{{short description|Proteins found in the urine and other secretions of many animals}} {{cs1 config|name-list-style=vanc|display-authors=6}} [[File:Mup1 PDB 1i04.png|thumb|Tertiary structure of a mouse major urinary protein. The protein has eight beta sheets (yellow) arranged in a beta barrel open at one end, with alpha helices (red) at both the amino- and carboxyl termini. The structure is resolved from Protein Data Bank entry {{PDB link|1i04}}. Find [https://www.ebi.ac.uk/pdbe-apps/widgets/unipdb?uniprot=P02762 all instances] of this protein in the PDB |alt=A ribbon diagram of a mouse major urinary protein, containing eight beta sheets and four alpha helices.]]

'''Major urinary proteins''' ('''Mups'''), also known as '''α<sub>2</sub>u-globulins''', are a subfamily of proteins found in abundance in the urine and other secretions of many animals. Mups provide a small range of identifying information about the donor animal, when detected by the vomeronasal organ of the receiving animal. They belong to a larger family of proteins known as lipocalins. Mups are encoded by a cluster of genes, located adjacent to each other on a single stretch of DNA, that varies greatly in number between species: from at least 21 functional genes in mice to none in humans. Mup proteins form a characteristic glove shape, encompassing a ligand-binding pocket that accommodates specific small organic chemicals.

Urinary proteins were first reported in rodents in 1932, during studies by Thomas Addis into the cause of proteinuria. They are potent human allergens and are largely responsible for a number of animal allergies, including to cats, horses and rodents. Their endogenous function within an animal is unknown but may involve regulating energy expenditure. However, as secreted proteins they play multiple roles in chemical communication between animals, functioning as pheromone transporters and stabilizers in rodents and pigs. Mups can also act as protein pheromones themselves. They have been demonstrated to promote aggression in male mice, and one specific Mup protein found in male mouse urine is sexually attractive to female mice. Mups can also function as signals between different species: mice display an instinctive fear response on the detection of Mups derived from predators such as cats and rats.

==Discovery== [[File:Phylogenetic tree of Mups.jpg|thumb|Phylogeny of ''Mup'' coding sequences in mammals.<ref name="Logan"/> The repeatability of the reconstruction was tested by bootstrapping. Interior branches with bootstrap support&nbsp;>&nbsp;50% are shown.|alt=A phylogenetic tree of major urinary protein genes in mammals showing 21 mouse genes, 9 rat genes, 3 horse genes, 2 lemur genes and one gene each from pig, dog, orangutan, macaque, bushbaby and opossum]] Humans in good health excrete urine that is largely free of protein. Therefore, since 1827 physicians and scientists have been interested in proteinuria, the excess of protein in human urine, as an indicator of kidney disease.<ref group="notes" name="note1">In that year Richard Bright first related kidney disease, later to become known as Bright's disease, with albuminous urine.</ref><ref name="Comper">{{cite journal | vauthors = Comper WD, Hilliard LM, Nikolic-Paterson DJ, Russo LM | title = Disease-dependent mechanisms of albuminuria | journal = American Journal of Physiology. Renal Physiology | volume = 295 | issue = 6 | pages = F1589-600 | date = December 2008 | pmid = 18579704 | doi = 10.1152/ajprenal.00142.2008 }}</ref> To better understand the etiology of proteinuria, some scientists attempted to study the phenomenon in laboratory animals.<ref name="Lemley">{{cite journal |vauthors=Lemley KV, Pauling L |title=Thomas Addis: 1881–1949 |journal=Biographical Memoirs of the National Academy of Sciences |volume=63 |pages=1–46 |year=1994 |url=http://books.nap.edu/openbook.php?record_id=4560&page=3}}</ref> Between 1932 and 1933 a number of scientists, including Thomas Addis, independently reported the surprising finding that some healthy rodents have protein in their urine.<ref name="Addis">{{cite journal | vauthors = Addis T |title=Proteinuria and cylinduria |journal=Proceedings of the California Academy of Sciences |volume=2 |pages=38–52 |year=1932}}</ref><ref name="Bell">{{cite journal | vauthors = Bell ME | title = Albuminuria in the normal male rat | journal = The Journal of Physiology | volume = 79 | issue = 2 | pages = 191–3 | date = September 1933 | pmid = 16994453 | pmc = 1394952 | doi = 10.1113/jphysiol.1933.sp003040 }}</ref><ref name="Perl">{{cite journal |vauthors=Parfentjev IA, Perlzweig WA |title=The Composition of the Urine of White Mice |journal=The Journal of Biological Chemistry |volume=100 |issue=2 |pages=551–55 |year=1933 |doi=10.1016/S0021-9258(18)75972-3 |url=http://www.jbc.org/content/100/2/557.full.pdf+html|doi-access=free }}</ref> However, it was not until the 1960s that the major urinary proteins of mice and rats were first described in detail.<ref name=Finlayson/><ref name=Roy1/> It was found that the proteins are primarily made in the liver of males and secreted through the kidneys into the urine in large quantities (milligrams per day).<ref name=Finlayson>{{cite journal | vauthors = Finlayson JS, Asofsky R, Potter M, Runner CC | title = Major urinary protein complex of normal mice: origin | journal = Science | volume = 149 | issue = 3687 | pages = 981–2 | date = August 1965 | pmid = 5827345 | doi = 10.1126/science.149.3687.981 | s2cid = 23007588 | bibcode = 1965Sci...149..981F }}</ref><ref name=Roy1>{{cite journal | vauthors = Roy AK, Neuhaus OW | title = Identification of rat urinary proteins by zone and immunoelectrophoresis | journal = Proceedings of the Society for Experimental Biology and Medicine | volume = 121 | issue = 3 | pages = 894–9 | date = March 1966 | pmid = 4160706 | doi = 10.3181/00379727-121-30917 | s2cid = 41096617 }}</ref><ref name=Roy2>{{cite journal | vauthors = Roy AK, Neuhaus OW | title = Proof of the hepatic synthesis of a sex-dependent protein in the rat | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 127 | issue = 1 | pages = 82–7 | date = September 1966 | pmid = 4165835 | doi = 10.1016/0304-4165(66)90478-8 }}</ref>

