Full text data of F11R
F11R
(JAM1, JCAM)
[Confidence: high (present in two of the MS resources)]
Junctional adhesion molecule A; JAM-A (Junctional adhesion molecule 1; JAM-1; Platelet F11 receptor; Platelet adhesion molecule 1; PAM-1; CD321; Flags: Precursor)
Junctional adhesion molecule A; JAM-A (Junctional adhesion molecule 1; JAM-1; Platelet F11 receptor; Platelet adhesion molecule 1; PAM-1; CD321; Flags: Precursor)
hRBCD
IPI00001754
IPI00001754 Junctional adhesion molecule 1 precursor Junctional adhesion molecule 1 precursor membrane n/a n/a 1 n/a 3 2 n/a 1 n/a n/a 1 3 2 2 n/a 1 1 n/a n/a 1 type I membrane protein n/a found at its expected molecular weight found at molecular weight
IPI00001754 Junctional adhesion molecule 1 precursor Junctional adhesion molecule 1 precursor membrane n/a n/a 1 n/a 3 2 n/a 1 n/a n/a 1 3 2 2 n/a 1 1 n/a n/a 1 type I membrane protein n/a found at its expected molecular weight found at molecular weight
UniProt
Q9Y624
ID JAM1_HUMAN Reviewed; 299 AA.
AC Q9Y624;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1999, sequence version 1.
DT 22-JAN-2014, entry version 142.
DE RecName: Full=Junctional adhesion molecule A;
DE Short=JAM-A;
DE AltName: Full=Junctional adhesion molecule 1;
DE Short=JAM-1;
DE AltName: Full=Platelet F11 receptor;
DE AltName: Full=Platelet adhesion molecule 1;
DE Short=PAM-1;
DE AltName: CD_antigen=CD321;
DE Flags: Precursor;
GN Name=F11R; Synonyms=JAM1, JCAM; ORFNames=UNQ264/PRO301;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10395639;
RA Ozaki H., Ishii K., Horiuchi H., Arai H., Kawamoto T., Okawa K.,
RA Iwamatsu A., Kita T.;
RT "Combined treatment of TNF-alpha and IFN-gamma causes redistribution
RT of junctional adhesion molecule in human endothelial cells.";
RL J. Immunol. 163:553-557(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10753840;
RA Sobocka M.B., Sobocki T., Banerjee P., Weiss C., Rushbrook J.I.,
RA Norin A.J., Hartwig J., Salifu M.O., Markell M.S., Babinska A.,
RA Ehrlich Y.H., Kornecki E.;
RT "Cloning of the human platelet F11 receptor: a cell adhesion molecule
RT member of the immunoglobulin superfamily involved in platelet
RT aggregation.";
RL Blood 95:2600-2609(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION.
RX PubMed=11171323;
RA Naik U.P., Naik M.U., Eckfeld K., Martin-DeLeon P., Spychala J.;
RT "Characterization and chromosomal localization of JAM-1, a platelet
RT receptor for a stimulatory monoclonal antibody.";
RL J. Cell Sci. 114:539-547(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=11230166; DOI=10.1101/gr.GR1547R;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S.,
RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
RA Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale
RT effort to identify novel human secreted and transmembrane proteins: a
RT bioinformatics assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 28-103 AND 123-130, AND GLYCOSYLATION.
RX PubMed=7646439;
RA Naik U.P., Ehrlich Y.H., Kornecki E.;
RT "Mechanisms of platelet activation by a stimulatory antibody: cross-
RT linking of a novel platelet receptor for monoclonal antibody F11 with
RT the Fc gamma RII receptor.";
RL Biochem. J. 310:155-162(1995).
RN [8]
RP PROTEIN SEQUENCE OF 28-42.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally
RT verified cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [9]
RP PROTEIN SEQUENCE OF 28-39.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [10]
RP INTERACTION WITH MPDZ.
RX PubMed=11489913; DOI=10.1083/jcb.200103047;
RA Itoh M., Sasaki H., Furuse M., Ozaki H., Kita T., Tsukita S.;
RT "Junctional adhesion molecule (JAM) binds to PAR-3: a possible
RT mechanism for the recruitment of PAR-3 to tight junctions.";
RL J. Cell Biol. 154:491-497(2001).
RN [11]
RP REVIEW, AND NOMENCLATURE.
RX PubMed=12810109; DOI=10.1016/S1471-4906(03)00117-0;
RA Muller W.A.;
RT "Leukocyte-endothelial-cell interactions in leukocyte transmigration
RT and the inflammatory response.";
RL Trends Immunol. 24:327-334(2003).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, AND MASS
RP SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-281; SER-284 AND
RP SER-287, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-185 AND ASN-191, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
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.,
RA Buerckstuemmer T., 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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 28-233.
RX PubMed=12697893; DOI=10.1073/pnas.0937718100;
RA Prota A.E., Campbell J.A., Schelling P., Forrest J.C., Watson M.J.,
RA Peters T.R., Aurrand-Lions M.A., Imhof B.A., Dermody T.S., Stehle T.;
RT "Crystal structure of human junctional adhesion molecule 1:
RT implications for reovirus binding.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:5366-5371(2003).
