ID JAML_HUMAN Reviewed; 394 AA. AC Q86YT9; B0YIV1; B0YIV2; Q496M1; Q5DTC6; Q7Z499; Q8N9I7; Q8NF70; DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2003, sequence version 1. DT 23-FEB-2022, entry version 154. DE RecName: Full=Junctional adhesion molecule-like {ECO:0000312|HGNC:HGNC:19084}; DE AltName: Full=Adhesion molecule interacting with CXADR antigen 1; DE AltName: Full=Dendritic cell-specific protein CREA7-1; DE Flags: Precursor; GN Name=JAML {ECO:0000312|HGNC:HGNC:19084}; Synonyms=AMICA1; GN ORFNames=UNQ722/PRO1387; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION IN LEUKOCYTE MIGRATION, RP INDUCTION, SUBCELLULAR LOCATION, DOMAIN, TISSUE SPECIFICITY, MUTAGENESIS OF RP LYS-54, AND VARIANT ALA-193. RC TISSUE=Bone marrow; RX PubMed=12869515; DOI=10.1182/blood-2002-11-3462; RA Moog-Lutz C., Cave-Riant F., Guibal F.C., Breau M.A., Di Gioia Y., RA Couraud P.O., Cayre Y.E., Bourdoulous S., Lutz P.G.; RT "JAML, a novel protein with characteristics of a junctional adhesion RT molecule, is induced during differentiation of myeloid leukemia cells."; RL Blood 102:3371-3378(2003). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ASN-94 AND ALA-193. RC TISSUE=Dendritic cell; RA Ahn J.H., Jung H.R., Lee B.-H., Jeon C.J., Bae Y.-S.; RT "Dendritic cell specific protein Crea7-1."; RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND VARIANTS RP ASN-94 AND ALA-193. RC TISSUE=Cerebellum, and Spleen; 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., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., 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., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA 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 [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NHLBI resequencing and genotyping service (RS&G); RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases. RN [6] 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., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP PROTEIN SEQUENCE OF 20-34. RX PubMed=15340161; DOI=10.1110/ps.04682504; RA Zhang Z., Henzel W.J.; RT "Signal peptide prediction based on analysis of experimentally verified RT cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [9] RP FUNCTION IN LEUKOCYTE MIGRATION, INTERACTION WITH CXADR, SUBCELLULAR RP LOCATION, AND DOMAIN. RX PubMed=15800062; DOI=10.1091/mbc.e05-01-0036; RA Zen K., Liu Y., McCall I.C., Wu T., Lee W., Babbin B.A., Nusrat A., RA Parkos C.A.; RT "Neutrophil migration across tight junctions is mediated by adhesive RT interactions between epithelial CAR and a JAM-like protein on RT neutrophils."; RL Mol. Biol. Cell 16:2694-2703(2005). RN [10] RP FUNCTION IN LEUKOCYTE MIGRATION, HOMODIMERIZATION, MUTAGENESIS OF LYS-54, RP INTERACTION WITH CXADR, AND TISSUE SPECIFICITY. RX PubMed=19064666; DOI=10.1083/jcb.200805061; RA Luissint A.C., Lutz P.G., Calderwood D.A., Couraud P.O., Bourdoulous S.; RT "JAM-L-mediated leukocyte adhesion to endothelial cells is regulated in cis RT by alpha4beta1 integrin activation."; RL J. Cell Biol. 183:1159-1173(2008). RN [11] RP FUNCTION IN LEUKOCYTE MIGRATION, AND TISSUE SPECIFICITY. RX PubMed=18948633; DOI=10.1161/atvbaha.108.177717; RA Guo Y.L., Bai R., Chen C.X., Liu D.Q., Liu Y., Zhang C.Y., Zen K.; RT "Role of junctional adhesion molecule-like protein in mediating monocyte RT transendothelial migration."; RL Arterioscler. Thromb. Vasc. Biol. 29:75-83(2009). CC -!