SORC2_MOUSE
ID SORC2_MOUSE Reviewed; 1159 AA.
AC Q9EPR5; B2RSI2; B2RSI4;
DT 13-DEC-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=VPS10 domain-containing receptor SorCS2;
DE Contains:
DE RecName: Full=SorCS2 122 kDa chain {ECO:0000305|PubMed:22155786};
DE Contains:
DE RecName: Full=SorCS2 104 kDa chain {ECO:0000305|PubMed:22155786};
DE Contains:
DE RecName: Full=SorCS2 18 kDa chain {ECO:0000305|PubMed:22155786};
DE Flags: Precursor;
GN Name=Sorcs2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6J;
RX PubMed=11165493; DOI=10.1016/s0925-4773(00)00523-2;
RA Rezgaoui M., Hermey G., Riedel I.B., Hampe W., Schaller H.C.,
RA Hermans-Borgmeyer I.;
RT "Identification of SorCS2, a novel member of the VPS10 domain containing
RT receptor family, prominently expressed in the developing mouse brain.";
RL Mech. Dev. 100:335-338(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-830.
RC TISSUE=Myoblast;
RX PubMed=19656770; DOI=10.1074/mcp.m900195-mcp200;
RA Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D.,
RA Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B.;
RT "The mouse C2C12 myoblast cell surface N-linked glycoproteome:
RT identification, glycosite occupancy, and membrane orientation.";
RL Mol. Cell. Proteomics 8:2555-2569(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, INTERACTION WITH NGF AND NGFR, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=22155786; DOI=10.1126/scisignal.2002060;
RA Deinhardt K., Kim T., Spellman D.S., Mains R.E., Eipper B.A., Neubert T.A.,
RA Chao M.V., Hempstead B.L.;
RT "Neuronal growth cone retraction relies on proneurotrophin receptor
RT signaling through Rac.";
RL Sci. Signal. 4:RA82-RA82(2011).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH NGFR, PROTEOLYTIC
RP CLEAVAGE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=24908487; DOI=10.1016/j.neuron.2014.04.022;
RA Glerup S., Olsen D., Vaegter C.B., Gustafsen C., Sjoegaard S.S., Hermey G.,
RA Kjolby M., Molgaard S., Ulrichsen M., Boggild S., Skeldal S.,
RA Fjorback A.N., Nyengaard J.R., Jacobsen J., Bender D., Bjarkam C.R.,
RA Soerensen E.S., Fuechtbauer E.M., Eichele G., Madsen P., Willnow T.E.,
RA Petersen C.M., Nykjaer A.;
RT "SorCS2 regulates dopaminergic wiring and is processed into an apoptotic
RT two-chain receptor in peripheral glia.";
RL Neuron 82:1074-1087(2014).
RN [8]
RP FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH NGFR AND NTRK2,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=27457814; DOI=10.1038/mp.2016.108;
RA Glerup S., Bolcho U., Moelgaard S., Boeggild S., Vaegter C.B., Smith A.H.,
RA Nieto-Gonzalez J.L., Ovesen P.L., Pedersen L.F., Fjorback A.N., Kjolby M.,
RA Login H., Holm M.M., Andersen O.M., Nyengaard J.R., Willnow T.E.,
RA Jensen K., Nykjaer A.;
RT "SorCS2 is required for BDNF-dependent plasticity in the hippocampus.";
RL Mol. Psychiatry 21:1740-1751(2016).
RN [9]
RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, INTERACTION WITH
RP VPS35 AND GRIN2A, AND TISSUE SPECIFICITY.
RX PubMed=28469074; DOI=10.1172/jci.insight.88995;
RA Ma Q., Yang J., Milner T.A., Vonsattel J.G., Palko M.E., Tessarollo L.,
RA Hempstead B.L.;
RT "SorCS2-mediated NR2A trafficking regulates motor deficits in Huntington's
RT disease.";
RL JCI Insight 2:0-0(2017).
RN [10]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=28346477; DOI=10.1371/journal.pgen.1006692;
RA Forge A., Taylor R.R., Dawson S.J., Lovett M., Jagger D.J.;
RT "Disruption of SorCS2 reveals differences in the regulation of
RT stereociliary bundle formation between hair cell types in the inner ear.";
RL PLoS Genet. 13:E1006692-E1006692(2017).
RN [11]
RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=29909994; DOI=10.1016/j.neuron.2018.05.024;
RA Giza J.I., Kim J., Meyer H.C., Anastasia A., Dincheva I., Zheng C.I.,
RA Lopez K., Bains H., Yang J., Bracken C., Liston C., Jing D.,
RA Hempstead B.L., Lee F.S.;
RT "The BDNF Val66Met Prodomain Disassembles Dendritic Spines Altering Fear
RT Extinction Circuitry and Behavior.";
RL Neuron 99:163-178(2018).
RN [12]
RP FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH SLC1A1, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=30840898; DOI=10.1016/j.celrep.2019.02.027;
RA Malik A.R., Szydlowska K., Nizinska K., Asaro A., van Vliet E.A., Popp O.,
RA Dittmar G., Fritsche-Guenther R., Kirwan J.A., Nykjaer A., Lukasiuk K.,
RA Aronica E., Willnow T.E.;
RT "SorCS2 Controls Functional Expression of Amino Acid Transporter EAAT3 and
RT Protects Neurons from Oxidative Stress and Epilepsy-Induced Pathology.";
RL Cell Rep. 26:2792-2804(2019).
RN [13] {ECO:0007744|PDB:6FFY, ECO:0007744|PDB:6FG9}
RP X-RAY CRYSTALLOGRAPHY (3.90 ANGSTROMS) OF 116-1077 IN COMPLEX WITH NGF,
RP SUBUNIT, INTERACTION WITH NGF AND BDNF, SUBCELLULAR LOCATION, GLYCOSYLATION
RP AT ASN-158; ASN-328; ASN-362; ASN-600; ASN-830; ASN-891 AND ASN-902,
RP DISULFIDE BONDS, AND MUTAGENESIS OF PHE-630.
RX PubMed=30061605; DOI=10.1038/s41467-018-05405-z;
RA Leloup N., Chataigner L.M.P., Janssen B.J.C.;
RT "Structural insights into SorCS2-Nerve Growth Factor complex formation.";
RL Nat. Commun. 9:2979-2979(2018).
CC -!- FUNCTION: The heterodimer formed by NGFR and SORCS2 functions as
CC receptor for the precursor forms of NGF (proNGF) and BDNF (proBDNF)
CC (PubMed:22155786, PubMed:24908487, PubMed:27457814, PubMed:29909994).
CC ProNGF and proBDNF binding both promote axon growth cone collapse (in
CC vitro) (PubMed:24908487). Plays a role in the regulation of dendritic
CC spine density in hippocampus neurons (PubMed:29909994). Required for
CC normal neurite branching and extension in response to BDNF
CC (PubMed:27457814, PubMed:29909994). Plays a role in BDNF-dependent
CC hippocampal synaptic plasticity (PubMed:29909994, PubMed:27457814).
CC Together with NGFR and NTRK2, is required both for BDNF-mediated
CC synaptic long-term depression and long-term potentiation
CC (PubMed:27457814). ProNGF binding promotes dissociation of TRIO from
CC the heterodimer, which leads to inactivation of RAC1 and/or RAC2 and
CC subsequent reorganization of the actin cytoskeleton (By similarity).
CC Together with the retromer complex subunit VPS35, required for normal
CC expression of GRIN2A at synapses and dendritic cell membranes
CC (PubMed:28469074). Required for normal expression of the amino acid
CC transporter SLC1A1 at the cell membrane, and thereby contributes to
CC protect cells against oxidative stress (PubMed:30840898).
