Reviewed, UniProtKB/Swiss-Prot Q6GTX8 (LAIR1_HUMAN)

Names and origin

Protein names

Recommended name:
    Leukocyte-associated immunoglobulin-like receptor 1
      Short name=LAIR-1
      Short name=hLAIR1
Alternative name(s):
    CD_antigen=CD305

Gene names

Name:	LAIR1
Synonyms:	CD305

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	287 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	Functions as an inhibitory receptor that plays a constitutive negative regulatory role on cytolytic function of natural killer (NK) cells, B-cells and T-cells. Activation by Tyr phosphorylation results in recruitment and activation of the phosphatases PTPN6 and PTPN11. It also reduces the increase of intracellular calcium evoked by B-cell receptor ligation. May also play its inhibitory role independently of SH2-containing phosphatases. Modulates cytokine production in CD4+ T-cells, downregulating IL2 and IFNG production while inducing secretion of transforming growth factor beta. Down-regulates also IgG and IgE production in B-cells as well as IL8, IL10 and TNF secretion. Inhibits proliferation and induces apoptosis in myeloid leukemia cell lines as well as prevents nuclear translocation of NF-kappa-B p65 subunit/RELA and phosphorylation of I-kappa-B alpha/CHUK in these cells. Inhibits the differentiation of peripheral blood precursors towards dendritic cells. Ref.1 Ref.2 Ref.3 Ref.6 Ref.8 Ref.9 Ref.10 Ref.14 Ref.15 Ref.16
Subunit structure	Interacts with SH2 domains of tyrosine-protein phosphatases PTPN6 and PTPN11. The interaction with PTPN6 is constitutive. Interacts with the SH2 domain of CSK. Ref.1 Ref.3 Ref.9 Ref.16
Subcellular location	Cell membrane; Single-pass type I membrane protein. Ref.1 Ref.2 Ref.9
Tissue specificity	Expressed on the majority of peripheral mononuclear cells, including natural killer (NK) cells, T-cells, B-cells, monocytes, and dendritic cells. Highly expressed in naive T-cells and B-cells but no expression on germinal center B-cells. Abnormally low expression in naive B-cells from HIV-1 infected patients. Very low expression in NK cells from a patient with chronic active Epstein-Barr virus infection. Ref.15 Ref.7 Ref.12 Ref.13
Developmental stage	Complete loss of expression when naive B-cells proliferates and differentiates into Ig-producing plasma cells under in vitro stimulation. Ref.7
Induction	By T-cell receptor stimulation in a process that requires p38 MAP kinase and ERK signaling. Ref.15
Domain	ITIM (immunoreceptor tyrosine-based inhibitor motif) motif is a cytoplasmic motif present in 2 copies in the intracellular part of LAIR1. When phosphorylated, ITIM motif can bind the SH2 domain of several SH2-containing phosphatases, leading to down-regulation of cell activation. Ref.1
Post-translational modification	Phosphorylation at Tyr-251 and Tyr-281 activates it. May be phosphorylated by LCK. N-glycosylated. Ref.1
Sequence similarities	Contains 1 Ig-like C2-type (immunoglobulin-like) domain.

Ontologies

Keywords
Biological process	Immune response
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Signal Transmembrane
Molecular function	Receptor
PTM	Glycoprotein Phosphoprotein
Gene Ontology (GO)
Biological process	immune response Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	protein binding Inferred from physical interaction. Source: UniProtKB receptor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q6GTX8-1)

Also known as: LAIR-1a;

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: Q6GTX8-2)

Also known as: LAIR-1b;

The sequence of this isoform differs from the canonical sequence as follows:
     122-138: Missing.

Notes: Functions as an inhibitory receptor in NK cells and T-cells.

Isoform 3 (identifier: Q6GTX8-3)

Also known as: LAIR-1c;

The sequence of this isoform differs from the canonical sequence as follows:
     23-23: Missing.
     122-138: Missing.

Isoform 4 (identifier: Q6GTX8-4)

Also known as: LAIR-1d;

The sequence of this isoform differs from the canonical sequence as follows:
     210-287: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 287	266	Leukocyte-associated immunoglobulin-like receptor 1		PRO_0000250682
Regions
	Topological domain	22 – 165	144	Extracellular Potential
	Transmembrane	166 – 186	21	Potential
	Topological domain	187 – 287	101	Cytoplasmic Potential
	Domain	29 – 117	89	Ig-like C2-type
	Motif	249 – 254	6	ITIM motif 1
	Motif	279 – 284	6	ITIM motif 2
Amino acid modifications
	Modified residue	251	1	Phosphotyrosine
	Modified residue	281	1	Phosphotyrosine
	Glycosylation	69	1	N-linked (GlcNAc...) Potential
	Disulfide bond	49 ↔ 101		By similarity
Natural variations
	Alternative sequence	23	1	Missing in isoform 3.		VSP_020710
	Alternative sequence	122 – 138	17	Missing in isoform 2 and isoform 3.		VSP_020711
	Alternative sequence	210 – 287	78	Missing in isoform 4.		VSP_020712
	Natural variant	63	1	E → D: dbSNP rs3745442.		VAR_027598
Experimental info
	Mutagenesis	251	1	Y → F: Reduced tyrosine phosphorylation and loss of binding to PTPN6 and CSK as well as complete loss of inhibitory activity. Loss of phosphorylation and of inhibition of calcium mobilization; when associated with F-281 Ref.3 Ref.16 Ref.11
	Mutagenesis	281	1	Y → F: Reduced tyrosine phosphorylation and loss of binding to PTPN6. Partial inhibition of cytotoxic activity Ref.3 Ref.16 Ref.11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (LAIR-1a) [UniParc]. Last modified July 19, 2004. Version 1. Checksum: 752EFB2FCC29B8E8	FASTA	287	31,412
	10 20 30 40 50 60 MSPHPTALLG LVLCLAQTIH TQEEDLPRPS ISAEPGTVIP LGSHVTFVCR GPVGVQTFRL 70 80 90 100 110 120 ERESRSTYND TEDVSQASPS ESEARFRIDS VSEGNAGPYR CIYYKPPKWS EQSDYLELLV 130 140 150 160 170 180 KETSGGPDSP DTEPGSSAGP TQRPSDNSHN EHAPASQGLK AEHLYILIGV SVVFLFCLLL 190 200 210 220 230 240 LVLFCLHRQN QIKQGPPRSK DEEQKPQQRP DLAVDVLERT ADKATVNGLP EKDRETDTSA 250 260 270 280 LAAGSSQEVT YAQLDHWALT QRTARAVSPQ STKPMAESIT YAAVARH
	Isoform 2 (LAIR-1b). Checksum: 8F7106914E4B4347		270	29,840
	10 20 30 40 50 60 MSPHPTALLG LVLCLAQTIH TQEEDLPRPS ISAEPGTVIP LGSHVTFVCR GPVGVQTFRL 70 80 90 100 110 120 ERESRSTYND TEDVSQASPS ESEARFRIDS VSEGNAGPYR CIYYKPPKWS EQSDYLELLV 130 140 150 160 170 180 KGPTQRPSDN SHNEHAPASQ GLKAEHLYIL IGVSVVFLFC LLLLVLFCLH RQNQIKQGPP 190 200 210 220 230 240 RSKDEEQKPQ QRPDLAVDVL ERTADKATVN GLPEKDRETD TSALAAGSSQ EVTYAQLDHW 250 260 270 ALTQRTARAV SPQSTKPMAE SITYAAVARH
	Isoform 3 (LAIR-1c). Checksum: CC0246DC14189301		269	29,710
	10 20 30 40 50 60 MSPHPTALLG LVLCLAQTIH TQEDLPRPSI SAEPGTVIPL GSHVTFVCRG PVGVQTFRLE 70 80 90 100 110 120 RESRSTYNDT EDVSQASPSE SEARFRIDSV SEGNAGPYRC IYYKPPKWSE QSDYLELLVK 130 140 150 160 170 180 GPTQRPSDNS HNEHAPASQG LKAEHLYILI GVSVVFLFCL LLLVLFCLHR QNQIKQGPPR 190 200 210 220 230 240 SKDEEQKPQQ RPDLAVDVLE RTADKATVNG LPEKDRETDT SALAAGSSQE VTYAQLDHWA 250 260 LTQRTARAVS PQSTKPMAES ITYAAVARH
	Isoform 4 (LAIR-1d). Checksum: 080127D8FC665567		209	23,049
	10 20 30 40 50 60 MSPHPTALLG LVLCLAQTIH TQEEDLPRPS ISAEPGTVIP LGSHVTFVCR GPVGVQTFRL 70 80 90 100 110 120 ERESRSTYND TEDVSQASPS ESEARFRIDS VSEGNAGPYR CIYYKPPKWS EQSDYLELLV 130 140 150 160 170 180 KETSGGPDSP DTEPGSSAGP TQRPSDNSHN EHAPASQGLK AEHLYILIGV SVVFLFCLLL 190 200 LVLFCLHRQN QIKQGPPRSK DEEQKPQQR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"LAIR-1, a novel inhibitory receptor expressed on human mononuclear leukocytes." Meyaard L., Adema G.J., Chang C., Woollatt E., Sutherland G.R., Lanier L.L., Phillips J.H. Immunity 7:283-290(1997) [PubMed: 9285412] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), GLYCOSYLATION, SUBCELLULAR LOCATION, DOMAIN ITIM MOTIF, INTERACTION WITH PTPN6 AND PTPN11, FUNCTION.
[2]	"Leukocyte-associated Ig-like receptor-1 functions as an inhibitory receptor on cytotoxic T cells." Meyaard L., Hurenkamp J., Clevers H., Lanier L.L., Phillips J.H. J. Immunol. 162:5800-5804(1999) [PubMed: 10229813] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION.
[3]	"Identification and characterization of leukocyte-associated Ig-like receptor-1 as a major anchor protein of tyrosine phosphatase SHP-1 in hematopoietic cells." Xu M.-J., Zhao R., Zhao Z.J. J. Biol. Chem. 275:17440-17446(2000) [PubMed: 10764762] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), FUNCTION, PHOSPHORYLATION AT TYR-251 AND TYR-281, MUTAGENESIS OF TYR-251 AND TYR-281, INTERACTION WITH PTPN6.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Pancreas.
[6]	"p40/LAIR-1 regulates the differentiation of peripheral blood precursors to dendritic cells induced by granulocyte-monocyte colony-stimulating factor." Poggi A., Tomasello E., Ferrero E., Zocchi M.R., Moretta L. Eur. J. Immunol. 28:2086-2091(1998) [PubMed: 9692876] [Abstract] Cited for: FUNCTION.
[7]	"Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is differentially expressed during human B cell differentiation and inhibits B cell receptor-mediated signaling." van der Vuurst de Vries A.-R., Clevers H., Logtenberg T., Meyaard L. Eur. J. Immunol. 29:3160-3167(1999) [PubMed: 10540327] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[8]	"Engagement of the leukocyte-associated Ig-like receptor-1 induces programmed cell death and prevents NF-kappaB nuclear translocation in human myeloid leukemias." Poggi A., Pellegatta F., Leone B.E., Moretta L., Zocchi M.R. Eur. J. Immunol. 30:2751-2758(2000) [PubMed: 11069054] [Abstract] Cited for: FUNCTION.
[9]	"Constitutive association of SHP-1 with leukocyte-associated Ig-like receptor-1 in human T cells." Sathish J.G., Johnson K.G., Fuller K.J., LeRoy F.G., Meyaard L., Sims M.J., Matthews R.J. J. Immunol. 166:1763-1770(2001) [PubMed: 11160222] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PTPN6, FUNCTION.
[10]	"Surface density expression of the leukocyte-associated Ig-like receptor-1 is directly related to inhibition of human T-cell functions." Saverino D., Fabbi M., Merlo A., Ravera G., Grossi C.E., Ciccone E. Hum. Immunol. 63:534-546(2002) [PubMed: 12072189] [Abstract] Cited for: FUNCTION.
[11]	"Differential contribution of the immunoreceptor tyrosine-based inhibitory motifs of human leukocyte-associated Ig-like receptor-1 to inhibitory function and phosphatase recruitment." Verbrugge A., de Ruiter T., Clevers H., Meyaard L. Int. Immunol. 15:1349-1358(2003) [PubMed: 14565933] [Abstract] Cited for: MUTAGENESIS OF TYR-251 AND TYR-281.
[12]	"Chronic active Epstein-Barr virus infection associated with low expression of leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) on natural killer cells." Aoukaty A., Lee I.-F., Wu J., Tan R. J. Clin. Immunol. 23:141-145(2003) [PubMed: 12757266] [Abstract] Cited for: TISSUE SPECIFICITY.
[13]	"Mechanisms of hypergammaglobulinemia and impaired antigen-specific humoral immunity in HIV-1 infection." De Milito A., Nilsson A., Titanji K., Thorstensson R., Reizenstein E., Narita M., Grutzmeier S., Sonnerborg A., Chiodi F. Blood 103:2180-2186(2004) [PubMed: 14604962] [Abstract] Cited for: TISSUE SPECIFICITY.
[14]	"Inhibitory receptors CD85j, LAIR-1, and CD152 down-regulate immunoglobulin and cytokine production by human B lymphocytes." Merlo A., Tenca C., Fais F., Battini L., Ciccone E., Grossi C.E., Saverino D. Clin. Diagn. Lab. Immunol. 12:705-712(2005) [PubMed: 15939744] [Abstract] Cited for: FUNCTION.
[15]	"The inhibitory leukocyte-associated Ig-like receptor-1 (LAIR-1) is expressed at high levels by human naive T cells and inhibits TCR mediated activation." Maasho K., Masilamani M., Valas R., Basu S., Coligan J.E., Borrego F. Mol. Immunol. 42:1521-1530(2005) [PubMed: 15950745] [Abstract] Cited for: FUNCTION, INDUCTION, TISSUE SPECIFICITY.
[16]	"Leukocyte-associated Ig-like receptor-1 has SH2 domain-containing phosphatase-independent function and recruits C-terminal Src kinase." Verbrugge A., Rijkers E.S.K., de Ruiter T., Meyaard L. Eur. J. Immunol. 36:190-198(2006) [PubMed: 16380958] [Abstract] Cited for: INTERACTION WITH CSK, MUTAGENESIS OF TYR-251 AND TYR-281, FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF013249 mRNA. Translation: AAB69324.1. AF109683 mRNA. Translation: AAF17107.1. AF251509 mRNA. Translation: AAF71274.2. AF251510 mRNA. Translation: AAF71275.2. CR542051 mRNA. Translation: CAG46848.1. BC027899 mRNA. Translation: AAH27899.1.
RefSeq	NP_002278.1. NP_068352.1.
UniGene	Hs.572535
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6GTX8. 1 interaction.
PTM databases
PhosphoSite	Q6GTX8.
Proteomic databases
PRIDE	Q6GTX8.
Genome annotation databases
Ensembl	ENSG00000167613. Homo sapiens. [Contig view]
GeneID	3903.
KEGG	hsa:3903.
Organism-specific databases
GeneCards	GC19M059557.
HGNC	HGNC:6477. LAIR1.
HPA	HPA011155.
MIM	602992. gene.
PharmGKB	PA30266.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q6GTX8.
Gene expression databases
ArrayExpress	Q6GTX8.
CleanEx	HS_LAIR1.
GermOnline	ENSG00000167613. Homo sapiens.
Family and domain databases
InterPro	IPR007110. Ig-like. IPR013783. Ig-like_fold. IPR003599. Ig_sub. [Graphical view]
Gene3D	G3DSA:2.60.40.10. Ig-like_fold. 1 hit.
SMART	SM00409. IG. 1 hit. [Graphical view]
PROSITE	PS50835. IG_LIKE. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	15321.
SOURCE	Search...

Entry information

Entry name

LAIR1_HUMAN

Accession

Primary (citable) accession number: Q6GTX8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 3, 2006
Last sequence update:	July 19, 2004
Last modified:	December 16, 2008
This is version 42 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)