O00254 (PAR3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Proteinase-activated receptor 3
Short name=PAR-3

Alternative name(s):
Coagulation factor II receptor-like 2
Thrombin receptor-like 2

Gene names

Name:	F2RL2
Synonyms:	PAR3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	374 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for activated thrombin coupled to G proteins that stimulate phosphoinositide hydrolysis. Ref.9
Subunit structure	Interacts with INSC/inscuteable and probably GPSM2. Ref.10
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Highest expression in the megakaryocytes of the bone marrow, lower in mature megakaryocytes, in platelets and in a variety of other tissues such as heart and gut. Ref.8
Post-translational modification	A proteolytic cleavage generates a new N-terminus that functions as a tethered ligand.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.
Sequence caution	The sequence CAD97628.1 differs from that shown. Reason: Frameshift at position 374.

Ontologies

Keywords
Biological process	Blood coagulation Hemostasis
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	blood coagulation Traceable author statement. Source: Reactome metabolic process Traceable author statement Ref.1. Source: GOC platelet activation Traceable author statement. Source: Reactome response to wounding Traceable author statement Ref.1. Source: ProtInc
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: Ensembl extracellular region Traceable author statement. Source: Reactome integral component of plasma membrane Traceable author statement Ref.1. Source: ProtInc plasma membrane Traceable author statement. Source: Reactome
Molecular_function	phosphatidylinositol phospholipase C activity Traceable author statement Ref.1. Source: ProtInc protein binding Inferred from physical interaction PubMed 17474147. Source: IntAct thrombin receptor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NCK1	P16333	2	EBI-1751853,EBI-389883

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O00254-1)

