SORC1_HUMAN
ID SORC1_HUMAN Reviewed; 1168 AA.
AC Q8WY21; A2RRF4; Q59GG7; Q5JVT7; Q5JVT8; Q5VY14; Q86WQ1; Q86WQ2; Q9H1Y1;
AC Q9H1Y2;
DT 13-DEC-2002, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 3.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=VPS10 domain-containing receptor SorCS1;
DE Short=hSorCS;
DE Flags: Precursor;
GN Name=SORCS1; Synonyms=SORCS;
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] (ISOFORMS 1; 3 AND 4).
RX PubMed=12482870; DOI=10.1074/jbc.m210851200;
RA Hermey G., Keat S.J., Madsen P., Jacobsen C., Petersen C.M., Gliemann J.;
RT "Characterization of sorCS1, an alternatively spliced receptor with
RT completely different cytoplasmic domains that mediate different trafficking
RT in cells.";
RL J. Biol. Chem. 278:7390-7396(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
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).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [6]
RP REVIEW.
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 [7]
RP GLYCOSYLATION AT THR-68, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=23234360; DOI=10.1021/pr300963h;
RA Halim A., Ruetschi U., Larson G., Nilsson J.;
RT "LC-MS/MS characterization of O-glycosylation sites and glycan structures
RT of human cerebrospinal fluid glycoproteins.";
RL J. Proteome Res. 12:573-584(2013).
RN [8]
RP VARIANT [LARGE SCALE ANALYSIS] ASN-223.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- INTERACTION:
CC Q8WY21; Q99523: SORT1; NbExp=4; IntAct=EBI-21198627, EBI-1057058;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=B;
CC IsoId=Q8WY21-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8WY21-2; Sequence=VSP_006204;
CC Name=3; Synonyms=C;
CC IsoId=Q8WY21-3; Sequence=VSP_015140;
CC Name=4; Synonyms=A;
CC IsoId=Q8WY21-4; Sequence=VSP_015141;
CC -!- TISSUE SPECIFICITY: Detected in fetal and infant brain and in fetal
CC retina.
CC -!- PTM: O-glycosylated. {ECO:0000269|PubMed:23234360}.
CC -!- SIMILARITY: Belongs to the VPS10-related sortilin family. SORCS
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD92379.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF284756; AAL56667.1; -; mRNA.
DR EMBL; AY099452; AAM43811.1; -; mRNA.
DR EMBL; AY099453; AAM43812.1; -; mRNA.
DR EMBL; AB209142; BAD92379.1; ALT_INIT; mRNA.
DR EMBL; AL133395; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL160010; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356255; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356308; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL357333; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW49583.1; -; Genomic_DNA.
DR EMBL; BC131597; AAI31598.1; -; mRNA.
DR CCDS; CCDS7559.1; -. [Q8WY21-1]
DR RefSeq; NP_001013049.1; NM_001013031.2. [Q8WY21-2]
DR RefSeq; NP_001193498.1; NM_001206569.1. [Q8WY21-3]
DR RefSeq; NP_001193499.1; NM_001206570.1.
DR RefSeq; NP_001193500.1; NM_001206571.1. [Q8WY21-4]
DR RefSeq; NP_001193501.1; NM_001206572.1.
DR RefSeq; NP_443150.3; NM_052918.4. [Q8WY21-1]
DR AlphaFoldDB; Q8WY21; -.
DR SMR; Q8WY21; -.
DR BioGRID; 125367; 3.
DR IntAct; Q8WY21; 2.
DR STRING; 9606.ENSP00000263054; -.
DR TCDB; 9.A.63.1.5; the retromer-dependent vacuolar protein sorting (r-vps) family.
DR GlyGen; Q8WY21; 10 sites.
DR iPTMnet; Q8WY21; -.
DR PhosphoSitePlus; Q8WY21; -.
DR BioMuta; SORCS1; -.
DR DMDM; 66774216; -.
DR EPD; Q8WY21; -.
DR jPOST; Q8WY21; -.
DR MassIVE; Q8WY21; -.
DR PaxDb; Q8WY21; -.
