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FLASH GENE

Symbol

F2RL3

contributors: mct - updated : 14-11-2015

HGNC name	coagulation factor II (thrombin) receptor-like 3
HGNC id	3540

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	like-sequence
STRUCTURE	3.00 kb     2 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003950 2 - 2731 NP_003941 - 385 - 2003 12871418

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 Cardiovascular heart         Homo sapiens Digestive intestine large intestine colon     Nervous brain         Homo sapiens Reproductive male system testis

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow       Muscular smooth       Homo sapiens Muscular striatum cardiac     Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic monocyte Blood/Hematopoietic platelet Homo sapiens Cardiovascular endothelial cell Homo sapiens Lymphoid/Immune macrophage

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

seven transmembrane segments (7TM) receptor

HOMOLOGY

Homologene

FAMILY

G protein coupled receptor superfamily

CATEGORY

receptor

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane

basic FUNCTION	cofactor for the cleavage and activation of PAR4 (F2RL3) by F2 (mouse)
	thrombin activated receptor
	activating platelets after binding thrombin
	is a previously unknown modulator of visceral nociception
	involved in signaling of platelet aggregation via Ca2+ mobilization and synergistic P2Y12 receptor activation
	F2R and F2RL3 stimulate different signaling pathways in platelets and likely cooperate to mediate the complete response of the platelets to thrombin
	is involved in sustained platelet activation, and it invokes sustained intracellular calcium response in platelets, phosphyltidylserine exposure, thrombin generation, and fibrin deposition

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	F2RL2 cofactor for activation by thrombin
	mediating cathepsin G dependent platelet secretion and aggregation
	interaction between F2R and F2RL3, F2RL3 also interacts with the P2Y12 receptor on platelets to alter signaling
	uses its anionic cluster to interact with alpha-thrombin and this interaction is important even in the presence of F2R
	is a target of MASP1 (MASP1-induced F2RL3 activation could contribute to the development of the inflammatory reaction)
	F2R and F2RL3 are functionally expressed in large myelinated fibre neurons, and are also expressed in small nociceptors of the peptidergic subclass, where they are able to potentiate TRPV1 activity
	promotes cell migration via F2RL3
	thrombin activates platelets by binding and cleaving protease-activated receptors F2R and F2RL3
	KLK1 gain de function in tubular epithelial cells may mediate pro-inflammatory pathway and F2RL3 activation during diabetic nephropathy
	PCTP is a regulator of platelet F2RL3 function

cell & other

REGULATION

activated by	thrombin or trypsin,mediates platelets response to cathepsin G
	proteases including thrombin (proteolytic cleavage of its extracellular N terminus,generating a new receptor N terminus which functions as a tethered ligand and activates the receptor
	independently of GPIbalpha and ADP

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   during the progression of colon and prostate cancers tumoral     --low   occurs frequently in gastric cancers, may result from hypermethylation of the promoter and exhibits association with more aggressive gastric cancer

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

blood-brain barrier disruption and cerebral edema were also attenuated in PAR4-/- mice compared with wild-type animals