|Blood Group Antigen Gene Mutation Database|
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Lutheran Blood Group System
Gene locus - BCAM
The protein carrying the antigens for the Lutheran blood group system is a product of a single gene LU, which consists of 15 exons distributed over ~12 kb. The gene encodes a type I integral membrane glycoprotein (Lu gp) present as two 85 kD and 78 kD isoforms differing at the C terminus, due to alternative splicing. The 85 kD isoform is the predominant species and the 78kD form is also known as B-CAM, the basal cell adhesion molecule antigen. The Lu glycoprotein is a member of the Ig superfamily that share a similar extracellular domain composed of five Ig-like domains. Lu glycoproteins thus belong to a subset of adhesion molecules and, in particular, function as laminin receptors (Parsons et al., Blood, 97:312, 2001, Nemer et al., J. Biol. Chem, 276, 23757, 2001).
Function of proteins
Plays a role in cell-cell and cell-substrate adhesion events; the extracellular and cytoplasmic domains contain motifs suggestive of possible receptor and signal-transduction functions. Functions as laminin receptor during erythropoiesis. More generally it is a ligand for the alpha 5 subunit of laminin.Recent studies, including high resolution crystal structure and site-directed mutagenesis, have demonstrated the moleculr basis for this interaction (Mankelow et al. Blood 2007 110:3398-3406).
Erythrocytes and a broad range of of human cells and tissues; expressed predominantly in the basal layer of the epithelium and the endothelium of blood vessels; not on lymphocytes, granulocytes, monocytes, platelets. Not expressed on a number of cell lines, such as K562, HEL,HL60 ,IM9, MOLT4. The level of expression of Lutheran antigens is regulated by two supressor genes, a dominant gene In(Lu) and a X-linked supressor gene; presence of these genes results in low expression. Recently,mutations in the transcription factor EKLF have been shown to be associated with almost a complete absence of Lu antigens, resulting in InLu phenotype (Singleton et al. Blood 2008 112 2081-2088).
None known directly; however, B-CAM is overexpressed or up-regulated in certain malignant tumors and cells. In sickle cell disease Lu gp may mediate adhesion of sickle cells to vascular endothelium (El Nemer et al., J. Biol. Chem. 273:16686, 1998). This adhesion appears to be regulated by phosphorylation of Lu gp by PKA (Gauthier et al. J. Biol. Chem. June, 2005). Also, interaction with laminin may be an important contributor to vaso-occlusive events.
Nineteen antigens have been documented serologically to be part of the Lutheran system; they are designated LU1 through LU21 but are also known by other common names (LU10 and LU15 are obsolete, Daniels et al. Vox Sang 2004 87 304). The epitopes for these antigens, all seem to reside at various sites of the LU glycoprotein and have been detected by the absence of the epitope on some individuals' erythrocytes or by production of specific antibodies. Thus, most of these antigens are high frequency but those whose eptopes may exhibit altered forms (antithetical) or are absent, have lower prevalence or are expressed in a few families only. Ten pairs of antigens have an antithetical relationship such as Lu6/Lu9.
LU18/LU19, also known as Aua/Aub, were first believed to specify the Auberger blood group system but then were shown to belong to the Lutheran system and to be associated with the Lu glycoprotein, the epitope residing at a site different from that specifying Lua and Lub; so far, from the reported DNA sequences it appears that the Aub epitope is identical to the corresponding sequence in Lubglycoprotein.
In the list of alleles, allele LUB (LU2) acc. no. X83425 is taken as reference; in that sequence, the first nucleotide of the coding sequence starts at nt. 23; the cDNA and translation changes are numbered from the codon for the initiator Met. Mutations in LUB(LU2) gene shown in the list give rise to alleles whose products can be identified as low incidence antigens.
When searching for a particular allele, use "name" if DNA alteration is known or, if you wish to search by phenotype or numerical terminology or the designation used by author, use "alias" (see "Details").
Other database IDs and links
Marion E. Reid, Immunohematology, New York Blood Center, 310 East 67 St., New York, N.Y. 10021
Geoff Daniels, Bristol Institute for Transfusion Sciences, Bristol, BS10 5ND, UK
Contributors for specific alleles are listed with the alleles.
Updated 2009-01-26 20:07:21.283