Since they were named, the proteins have been found to be differentially expressed in other glands that secrete products directly into the external environment. These include lacrimal, parotid, submaxillary, sublingual, preputial and mammary glands.<ref name=Held1>{{cite journal | vauthors = Held WA, Gallagher JF | title = Rat alpha 2u-globulin mRNA expression in the preputial gland | journal = Biochemical Genetics | volume = 23 | issue = 3–4 | pages = 281–90 | date = April 1985 | pmid = 2409959 | doi = 10.1007/BF00504325 | s2cid = 25646065 }}</ref><ref name=Gubits>{{cite journal | vauthors = Gubits RM, Lynch KR, Kulkarni AB, Dolan KP, Gresik EW, Hollander P, Feigelson P | title = Differential regulation of alpha 2u globulin gene expression in liver, lachrymal gland, and salivary gland | journal = The Journal of Biological Chemistry | volume = 259 | issue = 20 | pages = 12803–9 | date = October 1984 | doi = 10.1016/S0021-9258(18)90817-3 | pmid = 6208189 | doi-access = free }}</ref><ref name=Shahan1>{{cite journal | vauthors = Shahan K, Denaro M, Gilmartin M, Shi Y, Derman E | title = Expression of six mouse major urinary protein genes in the mammary, parotid, sublingual, submaxillary, and lachrymal glands and in the liver | journal = Molecular and Cellular Biology | volume = 7 | issue = 5 | pages = 1947–54 | date = May 1987 | pmid = 3600653 | pmc = 365300 | doi = 10.1128/MCB.7.5.1947 }}</ref> In some species, such as cats and pigs, Mups appear not to be expressed in urine at all and are mainly found in saliva.<ref name="pmid15544598"/><ref name=Loebel/> Sometimes the term ''urinary Mups'' (uMups) is used to distinguish those Mups expressed in urine from those in other tissues.<ref name= Beynon>{{cite journal | vauthors = Beynon RJ, Hurst JL | title = Multiple roles of major urinary proteins in the house mouse, Mus domesticus | journal = Biochemical Society Transactions | volume = 31 | issue = Pt 1 | pages = 142–6 | date = February 2003 | pmid = 12546672 | doi = 10.1042/BST0310142 }}</ref>

==Mup genes== Between 1979 and 1981, it was estimated that Mups are encoded by a gene family of between 15 and 35 genes and pseudogenes in the mouse and by an estimated 20 genes in the rat.<ref name="Kurtz1">{{cite journal | vauthors = Kurtz DT | title = Rat alpha 2u globulin is encoded by a multigene family | journal = Journal of Molecular and Applied Genetics | volume = 1 | issue = 1 | pages = 29–38 | year = 1981 | pmid = 6180115 }}</ref><ref name=Hastie1>{{cite journal | vauthors = Hastie ND, Held WA, Toole JJ | title = Multiple genes coding for the androgen-regulated major urinary proteins of the mouse | journal = Cell | volume = 17 | issue = 2 | pages = 449–57 | date = June 1979 | pmid = 88267 | doi = 10.1016/0092-8674(79)90171-5 | s2cid = 20636057 }}</ref><ref name=Bishop1>{{cite journal | vauthors = Bishop JO, Clark AJ, Clissold PM, Hainey S, Francke U | title = Two main groups of mouse major urinary protein genes, both largely located on chromosome 4 | journal = The EMBO Journal | volume = 1 | issue = 5 | pages = 615–20 | year = 1982 | pmid = 6329695 | pmc = 553096 | doi = 10.1002/j.1460-2075.1982.tb01217.x }}</ref> In 2008 a more precise number of Mup genes in a range of species was determined by analyzing the DNA sequence of whole genomes.<ref name="Logan">{{cite journal | vauthors = Logan DW, Marton TF, Stowers L | title = Species specificity in major urinary proteins by parallel evolution | journal = PLOS ONE | volume = 3 | issue = 9 | article-number = e3280 | date = September 2008 | pmid = 18815613 | pmc = 2533699 | doi = 10.1371/journal.pone.0003280 | bibcode = 2008PLoSO...3.3280L | doi-access = free }}</ref><ref name="Chamero1"/>

===Rodents=== [[File:Mup locus showing DNA repeats.jpg|thumb|left| A dot plot showing self-similarity within the mouse ''Mup'' cluster.<ref name="Mudge"/> The main diagonal represents the sequence's alignment with itself; lines off the main diagonal represent similar or repetitive patterns within the cluster. The pattern differs between the older, peripheral ''Class A'' and the newer, central ''Class B Mups''.|alt=A dot plot showing different patterns of self-similarity within the first five genes of the mouse ''Mup'' cluster]]

The mouse reference genome has at least 21 distinct Mup genes (with open reading frames) and a further 21 Mup pseudogenes (with reading frames disrupted by a nonsense mutation or an incomplete gene duplication). They are all clustered together, arrayed side by side across 1.92 megabases of DNA on chromosome 4. The 21 functional genes have been divided into two sub-classes based on position and sequence similarity: 6 peripheral ''Class A Mups'' and 15 central ''Class B Mups''.<ref name="Logan"/><ref name="Mudge"/> The central Class B Mup gene cluster formed through a number of sequential duplications from one of the Class A Mups. As all the Class B genes are almost identical to each other, researchers have concluded that these duplications occurred very recently in mouse evolution. Indeed, the repetitive structure of these central Mup genes means they are likely to be unstable and may vary in number among wild mice.<ref name="Mudge"/> The Class A Mups are more different from each other and are therefore likely to be more stable, older genes, but what, if any, functional differences the classes have are unknown.<ref name="Logan"/> The similarity between the genes makes the region difficult to study using current DNA sequencing technology. Consequently, the Mup gene cluster is one of the few parts of the mouse whole genome sequence with gaps remaining, and further genes may remain undiscovered.<ref name="Logan"/><ref name="Mudge"/>

Rat urine also contains homologous urinary proteins; although they were originally given a different name, α2<sub>u</sub>-globulins,<ref name=Roy1/><ref name=Roy2/> they have since become known as rat Mups.<ref name=Hurstchapter>{{cite book |vauthors=Hurst J, Beynon RJ, Roberts SC, Wyatt TD | title=Urinary Lipocalins in Rodenta:is there a Generic Model? | series=Chemical Signals in Vertebrates 11 | publisher=Springer New York | year=2007| isbn=978-0-387-73944-1 }}</ref><ref name="Cavaggioni">{{cite journal | vauthors = Cavaggioni A, Mucignat-Caretta C | title = Major urinary proteins, alpha(2U)-globulins and aphrodisin | journal = Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology | volume = 1482 | issue = 1–2 | pages = 218–28 | date = October 2000 | pmid = 11058763 | doi = 10.1016/S0167-4838(00)00149-7 }}</ref> Rats have 9 distinct Mup genes and a further 13 pseudogenes clustered together across 1.1 megabases of DNA on chromosome 5. Like in mice, the cluster formed by multiple duplications. However, this occurred independently of the duplications in mice, meaning that both rodent species expanded their Mup gene families separately, but in parallel.<ref name="Logan"/><ref name="McFadyen">{{cite journal | vauthors = McFadyen DA, Addison W, Locke J | title = Genomic organization of the rat alpha 2u-globulin gene cluster | journal = Mammalian Genome | volume = 10 | issue = 5 | pages = 463–70 | date = May 1999 | pmid = 10337619 | doi = 10.1007/s003359901024 | s2cid = 1121039 }}</ref>

===Nonrodents=== Most other mammals studied, including the pig, cow, cat, dog, bushbaby, macaque, chimpanzee and orangutan, have a single Mup gene. Some, however, have an expanded number: horses have three Mup genes, and gray mouse lemurs have at least two. Insects, fish, amphibia, birds and marsupials appear to have disrupted synteny at the chromosomal position of the Mup gene cluster, suggesting the gene family may be specific to placental mammals.<ref name="Logan"/> Humans are the only placental mammals found not to have any active Mup genes; instead, they have a single Mup pseudogene containing a mutation that causes missplicing, rendering it dysfunctional.<ref name="Logan"/>

== Function ==

===Transport proteins=== thumb|right|Mouse major urinary proteins bind 2-sec-butyl-4,5-dihydrothiazole (SBT), a mouse pheromone.<ref name="Böcskei">{{cite journal | vauthors = Böcskei Z, Groom CR, Flower DR, Wright CE, Phillips SE, Cavaggioni A, Findlay JB, North AC | title = Pheromone binding to two rodent urinary proteins revealed by X-ray crystallography | journal = Nature | volume = 360 | issue = 6400 | pages = 186–8 | date = November 1992 | pmid = 1279439 | doi = 10.1038/360186a0 | bibcode = 1992Natur.360..186B | s2cid = 4362015 }}</ref> The beta barrel forms a pocket, in which the SBT molecule is tightly bound. The structure is resolved from {{PDB link|1MUP}}. |alt=A ribbon diagram of a mouse major urinary protein with a small chemical ligand in its binding pocket.

Mups are members of a large family of low-molecular weight (~19&nbsp;kDa) proteins known as lipocalins.<ref name=Flower>{{cite journal | vauthors = Flower DR | title = The lipocalin protein family: structure and function | journal = The Biochemical Journal | volume = 318 ( Pt 1) | issue = 1 | pages = 1–14 | date = August 1996 | pmid = 8761444 | pmc = 1217580 | doi = 10.1042/bj3180001 }}</ref> They have a characteristic structure of eight beta sheets arranged in an anti-parallel beta barrel open on one face, with alpha helices at both ends.<ref name=Flower/> Consequently, they form a characteristic glove shape, encompassing a cup-like pocket that binds small organic chemicals with high affinity.<ref name="Logan"/><ref name=Ganfornina>{{cite journal | vauthors = Ganfornina MD, Gutiérrez G, Bastiani M, Sánchez D | title = A phylogenetic analysis of the lipocalin protein family | journal = Molecular Biology and Evolution | volume = 17 | issue = 1 | pages = 114–26 | date = January 2000 | pmid = 10666711 | doi = 10.1093/oxfordjournals.molbev.a026224 | doi-access = free }}</ref> A number of these ligands bind to mouse Mups, including 2-sec-butyl-4,5-dihydrothiazole (abbreviated as SBT or DHT), 6-hydroxy-6-methyl-3-heptanone (HMH) and 2,3 dihydro-exo-brevicomin (DHB).<ref name=Halpern1>{{cite journal | vauthors = Halpern M, Martínez-Marcos A | title = Structure and function of the vomeronasal system: an update | journal = Progress in Neurobiology | volume = 70 | issue = 3 | pages = 245–318 | date = June 2003 | pmid = 12951145 | doi = 10.1016/S0301-0082(03)00103-5 | s2cid = 31122845 | url = https://pdfs.semanticscholar.org/22f2/53336dbce6de5378b9733023db8a4ed70aa4.pdf | archive-url = https://web.archive.org/web/20171107010214/https://pdfs.semanticscholar.org/22f2/53336dbce6de5378b9733023db8a4ed70aa4.pdf | archive-date = 2017-11-07 }}</ref><ref name=Timm1>{{cite journal | vauthors = Timm DE, Baker LJ, Mueller H, Zidek L, Novotny MV | title = Structural basis of pheromone binding to mouse major urinary protein (MUP-I) | journal = Protein Science | volume = 10 | issue = 5 | pages = 997–1004 | date = May 2001 | pmid = 11316880 | pmc = 2374202 | doi = 10.1110/ps.52201 }}</ref><ref name=Armstrong1>{{cite journal | vauthors = Armstrong SD, Robertson DH, Cheetham SA, Hurst JL, Beynon RJ | title = Structural and functional differences in isoforms of mouse major urinary proteins: a male-specific protein that preferentially binds a male pheromone | journal = The Biochemical Journal | volume = 391 | issue = Pt 2 | pages = 343–50 | date = October 2005 | pmid = 15934926 | pmc = 1276933 | doi = 10.1042/BJ20050404 }}</ref> These are all urine-specific chemicals that have been shown to act as pheromones—molecular signals excreted by one individual that trigger an innate behavioural response in another member of the same species.<ref name=Halpern1/><ref name=Stowers1>{{cite journal | vauthors = Stowers L, Marton TF | title = What is a pheromone? Mammalian pheromones reconsidered | journal = Neuron | volume = 46 | issue = 5 | pages = 699–702 | date = June 2005 | pmid = 15924856 | doi = 10.1016/j.neuron.2005.04.032 | s2cid = 9354126 | doi-access = free }}</ref> Mouse Mups have also been shown to function as pheromone stabilizers, providing a slow release mechanism that extends the potency of volatile pheromones in male urine scent marks.<ref name=Hurst1>{{cite journal | vauthors = Hurst JL, Robertson DH, Tolladay U, Beynon RJ | title = Proteins in urine scent marks of male house mice extend the longevity of olfactory signals | journal = Animal Behaviour | volume = 55 | issue = 5 | pages = 1289–97 | date = May 1998 | pmid = 9632512 | doi = 10.1006/anbe.1997.0650 | s2cid = 9879771 }}</ref> Given the diversity of Mups in rodents, it was originally thought that different Mups may have differently shaped binding pockets and therefore bind different pheromones. However, detailed studies found that most variable sites are located on the surface of the proteins and appear to have little effect on ligand binding.<ref name=Darwish1>{{cite journal | vauthors = Darwish Marie A, Veggerby C, Robertson DH, Gaskell SJ, Hubbard SJ, Martinsen L, Hurst JL, Beynon RJ | title = Effect of polymorphisms on ligand binding by mouse major urinary proteins | journal = Protein Science | volume = 10 | issue = 2 | pages = 411–7 | date = February 2001 | pmid = 11266626 | pmc = 2373947 | doi = 10.1110/ps.31701 }}</ref>

Rat Mups bind different small chemicals. The most common ligand is 1-Chlorodecane, with 2-methyl-N-phenyl-2-propenamide, hexadecane and 2,6,11-trimethyl decane found to be less prominent.<ref name=Rajkumar>{{cite journal | vauthors = Rajkumar R, Ilayaraja R, Mucignat C, Cavaggioni A, Archunan G | title = Identification of alpha2u-globulin and bound volatiles in the Indian common house rat (Rattus rattus) | journal = Indian Journal of Biochemistry & Biophysics | volume = 46 | issue = 4 | pages = 319–24 | date = August 2009 | pmid = 19788064 }}</ref> Rat Mups also bind limonene-1,2-epoxide, resulting in a disease of the host's kidney, hyaline-droplet nephropathy, that progresses to cancer. Other species do not develop this disorder because their Mups do not bind that particular chemical.<ref name=Lehman1>{{cite journal | vauthors = Lehman-McKeeman LD, Caudill D | title = Biochemical basis for mouse resistance to hyaline droplet nephropathy: lack of relevance of the alpha 2u-globulin protein superfamily in this male rat-specific syndrome | journal = Toxicology and Applied Pharmacology | volume = 112 | issue = 2 | pages = 214–21 | date = February 1992 | pmid = 1371614 | doi = 10.1016/0041-008X(92)90190-4 }}</ref> Accordingly, when transgenic mice were engineered to express the rat Mup, their kidneys developed the disease.<ref name=Lehman2>{{cite journal | vauthors = Lehman-McKeeman LD, Caudill D | title = d-Limonene induced hyaline droplet nephropathy in alpha 2u-globulin transgenic mice | journal = Fundamental and Applied Toxicology | volume = 23 | issue = 4 | pages = 562–8 | date = November 1994 | pmid = 7532604 | doi = 10.1006/faat.1994.1141 }}</ref> The Mup found in pigs, named ''salivary lipocalin'' (SAL), is expressed in the salivary gland of males where it tightly binds androstenone and androstenol, both pheromones that cause female pigs to assume a mating stance.<ref name=Logan/><ref name=Loebel>{{cite journal | vauthors = Loebel D, Scaloni A, Paolini S, Fini C, Ferrara L, Breer H, Pelosi P | title = Cloning, post-translational modifications, heterologous expression and ligand-binding of boar salivary lipocalin | journal = The Biochemical Journal | volume = 350 Pt 2 | issue = Pt 2 | pages = 369–79 | date = September 2000 | pmid = 10947950 | pmc = 1221263 | doi = 10.1042/0264-6021:3500369 }}</ref>

Isothermal titration calorimetry studies performed with Mups and associated ligands (pyrazines,<ref>{{cite journal | vauthors = Bingham RJ, Findlay JB, Hsieh SY, Kalverda AP, Kjellberg A, Perazzolo C, Phillips SE, Seshadri K, Trinh CH, Turnbull WB, Bodenhausen G, Homans SW | title = Thermodynamics of binding of 2-methoxy-3-isopropylpyrazine and 2-methoxy-3-isobutylpyrazine to the major urinary protein | journal = Journal of the American Chemical Society | volume = 126 | issue = 6 | pages = 1675–81 | date = February 2004 | pmid = 14871097 | doi = 10.1021/ja038461i | bibcode = 2004JAChS.126.1675B | url = https://infoscience.epfl.ch/record/80419 }}</ref><ref>{{cite journal | vauthors = Barratt E, Bingham RJ, Warner DJ, Laughton CA, Phillips SE, Homans SW | title = Van der Waals interactions dominate ligand-protein association in a protein binding site occluded from solvent water | journal = Journal of the American Chemical Society | volume = 127 | issue = 33 | pages = 11827–34 | date = August 2005 | pmid = 16104761 | doi = 10.1021/ja0527525 }}</ref> alcohols,<ref name=Mucignat-Caretta/><ref>{{cite journal | vauthors = Malham R, Johnstone S, Bingham RJ, Barratt E, Phillips SE, Laughton CA, Homans SW | title = Strong solute-solute dispersive interactions in a protein-ligand complex | journal = Journal of the American Chemical Society | volume = 127 | issue = 48 | pages = 17061–7 | date = December 2005 | pmid = 16316253 | doi = 10.1021/ja055454g }}</ref> thiazolines,<ref>{{cite journal | vauthors = Sharrow SD, Novotny MV, Stone MJ | title = Thermodynamic analysis of binding between mouse major urinary protein-I and the pheromone 2-sec-butyl-4,5-dihydrothiazole | journal = Biochemistry | volume = 42 | issue = 20 | pages = 6302–9 | date = May 2003 | pmid = 12755635 | doi = 10.1021/bi026423q }}</ref><ref name="Timm1"/> 6-hydroxy-6-methyl-3-heptanone,<ref>{{cite journal | vauthors = Sharrow SD, Edmonds KA, Goodman MA, Novotny MV, Stone MJ | title = Thermodynamic consequences of disrupting a water-mediated hydrogen bond network in a protein:pheromone complex | journal = Protein Science | volume = 14 | issue = 1 | pages = 249–56 | date = January 2005 | pmid = 15608125 | pmc = 2253314 | doi = 10.1110/ps.04912605 }}</ref> and N-phenylnapthylamine,<ref>{{cite journal | vauthors = Pertinhez TA, Ferrari E, Casali E, Patel JA, Spisni A, Smith LJ | title = The binding cavity of mouse major urinary protein is optimised for a variety of ligand binding modes | journal = Biochemical and Biophysical Research Communications | volume = 390 | issue = 4 | pages = 1266–71 | date = December 2009 | pmid = 19878650 | doi = 10.1016/j.bbrc.2009.10.133 }}</ref><ref name= Homans>{{cite journal | vauthors = Homans SW | title = Water, water everywhere--except where it matters? | journal = Drug Discovery Today | volume = 12 | issue = 13–14 | pages = 534–9 | date = July 2007 | pmid = 17631247 | doi = 10.1016/j.drudis.2007.05.004 }}</ref>) revealed an unusual binding phenomena. The active site has been found to be suboptimally hydrated, resulting in ligand binding being driven by enthalpic dispersion forces. This is contrary to most other proteins, which exhibit entropy-driven binding forces from the reorganisation of water molecules. This unusual process has been termed the ''nonclassical hydrophobic effect''.<ref name= Homans/>

