LAIR1_HUMAN » Leukocyte-associated immunoglobulin-like receptor 1

LAIR1_HUMAN » Leukocyte-associated immunoglobulin-like receptor 1
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
LAIR1_HUMAN » Leukocyte-associated immunoglobulin-like receptor 1 » LAIR-1; hLAIR1;
Hydrophobic Thickness 36.0 ± 3.4 Å
Tilt Angle 0 ± 1°
ΔGtransfer -45.1 kcal/mol
ΔGfold -22.9 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, HMDB
Topology Out
TM Segments 163-187 (160-189)
Pathways none
PDB 3kgr (22-122), 3rp1 (22-123)
OPM none
Complexes

LAIR1:LAIR1_MOUSE

Interactions

A4, Complex: LAIR1:A4, PubMed

EPCAM, Complex: LAIR1:EPCAM, PubMed

LAIR1, Complex: Homodimer of leukocyte-associated Ig-like receptor 1, PDBID: 4ESK

Domains

AA: 28-120, PDBID: 3KGR, Subunit B, Seq Identity:100%, Immunoglobulin domain

UniProt annotation for LAIR1_HUMAN » Leukocyte-associated immunoglobulin-like receptor 1
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, 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.

SUBUNIT: 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.

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.

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

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

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.

UniProt features for LAIR1_HUMAN » Leukocyte-associated immunoglobulin-like receptor 1
SIGNAL 1 21 Potential.
CHAIN 22 287 Leukocyte-associated immunoglobulin-like receptor 1.
DOMAIN 29 117 Ig-like C2-type.
MOTIF 249 254 ITIM motif 1.
MOTIF 279 284 ITIM motif 2.
DISULFID 49 101
Amino Acid Sequence for LAIR1_HUMAN » Leukocyte-associated immunoglobulin-like receptor 1
MSPHPTALLG LVLCLAQTIH TQEEDLPRPS ISAEPGTVIP LGSHVTFVCR GPVGVQTFRL ERESRSTYND TEDVSQASPS ESEARFRIDS VSEGNAGPYR CIYYKPPKWS EQSDYLELLV KETSGGPDSP DTEPGSSAGP TQRPSDNSHN EHAPASQGLK AEHLYILIGV SVVFLFCLLL LVLFCLHRQN QIKQGPPRSK DEEQKPQQRP DLAVDVLERT ADKATVNGLP EKDRETDTSA LAAGSSQEVT YAQLDHWALT QRTARAVSPQ STKPMAESIT YAAVARH