGLLSEPGDETLVMTVFGHISFRSDWELVKVDFRPSFSRQCGEEDYSSWELSNLQGDRCIMGQQRSFRKRKSTSWCIKGRSFTSALTSRVCECRDSDFLCDYGFERSSSSESSTNKCSANFWFNPLSPPDDCALGQTYTSSLGYRKVVSNVCEGGVDMQQSQVQLQCPLTPPRGLQVSIQGEAVAVRPGEDVLFVVRQEQGDVLTTKYQVDLGDGFKAMYVNLTLTGEPIRHRYESPGIYRVSVRAENTAGHDEAVLFVQVNSPLQALYLEVVPVIGLNQEVNLTAVLLPLNPNLTVFYWWIGHSLQPLLSLDNSVTTRFSDTGDVRVTVQAACGNSVLQDSRVLRVLDQFQVMPLQFSKELDAYNPNTPEWREDVGLVVTRLLSKETSVPQELLVTVVKPGLPTLADLYVLLPPPRPTRKRSLSSDKRLAAIQQVLNAQKISFLLRGGVRVLVALRDTGTGAEQLGGGGGYWAVVVLFVIGLFAAGAFILYKFKRKRPGRTVYAQMHNEKEQEMTSPVSHSEDVQGAVQGNHSGVVLSINSREMHSYLVS | ||||||
Chain | PRO_0000447469 | 70-1159 | SorCS2 122 kDa chain | |||
Sequence: SPPAGRAEPGGGEDRQARGTEPGAPGPSPGPAPGPGEDGAPAAGYRRWERAAPLAGVASRAQVSLISTSFVLKGDATHNQAMVHWTGENSSVILILTKYYHADMGKVLESSLWRSSDFGTSYTKLTLQPGVTTVIDNFYICPTNKRKVILVSSSLSDRDQSLFLSADEGATFQKQPIPFFVETLIFHPKEEDKVLAYTKESKLYVSSDLGKKWTLLQERVTKDHVFWSVSGVDADPDLVHVEAQDLGGDFRYVTCAIHNCSEKMLTAPFAGPIDHGSLTVQDDYIFFKATSANQTKYYVSYRRNEFVLMKLPKYALPKDLQIISTDESQVFVAVQEWYQMDTYNLYQSDPRGVRYALVLQDVRSSRQAEESVLIDILEVRGVKGVFLANQKIDGKVMTLITYNKGRDWDYLRPPSMDMNGKPTNCKPPDCHLHLHLRWADNPYVSGTVHTKDTAPGLIMGAGNLGSQLVEYKEEMYITSDCGHTWRQVFEEEHHILYLDHGGVIVAIKDTSIPLKILKFSVDEGLTWSTHNFTSTSVFVDGLLSEPGDETLVMTVFGHISFRSDWELVKVDFRPSFSRQCGEEDYSSWELSNLQGDRCIMGQQRSFRKRKSTSWCIKGRSFTSALTSRVCECRDSDFLCDYGFERSSSSESSTNKCSANFWFNPLSPPDDCALGQTYTSSLGYRKVVSNVCEGGVDMQQSQVQLQCPLTPPRGLQVSIQGEAVAVRPGEDVLFVVRQEQGDVLTTKYQVDLGDGFKAMYVNLTLTGEPIRHRYESPGIYRVSVRAENTAGHDEAVLFVQVNSPLQALYLEVVPVIGLNQEVNLTAVLLPLNPNLTVFYWWIGHSLQPLLSLDNSVTTRFSDTGDVRVTVQAACGNSVLQDSRVLRVLDQFQVMPLQFSKELDAYNPNTPEWREDVGLVVTRLLSKETSVPQELLVTVVKPGLPTLADLYVLLPPPRPTRKRSLSSDKRLAAIQQVLNAQKISFLLRGGVRVLVALRDTGTGAEQLGGGGGYWAVVVLFVIGLFAAGAFILYKFKRKRPGRTVYAQMHNEKEQEMTSPVSHSEDVQGAVQGNHSGVVLSINSREMHSYLVS | ||||||
Chain | PRO_0000447470 | 120-1030 | SorCS2 104 kDa chain | |||
Sequence: AAPLAGVASRAQVSLISTSFVLKGDATHNQAMVHWTGENSSVILILTKYYHADMGKVLESSLWRSSDFGTSYTKLTLQPGVTTVIDNFYICPTNKRKVILVSSSLSDRDQSLFLSADEGATFQKQPIPFFVETLIFHPKEEDKVLAYTKESKLYVSSDLGKKWTLLQERVTKDHVFWSVSGVDADPDLVHVEAQDLGGDFRYVTCAIHNCSEKMLTAPFAGPIDHGSLTVQDDYIFFKATSANQTKYYVSYRRNEFVLMKLPKYALPKDLQIISTDESQVFVAVQEWYQMDTYNLYQSDPRGVRYALVLQDVRSSRQAEESVLIDILEVRGVKGVFLANQKIDGKVMTLITYNKGRDWDYLRPPSMDMNGKPTNCKPPDCHLHLHLRWADNPYVSGTVHTKDTAPGLIMGAGNLGSQLVEYKEEMYITSDCGHTWRQVFEEEHHILYLDHGGVIVAIKDTSIPLKILKFSVDEGLTWSTHNFTSTSVFVDGLLSEPGDETLVMTVFGHISFRSDWELVKVDFRPSFSRQCGEEDYSSWELSNLQGDRCIMGQQRSFRKRKSTSWCIKGRSFTSALTSRVCECRDSDFLCDYGFERSSSSESSTNKCSANFWFNPLSPPDDCALGQTYTSSLGYRKVVSNVCEGGVDMQQSQVQLQCPLTPPRGLQVSIQGEAVAVRPGEDVLFVVRQEQGDVLTTKYQVDLGDGFKAMYVNLTLTGEPIRHRYESPGIYRVSVRAENTAGHDEAVLFVQVNSPLQALYLEVVPVIGLNQEVNLTAVLLPLNPNLTVFYWWIGHSLQPLLSLDNSVTTRFSDTGDVRVTVQAACGNSVLQDSRVLRVLDQFQVMPLQFSKELDAYNPNTPEWREDVGLVVTRLLSKETSVPQELLVTVVKPGLPTLADLYVLLPPPRPTRKR | ||||||
Glycosylation | 158 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 324↔329 | |||||
Sequence: CAIHNC | ||||||
Glycosylation | 328 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 362 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 494↔499 | |||||
Sequence: CKPPDC | ||||||
Glycosylation | 600 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 649↔684 | |||||
Sequence: CGEEDYSSWELSNLQGDRCIMGQQRSFRKRKSTSWC | ||||||
Disulfide bond | 667↔699 | |||||
Sequence: CIMGQQRSFRKRKSTSWCIKGRSFTSALTSRVC | ||||||
Disulfide bond | 701↔760 | |||||
Sequence: CRDSDFLCDYGFERSSSSESSTNKCSANFWFNPLSPPDDCALGQTYTSSLGYRKVVSNVC | ||||||
Disulfide bond | 708↔725 | |||||
Sequence: CDYGFERSSSSESSTNKC | ||||||
Disulfide bond | 740↔775 | |||||
Sequence: CALGQTYTSSLGYRKVVSNVCEGGVDMQQSQVQLQC | ||||||
Glycosylation | 830 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 891 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 902 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Chain | PRO_0000447471 | 1031-1159 | SorCS2 18 kDa chain | |||
Sequence: SLSSDKRLAAIQQVLNAQKISFLLRGGVRVLVALRDTGTGAEQLGGGGGYWAVVVLFVIGLFAAGAFILYKFKRKRPGRTVYAQMHNEKEQEMTSPVSHSEDVQGAVQGNHSGVVLSINSREMHSYLVS |
Post-translational modification
Proteolytic cleavage removes a propeptide, giving rise to a 122 kDa chain that includes a cytoplasmic tail. Further cleavage gives rise to a 104 kDa chain that lacks the cytoplasmic tail, and a membrane-bound 18 kDa chain. The 104 kDa chain remains bound to the 18 kDa chain.
N-glycosylated.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Detected on neurons in the caudate region (PubMed:28469074).
Detected on neurons in the hippocampus (at protein level) (PubMed:30840898).
Highly expressed in brain and kidney. Detected at low levels in heart, liver, small intestine, skeletal muscle and thymus (PubMed:11499680).
Detected on neurons in the hippocampus (at protein level) (PubMed:30840898).