- FUNCTION: Transmembrane protein of the plasma membrane of leukocytes CC that control their migration and activation through interaction with CC CXADR, a plasma membrane receptor found on adjacent epithelial and CC endothelial cells. The interaction between both receptors mediates the CC activation of gamma-delta T-cells, a subpopulation of T-cells residing CC in epithelia and involved in tissue homeostasis and repair. Upon CC epithelial CXADR-binding, JAML induces downstream cell signaling events CC in gamma-delta T-cells through PI3-kinase and MAP kinases. It results CC in proliferation and production of cytokines and growth factors by T- CC cells that in turn stimulate epithelial tissues repair. It also CC controls the transmigration of leukocytes within epithelial and CC endothelial tissues through adhesive interactions with epithelial and CC endothelial CXADR. {ECO:0000269|PubMed:12869515, CC ECO:0000269|PubMed:15800062, ECO:0000269|PubMed:18948633, CC ECO:0000269|PubMed:19064666}. CC -!- SUBUNIT: Homodimer; active form in leukocyte-endothelial cell adhesion. CC Interacts (homodimeric form) with CXADR. Interacts (via cytoplasmic CC domain) with the PI3 kinase; upon CXADR-binding. Interacts with ITGA4 CC and ITGB1; integrin alpha-4/beta-1 may regulate leukocyte to CC endothelial cells adhesion by controlling JAML homodimerization. CC {ECO:0000269|PubMed:15800062, ECO:0000269|PubMed:19064666}. CC -!- INTERACTION: CC Q86YT9-2; P21145: MAL; NbExp=3; IntAct=EBI-17244059, EBI-3932027; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12869515}; CC Single-pass type I membrane protein {ECO:0000269|PubMed:12869515}. Cell CC junction {ECO:0000269|PubMed:12869515}. Note=Localized at the plasma CC membrane and enriched in areas of cell-cell contacts (PubMed:12869515). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q86YT9-1; Sequence=Displayed; CC Name=2; CC IsoId=Q86YT9-2; Sequence=VSP_014830; CC Name=3; CC IsoId=Q86YT9-3; Sequence=VSP_014831, VSP_014832; CC Name=4; CC IsoId=Q86YT9-4; Sequence=VSP_054911; CC -!- TISSUE SPECIFICITY: Expression is restricted to the hematopoietic CC tissues with the exception of liver. Expressed in fetal liver, spleen CC and thymus. Preferentially expressed by mature leukocytes (at protein CC level). {ECO:0000269|PubMed:12869515, ECO:0000269|PubMed:18948633, CC ECO:0000269|PubMed:19064666}. CC -!- INDUCTION: Up-regulated upon retinoic acid, Me2SO and PMA treatment in CC differentiating myeloid leukemia cells. {ECO:0000269|PubMed:12869515}. CC -!- DOMAIN: The Ig-like V-type domain 1 mediates interaction with CXADR (By CC similarity). The Ig-like V-type domain 2 may also play a role in the CC interaction (PubMed:15800062). {ECO:0000250, CC ECO:0000269|PubMed:12869515, ECO:0000269|PubMed:15800062}. CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAC03390.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ515553; CAD56620.2; -; mRNA. DR EMBL; AY093686; AAM15730.1; -; mRNA. DR EMBL; AY138965; AAN52117.1; -; mRNA. DR EMBL; AY358362; AAQ88728.1; -; mRNA. DR EMBL; AK090409; BAC03390.1; ALT_INIT; mRNA. DR EMBL; AK094399; BAC04347.1; -; mRNA. DR EMBL; EF444945; ACA05929.1; -; Genomic_DNA. DR EMBL; EF444945; ACA05930.1; -; Genomic_DNA. DR EMBL; AP002800; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC100797; AAI00798.1; -; mRNA. DR CCDS; CCDS41723.1; -. [Q86YT9-1] DR CCDS; CCDS66240.1; -. [Q86YT9-4] DR CCDS; CCDS8391.1; -. [Q86YT9-2] DR RefSeq; NP_001091996.1; NM_001098526.1. [Q86YT9-1] DR RefSeq; NP_001273499.1; NM_001286570.1. [Q86YT9-4] DR RefSeq; NP_001273500.1; NM_001286571.1. [Q86YT9-4] DR RefSeq; NP_694938.2; NM_153206.2. [Q86YT9-2] DR SMR; Q86YT9; -. DR BioGRID; 125686; 2. DR IntAct; Q86YT9; 5. DR STRING; 9606.ENSP00000348635; -. DR GlyGen; Q86YT9; 3 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q86YT9; -. DR PhosphoSitePlus; Q86YT9; -. DR SwissPalm; Q86YT9; -. DR BioMuta; JAML; -. DR DMDM; 71151910; -. DR jPOST; Q86YT9; -. DR MassIVE; Q86YT9; -. DR PaxDb; Q86YT9; -. DR PeptideAtlas; Q86YT9; -. DR PRIDE; Q86YT9; -. DR ProteomicsDB; 61996; -. DR ProteomicsDB; 70469; -. [Q86YT9-1] DR ProteomicsDB; 70470; -. [Q86YT9-2] DR ProteomicsDB; 70471; -. [Q86YT9-3] DR Antibodypedia; 32431; 287 antibodies from 27 providers. DR DNASU; 120425; -. DR Ensembl; ENST00000292067; ENSP00000292067; ENSG00000160593. [Q86YT9-2] DR Ensembl; ENST00000356289; ENSP00000348635; ENSG00000160593. DR Ensembl; ENST00000526620; ENSP00000431218; ENSG00000160593. [Q86YT9-4] DR GeneID; 120425; -. DR KEGG; hsa:120425; -. DR MANE-Select; ENST00000356289.10; ENSP00000348635.5; NM_001098526.2; NP_001091996.1. DR UCSC; uc001psi.3; human. [Q86YT9-1] DR CTD; 120425; -. DR DisGeNET; 120425; -. DR GeneCards; JAML; -. DR HGNC; HGNC:19084; JAML. DR HPA; ENSG00000160593; Tissue enhanced (lung, lymphoid tissue). DR MIM; 609770; gene. DR neXtProt; NX_Q86YT9; -. DR OpenTargets; ENSG00000160593; -. DR PharmGKB; PA38792; -. DR VEuPathDB; HostDB:ENSG00000160593; -. DR eggNOG; ENOG502SVGE; Eukaryota. DR GeneTree; ENSGT01030000234556; -. DR InParanoid; Q86YT9; -. DR OMA; EKHVYSS; -. DR OrthoDB; 1154501at2759; -. DR PhylomeDB; Q86YT9; -. DR TreeFam; TF331728; -. DR PathwayCommons; Q86YT9; -. DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell. DR Reactome; R-HSA-202733; Cell surface interactions at the vascular wall. DR SignaLink; Q86YT9; -. DR BioGRID-ORCS; 120425; 3 hits in 1038 CRISPR screens. DR ChiTaRS; JAML; human. DR GeneWiki; AMICA1; -. DR GenomeRNAi; 120425; -. DR Pharos; Q86YT9; Tbio. DR PRO; PR:Q86YT9; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q86YT9; protein. DR Bgee; ENSG00000160593; Expressed in monocyte and 186 other tissues. DR ExpressionAtlas; Q86YT9; baseline and differential. DR Genevisible; Q86YT9; HS. DR GO; GO:0005923; C:bicellular tight junction; IDA:UniProtKB. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0050839; F:cell adhesion molecule binding; IPI:UniProtKB. DR GO; GO:0005178; F:integrin binding; IPI:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0046629; P:gamma-delta T cell activation; ISS:UniProtKB. DR GO; GO:0007157; P:heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; IDA:UniProtKB. DR GO; GO:0035696; P:monocyte extravasation; IMP:UniProtKB. DR GO; GO:0030593; P:neutrophil chemotaxis; IMP:UniProtKB. DR GO; GO:0072672; P:neutrophil extravasation; IMP:UniProtKB. DR GO; GO:0060054; P:positive regulation of epithelial cell proliferation involved in wound healing; ISS:UniProtKB. DR Gene3D; 2.60.40.10; -; 2. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR013106; Ig_V-set. DR InterPro; IPR029871; JAML. DR InterPro; IPR000920; Myelin_P0-rel. DR PANTHER; PTHR13869; PTHR13869; 1. DR PANTHER; PTHR13869:SF22; PTHR13869:SF22; 1. DR Pfam; PF07686; V-set; 2. DR SMART; SM00409; IG; 2. DR SUPFAM; SSF48726; SSF48726; 2. DR PROSITE; PS50835; IG_LIKE; 2. PE 1: Evidence at protein level; KW Alternative splicing; Cell adhesion; Cell junction; Cell membrane; KW Direct protein sequencing; Disulfide bond; Glycoprotein; Immunity; KW Immunoglobulin domain; Membrane; Reference proteome; Repeat; Signal; KW Transmembrane; Transmembrane helix. FT SIGNAL 1..19 FT /evidence="ECO:0000269|PubMed:15340161" FT CHAIN 20..394 FT /note="Junctional adhesion molecule-like" FT /id="PRO_0000015074" FT TOPO_DOM 20..275 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 276..296 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 297..394 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 20..132 FT /note="Ig-like V-type 1" FT DOMAIN 137..250 FT /note="Ig-like V-type 2" FT REGION 369..394 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 76 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 231 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 42..116 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DISULFID 155..234 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT VAR_SEQ 1..39 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_054911" FT VAR_SEQ 1..14 FT /note="MFCPLKLILLPVLL -> MVSG (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_014830" FT VAR_SEQ 258..259 FT /note="TL -> SI (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_014831" FT VAR_SEQ 260..394 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_014832" FT VARIANT 94 FT /note="I -> N (in dbSNP:rs17121881)" FT /evidence="ECO:0000269|PubMed:14702039, ECO:0000269|Ref.2" FT /id="VAR_049974" FT VARIANT 193 FT /note="V -> A (in dbSNP:rs1793174)" FT /evidence="ECO:0000269|PubMed:12869515, FT ECO:0000269|PubMed:14702039, ECO:0000269|Ref.2" FT /id="VAR_049975" FT VARIANT 322 FT /note="I -> M (in dbSNP:rs2298831)" FT /id="VAR_049976" FT MUTAGEN 54 FT /note="K->E: Loss of the ability to homodimerize, loss of FT interaction with CXADR and loss of function in cell-cell FT adhesion." FT /evidence="ECO:0000269|PubMed:12869515, FT ECO:0000269|PubMed:19064666" FT CONFLICT 283 FT /note="C -> G (in Ref. 2; AAM15730)" FT /evidence="ECO:0000305" SQ SEQUENCE 394 AA; 44339 MW; 64B542F9384C7642 CRC64; MFCPLKLILL PVLLDYSLGL NDLNVSPPEL TVHVGDSALM GCVFQSTEDK CIFKIDWTLS PGEHAKDEYV LYYYSNLSVP IGRFQNRVHL MGDILCNDGS LLLQDVQEAD QGTYICEIRL KGESQVFKKA VVLHVLPEEP KELMVHVGGL IQMGCVFQST EVKHVTKVEW IFSGRRAKEE IVFRYYHKLR MSVEYSQSWG HFQNRVNLVG DIFRNDGSIM LQGVRESDGG NYTCSIHLGN LVFKKTIVLH VSPEEPRTLV TPAALRPLVL GGNQLVIIVG IVCATILLLP VLILIVKKTC GNKSSVNSTV LVKNTKKTNP EIKEKPCHFE RCEGEKHIYS PIIVREVIEE EEPSEKSEAT YMTMHPVWPS LRSDRNNSLE KKSGGGMPKT QQAF //