DR PeptideAtlas; Q8WY21; -.
DR PRIDE; Q8WY21; -.
DR ProteomicsDB; 75119; -. [Q8WY21-1]
DR ProteomicsDB; 75120; -. [Q8WY21-2]
DR ProteomicsDB; 75121; -. [Q8WY21-3]
DR ProteomicsDB; 75122; -. [Q8WY21-4]
DR TopDownProteomics; Q8WY21-3; -. [Q8WY21-3]
DR Antibodypedia; 2334; 130 antibodies from 25 providers.
DR DNASU; 114815; -.
DR Ensembl; ENST00000263054.11; ENSP00000263054.5; ENSG00000108018.16. [Q8WY21-1]
DR GeneID; 114815; -.
DR KEGG; hsa:114815; -.
DR MANE-Select; ENST00000263054.11; ENSP00000263054.5; NM_052918.5; NP_443150.3.
DR UCSC; uc001kym.4; human. [Q8WY21-1]
DR CTD; 114815; -.
DR DisGeNET; 114815; -.
DR GeneCards; SORCS1; -.
DR HGNC; HGNC:16697; SORCS1.
DR HPA; ENSG00000108018; Tissue enhanced (brain, retina, thyroid gland).
DR MIM; 606283; gene.
DR neXtProt; NX_Q8WY21; -.
DR OpenTargets; ENSG00000108018; -.
DR PharmGKB; PA134861284; -.
DR VEuPathDB; HostDB:ENSG00000108018; -.
DR eggNOG; KOG3511; Eukaryota.
DR GeneTree; ENSGT01030000234563; -.
DR InParanoid; Q8WY21; -.
DR OMA; RGSSIHC; -.
DR OrthoDB; 1046610at2759; -.
DR PhylomeDB; Q8WY21; -.
DR TreeFam; TF324918; -.
DR PathwayCommons; Q8WY21; -.
DR SignaLink; Q8WY21; -.
DR BioGRID-ORCS; 114815; 7 hits in 1072 CRISPR screens.
DR ChiTaRS; SORCS1; human.
DR GenomeRNAi; 114815; -.
DR Pharos; Q8WY21; Tbio.
DR PRO; PR:Q8WY21; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q8WY21; protein.
DR Bgee; ENSG00000108018; Expressed in cortical plate and 126 other tissues.
DR ExpressionAtlas; Q8WY21; baseline and differential.
DR Genevisible; Q8WY21; HS.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0008188; F:neuropeptide receptor activity; NAS:UniProtKB.
DR GO; GO:0007218; P:neuropeptide signaling pathway; NAS:UniProtKB.
DR GO; GO:0006892; P:post-Golgi vesicle-mediated transport; IBA:GO_Central.
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; PF00801; PKD; 1.
DR Pfam; PF15902; Sortilin-Vps10; 1.
DR Pfam; PF15901; Sortilin_C; 1.
DR SMART; SM00602; VPS10; 1.
DR SUPFAM; SSF49299; SSF49299; 2.
DR PROSITE; PS50093; PKD; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Glycoprotein; Membrane; Reference proteome; Repeat;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..33
FT /evidence="ECO:0000255"
FT CHAIN 34..1168
FT /note="VPS10 domain-containing receptor SorCS1"
FT /id="PRO_0000033170"
FT TOPO_DOM 34..1099
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1100..1120
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1121..1168
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 208..219
FT /note="BNR 1"
FT REPEAT 256..267
FT /note="BNR 2"
FT REPEAT 492..503
FT /note="BNR 3"
FT REPEAT 569..580
FT /note="BNR 4"
FT REPEAT 611..622
FT /note="BNR 5"
FT DOMAIN 803..894
FT /note="PKD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00151"
FT REGION 38..69
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 89..150
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1129..1168
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 42..56
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 107..127
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 68
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:23234360"
FT CARBOHYD 184
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 352
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 433
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 765
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 776
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 816
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 847
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 908
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 929
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1125..1168
FT /note="RVALPSPPSPSTQPGDSSLRLQRARHATPPSTPKRGSAGAQYAI -> KIPG
FT INVYAQMQNEKEQEMISPVSHSESRPNVPQTELRRPGQLIDEKVESQLIGSISIVAENQ
FT STKEIPTYVNV (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_006204"
FT VAR_SEQ 1125..1168
FT /note="RVALPSPPSPSTQPGDSSLRLQRARHATPPSTPKRGSAGAQYAI -> KIPG
FT INVYAQMQNEKEQEMISPVSHSESRPNVPQTELRRPGQLIDEKVESQLIGK (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:12482870"
FT /id="VSP_015140"
FT VAR_SEQ 1125..1168
FT /note="RVALPSPPSPSTQPGDSSLRLQRARHATPPSTPKRGSAGAQYAI -> CVSL
FT YPRSPTPDLFLLPDRFRSMCYSDVHSSDGFY (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:12482870"
FT /id="VSP_015141"
FT VARIANT 223
FT /note="K -> N (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036374"
FT CONFLICT 231
FT /note="S -> G (in Ref. 1; AAL56667)"
FT /evidence="ECO:0000305"
FT CONFLICT 487
FT /note="N -> Y (in Ref. 1; AAL56667)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1168 AA; 129635 MW; BAF8D4FB87A4F998 CRC64;
MGKVGAGGGS QARLSALLAG AGLLILCAPG VCGGGSCCPS PHPSSAPRSA STPRGFSHQG
RPGRAPATPL PLVVRPLFSV APGDRALSLE RARGTGASMA VAARSGRRRR SGADQEKAER
GEGASRSPRG VLRDGGQQEP GTRERDPDKA TRFRMEELRL TSTTFALTGD SAHNQAMVHW
SGHNSSVILI LTKLYDYNLG SITESSLWRS TDYGTTYEKL NDKVGLKTIL SYLYVCPTNK
RKIMLLTDPE IESSLLISSD EGATYQKYRL NFYIQSLLFH PKQEDWILAY SQDQKLYSSA
EFGRRWQLIQ EGVVPNRFYW SVMGSNKEPD LVHLEARTVD GHSHYLTCRM QNCTEANRNQ
PFPGYIDPDS LIVQDHYVFV QLTSGGRPHY YVSYRRNAFA QMKLPKYALP KDMHVISTDE
NQVFAAVQEW NQNDTYNLYI SDTRGVYFTL ALENVQSSRG PEGNIMIDLY EVAGIKGMFL
ANKKIDNQVK TFITYNKGRD WRLLQAPDTD LRGDPVHCLL PYCSLHLHLK VSENPYTSGI
IASKDTAPSI IVASGNIGSE LSDTDISMFV SSDAGNTWRQ IFEEEHSVLY LDQGGVLVAM
KHTSLPIRHL WLSFDEGRSW SKYSFTSIPL FVDGVLGEPG EETLIMTVFG HFSHRSEWQL
VKVDYKSIFD RRCAEEDYRP WQLHSQGEAC IMGAKRIYKK RKSERKCMQG KYAGAMESEP
CVCTEADFDC DYGYERHSNG QCLPAFWFNP SSLSKDCSLG QSYLNSTGYR KVVSNNCTDG
VREQYTAKPQ KCPGKAPRGL RIVTADGKLT AEQGHNVTLM VQLEEGDVQR TLIQVDFGDG
IAVSYVNLSS MEDGIKHVYQ NVGIFRVTVQ VDNSLGSDSA VLYLHVTCPL EHVHLSLPFV
TTKNKEVNAT AVLWPSQVGT LTYVWWYGNN TEPLITLEGS ISFRFTSEGM NTITVQVSAG
NAILQDTKTI AVYEEFRSLR LSFSPNLDDY NPDIPEWRRD IGRVIKKSLV EATGVPGQHI
LVAVLPGLPT TAELFVLPYQ DPAGENKRST DDLEQISELL IHTLNQNSVH FELKPGVRVL
VHAAHLTAAP LVDLTPTHSG SAMLMLLSVV FVGLAVFVIY KFKRRVALPS PPSPSTQPGD
SSLRLQRARH ATPPSTPKRG SAGAQYAI
