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FLASH GENE

Symbol

F2RL1

contributors: mct/npt - updated : 24-10-2016

HGNC name	coagulation factor II (thrombin) receptor-like 1
HGNC id	3538

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	5q13.3      Physical location : 76.114.832 - 76.131.139
Synonym name	thrombin-receptor, proteinase activated receptor 2
	G-protein coupled receptor 11
	protease-activated receptor 2
	thrombin receptor-like 1
Synonym symbol(s)	GPR11, PAR2, PAR-2

DNA

TYPE	like-sequence
STRUCTURE	16.31 kb     2 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

status

confirmed

Map	cen - D5S1977 - D5S424 - F2RL1 - F2R - F2RL2 - D5S2529 - D5S2596 - qter
Authors	Schmidt (97),Guyonnet Duperat (98)

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005242 2 - 2883 NP_005233 44.1 397 - Moriyuki (2008)

EXPRESSION

Type

widely

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 intestine small intestine     moderately   intestine large intestine colon   moderately   liver       moderately Endocrine pancreas       moderately Respiratory respiratory tract         Homo sapiens Urinary kidney       highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier/lining endothelium     Muscular smooth       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic eosinophil Blood/Hematopoietic monocyte Lymphoid/Immune macrophage Skin/Tegument keratinocyte

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	seven transmembrane segments (7TM) receptor, orphan receptor, coagulation
	multiple intracellular domains required for the interaction with COPS5

mono polymer

heteromer , dimer

HOMOLOGY

interspecies

homolog to murine F2rl1

Homologene

FAMILY	G protein coupled receptor superfamily
	protease activated receptor family

CATEGORY

receptor membrane G

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi

basic FUNCTION	mediating phagocytosis in a RhoA dependent manner in keratinocytes
	involved in the invasive phase of placentation
	modulating eosinophil function
	may have a role in the regulation of vascular tone
	may be an important regulator of skin mast cell function during cutaneous inflammation and hypersensitivity
	distinct roles of F2R, F2RL1 in signal transduction regulation of endothelial nitric oxide synthase
	regulates the F2R hyperplastic response to arterial injury leading to stenosis
	its activation contributes to determination of cells of both osteoblast and osteoclast lineages within bone marrow, and thereby participates in the regulation of skeletal growth and bone repair
	important role in the pathogenesis of collagen-induced arthritis
	receptor for inflammatory proteases, and is a major mediator of neurogenic inflammation and pain

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

inflammation

text	organogenesis
	anti-inflammatory signal

PATHWAY

metabolism

signaling

signal transduction

	mediating signal transduction by RhoA (ARHA)
	KLK6-signaling axis in CNS neurons that is mediated by F2R and F2RL1 and is positioned to contribute to neurodegeneration

a component

F2R and F2RL1 form a heterodimer that exhibits unique trafficking and signaling behaviors compared with receptor protomers

INTERACTION

DNA

RNA

small molecule

protein	F2RL1 and TMED2 interaction occurs between the N-terminal region of TMED2 p24A-GL (GOLD domain with a small linker)) and the second extracellular loop of F2RL1, and after receptor activation, F2RL1 dissociates from TMED2
	collectively, membrane PRTN3 acts as a non-opsonic phagocytosis receptor for bacteria probably by activating F2RL1 in neutrophils
	F3 mediates signalling through coagulation proteases that activate the G-protein-coupled receptors F2R and F2RL1
	KLK14, acting via F2RL1, represents an autocrine/paracrine regulator of colon tumorigenesis
	F3-binding to its ligand F7 induces activation of F2RL1 and this event is thought to considerably influence atherosclerosis and tumor angiogenesis
	F3 participates in protease-activated receptor F2R and F2RL1 activation
	F2RL1 activation generates a signal that induces sustained activation of TRPV4, which requires a key tyrosine residue (TRPV4-Tyr-110)
	ELANE stimulates the secretion of MUC5AC from airway epithelial cells, and can increase F2RL1 expression and MUC5AC release
	extra-pancreatic PRSS3 is produced by esophageal adenocarcinoma (EA) and activates likely F2RL1 in an autocrine manner (F2RL1 activation increases cancer cell proliferation, and promotes cancer cell survival)
	novel functional network of ELANE, secretases, and F2RL1 that regulate CXCR1 expression on neutrophils
	CTSS is a biased agonist of F2RL1 that causes F2RL1- and TRPV4-dependent inflammation and pain
	ELANE activates protease-activated receptor-2 (F2RL1) and transient receptor potential vanilloid 4 (TRPV4) to cause inflammation and pain
	TMPRSS11D displays its physiological functions via protease-activated receptor 2 F2RL1
	TMPRSS11D stimulates IL8 synthesis in airway epithelial cells via F2RL1 and could help to amplify inflammation in chronic respiratory tract disease
	activation of F2RL1 increases expression of BCLl2L12 in lung cancer cells

cell & other

REGULATION

activated by	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
	TMPRSS2

Other

regulated by plasmin and elastase

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       gain of function induced the redistribution of COPS5 from the plasma membrane to the cytosol, but did not influence expression of COPS5

Susceptibility

to arthritis to atopic dermatitis

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed miscelleaneous urinary chronic kidney disease F2RL1 antagonists could be useful disease-modifying, anti-inflammatory agents in kidney disease

ANIMAL & CELL MODELS