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Q9HCN6 (GPVI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Platelet glycoprotein VI

Short name=GPVI
Alternative name(s):
Glycoprotein 6
Gene names
Name:GP6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length339 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Collagen receptor involved in collagen-induced platelet adhesion and activation. Plays a key role in platelet procoagulant activity and subsequent thrombin and fibrin formation. This procoagulant function may contribute to arterial and venous thrombus formation. The signaling pathway involves the FcR gamma-chain, the Src kinases (likely Fyn/Lyn), the adapter protein LAT and leads to the activation of phospholipase C gamma2. Ref.2

Subunit structure

Associated with Fc receptor gamma chain. The GPVI-FcRgamma complex is associated with the Src kinase family Fyn and Lyn.

Subcellular location

Isoform 1: Cell membrane; Single-pass membrane protein.

Isoform 2: Cell membrane; Single-pass membrane protein.

Tissue specificity

Megakaryocytes and platelets. Ref.2

Post-translational modification

N-linked glycosylation at Asn-92 is not required for the cell surface expression, but contributes to maximal adhesion to type I collagen, collagen-related peptide (CRP), and, to a lesser extent, to the snake venom C-type lectin convulxin (CVX).

Involvement in disease

Bleeding disorder, platelet-type 11 (BDPLT11) [MIM:614201]: A mild to moderate bleeding disorder caused by defective platelet activation and aggregation in response to collagen.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.11

Sequence similarities

Contains 2 Ig-like C2-type (immunoglobulin-like) domains.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

LYNP079482EBI-515278,EBI-79452

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9HCN6-1)

Also known as: VI-1;

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.
Isoform 2 (identifier: Q9HCN6-2)

Also known as: VI-2;

The sequence of this isoform differs from the canonical sequence as follows:
     204-221: Missing.
Isoform 3 (identifier: Q9HCN6-3)

Also known as: VI-3;

The sequence of this isoform differs from the canonical sequence as follows:
     260-339: PARQYYTKGN...QDVHSRGLCS → ESCPPVLHQG...TGMNMSITLI
Note: Has no transmembrane domain. Does not interact with Fc receptor gamma chain. Does not bind to collagen-like peptides.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 Potential
Chain21 – 339319Platelet glycoprotein VI
PRO_0000232383

Regions

Topological domain21 – 267247Extracellular Potential
Transmembrane268 – 28821Helical; Potential
Topological domain289 – 33951Cytoplasmic Potential
Domain26 – 10479Ig-like C2-type 1
Domain114 – 19683Ig-like C2-type 2

Amino acid modifications

Glycosylation921N-linked (GlcNAc...) Ref.7
Disulfide bond48 ↔ 88 Ref.9
Disulfide bond134 ↔ 180 Ref.9

Natural variations

Alternative sequence204 – 22118Missing in isoform 2.
VSP_017879
Alternative sequence260 – 33980PARQY…RGLCS → ESCPPVLHQGQPGPDMPRGC DPNNPGGVSGRGLAQPEEAP AAQGQGCAEAASAPPAPPAD PEIKRGSGWRPTGCSQPRVM FMTAEPQARSYPREGSWHGR RLKDWRVWSVEAGGQRLQLW KRGHAASSWCSIREPFGQCL SVCLPLCLRAPSIWDGRNLW RPHPPPCTLWMTWYPGWTTY WPLSSTSLIWAPDGSLRFPA LRVDSVPSSVQNPPVLPFGP LCSCLVFPRNSHPHSISHCG LTNLLSSLRTGLAGSLGMSF IFLSVKLARCPLPFTLENKI SLCNMVKPHLYQQNKKTQKL ARCGGASLYSQQLRGLRWEN GLSLGGRGCSELRSHHCTLA RVTKPDFVSKNTGMNMSITL I in isoform 3.
VSP_017880
Natural variant581R → C in BDPLT11; results in abnormal protein migration and a loss of collagen binding. Ref.10
VAR_066590
Natural variant1751S → N in BDPLT11; shows strongly reduced membrane expression and decreased interaction with the snake toxin convulxin. Ref.11
VAR_066591
Natural variant2191P → S. Ref.1 Ref.3 Ref.5
Corresponds to variant rs1613662 [ dbSNP | Ensembl ].
VAR_060352
Natural variant2371E → K. Ref.1 Ref.3 Ref.5
Corresponds to variant rs1654416 [ dbSNP | Ensembl ].
VAR_060353
Natural variant2491A → T. Ref.1 Ref.3 Ref.5
Corresponds to variant rs2304167 [ dbSNP | Ensembl ].
VAR_060354
Natural variant3171L → Q. Ref.1 Ref.3 Ref.5
Corresponds to variant rs1654413 [ dbSNP | Ensembl ].
VAR_059389
Natural variant3221N → H. Ref.1 Ref.3 Ref.5
Corresponds to variant rs1671152 [ dbSNP | Ensembl ].
VAR_059390
Natural variant3351R → G.
Corresponds to variant rs1654412 [ dbSNP | Ensembl ].
VAR_060355

