The LU domain ( Ly-6 antigen/ uPAR) is an evolutionarily conserved protein domain of the

three-finger protein Three-finger proteins or three-finger protein domains (3FP or TFPD) are a protein superfamily consisting of small, roughly 60-80 amino acid residue protein domains with a common tertiary structure: three beta strand loops extended from a hydrophob ...

superfamily. This domain is found in the

extracellular domain An ectodomain is the domain of a membrane protein that extends into the extracellular space (the space outside a cell). Ectodomains are usually the parts of proteins that initiate contact with surfaces, which leads to signal transduction. A notabl ...

s of

cell-surface receptor Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving (binding to) extracellular molecules. They are specialized integral me ...

s and in either GPI-anchored or

secreted Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical mech ...

globular protein In biochemistry, globular proteins or spheroproteins are spherical ("globe-like") proteins and are one of the common protein types (the others being fibrous, disordered and membrane proteins). Globular proteins are somewhat water-soluble (form ...

s, for example the Ly-6 family,

CD59 CD59 glycoprotein, also known as MAC-inhibitory protein (MAC-IP), membrane inhibitor of reactive lysis (MIRL), or protectin, is a protein that in humans is encoded by the ''CD59'' gene. It is an LU domain and belongs to the LY6/ uPAR/ alpha-n ...

, 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, most contain only a single LU domain, though small numbers of exceptions are known; well-studied family member uPAR has three tandem LU domains.

Structure

This domain folds into five antiparallel

beta sheet The beta sheet (β-sheet, also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gene ...

s, a structure common to the

family Family (from ) is a Social group, group of people related either by consanguinity (by recognized birth) or Affinity (law), affinity (by marriage or other relationship). It forms the basis for social order. Ideally, families offer predictabili ...

. The domain typically contains ten well- conserved

cysteine Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...

residues involved in five

disulfide bond In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups. In inor ...

s, though some examples such as two of the three uPAR domains have fewer.

Examples

Besides uPAR, other receptors with LU domains include members of the transforming growth factor beta receptor (TGF-beta) superfamily, such as the

activin type 2 receptor The activin type 2 receptors belong to a larger TGF-beta receptor family and modulate signals for transforming growth factor beta ligands. These receptors are involved in a host of physiology, physiological processes including, cell growth, growt ...

; and bone morphogenetic protein receptor, type IA. Other LU domain proteins are small globular proteins such as

CD59 antigen CD59 glycoprotein, also known as MAC-inhibitory protein (MAC-IP), membrane inhibitor of reactive lysis (MIRL), or protectin, is a protein that in humans is encoded by the ''CD59'' gene. It is an LU domain and belongs to the LY6/Urokinase recept ...

, LYNX1,

SLURP1 Secreted Ly-6/uPAR-related protein 1 is a protein that in humans is encoded by the ''SLURP1'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides i ...

, and SLURP2.

Subfamilies

* Urokinase plasminogen activator surface receptor * Cell-surface glycoprotein Ly-6/CD59

Human proteins containing this domain

ARS;

CD177 CD177 antigen is a protein that in humans is encoded by the ''CD177'' gene. NB1, a glycosyl-phosphatidylinositol (GPI)-linked N-glycosylated cell surface glycoprotein, was first described in a case of neonatal alloimmune neutropenia (Lalezari et ...

;

; LY6D; LY6E; LY6H; LYNX1; LYPD2; LYPD3; LYPD4; LYPD5; LYPD6; PLAUR; PSCA; SLURP2;

; SPACA4; TEX101;

Functions

Many LU domain containing proteins are involved in

cholinergic Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word " choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium cation ...

signaling and bind

acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

receptors, notably linking their function to a common

mechanism Mechanism may refer to: *Mechanism (economics), a set of rules for a game designed to achieve a certain outcome **Mechanism design, the study of such mechanisms *Mechanism (engineering), rigid bodies connected by joints in order to accomplish a ...

of 3FTx toxicity. Members of the Ly6/uPAR family are believed to be the evolutionary ancestors of the

three-finger toxin Three-finger toxins (abbreviated 3FTx) are a protein superfamily of small toxin proteins found in the venom of snakes. Three-finger toxins are in turn members of a larger superfamily of three-finger protein domains which includes non-toxic prote ...

(3FTx). Other LU proteins, such as the

, have well-studied functions in regulation of the

immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

References

{{DEFAULTSORT:LU domain Protein domains Membrane proteins Blood antigen systems Transfusion medicine