WORKLIST ENTRIES (1):
MAJORURINARY View alignment View Structure Rodent urinary protein signature
Type of fingerprint: COMPOUND with 7 elements
Links:
PRINTS; PR00179 LIPOCALIN; PR00178 FATTYACIDBP
INTERPRO; IPR002971
PDB; 1MUP 3Dinfo
SCOP; 1MUP
CATH; 1MUP
Creation date 30-NOV-1999
1. PERVAIS, S. AND BREW, K.
Homology of beta-lactoglobulin, serum retinol-binding protein and
protein HC.
SCIENCE 228 335-337 (1985).
2. FLOWER, D.R.
The Lipocalin protein family: structure and function.
BIOCHEM.J. 318 1-14 (1996).
3. FLOWER, D.R., NORTH, A.C.T. AND ATTWOOD, T.K.
Structural and sequence relationships in the lipocalins and related
proteins.
PROTEIN SCI. 2 753-761 (1993).
4. FLOWER, D.R.
Multiple molecular recognition properties of the lipocalin protein family.
J.MOL.REC. 8 185-195 (1995).
5. BOCSKEI, Z., GROOM, C.R., FLOWER, D.R., WRIGHT, C.E., PHILLIPS, S.E.V.,
CAVAGGIONI, A., FINDLAY, J.B.C. AND NORTH, A.C.T.
Pheromone Binding to Two Rodent Urinary Proteins Revealed by X-Ray
Crystallography.
NATURE 360 186-190 (1992).
The lipocalins are a diverse, interesting, yet poorly understood family of
proteins composed, in the main, of extracellular ligand-binding proteins
displaying high specificity for small hydrophobic molecules [1,2]. Functions
of these proteins include transport of nutrients, control of cell regula-
tion, pheromone transport, cryptic colouration and the enzymatic synthesis
of prostaglandins.
The crystal structures of several lipocalins have been solved and show a
novel 8-stranded anti-parallel beta-barrel fold well conserved within the
family. Sequence similarity within the family is at a much lower level and
would seem to be restricted to conserved disulphides and 3 motifs, which
form a juxtaposed cluster that may act as a common cell surface receptor
site [2]. By contrast, at the more variable end of the fold are found an
internal ligand binding site and a putative surface for the formation of
macromolecular complexes [4]. The anti-parallel beta-barrel fold is also
exploited by the fatty acid-binding proteins (which function similarly by
binding small hydrophobic molecules), by avidin and the closely related
metalloprotease inhibitors, and by triabin. Similarity at the sequence
level, however, is less obvious, being confined to a single short
N-terminal motif.
The lipocalin family can be subdivided into kernal and outlier sets. The
kernal lipocalins form the largest self-consistent group (see LIPOCALIN
signature). The outlier lipocalins form several smaller distinct subgroups:
the OBPs, the von Ebner's gland proteins, alpha-1-acid glycoproteins,
tick histamine binding proteins and the nitrophorins.
Rodent urinary proteins (mouse MUPs and rat alpha-2u globulins) are the
major protein components of rodent urine and transport pheromones [5].
Rodent urine contains an unusually large amount of protein; this phenomenon
has been studied extensively in both rats and mice. The major site of MUP
synthesis is the liver; the protein is secreted by the liver into serum,
where it circulates at relatively low levels before being rapidly filtered
by the kidney and excreted. Expression of MUP mRNA is under different
developmental and hormonal control in different tissues. However,
constitutive expression of major urinary protein has been demonstrated in
the salivary and lachrymal glands.
The sex-dependent expression of MUP (adult male mice secrete 5-20 times
as much MUP as do females) and its ability to bind a number of odorant
molecules is consistent with the suggestion that MUP acts as a pheromone
transporter; the protein may be excreted into the urine carrying a bound
pheromone, which is released as the urine dries and the protein denatures.
This proposal is strongly supported by the work of Bacchini and colleagues,
who have successfully purified MUP from mouse urine with bound ligands. They
identified three components from the total ligand extracted from the
purified protein: the largest proportion (~70%) was 2-(s-butyl)thiazoline,
with 2,3-dehydroexobrevicomin and 4-(ethyl)phenol comprising minor fractions
of ~15% each. However, only ~40% of protein contained bound ligand. The
first two of these compounds are known to have pheromone activity in male
rat urine, eliciting many sexually related responses in female rats. A
recent report has shown that MUP, acting via the vomeronasal organ after
appropriate physical contact with male mouse urine in their environment, can
accelerate the onset of puberty in female mice. Interestingly, this seems to
be a function of the protein itself; MUP devoid of ligands, either by
extraction or competitive displacement, is still active, while an organic
extract containing these volatile ligands shows no activity. Moreover, a
peptide corresponding to the N-terminus of MUP is also active, suggesting
that MUP is not only a carrier of pheromones, but also a pheromone itself.
The crystal structure of MUP has been solved [5] and is known to be a
member of the lipocalin family.
Alpha-2u-globulin, a close homologue of MUP, accounts for 30-50% of total
excreted protein in adult male rat urine. As its electrophoretic mobility
is similar to that of serum a2 globulin, it was named 'alpha-2u-globulin',
the subscript 'u' denoting its origin in urine. Alpha-2u-globulin is
secreted into the plasma by a number of tissues, where it circulates before
filtration through the kidney; between 20 and 50% is reabsorbed by the
proximal tubule of the nephron, the rest being excreted. Although the exact
physiological role of alpha-2u-globulin is unclear, there is circumstantial
evidence that it functions in pheromone transport. This is consistent with
its observed binding properties, its close similarity with MUP and the known
properties of male rat urine. For example, acute exposure to many important
industrial and environmental chemicals, including components of unleaded
petrol, causes a toxic syndrome, known as a2u globulin nephropathy, in the
kidney of adult male rats. This syndrome is characterised by an excessive
accumulation, in proximal-tubule epithelial cells, of lysosomal protein
droplets composed of large amounts of alpha-2u-globulin, and the degeneration
and necrosis of cells lining the proximal tubule. Chronic exposure leads to
an escalating progression of symptoms, often resulting in kidney failure and
death.
MAJORURINARY is a 7-element fingerprint that provides a signature for rodent
urinary proteins. The fingerprint was derived from an initial alignment of
4 sequences: the motifs were drawn from conserved regions spanning virtually
the full alignment length - motif 1 covers the N-terminal peptide and 310
helix; motif 2, which includes the region encoded by PROSITE pattern
LIPOCALIN (PS00213) and corresponds to the first LIPOCALIN fingerprint motif,
spans the first beta-strand; motif 3 spans the distal region of the large
loop L1 and strands 2 and 3; motif 4 covers strand 4 and the anterior region
of strand 5; motif 5, which spans the C-terminus of strand 6 and strand 7,
corresponds to the second motif of the LIPOCALIN fingerprint; motif 6, which
spans strand 8 and the N-terminus of the main C-terminal alpha-helix, is
similar to the third LIPOCALIN motif; and motif 7 spans the C-terminal
peptide and includes the short beta-strand 9. Two iterations on SPRT37_10f
were required to reach convergence, at which point a true set comprising 11
sequences was identified. A single partial match was also found, horse
allergen 1 protein, which matches motifs 2, 4, 6 and 7.
SUMMARY INFORMATION
11 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
1 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
COMPOSITE FINGERPRINT INDEX
7| 11 11 11 11 11 11 11
6| 0 0 0 0 0 0 0
5| 0 0 0 0 0 0 0
4| 0 1 0 1 0 1 1
3| 0 0 0 0 0 0 0
2| 0 0 0 0 0 0 0
--+------------------------------------
| 1 2 3 4 5 6 7
True positives..