Experimental info

Mutagenesis611K → A: Increases collagen binding. Ref.8
Mutagenesis791K → E: Dramatically reduces collagen binding. Ref.8
Mutagenesis801R → A: Reduces collagen binding. Ref.8
Mutagenesis921N → A: Reduces collagen binding (65 to 70%). Ref.7
Mutagenesis941S → A: Reduces collagen binding (65 to 70%). Ref.7
Mutagenesis951L → H: No effect on collagen binding. Ref.7
Mutagenesis1861R → A: Reduces collagen binding. Ref.8
Isoform 3:
Sequence conflict3141P → A in BAB12247. Ref.1
Sequence conflict3231K → T in BAB12247. Ref.1
Sequence conflict5731R → G in BAB12247. Ref.1
Sequence conflict6061F → L in BAB12247. Ref.1

Secondary structure

................................ 339
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (VI-1) [UniParc].

Last modified April 5, 2011. Version 4.
Checksum: 3EFE2DD0E1676BA8

FASTA33936,866
        10         20         30         40         50         60 
MSPSPTALFC LGLCLGRVPA QSGPLPKPSL QALPSSLVPL EKPVTLRCQG PPGVDLYRLE 

        70         80         90        100        110        120 
KLSSSRYQDQ AVLFIPAMKR SLAGRYRCSY QNGSLWSLPS DQLELVATGV FAKPSLSAQP 

       130        140        150        160        170        180 
GPAVSSGGDV TLQCQTRYGF DQFALYKEGD PAPYKNPERW YRASFPIITV TAAHSGTYRC 

       190        200        210        220        230        240 
YSFSSRDPYL WSAPSDPLEL VVTGTSVTPS RLPTEPPSPV AEFSEATAEL TVSFTNEVFT 

       250        260        270        280        290        300 
TETSRSITAS PKESDSPAGP ARQYYTKGNL VRICLGAVIL IILAGFLAED WHSRRKRLRH 

       310        320        330 
RGRAVQRPLP PLPPLPLTRK SNGGQDGGRQ DVHSRGLCS 

« Hide

Isoform 2 (VI-2) [UniParc].

Checksum: EEE281373112DB21
Show »

FASTA32135,091
Isoform 3 (VI-3) [UniParc].

Checksum: F6DBAE2547664D7A
Show »

