CSPG5_HUMAN
ID CSPG5_HUMAN Reviewed; 566 AA.
AC O95196; Q71M39; Q71M40;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 3.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Chondroitin sulfate proteoglycan 5;
DE AltName: Full=Acidic leucine-rich EGF-like domain-containing brain protein;
DE AltName: Full=Neuroglycan C;
DE Flags: Precursor;
GN Name=CSPG5; Synonyms=CALEB, NGC;
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] (ISOFORM 2), TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, AND VARIANT VAL-188.
RC TISSUE=Brain;
RX PubMed=9950058; DOI=10.1016/s0168-0102(98)00098-4;
RA Yasuda Y., Tokita Y., Aono S., Matsui F., Ono T., Sonta S., Watanabe E.,
RA Nakanishi Y., Oohira A.;
RT "Cloning and chromosomal mapping of the human gene of neuroglycan C (NGC),
RT a neural transmembrane chondroitin sulfate proteoglycan with an EGF
RT module.";
RL Neurosci. Res. 32:313-322(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANT VAL-188.
RA Aono S., Tokita Y., Yamauchi S., Shuo T., Matsui F., Yasuda Y., Keino H.,
RA Shimada A., Kishikawa M., Asai M., Oohira A.;
RT "Expression of neuroglycan C (NGC), a transmembrane chondroitin sulfate
RT proteoglycan with an EGF module, in the human brain.";
RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP INTERACTION WITH GOPC.
RX PubMed=12885772; DOI=10.1074/jbc.m305577200;
RA Hassel B., Schreff M., Stuebe E.-M., Blaich U., Schumacher S.;
RT "CALEB/NGC interacts with the Golgi-associated protein PIST.";
RL J. Biol. Chem. 278:40136-40143(2003).
RN [5]
RP INTERACTION WITH ERBB3, AND FUNCTION.
RX PubMed=15358134; DOI=10.1016/j.bbrc.2004.07.066;
RA Kinugasa Y., Ishiguro H., Tokita Y., Oohira A., Ohmoto H., Higashiyama S.;
RT "Neuroglycan C, a novel member of the neuregulin family.";
RL Biochem. Biophys. Res. Commun. 321:1045-1049(2004).
RN [6]
RP GLYCOSYLATION AT SER-165, 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 function as a growth and differentiation factor involved
CC in neuritogenesis. May induce ERBB3 activation.
CC {ECO:0000269|PubMed:15358134}.
CC -!- SUBUNIT: Binds TNR and probably TNC (By similarity). Interacts with
CC ERBB3 and GOPC. Interacts with MDK; this interaction is independent of
CC the presence of chondroitin sulfate chains and promotes elongation of
CC oligodendroglial precursor-like cells (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q9ERQ6, ECO:0000269|PubMed:12885772,
CC ECO:0000269|PubMed:15358134}.
CC -!- INTERACTION:
CC O95196; Q8BH60: Gopc; Xeno; NbExp=3; IntAct=EBI-296349, EBI-296357;
CC O95196-2; O43681: GET3; NbExp=3; IntAct=EBI-18400097, EBI-2515857;
CC O95196-2; Q59EV6: PPGB; NbExp=3; IntAct=EBI-18400097, EBI-14210385;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9ERQ6};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q9ERQ6}.
CC Synaptic cell membrane {ECO:0000250|UniProtKB:Q71M36}; Single-pass type
CC I membrane protein {ECO:0000250|UniProtKB:Q71M36}. Endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:Q71M36}; Single-pass type I
CC membrane protein {ECO:0000250|UniProtKB:Q71M36}. Golgi apparatus
CC membrane {ECO:0000250|UniProtKB:Q71M36}; Single-pass type I membrane
CC protein {ECO:0000250|UniProtKB:Q71M36}. Cell surface
CC {ECO:0000250|UniProtKB:Q71M36}. Note=In neurons, localizes to synaptic
CC junctions. Also detected in the endoplasmic reticulum and the Golgi.
CC Partially enriched in lipid rafts. {ECO:0000250|UniProtKB:Q71M36,
CC ECO:0000250|UniProtKB:Q9ERQ6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O95196-1; Sequence=Displayed;
CC Name=2; Synonyms=CSPG5-I;
CC IsoId=O95196-2; Sequence=VSP_015761;
CC Name=3; Synonyms=CSPG5-II;
CC IsoId=O95196-3; Sequence=VSP_015760, VSP_015761;
CC -!- TISSUE SPECIFICITY: Restricted to brain (at protein level).
CC {ECO:0000269|PubMed:9950058}.
