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Protein

Glypican-1

Gene

GPC1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cell surface proteoglycan that bears heparan sulfate. Binds, via the heparan sulfate side chains, alpha-4 (V) collagen and participates in Schwann cell myelination (By similarity). May act as a catalyst in increasing the rate of conversion of prion protein PRPN(C) to PRNP(Sc) via associating (via the heparan sulfate side chains) with both forms of PRPN, targeting them to lipid rafts and facilitating their interaction. Required for proper skeletal muscle differentiation by sequestering FGF2 in lipid rafts preventing its binding to receptors (FGFRs) and inhibiting the FGF-mediated signaling.By similarity2 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Ligandi

Copper, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000063660-MONOMER.
ReactomeiR-HSA-1971475. A tetrasaccharide linker sequence is required for GAG synthesis.
R-HSA-2022928. HS-GAG biosynthesis.
R-HSA-2024096. HS-GAG degradation.
R-HSA-3560783. Defective B4GALT7 causes EDS, progeroid type.
R-HSA-3560801. Defective B3GAT3 causes JDSSDHD.
R-HSA-3656237. Defective EXT2 causes exostoses 2.
R-HSA-3656253. Defective EXT1 causes exostoses 1, TRPS2 and CHDS.
R-HSA-376176. Signaling by Robo receptor.
R-HSA-428540. Activation of Rac.
R-HSA-428543. Inactivation of Cdc42 and Rac.
R-HSA-428890. Role of Abl in Robo-Slit signaling.
R-HSA-4420332. Defective B3GALT6 causes EDSP2 and SEMDJL1.
R-HSA-975634. Retinoid metabolism and transport.
SIGNORiP35052.

Names & Taxonomyi

Protein namesi
Recommended name:
Glypican-1
Cleaved into the following chain:
Gene namesi
Name:GPC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:4449. GPC1.

Subcellular locationi

  • Cell membrane; Lipid-anchorGPI-anchor; Extracellular side
  • Endosome

  • Note: S-nitrosylated form recycled in endosomes. Localizes to CAV1-containing vesicles close to the cell surface. Cleavage of heparan sulfate side chains takes place mainly in late endosomes. Associates with both forms of PRNP in lipid rafts. Colocalizes with APP in perinuclear compartments and with CP in intracellular compartments. Associates with fibrillar APP Abeta peptides in lipid rafts in Alzheimer disease brains.

GO - Cellular componenti

  • anchored component of membrane Source: UniProtKB-KW
  • endosome Source: UniProtKB-SubCell
  • extracellular exosome Source: UniProtKB
  • extracellular space Source: ProtInc
  • Golgi lumen Source: Reactome
  • integral component of plasma membrane Source: ProtInc
  • lysosomal lumen Source: Reactome
  • membrane raft Source: UniProtKB
  • plasma membrane Source: Reactome
  • proteinaceous extracellular matrix Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Associates (via the heparan sulfate side chains) with fibrillar APP-beta amyloid peptides in primitive and classic amyloid plaques and may be involved in the deposition of these senile plaques in the Alzheimer disease (AD) brain (PubMed:15084524).

Misprocessing of GPC1 is found in fibroblasts of patients with Niemann-Pick Type C1 disease. This is due to the defective deaminative degradation of heparan sulfate chains (PubMed:16645004).

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi79N → Q: Protein yield reduced by half. Protein yield reduced by 90%, abolishes N-glycosylation but no effect on secondary structure; when associated with Q-116. 1 Publication1
Mutagenesisi116N → Q: No effect on protein yield. Protein yield reduced by 90%, abolishes N-glycosylation but no effect on secondary structure; when associated with Q-79. 1 Publication1

Organism-specific databases

DisGeNETi2817.
MalaCardsiGPC1.
OpenTargetsiENSG00000063660.
Orphaneti30391. Biliary atresia.
PharmGKBiPA28830.

