NCAN_HUMAN
ID NCAN_HUMAN Reviewed; 1321 AA.
AC O14594; Q9UPK6;
DT 27-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 3.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Neurocan core protein;
DE AltName: Full=Chondroitin sulfate proteoglycan 3;
DE Flags: Precursor;
GN Name=NCAN; Synonyms=CSPG3, NEUR;
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], AND VARIANT VAL-1254.
RX PubMed=9795216; DOI=10.1016/s0378-1119(98)00455-7;
RA Prange C.K., Pennacchio L.A., Lieuallen K., Fan W., Lennon G.G.;
RT "Characterization of the human neurocan gene, CSPG3.";
RL Gene 221:199-205(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP GLYCOSYLATION, 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).
CC -!- FUNCTION: May modulate neuronal adhesion and neurite growth during
CC development by binding to neural cell adhesion molecules (NG-CAM and N-
CC CAM). Chondroitin sulfate proteoglycan; binds to hyaluronic acid.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Brain.
CC -!- PTM: O-glycosylated. {ECO:0000269|PubMed:23234360}.
CC -!- SIMILARITY: Belongs to the aggrecan/versican proteoglycan family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC Note=Neurocan;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_Ctlect_213";
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DR EMBL; AF026547; AAC80576.1; -; mRNA.
DR EMBL; AC003110; AAB86655.1; -; Genomic_DNA.
DR EMBL; AC005254; AAC25581.1; -; Genomic_DNA.
DR CCDS; CCDS12397.1; -.
DR RefSeq; NP_004377.2; NM_004386.2.
DR AlphaFoldDB; O14594; -.
DR SMR; O14594; -.
DR BioGRID; 107845; 7.
DR IntAct; O14594; 3.
DR STRING; 9606.ENSP00000252575; -.
DR DrugBank; DB02379; Beta-D-Glucose.
DR DrugBank; DB08818; Hyaluronic acid.
DR DrugBank; DB04396; Thiodigalactoside.
DR GlyConnect; 1550; 14 N-Linked glycans (1 site).
DR GlyGen; O14594; 7 sites, 18 N-linked glycans (1 site), 2 O-linked glycans (3 sites).
DR iPTMnet; O14594; -.
DR PhosphoSitePlus; O14594; -.
DR BioMuta; NCAN; -.
DR jPOST; O14594; -.
DR MassIVE; O14594; -.
DR PaxDb; O14594; -.
DR PeptideAtlas; O14594; -.
DR PRIDE; O14594; -.
DR Antibodypedia; 28403; 210 antibodies from 32 providers.
DR DNASU; 1463; -.
DR Ensembl; ENST00000252575.11; ENSP00000252575.4; ENSG00000130287.14.
DR GeneID; 1463; -.
DR KEGG; hsa:1463; -.
DR MANE-Select; ENST00000252575.11; ENSP00000252575.4; NM_004386.3; NP_004377.2.
DR UCSC; uc002nlz.4; human.
DR CTD; 1463; -.
DR DisGeNET; 1463; -.
DR GeneCards; NCAN; -.
DR HGNC; HGNC:2465; NCAN.
DR HPA; ENSG00000130287; Tissue enriched (brain).
DR MIM; 600826; gene.
DR neXtProt; NX_O14594; -.
DR OpenTargets; ENSG00000130287; -.
DR PharmGKB; PA162396986; -.
DR VEuPathDB; HostDB:ENSG00000130287; -.
DR eggNOG; ENOG502QQ78; Eukaryota.
DR GeneTree; ENSGT00940000158649; -.
DR HOGENOM; CLU_000303_0_1_1; -.
DR InParanoid; O14594; -.
DR OMA; YPRRRAN; -.
DR OrthoDB; 174823at2759; -.
DR PhylomeDB; O14594; -.
DR TreeFam; TF332134; -.
DR PathwayCommons; O14594; -.
DR Reactome; R-HSA-1971475; A tetrasaccharide linker sequence is required for GAG synthesis.
DR Reactome; R-HSA-2022870; Chondroitin sulfate biosynthesis.
DR Reactome; R-HSA-2022923; Dermatan sulfate biosynthesis.
DR Reactome; R-HSA-2024101; CS/DS degradation.
DR Reactome; R-HSA-3000178; ECM proteoglycans.
DR Reactome; R-HSA-3560783; Defective B4GALT7 causes EDS, progeroid type.
DR Reactome; R-HSA-3560801; Defective B3GAT3 causes JDSSDHD.
DR Reactome; R-HSA-3595172; Defective CHST3 causes SEDCJD.
DR Reactome; R-HSA-3595174; Defective CHST14 causes EDS, musculocontractural type.
DR Reactome; R-HSA-3595177; Defective CHSY1 causes TPBS.
DR Reactome; R-HSA-373760; L1CAM interactions.
DR Reactome; R-HSA-419037; NCAM1 interactions.
DR Reactome; R-HSA-4420332; Defective B3GALT6 causes EDSP2 and SEMDJL1.
DR SignaLink; O14594; -.
DR BioGRID-ORCS; 1463; 17 hits in 1067 CRISPR screens.
DR ChiTaRS; NCAN; human.
DR GeneWiki; Neurocan; -.
DR GenomeRNAi; 1463; -.
DR Pharos; O14594; Tbio.
DR PRO; PR:O14594; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O14594; protein.
DR Bgee; ENSG00000130287; Expressed in ventricular zone and 91 other tissues.
DR ExpressionAtlas; O14594; baseline and differential.
DR Genevisible; O14594; HS.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR GO; GO:0005540; F:hyaluronic acid binding; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR GO; GO:0001501; P:skeletal system development; IBA:GO_Central.
DR CDD; cd00033; CCP; 1.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 3.10.100.10; -; 3.
DR InterPro; IPR001304; C-type_lectin-like.
DR InterPro; IPR016186; C-type_lectin-like/link_sf.
DR InterPro; IPR018378; C-type_lectin_CS.
DR InterPro; IPR016187; CTDL_fold.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013106; Ig_V-set.
DR InterPro; IPR000538; Link_dom.
DR InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR Pfam; PF00008; EGF; 1.
DR Pfam; PF00059; Lectin_C; 1.
DR Pfam; PF00084; Sushi; 1.
DR Pfam; PF07686; V-set; 1.
DR Pfam; PF00193; Xlink; 2.
DR PRINTS; PR01265; LINKMODULE.
DR SMART; SM00032; CCP; 1.
DR SMART; SM00034; CLECT; 1.
DR SMART; SM00181; EGF; 2.
DR SMART; SM00179; EGF_CA; 2.
DR SMART; SM00409; IG; 1.
DR SMART; SM00445; LINK; 2.
DR SUPFAM; SSF48726; SSF48726; 1.
DR SUPFAM; SSF56436; SSF56436; 3.
DR SUPFAM; SSF57535; SSF57535; 1.
DR PROSITE; PS00010; ASX_HYDROXYL; 1.
DR PROSITE; PS00615; C_TYPE_LECTIN_1; 1.
DR PROSITE; PS50041; C_TYPE_LECTIN_2; 1.
DR PROSITE; PS00022; EGF_1; 3.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS50026; EGF_3; 2.
DR PROSITE; PS01187; EGF_CA; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS01241; LINK_1; 2.
DR PROSITE; PS50963; LINK_2; 2.
DR PROSITE; PS50923; SUSHI; 1.
PE 1: Evidence at protein level;
KW Calcium; Cell adhesion; Disulfide bond; EGF-like domain; Glycoprotein;
KW Hyaluronic acid; Immunoglobulin domain; Lectin; Proteoglycan;
KW Reference proteome; Repeat; Secreted; Signal; Sushi.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..1321
FT /note="Neurocan core protein"
FT /id="PRO_0000017516"
FT DOMAIN 38..153
FT /note="Ig-like V-type"
FT DOMAIN 160..255
FT /note="Link 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT DOMAIN 259..357
FT /note="Link 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00323"
FT DOMAIN 1008..1044
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1046..1082
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1084..1213
FT /note="C-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DOMAIN 1213..1273
FT /note="Sushi"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT REGION 362..414
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 456..479
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 494..513
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 532..579
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 682..731
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 708..712