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: O00254-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-22: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Propeptide	22 – 38	17	Removed for receptor activation By similarity		PRO_0000012756
	Chain	39 – 374	336	Proteinase-activated receptor 3		PRO_0000012757
Regions
	Topological domain	39 – 94	56	Extracellular Potential
	Transmembrane	95 – 120	26	Helical; Name=1; Potential
	Topological domain	121 – 128	8	Cytoplasmic Potential
	Transmembrane	129 – 148	20	Helical; Name=2; Potential
	Topological domain	149 – 167	19	Extracellular Potential
	Transmembrane	168 – 189	22	Helical; Name=3; Potential
	Topological domain	190 – 206	17	Cytoplasmic Potential
	Transmembrane	207 – 230	24	Helical; Name=4; Potential
	Topological domain	231 – 260	30	Extracellular Potential
	Transmembrane	261 – 280	20	Helical; Name=5; Potential
	Topological domain	281 – 297	17	Cytoplasmic Potential
	Transmembrane	298 – 322	25	Helical; Name=6; Potential
	Topological domain	323 – 336	14	Extracellular Potential
	Transmembrane	337 – 361	25	Helical; Name=7; Potential
	Topological domain	362 – 374	13	Cytoplasmic Potential
Sites
	Site	38 – 39	2	Cleavage; by thrombin By similarity
Amino acid modifications
	Glycosylation	25	1	N-linked (GlcNAc...) Potential
	Glycosylation	82	1	N-linked (GlcNAc...) Potential
	Glycosylation	331	1	N-linked (GlcNAc...) Potential
	Disulfide bond	166 ↔ 245		By similarity
Natural variations
	Alternative sequence	1 – 22	22	Missing in isoform 2.		VSP_045116
	Natural variant	15	1	L → S. Ref.4 Corresponds to variant rs2069649 [ dbSNP | Ensembl ].		VAR_012849
	Natural variant	177	1	M → V. Ref.4 Corresponds to variant rs2069700 [ dbSNP | Ensembl ].		VAR_012850
	Natural variant	250	1	N → D. Ref.4 Corresponds to variant rs2069683 [ dbSNP | Ensembl ].		VAR_012851
Experimental info
	Mutagenesis	39	1	T → P: No proteolytic cleavage by thrombin. Ref.1
	Mutagenesis	40	1	F → A: Altered signal upon thrombin cleavage. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: C45C15A695DD1ABB	FASTA	374	42,508
	10 20 30 40 50 60 MKALIFAAAG LLLLLPTFCQ SGMENDTNNL AKPTLPIKTF RGAPPNSFEE FPFSALEGWT 70 80 90 100 110 120 GATITVKIKC PEESASHLHV KNATMGYLTS SLSTKLIPAI YLLVFVVGVP ANAVTLWMLF 130 140 150 160 170 180 FRTRSICTTV FYTNLAIADF LFCVTLPFKI AYHLNGNNWV FGEVLCRATT VIFYGNMYCS 190 200 210 220 230 240 ILLLACISIN RYLAIVHPFT YRGLPKHTYA LVTCGLVWAT VFLYMLPFFI LKQEYYLVQP 250 260 270 280 290 300 DITTCHDVHN TCESSSPFQL YYFISLAFFG FLIPFVLIIY CYAAIIRTLN AYDHRWLWYV 310 320 330 340 350 360 KASLLILVIF TICFAPSNII LIIHHANYYY NNTDGLYFIY LIALCLGSLN SCLDPFLYFL 370 MSKTRNHSTA YLTK
	Isoform 2 [UniParc]. Checksum: 36F6931ABB5C5393	FASTA	352	40,247
	10 20 30 40 50 60 MENDTNNLAK PTLPIKTFRG APPNSFEEFP FSALEGWTGA TITVKIKCPE ESASHLHVKN 70 80 90 100 110 120 ATMGYLTSSL STKLIPAIYL LVFVVGVPAN AVTLWMLFFR TRSICTTVFY TNLAIADFLF 130 140 150 160 170 180 CVTLPFKIAY HLNGNNWVFG EVLCRATTVI FYGNMYCSIL LLACISINRY LAIVHPFTYR 190 200 210 220 230 240 GLPKHTYALV TCGLVWATVF LYMLPFFILK QEYYLVQPDI TTCHDVHNTC ESSSPFQLYY 250 260 270 280 290 300 FISLAFFGFL IPFVLIIYCY AAIIRTLNAY DHRWLWYVKA SLLILVIFTI CFAPSNIILI 310 320 330 340 350 IHHANYYYNN TDGLYFIYLI ALCLGSLNSC LDPFLYFLMS KTRNHSTAYL TK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Protease-activated receptor 3 is a second thrombin receptor in humans." Ishihara H., Connolly A.J., Zeng D., Kahn M.L., Zheng Y.-W., Timmons C., Tram T., Coughlin S.R. Nature 386:502-506(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF THR-39 AND PHE-40.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Thymus.
[3]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Retina.
[4]	SeattleSNPs variation discovery resource Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-15; VAL-177 AND ASP-250.
[5]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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).
[8]	"The human proteinase-activated receptor-3 (PAR-3) gene. Identification within a PAR gene cluster and characterization in vascular endothelial cells and platelets." Schmidt V.A., Nierman W.C., Maglott D.R., Cupit L.D., Moskowitz K.A., Wainer J.A., Bahou W.F. J. Biol. Chem. 273:15061-15068(1998) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[9]	"Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin." Kahn M.L., Nakanishi-Matsui M., Shapiro M.J., Ishihara H., Coughlin S.R. J. Clin. Invest. 103:879-887(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"Two forms of human Inscuteable-related protein that links Par3 to the Pins homologues LGN and AGS3." Izaki T., Kamakura S., Kohjima M., Sumimoto H. Biochem. Biophys. Res. Commun. 341:1001-1006(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH INSC.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	U92971 mRNA. Translation: AAC51218.1. AK312848 mRNA. Translation: BAG35701.1. AK298585 mRNA. Translation: BAG60775.1. BX537386 mRNA. Translation: CAD97628.1. Frameshift. AF374726 Genomic DNA. Translation: AAK51564.1. AC026725 Genomic DNA. No translation available. CH471084 Genomic DNA. Translation: EAW95778.1. BC093648 mRNA. Translation: AAH93648.1. BC093650 mRNA. Translation: AAH93650.1.
CCDS	CCDS4031.1. [O00254-1] CCDS58959.1. [O00254-2]
RefSeq	NP_001243495.1. NM_001256566.1. [O00254-2] NP_004092.1. NM_004101.3. [O00254-1]
UniGene	Hs.42502.
3D structure databases
ProteinModelPortal	O00254.
SMR	O00254. Positions 86-363.
ModBase	Search...
MobiDB	Search...
Protein-protein interaction databases
BioGrid	108450. 1 interaction.
IntAct	O00254. 9 interactions.
MINT	MINT-3380783.
STRING	9606.ENSP00000296641.
Chemistry
ChEMBL	CHEMBL5477.
GuidetoPHARMACOLOGY	349.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	O00254.
Proteomic databases
PRIDE	O00254.
Protocols and materials databases
DNASU	2151.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000296641; ENSP00000296641; ENSG00000164220. [O00254-1] ENST00000504899; ENSP00000426703; ENSG00000164220. [O00254-2]
GeneID	2151.
KEGG	hsa:2151.
UCSC	uc003kem.4. human. [O00254-1]
Organism-specific databases
CTD	2151.
GeneCards	GC05M075947.
HGNC	HGNC:3539. F2RL2.
MIM	601919. gene.
neXtProt	NX_O00254.
PharmGKB	PA27948.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG146611.
HOGENOM	HOG000116291.
HOVERGEN	HBG105658.
InParanoid	O00254.
KO	K04235.
OMA	CRATTVI.
OrthoDB	EOG7QC7WD.
PhylomeDB	O00254.
TreeFam	TF330775.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction. REACT_604. Hemostasis.
Gene expression databases
Bgee	O00254.
CleanEx	HS_F2RL2.
Genevestigator	O00254.
Family and domain databases
Gene3D	1.20.1070.10. 1 hit.
InterPro	IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. IPR003943. Prot_act_rcpt_3. IPR003912. Protea_act_rcpt. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00237. GPCRRHODOPSN. PR01428. PROTEASEAR. PR01429. PROTEASEAR3.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GeneWiki	F2RL2.
GenomeRNAi	2151.
NextBio	8693.
PMAP-CutDB	O00254.
PRO	O00254.
SOURCE	Search...

Entry information

Entry name

PAR3_HUMAN

Accession

Primary (citable) accession number: O00254
Secondary accession number(s): B2R754 , B4DQ13, Q52M68, Q7Z3W3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	July 1, 1997
Last modified:	July 9, 2014
This is version 137 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.