CC -!- DEVELOPMENTAL STAGE: Expressed in brain of 3 months, 5 and 10-year-old
CC individuals. {ECO:0000269|PubMed:9950058}.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
CC -!- PTM: O-glycosylated; contains chondroitin sulfate glycans. Part-time
CC proteoglycan, expressed in part as a proteoglycan exhibiting
CC chondroitin sulfate glycans and in part as a non-proteoglycan form. The
CC relative amount of both forms depends on tissues and tissues maturation
CC (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated; in intracellular and extracellular parts.
CC {ECO:0000250}.
CC -!- MISCELLANEOUS: Different forms of various molecular weight have been
CC observed. Such forms are possibly due to different levels of
CC glycosylation, phosphorylation and/or protein cleavage (By similarity).
CC {ECO:0000250}.
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DR EMBL; AF059274; AAC69612.1; -; mRNA.
DR EMBL; AF461087; AAQ04774.1; -; mRNA.
DR EMBL; AF461088; AAQ04775.1; -; mRNA.
DR EMBL; AF461089; AAQ04776.1; -; mRNA.
DR EMBL; AC099778; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC112512; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS2757.1; -. [O95196-2]
DR CCDS; CCDS56252.1; -. [O95196-3]
DR CCDS; CCDS56253.1; -. [O95196-1]
DR RefSeq; NP_001193872.1; NM_001206943.1. [O95196-1]
DR RefSeq; NP_001193873.1; NM_001206944.1.
DR RefSeq; NP_006565.2; NM_006574.3. [O95196-2]
DR AlphaFoldDB; O95196; -.
DR BioGRID; 115917; 46.
DR IntAct; O95196; 9.
DR MINT; O95196; -.
DR STRING; 9606.ENSP00000373244; -.
DR GlyConnect; 657; 1 O-Linked glycan (1 site).
DR GlyGen; O95196; 3 sites, 2 O-linked glycans (1 site).
DR iPTMnet; O95196; -.
DR PhosphoSitePlus; O95196; -.
DR BioMuta; CSPG5; -.
DR jPOST; O95196; -.
DR MassIVE; O95196; -.
DR PaxDb; O95196; -.
DR PeptideAtlas; O95196; -.
DR PRIDE; O95196; -.
DR ProteomicsDB; 50697; -. [O95196-1]
DR ProteomicsDB; 50698; -. [O95196-2]
DR ProteomicsDB; 50699; -. [O95196-3]
DR Antibodypedia; 29949; 264 antibodies from 31 providers.
DR DNASU; 10675; -.
DR Ensembl; ENST00000264723.9; ENSP00000264723.4; ENSG00000114646.10. [O95196-2]
DR Ensembl; ENST00000383738.6; ENSP00000373244.2; ENSG00000114646.10. [O95196-1]
DR Ensembl; ENST00000456150.5; ENSP00000392096.1; ENSG00000114646.10. [O95196-3]
DR GeneID; 10675; -.
DR KEGG; hsa:10675; -.
DR MANE-Select; ENST00000264723.9; ENSP00000264723.4; NM_006574.4; NP_006565.2. [O95196-2]
DR UCSC; uc003crn.4; human. [O95196-1]
DR CTD; 10675; -.
DR DisGeNET; 10675; -.
DR GeneCards; CSPG5; -.
DR HGNC; HGNC:2467; CSPG5.
DR HPA; ENSG00000114646; Group enriched (brain, choroid plexus, retina).
DR MIM; 606775; gene.
DR neXtProt; NX_O95196; -.
DR OpenTargets; ENSG00000114646; -.
DR PharmGKB; PA26965; -.
DR VEuPathDB; HostDB:ENSG00000114646; -.
DR eggNOG; ENOG502QXSB; Eukaryota.
DR GeneTree; ENSGT00440000034270; -.
DR HOGENOM; CLU_034739_0_0_1; -.
DR InParanoid; O95196; -.
DR OMA; NIGAFCX; -.
DR OrthoDB; 433725at2759; -.
DR PhylomeDB; O95196; -.
DR TreeFam; TF338636; -.
DR PathwayCommons; O95196; -.
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-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-4420332; Defective B3GALT6 causes EDSP2 and SEMDJL1.
DR SignaLink; O95196; -.
DR BioGRID-ORCS; 10675; 14 hits in 1073 CRISPR screens.
DR ChiTaRS; CSPG5; human.
DR GenomeRNAi; 10675; -.
DR Pharos; O95196; Tbio.
DR PRO; PR:O95196; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; O95196; protein.
DR Bgee; ENSG00000114646; Expressed in endothelial cell and 148 other tissues.
DR ExpressionAtlas; O95196; baseline and differential.