Highly expressed in brain and kidney. Detected at low levels in heart, liver, small intestine, skeletal muscle and thymus (PubMed:11499680).
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homodimer (in vitro) (By similarity).
Heterodimer with NGFR. The extracellular domains of the heterodimer bind the precursor form of NGF (proNGF) (PubMed:22155786, PubMed:24908487).
Has much higher affinity for proNGF than for mature NGF (PubMed:24908487).
Can also bind mature NGF and BDNF (By similarity).
Each chain in the receptor dimer interacts (via extracellular domain) with an NGF dimer (in vitro) (By similarity).
Interacts with the precursor forms of BDNF (proBDNF) and NTF3 (proNT3) (PubMed:24908487).
The cytoplasmic region of the heterodimer formed by NGFR and SORCS2 binds TRIO. ProNGF binding mediates dissociation of TRIO from the receptor complex (PubMed:22155786).
Interacts with SLC1A1. Interacts with VPS35. Interacts (via extracellular domain) with NTRK2 (via extracellular domain). Interacts with VPS35. Interacts (via extracellular domain) with GRIN2A (By similarity).
Heterodimer with NGFR. The extracellular domains of the heterodimer bind the precursor form of NGF (proNGF) (PubMed:22155786, PubMed:24908487).
Has much higher affinity for proNGF than for mature NGF (PubMed:24908487).
Can also bind mature NGF and BDNF (By similarity).
Each chain in the receptor dimer interacts (via extracellular domain) with an NGF dimer (in vitro) (By similarity).
Interacts with the precursor forms of BDNF (proBDNF) and NTF3 (proNT3) (PubMed:24908487).
The cytoplasmic region of the heterodimer formed by NGFR and SORCS2 binds TRIO. ProNGF binding mediates dissociation of TRIO from the receptor complex (PubMed:22155786).
Interacts with SLC1A1. Interacts with VPS35. Interacts (via extracellular domain) with NTRK2 (via extracellular domain). Interacts with VPS35. Interacts (via extracellular domain) with GRIN2A (By similarity).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, repeat, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-36 | Disordered | ||||
Sequence: MAHRGPSRASKGPGPTARAPSPGAPPPPRSPRSRPL | ||||||
Compositional bias | 18-33 | Pro residues | ||||
Sequence: RAPSPGAPPPPRSPRS | ||||||
Region | 48-111 | Disordered | ||||
Sequence: AAGRSPEPGRLGPHAQLTRVPRSPPAGRAEPGGGEDRQARGTEPGAPGPSPGPAPGPGEDGAPA | ||||||
Repeat | 182-193 | BNR 1 | ||||
Sequence: WRSSDFGTSYTK | ||||||
Repeat | 232-243 | BNR 2 | ||||
Sequence: FLSADEGATFQK | ||||||
Repeat | 273-284 | BNR 3 | ||||
Sequence: YVSSDLGKKWTL | ||||||
Repeat | 468-479 | BNR 4 | ||||
Sequence: LITYNKGRDWDY | ||||||
Repeat | 545-556 | BNR 5 | ||||
Sequence: YITSDCGHTWRQ | ||||||
Repeat | 587-598 | BNR 6 | ||||
Sequence: KFSVDEGLTWST | ||||||
Domain | 786-876 | PKD | ||||
Sequence: SIQGEAVAVRPGEDVLFVVRQEQGDVLTTKYQVDLGDGFKAMYVNLTLTGEPIRHRYESPGIYRVSVRAENTAGHDEAVLFVQVNSPLQAL |
Sequence similarities
Belongs to the VPS10-related sortilin family. SORCS subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length1,159
- Mass (Da)128,152
- Last updated2010-05-18 v3
- Checksum61DEE8EF428B8B40
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
H0Y9I2 | H0Y9I2_HUMAN | SORCS2 | 101 |
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 18-33 | Pro residues | ||||
Sequence: RAPSPGAPPPPRSPRS | ||||||
Sequence conflict | 716 | in Ref. 3; BAA92567 | ||||
Sequence: S → P |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AC004169 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC080003 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC097382 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC112710 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC116316 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AF286190 EMBL· GenBank· DDBJ | AAL04014.1 EMBL· GenBank· DDBJ | mRNA | ||
AB037750 EMBL· GenBank· DDBJ | BAA92567.1 EMBL· GenBank· DDBJ | mRNA |