F2RL1 (F2R like trypsin receptor 1)

Gene

• Entrez ID: 2150
• Gene name: F2R like trypsin receptor 1
• Gene symbol: F2RL1
• Synonyms: GPR11, PAR2
• Chromosome: 5
• Chromosome location: 5q13.3
• Summary: This gene encodes a member of the G-protein coupled receptor 1 family of proteins. The encoded cell surface receptor is activated through proteolytic cleavage of its extracellular amino terminus, resulting in a new amino terminus that acts as a tethered ligand that binds to an extracellular loop domain. Activation of the receptor has been shown to stimulate vascular smooth muscle relaxation, dilate blood vessels, increase blood flow, and lower blood pressure. This protein is also important in the inflammatory response, as well as innate and adaptive immunity. [provided by RefSeq, Jun 2016]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT023577	hsa-miR-1-3p	Microarray	18668037
MIRT359183	hsa-miR-190a-3p	PAR-CLIP	23446348
MIRT359183	hsa-miR-190a-3p	PAR-CLIP	20371350
MIRT359183	hsa-miR-190a-3p	HITS-CLIP	21572407
MIRT359185	hsa-miR-410-3p	PAR-CLIP	23446348
MIRT359185	hsa-miR-410-3p	PAR-CLIP	20371350
MIRT359185	hsa-miR-410-3p	HITS-CLIP	21572407
MIRT359186	hsa-miR-511-3p	PAR-CLIP	23446348
MIRT359186	hsa-miR-511-3p	PAR-CLIP	20371350
MIRT359186	hsa-miR-511-3p	HITS-CLIP	21572407
MIRT359188	hsa-miR-1277-5p	PAR-CLIP	23446348
MIRT359188	hsa-miR-1277-5p	PAR-CLIP	20371350
MIRT359188	hsa-miR-1277-5p	HITS-CLIP	21572407
MIRT359189	hsa-miR-4495	PAR-CLIP	23446348
MIRT359189	hsa-miR-4495	PAR-CLIP	20371350
MIRT359189	hsa-miR-4495	HITS-CLIP	21572407
MIRT359191	hsa-miR-5011-5p	PAR-CLIP	23446348
MIRT359191	hsa-miR-5011-5p	PAR-CLIP	20371350
MIRT359191	hsa-miR-5011-5p	HITS-CLIP	21572407
MIRT509885	hsa-miR-223-5p	PAR-CLIP	23446348
MIRT509885	hsa-miR-223-5p	PAR-CLIP	20371350
MIRT509885	hsa-miR-223-5p	HITS-CLIP	21572407
MIRT509886	hsa-miR-205-3p	PAR-CLIP	23446348
MIRT509886	hsa-miR-205-3p	PAR-CLIP	20371350
MIRT523836	hsa-miR-640	PAR-CLIP	23446348
MIRT523837	hsa-miR-6821-3p	PAR-CLIP	23446348
MIRT523838	hsa-miR-6790-3p	PAR-CLIP	23446348
MIRT523839	hsa-miR-1224-3p	PAR-CLIP	23446348
MIRT523840	hsa-miR-6813-3p	PAR-CLIP	23446348
MIRT523840	hsa-miR-6813-3p	HITS-CLIP	23313552
MIRT629089	hsa-miR-744-3p	HITS-CLIP	23824327
MIRT629089	hsa-miR-744-3p	HITS-CLIP	19536157
MIRT629090	hsa-miR-4423-5p	HITS-CLIP	23824327
MIRT629090	hsa-miR-4423-5p	HITS-CLIP	19536157
MIRT629091	hsa-miR-6501-5p	HITS-CLIP	23824327
MIRT629091	hsa-miR-6501-5p	HITS-CLIP	19536157
MIRT629092	hsa-miR-4430	HITS-CLIP	23824327
MIRT629093	hsa-miR-3652	HITS-CLIP	23824327
MIRT629094	hsa-miR-122-5p	HITS-CLIP	23824327
MIRT629095	hsa-miR-504-3p	HITS-CLIP	23824327
MIRT629096	hsa-miR-3135b	HITS-CLIP	23824327
MIRT629097	hsa-miR-367-5p	HITS-CLIP	23824327
MIRT629097	hsa-miR-367-5p	HITS-CLIP	19536157
MIRT629098	hsa-miR-1266-3p	HITS-CLIP	23824327
MIRT629099	hsa-miR-454-3p	HITS-CLIP	23824327
MIRT629100	hsa-miR-4295	HITS-CLIP	23824327
MIRT629101	hsa-miR-3666	HITS-CLIP	23824327
MIRT629102	hsa-miR-301b-3p	HITS-CLIP	23824327
MIRT629103	hsa-miR-301a-3p	HITS-CLIP	23824327
MIRT629104	hsa-miR-130b-3p	HITS-CLIP	23824327
MIRT629105	hsa-miR-130a-3p	HITS-CLIP	23824327
MIRT685226	hsa-miR-5089-5p	HITS-CLIP	23313552
MIRT685227	hsa-miR-6878-3p	HITS-CLIP	23313552
MIRT685228	hsa-miR-466	HITS-CLIP	23313552
MIRT685229	hsa-miR-4672	HITS-CLIP	23313552
MIRT685230	hsa-miR-3941	HITS-CLIP	23313552
MIRT685231	hsa-miR-6744-3p	HITS-CLIP	23313552
MIRT685232	hsa-miR-4757-5p	HITS-CLIP	23313552
MIRT685233	hsa-miR-5589-5p	HITS-CLIP	23313552
MIRT685234	hsa-miR-4731-5p	HITS-CLIP	23313552
MIRT685235	hsa-miR-6778-3p	HITS-CLIP	23313552
MIRT685236	hsa-miR-6506-5p	HITS-CLIP	23313552
MIRT685237	hsa-miR-619-5p	HITS-CLIP	23313552
MIRT685238	hsa-miR-150-5p	HITS-CLIP	23313552
MIRT685239	hsa-miR-212-5p	HITS-CLIP	23313552
MIRT685240	hsa-miR-186-3p	HITS-CLIP	23313552
MIRT685241	hsa-miR-520h	HITS-CLIP	23313552
MIRT685242	hsa-miR-520g-3p	HITS-CLIP	23313552
MIRT685243	hsa-miR-512-3p	HITS-CLIP	23313552
MIRT685244	hsa-miR-603	HITS-CLIP	23313552
MIRT685245	hsa-miR-362-3p	HITS-CLIP	23313552
MIRT685246	hsa-miR-329-3p	HITS-CLIP	23313552
MIRT685247	hsa-miR-8485	HITS-CLIP	23313552
MIRT685248	hsa-miR-520e	HITS-CLIP	23313552
MIRT685249	hsa-miR-520d-3p	HITS-CLIP	23313552
MIRT685250	hsa-miR-520c-3p	HITS-CLIP	23313552
MIRT685251	hsa-miR-520b	HITS-CLIP	23313552
MIRT685252	hsa-miR-520a-3p	HITS-CLIP	23313552
MIRT685253	hsa-miR-373-3p	HITS-CLIP	23313552
MIRT685254	hsa-miR-372-3p	HITS-CLIP	23313552
MIRT685255	hsa-miR-302e	HITS-CLIP	23313552
MIRT685256	hsa-miR-302d-3p	HITS-CLIP	23313552
MIRT685257	hsa-miR-302c-3p	HITS-CLIP	23313552
MIRT685258	hsa-miR-302b-3p	HITS-CLIP	23313552
MIRT685259	hsa-miR-302a-3p	HITS-CLIP	23313552
MIRT685260	hsa-miR-93-5p	HITS-CLIP	23313552
MIRT685261	hsa-miR-526b-3p	HITS-CLIP	23313552
MIRT685262	hsa-miR-519d-3p	HITS-CLIP	23313552
MIRT685263	hsa-miR-20b-5p	HITS-CLIP	23313552
MIRT685264	hsa-miR-20a-5p	HITS-CLIP	23313552
MIRT685265	hsa-miR-17-5p	HITS-CLIP	23313552
MIRT685266	hsa-miR-106b-5p	HITS-CLIP	23313552
MIRT685267	hsa-miR-106a-5p	HITS-CLIP	23313552
MIRT724006	hsa-miR-6833-3p	HITS-CLIP	19536157
MIRT724007	hsa-miR-4768-5p	HITS-CLIP	19536157
MIRT724008	hsa-miR-6894-3p	HITS-CLIP	19536157
MIRT724009	hsa-miR-6514-3p	HITS-CLIP	19536157
MIRT724010	hsa-miR-6873-3p	HITS-CLIP	19536157
MIRT724011	hsa-miR-5581-5p	HITS-CLIP	19536157
MIRT724012	hsa-miR-4297	HITS-CLIP	19536157
MIRT724013	hsa-miR-4763-5p	HITS-CLIP	19536157
MIRT724014	hsa-miR-942-5p	HITS-CLIP	19536157
MIRT724015	hsa-miR-1304-3p	HITS-CLIP	19536157
MIRT724016	hsa-miR-6747-3p	HITS-CLIP	19536157
MIRT724017	hsa-miR-483-3p	HITS-CLIP	19536157

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001965	Function	G-protein alpha-subunit binding	ISS
GO:0002286	Process	T cell activation involved in immune response	ISS
GO:0002690	Process	Positive regulation of leukocyte chemotaxis	IDA	17991872
GO:0002720	Process	Positive regulation of cytokine production involved in immune response	IDA	11441110
GO:0003104	Process	Positive regulation of glomerular filtration	ISS
GO:0004930	Function	G protein-coupled receptor activity	IBA	21873635
GO:0004930	Function	G protein-coupled receptor activity	IMP	18622013, 28445455
GO:0004930	Function	G protein-coupled receptor activity	ISS
GO:0005102	Function	Signaling receptor binding	TAS	8615752
GO:0005515	Function	Protein binding	IPI	10725339, 15708858, 16410250, 16959886, 17693410, 20826780, 21219331, 28298427
GO:0005769	Component	Early endosome	IDA	22547407
GO:0005794	Component	Golgi apparatus	TAS	8615752
GO:0005886	Component	Plasma membrane	IDA	22547407, 28445455
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	IBA	21873635
GO:0005887	Component	Integral component of plasma membrane	IDA	17848177
GO:0006954	Process	Inflammatory response	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	IMP	28445455
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0007204	Process	Positive regulation of cytosolic calcium ion concentration	IDA	10725339
GO:0007204	Process	Positive regulation of cytosolic calcium ion concentration	ISS
GO:0007596	Process	Blood coagulation	IEA
GO:0010804	Process	Negative regulation of tumor necrosis factor-mediated signaling pathway	IDA	19781631
GO:0014068	Process	Positive regulation of phosphatidylinositol 3-kinase signaling	ISS
GO:0015057	Function	Thrombin-activated receptor activity	IEA
GO:0030193	Process	Regulation of blood coagulation	IDA	17848177
GO:0030335	Process	Positive regulation of cell migration	ISS
GO:0030836	Process	Positive regulation of actin filament depolymerization	IDA	17500066
GO:0031143	Component	Pseudopodium	ISS
GO:0031274	Process	Positive regulation of pseudopodium assembly	ISS
GO:0031681	Function	G-protein beta-subunit binding	ISS
GO:0032602	Process	Chemokine production	IDA	19494303, 21501162
GO:0032609	Process	Interferon-gamma production	ISS
GO:0032611	Process	Interleukin-1 beta production	IDA	15155775
GO:0032613	Process	Interleukin-10 production	IDA	18453611
GO:0032682	Process	Negative regulation of chemokine production	IDA	19865078
GO:0032755	Process	Positive regulation of interleukin-6 production	IDA	11447194, 15155775
GO:0032757	Process	Positive regulation of interleukin-8 production	IDA	15155775, 17404307, 18622013, 19865078
GO:0032930	Process	Positive regulation of superoxide anion generation	IDA	11714832