===Pheromones=== [[File:Protein gel showing mouse urinary proteins.jpg|thumb|left| The Mups in C57BL/6J mouse urine analyzed by native gel electrophoresis |alt=Different banding patterns of proteins from male and female mouse urine resolved by gel electrophoresis]]

Studies have sought to find the precise function of Mups in pheromone communication. Mup proteins have been shown to promote puberty and accelerate the estrus cycle in female mice, inducing the Vandenbergh and Whitten effects.<ref name=Mucignat-Caretta>{{cite journal | vauthors = Mucignat-Caretta C, Caretta A, Cavaggioni A | title = Acceleration of puberty onset in female mice by male urinary proteins | journal = The Journal of Physiology | volume = 486 ( Pt 2) | issue = Pt 2 | pages = 517–22 | date = July 1995 | pmid = 7473215 | pmc = 1156539 | doi = 10.1113/jphysiol.1995.sp020830 }}</ref><ref name=Marchlewska-koj>{{cite journal |vauthors =Marchlewska-koj A, Caretta A, Mucignat-Caretta C, Olejniczak, P|s2cid=9181177 |title=Stimulation of estrus in female mice by male urinary proteins |journal=Journal of Chemical Ecology |volume=26 |issue=10 |pages=2355–65 |year=2000 |doi=10.1023/A:1005578911652|bibcode=2000JCEco..26.2355M }}</ref> However, in both cases the Mups had to be presented to the female dissolved in male urine, indicating that the protein requires some urinary context to function. In 2007 Mups normally found in male mouse urine were made in transgenic bacteria, and therefore created devoid of the chemicals they normally bind. These Mups were shown to be sufficient to promote aggressive behaviour in males, even in the absence of urine.<ref name=Chamero1>{{cite journal | vauthors = Chamero P, Marton TF, Logan DW, Flanagan K, Cruz JR, Saghatelian A, Cravatt BF, Stowers L | title = Identification of protein pheromones that promote aggressive behaviour | journal = Nature | volume = 450 | issue = 7171 | pages = 899–902 | date = December 2007 | pmid = 18064011 | doi = 10.1038/nature05997 | bibcode = 2007Natur.450..899C | s2cid = 4398766 }}</ref> In addition, Mups made in bacteria were found to activate olfactory sensory neurons in the vomeronasal organ (VNO), a subsystem of the nose known to detect pheromones via specific sensory receptors, of mice and rats.<ref name=Chamero1/><ref name=Krieger1>{{cite journal | vauthors = Krieger J, Schmitt A, Löbel D, Gudermann T, Schultz G, Breer H, Boekhoff I | title = Selective activation of G protein subtypes in the vomeronasal organ upon stimulation with urine-derived compounds | journal = The Journal of Biological Chemistry | volume = 274 | issue = 8 | pages = 4655–62 | date = February 1999 | pmid = 9988702 | doi = 10.1074/jbc.274.8.4655 | doi-access = free }}</ref> Together, this demonstrated that Mup proteins can act as pheromones themselves, independent of their ligands.<ref name="BBCreport">{{cite web| title = Aggression protein found in mice | work = BBC News | date = 5 December 2007 | url = https://news.bbc.co.uk/1/hi/sci/tech/7129176.stm | access-date = 26 September 2009}}</ref> [[File:PrideandPrejudiceCH3detail.jpg|thumb|right|Fitzwilliam Darcy was the inspiration for the naming of ''darcin'', the Mup that attracts female mice to male urine. |alt=Illustration of Mr. Darcy and Elizabeth Bennet from ''Pride and Prejudice'', by C. E. Brock (1895)]]