Polymorphism and mutation databases

BioMutaiGPC1.
DMDMi292495012.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 231 PublicationAdd BLAST23
ChainiPRO_000001229524 – 530Glypican-1Add BLAST507
ChainiPRO_000033383724 – ?Secreted glypican-1
PropeptideiPRO_0000012296531 – 558Removed in mature formCuratedAdd BLAST28

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi32 ↔ 681 Publication
Disulfide bondi62 ↔ 2561 Publication
Disulfide bondi69 ↔ 2591 Publication
Glycosylationi79N-linked (GlcNAc...)2 Publications1
Glycosylationi116N-linked (GlcNAc...)3 Publications1
Disulfide bondi191 ↔ 3431 Publication
Disulfide bondi246 ↔ 2791 Publication
Disulfide bondi268 ↔ 4151 Publication
Disulfide bondi272 ↔ 4011 Publication
Glycosylationi486O-linked (Xyl...) (heparan sulfate)Curated1
Glycosylationi488O-linked (Xyl...) (heparan sulfate)Curated1
Glycosylationi490O-linked (Xyl...) (heparan sulfate)Curated1
Lipidationi530GPI-anchor amidated serine1 Publication1

Post-translational modificationi

S-nitrosylated in a Cu2+-dependent manner. Nitric acid (NO) is released from the nitrosylated cysteines by ascorbate or by some other reducing agent, in a Cu2+ or Zn2+ dependent manner. This free nitric oxide is then capable of cleaving the heparan sulfate side chains.
N- and O-glycosylated. N-glycosylation is mainly of the complex type containing sialic acid. O-glycosylated with heparan sulfate. The heparan sulfate chains can be cleaved either by the action of heparanase or, degraded by a deaminative process that uses nitric oxide (NO) released from the S-nitrosylated cysteines. This process is triggered by ascorbate, or by some other reducing agent, in a Cu2+- or Zn2+ dependent manner. Cu2+ ions are provided by ceruloproteins such as APP, PRNP or CP which associate with GCP1 in intracellular compartments or lipid rafts.8 Publications
This cell-associated glypican is further processed to give rise to a medium-released species.

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Heparan sulfate, Lipoprotein, Proteoglycan, S-nitrosylation

Proteomic databases

EPDiP35052.
MaxQBiP35052.
PaxDbiP35052.
PeptideAtlasiP35052.
PRIDEiP35052.

PTM databases

iPTMnetiP35052.
PhosphoSitePlusiP35052.
SwissPalmiP35052.

Expressioni

Gene expression databases

BgeeiENSG00000063660.
CleanExiHS_GPC1.
ExpressionAtlasiP35052. baseline and differential.
GenevisibleiP35052. HS.

Organism-specific databases

HPAiHPA030571.

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109079. 20 interactors.
IntActiP35052. 8 interactors.
STRINGi9606.ENSP00000264039.

Structurei

Secondary structure

1558
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi33 – 40Combined sources8
Turni41 – 43Combined sources3
Helixi46 – 48Combined sources3
Helixi56 – 58Combined sources3
Beta strandi60 – 62Combined sources3
Beta strandi64 – 68Combined sources5
Helixi71 – 130Combined sources60
Helixi132 – 135Combined sources4
Helixi138 – 153Combined sources16
Helixi159 – 178Combined sources20
Beta strandi180 – 182Combined sources3
Helixi187 – 192Combined sources6
Turni201 – 204Combined sources4
Helixi205 – 237Combined sources33
Helixi244 – 254Combined sources11
Helixi256 – 259Combined sources4
Helixi269 – 279Combined sources11
Helixi281 – 284Combined sources4
Helixi287 – 300Combined sources14
Helixi301 – 304Combined sources4
Beta strandi307 – 310Combined sources4
Helixi313 – 315Combined sources3
Helixi317 – 329Combined sources13
Helixi332 – 335Combined sources4
Helixi340 – 343Combined sources4
Helixi374 – 388Combined sources15
Helixi392 – 403Combined sources12
Beta strandi418 – 422Combined sources5
Beta strandi431 – 433Combined sources3
Helixi434 – 436Combined sources3
Beta strandi440 – 442Combined sources3
Helixi451 – 472Combined sources22

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4ACRX-ray2.55A/B/C/D24-479[»]
4AD7X-ray2.94A/B/C/D24-529[»]
4BWEX-ray2.46A/B/C/D24-479[»]
4YWTX-ray2.38A/B/C/D24-527[»]
ProteinModelPortaliP35052.
SMRiP35052.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the glypican family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3821. Eukaryota.
ENOG410XST2. LUCA.
GeneTreeiENSGT00550000074430.
HOGENOMiHOG000253003.
HOVERGENiHBG003464.
InParanoidiP35052.
KOiK08107.
OMAiMKLVYCP.
OrthoDBiEOG091G06T6.
PhylomeDBiP35052.
TreeFamiTF105317.

