ID   SORC3_HUMAN             Reviewed;        1222 AA.
AC   Q9UPU3; Q5VXF9; Q9NQJ2;
DT   13-DEC-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2002, sequence version 2.
DT   24-JAN-2024, entry version 173.
DE   RecName: Full=VPS10 domain-containing receptor SorCS3;
DE   Flags: Precursor;
GN   Name=SORCS3; Synonyms=KIAA1059;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Brain;
RX   PubMed=11499680; DOI=10.1007/s004390100504;
RA   Hampe W., Rezgaoui M., Hermans-Borgmeyer I., Schaller H.C.;
RT   "The genes for the human VPS10 domain-containing receptors are large and
RT   contain many small exons.";
RL   Hum. Genet. 108:529-536(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA   Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA   Kotani H., Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XIV. The
RT   complete sequences of 100 new cDNA clones from brain which code for large
RT   proteins in vitro.";
RL   DNA Res. 6:197-205(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164054; DOI=10.1038/nature02462;
RA   Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA   Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA   Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA   Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA   Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA   Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA   Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA   Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA   Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA   Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA   Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA   Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA   McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA   Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA   Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA   Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA   Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA   Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA   Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA   Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA   Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 10.";
RL   Nature 429:375-381(2004).
CC   -!- INTERACTION:
CC       Q9UPU3; P54253: ATXN1; NbExp=3; IntAct=EBI-7484437, EBI-930964;
CC       Q9UPU3; Q9BRQ0: PYGO2; NbExp=3; IntAct=EBI-7484437, EBI-932471;
CC   -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC   -!- TISSUE SPECIFICITY: Highly expressed in brain.
CC   -!- SIMILARITY: Belongs to the VPS10-related sortilin family. SORCS
CC       subfamily. {ECO:0000305}.
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DR   EMBL; AB028982; BAA83011.2; -; mRNA.
DR   EMBL; AL161646; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL353900; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL358949; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL365449; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL445492; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL596118; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS7558.1; -.
DR   RefSeq; NP_055793.1; NM_014978.2.
DR   AlphaFoldDB; Q9UPU3; -.
DR   SMR; Q9UPU3; -.
DR   BioGRID; 116635; 5.
DR   IntAct; Q9UPU3; 3.
DR   MINT; Q9UPU3; -.
DR   STRING; 9606.ENSP00000358715; -.
DR   TCDB; 9.A.63.1.4; the retromer-dependent vacuolar protein sorting (r-vps) family.
DR   GlyCosmos; Q9UPU3; 8 sites, No reported glycans.
DR   GlyGen; Q9UPU3; 8 sites.
DR   iPTMnet; Q9UPU3; -.
DR   PhosphoSitePlus; Q9UPU3; -.
DR   BioMuta; SORCS3; -.
DR   DMDM; 27151703; -.
DR   EPD; Q9UPU3; -.
DR   MassIVE; Q9UPU3; -.
DR   PaxDb; 9606-ENSP00000358715; -.
DR   PeptideAtlas; Q9UPU3; -.
DR   ProteomicsDB; 85445; -.
DR   Antibodypedia; 31628; 67 antibodies from 15 providers.
DR   DNASU; 22986; -.
DR   Ensembl; ENST00000369701.8; ENSP00000358715.3; ENSG00000156395.14.
DR   GeneID; 22986; -.
DR   KEGG; hsa:22986; -.
DR   MANE-Select; ENST00000369701.8; ENSP00000358715.3; NM_014978.3; NP_055793.1.
DR   UCSC; uc001kyi.1; human.
DR   AGR; HGNC:16699; -.
DR   CTD; 22986; -.
DR   DisGeNET; 22986; -.
DR   GeneCards; SORCS3; -.
DR   HGNC; HGNC:16699; SORCS3.
DR   HPA; ENSG00000156395; Group enriched (adrenal gland, brain).
DR   MIM; 606285; gene.
DR   neXtProt; NX_Q9UPU3; -.
DR   OpenTargets; ENSG00000156395; -.
DR   PharmGKB; PA134949387; -.
DR   VEuPathDB; HostDB:ENSG00000156395; -.
DR   eggNOG; KOG3511; Eukaryota.
DR   GeneTree; ENSGT01030000234563; -.
DR   HOGENOM; CLU_010702_0_0_1; -.
DR   InParanoid; Q9UPU3; -.
DR   OMA; RRNDGNC; -.
DR   OrthoDB; 5840at2759; -.
DR   PhylomeDB; Q9UPU3; -.
DR   TreeFam; TF324918; -.
DR   PathwayCommons; Q9UPU3; -.
DR   SignaLink; Q9UPU3; -.
DR   BioGRID-ORCS; 22986; 10 hits in 1151 CRISPR screens.
DR   ChiTaRS; SORCS3; human.
DR   GenomeRNAi; 22986; -.
DR   Pharos; Q9UPU3; Tbio.
DR   PRO; PR:Q9UPU3; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   RNAct; Q9UPU3; Protein.
DR   Bgee; ENSG00000156395; Expressed in ventricular zone and 86 other cell types or tissues.
DR   ExpressionAtlas; Q9UPU3; baseline and differential.
DR   GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR   GO; GO:0016020; C:membrane; NAS:UniProtKB.
DR   GO; GO:0098839; C:postsynaptic density membrane; IEA:Ensembl.
DR   GO; GO:0008188; F:neuropeptide receptor activity; NAS:UniProtKB.
DR   GO; GO:0007612; P:learning; IEA:Ensembl.
