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Q8N423 (LIRB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Leukocyte immunoglobulin-like receptor subfamily B member 2

Short name=LIR-2
Short name=Leukocyte immunoglobulin-like receptor 2
Alternative name(s):
CD85 antigen-like family member D
Immunoglobulin-like transcript 4
Short name=ILT-4
Monocyte/macrophage immunoglobulin-like receptor 10
Short name=MIR-10
CD_antigen=CD85d
Gene names
Name:LILRB2
Synonyms:ILT4, LIR2, MIR10
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length598 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor for class I MHC antigens. Recognizes a broad spectrum of HLA-A, HLA-B, HLA-C and HLA-G alleles. Involved in the down-regulation of the immune response and the development of tolerance. Competes with CD8A for binding to class I MHC antigens. Inhibits FCGR1A-mediated phosphorylation of cellular proteins and mobilization of intracellular calcium ions. Ref.1 Ref.5 Ref.6 Ref.7

Subunit structure

Binds PTPN6 when phosphorylated. Binds FCGR1A.

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Expressed on monocytes and B-cells, and at lower levels on dendritic cells. Detected at low levels in natural killer (NK) cells. Ref.1 Ref.5

Domain

Contains 3 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.

Post-translational modification

Phosphorylated on tyrosine residues. Dephosphorylated by PTPN6. Ref.5

Sequence similarities

Contains 4 Ig-like C2-type (immunoglobulin-like) domains.

Ontologies

Keywords
   Biological processAdaptive immunity
Immunity
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainImmunoglobulin domain
Repeat
Signal
Transmembrane
Transmembrane helix
   Molecular functionReceptor
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processFc receptor mediated inhibitory signaling pathway

Inferred from direct assay Ref.5. Source: UniProtKB

cell surface receptor signaling pathway

Traceable author statement PubMed 9079806. Source: ProtInc

cell-cell signaling

Traceable author statement PubMed 9382880. Source: ProtInc

cellular defense response

Traceable author statement PubMed 9382880. Source: ProtInc

cellular response to lipopolysaccharide

Inferred from mutant phenotype PubMed 14971032. Source: BHF-UCL

heterotypic cell-cell adhesion

Inferred from direct assay PubMed 19124746. Source: BHF-UCL

immune response

Traceable author statement PubMed 9079806. Source: ProtInc

immune response-inhibiting cell surface receptor signaling pathway

Inferred from direct assay PubMed 20702625. Source: BHF-UCL

negative regulation of T cell proliferation

Inferred from direct assay PubMed 19124746PubMed 20702625. Source: BHF-UCL

negative regulation of antigen processing and presentation

Inferred from direct assay PubMed 19124746. Source: BHF-UCL

negative regulation of calcium ion transport

Inferred from direct assay Ref.5. Source: UniProtKB

positive regulation of T cell proliferation

Inferred from direct assay PubMed 14971032. Source: BHF-UCL

positive regulation of T cell tolerance induction

Inferred from mutant phenotype PubMed 20008523PubMed 20448110. Source: BHF-UCL

positive regulation of interleukin-6 production

Non-traceable author statement PubMed 18550825. Source: BHF-UCL

positive regulation of regulatory T cell differentiation

Inferred from mutant phenotype PubMed 20448110. Source: BHF-UCL

regulation of dendritic cell differentiation

Inferred by curator PubMed 20008523. Source: BHF-UCL

regulation of immune response

Traceable author statement. Source: Reactome

signal transduction

Inferred from direct assay PubMed 20702625. Source: BHF-UCL

   Cellular_componentcell surface

Inferred from direct assay PubMed 14971032. Source: BHF-UCL

cytoplasm

Inferred from direct assay PubMed 19124746. Source: BHF-UCL

extracellular space

Inferred from direct assay PubMed 14971032. Source: BHF-UCL

integral component of plasma membrane

Inferred by curator PubMed 14971032. Source: BHF-UCL

membrane

Traceable author statement PubMed 9079806. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionMHC class I protein binding

Inferred from direct assay PubMed 18802077Ref.5. Source: UniProtKB

MHC class Ib protein binding

Inferred from physical interaction PubMed 20008523. Source: BHF-UCL

cell adhesion molecule binding

Inferred from physical interaction PubMed 19124746. Source: BHF-UCL

inhibitory MHC class I receptor activity

Inferred from direct assay PubMed 20702625. Source: BHF-UCL

protein binding

Inferred from physical interaction PubMed 18802077. Source: UniProtKB

protein phosphatase 1 binding

Inferred from physical interaction Ref.5. Source: UniProtKB

receptor activity

Traceable author statement PubMed 9382880. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8N423-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q8N423-2)

The sequence of this isoform differs from the canonical sequence as follows:
     437-437: Missing.
Note: Alternative use of an acceptor site. No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 598577Leukocyte immunoglobulin-like receptor subfamily B member 2
PRO_0000014821

Regions

Topological domain22 – 461440Extracellular Potential
Transmembrane462 – 48221Helical; Potential
Topological domain483 – 598116Cytoplasmic Potential
Domain27 – 11084Ig-like C2-type 1
Domain111 – 229119Ig-like C2-type 2
Domain230 – 31889Ig-like C2-type 3
Domain330 – 41990Ig-like C2-type 4
Motif531 – 5366ITIM motif 1
Motif560 – 5656ITIM motif 2
Motif590 – 5956ITIM motif 3

Amino acid modifications

Glycosylation2801N-linked (GlcNAc...) Potential
Glycosylation3011N-linked (GlcNAc...) Potential
Glycosylation3401N-linked (GlcNAc...) Potential
Disulfide bond49 ↔ 98 By similarity
Disulfide bond144 ↔ 196 By similarity
Disulfide bond156 ↔ 166 By similarity
Disulfide bond245 ↔ 296 Potential
Disulfide bond345 ↔ 396 Potential

Natural variations

Alternative sequence4371Missing in isoform 2.
VSP_008458
Natural variant201H → R.
Corresponds to variant rs383369 [ dbSNP | Ensembl ].
VAR_016997
Natural variant1611E → D. Ref.1 Ref.2 Ref.4
Corresponds to variant rs373032 [ dbSNP | Ensembl ].
VAR_016998
Natural variant2351V → M.
Corresponds to variant rs386056 [ dbSNP | Ensembl ].
VAR_047432
Natural variant3001H → Y. Ref.1 Ref.2 Ref.4
Corresponds to variant rs7247538 [ dbSNP | Ensembl ].
VAR_016999
Natural variant3061C → W. Ref.1 Ref.2 Ref.4
Corresponds to variant rs7247451 [ dbSNP | Ensembl ].
VAR_017000
Natural variant3221R → H. Ref.1 Ref.2 Ref.4
Corresponds to variant rs1128646 [ dbSNP | Ensembl ].
VAR_061314
Natural variant3241T → R.
Corresponds to variant rs7247055 [ dbSNP | Ensembl ].
VAR_047433
Natural variant3261F → S.
Corresponds to variant rs7246737 [ dbSNP | Ensembl ].
VAR_047434
Natural variant3491R → G.
Corresponds to variant rs7247025 [ dbSNP | Ensembl ].
VAR_047435
Natural variant4031D → N.
Corresponds to variant rs4993133 [ dbSNP | Ensembl ].
VAR_061315

Experimental info

Sequence conflict5831R → G in AAH36827. Ref.4

Secondary structure

.......................................................................... 598
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 2, 2010. Version 4.
Checksum: 33E9737AFCAFCE2D

FASTA59865,039
        10         20         30         40         50         60 
MTPIVTVLIC LGLSLGPRTH VQTGTIPKPT LWAEPDSVIT QGSPVTLSCQ GSLEAQEYRL 

        70         80         90        100        110        120 
YREKKSASWI TRIRPELVKN GQFHIPSITW EHTGRYGCQY YSRARWSELS DPLVLVMTGA 

       130        140        150        160        170        180 
YPKPTLSAQP SPVVTSGGRV TLQCESQVAF GGFILCKEGE EEHPQCLNSQ PHARGSSRAI 

       190        200        210        220        230        240 
FSVGPVSPNR RWSHRCYGYD LNSPYVWSSP SDLLELLVPG VSKKPSLSVQ PGPVVAPGES 

       250        260        270        280        290        300 
LTLQCVSDVG YDRFVLYKEG ERDLRQLPGR QPQAGLSQAN FTLGPVSRSY GGQYRCYGAH 

       310        320        330        340        350        360 
NLSSECSAPS DPLDILITGQ IRGTPFISVQ PGPTVASGEN VTLLCQSWRQ FHTFLLTKAG 

       370        380        390        400        410        420 
AADAPLRLRS IHEYPKYQAE FPMSPVTSAH AGTYRCYGSL NSDPYLLSHP SEPLELVVSG 

       430        440        450        460        470        480 
PSMGSSPPPT GPISTPAGPE DQPLTPTGSD PQSGLGRHLG VVIGILVAVV LLLLLLLLLF 

       490        500        510        520        530        540 
LILRHRRQGK HWTSTQRKAD FQHPAGAVGP EPTDRGLQWR SSPAADAQEE NLYAAVKDTQ 

       550        560        570        580        590 
PEDGVEMDTR AAASEAPQDV TYAQLHSLTL RRKATEPPPS QEREPPAEPS IYATLAIH 

« Hide

Isoform 2 [UniParc].

Checksum: E6C0FDA134C5F3C3
Show »

FASTA59764,968

References

« Hide 'large scale' references
[1]"A family of human lymphoid and myeloid Ig-like receptors, some of which bind to MHC class I molecules."
Borges L., Hsu M.-L., Fanger N., Kubin M., Cosman D.
J. Immunol. 159:5192-5196(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, FUNCTION, VARIANTS ASP-161; TYR-300; TRP-306 AND HIS-322.
Tissue: Dendritic cell and Peripheral blood monocyte.
[2]Canavez F.C.
Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANTS ASP-161; TYR-300; TRP-306 AND HIS-322.
[3]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS ASP-161; TYR-300; TRP-306 AND HIS-322.
Tissue: Peripheral blood leukocyte.
[5]"The MHC class I binding proteins LIR-1 and LIR-2 inhibit Fc receptor-mediated signaling in monocytes."
Fanger N.A., Cosman D., Peterson L., Braddy S.C., Maliszewski C.R., Borges L.
Eur. J. Immunol. 28:3423-3434(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PTPN6 AND FCGR1A, PHOSPHORYLATION, TISSUE SPECIFICITY, FUNCTION.
[6]"Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4."
Chang C.C., Ciubotariu R., Manavalan J.S., Yuan J., Colovai A.I., Piazza F., Lederman S., Colonna M., Cortesini R., Dalla-Favera R., Suciu-Foca N.
Nat. Immunol. 3:237-243(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Human inhibitory receptors Ig-like transcript 2 (ILT2) and ILT4 compete with CD8 for MHC class I binding and bind preferentially to HLA-G."
Shiroishi M., Tsumoto K., Amano K., Shirakihara Y., Colonna M., Braud V.M., Allan D.S.J., Makadzange A., Rowland-Jones S., Willcox B.E., Jones E.Y., van der Merwe P.A., Kumagai I., Maenaka K.
Proc. Natl. Acad. Sci. U.S.A. 100:8856-8861(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TYPE I MHC ALLELES, FUNCTION.
[8]"Crystal structure of LIR-2 (ILT4) at 1.8 A: differences from LIR-1 (ILT2) in regions implicated in the binding of the human cytomegalovirus class I MHC homolog UL18."
Willcox B.E., Thomas L.M., Chapman T.L., Heikema A.P., West A.P. Jr., Bjorkman P.J.
BMC Struct. Biol. 2:6-6(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 22-219.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF025528 mRNA. Translation: AAB87662.1.
AF283986 mRNA. Translation: AAL36990.1.
AF283987 mRNA. Translation: AAL36991.1.
AC010518 Genomic DNA. No translation available.
BC036827 mRNA. Translation: AAH36827.1.
UniGeneHs.655652.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2DYPX-ray2.50D24-219[»]
2GW5X-ray1.80A24-219[»]
4LLAX-ray2.50A/B/C222-419[»]
ProteinModelPortalQ8N423.
SMRQ8N423. Positions 26-419.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115577. 5 interactions.
DIPDIP-59888N.
IntActQ8N423. 3 interactions.
STRING9606.ENSP00000375629.

PTM databases

PhosphoSiteQ8N423.

Polymorphism databases

DMDM311033485.

Proteomic databases

PaxDbQ8N423.
PRIDEQ8N423.

Protocols and materials databases

DNASU10288.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000314446; ENSP00000319960; ENSG00000131042. [Q8N423-2]
ENST00000391748; ENSP00000375628; ENSG00000131042. [Q8N423-2]
ENST00000391749; ENSP00000375629; ENSG00000131042. [Q8N423-1]
KEGGhsa:10288.
UCSCuc002qfb.3. human. [Q8N423-1]
uc002qfc.3. human. [Q8N423-2]

Organism-specific databases

CTD10288.
GeneCardsGC19M054777.
HGNCHGNC:6606. LILRB2.
MIM604815. gene.
neXtProtNX_Q8N423.
PharmGKBPA30380.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG25855.
HOGENOMHOG000234395.
HOVERGENHBG074353.
InParanoidQ8N423.
KOK06512.
OMAKWIPREL.
OrthoDBEOG7R56S3.
PhylomeDBQ8N423.
TreeFamTF336644.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressQ8N423.
BgeeQ8N423.
CleanExHS_LILRB2.
GenevestigatorQ8N423.

Family and domain databases

Gene3D2.60.40.10. 4 hits.
InterProIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
[Graphical view]
SMARTSM00409. IG. 3 hits.
[Graphical view]
PROSITEPS50835. IG_LIKE. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ8N423.
GeneWikiLILRB2.
GenomeRNAi10288.
NextBio38982.
PROQ8N423.
SOURCESearch...

Entry information

Entry nameLIRB2_HUMAN
AccessionPrimary (citable) accession number: Q8N423
Secondary accession number(s): O75017, Q8NHJ7, Q8NHJ8
Entry history
Integrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: November 2, 2010
Last modified: July 9, 2014
This is version 122 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries