EPCR_HUMAN
ID EPCR_HUMAN Reviewed; 238 AA.
AC Q9UNN8; B2RC04; Q14218; Q6IB56; Q96CB3; Q9ULX1;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Endothelial protein C receptor;
DE AltName: Full=Activated protein C receptor;
DE Short=APC receptor;
DE AltName: Full=Endothelial cell protein C receptor;
DE AltName: CD_antigen=CD201;
DE Flags: Precursor;
GN Name=PROCR; Synonyms=EPCR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Endothelial cell;
RX PubMed=7929370; DOI=10.1016/s0021-9258(18)47220-1;
RA Fukudome K., Esmon C.T.;
RT "Identification, cloning, and regulation of a novel endothelial cell
RT protein C/activated protein C receptor.";
RL J. Biol. Chem. 269:26486-26491(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Flens M.J., Scheffer G.L.;
RL Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10397730;
RA Simmonds R.E., Lane D.A.;
RT "Structural and functional implications of the intron/exon organization of
RT the human endothelial cell protein C/activated protein C receptor (EPCR)
RT gene: comparison with the structure of CD1/major histocompatibility complex
RT alpha1 and alpha2 domains.";
RL Blood 94:632-641(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10570964; DOI=10.1016/s0378-1119(99)00360-1;
RA Hayashi T., Nakamura H., Okada A., Takebayashi S., Wakita T., Yuasa H.,
RA Okumura K., Suzuki K.;
RT "Organization and chromosomal localization of the human endothelial protein
RT C receptor gene.";
RL Gene 238:367-373(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLY-219.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-219.
RC TISSUE=Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP CHARACTERIZATION OF SOLUBLE FORM.
RX PubMed=10681599; DOI=10.1074/jbc.275.8.6038;
RA Xu J., Qu D., Esmon N.L., Esmon C.T.;
RT "Metalloproteolytic release of endothelial cell protein C receptor.";
RL J. Biol. Chem. 275:6038-6044(2000).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 18-210, GLYCOSYLATION AT ASN-47;
RP ASN-136 AND ASN-172, AND DISULFIDE BOND.
RX PubMed=12034704; DOI=10.1074/jbc.c200163200;
RA Oganesyan V., Oganesyan N., Terzyan S., Qu D., Dauter Z., Esmon N.L.,
RA Esmon C.T.;
RT "The crystal structure of the endothelial protein C receptor and a bound
RT phospholipid.";
RL J. Biol. Chem. 277:24851-24854(2002).
CC -!- FUNCTION: Binds activated protein C. Enhances protein C activation by
CC the thrombin-thrombomodulin complex; plays a role in the protein C
CC pathway controlling blood coagulation.
CC -!- INTERACTION:
CC Q9UNN8; P25116: F2R; NbExp=5; IntAct=EBI-719705, EBI-2803960;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed strongly in the endothelial cells of
CC arteries and veins in heart and lung, less intensely in capillaries in
CC the lung and skin, and not at all in the endothelium of small vessels
CC of the liver and kidney.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:12034704}.
CC -!- PTM: A soluble form exists; probably released by a metalloprotease.
CC Seems to have the same activity as the membrane-bound form.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/procr/";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; L35545; AAA63647.1; -; mRNA.
DR EMBL; X89079; CAA61450.1; -; mRNA.
DR EMBL; AF106202; AAD43967.1; -; Genomic_DNA.
DR EMBL; AB026584; BAA77249.2; -; Genomic_DNA.
DR EMBL; CR456948; CAG33229.1; -; mRNA.
DR EMBL; AF375468; AAK53045.1; -; Genomic_DNA.
DR EMBL; AK314887; BAG37401.1; -; mRNA.
DR EMBL; AL356652; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW76224.1; -; Genomic_DNA.
DR EMBL; BC014451; AAH14451.1; -; mRNA.
DR CCDS; CCDS13248.1; -.
DR PIR; A55365; A55365.
DR RefSeq; NP_006395.2; NM_006404.4.
DR PDB; 1L8J; X-ray; 2.00 A; A=18-210.
DR PDB; 1LQV; X-ray; 1.60 A; A/B=18-210.
DR PDB; 3JTC; X-ray; 1.60 A; A/B=18-210.
DR PDB; 4V3D; X-ray; 2.65 A; B/D=25-194.
DR PDB; 4V3E; X-ray; 2.90 A; B=25-195.
DR PDB; 6SNY; X-ray; 3.11 A; B/C=18-210.
DR PDBsum; 1L8J; -.
DR PDBsum; 1LQV; -.
DR PDBsum; 3JTC; -.
DR PDBsum; 4V3D; -.
DR PDBsum; 4V3E; -.
DR PDBsum; 6SNY; -.
DR AlphaFoldDB; Q9UNN8; -.
DR SMR; Q9UNN8; -.
DR BioGRID; 115797; 35.
DR DIP; DIP-48671N; -.
DR IntAct; Q9UNN8; 17.
DR MINT; Q9UNN8; -.
DR STRING; 9606.ENSP00000216968; -.
DR DrugBank; DB00055; Drotrecogin alfa.
DR DrugBank; DB04327; Phosphatidylethanolamine.
DR DrugBank; DB11328; Tetradecyl hydrogen sulfate (ester).
DR GlyConnect; 1936; 5 N-Linked glycans (1 site).
DR GlyGen; Q9UNN8; 4 sites, 5 N-linked glycans (1 site).
DR iPTMnet; Q9UNN8; -.
DR PhosphoSitePlus; Q9UNN8; -.
DR SwissPalm; Q9UNN8; -.
DR BioMuta; PROCR; -.
DR DMDM; 13626550; -.
DR CPTAC; non-CPTAC-2664; -.
DR EPD; Q9UNN8; -.
DR jPOST; Q9UNN8; -.
DR MassIVE; Q9UNN8; -.
DR MaxQB; Q9UNN8; -.
DR PaxDb; Q9UNN8; -.
DR PeptideAtlas; Q9UNN8; -.
DR PRIDE; Q9UNN8; -.
DR ProteomicsDB; 85317; -.
DR Antibodypedia; 11183; 695 antibodies from 39 providers.
DR DNASU; 10544; -.
DR Ensembl; ENST00000216968.5; ENSP00000216968.3; ENSG00000101000.6.
DR GeneID; 10544; -.
DR KEGG; hsa:10544; -.
DR MANE-Select; ENST00000216968.5; ENSP00000216968.3; NM_006404.5; NP_006395.2.
DR UCSC; uc002xbt.5; human.
DR CTD; 10544; -.
DR DisGeNET; 10544; -.
DR GeneCards; PROCR; -.
DR HGNC; HGNC:9452; PROCR.
DR HPA; ENSG00000101000; Tissue enhanced (adipose).
DR MIM; 600646; gene.
DR neXtProt; NX_Q9UNN8; -.
DR OpenTargets; ENSG00000101000; -.
DR Orphanet; 64738; NON RARE IN EUROPE: Non rare thrombophilia.
DR PharmGKB; PA33800; -.
DR VEuPathDB; HostDB:ENSG00000101000; -.
DR eggNOG; ENOG502S3SK; Eukaryota.
DR GeneTree; ENSGT00390000001159; -.
DR HOGENOM; CLU_1151498_0_0_1; -.
DR InParanoid; Q9UNN8; -.
DR OMA; QDPESWA; -.
DR OrthoDB; 1203534at2759; -.
DR PhylomeDB; Q9UNN8; -.
DR TreeFam; TF335868; -.
DR PathwayCommons; Q9UNN8; -.
DR Reactome; R-HSA-140875; Common Pathway of Fibrin Clot Formation.
DR Reactome; R-HSA-202733; Cell surface interactions at the vascular wall.
DR SignaLink; Q9UNN8; -.
DR BioGRID-ORCS; 10544; 16 hits in 1078 CRISPR screens.
DR ChiTaRS; PROCR; human.
DR EvolutionaryTrace; Q9UNN8; -.
DR GeneWiki; Endothelial_protein_C_receptor; -.
DR GenomeRNAi; 10544; -.
DR Pharos; Q9UNN8; Tbio.
DR PRO; PR:Q9UNN8; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9UNN8; protein.
DR Bgee; ENSG00000101000; Expressed in pericardium and 162 other tissues.
DR ExpressionAtlas; Q9UNN8; baseline and differential.
DR Genevisible; Q9UNN8; HS.
DR GO; GO:0009986; C:cell surface; HDA:UniProtKB.
DR GO; GO:0005813; C:centrosome; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc.
DR GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW.
DR GO; GO:0050819; P:negative regulation of coagulation; IMP:BHF-UCL.
DR Gene3D; 3.30.500.10; -; 1.
DR InterPro; IPR015669; Endothetial_C_recpt.
DR InterPro; IPR011161; MHC_I-like_Ag-recog.
DR InterPro; IPR037055; MHC_I-like_Ag-recog_sf.
DR InterPro; IPR011162; MHC_I/II-like_Ag-recog.
DR PANTHER; PTHR15349; PTHR15349; 1.
DR Pfam; PF16497; MHC_I_3; 1.
DR SUPFAM; SSF54452; SSF54452; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Blood coagulation; Disulfide bond; Glycoprotein; Hemostasis;
KW Membrane; Receptor; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..238
FT /note="Endothelial protein C receptor"
FT /id="PRO_0000021191"
FT TOPO_DOM 18..210
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 211..231
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 232..238
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 47
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12034704"
FT CARBOHYD 64
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 136
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12034704"
FT CARBOHYD 172
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12034704"
FT DISULFID 118..186
FT /evidence="ECO:0000269|PubMed:12034704"
FT VARIANT 219
FT /note="S -> G (in dbSNP:rs867186)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.6"
FT /id="VAR_012282"
FT CONFLICT 6
FT /note="L -> P (in Ref. 4; BAA77249)"
FT /evidence="ECO:0000305"
FT CONFLICT 47
FT /note="N -> A (in Ref. 4; BAA77249)"
FT /evidence="ECO:0000305"
FT STRAND 26..38
FT /evidence="ECO:0007829|PDB:1LQV"
FT STRAND 41..50
FT /evidence="ECO:0007829|PDB:1LQV"
FT STRAND 53..61
FT /evidence="ECO:0007829|PDB:1LQV"
FT STRAND 66..71
FT /evidence="ECO:0007829|PDB:1LQV"
FT HELIX 76..104
FT /evidence="ECO:0007829|PDB:1LQV"
FT STRAND 108..120
FT /evidence="ECO:0007829|PDB:1LQV"
FT STRAND 122..125
FT /evidence="ECO:0007829|PDB:6SNY"
FT STRAND 128..135
FT /evidence="ECO:0007829|PDB:1LQV"
FT STRAND 138..144
FT /evidence="ECO:0007829|PDB:1LQV"
FT TURN 145..148
FT /evidence="ECO:0007829|PDB:1LQV"
FT STRAND 149..153
FT /evidence="ECO:0007829|PDB:1LQV"
FT STRAND 154..156
FT /evidence="ECO:0007829|PDB:1L8J"
FT HELIX 159..168
FT /evidence="ECO:0007829|PDB:1LQV"
FT TURN 172..175
FT /evidence="ECO:0007829|PDB:1LQV"
FT HELIX 176..183
FT /evidence="ECO:0007829|PDB:1LQV"
FT HELIX 185..193
FT /evidence="ECO:0007829|PDB:1LQV"
SQ SEQUENCE 238 AA; 26671 MW; EA7F0658CD19695C CRC64;
MLTTLLPILL LSGWAFCSQD ASDGLQRLHM LQISYFRDPY HVWYQGNASL GGHLTHVLEG
PDTNTTIIQL QPLQEPESWA RTQSGLQSYL LQFHGLVRLV HQERTLAFPL TIRCFLGCEL
PPEGSRAHVF FEVAVNGSSF VSFRPERALW QADTQVTSGV VTFTLQQLNA YNRTRYELRE
FLEDTCVQYV QKHISAENTK GSQTSRSYTS LVLGVLVGSF IIAGVAVGIF LCTGGRRC