DR Genevisible; O95196; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030660; C:Golgi-associated vesicle membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; TAS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IEA:Ensembl.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; TAS:UniProtKB.
DR GO; GO:0031103; P:axon regeneration; IEA:Ensembl.
DR GO; GO:0048858; P:cell projection morphogenesis; IBA:GO_Central.
DR GO; GO:0007010; P:cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0106091; P:glial cell projection elongation; ISS:UniProtKB.
DR GO; GO:0046907; P:intracellular transport; TAS:UniProtKB.
DR GO; GO:0007399; P:nervous system development; TAS:UniProtKB.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; ISS:UniProtKB.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IEA:Ensembl.
DR GO; GO:0099550; P:trans-synaptic signaling, modulating synaptic transmission; IBA:GO_Central.
DR InterPro; IPR042382; CSPG5.
DR InterPro; IPR010555; CSPG5_S_attach_dom.
DR InterPro; IPR009505; Neural_ProG_Cyt.
DR PANTHER; PTHR15381; PTHR15381; 1.
DR Pfam; PF06566; Chon_Sulph_att; 1.
DR Pfam; PF06567; Neural_ProG_Cyt; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Developmental protein;
KW Differentiation; Disulfide bond; EGF-like domain; Endoplasmic reticulum;
KW Glycoprotein; Golgi apparatus; Growth regulation; Membrane; Neurogenesis;
KW Phosphoprotein; Proteoglycan; Reference proteome; Signal; Synapse;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT CHAIN 31..566
FT /note="Chondroitin sulfate proteoglycan 5"
FT /id="PRO_0000042151"
FT TOPO_DOM 31..423
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 424..444
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 445..566
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 371..413
FT /note="EGF-like"
FT REGION 39..82
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 143..202
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 215..248
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 262..354
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 264..301
FT /note="Interaction with TNC and TNR"
FT /evidence="ECO:0000250"
FT REGION 442..460
FT /note="Interaction with GOPC"
FT /evidence="ECO:0000269|PubMed:12885772"
FT COMPBIAS 230..244
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 271..294
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 319..333
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 467
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q71M36"
FT MOD_RES 475
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q71M36"
FT MOD_RES 483
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q71M36"
FT MOD_RES 543
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q71M36"
FT CARBOHYD 57
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 117
FT /note="O-linked (Xyl...) (chondroitin sulfate) serine"
FT /evidence="ECO:0000250"
FT CARBOHYD 165
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|PubMed:23234360"
FT DISULFID 374..387
FT /evidence="ECO:0000250"
FT DISULFID 381..397
FT /evidence="ECO:0000250"
FT DISULFID 399..412
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..138
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_015760"
FT VAR_SEQ 487..513
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:9950058, ECO:0000303|Ref.2"
FT /id="VSP_015761"
FT VARIANT 188
FT /note="G -> V (in dbSNP:rs3732530)"
FT /evidence="ECO:0000269|PubMed:9950058, ECO:0000269|Ref.2"
FT /id="VAR_055089"
FT VARIANT 417
FT /note="T -> P (in dbSNP:rs34016925)"
FT /id="VAR_055090"
SQ SEQUENCE 566 AA; 60016 MW; DD8DA045C1BE31E5 CRC64;
MGRAGGGGPG RGPPPLLLFL GAALVLASGA VPAREAGSAV EAEELVKGSP AWEPPANDTR
EEAGPPAAGE DEASWTAPGG ELAGPEEVLQ ESAAVTGTAW LEADSPGLGG VTAEAGSGDA
QALPATLQAP HEVLGQSIMP PAIPEATEAS GPPSPTPGDK LSPASELPKE SPLEVWLNLG
GSTPDPQGPE LTYPFQGTLE PQPASDIIDI DYFEGLDGEG RGADLGSFPG SPGTSENHPD
TEGETPSWSL LDLYDDFTPF DESDFYPTTS FYDDLDEEEE EEEDDKDAVG GGDLEDENEL
LVPTGKPGLG PGTGQPTSRW HAVPPQHTLG SVPGSSIALR PRPGEPGRDL ASSENGTECR
SGFVRHNGSC RSVCDLFPSY CHNGGQCYLV ENIGAFCRCN TQDYIWHKGM RCESIITDFQ
VMCVAVGSAA LVLLLLFMMT VFFAKKLYLL KTENTKLRRT NKFRTPSELH NDNFSLSTIA
EGSHPNVRKL CNTPRTSSPH ARALAHYDNV ICQDDPSAPH KIQEVLKSCL KEEESFNIQN
SMSPKLEGGK GDQADLDVNC LQNNLT