FT /note="O-glycosylated at one site"
FT REGION 820..844
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 876..955
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1275..1321
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 710..731
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 887..918
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 936..955
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1275..1306
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1307..1321
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1026
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1223
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 59..140
FT /evidence="ECO:0000250"
FT DISULFID 182..253
FT /evidence="ECO:0000250"
FT DISULFID 206..227
FT /evidence="ECO:0000250"
FT DISULFID 280..355
FT /evidence="ECO:0000250"
FT DISULFID 304..325
FT /evidence="ECO:0000250"
FT DISULFID 1012..1023
FT /evidence="ECO:0000250"
FT DISULFID 1017..1032
FT /evidence="ECO:0000250"
FT DISULFID 1034..1043
FT /evidence="ECO:0000250"
FT DISULFID 1050..1061
FT /evidence="ECO:0000250"
FT DISULFID 1055..1070
FT /evidence="ECO:0000250"
FT DISULFID 1072..1081
FT /evidence="ECO:0000250"
FT DISULFID 1088..1099
FT /evidence="ECO:0000250"
FT DISULFID 1116..1208
FT /evidence="ECO:0000250"
FT DISULFID 1184..1200
FT /evidence="ECO:0000250"
FT DISULFID 1215..1258
FT /evidence="ECO:0000250"
FT DISULFID 1244..1271
FT /evidence="ECO:0000250"
FT VARIANT 70
FT /note="A -> T (in dbSNP:rs2228601)"
FT /id="VAR_024521"
FT VARIANT 92
FT /note="P -> S (in dbSNP:rs2228603)"
FT /id="VAR_020213"
FT VARIANT 1254
FT /note="A -> V (in dbSNP:rs1064389)"
FT /evidence="ECO:0000269|PubMed:9795216"
FT /id="VAR_016176"
FT CONFLICT 1234
FT /note="Y -> N (in Ref. 1; AAC80576)"
FT /evidence="ECO:0000305"
FT CONFLICT 1282
FT /note="R -> G (in Ref. 1; AAC80576)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1321 AA; 143093 MW; 22E21FFA24CE9FB2 CRC64;
MGAPFVWALG LLMLQMLLFV AGEQGTQDIT DASERGLHMQ KLGSGSVQAA LAELVALPCL
FTLQPRPSAA RDAPRIKWTK VRTASGQRQD LPILVAKDNV VRVAKSWQGR VSLPSYPRRR
ANATLLLGPL RASDSGLYRC QVVRGIEDEQ DLVPLEVTGV VFHYRSARDR YALTFAEAQE
ACRLSSAIIA APRHLQAAFE DGFDNCDAGW LSDRTVRYPI TQSRPGCYGD RSSLPGVRSY
GRRNPQELYD VYCFARELGG EVFYVGPARR LTLAGARAQC RRQGAALASV GQLHLAWHEG
LDQCDPGWLA DGSVRYPIQT PRRRCGGPAP GVRTVYRFAN RTGFPSPAER FDAYCFRAHH
PTSQHGDLET PSSGDEGEIL SAEGPPVREL EPTLEEEEVV TPDFQEPLVS SGEEETLILE
EKQESQQTLS PTPGDPMLAS WPTGEVWLST VAPSPSDMGA GTAASSHTEV APTDPMPRRR
GRFKGLNGRY FQQQEPEPGL QGGMEASAQP PTSEAAVNQM EPPLAMAVTE MLGSGQSRSP
WADLTNEVDM PGAGSAGGKS SPEPWLWPPT MVPPSISGHS RAPVLELEKA EGPSARPATP
DLFWSPLEAT VSAPSPAPWE AFPVATSPDL PMMAMLRGPK EWMLPHPTPI STEANRVEAH
GEATATAPPS PAAETKVYSL PLSLTPTGQG GEAMPTTPES PRADFRETGE TSPAQVNKAE
HSSSSPWPSV NRNVAVGFVP TETATEPTGL RGIPGSESGV FDTAESPTSG LQATVDEVQD
PWPSVYSKGL DASSPSAPLG SPGVFLVPKV TPNLEPWVAT DEGPTVNPMD STVTPAPSDA
SGIWEPGSQV FEEAESTTLS PQVALDTSIV TPLTTLEQGD KVGVPAMSTL GSSSSQPHPE
PEDQVETQGT SGASVPPHQS SPLGKPAVPP GTPTAASVGE SASVSSGEPT VPWDPSSTLL
PVTLGIEDFE LEVLAGSPGV ESFWEEVASG EEPALPGTPM NAGAEEVHSD PCENNPCLHG
GTCNANGTMY GCSCDQGFAG ENCEIDIDDC LCSPCENGGT CIDEVNGFVC LCLPSYGGSF
CEKDTEGCDR GWHKFQGHCY RYFAHRRAWE DAEKDCRRRS GHLTSVHSPE EHSFINSFGH
ENTWIGLNDR IVERDFQWTD NTGLQFENWR ENQPDNFFAG GEDCVVMVAH ESGRWNDVPC
NYNLPYVCKK GTVLCGPPPA VENASLIGAR KAKYNVHATV RYQCNEGFAQ HHVATIRCRS
NGKWDRPQIV CTKPRRSHRM RRHHHHHQHH HQHHHHKSRK ERRKHKKHPT EDWEKDEGNF
C