CC -!- FUNCTION: Seems to play a role in epithelial tight junction
CC formation. Appears early in primordial forms of cell junctions and
CC recruits PARD3. The association of the PARD6-PARD3 complex may
CC prevent the interaction of PARD3 with JAM1, thereby preventing
CC tight junction assembly (By similarity). Plays a role in
CC regulating monocyte transmigration involved in integrity of
CC epithelial barrier. Involved in platelet activation. In case of
CC orthoreovirus infection, serves as receptor for the virus.
CC -!- SUBUNIT: Interacts with the ninth PDZ domain of MPDZ. Interacts
CC with the first PDZ domain of PARD3. The association between PARD3
CC and PARD6B probably disrupts this interaction. Interacts with the
CC orthoreovirus sigma-1 capsid protein (By similarity).
CC -!- INTERACTION:
CC Q8TEW0:PARD3; NbExp=2; IntAct=EBI-742600, EBI-81968;
CC -!- SUBCELLULAR LOCATION: Cell junction, tight junction. Cell
CC membrane; Single-pass type I membrane protein. Note=Localized at
CC tight junctions of both epithelial and endothelial cells.
CC -!- PTM: N-glycosylated.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily.
CC -!- SIMILARITY: Contains 2 Ig-like V-type (immunoglobulin-like)
CC domains.
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DR EMBL; AF111713; AAD42050.1; -; mRNA.
DR EMBL; AF207907; AAF22829.1; -; mRNA.
DR EMBL; AF172398; AAD48877.1; -; mRNA.
DR EMBL; AL136649; CAB66584.1; -; mRNA.
DR EMBL; AY358896; AAQ89255.1; -; mRNA.
DR EMBL; BC001533; AAH01533.1; -; mRNA.
DR PIR; A59406; S56749.
DR RefSeq; NP_058642.1; NM_016946.4.
DR UniGene; Hs.517293; -.
DR PDB; 1NBQ; X-ray; 2.90 A; A/B=27-233.
DR PDB; 3EOY; X-ray; 3.40 A; G/H/I/J/K/L=28-129.
DR PDB; 3TSZ; X-ray; 2.50 A; B=288-299.
DR PDBsum; 1NBQ; -.
DR PDBsum; 3EOY; -.
DR PDBsum; 3TSZ; -.
DR ProteinModelPortal; Q9Y624; -.
DR SMR; Q9Y624; 25-233.
DR IntAct; Q9Y624; 5.
DR MINT; MINT-154235; -.
DR STRING; 9606.ENSP00000289779; -.
DR PhosphoSite; Q9Y624; -.
DR DMDM; 10720061; -.
DR PaxDb; Q9Y624; -.
DR PeptideAtlas; Q9Y624; -.
DR PRIDE; Q9Y624; -.
DR DNASU; 50848; -.
DR Ensembl; ENST00000368026; ENSP00000357005; ENSG00000158769.
DR GeneID; 50848; -.
DR KEGG; hsa:50848; -.
DR UCSC; uc001fxf.4; human.
DR CTD; 50848; -.
DR GeneCards; GC01M160965; -.
DR GeneCards; GC01M160975; -.
DR HGNC; HGNC:14685; F11R.
DR HPA; CAB004671; -.
DR MIM; 605721; gene.
DR neXtProt; NX_Q9Y624; -.
DR PharmGKB; PA29991; -.
DR eggNOG; NOG150281; -.
DR HOVERGEN; HBG000518; -.
DR InParanoid; Q9Y624; -.
DR KO; K06089; -.
DR OrthoDB; EOG7MH0Z1; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111155; Cell-Cell communication.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR Reactome; REACT_604; Hemostasis.
DR ChiTaRS; F11R; human.
DR EvolutionaryTrace; Q9Y624; -.
DR GeneWiki; F11_receptor; -.
DR GenomeRNAi; 50848; -.
DR NextBio; 53317; -.
DR PRO; PR:Q9Y624; -.
DR ArrayExpress; Q9Y624; -.
DR Bgee; Q9Y624; -.
DR CleanEx; HS_F11R; -.
DR Genevestigator; Q9Y624; -.
DR GO; GO:0005911; C:cell-cell junction; TAS:ProtInc.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:LIFEdb.
DR GO; GO:0005923; C:tight junction; IEA:UniProtKB-SubCell.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0007155; P:cell adhesion; IEA:Ensembl.
DR GO; GO:0030855; P:epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; TAS:ProtInc.
DR GO; GO:0050900; P:leukocyte migration; TAS:Reactome.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0070830; P:tight junction assembly; TAS:Reactome.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:Reactome.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR013106; Ig_V-set.
DR InterPro; IPR003596; Ig_V-set_subgr.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00408; IGc2; 1.
DR SMART; SM00406; IGv; 1.
DR PROSITE; PS50835; IG_LIKE; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Cell junction; Cell membrane; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Host-virus interaction; Immunoglobulin domain; Membrane;
KW Phosphoprotein; Reference proteome; Repeat; Signal; Tight junction;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1 27
FT CHAIN 28 299 Junctional adhesion molecule A.
FT /FTId=PRO_0000015066.
FT TOPO_DOM 28 238 Extracellular (Potential).
FT TRANSMEM 239 259 Helical; (Potential).
FT TOPO_DOM 260 299 Cytoplasmic (Potential).
FT DOMAIN 28 125 Ig-like V-type 1.
FT DOMAIN 135 228 Ig-like V-type 2.
FT MOD_RES 281 281 Phosphoserine.
FT MOD_RES 284 284 Phosphoserine.
