LIRB3_HUMAN
ID LIRB3_HUMAN Reviewed; 631 AA.
AC O75022; C9J1P3; C9JIP1; O15471; Q86U49;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 3.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Leukocyte immunoglobulin-like receptor subfamily B member 3;
DE Short=LIR-3;
DE Short=Leukocyte immunoglobulin-like receptor 3;
DE AltName: Full=CD85 antigen-like family member A;
DE AltName: Full=Immunoglobulin-like transcript 5;
DE Short=ILT-5;
DE AltName: Full=Monocyte inhibitory receptor HL9;
DE AltName: CD_antigen=CD85a;
DE Flags: Precursor;
GN Name=LILRB3; Synonyms=ILT5, LIR3;
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 VARIANTS ASN-122 AND GLN-205.
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 GLN-59; GLN-90; ARG-400;
RP TYR-405; HIS-539 AND ALA-574, 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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 2), AND
RP VARIANT ARG-400.
RA Cuillerier B., Bahram S.;
RT "Genomics and diversity of the immunoglobulin-like transcript 5 locus.";
RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
RP IDENTIFICATION IN THE LRC.
RX PubMed=10941842; DOI=10.1007/s002510000187;
RA Wende H., Volz A., Ziegler A.;
RT "Extensive gene duplications and a large inversion characterize the human
RT leukocyte receptor cluster.";
RL Immunogenetics 51:703-713(2000).
RN [6]
RP ERRATUM OF PUBMED:10941842.
RA Wende H., Volz A., Ziegler A.;
RL Immunogenetics 52:3-4(2001).
RN [7]
RP VARIANT HIS-171.
RX PubMed=28087737; DOI=10.1093/hmg/ddx020;
RA Singh N., Kumble Bhat V., Tiwari A., Kodaganur S.G., Tontanahal S.J.,
RA Sarda A., Malini K.V., Kumar A.;
RT "A homozygous mutation in TRIM36 causes autosomal recessive anencephaly in
RT an Indian family.";
RL Hum. Mol. Genet. 26:1104-1114(2017).
CC -!- FUNCTION: May act as receptor for class I MHC antigens. Becomes
CC activated upon coligation of LILRB3 and immune receptors, such as
CC FCGR2B and the B-cell receptor. Down-regulates antigen-induced B-cell
CC activation by recruiting phosphatases to its immunoreceptor tyrosine-
CC based inhibitor motifs (ITIM). {ECO:0000250|UniProtKB:P97484}.
CC -!- SUBUNIT: Interacts with LYN, PTPN6/SHP-1 and PTPN11/SHP-2.
CC {ECO:0000250|UniProtKB:P97484}.
CC -!- INTERACTION:
CC O75022; P05783: KRT18; NbExp=3; IntAct=EBI-2830524, EBI-297888;
CC O75022; P05787: KRT8; NbExp=3; IntAct=EBI-2830524, EBI-297852;
CC O75022; P29350: PTPN6; NbExp=4; IntAct=EBI-2830524, EBI-78260;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O75022-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75022-2; Sequence=VSP_008459;
CC Name=3;
CC IsoId=O75022-3; Sequence=VSP_040126;
CC -!- TISSUE SPECIFICITY: Detected in monocytes and B-cells.
CC {ECO:0000269|PubMed:9548455}.
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 including PTPN6/SHP-1, resulting in the dephosphorylation of the
CC downstream protein kinases SYK and BTK. {ECO:0000250|UniProtKB:P97484}.
CC -!- PTM: Phosphorylated on tyrosine residues by LYN. Phosphorylation at
CC Tyr-595 and Tyr-625 is important for interaction with PTPN6/SHP-1 and
CC PTPN11/SHP-2. {ECO:0000250|UniProtKB:P97484}.
CC -!- MISCELLANEOUS: Belongs to the leukocyte receptor cluster (LRC) present
CC on 19q13.4.
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DR EMBL; U91928; AAB68668.1; -; mRNA.
