Coxsackie virus and adenovirus receptor: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (Robot: Automated text replacement (-{{WikiDoc Cardiology Network Infobox}} +, -<references /> +{{reflist|2}}, -{{reflist}} +{{reflist|2}}))
 
m (Bot: HTTP→HTTPS)
 
Line 1: Line 1:
<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Coxsackievirus and adenovirus receptor (CAR)''' is a [[protein]] that in humans is encoded by the ''CXADR'' [[gene]].<ref name="pmid9036860">{{cite journal | vauthors = Bergelson JM, Cunningham JA, Droguett G, Kurt-Jones EA, Krithivas A, Hong JS, Horwitz MS, Crowell RL, Finberg RW | title = Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5 | journal = Science | volume = 275 | issue = 5304 | pages = 1320–3 | date = Feb 1997 | pmid = 9036860 | pmc =  | doi = 10.1126/science.275.5304.1320 }}</ref><ref name="pmid9096397">{{cite journal | vauthors = Tomko RP, Xu R, Philipson L | title = HCAR and MCAR: the human and mouse cellular receptors for subgroup C adenoviruses and group B coxsackieviruses | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 7 | pages = 3352–6 | date = Apr 1997 | pmid = 9096397 | pmc = 20373 | doi = 10.1073/pnas.94.7.3352 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: CXADR coxsackie virus and adenovirus receptor| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1525| accessdate = }}</ref>  The protein encoded by this gene is a type I membrane [[Receptor (biochemistry)|receptor]] for  [[coxsackie B virus|group B coxsackie viruses]] and subgroup C [[adenovirus]]es. CAR [[protein]] is expressed in several tissues, including [[heart]], [[brain]], and, more generally, [[epithelial cell|epithelial]] and [[endothelial cell]]s. In [[cardiac muscle]], CAR is localized to [[intercalated disc]] structures, which electrically and mechanically couple adjacent [[cardiomyocyte]]s. CAR plays an important role in the pathogenesis of [[myocarditis]], [[dilated cardiomyopathy]], and in [[arrhythmia]] susceptibility following [[myocardial infarction]] or [[myocardium|myocardial]] [[ischemia]].
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Structure ==
{{GNF_Protein_box
| image = PBB_Protein_CXADR_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1eaj.
| PDB = {{PDB2|1eaj}}, {{PDB2|1f5w}}, {{PDB2|1jew}}, {{PDB2|1kac}}, {{PDB2|1p69}}, {{PDB2|1p6a}}, {{PDB2|1rsf}}, {{PDB2|2j12}}, {{PDB2|2j1k}}, {{PDB2|2npl}}
| Name = Coxsackie virus and adenovirus receptor
| HGNCid = 2559
| Symbol = CXADR
| AltSymbols =; CAR; HCAR
| OMIM = 602621
| ECnumber = 
| Homologene = 1024
| MGIid = 1201679
| GeneAtlas_image1 = PBB_GE_CXADR_203917_at_tn.png
| Function = {{GNF_GO|id=GO:0004872 |text = receptor activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}}
| Component = {{GNF_GO|id=GO:0005886 |text = plasma membrane}} {{GNF_GO|id=GO:0005887 |text = integral to plasma membrane}} {{GNF_GO|id=GO:0005923 |text = tight junction}}
| Process = {{GNF_GO|id=GO:0007005 |text = mitochondrion organization and biogenesis}} {{GNF_GO|id=GO:0007155 |text = cell adhesion}} {{GNF_GO|id=GO:0007507 |text = heart development}} {{GNF_GO|id=GO:0048739 |text = cardiac muscle fiber development}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 1525
    | Hs_Ensembl = ENSG00000154639
    | Hs_RefseqProtein = NP_001329
    | Hs_RefseqmRNA = NM_001338
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 21
    | Hs_GenLoc_start = 17807201
    | Hs_GenLoc_end = 17861135
    | Hs_Uniprot = P78310
    | Mm_EntrezGene = 13052
    | Mm_Ensembl = ENSMUSG00000022865
    | Mm_RefseqmRNA = NM_001025192
    | Mm_RefseqProtein = NP_001020363
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 16
    | Mm_GenLoc_start = 78184283
    | Mm_GenLoc_end = 78222167
    | Mm_Uniprot = Q3TV22
  }}
}}
'''Coxsackie virus and adenovirus receptor''', also known as '''CXADR''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: CXADR coxsackie virus and adenovirus receptor| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1525| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
Human CAR [[protein]] has a theoretical molecular weight of 40.0 kDa and is composed of 365 [[amino acid]]s.<ref>{{cite web|title=Protein sequence of human CXADR (Uniprot ID: P78310)|url=http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P78310|website=Cardiac Organellar Protein Atlas Knowledgebase (COPaKB)|accessdate=14 July 2015}}</ref> The human CAR gene (CXADR) is found on chromosome 21. Alternative splicing is known to produce at least 2 splice variants known as hCAR1 and hCAR2 and are each composed of at least 7 exons. Pseudogenes of this gene are found on chromosomes 15, 18, and 21.<ref name="entrez"/>
{{PBB_Summary
| section_title =
| summary_text = The protein encoded by this gene is a type I membrane receptor for group B coxsackieviruses and subgroup C adenoviruses. Pseudogenes of this gene are found on chromosomes 15, 18, and 21.<ref name="entrez">{{cite web | title = Entrez Gene: CXADR coxsackie virus and adenovirus receptor| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1525| accessdate = }}</ref>
}}


==References==
CAR is a [[Transmembrane protein|transmembrane bound protein]] with two [[immunoglobulin|Ig]]-like extracellular domains, a [[transmembrane domain]], a [[cytoplasm]]ic domain, and two N-linked [[glycosylation]] sites. CAR contains two [[disulfide bond]]ed loops (residues 35-130 and 155-220).<ref>{{cite journal | vauthors = Tomko RP, Xu R, Philipson L | title = HCAR and MCAR: the human and mouse cellular receptors for subgroup C adenoviruses and group B coxsackieviruses | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 7 | pages = 3352–6 | date = Apr 1997 | pmid = 9096397 | doi=10.1073/pnas.94.7.3352 | pmc=20373}}</ref> The [[N-terminus|N-terminal]] segment comprises the two extracellular domains (D1 and D2). D1 is most distal from the membrane and contains a V/[[immunoglobulin|Ig]]-like fold whereas D2 is more proximal. The [[cytoplasm]]ic tail of CAR contains the amino acids [[glycine|G]][[serine|S]][[isoleucine|I]][[valine|V]], which is characterized as a class 1 PDZ binding motif for interacting with proteins containing [[PDZ domain]]s.<ref name="ReferenceA">{{cite journal | vauthors = Excoffon KJ, Hruska-Hageman A, Klotz M, Traver GL, Zabner J | title = A role for the PDZ-binding domain of the coxsackie B virus and adenovirus receptor (CAR) in cell adhesion and growth | journal = Journal of Cell Science | volume = 117 | issue = Pt 19 | pages = 4401–9 | date = Sep 2004 | pmid = 15304526 | doi = 10.1242/jcs.01300 }}</ref>
{{reflist|2}}
 