FT MOD_RES 287 287 Phosphoserine.
FT CARBOHYD 185 185 N-linked (GlcNAc...).
FT CARBOHYD 191 191 N-linked (GlcNAc...).
FT DISULFID 50 109
FT DISULFID 153 212
FT STRAND 30 32
FT STRAND 36 40
FT STRAND 47 49
FT STRAND 51 54
FT STRAND 56 66
FT STRAND 69 75
FT STRAND 76 79
FT TURN 81 86
FT STRAND 88 90
FT STRAND 93 95
FT HELIX 101 103
FT STRAND 105 113
FT STRAND 123 125
FT STRAND 128 130
FT STRAND 140 144
FT STRAND 149 151
FT STRAND 163 168
FT STRAND 177 182
FT TURN 192 194
FT STRAND 197 201
FT HELIX 204 206
FT STRAND 210 215
FT STRAND 217 219
FT STRAND 230 232
SQ SEQUENCE 299 AA; 32583 MW; D95DE2FEA23D2851 CRC64;
MGTKAQVERK LLCLFILAIL LCSLALGSVT VHSSEPEVRI PENNPVKLSC AYSGFSSPRV
EWKFDQGDTT RLVCYNNKIT ASYEDRVTFL PTGITFKSVT REDTGTYTCM VSEEGGNSYG
EVKVKLIVLV PPSKPTVNIP SSATIGNRAV LTCSEQDGSP PSEYTWFKDG IVMPTNPKST
RAFSNSSYVL NPTTGELVFD PLSASDTGEY SCEARNGYGT PMTSNAVRME AVERNVGVIV
AAVLVTLILL GILVFGIWFA YSRGHFDRTK KGTSSKKVIY SQPSARSEGE FKQTSSFLV
//
ID JAM1_HUMAN Reviewed; 299 AA.
AC Q9Y624;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1999, sequence version 1.
DT 22-JAN-2014, entry version 142.
DE RecName: Full=Junctional adhesion molecule A;
DE Short=JAM-A;
DE AltName: Full=Junctional adhesion molecule 1;
DE Short=JAM-1;
DE AltName: Full=Platelet F11 receptor;
DE AltName: Full=Platelet adhesion molecule 1;
DE Short=PAM-1;
DE AltName: CD_antigen=CD321;
DE Flags: Precursor;
GN Name=F11R; Synonyms=JAM1, JCAM; ORFNames=UNQ264/PRO301;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10395639;
RA Ozaki H., Ishii K., Horiuchi H., Arai H., Kawamoto T., Okawa K.,
RA Iwamatsu A., Kita T.;
RT "Combined treatment of TNF-alpha and IFN-gamma causes redistribution
RT of junctional adhesion molecule in human endothelial cells.";
RL J. Immunol. 163:553-557(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10753840;
RA Sobocka M.B., Sobocki T., Banerjee P., Weiss C., Rushbrook J.I.,
RA Norin A.J., Hartwig J., Salifu M.O., Markell M.S., Babinska A.,
RA Ehrlich Y.H., Kornecki E.;
RT "Cloning of the human platelet F11 receptor: a cell adhesion molecule
RT member of the immunoglobulin superfamily involved in platelet
RT aggregation.";
RL Blood 95:2600-2609(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION.
RX PubMed=11171323;
RA Naik U.P., Naik M.U., Eckfeld K., Martin-DeLeon P., Spychala J.;
RT "Characterization and chromosomal localization of JAM-1, a platelet
RT receptor for a stimulatory monoclonal antibody.";
RL J. Cell Sci. 114:539-547(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=11230166; DOI=10.1101/gr.GR1547R;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S.,
RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
RA Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale
RT effort to identify novel human secreted and transmembrane proteins: a
RT bioinformatics assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 28-103 AND 123-130, AND GLYCOSYLATION.
RX PubMed=7646439;
RA Naik U.P., Ehrlich Y.H., Kornecki E.;
RT "Mechanisms of platelet activation by a stimulatory antibody: cross-
RT linking of a novel platelet receptor for monoclonal antibody F11 with
RT the Fc gamma RII receptor.";
RL Biochem. J. 310:155-162(1995).
RN [8]
RP PROTEIN SEQUENCE OF 28-42.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally
RT verified cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [9]
RP PROTEIN SEQUENCE OF 28-39.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [10]
RP INTERACTION WITH MPDZ.
RX PubMed=11489913; DOI=10.1083/jcb.200103047;
RA Itoh M., Sasaki H., Furuse M., Ozaki H., Kita T., Tsukita S.;
RT "Junctional adhesion molecule (JAM) binds to PAR-3: a possible
RT mechanism for the recruitment of PAR-3 to tight junctions.";
RL J. Cell Biol. 154:491-497(2001).
RN [11]
RP REVIEW, AND NOMENCLATURE.
RX PubMed=12810109; DOI=10.1016/S1471-4906(03)00117-0;
RA Muller W.A.;
RT "Leukocyte-endothelial-cell interactions in leukocyte transmigration
RT and the inflammatory response.";
RL Trends Immunol. 24:327-334(2003).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, AND MASS
RP SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-281; SER-284 AND
RP SER-287, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-185 AND ASN-191, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
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.,
RA Buerckstuemmer T., 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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 28-233.