Consistent with a role in male-male aggression, adult male mice secrete significantly more Mups into their urine than females, juveniles or castrated male mice. The precise mechanism driving this difference between the sexes is complex, but at least three hormones—testosterone, growth hormone and thyroxine—are known to positively influence the production of Mups in mice.<ref name="Knopf">{{cite journal | vauthors = Knopf JL, Gallagher JF, Held WA | title = Differential, multihormonal regulation of the mouse major urinary protein gene family in the liver | journal = Molecular and Cellular Biology | volume = 3 | issue = 12 | pages = 2232–40 | date = December 1983 | pmid = 6656765 | pmc = 370094 | doi = 10.1128/MCB.3.12.2232 }}</ref> Wild house mouse urine contains variable combinations of four to seven distinct Mup proteins per mouse.<ref name= Robertson1>{{cite journal | vauthors = Robertson DH, Hurst JL, Bolgar MS, Gaskell SJ, Beynon RJ | title = Molecular heterogeneity of urinary proteins in wild house mouse populations | journal = Rapid Communications in Mass Spectrometry | volume = 11 | issue = 7 | pages = 786–90 | year = 1997 | pmid = 9161047 | doi = 10.1002/(SICI)1097-0231(19970422)11:7<786::AID-RCM876>3.0.CO;2-8 | bibcode = 1997RCMS...11..786R }}</ref> Some inbred laboratory mouse strains, such as BALB/c and C57BL/6, also have different proteins expressed in their urine.<ref name="Mudge">{{cite journal | vauthors = Mudge JM, Armstrong SD, McLaren K, Beynon RJ, Hurst JL, Nicholson C, Robertson DH, Wilming LG, Harrow JL | title = Dynamic instability of the major urinary protein gene family revealed by genomic and phenotypic comparisons between C57 and 129 strain mice | journal = Genome Biology | volume = 9 | issue = 5 | pages = R91 | year = 2008 | pmid = 18507838 | pmc = 2441477 | doi = 10.1186/gb-2008-9-5-r91 | doi-access = free }}</ref> However, unlike wild mice, different individuals from the same strain express the same protein pattern, an artifact of many generations of inbreeding.<ref name= Robertson2>{{cite journal | vauthors = Robertson DH, Cox KA, Gaskell SJ, Evershed RP, Beynon RJ | title = Molecular heterogeneity in the Major Urinary Proteins of the house mouse Mus musculus | journal = The Biochemical Journal | volume = 316 ( Pt 1) | issue = Pt 1 | pages = 265–72 | date = May 1996 | pmid = 8645216 | pmc = 1217333 | doi = 10.1042/bj3160265 }}</ref><ref name=Cheetham1>{{cite journal | vauthors = Cheetham SA, Smith AL, Armstrong SD, Beynon RJ, Hurst JL | title = Limited variation in the major urinary proteins of laboratory mice | journal = Physiology & Behavior | volume = 96 | issue = 2 | pages = 253–61 | date = February 2009 | pmid = 18973768 | doi = 10.1016/j.physbeh.2008.10.005 | s2cid = 20637696 }}</ref> One unusual Mup is less variable than the others: it is consistently produced by a high proportion of wild male mice and is almost never found in female urine. When this Mup was made in bacteria and used in behavioural testing, it was found to attract female mice. Other Mups were tested but did not have the same attractive qualities, suggesting the male-specific Mup acts as a sex pheromone.<ref name="Brennan">{{cite journal | vauthors = Brennan PA | title = On the scent of sexual attraction | journal = BMC Biology | volume = 8 | issue = 1 | page = 71 | date = June 2010 | pmid = 20504292 | pmc = 2880966 | doi = 10.1186/1741-7007-8-71 | doi-access = free }}</ref> Scientists named this Mup ''darcin'' (''Mup20'', {{UniProt|Q5FW60}}) as a humorous reference to Fitzwilliam Darcy, the romantic hero from ''Pride and Prejudice''.<ref name="darcin">{{cite journal | vauthors = Roberts SA, Simpson DM, Armstrong SD, Davidson AJ, Robertson DH, McLean L, Beynon RJ, Hurst JL | title = Darcin: a male pheromone that stimulates female memory and sexual attraction to an individual male's odour | journal = BMC Biology | volume = 8 | issue = 1 | page = 75 | date = June 2010 | pmid = 20525243 | pmc = 2890510 | doi = 10.1186/1741-7007-8-75 | doi-access = free }}</ref><ref name="Fox">{{cite web |url=https://www.foxnews.com/scitech/2010/06/03/biologists-learn-mice-urine-darcin/ |title=Biologists Learn Why Mice Go Gaga for Urine | vauthors = Moskowitz C |date=3 June 2010 |work=FoxNews.com |publisher=FOX News Network |access-date=9 June 2010}}</ref> Taken together, the complex patterns of Mups produced has the potential to provide a range of information about the donor animal, such as gender, fertility, social dominance, age, genetic diversity or kinship.<ref name=Chamero1/><ref name=Hurst2>{{cite journal | vauthors = Hurst JL, Payne CE, Nevison CM, Marie AD, Humphries RE, Robertson DH, Cavaggioni A, Beynon RJ | title = Individual recognition in mice mediated by major urinary proteins | journal = Nature | volume = 414 | issue = 6864 | pages = 631–4 | date = December 2001 | pmid = 11740558 | doi = 10.1038/414631a | bibcode = 2001Natur.414..631H | s2cid = 464644 }}</ref><ref name=Thom1>{{cite journal | vauthors = Thom MD, Stockley P, Jury F, Ollier WE, Beynon RJ, Hurst JL | title = The direct assessment of genetic heterozygosity through scent in the mouse | journal = Current Biology | volume = 18 | issue = 8 | pages = 619–23 | date = April 2008 | pmid = 18424142 | doi = 10.1016/j.cub.2008.03.056 | s2cid = 268741 | doi-access = free | bibcode = 2008CBio...18..619T }}</ref> Wild mice (unlike laboratory mice that are genetically identical and which therefore also have identical patterns of Mups in the urine) have individual patterns of Mup expression in their urine that act as a "barcode" to uniquely identify the owner of a scent mark.<ref name= Hurst2/>

In the house mouse, the major MUP gene cluster provides a highly polymorphic scent signal of genetic identity. Wild mice breeding freely in semi-natural enclosures showed inbreeding avoidance. This avoidance resulted from a strong deficit in successful matings between mice sharing both MUP haplotypes (complete match).<ref>{{cite journal | vauthors = Sherborne AL, Thom MD, Paterson S, Jury F, Ollier WE, Stockley P, Beynon RJ, Hurst JL | title = The genetic basis of inbreeding avoidance in house mice | journal = Current Biology | volume = 17 | issue = 23 | pages = 2061–6 | date = December 2007 | pmid = 17997307 | pmc = 2148465 | doi = 10.1016/j.cub.2007.10.041 | bibcode = 2007CBio...17.2061S }}</ref> In another study, using white-footed mice, it was found that when mice derived from wild populations were inbred, there was reduced survival when such mice were reintroduced into a natural habitat.<ref>{{cite journal | vauthors = Jiménez JA, Hughes KA, Alaks G, Graham L, Lacy RC | title = An experimental study of inbreeding depression in a natural habitat | journal = Science | volume = 266 | issue = 5183 | pages = 271–3 | date = October 1994 | pmid = 7939661 | doi = 10.1126/science.7939661 | bibcode = 1994Sci...266..271J }}</ref> These findings suggest that inbreeding reduces fitness, and that scent signal recognition has evolved in mice as a means of avoiding inbreeding depression.

