LU domain


The LU domain is an evolutionally conserved protein domain of the three-finger protein superfamily. This domain is found in the extracellular domains of cell-surface receptors and in either GPI-anchored or secreted globular proteins, for example the Ly-6 family, CD59, and Sgp-2.
A variety of GPI-linked cell-surface glycoproteins are composed of one or more copies of a conserved LU domain of about 100 amino-acid residues. Among these proteins, U-PAR contains three tandem copies of the domain, while all the others are made up of a single domain.
Besides uPAR, other receptors with LU domains include members of the transforming growth factor beta receptor superfamily, such as the activin type 2 receptor; and bone morphogenetic protein receptor, type IA. Other LU domain proteins are small globular proteins such as CD59 antigen, LYNX1, SLURP1, and SLURP2.
Many LU domain containing proteins are involved in cholinergic signaling and bind acetylcholine receptors, notably linking their function to a common mechanism of 3FTx toxicity. Members of the Ly6/uPAR family are believed to be the evolutionary ancestors of the three-finger toxin. Other LU proteins, such as the CD59 antigen, have well-studied functions in regulation of the immune system.

Structure

This domain folds into five antiparallel beta sheets, a structure common to the three-finger superfamily.
As shown in the following schematic, this conserved domain contains 10 cysteine residues involved in five disulfide bonds - in U-PAR, the first copy of the domain lacks the fourth disulfide bond.
+------+ +------------------------+ +---+
| | | | | |
| | | |
+---------------------+ +--------------+
'C': conserved cysteine involved in a disulfide bond.

Subfamilies

ARS; CD177; CD59; LY6D; LY6E; LY6H; LYNX1;
LYPD2; LYPD3; LYPD4; LYPD5; LYPD6; PLAUR; PSCA;
SLURP2; SLURP1; SPACA4; TEX101;