==Further reading==
The protein is found to be expressed in various regions of the body including the [[heart]], [[brain]], and, more generally, [[epithelial cell|epithelial]] and [[endothelial cell]]s. Moreover, CAR expression is not found in normal or tumor cell lines. Expression of CAR in [[endothelial cell]]s can be regulated by treatment with drugs.<ref name="pmid20392896">{{cite journal | vauthors = Funke C, Farr M, Werner B, Dittmann S, Uberla K, Piper C, Niehaus K, Horstkotte D | title = Antiviral effect of Bosentan and Valsartan during coxsackievirus B3 infection of human endothelial cells | journal = The Journal of General Virology | volume = 91 | issue = Pt 8 | pages = 1959–70 | date = Aug 2010 | pmid = 20392896 | pmc =  | doi = 10.1099/vir.0.020065-0 }}</ref><ref name="pmid24316867">{{cite journal | vauthors = Werner B, Dittmann S, Funke C, Überla K, Piper C, Niehaus K, Horstkotte D, Farr M | title = Effect of lovastatin on coxsackievirus B3 infection in human endothelial cells | journal = Inflammation Research | volume = 63 | issue = 4 | pages = 267–76 | date = Apr 2014 | pmid = 24316867 | pmc =  | doi = 10.1007/s00011-013-0695-z }}</ref>
{{refbegin | 2}}
 
{{PBB_Further_reading
== Function ==
| citations =
It functions as a homophilic and heterophilic [[cell adhesion]] molecule through its interactions with [[extracellular matrix]] glycoproteins such as: [[fibronectin]], [[agrin]], [[laminin|laminin-1]] and [[tenascin-R]].<ref name="pmid20181587">{{cite journal | vauthors = Patzke C, Max KE, Behlke J, Schreiber J, Schmidt H, Dorner AA, Kröger S, Henning M, Otto A, Heinemann U, Rathjen FG | title = The coxsackievirus-adenovirus receptor reveals complex homophilic and heterophilic interactions on neural cells | journal = The Journal of Neuroscience | volume = 30 | issue = 8 | pages = 2897–910 | date = Feb 2010 | pmid = 20181587 | pmc =  | doi = 10.1523/JNEUROSCI.5725-09.2010 }}</ref> In addition, it is thought to regulate the [[cytoskeleton]] through interactions with [[actin]] and [[microtubule]]s. Moreover, its [[cytoplasm]]ic domain contains putative [[phosphorylation]] sites and a [[PDZ domain|PDZ-interaction motif]] which suggests a scaffolding role.
*{{cite journal | author=Carson SD |title=Receptor for the group B coxsackieviruses and adenoviruses: CAR. |journal=Rev. Med. Virol. |volume=11 |issue= 4 |pages= 219-26 |year= 2002 |pmid= 11479928 |doi= }}
 
*{{cite journal  | author=Selinka HC, Wolde A, Sauter M, ''et al.'' |title=Virus-receptor interactions of coxsackie B viruses and their putative influence on cardiotropism. |journal=Med. Microbiol. Immunol. |volume=193 |issue= 2-3 |pages= 127-31 |year= 2004 |pmid= 12920584 |doi= 10.1007/s00430-003-0193-y }}
===Cardiac===
*{{cite journal  | author=Bergelson JM, Cunningham JA, Droguett G, ''et al.'' |title=Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. |journal=Science |volume=275 |issue= 5304 |pages= 1320-3 |year= 1997 |pmid= 9036860 |doi= }}
CAR is essential for normal development of [[cardiomyocytes]]. The expression of CAR is high in developing tissues, including the heart and brain; postnatally it is expressed in [[epithelial cell]]s and in adult [[cardiac muscle]], it is localized at [[intercalated disc]]s.<ref>{{cite journal | vauthors = Kashimura T, Kodama M, Hotta Y, Hosoya J, Yoshida K, Ozawa T, Watanabe R, Okura Y, Kato K, Hanawa H, Kuwano R, Aizawa Y | title = Spatiotemporal changes of coxsackievirus and adenovirus receptor in rat hearts during postnatal development and in cultured cardiomyocytes of neonatal rat | journal = Virchows Archiv | volume = 444 | issue = 3 | pages = 283–92 | date = Mar 2004 | pmid = 14624362 | doi = 10.1007/s00428-003-0925-9 }}</ref> Knocking out CAR is embryonic lethal by day 11.5, coordinate with severe [[cardiac muscle]] abnormalities including left [[ventricle (heart)|ventricular]] [[hyperplasia]], [[heart valve|sinuatrial valve]] abnormalities, [[pericardium|pericardial]] [[edema]], thoracic [[hemorrhage|hemorrhaging]], [[myocardium|myocardial]] wall degeneration, regional apoptosis, reduced density and disorganization of [[myofibril]]s, and enlarged [[mitochondria]].<ref>{{cite journal | vauthors = Asher DR, Cerny AM, Weiler SR, Horner JW, Keeler ML, Neptune MA, Jones SN, Bronson RT, Depinho RA, Finberg RW | title = Coxsackievirus and adenovirus receptor is essential for cardiomyocyte development | journal = Genesis | volume = 42 | issue = 2 | pages = 77–85 | date = Jun 2005 | pmid = 15864812 | doi = 10.1002/gene.20127 }}</ref><ref>{{cite journal | vauthors = Dorner AA, Wegmann F, Butz S, Wolburg-Buchholz K, Wolburg H, Mack A, Nasdala I, August B, Westermann J, Rathjen FG, Vestweber D | title = Coxsackievirus-adenovirus receptor (CAR) is essential for early embryonic cardiac development | journal = Journal of Cell Science | volume = 118 | issue = Pt 15 | pages = 3509–21 | date = Aug 2005 | pmid = 16079292 | doi = 10.1242/jcs.02476 }}</ref><ref name="ReferenceB">{{cite journal | vauthors = Chen JW, Zhou B, Yu QC, Shin SJ, Jiao K, Schneider MD, Baldwin HS, Bergelson JM | title = Cardiomyocyte-specific deletion of the coxsackievirus and adenovirus receptor results in hyperplasia of the embryonic left ventricle and abnormalities of sinuatrial valves | journal = Circulation Research | volume = 98 | issue = 7 | pages = 923–30 | date = Apr 2006 | pmid = 16543498 | doi = 10.1161/01.RES.0000218041.41932.e3 }}</ref> [[Cardiomyocyte]]-specific deletion of CAR after embryonic day 11 had no noticeable effect on development and postnatal life, suggesting that CAR is critical during a temporal window of cardiac development.<ref name="ReferenceB"/>
*{{cite journal | author=Tomko RP, Xu R, Philipson L |title=HCAR and MCAR: the human and mouse cellular receptors for subgroup C adenoviruses and group B coxsackieviruses. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue= 7 |pages= 3352-6 |year= 1997 |pmid= 9096397 |doi= }}
 
*{{cite journal  | author=Carson SD, Chapman NN, Tracy SM |title=Purification of the putative coxsackievirus B receptor from HeLa cells. |journal=Biochem. Biophys. Res. Commun. |volume=233 |issue= 2 |pages= 325-8 |year= 1997 |pmid= 9144533 |doi= 10.1006/bbrc.1997.6449 }}
It is clear from studies employing transgenesis that CAR function at [[intercalated disc]]s in [[cardiac muscle]] is critical for normal heart function. Cardiac-specific knockout of CAR causes first degree block or complete block in the propagation of electrical conduction in the [[AV node]]. This was coordinate with the loss of [[GJC1|connexin-45]] at cell-cell junctions on the [[sarcolemma]]l membranes of [[AV node]] cells. Mice eventually developed [[cardiomyopathy]] associated with [[intercalated disc]] disorganization and loss of [[cardiomyocyte]] [[CTNNB1|beta-catenin]] and [[TJP1|ZO-1]] expression; studies also showed that CAR, and [[GJC1|connexin-45]] form a protein complex that requires the PDZ-binding motif on CAR for proper formation. Moreover, CAR is required for normal localization of [[GJC1|connexin-45]], [[CTNNB1|beta-catenin]] and [[TJP1|ZO-1]] at [[intercalated disc]]s.<ref>{{cite journal | vauthors = Lim BK, Xiong D, Dorner A, Youn TJ, Yung A, Liu TI, Gu Y, Dalton ND, Wright AT, Evans SM, Chen J, Peterson KL, McCulloch AD, Yajima T, Knowlton KU | title = Coxsackievirus and adenovirus receptor (CAR) mediates atrioventricular-node function and connexin 45 localization in the murine heart | journal = The Journal of Clinical Investigation | volume = 118 | issue = 8 | pages = 2758–70 | date = Aug 2008 | pmid = 18636119 | doi = 10.1172/JCI34777 | pmc=2467382}}</ref>
*{{cite journal  | author=Bergelson JM, Krithivas A, Celi L, ''et al.'' |title=The murine CAR homolog is a receptor for coxsackie B viruses and adenoviruses. |journal=J. Virol. |volume=72 |issue= 1 |pages= 415-9 |year= 1998 |pmid= 9420240 |doi= }}
 
*{{cite journal | author=Fechner H, Haack A, Wang H, ''et al.'' |title=Expression of coxsackie adenovirus receptor and alphav-integrin does not correlate with adenovector targeting in vivo indicating anatomical vector barriers. |journal=Gene Ther. |volume=6 |issue= 9 |pages= 1520-35 |year= 2000 |pmid= 10490761 |doi= 10.1038/sj.gt.3301030 }}
Studies from human hearts have shown that lower expression of ''CXADR'' [[mRNA]] is associated with a risk allele at chromosome 21q21, which may in fact predispose hearts to [[arrhythmia]]s. To discern the mechanistic underpinnings, hearts from heterozygous CAR knockout mice subjected to acute [[myocardium|myocardial]] [[ischemia]] were evaluated and showed slowed ventricular conduction, earlier onset of [[ventricle (heart)|ventricular]] [[arrhythmia]]s, and increased susceptibility to [[arrhythmia]]s. These findings were coordinate with a reduction in magnitude of the sodium current at [[intercalated disc]]s; interestingly, CAR coprecipitated with NaV1.5, which may provide a mechanistic link to this finding.<ref name="Marsman RF 2013">{{cite journal | vauthors = Marsman RF, Bezzina CR, Freiberg F, Verkerk AO, Adriaens ME, Podliesna S, Chen C, Purfürst B, Spallek B, Koopmann TT, Baczko I, Dos Remedios CG, George AL, Bishopric NH, Lodder EM, de Bakker JM, Fischer R, Coronel R, Wilde AA, Gotthardt M, Remme CA | title = Coxsackie and adenovirus receptor is a modifier of cardiac conduction and arrhythmia vulnerability in the setting of myocardial ischemia | journal = Journal of the American College of Cardiology | volume = 63 | issue = 6 | pages = 549–59 | date = Feb 2014 | pmid = 24291282 | doi = 10.1016/j.jacc.2013.10.062 | pmc=3926969}}</ref>
*{{cite journal | author=Bowles KR, Gibson J, Wu J, ''et al.'' |title=Genomic organization and chromosomal localization of the human Coxsackievirus B-adenovirus receptor gene. |journal=Hum. Genet. |volume=105 |issue= 4 |pages= 354-9 |year= 1999 |pmid= 10543405 |doi= }}
   
*{{cite journal | author=Bewley MC, Springer K, Zhang YB, ''et al.'' |title=Structural analysis of the mechanism of adenovirus binding to its human cellular receptor, CAR. |journal=Science |volume=286 |issue= 5444 |pages= 1579-83 |year= 1999 |pmid= 10567268 |doi= }}
===Neural and lymphatic===
*{{cite journal  | author=Tomko RP, Johansson CB, Totrov M, ''et al.'' |title=Expression of the adenovirus receptor and its interaction with the fiber knob. |journal=Exp. Cell Res. |volume=255 |issue= 1 |pages= 47-55 |year= 2000 |pmid= 10666333 |doi= 10.1006/excr.1999.4761 }}
CAR is strongly expressed in the developing central nervous system where it is thought to mediate [[neurite]] outgrowth. In contrast,expression of CAR is undetectable in the adult nervous system.<ref name="pmid20181587"/>
*{{cite journal | author=van Raaij MJ, Chouin E, van der Zandt H, ''et al.'' |title=Dimeric structure of the coxsackievirus and adenovirus receptor D1 domain at 1.7 A resolution. |journal=Structure |volume=8 |issue= 11 |pages= 1147-55 |year= 2001 |pmid= 11080637 |doi= }}
 
*{{cite journal  | author=Cohen CJ, Gaetz J, Ohman T, Bergelson JM |title=Multiple regions within the coxsackievirus and adenovirus receptor cytoplasmic domain are required for basolateral sorting. |journal=J. Biol. Chem. |volume=276 |issue= 27 |pages= 25392-8 |year= 2001 |pmid= 11316797 |doi= 10.1074/jbc.M009531200 }}
It has also been shown that CAR is critical for the development of lymphatic vasculature and in forming lymphatic [[endothelial cell|endothelial]] cell-cell junctions.<ref>{{cite journal | vauthors = Mirza M, Pang MF, Zaini MA, Haiko P, Tammela T, Alitalo K, Philipson L, Fuxe J, Sollerbrant K | title = Essential role of the coxsackie- and adenovirus receptor (CAR) in development of the lymphatic system in mice | journal = PLOS ONE | volume = 7 | issue = 5 | pages = e37523 | date = 2012 | pmid = 22624044 | doi = 10.1371/journal.pone.0037523 | pmc=3356332}}</ref>
*{{cite journal | author=Noutsias M, Fechner H, de Jonge H, ''et al.'' |title=Human coxsackie-adenovirus receptor is colocalized with integrins alpha(v)beta(3) and alpha(v)beta(5) on the cardiomyocyte sarcolemma and upregulated in dilated cardiomyopathy: implications for cardiotropic viral infections. |journal=Circulation |volume=104 |issue= 3 |pages= 275-80 |year= 2001 |pmid= 11457744 |doi= }}
 
*{{cite journal | author=Thoelen I, Magnusson C, Tågerud S, ''et al.'' |title=Identification of alternative splice products encoded by the human coxsackie-adenovirus receptor gene. |journal=Biochem. Biophys. Res. Commun. |volume=287 |issue= 1 |pages= 216-22 |year= 2001 |pmid= 11549277 |doi= 10.1006/bbrc.2001.5535 }}
==Clinical Significance==
*{{cite journal | author=He Y, Chipman PR, Howitt J, ''et al.'' |title=Interaction of coxsackievirus B3 with the full length coxsackievirus-adenovirus receptor. |journal=Nat. Struct. Biol. |volume=8 |issue= 10 |pages= 874-8 |year= 2001 |pmid= 11573093 |doi= 10.1038/nsb1001-874 }}
 
*{{cite journal  | author=Cohen CJ, Shieh JT, Pickles RJ, ''et al.'' |title=The coxsackievirus and adenovirus receptor is a transmembrane component of the tight junction. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=98 |issue= 26 |pages= 15191-6 |year= 2002 |pmid= 11734628 |doi= 10.1073/pnas.261452898 }}
CAR is a receptor for both [[Coxsackie B virus]] and [[adenovirus]] 2 and 5, which are structurally distinct.<ref>{{cite journal | vauthors = Bergelson JM, Cunningham JA, Droguett G, Kurt-Jones EA, Krithivas A, Hong JS, Horwitz MS, Crowell RL, Finberg RW | title = Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5 | journal = Science | volume = 275 | issue = 5304 | pages = 1320–3 | date = Feb 1997 | pmid = 9036860 | doi=10.1126/science.275.5304.1320}}</ref>
*{{cite journal | author=Law LK, Davidson BL |title=Adenovirus serotype 30 fiber does not mediate transduction via the coxsackie-adenovirus receptor. |journal=J. Virol. |volume=76 |issue= 2 |pages= 656-61 |year= 2002 |pmid= 11752156 |doi= }}
 
*{{cite journal | author=van't Hof W, Crystal RG |title=Fatty acid modification of the coxsackievirus and adenovirus receptor. |journal=J. Virol. |volume=76 |issue= 12 |pages= 6382-6 |year= 2002 |pmid= 12021372 |doi= }}
In patients with [[myocarditis]] or [[dilated cardiomyopathy]], elevated [[coxsackie B virus|Coxsackie B2]] viral [[nucleic acid]]s have been detected in [[myocardium|myocardial]] [[biopsy]] samples.<ref>{{cite journal | vauthors = Bowles NE, Richardson PJ, Olsen EG, Archard LC | title = Detection of Coxsackie-B-virus-specific RNA sequences in myocardial biopsy samples from patients with myocarditis and dilated cardiomyopathy | journal = Lancet | volume = 1 | issue = 8490 | pages = 1120–3 | date = May 1986 | pmid = 2871380 | doi=10.1016/s0140-6736(86)91837-4}}</ref> [[Adenovirus|Adenoviral]] genomic [[DNA]] has also been detected in [[myocardium|myocardial]] [[biopsy|biopsies]] of patients with idiopathic [[cardiomyopathy]], or impaired left [[ventricle (heart)|ventricular]] function of unknown origin.<ref>{{cite journal | vauthors = Pauschinger M, Bowles NE, Fuentes-Garcia FJ, Pham V, Kühl U, Schwimmbeck PL, Schultheiss HP, Towbin JA | title = Detection of adenoviral genome in the myocardium of adult patients with idiopathic left ventricular dysfunction | journal = Circulation | volume = 99 | issue = 10 | pages = 1348–54 | date = Mar 1999 | pmid = 10077520 | doi=10.1161/01.cir.99.10.1348}}</ref> Patients exhibiting sudden death from acute [[myocardial infarction]] had a higher proportion of active [[coxsackie B virus]] infection relative to matched controls, which was coordinate with disrupted [[sarcolemma]]l localization of [[dystrophin]], suggesting that [[enterovirus|enteroviral]] infection may worsen the outcome of patients with acute [[myocardial infarction]].<ref>{{cite journal | vauthors = Andréoletti L, Ventéo L, Douche-Aourik F, Canas F, Lorin de la Grandmaison G, Jacques J, Moret H, Jovenin N, Mosnier JF, Matta M, Duband S, Pluot M, Pozzetto B, Bourlet T | title = Active Coxsackieviral B infection is associated with disruption of dystrophin in endomyocardial tissue of patients who died suddenly of acute myocardial infarction | journal = Journal of the American College of Cardiology | volume = 50 | issue = 23 | pages = 2207–14 | date = Dec 2007 | pmid = 18061067 | doi = 10.1016/j.jacc.2007.07.080 }}</ref>
*{{cite journal | author=Walters RW, Freimuth P, Moninger TO, ''et al.'' |title=Adenovirus fiber disrupts CAR-mediated intercellular adhesion allowing virus escape. |journal=Cell |volume=110 |issue= 6 |pages= 789-99 |year= 2002 |pmid= 12297051 |doi= }}
 