CC {ECO:0000250|UniProtKB:Q96PQ0, ECO:0000269|PubMed:22155786,
CC ECO:0000269|PubMed:24908487, ECO:0000269|PubMed:27457814,
CC ECO:0000269|PubMed:28469074, ECO:0000269|PubMed:29909994,
CC ECO:0000269|PubMed:30840898}.
CC -!- SUBUNIT: Homodimer (in vitro) (PubMed:30061605). Heterodimer with NGFR
CC (PubMed:22155786, PubMed:24908487, PubMed:27457814). The extracellular
CC domains of the heterodimer bind the precursor form of NGF (proNGF)
CC (PubMed:22155786). Can also bind mature NGF and BDNF. Each chain in the
CC receptor dimer interacts (via extracellular domain) with an NGF dimer
CC (in vitro) (PubMed:30061605). Interacts with the precursor forms of
CC BDNF (proBDNF) and NTF3 (proNT3) (By similarity). The cytoplasmic
CC region of the heterodimer formed by NGFR and SORCS2 binds TRIO. ProNGF
CC binding mediates dissociation of TRIO from the receptor complex (By
CC similarity). Interacts with SLC1A1 (PubMed:30840898). Interacts with
CC VPS35. Interacts (via extracellular domain) with NTRK2 (via
CC extracellular domain) (PubMed:27457814). Interacts with VPS35.
CC Interacts (via extracellular domain) with GRIN2A (PubMed:28469074).
CC {ECO:0000250|UniProtKB:Q96PQ0, ECO:0000269|PubMed:22155786,
CC ECO:0000269|PubMed:24908487, ECO:0000269|PubMed:27457814,
CC ECO:0000269|PubMed:28469074, ECO:0000269|PubMed:30061605,
CC ECO:0000269|PubMed:30840898}.
CC -!- INTERACTION:
CC Q9EPR5; Q9Z0W1: Ngfr; NbExp=4; IntAct=EBI-9915438, EBI-4411273;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22155786,
CC ECO:0000269|PubMed:24908487, ECO:0000269|PubMed:27457814,
CC ECO:0000269|PubMed:30840898, ECO:0000305|PubMed:30061605}; Single-pass
CC type I membrane protein {ECO:0000305|PubMed:30061605}. Cell projection
CC {ECO:0000269|PubMed:24908487}. Cytoplasmic vesicle membrane
CC {ECO:0000269|PubMed:28469074, ECO:0000269|PubMed:30840898}; Single-pass
CC type I membrane protein {ECO:0000250|UniProtKB:Q96PQ0}. Early endosome
CC membrane {ECO:0000269|PubMed:30840898}. Recycling endosome membrane
CC {ECO:0000269|PubMed:30840898}. Synapse, synaptosome
CC {ECO:0000269|PubMed:30840898}. Perikaryon
CC {ECO:0000269|PubMed:28469074}. Cell projection, dendrite
CC {ECO:0000269|PubMed:27457814}. Cell projection, dendritic spine
CC {ECO:0000269|PubMed:29909994}. Synapse {ECO:0000269|PubMed:27457814}.
CC Postsynaptic density membrane {ECO:0000269|PubMed:27457814}.
CC -!- TISSUE SPECIFICITY: Detected in Purkinje cells and pyramidal neurons in
CC brain cortex, cerebellum, dentate gyrus, striatum and hippocampus, and
CC in glia cells in dorsal root ganglia (DRG) (PubMed:24908487,
CC PubMed:27457814, PubMed:28469074, PubMed:30840898). Not detected in
CC neurons from the dorsal root ganglia (PubMed:24908487). Detected in
CC hair cells and supporting cells in the organ of Corti, utricuar maculae
CC and cristae (at protein level) (PubMed:28346477). Detected in brain,
CC lung and testis (PubMed:11165493). Detected in the inner ear in
CC neonates (PubMed:28346477). {ECO:0000269|PubMed:11165493,
CC ECO:0000269|PubMed:24908487, ECO:0000269|PubMed:27457814,
CC ECO:0000269|PubMed:28346477, ECO:0000269|PubMed:28469074,
CC ECO:0000269|PubMed:30840898}.
