ID   JAM3_HUMAN              Reviewed;         310 AA.
AC   Q9BX67; Q8WWL8; Q96FL1;
DT   31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   25-JAN-2012, entry version 94.
DE   RecName: Full=Junctional adhesion molecule C;
DE            Short=JAM-C;
DE   AltName: Full=JAM-2;
DE   AltName: Full=Junctional adhesion molecule 3;
DE            Short=JAM-3;
DE   Flags: Precursor;
GN   Name=JAM3; ORFNames=UNQ859/PRO1868;
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], INTERACTION WITH JAM2, AND TISSUE
RP   SPECIFICITY.
RC   TISSUE=Brain;
RX   PubMed=11590146; DOI=10.1074/jbc.M105972200;
RA   Arrate M.P., Rodriguez J.M., Tran T.M., Brock T.A., Cunningham S.A.;
RT   "Cloning of human junctional adhesion molecule 3 (JAM3) and its
RT   identification as the JAM2 counter-receptor.";
RL   J. Biol. Chem. 276:45826-45832(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=11739175; DOI=10.1182/blood.V98.13.3699;
RA   Aurrand-Lions M.A., Johnson-Leger C., Wong C., Du Pasquier L.,
RA   Imhof B.A.;
RT   "Heterogeneity of endothelial junctions is reflected by differential
RT   expression and specific subcellular localization of the three JAM
RT   family members.";
RL   Blood 98:3699-3707(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND
RP   INTERACTION WITH ITGAM.
RX   PubMed=12208882; DOI=10.1084/jem.20020267;
RA   Santoso S., Sachs U.J.H., Kroll H., Linder M., Ruf A., Preissner K.T.,
RA   Chavakis T.;
RT   "The junctional adhesion molecule 3 (JAM-3) on human platelets is a
RT   counterreceptor for the leukocyte integrin Mac-1.";
RL   J. Exp. Med. 196:679-691(2002).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX   MEDLINE=21945252; PubMed=11944976; DOI=10.1006/geno.2002.6742;
RA   Phillips H.M., Renforth G.L., Spalluto C., Hearn T., Curtis A.R.J.,
RA   Craven L., Havarani B., Clement-Jones M., English C., Stumper O.,
RA   Salmon T., Hutchinson S., Jackson M.S., Wilson D.I.;
RT   "Narrowing the critical region within 11q24-qter for hypoplastic left
RT   heart and identification of a candidate gene, JAM3, expressed during
RT   cardiogenesis.";
RL   Genomics 79:475-478(2002).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   MEDLINE=22887296; 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   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16554811; DOI=10.1038/nature04632;
RA   Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA   Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA   Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA   FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA   Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA   Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA   Sakaki Y.;
RT   "Human chromosome 11 DNA sequence and analysis including novel gene
RT   identification.";
RL   Nature 440:497-500(2006).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Eye, and Uterus;
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   [9]
RP   PROTEIN SEQUENCE OF 32-46.
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   [10]
RP   REVIEW, AND NOMENCLATURE.
RX   MEDLINE=22695901; 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   [11]
RP   FUNCTION IN NEUTROPHIL TRANSEPITHELIAL MIGRATION, INTERACTION WITH
RP   ITGAM, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX   PubMed=15194813; DOI=10.1091/mbc.E04-04-0317;
RA   Zen K., Babbin B.A., Liu Y., Whelan J.B., Nusrat A., Parkos C.A.;
RT   "JAM-C is a component of desmosomes and a ligand for CD11b/CD18-
RT   mediated neutrophil transepithelial migration.";
RL   Mol. Biol. Cell 15:3926-3937(2004).
RN   [12]
RP   TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX   PubMed=15994945; DOI=10.1158/0008-5472.CAN-04-4012;
RA   Lamagna C., Hodivala-Dilke K.M., Imhof B.A., Aurrand-Lions M.;
RT   "Antibody against junctional adhesion molecule-C inhibits angiogenesis
RT   and tumor growth.";
RL   Cancer Res. 65:5703-5710(2005).
RN   [13]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-192 AND ASN-198, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19349973; DOI=10.1038/nbt.1532;
RA   Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA   Schiess R., Aebersold R., Watts J.D.;
RT   "Mass-spectrometric identification and relative quantification of N-
RT   linked cell surface glycoproteins.";
RL   Nat. Biotechnol. 27:378-386(2009).
RN   [14]
RP   INVOLVEMENT IN HDBSCC.
