PEAR1_HUMAN
ID PEAR1_HUMAN Reviewed; 1037 AA.
AC Q5VY43; Q8TEK2;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Platelet endothelial aggregation receptor 1;
DE Short=hPEAR1;
DE AltName: Full=Multiple epidermal growth factor-like domains protein 12;
DE Short=Multiple EGF-like domains protein 12;
DE Flags: Precursor;
GN Name=PEAR1; Synonyms=MEGF12;
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], PROTEIN SEQUENCE OF 873-881; 905-928; 930-938;
RP 948-966; 990-1011 AND 1026-1034, PHOSPHORYLATION AT TYR-925; SER-953 AND
RP SER-1029, IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH SHC2, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Platelet;
RX PubMed=15851471; DOI=10.1074/jbc.m413411200;
RA Nanda N., Bao M., Lin H., Clauser K., Komuves L., Quertermous T.,
RA Conley P.B., Phillips D.R., Hart M.J.;
RT "Platelet endothelial aggregation receptor 1 (PEAR1), a novel epidermal
RT growth factor repeat-containing transmembrane receptor, participates in
RT platelet contact-induced activation.";
RL J. Biol. Chem. 280:24680-24689(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 376-1037.
RC TISSUE=Spleen;
RA Jikuya H., Takano J., Nomura N., Kikuno R., Nagase T., Ohara O.;
RT "The nucleotide sequence of a long cDNA clone isolated from human spleen.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: When overexpressed, reduces the number of both early and late
CC non-adherent myeloid progenitor cells. {ECO:0000250}.
CC -!- SUBUNIT: Interacts with SHC2 upon its aggregation-induced tyrosine
CC phosphorylation. {ECO:0000269|PubMed:15851471}.
CC -!- INTERACTION:
CC Q5VY43; Q9BYR2: KRTAP4-5; NbExp=3; IntAct=EBI-1249608, EBI-11993254;
CC Q5VY43; P50539-3: MXI1; NbExp=3; IntAct=EBI-1249608, EBI-10211940;
CC Q5VY43; Q7Z417: NUFIP2; NbExp=3; IntAct=EBI-1249608, EBI-1210753;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass membrane
CC protein {ECO:0000305}. Note=Detected on the cell surface in resting
CC platelets. {ECO:0000269|PubMed:15851471}.
CC -!- TISSUE SPECIFICITY: Expressed in umbilical vein endothelial cells and
CC platelets (at protein level). Expressed in heart, kidney, skeletal
CC muscle, pancreas, ovary, breast, lung, brain cortex, hypothalamus,
CC spinal cord, dorsal root ganglion, endothelial cells of umbilical cord
CC artery and vein, megakaryocytes, osteoblasts, coronary muscle and
CC erythroid cells. Weakly expressed in peripheral blood leukocytes and
CC macrophages.
CC -!- PTM: Phosphorylated in the intracellular domain on tyrosine residues
CC (By similarity). Phosphorylated on tyrosine residues by SRC. Tyrosine
CC phosphorylation is detected upon platelet aggregation stimulated by
CC collagen, TRAP and thrombin and platelet-platelet contacts but not
CC after platelet activation. Tyrosine phosphorylation enhanced its
CC association with SHC1 and SHC2. {ECO:0000250,
CC ECO:0000269|PubMed:15851471}.
CC -!- SIMILARITY: Belongs to the MEGF family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB84947.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AL158169; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356104; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK074121; BAB84947.1; ALT_FRAME; mRNA.
DR CCDS; CCDS30892.1; -.
DR RefSeq; NP_001073940.1; NM_001080471.1.
DR RefSeq; XP_005245198.1; XM_005245141.3.
DR RefSeq; XP_011507812.1; XM_011509510.2.
DR RefSeq; XP_016856725.1; XM_017001236.1.
DR AlphaFoldDB; Q5VY43; -.
DR BioGRID; 131950; 10.
DR IntAct; Q5VY43; 5.
DR STRING; 9606.ENSP00000344465; -.
DR GlyGen; Q5VY43; 6 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q5VY43; -.
DR PhosphoSitePlus; Q5VY43; -.
DR BioMuta; PEAR1; -.
DR DMDM; 74757035; -.
DR jPOST; Q5VY43; -.
DR MassIVE; Q5VY43; -.
DR PaxDb; Q5VY43; -.
DR PeptideAtlas; Q5VY43; -.
DR PRIDE; Q5VY43; -.
DR ProteomicsDB; 65621; -.
DR Antibodypedia; 49426; 178 antibodies from 29 providers.
DR DNASU; 375033; -.
DR Ensembl; ENST00000292357.8; ENSP00000292357.7; ENSG00000187800.14.
DR Ensembl; ENST00000338302.7; ENSP00000344465.3; ENSG00000187800.14.
DR GeneID; 375033; -.
DR KEGG; hsa:375033; -.
DR MANE-Select; ENST00000292357.8; ENSP00000292357.7; NM_001080471.3; NP_001073940.1.
DR UCSC; uc001fqj.1; human.
DR CTD; 375033; -.
DR DisGeNET; 375033; -.
DR GeneCards; PEAR1; -.
DR HGNC; HGNC:33631; PEAR1.
DR HPA; ENSG00000187800; Low tissue specificity.
DR MIM; 610278; gene.
DR neXtProt; NX_Q5VY43; -.
DR OpenTargets; ENSG00000187800; -.
DR PharmGKB; PA162399233; -.
DR VEuPathDB; HostDB:ENSG00000187800; -.
DR eggNOG; KOG1218; Eukaryota.
DR GeneTree; ENSGT00940000154225; -.
DR HOGENOM; CLU_008281_1_0_1; -.
DR InParanoid; Q5VY43; -.
DR OMA; CNNHSSC; -.
DR OrthoDB; 561378at2759; -.
DR PhylomeDB; Q5VY43; -.
DR TreeFam; TF332598; -.
DR PathwayCommons; Q5VY43; -.
DR SignaLink; Q5VY43; -.
DR BioGRID-ORCS; 375033; 18 hits in 1070 CRISPR screens.
DR GenomeRNAi; 375033; -.
DR Pharos; Q5VY43; Tbio.
DR PRO; PR:Q5VY43; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q5VY43; protein.
DR Bgee; ENSG00000187800; Expressed in right coronary artery and 147 other tissues.
DR ExpressionAtlas; Q5VY43; baseline and differential.
DR Genevisible; Q5VY43; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0001891; C:phagocytic cup; IEA:Ensembl.
DR GO; GO:0038023; F:signaling receptor activity; IEA:Ensembl.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IEA:Ensembl.
DR GO; GO:0070527; P:platelet aggregation; IEA:Ensembl.
DR GO; GO:0043491; P:protein kinase B signaling; IEA:Ensembl.
DR GO; GO:0043654; P:recognition of apoptotic cell; IEA:Ensembl.
DR CDD; cd00055; EGF_Lam; 1.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR011489; EMI_domain.
DR InterPro; IPR002049; LE_dom.
DR Pfam; PF00053; Laminin_EGF; 3.
DR SMART; SM00181; EGF; 15.
DR SMART; SM00180; EGF_Lam; 12.
DR PROSITE; PS00022; EGF_1; 13.
DR PROSITE; PS01186; EGF_2; 12.
DR PROSITE; PS50026; EGF_3; 9.
DR PROSITE; PS51041; EMI; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Direct protein sequencing; Disulfide bond; EGF-like domain;
KW Glycoprotein; Membrane; Phosphoprotein; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..1037
FT /note="Platelet endothelial aggregation receptor 1"
FT /id="PRO_0000309737"
FT TOPO_DOM 21..755
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 756..776
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 777..1037
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 25..103
FT /note="EMI"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00384"
FT DOMAIN 102..132
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 225..260
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 268..303
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 311..346
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 400..435
FT /note="EGF-like 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 486..521
FT /note="EGF-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 577..607
FT /note="EGF-like 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 615..649
FT /note="EGF-like 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 657..692
FT /note="EGF-like 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 824..891
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 926..1037
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 863..878
