LIRA2_HUMAN
ID LIRA2_HUMAN Reviewed; 483 AA.
AC Q8N149; O75020;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 25-MAY-2022, sequence version 3.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Leukocyte immunoglobulin-like receptor subfamily A member 2;
DE AltName: Full=CD85 antigen-like family member H;
DE AltName: Full=Immunoglobulin-like transcript 1;
DE Short=ILT-1;
DE AltName: Full=Leukocyte immunoglobulin-like receptor 7 {ECO:0000303|PubMed:12529506};
DE Short=LIR-7 {ECO:0000303|PubMed:12529506};
DE AltName: CD_antigen=CD85h;
DE Flags: Precursor;
GN Name=LILRA2; Synonyms=ILT1, LIR7;
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), AND TISSUE SPECIFICITY.
RC TISSUE=Peripheral blood leukocyte;
RX PubMed=9548455;
RA Borges L., Hsu M.-L., Fanger N., Kubin M., Cosman D.;
RT "A family of human lymphoid and myeloid Ig-like receptors, some of which
RT bind to MHC class I molecules.";
RL J. Immunol. 159:5192-5196(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), SUBCELLULAR LOCATION
RP (ISOFORM 4), AND ALTERNATIVE SPLICING.
RX PubMed=19658091; DOI=10.1002/eji.200839080;
RA Jones D.C., Roghanian A., Brown D.P., Chang C., Allen R.L., Trowsdale J.,
RA Young N.T.;
RT "Alternative mRNA splicing creates transcripts encoding soluble proteins
RT from most LILR genes.";
RL Eur. J. Immunol. 39:3195-3206(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung, and Pancreas;
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 [4]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=12529506; DOI=10.1073/pnas.0337567100;
RA Tedla N., Bandeira-Melo C., Tassinari P., Sloane D.E., Samplaski M.,
RA Cosman D., Borges L., Weller P.F., Arm J.P.;
RT "Activation of human eosinophils through leukocyte immunoglobulin-like
RT receptor 7.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:1174-1179(2003).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=22479404; DOI=10.1371/journal.pone.0033478;
RA Lu H.K., Mitchell A., Endoh Y., Hampartzoumian T., Huynh O., Borges L.,
RA Geczy C., Bryant K., Tedla N.;
RT "LILRA2 selectively modulates LPS-mediated cytokine production and inhibits
RT phagocytosis by monocytes.";
RL PLoS ONE 7:E33478-E33478(2012).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=27572839; DOI=10.1038/nmicrobiol.2016.54;
RA Hirayasu K., Saito F., Suenaga T., Shida K., Arase N., Oikawa K.,
RA Yamaoka T., Murota H., Chibana H., Nakagawa I., Kubori T., Nagai H.,
RA Nakamaru Y., Katayama I., Colonna M., Arase H.;
RT "Microbially cleaved immunoglobulins are sensed by the innate immune
RT receptor LILRA2.";
RL Nat. Microbiol. 1:16054-16054(2016).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 24-219, FUNCTION, SUBUNIT, AND
RP DISULFIDE BONDS.
RX PubMed=19230061; DOI=10.1016/j.jmb.2009.01.006;
RA Chen Y., Gao F., Chu F., Peng H., Zong L., Liu Y., Tien P., Gao G.F.;
RT "Crystal structure of myeloid cell activating receptor leukocyte Ig-like
RT receptor A2 (LILRA2/ILT1/LIR-7) domain swapped dimer: molecular basis for
RT its non-binding to MHC complexes.";
RL J. Mol. Biol. 386:841-853(2009).
CC -!- FUNCTION: Part of the innate immune responses against microbial
CC infection (PubMed:12529506, PubMed:27572839). Specifically recognizes a
CC set of N-terminally truncated immunoglobulins that are produced via
CC cleavage by proteases from a range of pathogenic bacteria and fungi,
CC including L.pneumophila, M.hyorhinis, S.pneumoniae, S.aureus and
CC C.albicans (PubMed:27572839). Recognizes epitopes that are in part in
CC the variable region of the immunoglobulin light chains, but requires
CC also the constant region for signaling (PubMed:27572839). Binds to a
CC subset of cleaved IgM, IgG3 and IgG4 molecules, but does not bind
CC cleaved IgA1 (PubMed:27572839). Binding of N-terminally truncated
CC immunoglobulins mediates activation of neutrophils (PubMed:27572839).