RX PubMed=12697893; DOI=10.1073/pnas.0937718100;
RA Prota A.E., Campbell J.A., Schelling P., Forrest J.C., Watson M.J.,
RA Peters T.R., Aurrand-Lions M.A., Imhof B.A., Dermody T.S., Stehle T.;
RT "Crystal structure of human junctional adhesion molecule 1:
RT implications for reovirus binding.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:5366-5371(2003).
CC -!- FUNCTION: Seems to play a role in epithelial tight junction
CC formation. Appears early in primordial forms of cell junctions and
CC recruits PARD3. The association of the PARD6-PARD3 complex may
CC prevent the interaction of PARD3 with JAM1, thereby preventing
CC tight junction assembly (By similarity). Plays a role in
CC regulating monocyte transmigration involved in integrity of
CC epithelial barrier. Involved in platelet activation. In case of
CC orthoreovirus infection, serves as receptor for the virus.
CC -!- SUBUNIT: Interacts with the ninth PDZ domain of MPDZ. Interacts
CC with the first PDZ domain of PARD3. The association between PARD3
CC and PARD6B probably disrupts this interaction. Interacts with the
CC orthoreovirus sigma-1 capsid protein (By similarity).
CC -!- INTERACTION:
CC Q8TEW0:PARD3; NbExp=2; IntAct=EBI-742600, EBI-81968;
CC -!- SUBCELLULAR LOCATION: Cell junction, tight junction. Cell
CC membrane; Single-pass type I membrane protein. Note=Localized at
CC tight junctions of both epithelial and endothelial cells.
CC -!- PTM: N-glycosylated.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily.
CC -!- SIMILARITY: Contains 2 Ig-like V-type (immunoglobulin-like)
CC domains.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF111713; AAD42050.1; -; mRNA.
DR EMBL; AF207907; AAF22829.1; -; mRNA.
DR EMBL; AF172398; AAD48877.1; -; mRNA.
DR EMBL; AL136649; CAB66584.1; -; mRNA.
DR EMBL; AY358896; AAQ89255.1; -; mRNA.
DR EMBL; BC001533; AAH01533.1; -; mRNA.
DR PIR; A59406; S56749.
DR RefSeq; NP_058642.1; NM_016946.4.
DR UniGene; Hs.517293; -.
DR PDB; 1NBQ; X-ray; 2.90 A; A/B=27-233.
DR PDB; 3EOY; X-ray; 3.40 A; G/H/I/J/K/L=28-129.
DR PDB; 3TSZ; X-ray; 2.50 A; B=288-299.
DR PDBsum; 1NBQ; -.
DR PDBsum; 3EOY; -.
DR PDBsum; 3TSZ; -.
DR ProteinModelPortal; Q9Y624; -.
DR SMR; Q9Y624; 25-233.
DR IntAct; Q9Y624; 5.
DR MINT; MINT-154235; -.
DR STRING; 9606.ENSP00000289779; -.
DR PhosphoSite; Q9Y624; -.
DR DMDM; 10720061; -.
DR PaxDb; Q9Y624; -.
DR PeptideAtlas; Q9Y624; -.
DR PRIDE; Q9Y624; -.
DR DNASU; 50848; -.
DR Ensembl; ENST00000368026; ENSP00000357005; ENSG00000158769.
DR GeneID; 50848; -.
DR KEGG; hsa:50848; -.
DR UCSC; uc001fxf.4; human.
DR CTD; 50848; -.
DR GeneCards; GC01M160965; -.
DR GeneCards; GC01M160975; -.
DR HGNC; HGNC:14685; F11R.
DR HPA; CAB004671; -.
DR MIM; 605721; gene.
DR neXtProt; NX_Q9Y624; -.
DR PharmGKB; PA29991; -.
DR eggNOG; NOG150281; -.
DR HOVERGEN; HBG000518; -.
DR InParanoid; Q9Y624; -.
DR KO; K06089; -.
DR OrthoDB; EOG7MH0Z1; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111155; Cell-Cell communication.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR Reactome; REACT_604; Hemostasis.
DR ChiTaRS; F11R; human.
DR EvolutionaryTrace; Q9Y624; -.
DR GeneWiki; F11_receptor; -.
DR GenomeRNAi; 50848; -.
DR NextBio; 53317; -.
DR PRO; PR:Q9Y624; -.
DR ArrayExpress; Q9Y624; -.
DR Bgee; Q9Y624; -.
DR CleanEx; HS_F11R; -.
DR Genevestigator; Q9Y624; -.
DR GO; GO:0005911; C:cell-cell junction; TAS:ProtInc.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:LIFEdb.
DR GO; GO:0005923; C:tight junction; IEA:UniProtKB-SubCell.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0007155; P:cell adhesion; IEA:Ensembl.
DR GO; GO:0030855; P:epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; TAS:ProtInc.
DR GO; GO:0050900; P:leukocyte migration; TAS:Reactome.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0070830; P:tight junction assembly; TAS:Reactome.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:Reactome.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR013106; Ig_V-set.
DR InterPro; IPR003596; Ig_V-set_subgr.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00408; IGc2; 1.
DR SMART; SM00406; IGv; 1.
DR PROSITE; PS50835; IG_LIKE; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Cell junction; Cell membrane; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Host-virus interaction; Immunoglobulin domain; Membrane;
KW Phosphoprotein; Reference proteome; Repeat; Signal; Tight junction;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1 27
FT CHAIN 28 299 Junctional adhesion molecule A.
FT /FTId=PRO_0000015066.
FT TOPO_DOM 28 238 Extracellular (Potential).
FT TRANSMEM 239 259 Helical; (Potential).
FT TOPO_DOM 260 299 Cytoplasmic (Potential).
FT DOMAIN 28 125 Ig-like V-type 1.
FT DOMAIN 135 228 Ig-like V-type 2.
FT MOD_RES 281 281 Phosphoserine.
FT MOD_RES 284 284 Phosphoserine.
FT MOD_RES 287 287 Phosphoserine.
FT CARBOHYD 185 185 N-linked (GlcNAc...).
FT CARBOHYD 191 191 N-linked (GlcNAc...).
FT DISULFID 50 109
FT DISULFID 153 212
FT STRAND 30 32
FT STRAND 36 40
FT STRAND 47 49
FT STRAND 51 54
FT STRAND 56 66
FT STRAND 69 75
FT STRAND 76 79
FT TURN 81 86
FT STRAND 88 90
FT STRAND 93 95
FT HELIX 101 103
FT STRAND 105 113
FT STRAND 123 125
FT STRAND 128 130
FT STRAND 140 144
FT STRAND 149 151
FT STRAND 163 168
FT STRAND 177 182
FT TURN 192 194
FT STRAND 197 201
FT HELIX 204 206
FT STRAND 210 215
FT STRAND 217 219
FT STRAND 230 232
SQ SEQUENCE 299 AA; 32583 MW; D95DE2FEA23D2851 CRC64;
MGTKAQVERK LLCLFILAIL LCSLALGSVT VHSSEPEVRI PENNPVKLSC AYSGFSSPRV
EWKFDQGDTT RLVCYNNKIT ASYEDRVTFL PTGITFKSVT REDTGTYTCM VSEEGGNSYG
EVKVKLIVLV PPSKPTVNIP SSATIGNRAV LTCSEQDGSP PSEYTWFKDG IVMPTNPKST
RAFSNSSYVL NPTTGELVFD PLSASDTGEY SCEARNGYGT PMTSNAVRME AVERNVGVIV
AAVLVTLILL GILVFGIWFA YSRGHFDRTK KGTSSKKVIY SQPSARSEGE FKQTSSFLV
//
MIM
605721
*RECORD*
*FIELD* NO
605721
*FIELD* TI
*605721 JUNCTION ADHESION MOLECULE 1; JAM1
;;JUNCTION ADHESION MOLECULE, MOUSE, HOMOLOG OF; JAM;;
read moreJAM-A
*FIELD* TX
DESCRIPTION
JAM1 is an immunoglobulin-like molecule that colocalizes with tight
junctions in endothelium and epithelium and is also found on blood
leukocytes and platelets (summary by Arrate et al., 2001).
CLONING
By searching databases for sequences similar to mouse Jam, followed by
PCR of human umbilical vein endothelial cell cDNA library, Williams et
al. (1999) cloned JAM1. The deduced 299-amino acid type I transmembrane
protein contains an N-terminal signal peptide, followed by a 210-amino
acid extracellular region, a putative membrane-spanning domain, and a
38-amino acid cytoplasmic tail. The extracellular domain contains 2
immunoglobulin (Ig)-like V-subset domains. Northern blot analysis
detected a dominant transcript of about 4.4 kb and minor transcripts of
about 2.0 to 2.4 kb. Strongest expression was detected in liver, kidney,
lung, placenta, pancreas, and peripheral blood leukocytes. Weaker
expression was detected in spleen and heart, and very weak expression
was detected in skeletal muscle. No expression was detected in brain.
Western blot analysis detected widespread surface expression of JAM in
leukemia cell lines. By FACS, expression of JAM was detected in all
normal circulating monocytes and neutrophils and in the majority of
platelets. About half of circulating T and B lymphocytes expressed JAM1.
Expression of JAM1 was not increased in neutrophils or T lymphocytes by
any activation protocol examined.
Epithelial cells form a highly selective barrier and line many organs.
The epithelial barrier is maintained by closely apposed cell-cell
contacts containing tight junctions. Liu et al. (2000) reported the
cloning and tissue localization of an Ig superfamily member that likely
represents the human homolog of murine Jam. Analysis of the primary
structure of human JAM, which was cloned from T84 epithelial cells,
predicts a 299-amino acid transmembrane protein with an N-terminal
signal peptide, 2 potential N-glycosylation sites, and an extracellular
domain that contains 2 IgV loops. The mature mouse and human JAM
proteins are 70% identical. Monoclonal antibodies generated against the
putative extracellular domain were reactive with a 35- to 39-kD protein
from both T84 epithelial cells and human neutrophils. By
immunofluorescence, JAM monoclonal antibodies labeled epithelial cells
from intestine, lung, and kidney, prominently in the region of tight
junctions (colocalization with occludin (OCLN; 602876)) and also along
lateral cell membranes below the tight junctions. Flow cytometric
studies confirmed predominant JAM expression in epithelial cells but
also revealed expression on endothelial and hematopoietic cells of all
lineages.
Cera et al. (2004) showed that JAM1 is expressed in mouse and human
dendritic cells.
GENE FUNCTION
Functional studies by Liu et al. (2000) demonstrated that JAM-specific
monoclonal antibodies markedly inhibited transepithelial resistance
recovery of T84 monolayers after disruption of intercellular junctions,
including tight junctions, by transient calcium depletion. Morphologic
analysis revealed that after disassembly of cell-cell junctions,
anti-JAM inhibition of barrier function recovery correlated with a loss
of both occludin and JAM, but not ZO1 (601009), in reassembling tight
junction structure. These findings suggested that JAM plays an important
role in the regulation of tight junction assembly in epithelia.
Virus attachment to cells plays an essential role in viral tropism and
disease. Reovirus serotypes 1 and 3 differ in their capacity to target
distinct cell types in the murine nervous system and in their efficiency
to induce apoptosis. The binding of viral attachment protein sigma-1 to
unidentified receptors controls these phenotypes. Using expression
cloning, Barton et al. (2001) identified JAM as a reovirus receptor. JAM
binds directly to sigma-1 and permits reovirus infection of
nonpermissive cells. Ligation of JAM is required for reovirus-induced
activation of NF-kappa-B (see 164011) and apoptosis. Thus, reovirus
interaction with cell-surface receptors is a critical determinant of
both cell-type-specific tropism and virus-induced intracellular
signaling events that culminate in cell death.
By yeast 2-hybrid analysis and leukocyte adhesion assays, Ostermann et
al. (2002) demonstrated that under both static and physiologic flow
conditions, JAM1, through its membrane-proximal domain 2, is a ligand of
the LFA1 integrin (153370/600065) that contributes to the LFA1-dependent
transendothelial migration of CD45RO (151460)-positive memory T cells
expressing the CXCR4 (162643) chemokine receptor and of neutrophils.
These interactions also facilitated LFA1-mediated arrest of T cells.
Activation of endothelium with inflammatory cytokines enhanced memory
T-cell transmigration. Ostermann et al. (2002) suggested that a complex
interplay of heterophilic binding of LFA1 to JAM1 and homophilic
trans-interactions of JAM1 may provide a molecular 'zipper' for
leukocyte transmigration.
Prota et al. (2003) demonstrated that JAM1, but not the related proteins
JAM2 (606870) or JAM3 (606871), serves as a reovirus receptor.
Helicobacter pylori translocates the protein CagA into gastric
epithelial cells and has been linked to peptic ulcer disease and gastric
carcinoma. Amieva et al. (2003) showed that injected CagA associates
with the epithelial tight-junction scaffolding protein ZO-1 (601009) and
the transmembrane protein JAM1, causing an ectopic assembly of tight
junction components at sites of bacterial attachment, and altering the
composition and function of the apical-junctional complex. Long-term
CagA delivery to polarized epithelia caused a disruption of the
epithelial barrier function and dysplastic alterations in epithelial
cell morphology. CagA appears to target H. pylori to host cell
intercellular junctions and to disrupt junction-mediated functions.
BIOCHEMICAL FEATURES
Prota et al. (2003) determined the crystal structure of the human JAM1
extracellular region, which reveals 2 concatenated Ig-type domains with
a pronounced bend at the domain interface. Two JAM1 molecules form a
dimer that is stabilized by extensive ionic and hydrophobic contacts
between the N-terminal domains. This dimeric arrangement is similar to
that observed previously in the murine homolog of JAM1, indicating
physiologic relevance. However, differences in the dimeric structures of
human and murine JAM1 suggest that the interface is dynamic, perhaps as
a result of its ionic nature.
ANIMAL MODEL
Cera et al. (2004) generated Jam1 -/- mice and observed that in vitro,
Jam1 -/- dendritic cells (DCs) showed a selective increase in random
motility and in the capacity to transmigrate across lymphatic
endothelial cells. In vivo, Jam1 -/- mice showed enhanced DC migration
to lymph nodes, which was not observed in mice with
endothelium-restricted deficiency of the protein. Increased DC migration
to lymph nodes was associated with enhanced contact hypersensitivity.
Adoptive transfer experiments showed that Jam1-deficient DCs elicited
increased contact hypersensitivity in Jam1 +/+ mice, further supporting
the concept of a DC-specific effect. Cera et al. (2004) concluded that
JAM1 has a nonredundant role in controlling DC motility, trafficking to
lymph nodes, and activation of specific immunity.
*FIELD* RF
1. Amieva, M. R.; Vogelmann, R.; Covacci, A.; Tompkins, L. S.; Nelson,
W. J.; Falkow, S.: Disruption of the epithelial apical-junctional
complex by Helicobacter pylori CagA. Science 300: 1430-1434, 2003.
2. Arrate, M. P.; Rodriguez, J. M.; Tran, T. T.; Brock, T. A.; Cunningham,
S. A.: Cloning of human junctional adhesion molecule 3 (JAM3) and
its identification as the JAM2 counter-receptor. J. Biol. Chem. 276:
45826-45832, 2001.
3. Barton, E. S.; Forrest, J. C.; Connolly, J. L.; Chappell, J. D.;
Liu, Y.; Schnell, F. J.; Nusrat, A.; Parkos, C. A.; Dermody, T. S.
: Junction adhesion molecule is a receptor for reovirus. Cell 104:
441-451, 2001.
4. Cera, M. R.; Del Prete, A.; Vecchi, A.; Corada, M.; Martin-Padura,
I.; Motoike, T.; Tonetti, P.; Bazzoni, G.; Vermi, W.; Gentili, F.;
Bernasconi, S.; Sato, T. N.; Mantovani, A.; Dejana, E.: Increased
DC trafficking to lymph nodes and contact hypersensitivity in junctional
adhesion molecule-A-deficient mice. J. Clin. Invest. 114: 729-738,
2004.
5. Liu, Y.; Nusrat, A.; Schnell, F. J.; Reaves, T. A.; Walsh, S.;
Pochet, M.; Parkos, C. A.: Human junction adhesion molecule regulates
tight junction resealing in epithelia. J. Cell Sci. 113: 2363-2374,
2000.
6. Ostermann, G.; Weber, K. S. C.; Zernecke, A.; Schroder, A.; Weber,
C.: JAM-1 is a ligand of the beta-2 integrin LFA-1 involved in transendothelial
migration of leukocytes. Nature Immun. 3: 151-158, 2002.
7. Prota, A. E.; Campbell, J. A.; Schelling, P.; Forrest, J. C.; Watson,
M. J.; Peters, T. R.; Aurrand-Lions, M.; Imhof, B. A.; Dermody, T.
S.; Stehle, T.: Crystal structure of human junctional adhesion molecule
1: implications for reovirus binding. Proc. Nat. Acad. Sci. 100:
5366-5371, 2003.
8. Williams, L. A.; Martin-Padura, I.; Dejana, E.; Hogg, N.; Simmons,
D. L.: Identification and characterisation of human Junctional Adhesion
Molecule (JAM). Molec. Immun. 36: 1175-1188, 1999.
*FIELD* CN
Patricia A. Hartz - updated: 1/6/2005
Marla J. F. O'Neill - updated: 11/22/2004
Anne M. Stumpf - updated: 6/23/2003
Ada Hamosh - updated: 6/18/2003
Victor A. McKusick - updated: 6/13/2003
Paul J. Converse - updated: 4/29/2002
*FIELD* CD
Stylianos E. Antonarakis: 3/8/2001
*FIELD* ED
carol: 10/09/2013
carol: 5/16/2007
mgross: 1/10/2005
terry: 1/6/2005
tkritzer: 11/23/2004
tkritzer: 11/22/2004
alopez: 6/23/2003
alopez: 6/18/2003
terry: 6/13/2003
mgross: 4/29/2002
mgross: 4/22/2002
mgross: 3/8/2001
*RECORD*
*FIELD* NO
605721
*FIELD* TI
*605721 JUNCTION ADHESION MOLECULE 1; JAM1
;;JUNCTION ADHESION MOLECULE, MOUSE, HOMOLOG OF; JAM;;
read moreJAM-A
*FIELD* TX
DESCRIPTION
JAM1 is an immunoglobulin-like molecule that colocalizes with tight
junctions in endothelium and epithelium and is also found on blood
leukocytes and platelets (summary by Arrate et al., 2001).
CLONING
By searching databases for sequences similar to mouse Jam, followed by
PCR of human umbilical vein endothelial cell cDNA library, Williams et
al. (1999) cloned JAM1. The deduced 299-amino acid type I transmembrane
protein contains an N-terminal signal peptide, followed by a 210-amino
acid extracellular region, a putative membrane-spanning domain, and a
38-amino acid cytoplasmic tail. The extracellular domain contains 2
immunoglobulin (Ig)-like V-subset domains. Northern blot analysis
detected a dominant transcript of about 4.4 kb and minor transcripts of
about 2.0 to 2.4 kb. Strongest expression was detected in liver, kidney,
lung, placenta, pancreas, and peripheral blood leukocytes. Weaker
expression was detected in spleen and heart, and very weak expression
was detected in skeletal muscle. No expression was detected in brain.
Western blot analysis detected widespread surface expression of JAM in
leukemia cell lines. By FACS, expression of JAM was detected in all
normal circulating monocytes and neutrophils and in the majority of
platelets. About half of circulating T and B lymphocytes expressed JAM1.
Expression of JAM1 was not increased in neutrophils or T lymphocytes by
any activation protocol examined.
Epithelial cells form a highly selective barrier and line many organs.
The epithelial barrier is maintained by closely apposed cell-cell
contacts containing tight junctions. Liu et al. (2000) reported the
cloning and tissue localization of an Ig superfamily member that likely
represents the human homolog of murine Jam. Analysis of the primary
structure of human JAM, which was cloned from T84 epithelial cells,
predicts a 299-amino acid transmembrane protein with an N-terminal
signal peptide, 2 potential N-glycosylation sites, and an extracellular
domain that contains 2 IgV loops. The mature mouse and human JAM
proteins are 70% identical. Monoclonal antibodies generated against the
putative extracellular domain were reactive with a 35- to 39-kD protein
from both T84 epithelial cells and human neutrophils. By
immunofluorescence, JAM monoclonal antibodies labeled epithelial cells
from intestine, lung, and kidney, prominently in the region of tight
junctions (colocalization with occludin (OCLN; 602876)) and also along
lateral cell membranes below the tight junctions. Flow cytometric
studies confirmed predominant JAM expression in epithelial cells but
also revealed expression on endothelial and hematopoietic cells of all
lineages.
Cera et al. (2004) showed that JAM1 is expressed in mouse and human
dendritic cells.
