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Protein

Leukocyte-associated immunoglobulin-like receptor 1

Gene

LAIR1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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, down-regulating 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.10 Publications

GO - Biological processi

Keywordsi

Molecular functionReceptor
Biological processAdaptive immunity, Immunity

Enzyme and pathway databases

ReactomeiR-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-6798695 Neutrophil degranulation

Names & Taxonomyi

Protein namesi
Recommended name:
Leukocyte-associated immunoglobulin-like receptor 1
Short name:
LAIR-1
Short name:
hLAIR1
Alternative name(s):
CD_antigen: CD305
Gene namesi
Name:LAIR1
Synonyms:CD305
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000167613.15
HGNCiHGNC:6477 LAIR1
MIMi602992 gene
neXtProtiNX_Q6GTX8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini22 – 165ExtracellularSequence analysisAdd BLAST144
Transmembranei166 – 186HelicalSequence analysisAdd BLAST21
Topological domaini187 – 287CytoplasmicSequence analysisAdd BLAST101

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi251Y → 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. 3 Publications1
Mutagenesisi281Y → F: Reduced tyrosine phosphorylation and loss of binding to PTPN6. Partial inhibition of cytotoxic activity. 3 Publications1

Organism-specific databases

DisGeNETi3903
PharmGKBiPA30266

Polymorphism and mutation databases

BioMutaiLAIR1
DMDMi74736490

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000025068222 – 287Leukocyte-associated immunoglobulin-like receptor 1Add BLAST266

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi49 ↔ 1011 Publication
Glycosylationi69N-linked (GlcNAc...) asparagine1 Publication1
Modified residuei251Phosphotyrosine1 Publication1
Modified residuei281Phosphotyrosine1 Publication1

Post-translational modificationi

Phosphorylation at Tyr-251 and Tyr-281 activates it. May be phosphorylated by LCK.1 Publication
N-glycosylated.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ6GTX8
MaxQBiQ6GTX8
PaxDbiQ6GTX8
PeptideAtlasiQ6GTX8
PRIDEiQ6GTX8

PTM databases

iPTMnetiQ6GTX8
PhosphoSitePlusiQ6GTX8
SwissPalmiQ6GTX8

Expressioni

Tissue specificityi

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.4 Publications

Developmental stagei

Complete loss of expression when naive B-cells proliferates and differentiates into Ig-producing plasma cells under in vitro stimulation.1 Publication

Inductioni

By T-cell receptor stimulation in a process that requires p38 MAP kinase and ERK signaling.1 Publication

Gene expression databases

BgeeiENSG00000167613
CleanExiHS_LAIR1
ExpressionAtlasiQ6GTX8 baseline and differential
GenevisibleiQ6GTX8 HS

Organism-specific databases

HPAiHPA011155

Interactioni

Subunit structurei

Interacts with SH2 domains of tyrosine-protein phosphatases PTPN6 and PTPN11. The interaction with PTPN6 is constitutive. Interacts with the SH2 domain of CSK. Binds with high affinity to extracellular matrix collagens, the interaction is functionally important.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PTPN6P293505EBI-965864,EBI-78260

Protein-protein interaction databases

BioGridi110098, 4 interactors
IntActiQ6GTX8, 3 interactors
MINTiQ6GTX8
STRINGi9606.ENSP00000375622

Structurei

Secondary structure

1287
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi30 – 35Combined sources6
Beta strandi37 – 40Combined sources4
Beta strandi45 – 51Combined sources7
Beta strandi57 – 62Combined sources6
Helixi63 – 65Combined sources3
Beta strandi67 – 71Combined sources5
Beta strandi75 – 78Combined sources4
Beta strandi81 – 90Combined sources10
Helixi93 – 95Combined sources3
Beta strandi97 – 105Combined sources9
Beta strandi116 – 121Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3KGRX-ray1.80A/B/C22-122[»]
3RP1X-ray2.60A/B/C/D22-123[»]
ProteinModelPortaliQ6GTX8
SMRiQ6GTX8
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ6GTX8

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini29 – 117Ig-like C2-typeAdd BLAST89

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi249 – 254ITIM motif 16
Motifi279 – 284ITIM motif 26

Domaini

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.1 Publication

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410J37Q Eukaryota
ENOG41119RI LUCA
HOGENOMiHOG000015184
HOVERGENiHBG081887
InParanoidiQ6GTX8
KOiK06725
OrthoDBiEOG091G0TMA
PhylomeDBiQ6GTX8
TreeFamiTF336644

Family and domain databases

Gene3Di2.60.40.10, 1 hit
InterProiView protein in InterPro
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003599 Ig_sub
PfamiView protein in Pfam
PF13895 Ig_2, 1 hit
SMARTiView protein in SMART
SM00409 IG, 1 hit
SUPFAMiSSF48726 SSF48726, 1 hit

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6GTX8-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MSPHPTALLG LVLCLAQTIH TQEEDLPRPS ISAEPGTVIP LGSHVTFVCR
60 70 80 90 100
GPVGVQTFRL ERESRSTYND TEDVSQASPS ESEARFRIDS VSEGNAGPYR
110 120 130 140 150
CIYYKPPKWS EQSDYLELLV KETSGGPDSP DTEPGSSAGP TQRPSDNSHN
160 170 180 190 200
EHAPASQGLK AEHLYILIGV SVVFLFCLLL LVLFCLHRQN QIKQGPPRSK
210 220 230 240 250
DEEQKPQQRP DLAVDVLERT ADKATVNGLP EKDRETDTSA LAAGSSQEVT
260 270 280
YAQLDHWALT QRTARAVSPQ STKPMAESIT YAAVARH
Length:287
Mass (Da):31,412
Last modified:July 19, 2004 - v1
Checksum:i752EFB2FCC29B8E8
GO
Isoform 2 (identifier: Q6GTX8-2) [UniParc]FASTAAdd to basket
Also known as: LAIR-1b

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

Note: Functions as an inhibitory receptor in NK cells and T-cells.
Show »
Length:270
Mass (Da):29,840
Checksum:i8F7106914E4B4347
GO
Isoform 3 (identifier: Q6GTX8-3) [UniParc]FASTAAdd to basket
Also known as: LAIR-1c

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

Show »
Length:269
Mass (Da):29,710
Checksum:iCC0246DC14189301
GO
Isoform 4 (identifier: Q6GTX8-4) [UniParc]FASTAAdd to basket
Also known as: LAIR-1d

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

Show »
Length:209
Mass (Da):23,049
Checksum:i080127D8FC665567
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02759863E → D. Corresponds to variant dbSNP:rs3745442Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_02071023Missing in isoform 3. 1 Publication1
Alternative sequenceiVSP_020711122 – 138Missing in isoform 2 and isoform 3. 2 PublicationsAdd BLAST17
Alternative sequenceiVSP_020712210 – 287Missing in isoform 4. 1 PublicationAdd BLAST78

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS12891.1 [Q6GTX8-1]
CCDS12892.1 [Q6GTX8-2]
CCDS74448.1 [Q6GTX8-3]
RefSeqiNP_001275952.2, NM_001289023.2
NP_001275954.2, NM_001289025.2
NP_002278.2, NM_002287.5
NP_068352.2, NM_021706.4
UniGeneiHs.572535

Genome annotation databases

EnsembliENST00000348231; ENSP00000301193; ENSG00000167613
ENST00000391742; ENSP00000375622; ENSG00000167613
ENST00000474878; ENSP00000418998; ENSG00000167613
ENST00000610549; ENSP00000481204; ENSG00000276053 [Q6GTX8-3]
ENST00000614937; ENSP00000479006; ENSG00000278154 [Q6GTX8-3]
ENST00000614946; ENSP00000478853; ENSG00000274110 [Q6GTX8-3]
ENST00000616612; ENSP00000479682; ENSG00000278154 [Q6GTX8-1]
ENST00000618434; ENSP00000479133; ENSG00000274110 [Q6GTX8-1]
ENST00000619717; ENSP00000479707; ENSG00000276053 [Q6GTX8-1]
ENST00000619817; ENSP00000480619; ENSG00000276163 [Q6GTX8-2]
ENST00000620077; ENSP00000482922; ENSG00000276053 [Q6GTX8-2]
ENST00000620357; ENSP00000479649; ENSG00000278154 [Q6GTX8-2]
ENST00000620726; ENSP00000478405; ENSG00000276163 [Q6GTX8-3]
ENST00000622097; ENSP00000480659; ENSG00000274110 [Q6GTX8-2]
GeneIDi3903
KEGGihsa:3903
UCSCiuc032idt.2 human [Q6GTX8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiLAIR1_HUMAN
AccessioniPrimary (citable) accession number: Q6GTX8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 3, 2006
Last sequence update: July 19, 2004
Last modified: May 23, 2018
This is version 124 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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