}}
A role for CAR in [[arrhythmia]] susceptibility and [[ventricular fibrillation]] after [[myocardial infarction]] was shown in that ''CXADR'' lies near the 21q21 locus, which is strongly associated with these insults.<ref name="Marsman RF 2013"/><ref>{{cite journal | vauthors = Marsman RF, Wilde AA, Bezzina CR | title = Genetic predisposition for sudden cardiac death in myocardial ischaemia: the Arrhythmia Genetics in the NEtherlandS study | journal = Netherlands Heart Journal | volume = 19 | issue = 2 | pages = 96–100 | date = Feb 2011 | pmid = 21461030 | doi = 10.1007/s12471-010-0070-4 | pmc=3040308}}</ref><ref>{{cite journal | vauthors = Bezzina CR, Pazoki R, Bardai A, Marsman RF, de Jong JS, Blom MT, Scicluna BP, Jukema JW, Bindraban NR, Lichtner P, Pfeufer A, Bishopric NH, Roden DM, Meitinger T, Chugh SS, Myerburg RJ, Jouven X, Kääb S, Dekker LR, Tan HL, Tanck MW, Wilde AA | title = Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction | journal = Nature Genetics | volume = 42 | issue = 8 | pages = 688–91 | date = Aug 2010 | pmid = 20622880 | doi = 10.1038/ng.623 | pmc=3966292}}</ref><ref>{{cite journal | vauthors = Chopra N, Knollmann BC | title = Genetics of sudden cardiac death syndromes | journal = Current Opinion in Cardiology | volume = 26 | issue = 3 | pages = 196–203 | date = May 2011 | pmid = 21430528 | doi = 10.1097/HCO.0b013e3283459893 | pmc=3145336}}</ref>
 
== Interactions ==
 
CAR has been shown to [[protein-protein interaction|interact]] with:
[[MAGI1|MAGI-1b]],<ref name="ReferenceA"/>
[[PICK1]],<ref name="ReferenceA"/>
[[DLG4|PSD-95]],<ref name="ReferenceA"/>
[[TJP1|ZO-1]],<ref>{{cite journal | vauthors = Cohen CJ, Shieh JT, Pickles RJ, Okegawa T, Hsieh JT, Bergelson JM | title = The coxsackievirus and adenovirus receptor is a transmembrane component of the tight junction | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 26 | pages = 15191–6 | date = Dec 2001 | pmid = 11734628 | doi = 10.1073/pnas.261452898 | pmc=65005}}</ref>
[[SCN5A|NaV1.5]]<ref name="Marsman RF 2013"/>
 