GO:0034137	Process	Positive regulation of toll-like receptor 2 signaling pathway	IMP	19865078
GO:0034140	Process	Negative regulation of toll-like receptor 3 signaling pathway	IMP	19865078
GO:0034141	Process	Positive regulation of toll-like receptor 3 signaling pathway	IMP	19865078
GO:0034145	Process	Positive regulation of toll-like receptor 4 signaling pathway	IDA	18622013
GO:0035025	Process	Positive regulation of Rho protein signal transduction	IBA	21873635
GO:0035025	Process	Positive regulation of Rho protein signal transduction	IMP	20826780
GO:0035025	Process	Positive regulation of Rho protein signal transduction	ISS
GO:0038023	Function	Signaling receptor activity	TAS	8615752
GO:0042119	Process	Neutrophil activation	IDA	15155775
GO:0042311	Process	Vasodilation	ISS
GO:0043122	Process	Regulation of I-kappaB kinase/NF-kappaB signaling	IDA	18453611
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IDA	11413129
GO:0043311	Process	Positive regulation of eosinophil degranulation	IDA	11714832
GO:0043547	Process	Positive regulation of GTPase activity	IMP	23202369
GO:0045087	Process	Innate immune response	IEA
GO:0045217	Process	Cell-cell junction maintenance	IMP	23202369
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	16410250
GO:0046328	Process	Regulation of JNK cascade	IDA	16410250
GO:0046329	Process	Negative regulation of JNK cascade	IDA	19781631
GO:0046330	Process	Positive regulation of JNK cascade	IDA	11413129
GO:0050900	Process	Leukocyte migration	IDA	15155775
GO:0050921	Process	Positive regulation of chemotaxis	ISS
GO:0050927	Process	Positive regulation of positive chemotaxis	IDA	17991872
GO:0051482	Process	Positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway	IBA	21873635
GO:0051607	Process	Defense response to virus	IDA	18453611, 19494303
GO:0060100	Process	Positive regulation of phagocytosis, engulfment	IDA	21501162
GO:0061028	Process	Establishment of endothelial barrier	IDA	20826780
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	IDA	10725339
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	ISS
GO:0070493	Process	Thrombin-activated receptor signaling pathway	IEA
GO:0070661	Process	Leukocyte proliferation	ISS
GO:0070963	Process	Positive regulation of neutrophil mediated killing of gram-negative bacterium	IDA	21501162
GO:0097029	Process	Mature conventional dendritic cell differentiation	IDA	16478888
GO:0097029	Process	Mature conventional dendritic cell differentiation	ISS
GO:1900135	Process	Positive regulation of renin secretion into blood stream	ISS
GO:2000341	Process	Regulation of chemokine (C-X-C motif) ligand 2 production	IDA	21501162

Other IDs

• MIM: 600933
• HGNC: 3538
• e!Ensembl: ENSG00000164251

Protein

• UniProt ID: P55085
• Protein name: Proteinase-activated receptor 2 (PAR-2) (Coagulation factor II receptor-like 1) (G-protein coupled receptor 11) (Thrombin receptor-like 1) [Cleaved into: Proteinase-activated receptor 2, alternate cleaved 1; Proteinase-activated receptor 2, alternate cleaved 2]
• Protein function: Receptor for trypsin and trypsin-like enzymes coupled to G proteins (PubMed:28445455). Its function is mediated through the activation of several signaling pathways including phospholipase C (PLC), intracellular calcium, mitogen-activated protein kinase (MAPK), I-kappaB kinase/NF-kappaB and Rho (PubMed:28445455). Can also be transactivated by cleaved F2R/PAR1. Involved in modulation of inflammatory responses and regulation of innate and adaptive immunity, and acts as a sensor for proteolytic enzymes generated during infection. Generally is promoting inflammation. Can signal synergistically with TLR4 and probably TLR2 in inflammatory responses and modulates TLR3 signaling. Has a protective role in establishing the endothelial barrier; the activity involves coagulation factor X. Regulates endothelial cell barrier integrity during neutrophil extravasation, probably following proteolytic cleavage by PRTN3 (PubMed:23202369). Proposed to have a bronchoprotective role in airway epithelium, but also shown to compromise the airway epithelial barrier by interrupting E-cadherin adhesion (PubMed:10086357). Involved in the regulation of vascular tone; activation results in hypotension presumably mediated by vasodilation. Associates with a subset of G proteins alpha subunits such as GNAQ, GNA11, GNA14, GNA12 and GNA13, but probably not with G(o) alpha, G(i) subunit alpha-1 and G(i) subunit alpha-2. However, according to PubMed:21627585 can signal through G(i) subunit alpha. Believed to be a class B receptor which internalizes as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptor, for extended periods of time. Mediates inhibition of TNF-alpha stimulated JNK phosphorylation via coupling to GNAQ and GNA11; the function involves dissociation of RIPK1 and TRADD from TNFR1. Mediates phosphorylation of nuclear factor NF-kappa-B RELA subunit at 'Ser-536'; the function involves IKBKB and is predominantly independent of G proteins. Involved in cellular migration. Involved in cytoskeletal rearrangement and chemotaxis through beta-arrestin-promoted scaffolds; the function is independent of GNAQ and GNA11 and involves promotion of cofilin dephosphorylation and actin filament severing. Induces redistribution of COPS5 from the plasma membrane to the cytosol and activation of the JNK cascade is mediated by COPS5. Involved in the recruitment of leukocytes to the sites of inflammation and is the major PAR receptor capable of modulating eosinophil function such as proinflammatory cytokine secretion, superoxide production and degranulation. During inflammation promotes dendritic cell maturation, trafficking to the lymph nodes and subsequent T-cell activation. Involved in antimicrobial response of innate immune cells; activation enhances phagocytosis of Gram-positive and killing of Gram-negative bacteria. Acts synergistically with interferon-gamma in enhancing antiviral responses. Implicated in a number of acute and chronic inflammatory diseases such as of the joints, lungs, brain, gastrointestinal tract, periodontium, skin, and vascular systems, and in autoimmune disorders.
• PDB: 5NDD, 5NDZ, 5NJ6
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00001	7tm_1	92 → 344	7 transmembrane receptor (rhodopsin family)	Family

• Sequence:

  MRSPSAAWLLGAAILLAASLSCSGTIQGTNRSSKGRSLIGKVDGTSHVTGKGVTVETVFS
  VDEFSASVLTGKLTTVFLPIVYTIVFVVGLPSNGMALWVFLFRTKKKHPAVIYMANLALA
  DLLSVIWFPLKIAYHIHGNNWIYGEALCNVLIGFFYGNMYCSILFMTCLSVQRYWVIVNP
  MGHSRKKANIAIGISLAIWLLILLVTIPLYVVKQTIFIPALNITTCHDVLPEQLLVGDMF
  NYFLSLAIGVFLFPAFLTASAYVLMIRMLRSSAMDENSEKKRKRAIKLIVTVLAMYLICF
  TPSNLLLVVHYFLIKSQGQSHVYALYIVALCLSTLNSCIDPFVYYFVSHDFRDHAKNALL
  CRSVRTVKQMQVSLTSKKHSRKSSSYSSSSTTVKTSY

• Sequence length: 397