DR   GO; GO:0007613; P:memory; IEA:Ensembl.
DR   GO; GO:0007218; P:neuropeptide signaling pathway; NAS:UniProtKB.
DR   GO; GO:0099170; P:postsynaptic modulation of chemical synaptic transmission; IEA:Ensembl.
DR   GO; GO:1900452; P:regulation of long-term synaptic depression; IEA:Ensembl.
DR   Gene3D; 2.10.70.80; -; 1.
DR   Gene3D; 3.30.60.270; -; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 1.
DR   Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 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   PANTHER; PTHR12106; SORTILIN RELATED; 1.
DR   PANTHER; PTHR12106:SF10; VPS10 DOMAIN-CONTAINING RECEPTOR SORCS3; 1.
DR   Pfam; PF00801; PKD; 1.
DR   Pfam; PF15902; Sortilin-Vps10; 1.
DR   Pfam; PF15901; Sortilin_C; 1.
DR   SMART; SM00602; VPS10; 1.
DR   SUPFAM; SSF110296; Oligoxyloglucan reducing end-specific cellobiohydrolase; 1.
DR   SUPFAM; SSF49299; PKD domain; 2.
DR   PROSITE; PS50093; PKD; 1.
DR   Genevisible; Q9UPU3; HS.
PE   1: Evidence at protein level;
KW   Glycoprotein; Membrane; Reference proteome; Repeat; Signal; Transmembrane;
KW   Transmembrane helix.
FT   SIGNAL          1..33
FT                   /evidence="ECO:0000255"
FT   CHAIN           34..1222
FT                   /note="VPS10 domain-containing receptor SorCS3"
FT                   /id="PRO_0000033174"
FT   TOPO_DOM        34..1125
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1126..1146
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1147..1222
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REPEAT          231..242
FT                   /note="BNR 1"
FT   REPEAT          279..290
FT                   /note="BNR 2"
FT   REPEAT          320..331
FT                   /note="BNR 3"
FT   REPEAT          515..526
FT                   /note="BNR 4"
FT   REPEAT          592..603
FT                   /note="BNR 5"
FT   REPEAT          634..645
FT                   /note="BNR 6"
FT   DOMAIN          827..917
FT                   /note="PKD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00151"
FT   REGION          40..70
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          87..180
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        159..173
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        207
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        456
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        789
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        800
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        840
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        932
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        953
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1065
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   1222 AA;  135755 MW;  57671F993B09D597 CRC64;
     MEAARTERPA GRPGAPLVRT GLLLLSTWVL AGAEITWDAT GGPGRPAAPA SRPPALSPLS
     PRAVASQWPE ELASARRAAV LGRRAGPELL PQQGGGRGGE MQVEAGGTSP AGERRGRGIP
     APAKLGGARR SRRAQPPITQ ERGDAWATAP ADGSRGSRPL AKGSREEVKA PRAGGSAAED
     LRLPSTSFAL TGDSAHNQAM VHWSGHNSSV ILILTKLYDF NLGSVTESSL WRSTDYGTTY
     EKLNDKVGLK TVLSYLYVNP TNKRKIMLLS DPEMESSILI SSDEGATYQK YRLTFYIQSL
     LFHPKQEDWV LAYSLDQKLY SSMDFGRRWQ LMHERITPNR FYWSVAGLDK EADLVHMEVR
     TTDGYAHYLT CRIQECAETT RSGPFARSID ISSLVVQDEY IFIQVTTSGR ASYYVSYRRE
     AFAQIKLPKY SLPKDMHIIS TDENQVFAAV QEWNQNDTYN LYISDTRGIY FTLAMENIKS
     SRGLMGNIII ELYEVAGIKG IFLANKKVDD QVKTYITYNK GRDWRLLQAP DVDLRGSPVH
     CLLPFCSLHL HLQLSENPYS SGRISSKETA PGLVVATGNI GPELSYTDIG VFISSDGGNT
     WRQIFDEEYN VWFLDWGGAL VAMKHTPLPV RHLWVSFDEG HSWDKYGFTS VPLFVDGALV
     EAGMETHIMT VFGHFSLRSE WQLVKVDYKS IFSRHCTKED YQTWHLLNQG EPCVMGERKI
     FKKRKPGAQC ALGRDHSGSV VSEPCVCANW DFECDYGYER HGESQCVPAF WYNPASPSKD
     CSLGQSYLNS TGYRRIVSNN CTDGLREKYT AKAQMCPGKA PRGLHVVTTD GRLVAEQGHN
     ATFIILMEEG DLQRTNIQLD FGDGIAVSYA NFSPIEDGIK HVYKSAGIFQ VTAYAENNLG
     SDTAVLFLHV VCPVEHVHLR VPFVAIRNKE VNISAVVWPS QLGTLTYFWW FGNSTKPLIT
     LDSSISFTFL AEGTDTITVQ VAAGNALIQD TKEIAVHEYF QSQLLSFSPN LDYHNPDIPE
     WRKDIGNVIK RALVKVTSVP EDQILIAVFP GLPTSAELFI LPPKNLTERR KGNEGDLEQI
     VETLFNALNQ NLVQFELKPG VQVIVYVTQL TLAPLVDSSA GHSSSAMLML LSVVFVGLAV
     FLIYKFKRKI PWINIYAQVQ HDKEQEMIGS VSQSENAPKI TLSDFTEPEE LLDKELDTRV
     IGGIATIANS ESTKEIPNCT SV
//