== References ==
{{reflist|33em}}
 
== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Carson SD | title = Receptor for the group B coxsackieviruses and adenoviruses: CAR | journal = Reviews in Medical Virology | volume = 11 | issue = 4 | pages = 219–26 | year = 2002 | pmid = 11479928 | doi = 10.1002/rmv.318 }}
* {{cite journal | vauthors = Selinka HC, Wolde A, Sauter M, Kandolf R, Klingel K | title = Virus-receptor interactions of coxsackie B viruses and their putative influence on cardiotropism | journal = Medical Microbiology and Immunology | volume = 193 | issue = 2–3 | pages = 127–31 | date = May 2004 | pmid = 12920584 | doi = 10.1007/s00430-003-0193-y }}
* {{cite journal | vauthors = Carson SD, Chapman NN, Tracy SM | title = Purification of the putative coxsackievirus B receptor from HeLa cells | journal = Biochemical and Biophysical Research Communications | volume = 233 | issue = 2 | pages = 325–8 | date = Apr 1997 | pmid = 9144533 | doi = 10.1006/bbrc.1997.6449 }}
* {{cite journal | vauthors = Bergelson JM, Krithivas A, Celi L, Droguett G, Horwitz MS, Wickham T, Crowell RL, Finberg RW | title = The murine CAR homolog is a receptor for coxsackie B viruses and adenoviruses | journal = Journal of Virology | volume = 72 | issue = 1 | pages = 415–9 | date = Jan 1998 | pmid = 9420240 | pmc = 109389 | doi =  }}
* {{cite journal | vauthors = Fechner H, Haack A, Wang H, Wang X, Eizema K, Pauschinger M, Schoemaker R, Veghel R, Houtsmuller A, Schultheiss HP, Lamers J, Poller W | title = Expression of coxsackie adenovirus receptor and alphav-integrin does not correlate with adenovector targeting in vivo indicating anatomical vector barriers | journal = Gene Therapy | volume = 6 | issue = 9 | pages = 1520–35 | date = Sep 1999 | pmid = 10490761 | doi = 10.1038/sj.gt.3301030 }}
* {{cite journal | vauthors = Bowles KR, Gibson J, Wu J, Shaffer LG, Towbin JA, Bowles NE | title = Genomic organization and chromosomal localization of the human Coxsackievirus B-adenovirus receptor gene | journal = Human Genetics | volume = 105 | issue = 4 | pages = 354–9 | date = Oct 1999 | pmid = 10543405 | doi = 10.1007/s004390051114 }}
* {{cite journal | vauthors = Bewley MC, Springer K, Zhang YB, Freimuth P, Flanagan JM | title = Structural analysis of the mechanism of adenovirus binding to its human cellular receptor, CAR | journal = Science | volume = 286 | issue = 5444 | pages = 1579–83 | date = Nov 1999 | pmid = 10567268 | doi = 10.1126/science.286.5444.1579 }}
* {{cite journal | vauthors = Tomko RP, Johansson CB, Totrov M, Abagyan R, Frisén J, Philipson L | title = Expression of the adenovirus receptor and its interaction with the fiber knob | journal = Experimental Cell Research | volume = 255 | issue = 1 | pages = 47–55 | date = Feb 2000 | pmid = 10666333 | doi = 10.1006/excr.1999.4761 }}
* {{cite journal | vauthors = van Raaij MJ, Chouin E, van der Zandt H, Bergelson JM, Cusack S | title = Dimeric structure of the coxsackievirus and adenovirus receptor D1 domain at 1.7 A resolution | journal = Structure | volume = 8 | issue = 11 | pages = 1147–55 | date = Nov 2000 | pmid = 11080637 | doi = 10.1016/S0969-2126(00)00528-1 }}
* {{cite journal | vauthors = Cohen CJ, Gaetz J, Ohman T, Bergelson JM | title = Multiple regions within the coxsackievirus and adenovirus receptor cytoplasmic domain are required for basolateral sorting | journal = The Journal of Biological Chemistry | volume = 276 | issue = 27 | pages = 25392–8 | date = Jul 2001 | pmid = 11316797 | doi = 10.1074/jbc.M009531200 }}
* {{cite journal | vauthors = Noutsias M, Fechner H, de Jonge H, Wang X, Dekkers D, Houtsmuller AB, Pauschinger M, Bergelson J, Warraich R, Yacoub M, Hetzer R, Lamers J, Schultheiss HP, Poller W | title = Human coxsackie-adenovirus receptor is colocalized with integrins alpha(v)beta(3) and alpha(v)beta(5) on the cardiomyocyte sarcolemma and upregulated in dilated cardiomyopathy: implications for cardiotropic viral infections | journal = Circulation | volume = 104 | issue = 3 | pages = 275–80 | date = Jul 2001 | pmid = 11457744 | doi = 10.1161/01.cir.104.3.275 }}
* {{cite journal | vauthors = Thoelen I, Magnusson C, Tågerud S, Polacek C, Lindberg M, Van Ranst M | title = Identification of alternative splice products encoded by the human coxsackie-adenovirus receptor gene | journal = Biochemical and Biophysical Research Communications | volume = 287 | issue = 1 | pages = 216–22 | date = Sep 2001 | pmid = 11549277 | doi = 10.1006/bbrc.2001.5535 }}
* {{cite journal | vauthors = He Y, Chipman PR, Howitt J, Bator CM, Whitt MA, Baker TS, Kuhn RJ, Anderson CW, Freimuth P, Rossmann MG | title = Interaction of coxsackievirus B3 with the full length coxsackievirus-adenovirus receptor | journal = Nature Structural Biology | volume = 8 | issue = 10 | pages = 874–8 | date = Oct 2001 | pmid = 11573093 | doi = 10.1038/nsb1001-874 }}
* {{cite journal | vauthors = Cohen CJ, Shieh JT, Pickles RJ, Okegawa T, Hsieh JT, Bergelson JM | title = The coxsackievirus and adenovirus receptor is a transmembrane component of the tight junction | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 26 | pages = 15191–6 | date = Dec 2001 | pmid = 11734628 | pmc = 65005 | doi = 10.1073/pnas.261452898 }}
* {{cite journal | vauthors = Law LK, Davidson BL | title = Adenovirus serotype 30 fiber does not mediate transduction via the coxsackie-adenovirus receptor | journal = Journal of Virology | volume = 76 | issue = 2 | pages = 656–61 | date = Jan 2002 | pmid = 11752156 | pmc = 136819 | doi = 10.1128/JVI.76.2.656-661.2002 }}
* {{cite journal | vauthors = van't Hof W, Crystal RG | title = Fatty acid modification of the coxsackievirus and adenovirus receptor | journal = Journal of Virology | volume = 76 | issue = 12 | pages = 6382–6 | date = Jun 2002 | pmid = 12021372 | pmc = 136239 | doi = 10.1128/JVI.76.12.6382-6386.2002 }}
* {{cite journal | vauthors = Walters RW, Freimuth P, Moninger TO, Ganske I, Zabner J, Welsh MJ | title = Adenovirus fiber disrupts CAR-mediated intercellular adhesion allowing virus escape | journal = Cell | volume = 110 | issue = 6 | pages = 789–99 | date = Sep 2002 | pmid = 12297051 | doi = 10.1016/S0092-8674(02)00912-1 }}
{{refend}}
{{refend}}
{{PDB Gallery|geneid=1525}}


{{gene-21-stub}}
[[Category:Adenoviridae]]

Latest revision as of 17:03, 30 August 2017

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Coxsackievirus and adenovirus receptor (CAR) is a protein that in humans is encoded by the CXADR gene.[1][2][3] The protein encoded by this gene is a type I membrane receptor for group B coxsackie viruses and subgroup C adenoviruses. CAR protein is expressed in several tissues, including heart, brain, and, more generally, epithelial and endothelial cells. In cardiac muscle, CAR is localized to intercalated disc structures, which electrically and mechanically couple adjacent cardiomyocytes. CAR plays an important role in the pathogenesis of myocarditis, dilated cardiomyopathy, and in arrhythmia susceptibility following myocardial infarction or myocardial ischemia.

Structure

Human CAR protein has a theoretical molecular weight of 40.0 kDa and is composed of 365 amino acids.[4] The human CAR gene (CXADR) is found on chromosome 21. Alternative splicing is known to produce at least 2 splice variants known as hCAR1 and hCAR2 and are each composed of at least 7 exons. Pseudogenes of this gene are found on chromosomes 15, 18, and 21.[3]

CAR is a transmembrane bound protein with two Ig-like extracellular domains, a transmembrane domain, a cytoplasmic domain, and two N-linked glycosylation sites. CAR contains two disulfide bonded loops (residues 35-130 and 155-220).[5] The N-terminal segment comprises the two extracellular domains (D1 and D2). D1 is most distal from the membrane and contains a V/Ig-like fold whereas D2 is more proximal. The cytoplasmic tail of CAR contains the amino acids GSIV, which is characterized as a class 1 PDZ binding motif for interacting with proteins containing PDZ domains.[6]

The protein is found to be expressed in various regions of the body including the heart, brain, and, more generally, epithelial and endothelial cells. Moreover, CAR expression is not found in normal or tumor cell lines. Expression of CAR in endothelial cells can be regulated by treatment with drugs.[7][8]

Function

It functions as a homophilic and heterophilic cell adhesion molecule through its interactions with extracellular matrix glycoproteins such as: fibronectin, agrin, laminin-1 and tenascin-R.[9] In addition, it is thought to regulate the cytoskeleton through interactions with actin and microtubules. Moreover, its cytoplasmic domain contains putative phosphorylation sites and a PDZ-interaction motif which suggests a scaffolding role.

