LIRA4_HUMAN
ID LIRA4_HUMAN Reviewed; 499 AA.
AC P59901; Q32MC4;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 3.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Leukocyte immunoglobulin-like receptor subfamily A member 4 {ECO:0000305};
DE AltName: Full=CD85 antigen-like family member G;
DE AltName: Full=Immunoglobulin-like transcript 7 {ECO:0000303|PubMed:24586760, ECO:0000303|Ref.1};
DE Short=ILT-7 {ECO:0000303|PubMed:16735691, ECO:0000303|PubMed:24586760};
DE AltName: CD_antigen=CD85g;
DE Flags: Precursor;
GN Name=LILRA4 {ECO:0000312|HGNC:HGNC:15503};
GN Synonyms=ILT7 {ECO:0000303|PubMed:16735691, ECO:0000303|PubMed:19564354,
GN ECO:0000303|PubMed:24586760};
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).
RA Colonna M.;
RT "Immunoglobulin-like transcript 7.";
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-235 (ISOFORM 1).
RC TISSUE=Pancreas, and Spleen;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 35-494 (ISOFORM 1).
RA Canavez F.C.;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NITRATION [LARGE SCALE ANALYSIS] AT TYR-404, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Pituitary adenoma;
RX PubMed=16777052; DOI=10.1016/j.ab.2006.05.024;
RA Zhan X., Desiderio D.M.;
RT "Nitroproteins from a human pituitary adenoma tissue discovered with a
RT nitrotyrosine affinity column and tandem mass spectrometry.";
RL Anal. Biochem. 354:279-289(2006).
RN [6]
RP FUNCTION, INTERACTION WITH FCER1G, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=16735691; DOI=10.1084/jem.20052454;
RA Cao W., Rosen D.B., Ito T., Bover L., Bao M., Watanabe G., Yao Z.,
RA Zhang L., Lanier L.L., Liu Y.J.;
RT "Plasmacytoid dendritic cell-specific receptor ILT7-Fc epsilonRI gamma
RT inhibits Toll-like receptor-induced interferon production.";
RL J. Exp. Med. 203:1399-1405(2006).
RN [7]
RP FUNCTION, INTERACTION WITH BST2, AND SUBCELLULAR LOCATION.
RX PubMed=19564354; DOI=10.1084/jem.20090547;
RA Cao W., Bover L., Cho M., Wen X., Hanabuchi S., Bao M., Rosen D.B.,
RA Wang Y.H., Shaw J.L., Du Q., Li C., Arai N., Yao Z., Lanier L.L., Liu Y.J.;
RT "Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and
RT ILT7 receptor interaction.";
RL J. Exp. Med. 206:1603-1614(2009).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=24586760; DOI=10.1371/journal.pone.0089414;
RA Tavano B., Boasso A.;
RT "Effect of immunoglobin-like transcript 7 cross-linking on plasmacytoid
RT dendritic cells differentiation into antigen-presenting cells.";
RL PLoS ONE 9:E89414-E89414(2014).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BST2.
RX PubMed=26172439; DOI=10.1371/journal.ppat.1005024;
RA Bego M.G., Cote E., Aschman N., Mercier J., Weissenhorn W., Cohen E.A.;
RT "Vpu exploits the cross-talk between BST2 and the ILT7 receptor to suppress
RT anti-HIV-1 responses by plasmacytoid dendritic Cells.";
RL PLoS Pathog. 11:E1005024-E1005024(2015).
CC -!- FUNCTION: Functions coreceptor to limit the innate immune responses to
CC viral infections; signaling occurs via FCER1G (PubMed:16735691,
CC PubMed:19564354). Down-regulates the production of IFNA1, IFNA2, IFNA4,
CC IFNB1 and TNF by plasmacytoid dendritic cells that have been exposed to
CC influenza virus or cytidine-phosphate-guanosine (CpG) dinucleotides,
CC indicating it functions as negative regulator of TLR7 and TLR9
CC signaling cascades (PubMed:16735691, PubMed:19564354, PubMed:24586760).
CC Down-regulates interferon production in response to interaction with
CC BST2 on HIV-1 infected cells (PubMed:26172439). Activates a signaling
CC cascade in complex with FCER1G that results in phosphorylation of Src
CC family and Syk kinases and thereby triggers mobilization of
CC intracellular Ca(2+) (PubMed:16735691, PubMed:19564354). Does not
CC interfere with the differentiation of plasmacytoid dendritic cells into
CC antigen-presenting cells (PubMed:24586760).
CC {ECO:0000269|PubMed:16735691, ECO:0000269|PubMed:19564354,
CC ECO:0000269|PubMed:24586760, ECO:0000269|PubMed:26172439}.
CC -!- SUBUNIT: Interacts with FCER1G; this stabilizes the expression of both
CC proteins at the cell membrane (PubMed:16735691). Interacts with BST2;
CC leads to activation of LILRA4-mediated signaling and down-regulation of
CC the innate immune response to viral pathogens (PubMed:19564354,
CC PubMed:26172439). {ECO:0000269|PubMed:16735691,
CC ECO:0000269|PubMed:19564354, ECO:0000269|PubMed:26172439}.
CC -!- INTERACTION:
CC P59901; Q10589: BST2; NbExp=2; IntAct=EBI-2841591, EBI-2476339;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16735691,
CC ECO:0000269|PubMed:19564354, ECO:0000269|PubMed:24586760,
CC ECO:0000269|PubMed:26172439}; Single-pass type I membrane protein
CC {ECO:0000305|PubMed:16735691, ECO:0000305|PubMed:19564354,
CC ECO:0000305|PubMed:24586760, ECO:0000305|PubMed:26172439}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P59901-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P59901-2; Sequence=VSP_038694;
CC -!- TISSUE SPECIFICITY: Detected on plasmacytoid dendritic cells (at
CC protein level). Detected on plasmacytoid dendritic cells, but not on
CC monocytes or B cells. {ECO:0000269|PubMed:16735691}.
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DR EMBL; AF041261; AAD02203.1; -; mRNA.
DR EMBL; AC245884; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC109198; AAI09199.1; -; mRNA.
DR EMBL; BI834924; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF283989; AAL36993.1; -; mRNA.
DR CCDS; CCDS12890.1; -. [P59901-1]
DR RefSeq; NP_036408.4; NM_012276.4.
DR AlphaFoldDB; P59901; -.
DR IntAct; P59901; 2.
DR STRING; 9606.ENSP00000291759; -.
DR GlyGen; P59901; 4 sites.
DR iPTMnet; P59901; -.
DR PhosphoSitePlus; P59901; -.
DR BioMuta; LILRA4; -.
DR DMDM; 288558815; -.
DR jPOST; P59901; -.
DR MassIVE; P59901; -.
DR PaxDb; P59901; -.
DR PeptideAtlas; P59901; -.
DR PRIDE; P59901; -.
DR TopDownProteomics; P59901-1; -. [P59901-1]
DR ABCD; P59901; 3 sequenced antibodies.
DR Antibodypedia; 32892; 301 antibodies from 28 providers.
DR DNASU; 23547; -.
DR Ensembl; ENST00000291759.5; ENSP00000291759.4; ENSG00000239961.3. [P59901-1]
DR Ensembl; ENST00000613813.1; ENSP00000479979.1; ENSG00000277092.4.
DR Ensembl; ENST00000616790.1; ENSP00000483846.1; ENSG00000274185.4.
DR Ensembl; ENST00000619832.1; ENSP00000481073.1; ENSG00000276798.4.
DR GeneID; 23547; -.
DR KEGG; hsa:23547; -.
DR MANE-Select; ENST00000291759.5; ENSP00000291759.4; NM_012276.5; NP_036408.4.
DR UCSC; uc002qfj.4; human. [P59901-1]
DR CTD; 23547; -.
DR DisGeNET; 23547; -.
DR GeneCards; LILRA4; -.
DR HGNC; HGNC:15503; LILRA4.
DR HPA; ENSG00000239961; Tissue enriched (lymphoid).
DR MIM; 607517; gene.
DR neXtProt; NX_P59901; -.
DR OpenTargets; ENSG00000239961; -.
DR PharmGKB; PA142671546; -.
DR VEuPathDB; HostDB:ENSG00000239961; -.
DR eggNOG; ENOG502RYEX; Eukaryota.
DR GeneTree; ENSGT01000000214458; -.
DR HOGENOM; CLU_021100_2_0_1; -.
DR InParanoid; P59901; -.
DR OrthoDB; 1000446at2759; -.
DR PhylomeDB; P59901; -.
DR TreeFam; TF336644; -.
DR PathwayCommons; P59901; -.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR SignaLink; P59901; -.
DR BioGRID-ORCS; 23547; 12 hits in 1054 CRISPR screens.
DR GeneWiki; LILRA4; -.
DR GenomeRNAi; 23547; -.
DR Pharos; P59901; Tbio.
DR PRO; PR:P59901; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P59901; protein.
DR Bgee; ENSG00000239961; Expressed in granulocyte and 88 other tissues.
DR ExpressionAtlas; P59901; baseline and differential.
DR Genevisible; P59901; HS.
DR GO; GO:0032998; C:Fc-epsilon receptor I complex; IDA:UniProtKB.
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:0015026; F:coreceptor activity; IDA:UniProtKB.
DR GO; GO:0032396; F:inhibitory MHC class I receptor activity; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0032687; P:negative regulation of interferon-alpha production; IMP:UniProtKB.
DR GO; GO:0034156; P:negative regulation of toll-like receptor 7 signaling pathway; IMP:UniProtKB.
DR GO; GO:0034164; P:negative regulation of toll-like receptor 9 signaling pathway; IMP:UniProtKB.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IMP:UniProtKB.
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; 2.
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; 3.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein;
KW Immunity; Immunoglobulin domain; Innate immunity; Membrane; Nitration;
KW Receptor; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..499
FT /note="Leukocyte immunoglobulin-like receptor subfamily A
FT member 4"
FT /id="PRO_0000014819"
FT TOPO_DOM 24..446
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 447..467
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 468..499
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 24..118
FT /note="Ig-like C2-type 1"
FT DOMAIN 123..213
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:0007744|PubMed:16777052"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 239
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 DISULFID 49..98
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 143..195
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
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 1..66
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_038694"
FT VARIANT 27
FT /note="L -> P (in dbSNP:rs2241384)"
FT /id="VAR_056054"
FT VARIANT 155
FT /note="I -> V (in dbSNP:rs10419832)"
FT /id="VAR_056055"
FT CONFLICT 3
FT /note="L -> P (in Ref. 1; AAD02203)"
FT /evidence="ECO:0000305"
FT CONFLICT 7
FT /note="S -> V (in Ref. 1; AAD02203)"
FT /evidence="ECO:0000305"
FT CONFLICT 9..11
FT /note="LFF -> ICL (in Ref. 1; AAD02203)"
FT /evidence="ECO:0000305"
FT CONFLICT 235
FT /note="T -> N (in Ref. 4; BI834924)"
FT /evidence="ECO:0000305"
FT CONFLICT 398
FT /note="S -> T (in Ref. 1; AAD02203)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 499 AA; 55181 MW; DE8728D2BEC28141 CRC64;
MTLILTSLLF FGLSLGPRTR VQAENLLKPI LWAEPGPVIT WHNPVTIWCQ GTLEAQGYRL
DKEGNSMSRH ILKTLESENK VKLSIPSMMW EHAGRYHCYY QSPAGWSEPS DPLELVVTAY
SRPTLSALPS PVVTSGVNVT LRCASRLGLG RFTLIEEGDH RLSWTLNSHQ HNHGKFQALF
PMGPLTFSNR GTFRCYGYEN NTPYVWSEPS DPLQLLVSGV SRKPSLLTLQ GPVVTPGENL
TLQCGSDVGY IRYTLYKEGA DGLPQRPGRQ PQAGLSQANF TLSPVSRSYG GQYRCYGAHN
VSSEWSAPSD PLDILIAGQI SDRPSLSVQP GPTVTSGEKV TLLCQSWDPM FTFLLTKEGA
AHPPLRLRSM YGAHKYQAEF PMSPVTSAHA GTYRCYGSRS SNPYLLSHPS EPLELVVSGA
TETLNPAQKK SDSKTAPHLQ DYTVENLIRM GVAGLVLLFL GILLFEAQHS QRSPPRCSQE
ANSRKDNAPF RVVEPWEQI
