LIRB4_HUMAN
ID LIRB4_HUMAN Reviewed; 448 AA.
AC Q8NHJ6; A8MVL8; O15468; O75021; Q6FGQ9; Q8N1C7; Q8NHL5;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 08-FEB-2011, sequence version 3.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Leukocyte immunoglobulin-like receptor subfamily B member 4;
DE Short=B4 {ECO:0000303|PubMed:34089617};
DE AltName: Full=CD85 antigen-like family member K;
DE AltName: Full=Immunoglobulin-like transcript 3;
DE Short=ILT-3;
DE AltName: Full=Leukocyte immunoglobulin-like receptor 5;
DE Short=LIR-5;
DE AltName: Full=Monocyte inhibitory receptor HM18;
DE AltName: CD_antigen=CD85k;
DE Flags: Precursor;
GN Name=LILRB4; Synonyms=ILT3, LIR5;
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), TISSUE SPECIFICITY, AND VARIANT
RP GLY-223.
RC TISSUE=Monocyte;
RX PubMed=9278324;
RA Arm J.P., Nwankwo C., Austen K.F.;
RT "Molecular identification of a novel family of human Ig superfamily members
RT that possess immunoreceptor tyrosine-based inhibition motifs and homology
RT to the mouse gp49B1 inhibitory receptor.";
RL J. Immunol. 159:2342-2349(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS GLY-223 AND ARG-414, AND
RP 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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANTS LEU-5; GLY-223
RP AND GLU-362.
RX PubMed=10941837; DOI=10.1007/s002510000183;
RA Liu W.R., Kim J., Nwankwo C., Ashworth L.K., Arm J.P.;
RT "Genomic organization of the human leukocyte immunoglobulin-like receptors
RT within the leukocyte receptor complex on chromosome 19q13.4.";
RL Immunogenetics 51:659-669(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Canavez F.C.;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Placenta;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS ASP-20;
RP GLY-223 AND ARG-414.
RC TISSUE=Brain;
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 [9]
RP FUNCTION, INTERACTION WITH PTPN6, PHOSPHORYLATION, TISSUE SPECIFICITY, AND
RP SUBCELLULAR LOCATION.
RX PubMed=9151699; DOI=10.1084/jem.185.10.1743;
RA Cella M., Doehring C., Samaridis J., Dessing M., Brockhaus M.,
RA Lanzavecchia A., Colonna M.;
RT "A novel inhibitory receptor (ILT3) expressed on monocytes, macrophages,
RT and dendritic cells involved in antigen processing.";
RL J. Exp. Med. 185:1743-1751(1997).
RN [10]
RP FUNCTION, AND INDUCTION.
RX PubMed=11875462; DOI=10.1038/ni760;
RA Chang C.C., Ciubotariu R., Manavalan J.S., Yuan J., Colovai A.I.,
RA Piazza F., Lederman S., Colonna M., Cortesini R., Dalla-Favera R.,
RA Suciu-Foca N.;
RT "Tolerization of dendritic cells by T(S) cells: the crucial role of
RT inhibitory receptors ILT3 and ILT4.";
RL Nat. Immunol. 3:237-243(2002).
RN [11]
RP FUNCTION, AND INTERACTION WITH PTPN6.
RX PubMed=16493035; DOI=10.4049/jimmunol.176.5.2790;
RA Kim-Schulze S., Scotto L., Vlad G., Piazza F., Lin H., Liu Z.,
RA Cortesini R., Suciu-Foca N.;
RT "Recombinant Ig-like transcript 3-Fc modulates T cell responses via
RT induction of Th anergy and differentiation of CD8+ T suppressor cells.";
RL J. Immunol. 176:2790-2798(2006).
RN [12]
RP FUNCTION, AND INDUCTION.
RX PubMed=19860908; DOI=10.1186/1471-2172-10-56;
RA Brown D.P., Jones D.C., Anderson K.J., Lapaque N., Buerki R.A.,
RA Trowsdale J., Allen R.L.;
RT "The inhibitory receptor LILRB4 (ILT3) modulates antigen presenting cell
RT phenotype and, along with LILRB2 (ILT4), is upregulated in response to
RT Salmonella infection.";
RL BMC Immunol. 10:56-56(2009).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=19833736; DOI=10.1074/jbc.m109.035683;
RA Lu H.K., Rentero C., Raftery M.J., Borges L., Bryant K., Tedla N.;
RT "Leukocyte Ig-like receptor B4 (LILRB4) is a potent inhibitor of FcgammaRI-
RT mediated monocyte activation via dephosphorylation of multiple kinases.";
RL J. Biol. Chem. 284:34839-34848(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-319, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [15]
RP FUNCTION.