Cardiac

CAR is essential for normal development of cardiomyocytes. The expression of CAR is high in developing tissues, including the heart and brain; postnatally it is expressed in epithelial cells and in adult cardiac muscle, it is localized at intercalated discs.[10] Knocking out CAR is embryonic lethal by day 11.5, coordinate with severe cardiac muscle abnormalities including left ventricular hyperplasia, sinuatrial valve abnormalities, pericardial edema, thoracic hemorrhaging, myocardial wall degeneration, regional apoptosis, reduced density and disorganization of myofibrils, and enlarged mitochondria.[11][12][13] Cardiomyocyte-specific deletion of CAR after embryonic day 11 had no noticeable effect on development and postnatal life, suggesting that CAR is critical during a temporal window of cardiac development.[13]

It is clear from studies employing transgenesis that CAR function at intercalated discs in cardiac muscle is critical for normal heart function. Cardiac-specific knockout of CAR causes first degree block or complete block in the propagation of electrical conduction in the AV node. This was coordinate with the loss of connexin-45 at cell-cell junctions on the sarcolemmal membranes of AV node cells. Mice eventually developed cardiomyopathy associated with intercalated disc disorganization and loss of cardiomyocyte beta-catenin and ZO-1 expression; studies also showed that CAR, and connexin-45 form a protein complex that requires the PDZ-binding motif on CAR for proper formation. Moreover, CAR is required for normal localization of connexin-45, beta-catenin and ZO-1 at intercalated discs.[14]

Studies from human hearts have shown that lower expression of CXADR mRNA is associated with a risk allele at chromosome 21q21, which may in fact predispose hearts to arrhythmias. To discern the mechanistic underpinnings, hearts from heterozygous CAR knockout mice subjected to acute myocardial ischemia were evaluated and showed slowed ventricular conduction, earlier onset of ventricular arrhythmias, and increased susceptibility to arrhythmias. These findings were coordinate with a reduction in magnitude of the sodium current at intercalated discs; interestingly, CAR coprecipitated with NaV1.5, which may provide a mechanistic link to this finding.[15]

Neural and lymphatic

CAR is strongly expressed in the developing central nervous system where it is thought to mediate neurite outgrowth. In contrast,expression of CAR is undetectable in the adult nervous system.[9]

It has also been shown that CAR is critical for the development of lymphatic vasculature and in forming lymphatic endothelial cell-cell junctions.[16]

Clinical Significance

CAR is a receptor for both Coxsackie B virus and adenovirus 2 and 5, which are structurally distinct.[17]

In patients with myocarditis or dilated cardiomyopathy, elevated Coxsackie B2 viral nucleic acids have been detected in myocardial biopsy samples.[18] Adenoviral genomic DNA has also been detected in myocardial biopsies of patients with idiopathic cardiomyopathy, or impaired left ventricular function of unknown origin.[19] Patients exhibiting sudden death from acute myocardial infarction had a higher proportion of active coxsackie B virus infection relative to matched controls, which was coordinate with disrupted sarcolemmal localization of dystrophin, suggesting that enteroviral infection may worsen the outcome of patients with acute myocardial infarction.[20]

A role for CAR in arrhythmia susceptibility and ventricular fibrillation after myocardial infarction was shown in that CXADR lies near the 21q21 locus, which is strongly associated with these insults.[15][21][22][23]

Interactions

CAR has been shown to interact with: MAGI-1b,[6] PICK1,[6] PSD-95,[6] ZO-1,[24] NaV1.5[15]

References

  1. ↑ Bergelson JM, Cunningham JA, Droguett G, Kurt-Jones EA, Krithivas A, Hong JS, Horwitz MS, Crowell RL, Finberg RW (Feb 1997). "Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5". Science. 275 (5304): 1320–3. doi:10.1126/science.275.5304.1320. PMID 9036860.
  2. ↑ Tomko RP, Xu R, Philipson L (Apr 1997). "HCAR and MCAR: the human and mouse cellular receptors for subgroup C adenoviruses and group B coxsackieviruses". Proceedings of the National Academy of Sciences of the United States of America. 94 (7): 3352–6. doi:10.1073/pnas.94.7.3352. PMC 20373. PMID 9096397.
  3. ↑ 3.0 3.1 "Entrez Gene: CXADR coxsackie virus and adenovirus receptor".
  4. ↑ "Protein sequence of human CXADR (Uniprot ID: P78310)". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Retrieved 14 July 2015.
  5. ↑ Tomko RP, Xu R, Philipson L (Apr 1997). "HCAR and MCAR: the human and mouse cellular receptors for subgroup C adenoviruses and group B coxsackieviruses". Proceedings of the National Academy of Sciences of the United States of America. 94 (7): 3352–6. doi:10.1073/pnas.94.7.3352. PMC 20373. PMID 9096397.
  6. ↑ 6.0 6.1 6.2 6.3 Excoffon KJ, Hruska-Hageman A, Klotz M, Traver GL, Zabner J (Sep 2004). "A role for the PDZ-binding domain of the coxsackie B virus and adenovirus receptor (CAR) in cell adhesion and growth". Journal of Cell Science. 117 (Pt 19): 4401–9. doi:10.1242/jcs.01300. PMID 15304526.
  7. ↑ Funke C, Farr M, Werner B, Dittmann S, Uberla K, Piper C, Niehaus K, Horstkotte D (Aug 2010). "Antiviral effect of Bosentan and Valsartan during coxsackievirus B3 infection of human endothelial cells". The Journal of General Virology. 91 (Pt 8): 1959–70. doi:10.1099/vir.0.020065-0. PMID 20392896.
  8. ↑ Werner B, Dittmann S, Funke C, Überla K, Piper C, Niehaus K, Horstkotte D, Farr M (Apr 2014). "Effect of lovastatin on coxsackievirus B3 infection in human endothelial cells". Inflammation Research. 63 (4): 267–76. doi:10.1007/s00011-013-0695-z. PMID 24316867.
  9. ↑ 9.0 9.1 Patzke C, Max KE, Behlke J, Schreiber J, Schmidt H, Dorner AA, Kröger S, Henning M, Otto A, Heinemann U, Rathjen FG (Feb 2010). "The coxsackievirus-adenovirus receptor reveals complex homophilic and heterophilic interactions on neural cells". The Journal of Neuroscience. 30 (8): 2897–910. doi:10.1523/JNEUROSCI.5725-09.2010. PMID 20181587.
  10. ↑ Kashimura T, Kodama M, Hotta Y, Hosoya J, Yoshida K, Ozawa T, Watanabe R, Okura Y, Kato K, Hanawa H, Kuwano R, Aizawa Y (Mar 2004). "Spatiotemporal changes of coxsackievirus and adenovirus receptor in rat hearts during postnatal development and in cultured cardiomyocytes of neonatal rat". Virchows Archiv. 444 (3): 283–92. doi:10.1007/s00428-003-0925-9. PMID 14624362.
  11. ↑ Asher DR, Cerny AM, Weiler SR, Horner JW, Keeler ML, Neptune MA, Jones SN, Bronson RT, Depinho RA, Finberg RW (Jun 2005). "Coxsackievirus and adenovirus receptor is essential for cardiomyocyte development". Genesis. 42 (2): 77–85. doi:10.1002/gene.20127. PMID 15864812.
  12. ↑ Dorner AA, Wegmann F, Butz S, Wolburg-Buchholz K, Wolburg H, Mack A, Nasdala I, August B, Westermann J, Rathjen FG, Vestweber D (Aug 2005). "Coxsackievirus-adenovirus receptor (CAR) is essential for early embryonic cardiac development". Journal of Cell Science. 118 (Pt 15): 3509–21. doi:10.1242/jcs.02476. PMID 16079292.
  13. ↑ 13.0 13.1 Chen JW, Zhou B, Yu QC, Shin SJ, Jiao K, Schneider MD, Baldwin HS, Bergelson JM (Apr 2006). "Cardiomyocyte-specific deletion of the coxsackievirus and adenovirus receptor results in hyperplasia of the embryonic left ventricle and abnormalities of sinuatrial valves". Circulation Research. 98 (7): 923–30. doi:10.1161/01.RES.0000218041.41932.e3. PMID 16543498.
  14. ↑ Lim BK, Xiong D, Dorner A, Youn TJ, Yung A, Liu TI, Gu Y, Dalton ND, Wright AT, Evans SM, Chen J, Peterson KL, McCulloch AD, Yajima T, Knowlton KU (Aug 2008). "Coxsackievirus and adenovirus receptor (CAR) mediates atrioventricular-node function and connexin 45 localization in the murine heart". The Journal of Clinical Investigation. 118 (8): 2758–70. doi:10.1172/JCI34777. PMC 2467382. PMID 18636119.
  15. ↑ 15.0 15.1 15.2 Marsman RF, Bezzina CR, Freiberg F, Verkerk AO, Adriaens ME, Podliesna S, Chen C, Purfürst B, Spallek B, Koopmann TT, Baczko I, Dos Remedios CG, George AL, Bishopric NH, Lodder EM, de Bakker JM, Fischer R, Coronel R, Wilde AA, Gotthardt M, Remme CA (Feb 2014). "Coxsackie and adenovirus receptor is a modifier of cardiac conduction and arrhythmia vulnerability in the setting of myocardial ischemia". Journal of the American College of Cardiology. 63 (6): 549–59. doi:10.1016/j.jacc.2013.10.062. PMC 3926969. PMID 24291282.
  16. ↑ Mirza M, Pang MF, Zaini MA, Haiko P, Tammela T, Alitalo K, Philipson L, Fuxe J, Sollerbrant K (2012). "Essential role of the coxsackie- and adenovirus receptor (CAR) in development of the lymphatic system in mice". PLOS ONE. 7 (5): e37523. doi:10.1371/journal.pone.0037523. PMC 3356332. PMID 22624044.
  17. ↑ Bergelson JM, Cunningham JA, Droguett G, Kurt-Jones EA, Krithivas A, Hong JS, Horwitz MS, Crowell RL, Finberg RW (Feb 1997). "Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5". Science. 275 (5304): 1320–3. doi:10.1126/science.275.5304.1320. PMID 9036860.
  18. ↑ Bowles NE, Richardson PJ, Olsen EG, Archard LC (May 1986). "Detection of Coxsackie-B-virus-specific RNA sequences in myocardial biopsy samples from patients with myocarditis and dilated cardiomyopathy". Lancet. 1 (8490): 1120–3. doi:10.1016/s0140-6736(86)91837-4. PMID 2871380.
  19. ↑ Pauschinger M, Bowles NE, Fuentes-Garcia FJ, Pham V, Kühl U, Schwimmbeck PL, Schultheiss HP, Towbin JA (Mar 1999). "Detection of adenoviral genome in the myocardium of adult patients with idiopathic left ventricular dysfunction". Circulation. 99 (10): 1348–54. doi:10.1161/01.cir.99.10.1348. PMID 10077520.
  20. ↑ Andréoletti L, Ventéo L, Douche-Aourik F, Canas F, Lorin de la Grandmaison G, Jacques J, Moret H, Jovenin N, Mosnier JF, Matta M, Duband S, Pluot M, Pozzetto B, Bourlet T (Dec 2007). "Active Coxsackieviral B infection is associated with disruption of dystrophin in endomyocardial tissue of patients who died suddenly of acute myocardial infarction". Journal of the American College of Cardiology. 50 (23): 2207–14. doi:10.1016/j.jacc.2007.07.080. PMID 18061067.
  21. ↑ Marsman RF, Wilde AA, Bezzina CR (Feb 2011). "Genetic predisposition for sudden cardiac death in myocardial ischaemia: the Arrhythmia Genetics in the NEtherlandS study". Netherlands Heart Journal. 19 (2): 96–100. doi:10.1007/s12471-010-0070-4. PMC 3040308. PMID 21461030.
  22. ↑ Bezzina CR, Pazoki R, Bardai A, Marsman RF, de Jong JS, Blom MT, Scicluna BP, Jukema JW, Bindraban NR, Lichtner P, Pfeufer A, Bishopric NH, Roden DM, Meitinger T, Chugh SS, Myerburg RJ, Jouven X, Kääb S, Dekker LR, Tan HL, Tanck MW, Wilde AA (Aug 2010). "Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction". Nature Genetics. 42 (8): 688–91. doi:10.1038/ng.623. PMC 3966292. PMID 20622880.
  23. ↑ Chopra N, Knollmann BC (May 2011). "Genetics of sudden cardiac death syndromes". Current Opinion in Cardiology. 26 (3): 196–203. doi:10.1097/HCO.0b013e3283459893. PMC 3145336. PMID 21430528.
  24. ↑ Cohen CJ, Shieh JT, Pickles RJ, Okegawa T, Hsieh JT, Bergelson JM (Dec 2001). "The coxsackievirus and adenovirus receptor is a transmembrane component of the tight junction". Proceedings of the National Academy of Sciences of the United States of America. 98 (26): 15191–6. doi:10.1073/pnas.261452898. PMC 65005. PMID 11734628.

Further reading

Retrieved from "https://www.wikidoc.org/index.php?title=Coxsackie_virus_and_adenovirus_receptor&oldid=1419821"