Family and domain databases

InterProiIPR001863. Glypican.
IPR015502. Glypican-1.
IPR019803. Glypican_CS.
[Graphical view]
PANTHERiPTHR10822. PTHR10822. 1 hit.
PTHR10822:SF8. PTHR10822:SF8. 1 hit.
PfamiPF01153. Glypican. 1 hit.
[Graphical view]
PROSITEiPS01207. GLYPICAN. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P35052-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MELRARGWWL LCAAAALVAC ARGDPASKSR SCGEVRQIYG AKGFSLSDVP
60 70 80 90 100
QAEISGEHLR ICPQGYTCCT SEMEENLANR SHAELETALR DSSRVLQAML
110 120 130 140 150
ATQLRSFDDH FQHLLNDSER TLQATFPGAF GELYTQNARA FRDLYSELRL
160 170 180 190 200
YYRGANLHLE ETLAEFWARL LERLFKQLHP QLLLPDDYLD CLGKQAEALR
210 220 230 240 250
PFGEAPRELR LRATRAFVAA RSFVQGLGVA SDVVRKVAQV PLGPECSRAV
260 270 280 290 300
MKLVYCAHCL GVPGARPCPD YCRNVLKGCL ANQADLDAEW RNLLDSMVLI
310 320 330 340 350
TDKFWGTSGV ESVIGSVHTW LAEAINALQD NRDTLTAKVI QGCGNPKVNP
360 370 380 390 400
QGPGPEEKRR RGKLAPRERP PSGTLEKLVS EAKAQLRDVQ DFWISLPGTL
410 420 430 440 450
CSEKMALSTA SDDRCWNGMA RGRYLPEVMG DGLANQINNP EVEVDITKPD
460 470 480 490 500
MTIRQQIMQL KIMTNRLRSA YNGNDVDFQD ASDDGSGSGS GDGCLDDLCS
510 520 530 540 550
RKVSRKSSSS RTPLTHALPG LSEQEGQKTS AASCPQPPTF LLPLLLFLAL

TVARPRWR
Length:558
Mass (Da):61,680
Last modified:March 23, 2010 - v2
Checksum:i16553B56080A83C8
GO
Isoform 2 (identifier: P35052-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-72: Missing.
     295-359: DSMVLITDKF...PQGPGPEEKR → GEPPPARAAW...GCLLNVLSDV
     360-558: Missing.

Note: No experimental confirmation available.
Show »
Length:287
Mass (Da):31,931
Checksum:iD986658ECFD5AA92
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036044337A → D in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_033977500S → G.2 PublicationsCorresponds to variant rs2228331dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0552251 – 72Missing in isoform 2. 1 PublicationAdd BLAST72
Alternative sequenceiVSP_055226295 – 359DSMVL…PEEKR → GEPPPARAAWNCLGECTTGG PGGRVVPSLELGPRDLIRDA LTRARSGWCCRVEGPGCLLN VLSDV in isoform 2. 1 PublicationAdd BLAST65
Alternative sequenceiVSP_055227360 – 558Missing in isoform 2. 1 PublicationAdd BLAST199

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54232 mRNA. Translation: CAA38139.1.
AK095397 mRNA. Translation: BAG53043.1.
AK096638 mRNA. Translation: BAG53345.1.
AC110619 Genomic DNA. Translation: AAY24160.1.
CH471063 Genomic DNA. Translation: EAW71180.1.
CH471063 Genomic DNA. Translation: EAW71183.1.
BC051279 mRNA. Translation: AAH51279.1.
CCDSiCCDS2534.1. [P35052-1]
PIRiA36347.
RefSeqiNP_002072.2. NM_002081.2. [P35052-1]
UniGeneiHs.328232.

