Ly-49 Ly-49 family
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 2 glycoprotein
Thymocyte, Dim
T Cell, Dim
NK Cell, Dim
35 / 100

Expression
Ly-49A is expressed at low levels on mouse thymocytes and T cells and at higher levels on 15%-20% of NK cells.  Ly-49C is expressed on a similar proportion on ~26% of NK cells, with ~5% of the cells expressing both Ly-49A and C.  Ly-49G, LGL-1 is expressed on ~40% of the NK cells with 8% expressing both Ly-49G and Ly-49A.  Because of a lack of suitable reagents the expression pattern of other mouse and rat Ly-49 molecules is not known.

Structure
Ly-49 family members: Mouse - Ly-49A (A1, YE1/48); Ly-49B; Ly-49C (5E6); Ly-49D; Ly-49E; Ly-49F; Ly-49G (LGL-1) and Ly-49H. Rat - rLy-49.9; rLy-49.12 and rLy-49.29.

Ly-49A, Ly-49C and Ly-49G have been shown to be expressed as disulfide-linked homodimeric type 2 glycoproteins.  Proteins within the rat and mouse Ly-49 gene families share a 62%-90% aa and a 48%-91% aa identity, respectively, and there is a 46%-81% identity between the rat and mouse Ly-49 families.  Sequence comparisons suggest that all members have a similar overall structure.  The 2 transmembrane proteins have no signal peptide and an extracellular C-type lectin domain.  The cytoplasmic regions show some heterogeneity which may reflect different signaling functions.  For example ITIM motifs (I/V XYXX(L/V are found in mouse Ly-49A, C, F, G1 and G4 and rat Ly-49.9.  Putative Gi-binding motifs are found in mouse Ly-49A and D and rat Ly-49.9.

MOLECULAR MASS
Cell Type Unreduced Reduced
85 - 95 kDa 40 - 50 kDa



Ligands
Ly-49A has been shown to bind to the MHC class I alleles H-2Dd and H-2Dk whereas Ly-49C interacts with the H-2Db,d, k,and s alleles.  Preliminary evidence suggests that Ly-49G  interacts with H-2Dd and H-2Ld.  Ly-49A and Ly-49C have both been shown to interact with carbohydrates, presumably through their C-type lectin domains, and there is suggestive evidence that their interaction with MHC class I molecules involves carbohydrate determinants.  Peptides comprising the phosphorylated ITIM motif of LY-49A bind to the cytoplasmic tyrosine phosphatases SHP-1, PTP1C, and SHP-2, PTP1D, SYP, suggesting a mechanism for the inhibitory effect of this receptor.

Function
Several members of the Ly-49 family, Ly-49A, Ly-49C, and Ly-49G have been implicated in the recognition by murine NK cells of MHC class I molecules on target cells.  Of these the role of Ly-49A is the best documented.  In general, ligation of Ly-49 members by MHC class I molecules inhibits NK cell function, consistent with the notion that Ly-49 molecules are involved in the recognition of the 'missing self' on target cells.  No human Ly-49 orthologues have been identified.  Instead CD94/NKG-2 receptors and IgSF domain-containing killer inhibitory receptors (KIR) appear to have an equivalent function on human NK cells.

Comments
The NK gene complex (NKC) is a chromosomal region containing several genes and multigene families which encode cell surface C-type lectins expressed on NK cells.  It was first identified in the mouse on chromosome 6 and subsequently in humans on chromosome 12 and the rat on chromosome 4.  Ly-49, NKR-P1 and CD69 genes have been identified in the mouse NKC.  NKR-P1, CD69, CD94 and NKG2 genes have been identified in the human NKC.  Ly-49 and NKR-P1 genes have been identified in the rat NKC.  cDNA clones have been obtained corresponding to 8 mouse and 3 rat Ly-49 genes, but no human Ly-49 homologues have been identified.  In the mouse multiple alleles have been identified for some genes, Ly-49A, Ly-49C, and Ly-49G, and mice heterozygous for Ly-49A and Ly-49C may undergo allelic exclusion at these loci.  Identification of 4 probable splice variants of LY-49G have been made, 1 of which Ly-49G2 corresponds to LGL-1..

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
MouseP20937M25775
MouseI49058U10304
MouseI49059U01305
MouseU10090
MouseU10091
MouseU10092
MouseU10093
MouseU10094
MouseU10095
MouseU12890
MouseU12889
RatU56863
RatU56822
RatU56824
Antibodies

Revised June 25, 2008


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