CC In monocytes, activation leads to the release of CSF2, CF3, IL6, CXCL8
CC and CCL3 and down-regulates responses to bacterial lipopolysaccharide
CC (LPS), possibly via down-regulation of TLR4 expression and reduced
CC signaling via TLR4 (PubMed:22479404). In eosinophils, activation by
CC ligand binding leads to the release of RNASE2, IL4 and leukotriene C4
CC (PubMed:12529506). Does not bind class I MHC antigens
CC (PubMed:19230061). {ECO:0000269|PubMed:12529506,
CC ECO:0000269|PubMed:19230061, ECO:0000269|PubMed:22479404,
CC ECO:0000269|PubMed:27572839}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:19230061}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12529506,
CC ECO:0000269|PubMed:22479404, ECO:0000269|PubMed:27572839}; Single-pass
CC type I membrane protein {ECO:0000305|PubMed:12529506,
CC ECO:0000305|PubMed:22479404}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Secreted
CC {ECO:0000303|PubMed:19658091}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q8N149-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N149-2; Sequence=VSP_008455;
CC Name=3;
CC IsoId=Q8N149-3; Sequence=VSP_057085, VSP_057086;
CC Name=4;
CC IsoId=Q8N149-4; Sequence=VSP_057086;
CC -!- TISSUE SPECIFICITY: Detected on the surface of all peripheral blood
CC monocytes, neutrophils, basophils and eosinophils (at protein level)
CC (PubMed:12529506, PubMed:22479404). Expression levels are very low or
CC not detectable on monocytes, T-cells, B-cells, dendritic cells and
CC natural killer (NK) cells (PubMed:9548455).
CC {ECO:0000269|PubMed:12529506, ECO:0000269|PubMed:22479404,
CC ECO:0000269|PubMed:9548455}.
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DR EMBL; AF025531; AAB87665.1; -; mRNA.
DR EMBL; EU915609; ACK56075.1; -; mRNA.
DR EMBL; EU915610; ACK56076.1; -; mRNA.
DR EMBL; BC017412; AAH17412.1; -; mRNA.
DR EMBL; BC027916; AAH27916.1; -; mRNA.
DR CCDS; CCDS12900.1; -. [Q8N149-2]
DR CCDS; CCDS46179.1; -. [Q8N149-1]
DR RefSeq; NP_006857.2; NM_006866.3.
DR PDB; 2OTP; X-ray; 2.60 A; A/B=24-219.
DR PDBsum; 2OTP; -.
DR AlphaFoldDB; Q8N149; -.
DR SMR; Q8N149; -.
DR STRING; 9606.ENSP00000251377; -.
DR GlyGen; Q8N149; 7 sites.
DR iPTMnet; Q8N149; -.
DR PhosphoSitePlus; Q8N149; -.
DR BioMuta; LILRA2; -.
DR DMDM; 37537906; -.
DR jPOST; Q8N149; -.
DR MassIVE; Q8N149; -.
DR PaxDb; Q8N149; -.
DR PeptideAtlas; Q8N149; -.
DR PRIDE; Q8N149; -.
DR ProteomicsDB; 71558; -. [Q8N149-1]
DR ProteomicsDB; 71559; -. [Q8N149-2]
DR Antibodypedia; 34828; 339 antibodies from 29 providers.
DR DNASU; 11027; -.
DR Ensembl; ENST00000251376.7; ENSP00000251376.3; ENSG00000239998.7. [Q8N149-2]
DR Ensembl; ENST00000251377.7; ENSP00000251377.3; ENSG00000239998.7. [Q8N149-1]
DR Ensembl; ENST00000391738.8; ENSP00000375618.3; ENSG00000239998.7. [Q8N149-1]
DR Ensembl; ENST00000611940.4; ENSP00000478981.1; ENSG00000275290.4.
DR Ensembl; ENST00000613573.4; ENSP00000479743.1; ENSG00000275290.4.
DR Ensembl; ENST00000616629.1; ENSP00000481338.1; ENSG00000275290.4.
DR Ensembl; ENST00000617409.4; ENSP00000479914.1; ENSG00000274000.4.
DR Ensembl; ENST00000620279.4; ENSP00000480939.1; ENSG00000274000.4.
DR Ensembl; ENST00000621721.4; ENSP00000484762.1; ENSG00000278634.4.
DR Ensembl; ENST00000622640.3; ENSP00000483906.1; ENSG00000278634.4.
DR GeneID; 11027; -.
DR KEGG; hsa:11027; -.
DR MANE-Select; ENST00000391738.8; ENSP00000375618.3; NM_001130917.3; NP_001124389.2.
DR UCSC; uc002qgf.5; human. [Q8N149-1]
DR CTD; 11027; -.
DR DisGeNET; 11027; -.
DR GeneCards; LILRA2; -.
DR HGNC; HGNC:6603; LILRA2.
DR HPA; ENSG00000239998; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 604812; gene.
DR neXtProt; NX_Q8N149; -.
DR OpenTargets; ENSG00000239998; -.
DR PharmGKB; PA30377; -.
DR VEuPathDB; HostDB:ENSG00000239998; -.
DR eggNOG; ENOG502RYEX; Eukaryota.
DR GeneTree; ENSGT01000000214458; -.
DR HOGENOM; CLU_021100_2_0_1; -.
DR InParanoid; Q8N149; -.
DR OrthoDB; 1000446at2759; -.
DR PhylomeDB; Q8N149; -.
DR TreeFam; TF336644; -.
DR PathwayCommons; Q8N149; -.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR BioGRID-ORCS; 11027; 10 hits in 1053 CRISPR screens.
DR ChiTaRS; LILRA2; human.
DR EvolutionaryTrace; Q8N149; -.
DR GeneWiki; LILRA2; -.
DR GenomeRNAi; 11027; -.
DR Pharos; Q8N149; Tbio.
DR PRO; PR:Q8N149; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8N149; protein.
DR Bgee; ENSG00000239998; Expressed in blood and 96 other tissues.
DR ExpressionAtlas; Q8N149; baseline and differential.
DR Genevisible; Q8N149; HS.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0003823; F:antigen binding; TAS:ProtInc.
DR GO; GO:0001791; F:IgM binding; IDA:UniProtKB.
DR GO; GO:0032396; F:inhibitory MHC class I receptor activity; IBA:GO_Central.
DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0006952; P:defense response; TAS:ProtInc.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0002220; P:innate immune response activating cell surface receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0031665; P:negative regulation of lipopolysaccharide-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0034144; P:negative regulation of toll-like receptor 4 signaling pathway; IMP:UniProtKB.
DR GO; GO:0002283; P:neutrophil activation involved in immune response; IDA:UniProtKB.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; IDA:UniProtKB.
DR GO; GO:0050867; P:positive regulation of cell activation; IDA:UniProtKB.
DR GO; GO:0071657; P:positive regulation of granulocyte colony-stimulating factor production; IMP:UniProtKB.
DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; IMP:UniProtKB.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IDA:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:UniProtKB.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IMP:UniProtKB.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR Gene3D; 2.60.40.10; -; 4.
DR InterPro; IPR016332; A1B_glyco/leuk_Ig-like_rcpt.
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; IPR003598; Ig_sub2.
DR InterPro; IPR013151; Immunoglobulin.
DR Pfam; PF00047; ig; 1.
DR Pfam; PF13895; Ig_2; 1.
DR PIRSF; PIRSF001979; Alpha_1B_glycoprot_prd; 1.
DR SMART; SM00409; IG; 4.
DR SMART; SM00408; IGc2; 3.
DR SUPFAM; SSF48726; SSF48726; 4.
DR PROSITE; PS50835; IG_LIKE; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Disulfide bond;
KW Glycoprotein; Immunity; Immunoglobulin domain; Innate immunity; Membrane;
KW Nitration; Receptor; Reference proteome; Repeat; Secreted; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..483
FT /note="Leukocyte immunoglobulin-like receptor subfamily A
FT member 2"
FT /id="PRO_0000014817"
FT TOPO_DOM 24..449
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 450..470
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 471..483
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 27..113
FT /note="Ig-like C2-type 1"
FT DOMAIN 117..222
FT /note="Ig-like C2-type 2"
FT DOMAIN 224..313
FT /note="Ig-like C2-type 3"
FT DOMAIN 324..413
FT /note="Ig-like C2-type 4"
FT MOD_RES 404
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P59901"
FT CARBOHYD 64
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 279
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 300
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 339
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 429
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 49..97
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:19230061"
FT DISULFID 143..195
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:19230061"
FT DISULFID 244..295
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 344..395
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 12..23
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:19658091"
FT /id="VSP_057085"
FT VAR_SEQ 419..436
FT /note="EAAETLSPSQNKTDSTTT -> A (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008455"
FT VAR_SEQ 436..483
FT /note="TSLGQHPQDYTVENLIRMGVAGLVLVVLGILLFEAQHSQRSLQDAAGR ->
FT SE (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:19658091"
FT /id="VSP_057086"
FT VARIANT 25
FT /note="H -> L (in dbSNP:rs1834697)"
FT /id="VAR_016988"
FT VARIANT 25
FT /note="H -> N (in dbSNP:rs1834698)"
FT /id="VAR_016989"
FT VARIANT 331
FT /note="V -> G (in dbSNP:rs7249811)"
FT /id="VAR_056051"
FT VARIANT 361
FT /note="G -> A (in dbSNP:rs7249154)"
FT /id="VAR_056052"
FT VARIANT 381
FT /note="R -> C (in dbSNP:rs7249054)"
FT /id="VAR_056053"
FT STRAND 30..35
FT /evidence="ECO:0007829|PDB:2OTP"
FT STRAND 37..42
FT /evidence="ECO:0007829|PDB:2OTP"
FT STRAND 45..50
FT /evidence="ECO:0007829|PDB:2OTP"
FT STRAND 83..86
FT /evidence="ECO:0007829|PDB:2OTP"
FT STRAND 93..95
FT /evidence="ECO:0007829|PDB:2OTP"
FT STRAND 112..117
FT /evidence="ECO:0007829|PDB:2OTP"
FT STRAND 124..129
FT /evidence="ECO:0007829|PDB:2OTP"
FT STRAND 139..144
FT /evidence="ECO:0007829|PDB:2OTP"
FT STRAND 152..156
FT /evidence="ECO:0007829|PDB:2OTP"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:2OTP"
FT STRAND 164..170
FT /evidence="ECO:0007829|PDB:2OTP"
FT STRAND 173..175
FT /evidence="ECO:0007829|PDB:2OTP"
FT STRAND 178..182
FT /evidence="ECO:0007829|PDB:2OTP"
FT STRAND 192..195
FT /evidence="ECO:0007829|PDB:2OTP"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:2OTP"
SQ SEQUENCE 483 AA; 52966 MW; 07F891B9515BC1B6 CRC64;
MTPILTVLIC LGLSLGPRTH VQAGHLPKPT LWAEPGSVII QGSPVTLRCQ GSLQAEEYHL
YRENKSASWV RRIQEPGKNG QFPIPSITWE HAGRYHCQYY SHNHSSEYSD PLELVVTGAY
SKPTLSALPS PVVTSGGNVT LQCVSQVAFD GFILCKEGED EHPQRLNSHS HARGWSWAIF
SVGPVSPSRR WSYRCYAYDS NSPYVWSLPS DLLELLVPGV SKKPSLSVQP GPMVAPGESL
TLQCVSDVGY DRFVLYKEGE RDFLQRPGWQ PQAGLSQANF TLGPVSPSHG GQYRCYSAHN
LSSEWSAPSD PLDILITGQF YDRPSLSVQP VPTVAPGKNV TLLCQSRGQF HTFLLTKEGA
GHPPLHLRSE HQAQQNQAEF RMGPVTSAHV GTYRCYSSLS SNPYLLSLPS DPLELVVSEA
AETLSPSQNK TDSTTTSLGQ HPQDYTVENL IRMGVAGLVL VVLGILLFEA QHSQRSLQDA
AGR
