PECA1_BOVIN
ID PECA1_BOVIN Reviewed; 739 AA.
AC P51866;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Platelet endothelial cell adhesion molecule;
DE Short=PECAM-1;
DE AltName: CD_antigen=CD31;
DE Flags: Precursor;
GN Name=PECAM1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RX PubMed=8558001;
RA Stewart R.J., Kashour T.S., Marsden P.A.;
RT "Vascular endothelial platelet endothelial adhesion molecule-1 (PECAM-1)
RT expression is decreased by TNF-alpha and IFN-gamma. Evidence for cytokine-
RT induced destabilization of messenger ribonucleic acid transcripts in bovine
RT endothelial cells.";
RL J. Immunol. 156:1221-1228(1996).
RN [2]
RP PHOSPHORYLATION AT TYR-689 AND TYR-714, MUTAGENESIS OF TYR-689 AND TYR-714,
RP AND INTERACTION WITH FER AND PTPN11.
RX PubMed=12972546; DOI=10.1091/mbc.e03-02-0080;
RA Kogata N., Masuda M., Kamioka Y., Yamagishi A., Endo A., Okada M.,
RA Mochizuki N.;
RT "Identification of Fer tyrosine kinase localized on microtubules as a
RT platelet endothelial cell adhesion molecule-1 phosphorylating kinase in
RT vascular endothelial cells.";
RL Mol. Biol. Cell 14:3553-3564(2003).
CC -!- FUNCTION: Cell adhesion molecule which is required for leukocyte
CC transendothelial migration (TEM) under most inflammatory conditions.
CC Tyr-689 plays a critical role in TEM and is required for efficient
CC trafficking of PECAM1 to and from the lateral border recycling
CC compartment (LBRC) and is also essential for the LBRC membrane to be
CC targeted around migrating leukocytes. Trans-homophilic interaction may
CC play a role in endothelial cell-cell adhesion via cell junctions.
CC Heterophilic interaction with CD177 plays a role in transendothelial
CC migration of neutrophils. Homophilic ligation of PECAM1 prevents
CC macrophage-mediated phagocytosis of neighboring viable leukocytes by
CC transmitting a detachment signal. Promotes macrophage-mediated
CC phagocytosis of apoptotic leukocytes by tethering them to the
CC phagocytic cells; PECAM1-mediated detachment signal appears to be
CC disabled in apoptotic leukocytes. Modulates bradykinin receptor BDKRB2
CC activation. Regulates bradykinin- and hyperosmotic shock-induced ERK1/2
CC activation in endothelial cells. Induces susceptibility to
CC atherosclerosis. {ECO:0000250|UniProtKB:P16284,
CC ECO:0000250|UniProtKB:Q08481}.
CC -!- SUBUNIT: Trans-homodimer (via Ig-like C2-type 1 and Ig-like C2-type 2
CC domains); trans-homodimerization is required for cell-cell interaction
CC (By similarity). Forms a complex with BDKRB2 and GNAQ (By similarity).
CC Interacts with BDKRB2 and GNAQ (By similarity). Interacts with PTPN11;
CC Tyr-714 is critical for PTPN11 recruitment (PubMed:12972546). Interacts
CC with FER (PubMed:12972546). Interacts with CD177; the interaction is
CC Ca(2+)-dependent; the interaction is direct (By similarity).
CC {ECO:0000250|UniProtKB:P16284, ECO:0000269|PubMed:12972546}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P16284};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P16284}.
CC Membrane raft {ECO:0000250|UniProtKB:P16284}. Cell junction
CC {ECO:0000250|UniProtKB:P16284}. Note=Localizes to the lateral border
CC recycling compartment (LBRC) and recycles from the LBRC to the junction
CC in resting endothelial cells. Cell surface expression on neutrophils is
CC down-regulated upon fMLP or CXCL8/IL8-mediated stimulation.
CC {ECO:0000250|UniProtKB:P16284}.
CC -!- DOMAIN: The Ig-like C2-type domains 2 and 3 contribute to formation of
CC the complex with BDKRB2 and in regulation of its activity.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylated on Ser and Tyr residues by src kinases after
CC cellular activation (PubMed:12972546). Upon activation, phosphorylated
CC on Ser-730 which probably initiates the dissociation of the membrane-
CC interaction segment (residues 708-730) from the cell membrane allowing
CC the sequential phosphorylation of Tyr-714 and Tyr-689 (By similarity).
CC Constitutively phosphorylated on Ser-735 in resting platelets (By
CC similarity). Phosphorylated on tyrosine residues by FER and FES in
CC response to FCER1 activation (PubMed:12972546). In endothelial cells
CC Fyn mediates mechanical-force (stretch or pull) induced tyrosine
CC phosphorylation (By similarity). {ECO:0000250|UniProtKB:P16284,
CC ECO:0000269|PubMed:12972546}.
CC -!- PTM: Palmitoylation by ZDHHC21 is necessary for cell surface expression
CC in endothelial cells and enrichment in membrane rafts.
CC {ECO:0000250|UniProtKB:P16284}.
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DR EMBL; U35433; AAC48566.1; -; mRNA.
DR AlphaFoldDB; P51866; -.
DR SMR; P51866; -.
DR STRING; 9913.ENSBTAP00000040327; -.
DR iPTMnet; P51866; -.
DR PaxDb; P51866; -.
DR PRIDE; P51866; -.
DR eggNOG; ENOG502QW63; Eukaryota.
DR InParanoid; P51866; -.
DR OrthoDB; 419506at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IBA:GO_Central.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0098742; P:cell-cell adhesion via plasma-membrane adhesion molecules; IBA:GO_Central.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:ARUK-UCL.
DR Gene3D; 2.60.40.10; -; 6.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR040878; Ig_C17orf99.
DR InterPro; IPR003599; Ig_sub.
DR Pfam; PF13895; Ig_2; 3.
DR Pfam; PF17736; Ig_C17orf99; 1.
DR SMART; SM00409; IG; 5.
DR SUPFAM; SSF48726; SSF48726; 5.
DR PROSITE; PS50835; IG_LIKE; 4.
PE 1: Evidence at protein level;
KW Cell adhesion; Cell junction; Cell membrane; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Lipoprotein; Membrane; Palmitate; Phosphoprotein;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..27
FT /evidence="ECO:0000250"
FT CHAIN 28..739
FT /note="Platelet endothelial cell adhesion molecule"
FT /id="PRO_0000014894"
FT TOPO_DOM 28..599
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 600..618
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 619..739
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 35..120
FT /note="Ig-like C2-type 1"
FT DOMAIN 145..213
FT /note="Ig-like C2-type 2"
FT DOMAIN 236..315
FT /note="Ig-like C2-type 3"
FT DOMAIN 328..403
FT /note="Ig-like C2-type 4"
FT DOMAIN 424..493
FT /note="Ig-like C2-type 5"
FT DOMAIN 499..590
FT /note="Ig-like C2-type 6"
FT REGION 708..730
FT /note="Membrane-bound segment which detaches upon
FT phosphorylation"
FT /evidence="ECO:0000250|UniProtKB:P16284"
FT REGION 722..739
FT /note="May play a role in cytoprotective signaling"
FT /evidence="ECO:0000250"
FT MOTIF 687..692
FT /note="ITIM motif 1"
FT /evidence="ECO:0000250|UniProtKB:P16284"
FT MOTIF 712..717
FT /note="ITIM motif 2"
FT /evidence="ECO:0000250|UniProtKB:P16284"
FT MOD_RES 689
FT /note="Phosphotyrosine; by FER"
FT /evidence="ECO:0000269|PubMed:12972546"
FT MOD_RES 714
FT /note="Phosphotyrosine; by FER"
FT /evidence="ECO:0000269|PubMed:12972546"
FT MOD_RES 730
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16284"
FT MOD_RES 735
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16284"
FT LIPID 620
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 52
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 84
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 151
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 301
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 320
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 356
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 371
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 435
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 446
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 453
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 550
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 578
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 57..109
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 152..206
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 256..304
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 347..386
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 431..476
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 522..571
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT MUTAGEN 689
FT /note="Y->F: Strongly reduced phosphorylation by FER.
FT Abolishes phosphorylation by FER; when associated with F-
FT 714."
FT /evidence="ECO:0000269|PubMed:12972546"
FT MUTAGEN 714
FT /note="Y->F: Reduced phosphorylation by FER. Abolishes
FT phosphorylation by FER; when associated with F-689."
FT /evidence="ECO:0000269|PubMed:12972546"
SQ SEQUENCE 739 AA; 82586 MW; 23277383D52E0113 CRC64;
MQLRWTQRGM MWLGALLTLL LCSSLKGQEN SFTINSIHMQ ILPHSTVQNG ENLTLQCLVD
VSTTSRVKPL HQVLFYKDDV LLHNVSSRRN TESYLIPHVR VCDSGRYKCN VILNNKEKTT
PEYEVWVKGV SDPRVTLDKK EVIEGGVVVV NCSVPEEKAP VHFTIEKFEL NIRGAKKKRE
KTSQNQNFVT LEFTVEEQDR TIRFQCQAKI FSGSNVESSR PIQSDLVTVR ESFSNPKFHI
IPEGKVMEGD DLQVKCTVQV THQAQSFPEI IIQKDREIVA HNSLSSEAVY SVMATTEHNG
NYTCKVEASR ISKVSSVVVN VTELFSKPKL ESSATHLDQG EDLNLLCSIP GAPPANFTIQ
KGGMTVSQTQ NFTKRVSEWD SGLYTCVAGV GRVFKRSNTV QITVCEMLSK PSIFHDSRSE
VIKGQTIEVS CQSVNGTAPI FYQLSNTSKP VANQSVGSNK PAIFRVKPTK DVEYCCSADN
CHSHSKMFSE VLRVKVIAPV DEAQLVVLKG EVEPGEPIVF YCSVNEGSFP ITYKFYKEKE
SKPFYQDTIN ATQIMWHKTT ASKEYEGQYY CTASNRANLS KHVIQSNTLT VRVYLPLEKG
LIAVVVIGVI IVTLVLGAKC YFLKKAKAKQ MPVEMSRPAV PLLNSNNEKT LSDAGTEADR
HYGYNEDVGN HAMKPLNENK EPLTLDVEYT EVEVTSPEPH QGLGTKGTET ETVYSEIRKA
DPDFVENRYS RTEGSLDGS