FASTA62067,476

References

« Hide 'large scale' references
[1]"Molecular cloning, genomic structure, chromosomal localization, and alternative splice forms of the platelet collagen receptor glycoprotein VI."
Ezumi Y., Uchiyama T., Takayama H.
Biochem. Biophys. Res. Commun. 277:27-36(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), PROTEIN SEQUENCE OF 28-41; 62-79 AND 114-142, VARIANTS SER-219; LYS-237; THR-249; GLN-317 AND HIS-322.
[2]"Cloning, characterization, and functional studies of human and mouse glycoprotein VI: a platelet-specific collagen receptor from the immunoglobulin superfamily."
Jandrot-Perrus M., Busfield S., Lagrue A.-H., Xiong X., Debili N., Chickering T., Le Couedic J.-P., Goodearl A., Dussault B., Fraser C., Vainchenker W., Villeval J.-L.
Blood 96:1798-1807(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH FC RECEPTOR GAMMA CHAIN, TISSUE SPECIFICITY.
Tissue: Megakaryocyte.
[3]"Platelet glycoprotein VI."
Miura Y.
Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS SER-219; LYS-237; THR-249; GLN-317 AND HIS-322.
[4]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS SER-219; LYS-237; THR-249; GLN-317 AND HIS-322.
[6]"A novel association of Fc receptor gamma-chain with glycoprotein VI and their co-expression as a collagen receptor in human platelets."
Tsuji M., Ezumi Y., Arai M., Takayama H.
J. Biol. Chem. 272:23528-23531(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FC RECEPTOR GAMMA CHAIN.
[7]"The influence of N-linked glycosylation on the function of platelet glycoprotein VI."
Kunicki T.J., Cheli Y., Moroi M., Furihata K.
Blood 106:2744-2749(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-92, MUTAGENESIS OF ASN-92; SER-94 AND LEU-95.
[8]"Gain- and loss-of-function mutants confirm the importance of apical residues to the primary interaction of human glycoprotein VI with collagen."
O'connor M.N., Smethurst P.A., Farndale R.W., Ouwehand W.H.
J. Thromb. Haemost. 4:869-873(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF LYS-61; LYS-79; ARG-80 AND ARG-186.
[9]"Structural basis for platelet collagen responses by the immune-type receptor glycoprotein VI."
Horii K., Kahn M.L., Herr A.B.
Blood 108:936-942(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 21-203, DISULFIDE BONDS.
[10]"Absence of collagen-induced platelet activation caused by compound heterozygous GPVI mutations."
Dumont B., Lasne D., Rothschild C., Bouabdelli M., Ollivier V., Oudin C., Ajzenberg N., Grandchamp B., Jandrot-Perrus M.
Blood 114:1900-1903(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BDPLT11 CYS-58, CHARACTERIZATION OF VARIANT BDPLT11 CYS-58.
[11]"A compound heterozygous mutation in glycoprotein VI in a patient with a bleeding disorder."
Hermans C., Wittevrongel C., Thys C., Smethurst P.A., Van Geet C., Freson K.
J. Thromb. Haemost. 7:1356-1363(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BDPLT11 ASN-175, CHARACTERIZATION OF VARIANT BDPLT11 ASN-175.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB043819 mRNA. Translation: BAB12245.1.
AB043820 mRNA. Translation: BAB12246.1.
AB043821 mRNA. Translation: BAB12247.1.
AB035073 mRNA. Translation: BAA89353.1.
AC011476 Genomic DNA. No translation available.
BC104832 mRNA. Translation: AAI04833.1.
BC111963 mRNA. Translation: AAI11964.1.
PIRJC7509.
RefSeqNP_001077368.2. NM_001083899.2.
NP_001242946.2. NM_001256017.2.
NP_057447.5. NM_016363.5.
UniGeneHs.661752.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2GI7X-ray2.40A/B21-203[»]
ProteinModelPortalQ9HCN6.
SMRQ9HCN6. Positions 22-261.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119379. 8 interactions.
DIPDIP-33875N.
IntActQ9HCN6. 4 interactions.
MINTMINT-258007.
STRING9606.ENSP00000308782.

Protein family/group databases

MEROPSI43.001.

PTM databases

PhosphoSiteQ9HCN6.

Polymorphism databases

DMDM327478600.

Proteomic databases

PaxDbQ9HCN6.
PRIDEQ9HCN6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000310373; ENSP00000308782; ENSG00000088053. [Q9HCN6-3]
ENST00000333884; ENSP00000334552; ENSG00000088053. [Q9HCN6-2]
ENST00000417454; ENSP00000394922; ENSG00000088053. [Q9HCN6-1]
ENST00000570488; ENSP00000461307; ENSG00000262239. [Q9HCN6-3]
ENST00000570691; ENSP00000459479; ENSG00000262069. [Q9HCN6-3]
ENST00000571038; ENSP00000460456; ENSG00000262729. [Q9HCN6-2]
ENST00000571040; ENSP00000459136; ENSG00000262797. [Q9HCN6-3]
ENST00000571499; ENSP00000461350; ENSG00000262069. [Q9HCN6-1]
ENST00000571588; ENSP00000459854; ENSG00000261961. [Q9HCN6-2]
ENST00000571788; ENSP00000460120; ENSG00000262729. [Q9HCN6-1]
ENST00000571871; ENSP00000458353; ENSG00000262239. [Q9HCN6-2]
ENST00000572462; ENSP00000461591; ENSG00000262867. [Q9HCN6-1]
ENST00000572481; ENSP00000458990; ENSG00000261961. [Q9HCN6-1]
ENST00000572667; ENSP00000461472; ENSG00000262131. [Q9HCN6-2]
ENST00000572758; ENSP00000461769; ENSG00000263239. [Q9HCN6-1]
ENST00000572791; ENSP00000461893; ENSG00000262797. [Q9HCN6-1]
ENST00000573240; ENSP00000459929; ENSG00000262729. [Q9HCN6-3]
ENST00000573444; ENSP00000459377; ENSG00000263239. [Q9HCN6-3]
ENST00000573560; ENSP00000458588; ENSG00000261961. [Q9HCN6-3]
ENST00000573764; ENSP00000460988; ENSG00000262069. [Q9HCN6-2]
ENST00000573811; ENSP00000461262; ENSG00000262797. [Q9HCN6-2]
ENST00000574117; ENSP00000461858; ENSG00000262131. [Q9HCN6-1]
ENST00000574603; ENSP00000460778; ENSG00000263239. [Q9HCN6-2]
ENST00000575496; ENSP00000458876; ENSG00000262239. [Q9HCN6-1]
ENST00000575642; ENSP00000458153; ENSG00000262131. [Q9HCN6-3]
ENST00000575740; ENSP00000458526; ENSG00000262867. [Q9HCN6-2]
ENST00000576196; ENSP00000459588; ENSG00000262867. [Q9HCN6-3]
ENST00000603026; ENSP00000474218; ENSG00000270886. [Q9HCN6-1]
ENST00000603929; ENSP00000474113; ENSG00000270886. [Q9HCN6-3]
ENST00000605588; ENSP00000474340; ENSG00000270886. [Q9HCN6-2]
GeneID51206.
KEGGhsa:51206.
UCSCuc002qik.3. human. [Q9HCN6-1]
uc002qil.3. human. [Q9HCN6-3]
uc010esq.3. human. [Q9HCN6-2]

Organism-specific databases

CTD51206.
GeneCardsGC19M055525.
HGNCHGNC:14388. GP6.
MIM605546. gene.
614201. phenotype.
neXtProtNX_Q9HCN6.
Orphanet98885. Bleeding diathesis due to glycoprotein VI deficiency.
PharmGKBPA28824.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG79029.
HOGENOMHOG000234395.
HOVERGENHBG074353.
KOK06264.
OMAASSWCSI.
PhylomeDBQ9HCN6.
TreeFamTF336644.

Enzyme and pathway databases

ReactomeREACT_604. Hemostasis.

Gene expression databases

ArrayExpressQ9HCN6.
BgeeQ9HCN6.
CleanExHS_GP6.
GenevestigatorQ9HCN6.

Family and domain databases

Gene3D2.60.40.10. 2 hits.
InterProIPR013783. Ig-like_fold.
IPR003599. Ig_sub.
[Graphical view]
SMARTSM00409. IG. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9HCN6.
GeneWikiGPVI.
GenomeRNAi51206.
NextBio54258.
PROQ9HCN6.
SOURCESearch...

Entry information

Entry nameGPVI_HUMAN
AccessionPrimary (citable) accession number: Q9HCN6
Secondary accession number(s): Q9HCN7, Q9UIF2
Entry history
Integrated into UniProtKB/Swiss-Prot: April 4, 2006
Last sequence update: April 5, 2011
Last modified: April 16, 2014
This is version 109 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM