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   13-FEB-2019, entry version 171.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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.,
RA   Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA   Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA   Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA   Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA   Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA   Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA   Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA   Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA   Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA   Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA   Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA   Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA   Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA   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
RT   structures 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
CC       and N-CAM). Chondroitin sulfate proteoglycan; binds to hyaluronic
CC       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   UniGene; Hs.169047; -.
DR   ProteinModelPortal; O14594; -.
DR   SMR; O14594; -.
DR   BioGrid; 107845; 5.
DR   IntAct; O14594; 2.
DR   STRING; 9606.ENSP00000252575; -.
DR   DrugBank; DB02379; Beta-D-Glucose.
DR   DrugBank; DB08818; Hyaluronic acid.
DR   DrugBank; DB04396; Thiodigalactoside.
DR   GlyConnect; 1550; -.
DR   iPTMnet; O14594; -.
DR   PhosphoSitePlus; O14594; -.
DR   BioMuta; NCAN; -.
DR   jPOST; O14594; -.
DR   PaxDb; O14594; -.
DR   PeptideAtlas; O14594; -.
DR   PRIDE; O14594; -.
DR   ProteomicsDB; 48103; -.
DR   DNASU; 1463; -.
DR   Ensembl; ENST00000252575; ENSP00000252575; ENSG00000130287.
DR   GeneID; 1463; -.
DR   KEGG; hsa:1463; -.
DR   UCSC; uc002nlz.4; human.
DR   CTD; 1463; -.
DR   DisGeNET; 1463; -.
DR   EuPathDB; HostDB:ENSG00000130287.13; -.
DR   GeneCards; NCAN; -.
DR   H-InvDB; HIX0027449; -.
DR   HGNC; HGNC:2465; NCAN.
DR   HPA; HPA036814; -.
DR   MIM; 600826; gene.
DR   neXtProt; NX_O14594; -.
DR   OpenTargets; ENSG00000130287; -.
DR   PharmGKB; PA162396986; -.
DR   eggNOG; ENOG410IJ1R; Eukaryota.
DR   eggNOG; ENOG410YR39; LUCA.
DR   GeneTree; ENSGT00940000158649; -.
DR   HOVERGEN; HBG078994; -.
DR   InParanoid; O14594; -.
DR   KO; K06794; -.
DR   OMA; APRIKWT; -.
DR   OrthoDB; 174823at2759; -.
DR   PhylomeDB; O14594; -.
DR   TreeFam; TF332134; -.
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   ChiTaRS; NCAN; human.
DR   GeneWiki; Neurocan; -.
DR   GenomeRNAi; 1463; -.
DR   PRO; PR:O14594; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   Bgee; ENSG00000130287; Expressed in 87 organ(s), highest expression level in spinal cord.
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:0030206; P:chondroitin sulfate biosynthetic process; TAS:Reactome.
DR   GO; GO:0030207; P:chondroitin sulfate catabolic process; TAS:Reactome.
DR   GO; GO:0030208; P:dermatan sulfate biosynthetic process; TAS:Reactome.
DR   GO; GO:0030198; P:extracellular matrix organization; TAS:Reactome.
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; IPR013032; EGF-like_CS.
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; Complete proteome; Disulfide bond;
KW   EGF-like domain; Glycoprotein; Hyaluronic acid; Immunoglobulin domain;
KW   Lectin; Polymorphism; Proteoglycan; Reference proteome; Repeat;
KW   Secreted; Signal; Sushi.
FT   SIGNAL        1     22       {ECO:0000255}.
FT   CHAIN        23   1321       Neurocan core protein.
FT                                /FTId=PRO_0000017516.
FT   DOMAIN       38    153       Ig-like V-type.
FT   DOMAIN      160    255       Link 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00323}.
FT   DOMAIN      259    357       Link 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00323}.
FT   DOMAIN     1008   1044       EGF-like 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN     1046   1082       EGF-like 2; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DOMAIN     1084   1213       C-type lectin. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00040}.
FT   DOMAIN     1213   1273       Sushi. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00302}.
FT   REGION      708    712       O-glycosylated at one site.
FT   CARBOHYD    122    122       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    340    340       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1026   1026       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1223   1223       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID     59    140       {ECO:0000250}.
FT   DISULFID    182    253       {ECO:0000250}.
FT   DISULFID    206    227       {ECO:0000250}.
FT   DISULFID    280    355       {ECO:0000250}.
FT   DISULFID    304    325       {ECO:0000250}.
FT   DISULFID   1012   1023       {ECO:0000250}.
FT   DISULFID   1017   1032       {ECO:0000250}.
FT   DISULFID   1034   1043       {ECO:0000250}.
FT   DISULFID   1050   1061       {ECO:0000250}.
FT   DISULFID   1055   1070       {ECO:0000250}.
FT   DISULFID   1072   1081       {ECO:0000250}.
FT   DISULFID   1088   1099       {ECO:0000250}.
FT   DISULFID   1116   1208       {ECO:0000250}.
FT   DISULFID   1184   1200       {ECO:0000250}.
FT   DISULFID   1215   1258       {ECO:0000250}.
FT   DISULFID   1244   1271       {ECO:0000250}.
FT   VARIANT      70     70       A -> T (in dbSNP:rs2228601).
FT                                /FTId=VAR_024521.
FT   VARIANT      92     92       P -> S (in dbSNP:rs2228603).
FT                                /FTId=VAR_020213.
FT   VARIANT    1254   1254       A -> V (in dbSNP:rs1064389).
FT                                {ECO:0000269|PubMed:9795216}.
FT                                /FTId=VAR_016176.
FT   CONFLICT   1234   1234       Y -> N (in Ref. 1; AAC80576).
FT                                {ECO:0000305}.
FT   CONFLICT   1282   1282       R -> G (in Ref. 1; AAC80576).
FT                                {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
//