CC -!- DEVELOPMENTAL STAGE: Expression is highest in developing brain.
CC Transiently expressed in all 3 germ layers (PubMed:11165493). Detected
CC in midbrain, spinal cord, heart and lung at 15.5 dpc (PubMed:24908487).
CC Coexpressed with NGFR in neurons in the ventral part of the hippocampus
CC CA1 region at 23 and 30 days after birth. The number of neurons that
CC coexpress SORCS2 and NGFR is increased 30 days after birth. SORCS2 and
CC NGFR are no longer coexpressed in hippocampus neurons in 60 day old
CC adults (PubMed:29909994). {ECO:0000269|PubMed:11165493,
CC ECO:0000269|PubMed:24908487, ECO:0000269|PubMed:29909994}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q96PQ0}.
CC -!- PTM: Proteolytic cleavage removes a propeptide, giving rise to a 122
CC kDa chain that includes a cytoplasmic tail. Further cleavage gives rise
CC to a 104 kDa chain that lacks the cytoplasmic tail, and a membrane-
CC bound 18 kDa chain (PubMed:24908487). The 104 kDa chain remains bound
CC to the 18 kDa chain (By similarity). {ECO:0000250|UniProtKB:Q96PQ0,
CC ECO:0000269|PubMed:24908487}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile and display no
CC obvious phenotype, but their neurons do not display growth cone
CC collapse in response to proBDNF (PubMed:24908487, PubMed:29909994).
CC Cultured neurons from mutant mice display longer neurites than wild-
CC type neurons, and the frontal cortex of 12 week old mice is
CC hyperinnervated with fibers from tyrosine hydroxylase-positive neurons
CC (PubMed:24908487, PubMed:29909994). Mutant mice display mildly
CC increased spontaneous locomotor activity; contrary to wild-type,
CC treatment with amphetamine decreases their locomotor activity. After
CC sciatic nerve injury, 2 day old and adult mice show discreased Schwann
CC cell apoptosis distal to the lesion (PubMed:24908487). Mutant mice show
CC increased mortality after seizures caused by repeated treatments with
CC the convulsant pentylenetetrazol (PTZ). Hippocampus neurons from mutant
CC mice display increased levels of oxidative stress and increased
CC apoptosis (PubMed:30840898). Mutant mice display subtle behavorial
CC defects, with hyperactivity, altered acquisition of spatial memory, but
CC a normal startle response to noise (PubMed:27457814). Heterozygous mice
CC have normal body weight and motor skills, but combination with a mouse
CC model for Huntington disease (HD) gives rise to increased severity of
CC impaired motor skills (PubMed:28469074). After a cross of mice carrying
CC a Cre construct under the control of the Tek promoter with mice
CC carrying a floxed Nppc gene a subset of the offspring displayed
CC behavorial defects, including hyperactivity and hanging from cage tops.
CC A subset (11 out of 33 mice) displayed strongly reduced body weight and
CC profound deafness, with defects in the organization of the outer and
CC inner hair cell bundles in the organ of Corti. Analysis of the genomic
CC DNA from deaf mice showed that in 13 cases, these mice had the Cre
CC construct inserted into the first intron of the Sorcs2 gene, but in 21
CC cases, the insertion had occured in an Ig kappa locus
CC (PubMed:28346477). {ECO:0000269|PubMed:24908487,
CC ECO:0000269|PubMed:27457814, ECO:0000269|PubMed:28346477,
CC ECO:0000269|PubMed:28469074, ECO:0000269|PubMed:29909994,
CC ECO:0000269|PubMed:30840898}.
CC -!- MISCELLANEOUS: SORCS2 expression is decreased after the onset of
CC symptoms in mouse models for Huntington disease (HD). SORCS2 does not
CC interact with wild-type HTT, but does interact with mutant HTT
CC containing a long polyglutamine stretch. {ECO:0000269|PubMed:28469074}.
CC -!- SIMILARITY: Belongs to the VPS10-related sortilin family. SORCS
CC subfamily. {ECO:0000305}.
CC -!- CAUTION: Gene disruption gives rise to contradictory results
CC (PubMed:24908487, PubMed:27457814, PubMed:28469074, PubMed:28346477,
CC PubMed:30840898). The majority of studies report normal body weight,
CC normal startle responses to noise and relatively minor behavorial
CC defects (PubMed:24908487, PubMed:27457814, PubMed:28469074,
CC PubMed:30840898). Another publication finds that gene disruption gives
CC rise to mice with strongly reduced body weight and profound deafness.
CC Gene disruption was due to random insertion of a Cre construct under
CC the control of the TEK promoter. Analysis of the genomic DNA showed
CC that in 21 cases the Cre construct had inserted in an Ig kappa locus,
CC and in 13 cases the construct had inserted into the first intron of the
CC SORCS2 gene, leading to strongly reduced SORCS2 expression
CC (PubMed:28346477). The reasons for these discrepancies are not clear,
CC but may be due to the way the experiments were done. The fact that an
CC identical phenotype was found when the Cre construct under the control
CC of the TEK promoter had inserted in an Ig kappa locus suggests that
CC there are additional, unidentified causes that play a role in the
CC observed defects. {ECO:0000269|PubMed:24908487,
CC ECO:0000269|PubMed:27457814, ECO:0000269|PubMed:28346477,
CC ECO:0000269|PubMed:28469074, ECO:0000269|PubMed:30840898,
CC ECO:0000305|PubMed:28346477}.
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DR EMBL; AY004316; AAF88135.1; -; mRNA.
DR EMBL; CH466524; EDL37502.1; -; Genomic_DNA.
DR EMBL; BC138873; AAI38874.1; -; mRNA.
DR EMBL; BC138875; AAI38876.1; -; mRNA.
DR CCDS; CCDS19237.1; -.
DR RefSeq; NP_112151.2; NM_030889.2.
DR PDB; 6FFY; X-ray; 3.90 A; A=116-1077.
DR PDB; 6FG9; X-ray; 4.20 A; A/B=116-1077.
DR PDBsum; 6FFY; -.
DR PDBsum; 6FG9; -.
DR AlphaFoldDB; Q9EPR5; -.
DR SMR; Q9EPR5; -.
DR BioGRID; 219891; 4.
DR IntAct; Q9EPR5; 3.
DR STRING; 10090.ENSMUSP00000041828; -.
DR GlyConnect; 2824; 1 N-Linked glycan (1 site).
DR GlyGen; Q9EPR5; 8 sites, 1 N-linked glycan (1 site).
DR iPTMnet; Q9EPR5; -.
DR PhosphoSitePlus; Q9EPR5; -.
DR MaxQB; Q9EPR5; -.
DR PaxDb; Q9EPR5; -.
DR PRIDE; Q9EPR5; -.
DR ProteomicsDB; 261112; -.
DR Antibodypedia; 22709; 85 antibodies from 18 providers.
DR DNASU; 81840; -.
DR Ensembl; ENSMUST00000037370; ENSMUSP00000041828; ENSMUSG00000029093.
DR GeneID; 81840; -.
DR KEGG; mmu:81840; -.
DR UCSC; uc008xek.1; mouse.
DR CTD; 57537; -.
DR MGI; MGI:1932289; Sorcs2.
DR VEuPathDB; HostDB:ENSMUSG00000029093; -.
DR eggNOG; KOG3511; Eukaryota.
DR GeneTree; ENSGT01030000234563; -.
DR HOGENOM; CLU_010702_0_0_1; -.
DR InParanoid; Q9EPR5; -.
DR OMA; SDKRLMA; -.
DR OrthoDB; 1046610at2759; -.
DR PhylomeDB; Q9EPR5; -.
DR TreeFam; TF324918; -.
DR BioGRID-ORCS; 81840; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Sorcs2; mouse.
DR PRO; PR:Q9EPR5; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9EPR5; protein.