GENE FUNCTION
Functional studies by Liu et al. (2000) demonstrated that JAM-specific
monoclonal antibodies markedly inhibited transepithelial resistance
recovery of T84 monolayers after disruption of intercellular junctions,
including tight junctions, by transient calcium depletion. Morphologic
analysis revealed that after disassembly of cell-cell junctions,
anti-JAM inhibition of barrier function recovery correlated with a loss
of both occludin and JAM, but not ZO1 (601009), in reassembling tight
junction structure. These findings suggested that JAM plays an important
role in the regulation of tight junction assembly in epithelia.
Virus attachment to cells plays an essential role in viral tropism and
disease. Reovirus serotypes 1 and 3 differ in their capacity to target
distinct cell types in the murine nervous system and in their efficiency
to induce apoptosis. The binding of viral attachment protein sigma-1 to
unidentified receptors controls these phenotypes. Using expression
cloning, Barton et al. (2001) identified JAM as a reovirus receptor. JAM
binds directly to sigma-1 and permits reovirus infection of
nonpermissive cells. Ligation of JAM is required for reovirus-induced
activation of NF-kappa-B (see 164011) and apoptosis. Thus, reovirus
interaction with cell-surface receptors is a critical determinant of
both cell-type-specific tropism and virus-induced intracellular
signaling events that culminate in cell death.
By yeast 2-hybrid analysis and leukocyte adhesion assays, Ostermann et
al. (2002) demonstrated that under both static and physiologic flow
conditions, JAM1, through its membrane-proximal domain 2, is a ligand of
the LFA1 integrin (153370/600065) that contributes to the LFA1-dependent
transendothelial migration of CD45RO (151460)-positive memory T cells
expressing the CXCR4 (162643) chemokine receptor and of neutrophils.
These interactions also facilitated LFA1-mediated arrest of T cells.
Activation of endothelium with inflammatory cytokines enhanced memory
T-cell transmigration. Ostermann et al. (2002) suggested that a complex
interplay of heterophilic binding of LFA1 to JAM1 and homophilic
trans-interactions of JAM1 may provide a molecular 'zipper' for
leukocyte transmigration.
Prota et al. (2003) demonstrated that JAM1, but not the related proteins
JAM2 (606870) or JAM3 (606871), serves as a reovirus receptor.
Helicobacter pylori translocates the protein CagA into gastric
epithelial cells and has been linked to peptic ulcer disease and gastric
carcinoma. Amieva et al. (2003) showed that injected CagA associates
with the epithelial tight-junction scaffolding protein ZO-1 (601009) and
the transmembrane protein JAM1, causing an ectopic assembly of tight
junction components at sites of bacterial attachment, and altering the
composition and function of the apical-junctional complex. Long-term
CagA delivery to polarized epithelia caused a disruption of the
epithelial barrier function and dysplastic alterations in epithelial
cell morphology. CagA appears to target H. pylori to host cell
intercellular junctions and to disrupt junction-mediated functions.
BIOCHEMICAL FEATURES
Prota et al. (2003) determined the crystal structure of the human JAM1
extracellular region, which reveals 2 concatenated Ig-type domains with
a pronounced bend at the domain interface. Two JAM1 molecules form a
dimer that is stabilized by extensive ionic and hydrophobic contacts
between the N-terminal domains. This dimeric arrangement is similar to
that observed previously in the murine homolog of JAM1, indicating
physiologic relevance. However, differences in the dimeric structures of
human and murine JAM1 suggest that the interface is dynamic, perhaps as
a result of its ionic nature.
ANIMAL MODEL
Cera et al. (2004) generated Jam1 -/- mice and observed that in vitro,
Jam1 -/- dendritic cells (DCs) showed a selective increase in random
motility and in the capacity to transmigrate across lymphatic
endothelial cells. In vivo, Jam1 -/- mice showed enhanced DC migration
to lymph nodes, which was not observed in mice with
endothelium-restricted deficiency of the protein. Increased DC migration
to lymph nodes was associated with enhanced contact hypersensitivity.
Adoptive transfer experiments showed that Jam1-deficient DCs elicited
increased contact hypersensitivity in Jam1 +/+ mice, further supporting
the concept of a DC-specific effect. Cera et al. (2004) concluded that
JAM1 has a nonredundant role in controlling DC motility, trafficking to
lymph nodes, and activation of specific immunity.
*FIELD* RF
1. Amieva, M. R.; Vogelmann, R.; Covacci, A.; Tompkins, L. S.; Nelson,
W. J.; Falkow, S.: Disruption of the epithelial apical-junctional
complex by Helicobacter pylori CagA. Science 300: 1430-1434, 2003.
2. Arrate, M. P.; Rodriguez, J. M.; Tran, T. T.; Brock, T. A.; Cunningham,
S. A.: Cloning of human junctional adhesion molecule 3 (JAM3) and
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*FIELD* CN
Patricia A. Hartz - updated: 1/6/2005
Marla J. F. O'Neill - updated: 11/22/2004
Anne M. Stumpf - updated: 6/23/2003
Ada Hamosh - updated: 6/18/2003
Victor A. McKusick - updated: 6/13/2003
Paul J. Converse - updated: 4/29/2002
*FIELD* CD
Stylianos E. Antonarakis: 3/8/2001
*FIELD* ED
carol: 10/09/2013
carol: 5/16/2007
mgross: 1/10/2005
terry: 1/6/2005
tkritzer: 11/23/2004
tkritzer: 11/22/2004
alopez: 6/23/2003
alopez: 6/18/2003
terry: 6/13/2003
mgross: 4/29/2002
mgross: 4/22/2002
mgross: 3/8/2001