{{Short description|Protein domain}} {{Pfam_box | Symbol = UPAR_LY6 | Name = u-PAR/Ly-6 domain | image = Cd59b.png | width = | caption = Crystallographic structure of non-glycosylated human CD59.<ref name="pmid17671359">{{PDB|2J8B}}; {{cite journal | vauthors = Leath KJ, Johnson S, Roversi P, Hughes TR, Smith RA, Mackenzie L, Morgan BP, Lea SM | title = High-resolution structures of bacterially expressed soluble human CD59 | journal = Acta Crystallographica. Section F, Structural Biology and Crystallization Communications | volume = 63 | issue = Pt 8 | pages = 648–52 | date = August 2007 | pmid = 17671359 | pmc = 2335151 | doi = 10.1107/S1744309107033477 }}</ref> | Pfam= PF00021 | InterPro= IPR001526 | SMART= | Prosite = PDOC00756 | SCOP = 1erg | CATH = 1erg | TCDB = | OPM family= | OPM protein= | CDD = cd00117 | PDB= {{PDB3|1cds}} :28-95 {{PDB3|1cdr}} :28-95 {{PDB3|1cdq}} :28-95 {{PDB3|1erg}} :28-95 {{PDB3|1ywh}}C:25-99 {{PDB3|1vye}}A:23-80 }}
The '''LU domain''' (Ly-6 antigen/uPAR) is an evolutionarily 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.<ref name=kessler_2017>{{cite journal | vauthors = Kessler P, Marchot P, Silva M, Servent D | title = The three-finger toxin fold: a multifunctional structural scaffold able to modulate cholinergic functions | journal = Journal of Neurochemistry | volume = 142 | pages = 7–18 | date = August 2017 | issue = Suppl 2 | pmid = 28326549 | doi = 10.1111/jnc.13975 | doi-access = free }}</ref><ref name=loughner_2016>{{cite journal | vauthors = Loughner CL, Bruford EA, McAndrews MS, Delp EE, Swamynathan S, Swamynathan SK | title = Organization, evolution and functions of the human and mouse Ly6/uPAR family genes | journal = Human Genomics | volume = 10 | pages = 10 | date = April 2016 | pmid = 27098205 | pmc = 4839075 | doi = 10.1186/s40246-016-0074-2 | doi-access = free }}</ref>
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.<ref name="PUB00002692">{{cite journal | vauthors = Behrendt N, Ploug M, Patthy L, Houen G, Blasi F, Danø K | title = The ligand-binding domain of the cell surface receptor for urokinase-type plasminogen activator | journal = The Journal of Biological Chemistry | volume = 266 | issue = 12 | pages = 7842–7 | date = April 1991 | doi = 10.1016/S0021-9258(20)89526-X | pmid = 1850423 | doi-access = free }}</ref><ref name="PUB00002796">{{cite journal | vauthors = Ploug M, Kjalke M, Rønne E, Weidle U, Høyer-Hansen G, Danø K | title = Localization of the disulfide bonds in the NH2-terminal domain of the cellular receptor for human urokinase-type plasminogen activator. A domain structure belonging to a novel superfamily of glycolipid-anchored membrane proteins | journal = The Journal of Biological Chemistry | volume = 268 | issue = 23 | pages = 17539–46 | date = August 1993 | doi = 10.1016/S0021-9258(19)85366-8 | pmid = 8394346 | doi-access = free }}</ref> 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.<ref name=loughner_2016 />
== Structure == This domain folds into five antiparallel beta sheets, a structure common to the three-finger protein family. The domain typically contains ten well-conserved cysteine residues involved in five disulfide bonds, though some examples such as two of the three uPAR domains have fewer.<ref name=loughner_2016 />
== 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;<ref name=greenwald_1999>{{cite journal | vauthors = Greenwald J, Fischer WH, Vale WW, Choe S | title = Three-finger toxin fold for the extracellular ligand-binding domain of the type II activin receptor serine kinase | journal = Nature Structural Biology | volume = 6 | issue = 1 | pages = 18–22 | date = January 1999 | pmid = 9886286 | doi = 10.1038/4887 | s2cid = 26301441 }}</ref> and bone morphogenetic protein receptor, type IA.<ref>{{cite journal | vauthors = Kirsch T, Sebald W, Dreyer MK | title = Crystal structure of the BMP-2-BRIA ectodomain complex | journal = Nature Structural Biology | volume = 7 | issue = 6 | pages = 492–6 | date = June 2000 | pmid = 10881198 | doi = 10.1038/75903 | s2cid = 19403233 }}</ref> Other LU domain proteins are small globular proteins such as CD59 antigen, LYNX1, SLURP1, and SLURP2.<ref name=kessler_2017 /><ref name=galat_2008>{{cite journal | vauthors = Galat A | title = The three-fingered protein domain of the human genome | journal = Cellular and Molecular Life Sciences | volume = 65 | issue = 21 | pages = 3481–93 | date = November 2008 | pmid = 18821057 | doi = 10.1007/s00018-008-8473-8 | s2cid = 19931506 | pmc = 11131612 }}</ref>
===Subfamilies=== * Urokinase plasminogen activator surface receptor {{InterPro|IPR003631}} * Cell-surface glycoprotein Ly-6/CD59 {{InterPro|IPR003632}}
===Human proteins containing this domain=== ARS; CD177; CD59; LY6D; LY6E; LY6H; LYNX1; LYPD2; LYPD3; LYPD4; LYPD5; LYPD6; PLAUR; PSCA; SLURP2; SLURP1; SPACA4; TEX101;
==Functions== 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.<ref name=kessler_2017 /><ref name=loughner_2016 /><ref name=tsetlin_2015>{{cite journal | vauthors = Tsetlin VI | title = Three-finger snake neurotoxins and Ly6 proteins targeting nicotinic acetylcholine receptors: pharmacological tools and endogenous modulators | journal = Trends in Pharmacological Sciences | volume = 36 | issue = 2 | pages = 109–23 | date = February 2015 | pmid = 25528970 | doi = 10.1016/j.tips.2014.11.003 }}</ref> Members of the Ly6/uPAR family are believed to be the evolutionary ancestors of the three-finger toxin (3FTx).<ref name=fry_2005>{{cite journal | vauthors = Fry BG | title = From genome to "venome": molecular origin and evolution of the snake venom proteome inferred from phylogenetic analysis of toxin sequences and related body proteins | journal = Genome Research | volume = 15 | issue = 3 | pages = 403–20 | date = March 2005 | pmid = 15741511 | pmc = 551567 | doi = 10.1101/gr.3228405 }}</ref> Other LU proteins, such as the CD59 antigen, have well-studied functions in regulation of the immune system.<ref name=tsetlin_2015 />
== References == {{reflist|32em}}
{{InterPro content|IPR001526}}
{{DEFAULTSORT:LU domain}} Category:Protein domains Category:Membrane proteins Category:Blood antigen systems Category:Transfusion medicine