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UniProtKB - P35052 (GPC1_HUMAN)

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Protein

Glypican-1

Gene

GPC1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • copper ion binding Source: UniProtKB
  • fibroblast growth factor binding Source: UniProtKB
  • laminin binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

LigandCopper, Zinc

Enzyme and pathway databases

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-202733 Cell surface interactions at the vascular wall
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 receptors
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:
Secreted glypican-1
Gene namesi
Name:GPC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000063660.8
HGNCiHGNC:4449 GPC1
MIMi600395 gene
neXtProtiNX_P35052

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Associates (via the heparan sulfate side chains) with fibrillar APP amyloid-beta 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).1 Publication
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).1 Publication

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...) asparagine2 Publications1
Glycosylationi116N-linked (GlcNAc...) asparagine3 Publications1
Disulfide bondi191 ↔ 3431 Publication
Disulfide bondi246 ↔ 2791 Publication
Disulfide bondi268 ↔ 4151 Publication
Disulfide bondi272 ↔ 4011 Publication
Glycosylationi486O-linked (Xyl...) (heparan sulfate) serineCurated1
Glycosylationi488O-linked (Xyl...) (heparan sulfate) serineCurated1
Glycosylationi490O-linked (Xyl...) (heparan sulfate) serineCurated1
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
ProteomicsDBi54976

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

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi109079, 25 interactors
IntActiP35052, 11 interactors
MINTiP35052
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

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
OMAiCWNGMTK
OrthoDBiEOG091G06T6
PhylomeDBiP35052
TreeFamiTF105317

Family and domain databases

InterProiView protein in InterPro
IPR001863 Glypican
IPR015502 Glypican-1
IPR019803 Glypican_CS
PANTHERiPTHR10822 PTHR10822, 1 hit
PTHR10822:SF8 PTHR10822:SF8, 1 hit
PfamiView protein in Pfam
PF01153 Glypican, 1 hit
PROSITEiView protein in PROSITE
PS01207 GLYPICAN, 1 hit

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 → G2 PublicationsCorresponds to variant dbSNP:rs2228331Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiGPC1_HUMAN
AccessioniPrimary (citable) accession number: P35052
Secondary accession number(s): B3KTD1, Q53QM4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: March 23, 2010
Last modified: July 18, 2018
This is version 158 of the entry and version 2 of the sequence. See 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

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