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 13-FEB-2019, entry version 164. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ASN-122 AND RP 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 RT members that possess immunoreceptor tyrosine-based inhibition motifs RT and homology 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; RP ARG-400; 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 RT which bind to MHC class I molecules."; RL J. Immunol. 159:5192-5196(1997). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 2), RP AND VARIANT ARG-400. RA Cuillerier B., Bahram S.; RT "Genomics and diversity of the immunoglobulin-like transcript 5 RT 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., RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M., RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., RA 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 RT human leukocyte receptor cluster."; RL Immunogenetics 51:703-713(2000). RN [6] RP ERRATUM. 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 RT anencephaly in 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- CC cell activation by recruiting phosphatases to its immunoreceptor CC tyrosine-based inhibitor motifs (ITIM). CC {ECO:0000250|UniProtKB:P97484}. CC -!- SUBUNIT: Interacts with LYN, PTPN6/SHP-1 and PTPN11/SHP-2. CC {ECO:0000250|UniProtKB:P97484}. CC -!- INTERACTION: CC P05783:KRT18; NbExp=3; IntAct=EBI-2830524, EBI-297888; CC P05787:KRT8; NbExp=3; IntAct=EBI-2830524, EBI-297852; CC 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 Note=No experimental confirmation available.; 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 CC to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). CC This motif is involved in modulation of cellular responses. The CC phosphorylated ITIM motif can bind the SH2 domain of several SH2- CC containing phosphatases, including PTPN6/SHP-1, resulting in the CC dephosphorylation of the downstream protein kinases SYK and BTK. CC {ECO:0000250|UniProtKB:P97484}. CC -!- PTM: Phosphorylated on tyrosine residues by LYN. Phosphorylation CC at Tyr-595 and Tyr-625 is important for interaction with CC PTPN6/SHP-1 and PTPN11/SHP-2. {ECO:0000250|UniProtKB:P97484}. CC -!- MISCELLANEOUS: Belongs to the leukocyte receptor cluster (LRC) CC present on 19q13.4. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- 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; 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 UniGene; Hs.631592; -. DR UniGene; Hs.688335; -. DR ProteinModelPortal; O75022; -. DR SMR; O75022; -. DR IntAct; O75022; 7. DR STRING; 9606.ENSP00000245620; -. DR iPTMnet; O75022; -. DR PhosphoSitePlus; O75022; -. DR BioMuta; LILRB3; -. DR jPOST; O75022; -. DR PaxDb; O75022; -. DR PeptideAtlas; O75022; -. DR PRIDE; O75022; -. DR ProteomicsDB; 49696; -. DR ProteomicsDB; 49697; -. [O75022-2] DR ProteomicsDB; 49698; -. [O75022-3] DR Ensembl; ENST00000245620; ENSP00000245620; ENSG00000204577. DR Ensembl; ENST00000391750; ENSP00000375630; ENSG00000204577. DR Ensembl; ENST00000611086; ENSP00000483625; ENSG00000274587. [O75022-1] DR Ensembl; ENST00000613698; ENSP00000479234; ENSG00000275019. DR Ensembl; ENST00000621210; ENSP00000484925; ENSG00000275019. DR GeneID; 102725035; -. DR GeneID; 107987462; -. DR KEGG; hsa:102725035; -. DR KEGG; hsa:107987462; -. DR UCSC; uc032icw.2; human. [O75022-1] DR DisGeNET; 102725035; -. DR DisGeNET; 107987462; -. DR DisGeNET; 11025; -. DR EuPathDB; HostDB:ENSG00000204577.11; -. DR GeneCards; LILRB3; -. DR H-InvDB; HIX0015438; -. DR HGNC; HGNC:6607; LILRB3. DR MIM; 604820; gene. DR neXtProt; NX_O75022; -. DR PharmGKB; PA30381; -. DR eggNOG; ENOG410IKJD; Eukaryota. DR eggNOG; ENOG41116BR; LUCA. DR HOGENOM; HOG000234395; -. DR HOVERGEN; HBG074353; -. DR InParanoid; O75022; -. DR KO; K06512; -. DR OrthoDB; 1000446at2759; -. DR PhylomeDB; O75022; -. DR TreeFam; TF336644; -. DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR ChiTaRS; LILRB3; human. DR PRO; PR:O75022; -. DR Proteomes; UP000005640; Chromosome 19. DR Bgee; ENSG00000204577; Expressed in 225 organ(s), highest expression level in blood. 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; TAS:Reactome. DR GO; GO:0030667; C:secretory granule membrane; TAS:Reactome. 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:0006952; P:defense response; TAS:ProtInc. DR GO; GO:0045671; P:negative regulation of osteoclast differentiation; IDA:UniProtKB. DR GO; GO:0043312; P:neutrophil degranulation; TAS:Reactome. 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; KW Complete proteome; Disulfide bond; Glycoprotein; Immunity; KW Immunoglobulin domain; Membrane; Phosphoprotein; Polymorphism; KW Receptor; Reference proteome; Repeat; Signal; Transmembrane; KW Transmembrane helix. FT SIGNAL 1 23 {ECO:0000255}. FT CHAIN 24 631 Leukocyte immunoglobulin-like receptor FT subfamily B member 3. FT /FTId=PRO_0000014822. FT TOPO_DOM 24 443 Extracellular. {ECO:0000255}. FT TRANSMEM 444 464 Helical. {ECO:0000255}. FT TOPO_DOM 465 631 Cytoplasmic. {ECO:0000255}. FT DOMAIN 42 100 Ig-like C2-type 1. FT DOMAIN 111 229 Ig-like C2-type 2. FT DOMAIN 225 314 Ig-like C2-type 3. FT DOMAIN 338 419 Ig-like C2-type 4. FT MOTIF 512 517 ITIM motif 1. FT MOTIF 593 598 ITIM motif 2. FT MOTIF 623 628 ITIM motif 3. FT MOD_RES 595 595 Phosphotyrosine; by LYN. FT {ECO:0000250|UniProtKB:P97484}. FT MOD_RES 625 625 Phosphotyrosine; by LYN. FT {ECO:0000250|UniProtKB:P97484}. FT CARBOHYD 139 139 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 280 280 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 301 301 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 340 340 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 49 98 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 144 196 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 245 296 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 345 396 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT VAR_SEQ 437 437 G -> GGPEDQPLNPPGSGPQNG (in isoform 2). FT {ECO:0000305}. FT /FTId=VSP_008459. FT VAR_SEQ 530 530 S -> SQ (in isoform 3). {ECO:0000305}. FT /FTId=VSP_040126. FT VARIANT 21 21 V -> M (in dbSNP:rs1132588). FT /FTId=VAR_017001. FT VARIANT 59 59 R -> Q (in dbSNP:rs678876). FT {ECO:0000269|PubMed:9548455}. FT /FTId=VAR_017002. FT VARIANT 69 69 L -> W (in dbSNP:rs80077296). FT /FTId=VAR_017003. FT VARIANT 90 90 E -> Q (in dbSNP:rs1052963). FT {ECO:0000269|PubMed:9548455}. FT /FTId=VAR_017004. FT VARIANT 122 122 S -> N (in dbSNP:rs200783306). FT {ECO:0000269|PubMed:9278324}. FT /FTId=VAR_017005. FT VARIANT 171 171 Q -> H (in dbSNP:rs557014003). FT {ECO:0000269|PubMed:28087737}. FT /FTId=VAR_079582. FT VARIANT 205 205 W -> Q (requires 2 nucleotide FT substitutions; dbSNP:rs1063805). FT {ECO:0000269|PubMed:9278324}. FT /FTId=VAR_017006. FT VARIANT 400 400 Y -> F (in dbSNP:rs8105096). FT /FTId=VAR_017009. FT VARIANT 400 400 Y -> H (in dbSNP:rs1052992). FT /FTId=VAR_017008. FT VARIANT 400 400 Y -> R (requires 2 nucleotide FT substitutions). FT {ECO:0000269|PubMed:9548455, FT ECO:0000269|Ref.3}. FT /FTId=VAR_017007. FT VARIANT 405 405 H -> Y (in dbSNP:rs1132604). FT {ECO:0000269|PubMed:9548455}. FT /FTId=VAR_017010. FT VARIANT 539 539 Q -> H (in dbSNP:rs1053002). FT {ECO:0000269|PubMed:9548455}. FT /FTId=VAR_017012. FT VARIANT 574 574 V -> A (in dbSNP:rs1053008). FT {ECO:0000269|PubMed:9548455}. FT /FTId=VAR_017013. FT CONFLICT 53 53 Q -> L (in Ref. 1; AAB68668 and 2; FT AAB87667). {ECO:0000305}. FT CONFLICT 61 61 H -> D (in Ref. 1; AAB68668 and 2; FT AAB87667). {ECO:0000305}. FT CONFLICT 115 115 M -> L (in Ref. 1; AAB68668 and 2; FT AAB87667). {ECO:0000305}. FT CONFLICT 120 120 A -> F (in Ref. 1; AAB68668). FT {ECO:0000305}. FT CONFLICT 149 149 G -> R (in Ref. 2; AAB87667). FT {ECO:0000305}. FT CONFLICT 175 175 R -> G (in Ref. 1; AAB68668 and 2; FT AAB87667). {ECO:0000305}. FT CONFLICT 187 187 T -> N (in Ref. 1; AAB68668, 2; AAB87667 FT and 3; AAP30716). {ECO:0000305}. FT CONFLICT 201 201 T -> M (in Ref. 1; AAB68668 and 2; FT AAB87667). {ECO:0000305}. FT CONFLICT 205 205 W -> R (in Ref. 2; AAB87667). FT {ECO:0000305}. FT CONFLICT 252 252 N -> D (in Ref. 1; AAB68668 and 2; FT AAB87667). {ECO:0000305}. FT CONFLICT 263 263 D -> A (in Ref. 3; AAP30716). FT {ECO:0000305}. FT CONFLICT 268 268 P -> S (in Ref. 3; AAP30716). FT {ECO:0000305}. FT CONFLICT 290 290 N -> H (in Ref. 1; AAB68668). FT {ECO:0000305}. FT CONFLICT 409 409 H -> F (in Ref. 1; AAB68668). FT {ECO:0000305}. FT CONFLICT 417 417 V -> M (in Ref. 1; AAB68668). FT {ECO:0000305}. FT CONFLICT 525 525 R -> G (in Ref. 2; AAB87667). FT {ECO:0000305}. FT CONFLICT 561 561 S -> P (in Ref. 2; AAB87667). FT {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 //