===Kairomones=== In addition to serving as social cues between members of the same species, Mups can act as kairomones—chemical signals that transmit information between species.<ref name="Papes">{{cite journal | vauthors = Papes F, Logan DW, Stowers L | title = The vomeronasal organ mediates interspecies defensive behaviors through detection of protein pheromone homologs | journal = Cell | volume = 141 | issue = 4 | pages = 692–703 | date = May 2010 | pmid = 20478258 | pmc = 2873972 | doi = 10.1016/j.cell.2010.03.037 }}</ref><ref name="Rodriguez">{{cite journal | vauthors = Rodriguez I | title = The chemical MUPpeteer | journal = Cell | volume = 141 | issue = 4 | pages = 568–70 | date = May 2010 | pmid = 20478249 | doi = 10.1016/j.cell.2010.04.032 | s2cid = 13992615 | doi-access = free }}</ref><ref name="BBCreport2">{{cite web |url=https://www.bbc.co.uk/news/10117428 |title=Why mice fear the smell of cats |date=17 May 2010 |work=BBC News |access-date=18 May 2010}}</ref> Mice are instinctively afraid of the smell of their natural predators, including cats and rats. This occurs even in laboratory mice that have been isolated from predators for hundreds of generations.<ref name="Sciencenews">{{cite news |title=Fight or flee, it's in the pee |first=Rachel |last=Ehrenberg |newspaper=Science News |date=5 June 2010 |url=http://www.sciencenews.org/view/generic/id/59205/title/Fight_or_flee,_it%E2%80%99s_in_the_pee |access-date=10 June 2010 |archive-date=12 October 2012 |archive-url=https://web.archive.org/web/20121012052558/http://www.sciencenews.org/view/generic/id/59205/title/Fight_or_flee%2C_it%E2%80%99s_in_the_pee }}</ref> When the chemical cues responsible for the fear response were purified from cat saliva and rat urine, two homologous protein signals were identified: Fel&nbsp;d&nbsp;4 (''Felis domesticus'' allergen 4; {{UniProt|Q5VFH6}}), the product of the cat ''Mup'' gene, and Rat&nbsp;n&nbsp;1 (''Rattus norvegicus'' allergen 1; {{UniProt|P02761}}), the product of the rat ''Mup13'' gene.<ref name="Rodriguez"/> Mice are fearful of these Mups even when they are made in bacteria, but mutant animals that are unable to detect the Mups showed no fear of rats, demonstrating their importance in initiating fearful behaviour.<ref name="Papes"/><ref name="NYT">{{cite news |title=When a Mouse Smells a Rat |first=Sindya |last=Bhanoo |newspaper= The New York Times |date=17 May 2010 |url=https://www.nytimes.com/2010/05/18/science/18obmouse.html}}</ref> It is not known exactly how Mups from different species initiate disparate behaviours, but mouse Mups and predator Mups have been shown to activate unique patterns of sensory neurons in the nose of recipient mice. This implies the mouse perceives them differently, via distinct neural circuits.<ref name="Papes"/><ref name="Rodriguez"/> The pheromone receptors responsible for Mup detection are also unknown, though they are thought be members of the V2R receptor class.<ref name="Chamero1"/><ref name="Rodriguez"/>

===Metabolism=== While the detection of Mups excreted by other animals has been well studied, the functional role in the producing animal is less clear. However, in 2009, Mups were shown to be associated with the regulation of energy expenditure in mice. Scientists found that genetically induced obese, diabetic mice produce thirty times less Mup RNA than their lean siblings.<ref name="Hui"/> When they delivered Mup protein directly into the bloodstream of these mice, they observed an increase in energy expenditure, physical activity and body temperature and a corresponding decrease in glucose intolerance and insulin resistance. They propose that Mups' beneficial effects on energy metabolism occurs by enhancing mitochondrial function in skeletal muscle.<ref name="Hui">{{cite journal | vauthors = Hui X, Zhu W, Wang Y, Lam KS, Zhang J, Wu D, Kraegen EW, Li Y, Xu A | title = Major urinary protein-1 increases energy expenditure and improves glucose intolerance through enhancing mitochondrial function in skeletal muscle of diabetic mice | journal = The Journal of Biological Chemistry | volume = 284 | issue = 21 | pages = 14050–7 | date = May 2009 | pmid = 19336396 | pmc = 2682853 | doi = 10.1074/jbc.M109.001107 | doi-access = free }}</ref> Another study found Mups were reduced in diet-induced obese mice. In this case, the presence of Mups in the bloodstream of mice restricted glucose production by directly inhibiting the expression of genes in the liver.<ref name="pmid19258313">{{cite journal | vauthors = Zhou Y, Jiang L, Rui L | title = Identification of MUP1 as a regulator for glucose and lipid metabolism in mice | journal = The Journal of Biological Chemistry | volume = 284 | issue = 17 | pages = 11152–9 | date = April 2009 | pmid = 19258313 | pmc = 2670120 | doi = 10.1074/jbc.M900754200 | doi-access = free }}</ref>