Genome annotation databases

EnsembliENST00000264039; ENSP00000264039; ENSG00000063660. [P35052-1]
GeneIDi2817.
KEGGihsa:2817.
UCSCiuc002vyw.5. human. [P35052-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54232 mRNA. Translation: CAA38139.1.
AK095397 mRNA. Translation: BAG53043.1.
AK096638 mRNA. Translation: BAG53345.1.
AC110619 Genomic DNA. Translation: AAY24160.1.
CH471063 Genomic DNA. Translation: EAW71180.1.
CH471063 Genomic DNA. Translation: EAW71183.1.
BC051279 mRNA. Translation: AAH51279.1.
CCDSiCCDS2534.1. [P35052-1]
PIRiA36347.
RefSeqiNP_002072.2. NM_002081.2. [P35052-1]
UniGeneiHs.328232.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4ACRX-ray2.55A/B/C/D24-479[»]
4AD7X-ray2.94A/B/C/D24-529[»]
4BWEX-ray2.46A/B/C/D24-479[»]
4YWTX-ray2.38A/B/C/D24-527[»]
ProteinModelPortaliP35052.
SMRiP35052.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109079. 20 interactors.
IntActiP35052. 8 interactors.
STRINGi9606.ENSP00000264039.

PTM databases

iPTMnetiP35052.
PhosphoSitePlusiP35052.
SwissPalmiP35052.

Polymorphism and mutation databases

BioMutaiGPC1.
DMDMi292495012.

Proteomic databases

EPDiP35052.
MaxQBiP35052.
PaxDbiP35052.
PeptideAtlasiP35052.
PRIDEiP35052.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264039; ENSP00000264039; ENSG00000063660. [P35052-1]
GeneIDi2817.
KEGGihsa:2817.
UCSCiuc002vyw.5. human. [P35052-1]

Organism-specific databases

CTDi2817.
DisGeNETi2817.
GeneCardsiGPC1.
H-InvDBHIX0002996.
HGNCiHGNC:4449. GPC1.
HPAiHPA030571.
MalaCardsiGPC1.
MIMi600395. gene.
neXtProtiNX_P35052.
OpenTargetsiENSG00000063660.
Orphaneti30391. Biliary atresia.
PharmGKBiPA28830.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3821. Eukaryota.
ENOG410XST2. LUCA.
GeneTreeiENSGT00550000074430.
HOGENOMiHOG000253003.
HOVERGENiHBG003464.
InParanoidiP35052.
KOiK08107.
OMAiMKLVYCP.
OrthoDBiEOG091G06T6.
PhylomeDBiP35052.
TreeFamiTF105317.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000063660-MONOMER.
ReactomeiR-HSA-1971475. A tetrasaccharide linker sequence is required for GAG synthesis.
R-HSA-2022928. HS-GAG biosynthesis.
R-HSA-2024096. HS-GAG degradation.
R-HSA-3560783. Defective B4GALT7 causes EDS, progeroid type.
R-HSA-3560801. Defective B3GAT3 causes JDSSDHD.
R-HSA-3656237. Defective EXT2 causes exostoses 2.
R-HSA-3656253. Defective EXT1 causes exostoses 1, TRPS2 and CHDS.
R-HSA-376176. Signaling by Robo receptor.
R-HSA-428540. Activation of Rac.
R-HSA-428543. Inactivation of Cdc42 and Rac.
R-HSA-428890. Role of Abl in Robo-Slit signaling.
R-HSA-4420332. Defective B3GALT6 causes EDSP2 and SEMDJL1.
R-HSA-975634. Retinoid metabolism and transport.
SIGNORiP35052.

Miscellaneous databases

ChiTaRSiGPC1. human.
GeneWikiiGlypican_1.
GenomeRNAii2817.
PROiP35052.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000063660.
CleanExiHS_GPC1.
ExpressionAtlasiP35052. baseline and differential.
GenevisibleiP35052. HS.

Family and domain databases

InterProiIPR001863. Glypican.
IPR015502. Glypican-1.
IPR019803. Glypican_CS.
[Graphical view]
PANTHERiPTHR10822. PTHR10822. 1 hit.
PTHR10822:SF8. PTHR10822:SF8. 1 hit.
PfamiPF01153. Glypican. 1 hit.
[Graphical view]
PROSITEiPS01207. GLYPICAN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGPC1_HUMAN
AccessioniPrimary (citable) accession number: P35052
Secondary accession number(s): B3KTD1, Q53QM4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: March 23, 2010
Last modified: November 2, 2016
This is version 144 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.