DR Bgee; ENSMUSG00000029093; Expressed in CA2 field of hippocampus and 238 other tissues.
DR ExpressionAtlas; Q9EPR5; baseline and differential.
DR Genevisible; Q9EPR5; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0014069; C:postsynaptic density; IDA:UniProtKB.
DR GO; GO:0098839; C:postsynaptic density membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0055038; C:recycling endosome membrane; IDA:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; IMP:UniProtKB.
DR GO; GO:0060292; P:long-term synaptic depression; IMP:UniProtKB.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR000601; PKD_dom.
DR InterPro; IPR035986; PKD_dom_sf.
DR InterPro; IPR031777; Sortilin_C.
DR InterPro; IPR031778; Sortilin_N.
DR InterPro; IPR006581; VPS10.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR Pfam; PF15902; Sortilin-Vps10; 1.
DR Pfam; PF15901; Sortilin_C; 1.
DR SMART; SM00602; VPS10; 1.
DR SUPFAM; SSF49299; SSF49299; 1.
DR PROSITE; PS50093; PKD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cell projection; Cytoplasmic vesicle;
KW Disulfide bond; Endosome; Glycoprotein; Membrane;
KW Postsynaptic cell membrane; Reference proteome; Repeat; Signal; Synapse;
KW Synaptosome; Transmembrane; Transmembrane helix.
FT SIGNAL 1..49
FT /evidence="ECO:0000255"
FT CHAIN 50..1159
FT /note="VPS10 domain-containing receptor SorCS2"
FT /id="PRO_0000033173"
FT CHAIN 118..1030
FT /note="SorCS2 104 kDa chain"
FT /evidence="ECO:0000305|PubMed:22155786"
FT /id="PRO_0000447472"
FT CHAIN 1031..1159
FT /note="SorCS2 18 kDa chain"
FT /evidence="ECO:0000305|PubMed:22155786"
FT /id="PRO_0000447473"
FT CHAIN ?..1159
FT /note="SorCS2 122 kDa chain"
FT /evidence="ECO:0000305|PubMed:22155786"
FT /id="PRO_0000447474"
FT TOPO_DOM 50..1078
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1079..1099
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1100..1159
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REPEAT 182..193
FT /note="BNR 1"
FT REPEAT 232..243
FT /note="BNR 2"
FT REPEAT 273..284
FT /note="BNR 3"
FT REPEAT 468..479
FT /note="BNR 4"
FT REPEAT 545..556
FT /note="BNR 5"
FT REPEAT 587..598
FT /note="BNR 6"
FT DOMAIN 786..876
FT /note="PKD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00151"
FT REGION 52..120
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 117..118
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q96PQ0"
FT SITE 1030..1031
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q96PQ0"
FT CARBOHYD 158
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:30061605,
FT ECO:0007744|PDB:6FG9"
FT CARBOHYD 328
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:30061605,
FT ECO:0007744|PDB:6FG9"
FT CARBOHYD 362
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:30061605,
FT ECO:0007744|PDB:6FG9"
FT CARBOHYD 600
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:30061605,
FT ECO:0007744|PDB:6FG9"
FT CARBOHYD 830
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19656770,
FT ECO:0000269|PubMed:30061605, ECO:0007744|PDB:6FG9"
FT CARBOHYD 891
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:30061605,
FT ECO:0007744|PDB:6FG9"
FT CARBOHYD 902
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:30061605,
FT ECO:0007744|PDB:6FG9"
FT DISULFID 324..329
FT /evidence="ECO:0000269|PubMed:30061605,
FT ECO:0007744|PDB:6FFY, ECO:0007744|PDB:6FG9"
FT DISULFID 494..499
FT /evidence="ECO:0000269|PubMed:30061605,
FT ECO:0007744|PDB:6FFY, ECO:0007744|PDB:6FG9"
FT DISULFID 649..684
FT /evidence="ECO:0000269|PubMed:30061605,
FT ECO:0007744|PDB:6FFY, ECO:0007744|PDB:6FG9"
FT DISULFID 667..699
FT /evidence="ECO:0000269|PubMed:30061605,
FT ECO:0007744|PDB:6FFY, ECO:0007744|PDB:6FG9"
FT DISULFID 701..760
FT /evidence="ECO:0000269|PubMed:30061605,
FT ECO:0007744|PDB:6FFY, ECO:0007744|PDB:6FG9"
FT DISULFID 708..725
FT /evidence="ECO:0000269|PubMed:30061605,
FT ECO:0007744|PDB:6FFY, ECO:0007744|PDB:6FG9"
FT DISULFID 740..775
FT /evidence="ECO:0000269|PubMed:30061605,
FT ECO:0007744|PDB:6FFY, ECO:0007744|PDB:6FG9"
FT MUTAGEN 630
FT /note="F->N: Introduces an N-glycosylation site and
FT disrupts interaction with NGF and BDNF."
