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   24-JAN-2024, entry version 161.
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,
GN   ECO:0000303|PubMed:19564354, 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 a 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. [P59901-1]
DR   AlphaFoldDB; P59901; -.
DR   SMR; P59901; -.
DR   IntAct; P59901; 2.
DR   STRING; 9606.ENSP00000291759; -.
DR   ChEMBL; CHEMBL4804246; -.
DR   GlyCosmos; P59901; 4 sites, No reported glycans.
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; 9606-ENSP00000291759; -.
DR   PeptideAtlas; P59901; -.
DR   TopDownProteomics; P59901-1; -. [P59901-1]
DR   ABCD; P59901; 3 sequenced antibodies.
DR   Antibodypedia; 32892; 335 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   AGR; HGNC:15503; -.
DR   CTD; 23547; -.
DR   DisGeNET; 23547; -.
DR   GeneCards; LILRA4; -.
DR   HGNC; HGNC:15503; LILRA4.
DR   HPA; ENSG00000239961; Group enriched (brain, lymphoid tissue).
DR   MIM; 607517; gene.
DR   neXtProt; NX_P59901; -.
DR   OpenTargets; ENSG00000239961; -.
DR   PharmGKB; PA142671546; -.
DR   VEuPathDB; HostDB:ENSG00000239961; -.
DR   eggNOG; ENOG502RYEX; Eukaryota.
DR   GeneTree; ENSGT01100000263478; -.
DR   HOGENOM; CLU_021100_2_0_1; -.
DR   InParanoid; P59901; -.
DR   OMA; FENNTPY; -.
DR   OrthoDB; 5353978at2759; -.
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 1132 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 89 other cell types or tissues.
DR   ExpressionAtlas; P59901; baseline and differential.
DR   GO; GO:0032998; C:Fc-epsilon receptor I complex; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
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   CDD; cd05751; IgC2_D1_LILR_KIR_like; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 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   PANTHER; PTHR11738:SF98; LEUKOCYTE IMMUNOGLOBULIN-LIKE RECEPTOR SUBFAMILY A MEMBER 4; 1.
DR   PANTHER; PTHR11738; MHC CLASS I NK CELL RECEPTOR; 1.
DR   Pfam; PF00047; ig; 2.
DR   Pfam; PF13895; Ig_2; 1.
DR   Pfam; PF13927; Ig_3; 1.
DR   PIRSF; PIRSF001979; Alpha_1B_glycoprot_prd; 1.
DR   SMART; SM00409; IG; 4.
DR   SMART; SM00408; IGc2; 3.
DR   SUPFAM; SSF48726; Immunoglobulin; 4.
DR   PROSITE; PS50835; IG_LIKE; 3.
DR   Genevisible; P59901; HS.
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
//