Q8N423 (LIRB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	598 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Adaptive immunity Immunity
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Fc receptor mediated inhibitory signaling pathway Inferred from direct assay Ref.5. Source: UniProtKB 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 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
Cellular_component	cell 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 to plasma membrane Inferred by curator PubMed 14971032. Source: BHF-UCL
Molecular_function	MHC class I protein binding Inferred from direct assay PubMed 18802077Ref.5. Source: UniProtKB eukaryotic cell surface binding Inferred from direct assay PubMed 14971032. Source: BHF-UCL inhibitory MHC class I receptor activity Inferred from direct assay PubMed 20702625. Source: BHF-UCL
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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Potential

Chain

22 – 598

577

Leukocyte immunoglobulin-like receptor subfamily B member 2

PRO_0000014821

Regions

Topological domain

22 – 461

440

Extracellular Potential

Transmembrane

462 – 482

21

Helical; Potential

Topological domain

483 – 598

116

Cytoplasmic Potential

Domain

27 – 110

84

Ig-like C2-type 1

Domain

111 – 229

119

Ig-like C2-type 2

Domain

230 – 318

89

Ig-like C2-type 3

Domain

330 – 419

90

Ig-like C2-type 4

Motif

531 – 536

6

ITIM motif 1

Motif

560 – 565

6

ITIM motif 2

Motif

590 – 595

6

ITIM motif 3

Amino acid modifications

Glycosylation

280

1

N-linked (GlcNAc...) Potential

Glycosylation

301

1

N-linked (GlcNAc...) Potential

Glycosylation

340

1

N-linked (GlcNAc...) Potential

Disulfide bond

49 ↔ 98

By similarity

Disulfide bond

144 ↔ 196

By similarity

Disulfide bond

156 ↔ 166

By similarity

Disulfide bond

245 ↔ 296

Potential

Disulfide bond

345 ↔ 396

Potential

Natural variations

Alternative sequence

437

1

Missing in isoform 2.

VSP_008458

Natural variant

20

1

H → R.
Corresponds to variant rs383369 [ dbSNP | Ensembl ].

VAR_016997

Natural variant

161

1

E → D. Ref.1 Ref.2 Ref.4
Corresponds to variant rs373032 [ dbSNP | Ensembl ].

VAR_016998

Natural variant

235

1

V → M.
Corresponds to variant rs386056 [ dbSNP | Ensembl ].

VAR_047432

Natural variant

300

1

H → Y. Ref.1 Ref.2 Ref.4
Corresponds to variant rs7247538 [ dbSNP | Ensembl ].

VAR_016999

Natural variant

306

1

C → W. Ref.1 Ref.2 Ref.4
Corresponds to variant rs7247451 [ dbSNP | Ensembl ].

VAR_017000

Natural variant

322

1

R → H. Ref.1 Ref.2 Ref.4
Corresponds to variant rs1128646 [ dbSNP | Ensembl ].

VAR_061314

Natural variant

324

1

T → R.
Corresponds to variant rs7247055 [ dbSNP | Ensembl ].

VAR_047433

Natural variant

326

1

F → S.
Corresponds to variant rs7246737 [ dbSNP | Ensembl ].

VAR_047434

Natural variant

349

1

R → G.
Corresponds to variant rs7247025 [ dbSNP | Ensembl ].

VAR_047435

Natural variant

403

1

D → N.
Corresponds to variant rs4993133 [ dbSNP | Ensembl ].

VAR_061315

Experimental info

Sequence conflict

583

1

R → G in AAH36827. Ref.4

Secondary structure

1

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598

Helix Strand Turn

Details...

Beta strand

30 – 35

6

Beta strand

37 – 40

4

Beta strand

45 – 50

6

Beta strand

57 – 63

7

Beta strand

71 – 73

3

Helix

75 – 77

3

Helix

78 – 80

3

Beta strand

82 – 87

6

Turn

90 – 92

3

Beta strand

94 – 102

9

Beta strand

113 – 118

6

Beta strand

125 – 130

6

Beta strand

140 – 158

19

Beta strand

166 – 168

3

Beta strand

176 – 183

8

Beta strand

188 – 190

3

Beta strand

193 – 199

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 2, 2010. Version 4. Checksum: 33E9737AFCAFCE2D	FASTA	598	65,039
	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
	Isoform 2 [UniParc]. Checksum: E6C0FDA134C5F3C3	FASTA	597	64,968
	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 GPISTPGPED QPLTPTGSDP QSGLGRHLGV VIGILVAVVL LLLLLLLLFL 490 500 510 520 530 540 ILRHRRQGKH WTSTQRKADF QHPAGAVGPE PTDRGLQWRS SPAADAQEEN LYAAVKDTQP 550 560 570 580 590 EDGVEMDTRA AASEAPQDVT YAQLHSLTLR RKATEPPPSQ EREPPAEPSI YATLAIH

References

	« Hide 'large scale' referencesShow '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. , 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.

IPI

IPI00376762.
IPI00893900.

RefSeq

NP_001074447.1. NM_001080978.2.
NP_005865.2. NM_005874.3.

UniGene

Hs.655652.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DYP	X-ray	2.50	D	24-219	[»]
2GW5	X-ray	1.80	A	24-220	[»]

ProteinModelPortal

Q8N423.

SMR

Q8N423. Positions 26-419.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-59888N.

IntAct

Q8N423. 3 interactions.

STRING

9606.ENSP00000375629.

PTM databases

PhosphoSite

Q8N423.

Polymorphism databases

DMDM

311033485.

Proteomic databases

PaxDb

Q8N423.

PRIDE

Q8N423.

Protocols and materials databases

DNASU

10288.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000314446; ENSP00000319960; ENSG00000131042.
ENST00000391748; ENSP00000375628; ENSG00000131042.
ENST00000391749; ENSP00000375629; ENSG00000131042.

GeneID

10288.

KEGG

hsa:10288.

UCSC

uc002qfb.3. human.
uc002qfc.3. human.

Organism-specific databases

CTD

10288.

GeneCards

GC19M054777.

HGNC

HGNC:6606. LILRB2.

MIM

604815. gene.

neXtProt

NX_Q8N423.

PharmGKB

PA30380.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG25855.

HOGENOM

HOG000234395.

HOVERGEN

HBG074353.

InParanoid

Q8N423.

KO

K06512.

OMA

CEYSSSE.

PhylomeDB

Q8N423.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q8N423.

Bgee

Q8N423.

CleanEx

HS_LILRB2.

Genevestigator

Q8N423.

GermOnline

ENSG00000131042. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 4 hits.

InterPro

IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
[Graphical view]

SMART

SM00409. IG. 3 hits.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q8N423.

GenomeRNAi

10288.

NextBio

38982.

SOURCE

Search...

Entry information

Entry name

LIRB2_HUMAN

Accession

Primary (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:	April 3, 2013
This is version 112 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.