ID BY55_HUMAN Reviewed; 181 AA. AC O95971; A0A0B4J2A1; B8PRF2; Q5T2V6; DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 13-FEB-2019, entry version 158. DE RecName: Full=CD160 antigen; DE AltName: Full=Natural killer cell receptor BY55; DE AltName: CD_antigen=CD160 {ECO:0000303|PubMed:16809620}; DE Contains: DE RecName: Full=CD160 antigen, soluble form {ECO:0000303|PubMed:17237375}; DE Flags: Precursor; GN Name=CD160 {ECO:0000303|PubMed:16809620, ECO:0000312|HGNC:HGNC:17013}; GN Synonyms=BY55 {ECO:0000303|PubMed:9743336}; 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] (ISOFORM 1), TISSUE SPECIFICITY, RP SUBCELLULAR LOCATION, AND SUBUNIT. RX PubMed=9743336; RA Anumanthan A., Bensussan A., Boumsell L., Christ A.D., Blumberg R.S., RA Voss S.D., Patel A.T., Robertson M.J., Nadler L.M., Freeman G.J.; RT "Cloning of BY55, a novel Ig superfamily member expressed on NK cells, RT CTL, and intestinal intraepithelial lymphocytes."; RL J. Immunol. 161:2780-2790(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), ALTERNATIVE SPLICING, RP TISSUE SPECIFICITY, AND FUNCTION. RX PubMed=19109136; RA Giustiniani J., Bensussan A., Marie-Cardine A.; RT "Identification and characterization of a transmembrane isoform of RT CD160 (CD160-TM), a unique activating receptor selectively expressed RT upon human NK cell activation."; RL J. Immunol. 182:63-71(2009). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Blood; 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 [5] RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND INTERACTION WITH RP HLA-A2-B2M. RX PubMed=9973372; RA Agrawal S., Marquet J., Freeman G.J., Tawab A., Bouteiller P.L., RA Roth P., Bolton W., Ogg G., Boumsell L., Bensussan A.; RT "MHC class I triggering by a novel cell surface ligand costimulates RT proliferation of activated human T cells."; RL J. Immunol. 162:1223-1226(1999). RN [6] RP FUNCTION, SUBUNIT, INTERACTION WITH LCK, INTERACTION WITH CD247, AND RP TISSUE SPECIFICITY. RX PubMed=11978774; RA Nikolova M., Marie-Cardine A., Boumsell L., Bensussan A.; RT "BY55/CD160 acts as a co-receptor in TCR signal transduction of a RT human circulating cytotoxic effector T lymphocyte subset lacking CD28 RT expression."; RL Int. Immunol. 14:445-451(2002). RN [7] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=12486241; DOI=10.1073/pnas.012681099; RA Le Bouteiller P., Barakonyi A., Giustiniani J., Lenfant F., RA Marie-Cardine A., Aguerre-Girr M., Rabot M., Hilgert I., RA Mami-Chouaib F., Tabiasco J., Boumsell L., Bensussan A.; RT "Engagement of CD160 receptor by HLA-C is a triggering mechanism used RT by circulating natural killer (NK) cells to mediate cytotoxicity."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16963-16968(2002). RN [8] RP FUNCTION, SUBUNIT, INTERACTION WITH HLA-G, AND TISSUE SPECIFICITY. RX PubMed=16809620; DOI=10.1182/blood-2005-12-019919; RA Fons P., Chabot S., Cartwright J.E., Lenfant F., L'Faqihi F., RA Giustiniani J., Herault J.P., Gueguen G., Bono F., Savi P., RA Aguerre-Girr M., Fournel S., Malecaze F., Bensussan A., Plouet J., RA Le Bouteiller P.; RT "Soluble HLA-G1 inhibits angiogenesis through an apoptotic pathway and RT by direct binding to CD160 receptor expressed by endothelial cells."; RL Blood 108:2608-2615(2006). RN [9] RP FUNCTION. RX PubMed=17307798; DOI=10.1093/intimm/dxm005; RA Rabot M., El Costa H., Polgar B., Marie-Cardine A., Aguerre-Girr M., RA Barakonyi A., Valitutti S., Bensussan A., Le Bouteiller P.; RT "CD160-activating NK cell effector functions depend on the RT phosphatidylinositol 3-kinase recruitment."; RL Int. Immunol. 19:401-409(2007). RN [10] RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION BY IL15. RX PubMed=17237375; RA Giustiniani J., Marie-Cardine A., Bensussan A.; RT "A soluble form of the MHC class I-specific CD160 receptor is released RT from human activated NK lymphocytes and inhibits cell-mediated RT cytotoxicity."; RL J. Immunol. 178:1293-1300(2007). RN [11] RP FUNCTION, TISSUE SPECIFICITY, INDUCTION, SUBCELLULAR LOCATION, RP SUBUNIT, AND INTERACTION WITH TNFRSF14. RX PubMed=18193050; DOI=10.1038/ni1554; RA Cai G., Anumanthan A., Brown J.A., Greenfield E.A., Zhu B., RA Freeman G.J.; RT "CD160 inhibits activation of human CD4+ T cells through interaction RT with herpesvirus entry mediator."; RL Nat. Immunol. 9:176-185(2008). RN [12] RP TISSUE SPECIFICITY, SUBUNIT, INTERACTION WITH TNFRSF14, AND RP SUBCELLULAR LOCATION. RX PubMed=23761635; DOI=10.4049/jimmunol.1300894; RA Sedy J.R., Bjordahl R.L., Bekiaris V., Macauley M.G., Ware B.C., RA Norris P.S., Lurain N.S., Benedict C.A., Ware C.F.; RT "CD160 activation by herpesvirus entry mediator augments inflammatory RT cytokine production and cytolytic function by NK cells."; RL J. Immunol. 191:828-836(2013). RN [13] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=25255144; DOI=10.1371/journal.ppat.1004380; RA Vigano S., Banga R., Bellanger F., Pellaton C., Farina A., Comte D., RA Harari A., Perreau M.; RT "CD160-associated CD8 T-cell functional impairment is independent of RT PD-1 expression."; RL PLoS Pathog. 10:E1004380-E1004380(2014). CC -!- FUNCTION: CD160 antigen: Receptor on immune cells capable to CC deliver stimulatory or inhibitory signals that regulate cell CC activation and differentiation. Exists as a GPI-anchored and as a CC transmembrane form, each likely initiating distinct signaling CC pathways via phosphoinositol 3-kinase in activated NK cells and CC via LCK and CD247/CD3 zeta chain in activated T cells CC (PubMed:19109136, PubMed:11978774, PubMed:17307798). Receptor for CC both classical and non-classical MHC class I molecules CC (PubMed:9973372, PubMed:12486241). In the context of acute viral CC infection, recognizes HLA-C and triggers NK cell cytotoxic CC activity, likely playing a role in anti-viral innate immune CC response (PubMed:12486241). On CD8+ T cells, binds HLA-A2-B2M in CC complex with a viral peptide and provides a costimulatory signal CC to activated/memory T cells (PubMed:9973372). Upon persistent CC antigen stimulation, such as occurs during chronic viral CC infection, may progressively inhibit TCR signaling in memory CD8+ CC T cells, contributing to T cell exhaustion (PubMed:25255144). On CC endothelial cells, recognizes HLA-G and controls angiogenesis in CC immune privileged sites (PubMed:16809620). Receptor or ligand for CC TNF superfamily member TNFRSF14, participating in bidirectional CC cell-cell contact signaling between antigen presenting cells and CC lymphocytes. Upon ligation of TNFRSF14, provides stimulatory CC signal to NK cells enhancing IFNG production and anti-tumor immune CC response (By similarity). On activated CD4+ T cells, interacts CC with TNFRSF14 and downregulates CD28 costimulatory signaling, CC restricting memory and alloantigen-specific immune response CC (PubMed:18193050). In the context of bacterial infection, acts as CC a ligand for TNFRSF14 on epithelial cells, triggering the CC production of antimicrobial proteins and proinflammatory cytokines CC (By similarity). {ECO:0000250|UniProtKB:O88875, CC ECO:0000269|PubMed:11978774, ECO:0000269|PubMed:12486241, CC ECO:0000269|PubMed:16809620, ECO:0000269|PubMed:17307798, CC ECO:0000269|PubMed:18193050, ECO:0000269|PubMed:19109136, CC ECO:0000269|PubMed:25255144, ECO:0000269|PubMed:9973372}. CC -!- FUNCTION: CD160 antigen, soluble form: The soluble GPI-cleaved CC form, usually released by activated lymphocytes, might play an CC immune regulatory role by limiting lymphocyte effector functions. CC {ECO:0000269|PubMed:17237375}. CC -!- SUBUNIT: Homomultimer; disulfide-linked (Probable). Interacts with CC HLA-G (PubMed:16809620). Interacts with HLA-A2-B2M in complex with CC an HIV-derived peptide (PubMed:9973372). Interacts with TNFRSF14 CC (via cysteine-rich domain 1); this interaction is direct CC (PubMed:18193050). Interacts with LCK and CD247/CD3 zeta chain CC (PubMed:11978774). {ECO:0000269|PubMed:11978774, CC ECO:0000269|PubMed:16809620, ECO:0000269|PubMed:18193050, CC ECO:0000269|PubMed:9973372, ECO:0000305|PubMed:9743336}. CC -!- INTERACTION: CC Q6RW13:AGTRAP; NbExp=3; IntAct=EBI-4314390, EBI-741181; CC O15151:MDM4; NbExp=5; IntAct=EBI-4314390, EBI-398437; CC -!- SUBCELLULAR LOCATION: CD160 antigen: Cell membrane CC {ECO:0000269|PubMed:12486241, ECO:0000269|PubMed:18193050, CC ECO:0000269|PubMed:9973372}; Lipid-anchor, GPI-anchor CC {ECO:0000269|PubMed:23761635, ECO:0000269|PubMed:9743336}. CC -!- SUBCELLULAR LOCATION: CD160 antigen, soluble form: Secreted. CC Note=Released from the cell membrane by GPI cleavage. CC {ECO:0000269|PubMed:17237375, ECO:0000269|PubMed:23761635, CC ECO:0000269|PubMed:9743336}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=CD160 {ECO:0000303|PubMed:19109136}; CC IsoId=O95971-1; Sequence=Displayed; CC Name=2; Synonyms=CD160deltaIg {ECO:0000303|PubMed:19109136}; CC IsoId=O95971-2; Sequence=VSP_060018; CC Name=3; Synonyms=CD160-TM {ECO:0000303|PubMed:19109136}; CC IsoId=O95971-3; Sequence=VSP_060019; CC Note=Mutagenesis of TYR-225 to Phe abolishes intracellular CC signaling. {ECO:0000269|PubMed:19109136}; CC Name=4; Synonyms=CD160deltaIg-TM {ECO:0000303|PubMed:19109136}; CC IsoId=O95971-4; Sequence=VSP_060017; CC -!- TISSUE SPECIFICITY: Expression is restricted to functional NK and CC cytotoxic T lymphocytes. Expressed in viral-specific effector CC memory and terminally differentiated effector memory CD8+ T cells. CC Expressed in memory and activated CD4+ T cell subsets (at protein CC level) (PubMed:9743336, PubMed:18193050, PubMed:11978774, CC PubMed:25255144). Expressed at high levels in intraepithelial CC lymphocytes (at protein level) (PubMed:9743336). Expressed in both CC alpha-beta and gamma-delta CD8+ T cell subsets (at protein level) CC (PubMed:9743336, PubMed:18193050, PubMed:11978774). Expressed in CC umbilical vein endothelial cells (at protein level) CC (PubMed:16809620). Expressed in monocytes and at lower levels in B CC cells (PubMed:23761635). Isoform 3: Expressed exclusively in CC activated NK cells (at protein level) (PubMed:19109136). CC {ECO:0000269|PubMed:11978774, ECO:0000269|PubMed:16809620, CC ECO:0000269|PubMed:18193050, ECO:0000269|PubMed:19109136, CC ECO:0000269|PubMed:23761635, ECO:0000269|PubMed:25255144, CC ECO:0000269|PubMed:9743336}. CC -!- INDUCTION: Up-regulated on CD4+ T cells upon stimulation via T CC cell receptor plus costimulation via CD28 (PubMed:18193050). Up- CC regulated by IL15 on immunoregulatory NCAM1/CD56-bright NK cells CC (PubMed:17237375). {ECO:0000269|PubMed:17237375, CC ECO:0000269|PubMed:18193050}. 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; AF060981; AAC72302.1; -; mRNA. DR EMBL; EU016100; ABV89736.1; -; mRNA. DR EMBL; EU016101; ABV89737.1; -; mRNA. DR EMBL; AL390725; CAI13714.1; -; Genomic_DNA. DR EMBL; AC242845; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC014465; AAH14465.1; -; mRNA. DR CCDS; CCDS72861.1; -. [O95971-1] DR RefSeq; NP_008984.1; NM_007053.3. DR RefSeq; XP_005272986.1; XM_005272929.3. DR RefSeq; XP_011507406.1; XM_011509104.2. DR UniGene; Hs.488237; -. DR UniGene; Hs.740780; -. DR ProteinModelPortal; O95971; -. DR SMR; O95971; -. DR BioGrid; 116299; 41. DR IntAct; O95971; 9. DR MINT; O95971; -. DR STRING; 9606.ENSP00000235933; -. DR iPTMnet; O95971; -. DR PhosphoSitePlus; O95971; -. DR BioMuta; CD160; -. DR EPD; O95971; -. DR PaxDb; O95971; -. DR PeptideAtlas; O95971; -. DR PRIDE; O95971; -. DR ProteomicsDB; 51154; -. DR DNASU; 11126; -. DR Ensembl; ENST00000235933; ENSP00000235933; ENSG00000117281. DR Ensembl; ENST00000369288; ENSP00000358294; ENSG00000117281. DR GeneID; 11126; -. DR KEGG; hsa:11126; -. DR CTD; 11126; -. DR DisGeNET; 11126; -. DR EuPathDB; HostDB:ENSG00000117281.15; -. DR GeneCards; CD160; -. DR HGNC; HGNC:17013; CD160. DR MIM; 604463; gene. DR neXtProt; NX_O95971; -. DR OpenTargets; ENSG00000117281; -. DR PharmGKB; PA134943137; -. DR eggNOG; ENOG410IX7D; Eukaryota. DR eggNOG; ENOG411156J; LUCA. DR GeneTree; ENSGT00390000007258; -. DR HOGENOM; HOG000095285; -. DR HOVERGEN; HBG018849; -. DR InParanoid; O95971; -. DR KO; K06542; -. DR OMA; YQCCATS; -. DR OrthoDB; 1278184at2759; -. DR PhylomeDB; O95971; -. DR TreeFam; TF338321; -. DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell. DR GeneWiki; CD160; -. DR GenomeRNAi; 11126; -. DR PRO; PR:O95971; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; ENSG00000117281; Expressed in 116 organ(s), highest expression level in leukocyte. DR ExpressionAtlas; O95971; baseline and differential. DR Genevisible; O95971; HS. DR GO; GO:0046658; C:anchored component of plasma membrane; IDA:HGNC. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0032393; F:MHC class I receptor activity; IDA:HGNC. DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc. DR GO; GO:0005102; F:signaling receptor binding; IDA:HGNC. DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW. DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW. DR GO; GO:0008283; P:cell population proliferation; TAS:ProtInc. DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc. DR GO; GO:0006968; P:cellular defense response; TAS:ProtInc. DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IEA:Ensembl. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0016525; P:negative regulation of angiogenesis; IDA:UniProtKB. DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; IDA:UniProtKB. DR GO; GO:0050776; P:regulation of immune response; TAS:Reactome. DR Gene3D; 2.60.40.10; -; 1. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR SUPFAM; SSF48726; SSF48726; 1. PE 1: Evidence at protein level; KW Adaptive immunity; Alternative splicing; Angiogenesis; Cell membrane; KW Complete proteome; Disulfide bond; Glycoprotein; GPI-anchor; Immunity; KW Immunoglobulin domain; Innate immunity; Lipoprotein; Membrane; KW Polymorphism; Receptor; Reference proteome; Secreted; Signal. FT SIGNAL 1 24 {ECO:0000255}. FT CHAIN 25 159 CD160 antigen. FT /FTId=PRO_0000014543. FT CHAIN 25 159 CD160 antigen, soluble form. FT {ECO:0000305|PubMed:17237375, FT ECO:0000305|PubMed:23761635, FT ECO:0000305|PubMed:9743336}. FT /FTId=PRO_0000446049. FT PROPEP 160 181 Removed in mature form. {ECO:0000255}. FT /FTId=PRO_0000014544. FT DOMAIN 25 133 Ig-like V-type. FT {ECO:0000305|PubMed:19109136}. FT LIPID 159 159 GPI-anchor amidated serine. FT {ECO:0000250}. FT CARBOHYD 28 28 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 137 137 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 44 112 {ECO:0000255}. FT DISULFID 61 68 {ECO:0000255}. FT VAR_SEQ 25 181 GCINITSSASQEGTRLNLICTVWHKKEEAEGFVVFLCKDRS FT GDCSPETSLKQLRLKRDPGIDGVGEISSQLMFTISQVTPLH FT SGTYQCCARSQKSGIRLQGHFFSILFTETGNYTVTGLKQRQ FT HLEFSHNEGTLSSGFLQEKVWVMLVTSLVALQAL -> ETG FT NYTVTGLKQRQHLEFSHNEGTLSSGFLQEKVWVMLVTSLVA FT LQGMSKRAVSTPSNEGAIIFLPPWLFSRRRRLERMSRGREK FT CYSSPGYPQESSNQFH (in isoform 4). FT /FTId=VSP_060017. FT VAR_SEQ 25 133 Missing (in isoform 2). FT /FTId=VSP_060018. FT VAR_SEQ 180 181 AL -> GMSKRAVSTPSNEGAIIFLPPWLFSRRRRLERMSR FT GREKCYSSPGYPQESSNQFH (in isoform 3). FT {ECO:0000305|PubMed:19109136}. FT /FTId=VSP_060019. FT VARIANT 91 91 I -> V (in dbSNP:rs2231373). FT /FTId=VAR_027747. SQ SEQUENCE 181 AA; 19810 MW; EF0B981ACC7478BD CRC64; MLLEPGRGCC ALAILLAIVD IQSGGCINIT SSASQEGTRL NLICTVWHKK EEAEGFVVFL CKDRSGDCSP ETSLKQLRLK RDPGIDGVGE ISSQLMFTIS QVTPLHSGTY QCCARSQKSG IRLQGHFFSI LFTETGNYTV TGLKQRQHLE FSHNEGTLSS GFLQEKVWVM LVTSLVALQA L //