RX PubMed=29263213; DOI=10.4049/jimmunol.1700553;
RA Xu Z., Chang C.C., Li M., Zhang Q.Y., Vasilescu E.M., D'Agati V.,
RA Floratos A., Vlad G., Suciu-Foca N.;
RT "ILT3.Fc-CD166 Interaction Induces Inactivation of p70 S6 Kinase and
RT Inhibits Tumor Cell Growth.";
RL J. Immunol. 200:1207-1219(2018).
RN [16]
RP FUNCTION, TISSUE SPECIFICITY, ROLE IN TUMOR CELL INFILTRATION, AND
RP MUTAGENESIS OF THR-30; PRO-35; TRP-41; ARG-59; GLU-63; GLU-64; SER-65;
RP PRO-66; PRO-68; ASP-91; ARG-95; ARG-97; PRO-103; TRP-106; PRO-109; ASP-111;
RP PRO-112; LEU-113; GLU-114; TYR-121; SER-122; ARG-147; PRO-149; HIS-162;
RP LEU-164; LEU-165; LEU-167; GLU-170; SER-183; PRO-184; THR-186; VAL-188;
RP HIS-199; PHE-201 AND SER-202.
RX PubMed=30333625; DOI=10.1038/s41586-018-0615-z;
RA Deng M., Gui X., Kim J., Xie L., Chen W., Li Z., He L., Chen Y., Chen H.,
RA Luo W., Lu Z., Xie J., Churchill H., Xu Y., Zhou Z., Wu G., Yu C., John S.,
RA Hirayasu K., Nguyen N., Liu X., Huang F., Li L., Deng H., Tang H.,
RA Sadek A.H., Zhang L., Huang T., Zou Y., Chen B., Zhu H., Arase H., Xia N.,
RA Jiang Y., Collins R., You M.J., Homsi J., Unni N., Lewis C., Chen G.Q.,
RA Fu Y.X., Liao X.C., An Z., Zheng J., Zhang N., Zhang C.C.;
RT "LILRB4 signalling in leukaemia cells mediates T cell suppression and
RT tumour infiltration.";
RL Nature 562:605-609(2018).
RN [17]
RP FUNCTION.
RX PubMed=34089617; DOI=10.1093/intimm/dxab028;
RA Su M.T., Inui M., Wong Y.L., Takahashi M., Sugahara-Tobinai A., Ono K.,
RA Miyamoto S., Murakami K., Itoh-Nakadai A., Kezuka D., Itoi S., Endo S.,
RA Hirayasu K., Arase H., Takai T.;
RT "Blockade of checkpoint ILT3/LILRB4/gp49B binding to fibronectin
RT ameliorates autoimmune disease in BXSB/Yaa mice.";
RL Int. Immunol. 33:447-458(2021).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 24-219, AND DISULFIDE BONDS.
RX PubMed=21454581; DOI=10.1074/jbc.m111.221028;
RA Cheng H., Mohammed F., Nam G., Chen Y., Qi J., Garner L.I., Allen R.L.,
RA Yan J., Willcox B.E., Gao G.F.;
RT "Crystal structure of leukocyte Ig-like receptor LILRB4 (ILT3/LIR-5/CD85k):
RT a myeloid inhibitory receptor involved in immune tolerance.";
RL J. Biol. Chem. 286:18013-18025(2011).
CC -!- FUNCTION: Inhibitory receptor involved in the down-regulation of the
CC immune response and the development of immune tolerance
CC (PubMed:11875462). Receptor for FN1 (PubMed:34089617). Receptor for
CC apolipoprotein APOE (PubMed:30333625). Receptor for ALCAM/CD166
CC (PubMed:29263213). Inhibits receptor-mediated phosphorylation of
CC cellular proteins and mobilization of intracellular calcium ions
CC (PubMed:9151699). Inhibits FCGR1A/CD64-mediated monocyte activation by
CC inducing phosphatase-mediated down-regulation of the phosphorylation of
CC multiple proteins including LCK, SYK, LAT and ERK, leading to a
CC reduction in TNF production (PubMed:19833736). This inhibition of
CC monocyte activation occurs at least in part via binding to FN1
CC (PubMed:34089617). Inhibits T cell proliferation, inducing anergy,
CC suppressing the differentiation of IFNG-producing CD8+ cytoxic T cells
CC and enhancing the generation of CD8+ T suppressor cells
CC (PubMed:16493035, PubMed:19833736, PubMed:29263213). Induces up-
CC regulation of CD86 on dendritic cells (PubMed:19860908). Interferes
CC with TNFRSF5-signaling and NF-kappa-B up-regulation (PubMed:11875462).
