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FLASH GENE

Symbol

GP6

contributors: mct/pgu - updated : 27-06-2018

HGNC name	glycoprotein VI (platelet)
HGNC id	14388

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	19q13.42      Physical location : 55.525.076 - 55.549.632
Synonym name	platelet collagen receptor
Synonym symbol(s)	GPIV, GPVI, MGC138168, BDPLT11

DNA

TYPE	functioning gene
STRUCTURE	24.56 kb     8 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_016363 8 - 2264 NP_057447 58 339 - 2000 11027634 NM_001256017 7 splicing 2210 NP_001242946 - 321 - 2000 11027634 NM_001083899 8 splicing 2268 NP_001077368 - 620 - 2000 11027634

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive mouth tongue         pharynx         Endocrine thyroid

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic megakaryocyte Homo sapiens Blood/Hematopoietic platelet Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

several ligand binding sites

conjugated

GlycoP

mono polymer

homomer , dimer

HOMOLOGY

Homologene

FAMILY

paired Ig-like receptor family

CATEGORY

immunity/defense , signaling , receptor

SUBCELLULAR LOCALIZATION

plasma membrane

basic FUNCTION	playing a role in collagen-induced activation and aggregation of platelets
	has a crucial role in platelet responses to collagen
	mediates platelet activation on exposed subendothelial collagens at sites of vascular injury and thereby contributes to normal hemostasis, but also to the occlusion of diseased vessels in the setting of myocardial infarction or stroke
	GP6 shedding is implicated in the pathology of acute ischemic stroke
	GP6 and CLEC1B can be simultaneously downregulated in platelets, suggesting an unexpected functional redundancy of the 2 receptors in hemostasis and thrombosis
	GP6 is a platelet receptor for polymerized fibrin with 2 major functions: (1) amplification of thrombin generation and (2) recruitment of circulating platelets to clots
	GP6 is a receptor for fibrin and this interaction contributes to thrombus growth and stability
	platelet adhesion to collagen induces GP6 dimer clustering, increasing both avidity for collagen and the proximity of GP6-associated signaling molecules, which may be crucial for the initiation and persistence of signaling

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

coagulation/hemostasis

PATHWAY

metabolism

signaling

signal transduction

a component

FCER1G -GP6

INTERACTION

DNA

RNA

small molecule

protein	FCER1G
	interacting as a dimer exclusively with fibrous collagen
	regulating protein-kinase B
	specific binding to BSG (platelet GP6 is a novel receptor for BSG and can mediate platelet rolling via GP6-BSG interaction)
	interacting with UBASH3B (functions as a negative regulator of GP6 signaling in platelets) )
	interacting with PECAM1 and LYN (PECAM1 and the Src family kinase LYN inhibit platelet activation by the glycoprotein VI (GP6) collagen receptor)
	PDLIM1 acts as a negative regulator of GP6 signaling, and acts as a negative regulator of GP6 signaling also under flow
	BSG, which binds to the platelet-specific collagen receptor glycoprotein (GP6), is expressed in a range of cell types including platelets and leukocytes, and has been implicated in neoplastic disease and atherosclerotic coronary disease
	RHOG is essential for normal granule secretion downstream of the collagen receptor GP6
	TSPAN14 was unique in reducing cleavage of the platelet collagen receptor GP6
	UBASH3B suppresses activation of SYK through the GP6 platelet receptor for collagen by dephosphorylating Tyr(P)346, a regulatory site of SYK
	TSPAN9 plays a fine-tuning role in platelet activation by regulating GP6 membrane dynamics
	ceramidase critically affects GP6-dependent platelet activation and thrombus formation

cell & other

REGULATION

induced by

thrombopoietin

inhibited by

SLA2 that may have function as a negative regulator of GP6-mediated signaling by interacting with CBL, being similar to that reported in T cells

repressed by

PECAM1/PTPN11 complexes, formed in a LYN-dependent manner, that suppress GP6 signaling

Other	bound by its cytoplasmic domain and regulated by calmodulin
	only expressed in presence of FLI1,GATA1 and SPI1

ASSOCIATED DISORDERS

corresponding disease(s)

Susceptibility

to platelet hyperaggregability and miscarriage

Variant & Polymorphism SNP	significant higher occurrence of two haplotypes (ACGG, CCGT) increasing the risk of platelet hyperaggregability and miscarriage

Candidate gene
Marker	platelet GP6 surface expression is enhanced in patients at risk for an acute coronary syndrome and is an early marker for imminent acute coronary events in patients with chest pain
	measurement of soluble GP6 level is considered to be important for the diagnosis and evaluation of thrombotic microangiopathy (TMA)
Therapy target
	System Type Disorder Pubmed blood coagulation   ectodomain shedding of GPVI can be mediated through multiple differentially regulated platelet-expressed proteinases with obvious therapeutic implications in thrombosis blood coagulation   Blockade of collagen binding to GPVI would prevent initial adhesion and further activation of the platelet and would have an enormous impact in antithrombotic therapy

ANIMAL & CELL MODELS