The LU domain ( Ly-6 antigen/

uPAR The Urokinase receptor, also known as urokinase plasminogen activator surface receptor (uPAR) or CD87 (Cluster of Differentiation 87), is a protein encoded in humans by the PLAUR gene. It is a multidomain glycoprotein tethered to the cell membran ...

) 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 notable ...

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 440px 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 classica ...

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 (fo ...

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-ne ...

, 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

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 gen ...

s, a structure common to the

family Family (from la, familia) is a group of people related either by consanguinity (by recognized birth) or affinity (by marriage or other relationship). The purpose of the family is to maintain the well-being of its members and of society. Idea ...

. The domain typically contains ten well- conserved

cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, s ...

residues involved in five

disulfide bond In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups ...

s, though some examples such as two of the three

domains have fewer.

Examples

Besides uPAR, other receptors with LU domains include members of the

transforming growth factor beta receptor Transforming growth factor beta (TGFβ) receptors are single pass serine/threonine kinase receptors that belong to TGFβ receptor family. They exist in several different isoforms that can be homo- or heterodimeric. (free full text) The number ...

(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 physiological processes including, growth, cell differentiation, ...

; and

bone morphogenetic protein receptor, type IA The bone morphogenetic protein receptor, type IA also known as BMPR1A is a protein which in humans is encoded by the ''BMPR1A'' gene. BMPR1A has also been designated as CD292 ( cluster of differentiation 292). Function The bone morphogenetic p ...

. 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/uPAR/alpha-neuro ...

, LYNX1, SLURP1, and SLURP2.

Subfamilies

Urokinase plasminogen activator surface receptor The Urokinase receptor, also known as urokinase plasminogen activator surface receptor (uPAR) or CD87 (Cluster of Differentiation 87), is a protein encoded in humans by the PLAUR gene. It is a multidomain glycoprotein tethered to the cell memb ...

* 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 e ...

;

; LY6D;

LY6E Lymphocyte antigen 6E is a protein that in humans is encoded by the ''LY6E'' gene. Increased expression of ''Ly6E'' is associated with poor survival outcome in multiple malignancies as determined by a survey of more than 130 published clinical ...

; LY6H; LYNX1; LYPD2;

LYPD3 Ly6/PLAUR domain-containing protein 3 is a protein that in humans is encoded by the ''LYPD3'' gene. References Further reading

* * * * * * * * * * * {{gene-19-stub ...

; LYPD4; LYPD5; LYPD6; PLAUR; PSCA; SLURP2; SLURP1; 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 chemical 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 (engineering), rigid bodies connected by joints in order to accomplish a desired force and/or motion transmission *Mechanism (biology), explaining how a feature is created *Mechanism (philosophy), a theory that 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 processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as Tumor immunology, cancer cells and objects such ...

References

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