DR EMBL; AF025533; AAB87667.1; -; mRNA.
DR EMBL; AF256195; AAP30716.1; -; Genomic_DNA.
DR EMBL; AC010492; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC012314; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS33105.1; -. [O75022-1]
DR CCDS; CCDS46175.1; -. [O75022-3]
DR RefSeq; NP_001074919.2; NM_001081450.3.
DR RefSeq; XP_006726377.1; XM_006726314.3.
DR RefSeq; XP_016885785.1; XM_017030296.1. [O75022-3]
DR RefSeq; XP_016885786.1; XM_017030297.1. [O75022-1]
DR AlphaFoldDB; O75022; -.
DR SMR; O75022; -.
DR IntAct; O75022; 14.
DR STRING; 9606.ENSP00000245620; -.
DR GlyGen; O75022; 5 sites, 1 O-linked glycan (1 site).
DR iPTMnet; O75022; -.
DR PhosphoSitePlus; O75022; -.
DR BioMuta; LILRB3; -.
DR jPOST; O75022; -.
DR MassIVE; O75022; -.
DR PaxDb; O75022; -.
DR PeptideAtlas; O75022; -.
DR PRIDE; O75022; -.
DR Antibodypedia; 34955; 410 antibodies from 26 providers.
DR Ensembl; ENST00000245620.13; ENSP00000245620.9; ENSG00000204577.12.
DR Ensembl; ENST00000391750.5; ENSP00000375630.1; ENSG00000204577.12.
DR Ensembl; ENST00000611086.4; ENSP00000483625.1; ENSG00000274587.5. [O75022-1]
DR Ensembl; ENST00000613698.4; ENSP00000479234.1; ENSG00000275019.5.
DR GeneID; 102725035; -.
DR GeneID; 107987462; -.
DR GeneID; 11025; -.
DR KEGG; hsa:102725035; -.
DR KEGG; hsa:107987462; -.
DR KEGG; hsa:11025; -.
DR UCSC; uc032icw.2; human. [O75022-1]
DR CTD; 11025; -.
DR DisGeNET; 102725035; -.
DR DisGeNET; 107987462; -.
DR GeneCards; LILRB3; -.
DR HGNC; HGNC:6607; LILRB3.
DR HPA; ENSG00000204577; Tissue enhanced (lung, lymphoid tissue).
DR MIM; 604820; gene.
DR neXtProt; NX_O75022; -.
DR PharmGKB; PA30381; -.
DR VEuPathDB; HostDB:ENSG00000204577; -.
DR eggNOG; ENOG502RYEX; Eukaryota.
DR HOGENOM; CLU_021100_2_3_1; -.
DR InParanoid; O75022; -.
DR OrthoDB; 1000446at2759; -.
DR PhylomeDB; O75022; -.
DR TreeFam; TF336644; -.
DR PathwayCommons; O75022; -.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; O75022; -.
DR BioGRID-ORCS; 102725035; 0 hits in 3 CRISPR screens.
DR BioGRID-ORCS; 107987462; 0 hits in 4 CRISPR screens.
DR ChiTaRS; LILRB3; human.
DR Pharos; O75022; Tbio.
DR PRO; PR:O75022; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O75022; protein.
DR Bgee; ENSG00000204577; Expressed in blood and 96 other tissues.
DR ExpressionAtlas; O75022; baseline and differential.
DR Genevisible; O75022; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0030667; C:secretory granule membrane; TAS:Reactome.
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:0004888; F:transmembrane signaling receptor activity; TAS:ProtInc.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; 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:0045671; P:negative regulation of osteoclast differentiation; IDA:UniProtKB.
DR Gene3D; 2.60.40.10; -; 4.
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 Pfam; PF13895; Ig_2; 1.
DR SMART; SM00409; IG; 3.
DR SMART; SM00408; IGc2; 3.
DR SUPFAM; SSF48726; SSF48726; 4.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Alternative splicing; Cell membrane; Disulfide bond;
KW Glycoprotein; Immunity; Immunoglobulin domain; Membrane; Phosphoprotein;
KW Receptor; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..631
FT /note="Leukocyte immunoglobulin-like receptor subfamily B
FT member 3"
FT /id="PRO_0000014822"
FT TOPO_DOM 24..443
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 444..464
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 465..631
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 42..100
FT /note="Ig-like C2-type 1"
FT DOMAIN 111..229
FT /note="Ig-like C2-type 2"
FT DOMAIN 225..314
FT /note="Ig-like C2-type 3"
FT DOMAIN 338..419
FT /note="Ig-like C2-type 4"
FT REGION 59..78
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 470..631
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 512..517
FT /note="ITIM motif 1"
FT MOTIF 593..598
FT /note="ITIM motif 2"
FT MOTIF 623..628
FT /note="ITIM motif 3"
FT COMPBIAS 59..77
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 474..501
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 517..534
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 568..583
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 584..598
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 595
FT /note="Phosphotyrosine; by LYN"
FT /evidence="ECO:0000250|UniProtKB:P97484"
FT MOD_RES 625
FT /note="Phosphotyrosine; by LYN"
FT /evidence="ECO:0000250|UniProtKB:P97484"
FT CARBOHYD 139
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 280
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 301
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 49..98
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 144..196
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 245..296
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 345..396
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 437
FT /note="G -> GGPEDQPLNPPGSGPQNG (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_008459"
FT VAR_SEQ 530
FT /note="S -> SQ (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_040126"
FT VARIANT 21
FT /note="V -> M (in dbSNP:rs1132588)"
FT /id="VAR_017001"
FT VARIANT 59
FT /note="R -> Q (in dbSNP:rs678876)"
FT /evidence="ECO:0000269|PubMed:9548455"
FT /id="VAR_017002"
FT VARIANT 69
FT /note="L -> W (in dbSNP:rs80077296)"
FT /id="VAR_017003"
FT VARIANT 90
FT /note="E -> Q (in dbSNP:rs1052963)"
FT /evidence="ECO:0000269|PubMed:9548455"
FT /id="VAR_017004"
FT VARIANT 122
FT /note="S -> N (in dbSNP:rs200783306)"
FT /evidence="ECO:0000269|PubMed:9278324"
FT /id="VAR_017005"
FT VARIANT 171
FT /note="Q -> H (in dbSNP:rs557014003)"
FT /evidence="ECO:0000269|PubMed:28087737"
FT /id="VAR_079582"
FT VARIANT 205
FT /note="W -> Q (requires 2 nucleotide substitutions;
FT dbSNP:rs1063805)"
FT /evidence="ECO:0000269|PubMed:9278324"
FT /id="VAR_017006"
FT VARIANT 400
FT /note="Y -> F (in dbSNP:rs8105096)"
FT /id="VAR_017009"
FT VARIANT 400
FT /note="Y -> H (in dbSNP:rs1052992)"
FT /id="VAR_017008"
FT VARIANT 400
FT /note="Y -> R (requires 2 nucleotide substitutions)"
FT /evidence="ECO:0000269|PubMed:9548455, ECO:0000269|Ref.3"
FT /id="VAR_017007"
FT VARIANT 405
FT /note="H -> Y (in dbSNP:rs1132604)"
FT /evidence="ECO:0000269|PubMed:9548455"
FT /id="VAR_017010"
FT VARIANT 539
FT /note="Q -> H (in dbSNP:rs1053002)"
FT /evidence="ECO:0000269|PubMed:9548455"
FT /id="VAR_017012"
FT VARIANT 574
FT /note="V -> A (in dbSNP:rs1053008)"
FT /evidence="ECO:0000269|PubMed:9548455"
FT /id="VAR_017013"
FT CONFLICT 53
FT /note="Q -> L (in Ref. 1; AAB68668 and 2; AAB87667)"
FT /evidence="ECO:0000305"
FT CONFLICT 61
FT /note="H -> D (in Ref. 1; AAB68668 and 2; AAB87667)"
FT /evidence="ECO:0000305"
FT CONFLICT 115
FT /note="M -> L (in Ref. 1; AAB68668 and 2; AAB87667)"
FT /evidence="ECO:0000305"
FT CONFLICT 120
FT /note="A -> F (in Ref. 1; AAB68668)"
FT /evidence="ECO:0000305"
FT CONFLICT 149
FT /note="G -> R (in Ref. 2; AAB87667)"
FT /evidence="ECO:0000305"
FT CONFLICT 175
FT /note="R -> G (in Ref. 1; AAB68668 and 2; AAB87667)"
FT /evidence="ECO:0000305"
FT CONFLICT 187
FT /note="T -> N (in Ref. 1; AAB68668, 2; AAB87667 and 3;
FT AAP30716)"
FT /evidence="ECO:0000305"
FT CONFLICT 201
FT /note="T -> M (in Ref. 1; AAB68668 and 2; AAB87667)"
FT /evidence="ECO:0000305"
FT CONFLICT 205
FT /note="W -> R (in Ref. 2; AAB87667)"
FT /evidence="ECO:0000305"
FT CONFLICT 252
FT /note="N -> D (in Ref. 1; AAB68668 and 2; AAB87667)"
FT /evidence="ECO:0000305"
FT CONFLICT 263
FT /note="D -> A (in Ref. 3; AAP30716)"
FT /evidence="ECO:0000305"
FT CONFLICT 268
FT /note="P -> S (in Ref. 3; AAP30716)"
FT /evidence="ECO:0000305"
FT CONFLICT 290
FT /note="N -> H (in Ref. 1; AAB68668)"
FT /evidence="ECO:0000305"
FT CONFLICT 409
FT /note="H -> F (in Ref. 1; AAB68668)"
FT /evidence="ECO:0000305"
FT CONFLICT 417
FT /note="V -> M (in Ref. 1; AAB68668)"
FT /evidence="ECO:0000305"
FT CONFLICT 525
FT /note="R -> G (in Ref. 2; AAB87667)"
FT /evidence="ECO:0000305"
FT CONFLICT 561
FT /note="S -> P (in Ref. 2; AAB87667)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 631 AA; 69386 MW; 595B1BD5283A7E3E CRC64;
MTPALTALLC LGLSLGPRTR VQAGPFPKPT LWAEPGSVIS WGSPVTIWCQ GSQEAQEYRL
HKEGSPEPLD RNNPLEPKNK ARFSIPSMTE HHAGRYRCHY YSSAGWSEPS DPLEMVMTGA
YSKPTLSALP SPVVASGGNM TLRCGSQKGY HHFVLMKEGE HQLPRTLDSQ QLHSRGFQAL
FPVGPVTPSH RWRFTCYYYY TNTPWVWSHP SDPLEILPSG VSRKPSLLTL QGPVLAPGQS
LTLQCGSDVG YNRFVLYKEG ERDFLQRPGQ QPQAGLSQAN FTLGPVSPSN GGQYRCYGAH
NLSSEWSAPS DPLNILMAGQ IYDTVSLSAQ PGPTVASGEN VTLLCQSWWQ FDTFLLTKEG
AAHPPLRLRS MYGAHKYQAE FPMSPVTSAH AGTYRCYGSY SSNPHLLSHP SEPLELVVSG
HSGGSSLPPT GPPSTPGLGR YLEVLIGVSV AFVLLLFLLL FLLLRRQRHS KHRTSDQRKT
DFQRPAGAAE TEPKDRGLLR RSSPAADVQE ENLYAAVKDT QSEDRVELDS QSPHDEDPQA
VTYAPVKHSS PRREMASPPS SLSGEFLDTK DRQVEEDRQM DTEAAASEAS QDVTYAQLHS
LTLRRKATEP PPSQEGEPPA EPSIYATLAI H