==Allergens== [[File:Crystal structure of Equ c 1 dimer.jpg|thumb|350px|right| The three-dimensional structure of ''Equ c 1'', shown in the crystallized dimeric form.<ref name="Lascombe">{{cite journal | vauthors = Lascombe MB, Grégoire C, Poncet P, Tavares GA, Rosinski-Chupin I, Rabillon J, Goubran-Botros H, Mazié JC, David B, Alzari PM | title = Crystal structure of the allergen Equ c 1. A dimeric lipocalin with restricted IgE-reactive epitopes | journal = The Journal of Biological Chemistry | volume = 275 | issue = 28 | pages = 21572–7 | date = July 2000 | pmid = 10787420 | doi = 10.1074/jbc.M002854200 | doi-access = free }}</ref> The structure is resolved from {{PDB link|1EW3}}. |alt=A ribbon diagram of two identical horse allergen molecules, symmetrically arranged in a crystal structure.]] Along with other members of the lipocalin protein family, major urinary proteins can be potent allergens to humans.<ref name=Lockeychapter>{{cite book |vauthors=Lockey R, Ledford DK |title=Allergens and Allergen Immunotherapy |series=Volume 21 of Clinical allergy and immunology |pages=201–218 |chapter=Mammalian Allergens |publisher=Informa Health Care |year=2008 |isbn=978-1-4200-6197-0}}</ref> The reason for this is not known; however, molecular mimicry between Mups and structurally similar human lipocalins has been proposed as a possible explanation.<ref name="Virtanen">{{cite journal | vauthors = Virtanen T, Zeiler T, Mäntyjärvi R | title = Important animal allergens are lipocalin proteins: why are they allergenic? | journal = International Archives of Allergy and Immunology | volume = 120 | issue = 4 | pages = 247–58 | date = December 1999 | pmid = 10640908 | doi = 10.1159/000024277 | s2cid = 1171463 }}</ref> The protein product of the mouse ''Mup6'' and ''Mup2'' genes (previously mistaken as ''Mup17'' due to the similarity among mouse MUPs), known as Mus&nbsp;m&nbsp;1, Ag1 or MA1,<ref>{{cite web |title=Mus m 1 Allergen Details |url=https://www.allergen.org/viewallergen.php?aid=450 |website=www.allergen.org}}</ref> accounts for much of the allergenic properties of mouse urine.<ref name="Logan"/><ref name="Lorusso">{{cite journal | vauthors = Lorusso JR, Moffat S, Ohman JL | title = Immunologic and biochemical properties of the major mouse urinary allergen (Mus m 1) | journal = The Journal of Allergy and Clinical Immunology | volume = 78 | issue = 5 Pt 1 | pages = 928–37 | date = November 1986 | pmid = 3097107 | doi = 10.1016/0091-6749(86)90242-3 }}</ref> The protein is extremely stable in the environment; studies have found 95% of inner city homes and 82% of all types of homes in the United States have detectable levels in at least one room.<ref name="Cohn">{{cite journal | vauthors = Cohn RD, Arbes SJ, Yin M, Jaramillo R, Zeldin DC | title = National prevalence and exposure risk for mouse allergen in US households | journal = The Journal of Allergy and Clinical Immunology | volume = 113 | issue = 6 | pages = 1167–71 | date = June 2004 | pmid = 15208600 | doi = 10.1016/j.jaci.2003.12.592 | url = https://zenodo.org/record/1259079 | doi-access = free }}</ref><ref name="Phipatanakul">{{cite journal | vauthors = Phipatanakul W, Eggleston PA, Wright EC, Wood RA | title = Mouse allergen. I. The prevalence of mouse allergen in inner-city homes. The National Cooperative Inner-City Asthma Study | journal = The Journal of Allergy and Clinical Immunology | volume = 106 | issue = 6 | pages = 1070–4 | date = December 2000 | pmid = 11112888 | doi = 10.1067/mai.2000.110796 }}</ref> Similarly, Rat&nbsp;n&nbsp;1 is a known human allergen.<ref name=Lockeychapter/> A US study found its presence in 33% of inner city homes, and 21% of occupants were sensitized to the allergen.<ref name="Perry">{{cite journal | vauthors = Perry T, Matsui E, Merriman B, Duong T, Eggleston P | title = The prevalence of rat allergen in inner-city homes and its relationship to sensitization and asthma morbidity | journal = The Journal of Allergy and Clinical Immunology | volume = 112 | issue = 2 | pages = 346–52 | date = August 2003 | pmid = 12897741 | doi = 10.1067/mai.2003.1640 | s2cid = 25216587 }}</ref> Exposure and sensitization to rodent Mup proteins is considered a risk factor for childhood asthma and is a leading cause of laboratory animal allergy (LAA)—an occupational disease of laboratory animal technicians and scientists.<ref name="Wood">{{cite journal | vauthors = Wood RA | title = Laboratory animal allergens | journal = ILAR Journal | volume = 42 | issue = 1 | pages = 12–6 | year = 2001 | pmid = 11123185 | doi = 10.1093/ilar.42.1.12 | doi-access = free }}</ref><ref name="Gaffin">{{cite journal | vauthors = Gaffin JM, Phipatanakul W | title = The role of indoor allergens in the development of asthma | journal = Current Opinion in Allergy and Clinical Immunology | volume = 9 | issue = 2 | pages = 128–35 | date = April 2009 | pmid = 19326507 | pmc = 2674017 | doi = 10.1097/ACI.0b013e32832678b0 }}</ref><ref name="Pongracic">{{cite journal | vauthors = Pongracic JA, Visness CM, Gruchalla RS, Evans R, Mitchell HE | title = Effect of mouse allergen and rodent environmental intervention on asthma in inner-city children | journal = Annals of Allergy, Asthma & Immunology | volume = 101 | issue = 1 | pages = 35–41 | date = July 2008 | pmid = 18681082 | doi = 10.1016/S1081-1206(10)60832-0 }}</ref><ref name="Gordon">{{cite journal | vauthors = Gordon S, Preece R | title = Prevention of laboratory animal allergy | journal = Occupational Medicine | volume = 53 | issue = 6 | pages = 371–7 | date = September 2003 | pmid = 14514903 | doi = 10.1093/occmed/kqg117 | doi-access = free }}</ref> One study found that two-thirds of laboratory workers who had developed asthmatic reactions to animals had antibodies to Rat&nbsp;n&nbsp;1.<ref name="Platts-Mills">{{cite journal | vauthors = Platts-Mills TA, Longbottom J, Edwards J, Cockroft A, Wilkins S | title = Occupational asthma and rhinitis related to laboratory rats: serum IgG and IgE antibodies to the rat urinary allergen | journal = The Journal of Allergy and Clinical Immunology | volume = 79 | issue = 3 | pages = 505–15 | date = March 1987 | pmid = 3819230 | doi = 10.1016/0091-6749(87)90369-1 }}</ref>

''Mup'' genes from other mammals also encode allergenic proteins, for example Fel&nbsp;d&nbsp;4 is primarily produced in the submandibular salivary gland and is deposited onto dander as the cat grooms itself. A study found that 63% of cat allergic people have antibodies against the protein. Most had higher titres of antibodies against Fel&nbsp;d&nbsp;4 than against Fel&nbsp;d&nbsp;1, another prominent cat allergen.<ref name="pmid15544598">{{cite journal | vauthors = Smith W, Butler AJ, Hazell LA, Chapman MD, Pomés A, Nickels DG, Thomas WR | title = Fel d 4, a cat lipocalin allergen | journal = Clinical and Experimental Allergy | volume = 34 | issue = 11 | pages = 1732–8 | date = November 2004 | pmid = 15544598 | doi = 10.1111/j.1365-2222.2004.02090.x | s2cid = 20266013 }}</ref> Likewise, ''Equ&nbsp;c 1'' (''Equus caballus'' allergen 1; {{UniProt|Q95182}}) is the protein product of a horse ''Mup'' gene that is found in the liver, sublingual and submaxillary salivary glands.<ref name="Logan"/><ref name="Gregoire">{{cite journal | vauthors = Gregoire C, Rosinski-Chupin I, Rabillon J, Alzari PM, David B, Dandeu JP | title = cDNA cloning and sequencing reveal the major horse allergen Equ c1 to be a glycoprotein member of the lipocalin superfamily | journal = The Journal of Biological Chemistry | volume = 271 | issue = 51 | pages = 32951–9 | date = December 1996 | pmid = 8955138 | doi = 10.1074/jbc.271.51.32951 | doi-access = free }}</ref> It is responsible for about 80% of the antibody response in patients who are chronically exposed to horse allergens.<ref name="Gregoire"/>

== See also == {{Portal|Biology}} * Cis-vaccenyl acetate, an insect aggression pheromone * Major histocompatibility complex, peptides also implicated in individual recognition in mice * Proteins produced and secreted by the liver

==Notes== {{reflist|group="notes"}}

== References == {{reflist|colwidth=30em}}

== External links == {{Commons category|Major urinary protein or alpha-2u-globulin}} * [https://web.archive.org/web/20090308164052/http://whyfiles.org/shorties/093urine/ Scent of a Rodent], The Why Files – The Science Behind The News * {{YouTube|id = yh2JFcQCgFQ|title = Fear Signals from Predators}}, a video describing the research that determined Mups were kairomones

{{Carrier proteins}} {{featured article}}

Category:Pheromones Category:Allergology Category:Protein families Category:Urine Category:Mouse proteins Category:Lipocalins