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 958..980
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 925
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:15851471"
FT MOD_RES 953
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15851471"
FT MOD_RES 1029
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15851471"
FT CARBOHYD 152
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 271
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 476
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 575
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 634
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 29..91
FT /evidence="ECO:0000255"
FT DISULFID 55..65
FT /evidence="ECO:0000255"
FT DISULFID 90..101
FT /evidence="ECO:0000255"
FT DISULFID 105..114
FT /evidence="ECO:0000250"
FT DISULFID 109..120
FT /evidence="ECO:0000250"
FT DISULFID 122..131
FT /evidence="ECO:0000250"
FT DISULFID 235..248
FT /evidence="ECO:0000250"
FT DISULFID 250..259
FT /evidence="ECO:0000250"
FT DISULFID 272..284
FT /evidence="ECO:0000250"
FT DISULFID 278..291
FT /evidence="ECO:0000250"
FT DISULFID 293..302
FT /evidence="ECO:0000250"
FT DISULFID 315..327
FT /evidence="ECO:0000250"
FT DISULFID 321..334
FT /evidence="ECO:0000250"
FT DISULFID 336..345
FT /evidence="ECO:0000250"
FT DISULFID 404..416
FT /evidence="ECO:0000250"
FT DISULFID 410..423
FT /evidence="ECO:0000250"
FT DISULFID 425..434
FT /evidence="ECO:0000250"
FT DISULFID 490..502
FT /evidence="ECO:0000250"
FT DISULFID 496..509
FT /evidence="ECO:0000250"
FT DISULFID 511..520
FT /evidence="ECO:0000250"
FT DISULFID 580..588
FT /evidence="ECO:0000250"
FT DISULFID 582..595
FT /evidence="ECO:0000250"
FT DISULFID 597..606
FT /evidence="ECO:0000250"
FT DISULFID 619..630
FT /evidence="ECO:0000250"
FT DISULFID 624..637
FT /evidence="ECO:0000250"
FT DISULFID 639..648
FT /evidence="ECO:0000250"
FT DISULFID 661..673
FT /evidence="ECO:0000250"
FT DISULFID 667..680
FT /evidence="ECO:0000250"
FT DISULFID 682..691
FT /evidence="ECO:0000250"
FT VARIANT 234
FT /note="S -> P (in dbSNP:rs1952294)"
FT /id="VAR_048978"
FT VARIANT 848
FT /note="N -> K (in dbSNP:rs822442)"
FT /id="VAR_061158"
FT VARIANT 885
FT /note="R -> H (in dbSNP:rs11264581)"
FT /id="VAR_048979"
FT VARIANT 903
FT /note="N -> D (in dbSNP:rs12137505)"
FT /id="VAR_048980"
SQ SEQUENCE 1037 AA; 110666 MW; D0DBB323D5F8C7E3 CRC64;
MSPPLCPLLL LAVGLRLAGT LNPSDPNTCS FWESFTTTTK ESHSRPFSLL PSEPCERPWE
GPHTCPQPTV VYRTVYRQVV KTDHRQRLQC CHGFYESRGF CVPLCAQECV HGRCVAPNQC
QCVPGWRGDD CSSECAPGMW GPQCDKPCSC GNNSSCDPKS GVCSCPSGLQ PPNCLQPCTP
GYYGPACQFR CQCHGAPCDP QTGACFCPAE RTGPSCDVSC SQGTSGFFCP STHSCQNGGV
FQTPQGSCSC PPGWMGTICS LPCPEGFHGP NCSQECRCHN GGLCDRFTGQ CRCAPGYTGD
RCREECPVGR FGQDCAETCD CAPDARCFPA NGACLCEHGF TGDRCTDRLC PDGFYGLSCQ
APCTCDREHS LSCHPMNGEC SCLPGWAGLH CNESCPQDTH GPGCQEHCLC LHGGVCQATS
GLCQCAPGYT GPHCASLCPP DTYGVNCSAR CSCENAIACS PIDGECVCKE GWQRGNCSVP
CPPGTWGFSC NASCQCAHEA VCSPQTGACT CTPGWHGAHC QLPCPKGQFG EGCASRCDCD
HSDGCDPVHG RCQCQAGWMG ARCHLSCPEG LWGVNCSNTC TCKNGGTCLP ENGNCVCAPG
FRGPSCQRSC QPGRYGKRCV PCKCANHSFC HPSNGTCYCL AGWTGPDCSQ PCPPGHWGEN
CAQTCQCHHG GTCHPQDGSC ICPLGWTGHH CLEGCPLGTF GANCSQPCQC GPGEKCHPET
GACVCPPGHS GAPCRIGIQE PFTVMPTTPV AYNSLGAVIG IAVLGSLVVA LVALFIGYRH
WQKGKEHHHL AVAYSSGRLD GSEYVMPDVP PSYSHYYSNP SYHTLSQCSP NPPPPNKVPG
PLFASLQNPE RPGGAQGHDN HTTLPADWKH RREPPPGPLD RGSSRLDRSY SYSYSNGPGP
FYNKGLISEE ELGASVASLS SENPYATIRD LPSLPGGPRE SSYMEMKGPP SGSPPRQPPQ
FWDSQRRRQP QPQRDSGTYE QPSPLIHDRD SVGSQPPLPP GLPPGHYDSP KNSHIPGHYD
LPPVRHPPSP PLRRQDR