RX   PubMed=21109224; DOI=10.1016/j.ajhg.2010.10.026;
RA   Mochida G.H., Ganesh V.S., Felie J.M., Gleason D., Hill R.S.,
RA   Clapham K.R., Rakiec D., Tan W.H., Akawi N., Al-Saffar M.,
RA   Partlow J.N., Tinschert S., Barkovich A.J., Ali B., Al-Gazali L.,
RA   Walsh C.A.;
RT   "A homozygous mutation in the tight-junction protein JAM3 causes
RT   hemorrhagic destruction of the brain, subependymal calcification, and
RT   congenital cataracts.";
RL   Am. J. Hum. Genet. 87:882-889(2010).
RN   [15]
RP   FUNCTION IN ANGIOGENESIS, TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP   AND PROTEOLYTIC CLEAVAGE BY ADAM10 AND ADAM17.
RX   PubMed=20592283; DOI=10.4049/jimmunol.1000556;
RA   Rabquer B.J., Amin M.A., Teegala N., Shaheen M.K., Tsou P.S.,
RA   Ruth J.H., Lesch C.A., Imhof B.A., Koch A.E.;
RT   "Junctional adhesion molecule-C is a soluble mediator of
RT   angiogenesis.";
RL   J. Immunol. 185:1777-1785(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).
CC   -!- FUNCTION: Participates in cell-cell adhesion. It is a
CC       counterreceptor for ITGAM, mediating leukocyte-platelet
CC       interactions and is involved in the regulation of transepithelial
CC       migration of polymorphonuclear neutrophils (PMN). The soluble form
CC       is a mediator of angiogenesis.
CC   -!- SUBUNIT: Interacts with JAM2. Interacts with ITGAM.
CC   -!- INTERACTION:
CC       P57087:JAM2; NbExp=2; IntAct=EBI-4314733, EBI-3918416;
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC       protein (Potential). Cell junction, desmosome. Secreted,
CC       extracellular space. Note=In epithelial cells, it is expressed at
CC       desmosomes but not at tight junctions. Localizes at the cell
CC       surface of endothelial cells; treatment of endothelial cells with
CC       vascular endothelial growth factor stimulates recruitement of JAM3
CC       to cell-cell contacts.
CC   -!- TISSUE SPECIFICITY: Highest expression in placenta, brain and
CC       kidney. Significant expression is detected on platelets. Expressed
CC       in intestinal mucosa cells. Expressed in the vascular endothelium.
CC       Found in serum (at protein level). Also detected in the synovial
CC       fluid of patients with rheumatoid arthritis, psoriatic arthritis
CC       or ostearthritis (at protein level).
CC   -!- PTM: Proteolytically cleaved from endothelial cells surface into a
CC       soluble form by ADAM10 and ADAM17; the release of soluble JAM3 is
CC       increased by proinflammatory factors.
CC   -!- DISEASE: Defects in JAM3 are the cause of hemorrhagic destruction
CC       of the brain with subependymal calcification and cataracts
CC       (HDBSCC) [MIM:613730]. A syndrome characterized by congenital
CC       cataracts and severe brain abnormalities apparently resulting from
CC       hemorrhagic destruction of the brain tissue, including the
CC       cerebral white matter and basal ganglia. Patients manifest
CC       profound developmental delay, and other neurologic features
CC       included seizures, spasticity, and hyperreflexia. Brain imaging
CC       shows multifocal intraparenchymal hemorrhage with associated
CC       liquefaction and massive cystic degeneration, and calcification in
CC       the subependymal region and in brain tissue.
CC   -!- SIMILARITY: Belongs to the immunoglobulin superfamily.
CC   -!- SIMILARITY: Contains 1 Ig-like C2-type (immunoglobulin-like)
CC       domain.
CC   -!- SIMILARITY: Contains 1 Ig-like V-type (immunoglobulin-like)
CC       domain.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAC94776.1; Type=Erroneous initiation;
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DR   EMBL; AF356518; AAK27221.1; -; mRNA.
DR   EMBL; AJ344431; CAC69845.1; -; mRNA.
DR   EMBL; AF448478; AAM20925.1; -; mRNA.
DR   EMBL; AJ416101; CAC94776.1; ALT_INIT; mRNA.
DR   EMBL; AK074769; BAC11195.1; -; mRNA.
DR   EMBL; AK075309; BAC11538.1; -; mRNA.
DR   EMBL; AY358335; AAQ88701.1; -; mRNA.
DR   EMBL; AP000911; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AP001775; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC010690; AAH10690.1; -; mRNA.
DR   EMBL; BC012147; AAH12147.1; -; mRNA.
DR   IPI; IPI00152850; -.
DR   RefSeq; NP_116190.3; NM_032801.4.
DR   UniGene; Hs.150718; -.
DR   UniGene; Hs.728339; -.
DR   ProteinModelPortal; Q9BX67; -.
DR   SMR; Q9BX67; 34-244.