CC {ECO:0000269|PubMed:11875462, ECO:0000269|PubMed:16493035,
CC ECO:0000269|PubMed:19833736, ECO:0000269|PubMed:19860908,
CC ECO:0000269|PubMed:29263213, ECO:0000269|PubMed:30333625,
CC ECO:0000269|PubMed:34089617, ECO:0000269|PubMed:9151699}.
CC -!- SUBUNIT: Interacts with PTPN6. {ECO:0000269|PubMed:16493035,
CC ECO:0000269|PubMed:9151699}.
CC -!- INTERACTION:
CC Q8NHJ6; P29350: PTPN6; NbExp=4; IntAct=EBI-2805248, EBI-78260;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19833736,
CC ECO:0000269|PubMed:9151699}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:9151699}. Note=Ligand binding leads to
CC internalization and translocation to an antigen-processing compartment.
CC {ECO:0000269|PubMed:9151699}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8NHJ6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NHJ6-2; Sequence=VSP_008460;
CC Name=3;
CC IsoId=Q8NHJ6-3; Sequence=VSP_035939;
CC -!- TISSUE SPECIFICITY: Detected on monocytes, macrophages, dendritic
CC cells, natural killer cells and B-cells (at protein level). Expressed
CC in the lung. {ECO:0000269|PubMed:19833736, ECO:0000269|PubMed:30333625,
CC ECO:0000269|PubMed:9151699, ECO:0000269|PubMed:9278324,
CC ECO:0000269|PubMed:9548455}.
CC -!- INDUCTION: Induced on monocyte-derived macrophages by S.typhimurium
CC infection (PubMed:19860908). Induced on monocytes and dendritic cells
CC upon contact with CD8(+)CD28(-) alloantigen-specific T suppressor (Ts)
CC cells (PubMed:11875462). {ECO:0000269|PubMed:11875462,
CC ECO:0000269|PubMed:19860908}.
CC -!- DOMAIN: Contains 3 copies of a cytoplasmic motif that is referred to as
CC the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is
CC involved in modulation of cellular responses. The phosphorylated ITIM
CC motif can bind the SH2 domain of several SH2-containing phosphatases.
CC -!- MISCELLANEOUS: Activated by APOE on acute myeloid leukemia (AML) cells
CC which leads to suppression of T cell proliferation and promotion of AML
CC cell migration and infiltration (PubMed:30333625). LILRB4 signaling on
CC AML cells is mediated by PTPN11/SHP-2 (PubMed:30333625).
CC {ECO:0000269|PubMed:30333625}.
CC -!- MISCELLANEOUS: [Isoform 2]: Alternative use of an acceptor site.
CC {ECO:0000305}.
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DR EMBL; U91925; AAB68665.1; -; mRNA.
DR EMBL; AF025532; AAB87666.1; -; mRNA.
DR EMBL; AF189768; AAG02024.1; -; Genomic_DNA.
DR EMBL; AF283988; AAL36992.1; -; mRNA.
DR EMBL; CR542048; CAG46845.1; -; mRNA.
DR EMBL; CR609786; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC009892; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC011515; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC026309; AAH26309.1; -; mRNA.
DR CCDS; CCDS12902.1; -. [Q8NHJ6-1]
DR CCDS; CCDS42618.1; -. [Q8NHJ6-2]
DR RefSeq; NP_001265355.2; NM_001278426.3.
DR RefSeq; NP_001265356.2; NM_001278427.3.
DR RefSeq; NP_001265357.2; NM_001278428.3.
DR RefSeq; NP_001265358.2; NM_001278429.3.
DR RefSeq; NP_001265359.2; NM_001278430.3.
DR PDB; 3P2T; X-ray; 1.70 A; A=24-219.
DR PDB; 6K7O; X-ray; 3.00 A; A/P/Q/R=24-118.
DR PDBsum; 3P2T; -.
DR PDBsum; 6K7O; -.
DR AlphaFoldDB; Q8NHJ6; -.
DR SMR; Q8NHJ6; -.
DR BioGRID; 116197; 26.
DR IntAct; Q8NHJ6; 15.
DR STRING; 9606.ENSP00000375616; -.
DR GlyGen; Q8NHJ6; 2 sites, 3 O-linked glycans (2 sites).
DR iPTMnet; Q8NHJ6; -.
DR PhosphoSitePlus; Q8NHJ6; -.
DR BioMuta; LILRB4; -.
DR DMDM; 322510117; -.
DR jPOST; Q8NHJ6; -.
DR MassIVE; Q8NHJ6; -.
DR PaxDb; Q8NHJ6; -.
DR PeptideAtlas; Q8NHJ6; -.
DR PRIDE; Q8NHJ6; -.
DR ProteomicsDB; 73714; -. [Q8NHJ6-1]
DR ProteomicsDB; 73715; -. [Q8NHJ6-2]
DR ProteomicsDB; 73716; -. [Q8NHJ6-3]
DR Antibodypedia; 35096; 284 antibodies from 28 providers.
DR DNASU; 11006; -.
DR Ensembl; ENST00000391736.5; ENSP00000375616.1; ENSG00000186818.12.
DR Ensembl; ENST00000612454.4; ENSP00000479829.1; ENSG00000275730.4. [Q8NHJ6-1]
DR Ensembl; ENST00000614699.4; ENSP00000478542.1; ENSG00000275730.4. [Q8NHJ6-3]
DR Ensembl; ENST00000621693.4; ENSP00000482234.1; ENSG00000275730.4. [Q8NHJ6-2]
DR GeneID; 11006; -.
DR KEGG; hsa:11006; -.
DR UCSC; uc002qgp.5; human. [Q8NHJ6-1]
DR CTD; 11006; -.
DR DisGeNET; 11006; -.
DR GeneCards; LILRB4; -.
DR HGNC; HGNC:6608; LILRB4.
DR HPA; ENSG00000186818; Tissue enhanced (lung, lymphoid tissue).
DR MIM; 604821; gene.
DR neXtProt; NX_Q8NHJ6; -.
DR PharmGKB; PA30382; -.
DR VEuPathDB; HostDB:ENSG00000186818; -.
DR eggNOG; ENOG502RU0A; Eukaryota.
DR InParanoid; Q8NHJ6; -.
DR OrthoDB; 1000446at2759; -.
DR PhylomeDB; Q8NHJ6; -.
DR TreeFam; TF336644; -.
DR PathwayCommons; Q8NHJ6; -.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR SignaLink; Q8NHJ6; -.
DR SIGNOR; Q8NHJ6; -.
DR BioGRID-ORCS; 11006; 7 hits in 1058 CRISPR screens.
DR ChiTaRS; LILRB4; human.
DR GeneWiki; LILRB4; -.
DR GenomeRNAi; 11006; -.
DR Pharos; Q8NHJ6; Tbio.
DR PRO; PR:Q8NHJ6; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8NHJ6; protein.
DR Bgee; ENSG00000186818; Expressed in vermiform appendix and 101 other tissues.
DR ExpressionAtlas; Q8NHJ6; baseline and differential.
DR Genevisible; Q8NHJ6; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0098752; C:integral component of the cytoplasmic side of the plasma membrane; TAS:ARUK-UCL.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0034185; F:apolipoprotein binding; IDA:UniProtKB.
DR GO; GO:0001968; F:fibronectin binding; IDA:UniProtKB.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:ARUK-UCL.
DR GO; GO:0030547; F:signaling receptor inhibitor activity; IDA:ARUK-UCL.
DR GO; GO:0030293; F:transmembrane receptor protein tyrosine kinase inhibitor activity; IDA:ARUK-UCL.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0002774; P:Fc receptor mediated inhibitory signaling pathway; IDA:ARUK-UCL.
DR GO; GO:0140105; P:interleukin-10-mediated signaling pathway; IEP:ARUK-UCL.
DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; IMP:ARUK-UCL.
DR GO; GO:0032682; P:negative regulation of chemokine production; IMP:ARUK-UCL.
DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; IMP:ARUK-UCL.
DR GO; GO:0045584; P:negative regulation of cytotoxic T cell differentiation; IMP:ARUK-UCL.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IMP:ARUK-UCL.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; IDA:ARUK-UCL.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IMP:ARUK-UCL.
DR GO; GO:0032693; P:negative regulation of interleukin-10 production; IDA:ARUK-UCL.
DR GO; GO:0032703; P:negative regulation of interleukin-2 production; IDA:ARUK-UCL.
DR GO; GO:0032714; P:negative regulation of interleukin-5 production; IDA:ARUK-UCL.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IMP:ARUK-UCL.
DR GO; GO:0071659; P:negative regulation of IP-10 production; IMP:ARUK-UCL.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IMP:ARUK-UCL.
DR GO; GO:1902894; P:negative regulation of miRNA transcription; IDA:BHF-UCL.
DR GO; GO:0150102; P:negative regulation of monocyte activation; IDA:UniProtKB.
DR GO; GO:0045671; P:negative regulation of osteoclast differentiation; IDA:UniProtKB.
DR GO; GO:1900181; P:negative regulation of protein localization to nucleus; IDA:BHF-UCL.
DR GO; GO:0061099; P:negative regulation of protein tyrosine kinase activity; IDA:ARUK-UCL.
DR GO; GO:2000272; P:negative regulation of signaling receptor activity; IDA:ARUK-UCL.
DR GO; GO:2000524; P:negative regulation of T cell costimulation; IMP:ARUK-UCL.
DR GO; GO:0002725; P:negative regulation of T cell cytokine production; IDA:ARUK-UCL.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IMP:ARUK-UCL.
DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IDA:UniProtKB.
DR GO; GO:0043378; P:positive regulation of CD8-positive, alpha-beta T cell differentiation; IDA:ARUK-UCL.
DR GO; GO:0045591; P:positive regulation of regulatory T cell differentiation; IDA:ARUK-UCL.
DR GO; GO:0002669; P:positive regulation of T cell anergy; IMP:ARUK-UCL.
DR GO; GO:0031623; P:receptor internalization; IMP:ARUK-UCL.
DR GO; GO:0002507; P:tolerance induction; IDA:ARUK-UCL.
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; IPR013151; Immunoglobulin.
DR Pfam; PF00047; ig; 1.
DR Pfam; PF13895; Ig_2; 1.
DR SUPFAM; SSF48726; SSF48726; 2.
DR PROSITE; PS50835; IG_LIKE; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; Cell membrane;
KW Disulfide bond; Immunity; Immunoglobulin domain; Membrane; Phosphoprotein;
KW Receptor; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..448
FT /note="Leukocyte immunoglobulin-like receptor subfamily B
FT member 4"
FT /id="PRO_0000014823"
FT TOPO_DOM 22..259
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 260..280
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 281..448
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 27..118
FT /note="Ig-like C2-type 1"
FT DOMAIN 124..218
FT /note="Ig-like C2-type 2"
FT REGION 217..248
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 297..448
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 358..363
FT /note="ITIM motif 1"
FT MOTIF 410..415
FT /note="ITIM motif 2"
FT MOTIF 440..445
FT /note="ITIM motif 3"
FT COMPBIAS 340..371
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 385..400
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 410..429
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 35
FT /note="Required for APOE-mediated activation of LILRB4"
FT /evidence="ECO:0000269|PubMed:30333625"
FT SITE 106
FT /note="Required for APOE-mediated activation of LILRB4"
FT /evidence="ECO:0000269|PubMed:30333625"
FT SITE 121
FT /note="Required for APOE-mediated activation of LILRB4"
FT /evidence="ECO:0000269|PubMed:30333625"
FT MOD_RES 319
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT DISULFID 49..98
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:21454581"
FT DISULFID 144..195
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:21454581"
FT VAR_SEQ 330
FT /note="C -> SG (in isoform 3)"
FT /evidence="ECO:0000303|Ref.6"
FT /id="VSP_035939"
FT VAR_SEQ 348
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4, ECO:0000303|Ref.5"
FT /id="VSP_008460"
FT VARIANT 5
FT /note="F -> L (in dbSNP:rs28366008)"
FT /evidence="ECO:0000269|PubMed:10941837"
FT /id="VAR_025501"
FT VARIANT 18
FT /note="R -> S (in dbSNP:rs11540761)"
FT /id="VAR_025502"
FT VARIANT 20
FT /note="H -> D (in dbSNP:rs11540762)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_047846"
FT VARIANT 223
FT /note="D -> G (in dbSNP:rs731170)"
FT /evidence="ECO:0000269|PubMed:10941837,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9278324,
FT ECO:0000269|PubMed:9548455"
FT /id="VAR_017014"
FT VARIANT 330
FT /note="C -> Y (in dbSNP:rs11574575)"
FT /id="VAR_025503"
FT VARIANT 335
FT /note="N -> D (in dbSNP:rs11574576)"
FT /id="VAR_025504"
FT VARIANT 362
FT /note="K -> E (in dbSNP:rs2764337)"
FT /evidence="ECO:0000269|PubMed:10941837"
FT /id="VAR_017015"
FT VARIANT 362
FT /note="K -> T (in dbSNP:rs11574589)"
FT /id="VAR_030939"
FT VARIANT 414
FT /note="Q -> R (in dbSNP:rs1048801)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:9548455"
FT /id="VAR_025505"
FT MUTAGEN 30
FT /note="T->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 35
FT /note="P->A: Significant reduction in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 41
FT /note="W->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 59
FT /note="R->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 63
FT /note="E->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 64
FT /note="E->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 65
FT /note="S->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 66
FT /note="P->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 68
FT /note="P->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 91
FT /note="D->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 95
FT /note="R->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 97
FT /note="R->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 103
FT /note="P->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 106
FT /note="W->A: Significant reduction in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 109
FT /note="P->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 111
FT /note="D->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 112
FT /note="P->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 113
FT /note="L->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 114
FT /note="E->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 121
FT /note="Y->A: Significant reduction in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 122
FT /note="S->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 147
FT /note="R->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 149
FT /note="P->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 162
FT /note="H->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 164
FT /note="L->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 165
FT /note="L->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 167
FT /note="L->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 170
FT /note="E->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 183
FT /note="S->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 184
FT /note="P->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 186
FT /note="T->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 188
FT /note="V->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 199
FT /note="H->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 201
FT /note="F->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT MUTAGEN 202
FT /note="S->A: No significant change in APOE-mediated
FT activation of LILRB4."
FT /evidence="ECO:0000269|PubMed:30333625"
FT STRAND 30..35
FT /evidence="ECO:0007829|PDB:3P2T"
FT STRAND 37..40
FT /evidence="ECO:0007829|PDB:3P2T"
FT STRAND 45..50
FT /evidence="ECO:0007829|PDB:3P2T"
FT STRAND 57..62
FT /evidence="ECO:0007829|PDB:3P2T"
FT STRAND 69..72
FT /evidence="ECO:0007829|PDB:3P2T"
FT STRAND 76..87
FT /evidence="ECO:0007829|PDB:3P2T"
FT HELIX 90..92
FT /evidence="ECO:0007829|PDB:3P2T"
FT STRAND 94..102
FT /evidence="ECO:0007829|PDB:3P2T"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:3P2T"
FT STRAND 113..118
FT /evidence="ECO:0007829|PDB:3P2T"
FT STRAND 125..130
FT /evidence="ECO:0007829|PDB:3P2T"
FT STRAND 132..135
FT /evidence="ECO:0007829|PDB:3P2T"
FT STRAND 140..157
FT /evidence="ECO:0007829|PDB:3P2T"
FT HELIX 163..165
FT /evidence="ECO:0007829|PDB:3P2T"
FT STRAND 166..182
FT /evidence="ECO:0007829|PDB:3P2T"
FT HELIX 187..189
FT /evidence="ECO:0007829|PDB:3P2T"
FT STRAND 191..198
FT /evidence="ECO:0007829|PDB:3P2T"
FT HELIX 200..202
FT /evidence="ECO:0007829|PDB:3P2T"
FT STRAND 213..218
FT /evidence="ECO:0007829|PDB:3P2T"
SQ SEQUENCE 448 AA; 49356 MW; C18C21694F283FBB CRC64;
MIPTFTALLC LGLSLGPRTH MQAGPLPKPT LWAEPGSVIS WGNSVTIWCQ GTLEAREYRL
DKEESPAPWD RQNPLEPKNK ARFSIPSMTE DYAGRYRCYY RSPVGWSQPS DPLELVMTGA
YSKPTLSALP SPLVTSGKSV TLLCQSRSPM DTFLLIKERA AHPLLHLRSE HGAQQHQAEF
PMSPVTSVHG GTYRCFSSHG FSHYLLSHPS DPLELIVSGS LEDPRPSPTR SVSTAAGPED
QPLMPTGSVP HSGLRRHWEV LIGVLVVSIL LLSLLLFLLL QHWRQGKHRT LAQRQADFQR
PPGAAEPEPK DGGLQRRSSP AADVQGENFC AAVKNTQPED GVEMDTRQSP HDEDPQAVTY
AKVKHSRPRR EMASPPSPLS GEFLDTKDRQ AEEDRQMDTE AAASEAPQDV TYAQLHSFTL
RQKATEPPPS QEGASPAEPS VYATLAIH