FT /evidence="ECO:0000269|PubMed:30061605"
FT CONFLICT 252
FT /note="M -> T (in Ref. 1; AAF88135 and 3; AAI38876)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1159 AA; 128902 MW; 551F42E2BFEFD457 CRC64;
MAHRGPPSAP KRPGPTAPDR SFQALLPPCW PRSWPLLLLL LVLVAACGAM GRSPQPGRQG
PGVQITRLLP AGRTESGDRK DPQARESEPS VPGLGPGSAS GPSTDGAPAP GKGRRARAVP
VAGAASASRA QVSLISTSFV LKGDATHNQA MVHWTGENSS VILILTKYYH ADMGKVLESS
LWRSSDFGTT YTKLTLQPGV TTVIDNFYIC PANKRKIILV SSSLGDREQS LFLSTDEGAT
FQKYPVPFLV EMLLFHPKEE DKVLAYTKDS KLYVSSDLGK KWTLLQERVT KDHVFWAVSG
VDDDPNLVHV EAQDLSGGYR YYTCLIYNCS AQPHIAPFSG PIDRGSLTVQ DEYIFLKATS
TNRTKYYVSY RRSDFVLMKL PKYALPKDLQ IISTDEQQVF VAVQEWNQVD TYNLYQSDLR
GVRYSLVLEN VRSSRQAEEN VVIDILEVRG VKGVFLANQK VDGKVTTVIT YNKGRDWDYL
RPPSTDMNGK PTNCQPPDCY LHLHLRWADN PYVSGTVHTK DTAPGLIMGA GNLGSQLVEY
KEEMYITSDC GHTWRQVFEE EHHVLYLDHG GVIAAIKDTS IPLKILKFSV DEGHTWSTHN
FTSTSVFVDG LLSEPGDETL VMTVFGHISF RSDWELVKVD FRPSFPRQCG EDDYSSWDLT
DLQGDHCIMG QQRSYRKRKS TSWCVKGRSF TSALTSRVCK CRDSDFLCDY GFERSSSSES
TANKCSANFW FNPLSPPEDC VLGQTYTSSL GYRKVVSNVC EGGVDLQQSP VQLQCPLQAP
RGLQVSIRGE AVAVRPREDV LFVVRQEQGD VLTTKYQVDL GDGFKAMYVN LTLTGEPIRH
HYESPGIYRV SVRAENMAGH DEAVLFVQVN SPLQALYLEV VPVIGVNQEV NLTAVLLPLN
PNLTVFYWWI GHSLQPLLSL DNSVTTKFTD AGDVRVTVQA ACGNSVLQDS RLVRVLDQFQ
VVPLRFSREL DTFNPNTPEW REDVGLVVTR LLSKETSIPE ELLVTVVKPG LPTIADLYVL
LPLPRPTRKR SLTSDKRLAA VQQALNSHRI SFILRGGLRI LVELRDTDTG PQRPGGSGGY
WAVVVLFVIG LFAVGAFILY KFKRKRPGRT VYAQMHNEKE QEMTSPVSHS EDAQSTMQGN
HSGVVLSINS REMHSYLVG