DR   IntAct; Q9BX67; 3.
DR   MINT; MINT-4085421; -.
DR   STRING; Q9BX67; -.
DR   DMDM; 51701611; -.
DR   PRIDE; Q9BX67; -.
DR   Ensembl; ENST00000299106; ENSP00000299106; ENSG00000166086.
DR   GeneID; 83700; -.
DR   KEGG; hsa:83700; -.
DR   UCSC; uc001qhb.1; human.
DR   CTD; 83700; -.
DR   GeneCards; GC11P133972; -.
DR   HGNC; HGNC:15532; JAM3.
DR   HPA; HPA003417; -.
DR   MIM; 606871; gene.
DR   MIM; 613730; phenotype.
DR   neXtProt; NX_Q9BX67; -.
DR   PharmGKB; PA29993; -.
DR   eggNOG; prNOG05172; -.
DR   GeneTree; ENSGT00600000084033; -.
DR   HOGENOM; HBG446408; -.
DR   HOVERGEN; HBG000518; -.
DR   InParanoid; Q9BX67; -.
DR   OrthoDB; EOG4D26QH; -.
DR   Pathway_Interaction_DB; amb2_neutrophils_pathway; amb2 Integrin signaling.
DR   Reactome; REACT_111102; Signal Transduction.
DR   Reactome; REACT_604; Hemostasis.
DR   NextBio; 72688; -.
DR   ArrayExpress; Q9BX67; -.
DR   Bgee; Q9BX67; -.
DR   CleanEx; HS_JAM3; -.
DR   Genevestigator; Q9BX67; -.
DR   GermOnline; ENSG00000166086; Homo sapiens.
DR   GO; GO:0044291; C:cell-cell contact zone; IDA:UniProtKB.
DR   GO; GO:0030057; C:desmosome; IDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005178; F:integrin binding; IPI:UniProtKB.
DR   GO; GO:0001525; P:angiogenesis; IDA:UniProtKB.
DR   GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR   GO; GO:0090022; P:regulation of neutrophil chemotaxis; IDA:UniProtKB.
DR   InterPro; IPR007110; Ig-like.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR013098; Ig_I-set.
DR   InterPro; IPR003599; Ig_sub.
DR   InterPro; IPR003598; Ig_sub2.
DR   InterPro; IPR013106; Ig_V-set.
DR   Gene3D; G3DSA:2.60.40.10; Ig-like_fold; 2.
DR   KO; K06785; -.
DR   Pfam; PF07679; I-set; 1.
DR   Pfam; PF07686; V-set; 1.
DR   SMART; SM00409; IG; 1.
DR   SMART; SM00408; IGc2; 1.
DR   PROSITE; PS50835; IG_LIKE; 2.
PE   1: Evidence at protein level;
KW   Angiogenesis; Cell adhesion; Cell junction; Cell membrane;
KW   Complete proteome; Direct protein sequencing; Disulfide bond;
KW   Glycoprotein; Immunoglobulin domain; Membrane; Reference proteome;
KW   Secreted; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL        1     31
FT   CHAIN        32    310       Junctional adhesion molecule C.
FT                                /FTId=PRO_0000015071.
FT   TOPO_DOM     32    241       Extracellular (Potential).
FT   TRANSMEM    242    262       Helical; (Potential).
FT   TOPO_DOM    263    310       Cytoplasmic (Potential).
FT   DOMAIN       35    127       Ig-like V-type.
FT   DOMAIN      139    236       Ig-like C2-type.
FT   CARBOHYD    104    104       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    192    192       N-linked (GlcNAc...).
FT   CARBOHYD    198    198       N-linked (GlcNAc...).
FT   DISULFID     53    115       Potential.
FT   DISULFID    160    219       Potential.
FT   CONFLICT    136    136       Q -> R (in Ref. 8; AAH10690).
SQ   SEQUENCE   310 AA;  35020 MW;  CE39ADF33EA1DAB9 CRC64;
     MALRRPPRLR LCARLPDFFL LLLFRGCLIG AVNLKSSNRT PVVQEFESVE LSCIITDSQT
     SDPRIEWKKI QDEQTTYVFF DNKIQGDLAG RAEILGKTSL KIWNVTRRDS ALYRCEVVAR
     NDRKEIDEIV IELTVQVKPV TPVCRVPKAV PVGKMATLHC QESEGHPRPH YSWYRNDVPL
     PTDSRANPRF RNSSFHLNSE TGTLVFTAVH KDDSGQYYCI ASNDAGSARC EEQEMEVYDL
     NIGGIIGGVL VVLAVLALIT LGICCAYRRG YFINNKQDGE SYKNPGKPDG VNYIRTDEEG
     DFRHKSSFVI
//