MUP1_MOUSE MUP6_MOUSE MUP2_MOUSE Q61921
MUP5_MOUSE MUP_RAT Q63024 Q63025
MUP4_MOUSE Q63213 MUPM_MOUSE
Subfamily: Codes involving 4 elements
Subfamily True positives..
ALL1_HORSE
PROTEIN TITLES
MUP1_MOUSE MAJOR URINARY PROTEIN 1 PRECURSOR (MUP 1) - MUS MUSCULUS (MO
MUP6_MOUSE MAJOR URINARY PROTEIN 6 PRECURSOR (MUP 6) (ALPHA-2U-GLOBULIN
MUP2_MOUSE MAJOR URINARY PROTEIN 2 PRECURSOR (MUP 2) - MUS MUSCULUS (MO
Q61921 MAJOR URINARY PROTEIN - MUS MUSCULUS (MOUSE).
MUP5_MOUSE MAJOR URINARY PROTEIN 5 PRECURSOR (MUP 5) - MUS MUSCULUS (MO
MUP_RAT MAJOR URINARY PROTEIN PRECURSOR (MUP) (ALPHA-2U-GLOBULIN) (1
Q63024 RAT ALPHA-2U-GLOBULIN (L TYPE) - RATTUS NORVEGICUS (RAT).
Q63025 RAT ALPHA-2U-GLOBULIN (S TYPE) - RATTUS NORVEGICUS (RAT).
MUP4_MOUSE MAJOR URINARY PROTEIN 4 PRECURSOR (MUP 4) - MUS MUSCULUS (MO
Q63213 ALPHA-2U GLOBULIN (RAT SALIVARY GLAND (ALPHA)2(MU) GLOBULIN,
MUPM_MOUSE MINOR MAJOR URINARY PROTEIN 15 PRECURSOR (NON-GROUP 1/GROUP
ALL1_HORSE MAJOR ALLERGEN EQU C 1 PRECURSOR - EQUUS CABALLUS (HORSE).
SCAN HISTORY
SPTR37_10f 2 15 NSINGLE
INITIAL MOTIF SETS
MAJORURINARY1 Length of motif = 15 Motif number = 1
Rodent urinary protein motif I - 1
PCODE ST INT
HAEEASFERGNLDVD Q63213 18 18
HAEESSSMERNFNVE MUPM_MOUSE 21 21
HAEEASSTGRNFNVE Q61921 15 15
HAEEATSKGQNLNVE MUP4_MOUSE 15 15
MAJORURINARY2 Length of motif = 19 Motif number = 2
Rodent urinary protein motif II - 1
PCODE ST INT
NGDWFSIVVASDKREKIEE Q63213 35 2
SGYWFSIAEASYEREKIEE MUPM_MOUSE 38 2
NGEWHTIILAFDKREKIED Q61921 32 2
NGEWFSILLASDKREKIEE MUP4_MOUSE 32 2
MAJORURINARY3 Length of motif = 22 Motif number = 3
Rodent urinary protein motif III - 1
PCODE ST INT
IDVLENSLGFTFRIKENGVCTE Q63213 64 10
ITVLENSLVFKFHLIVNEECTE MUPM_MOUSE 67 10
IHVLENSLVLKFHTVRDEECSE Q61921 61 10
IHVLENSLAFKFHTVIDGECSE MUP4_MOUSE 61 10
MAJORURINARY4 Length of motif = 13 Motif number = 4
Rodent urinary protein motif IV - 1
PCODE ST INT
GEYFVEYDGENTF Q63213 97 11
GIYYMNYDGFNTF MUPM_MOUSE 100 11
GEYSVTYDGFNTF Q61921 94 11
GEYSVMYDGFNTF MUP4_MOUSE 94 11
MAJORURINARY5 Length of motif = 16 Motif number = 5
Rodent urinary protein motif V - 1
PCODE ST INT
ILKTDYDNYVMFHLVN Q63213 111 1
ILKTDYDNYIMIHLIN MUPM_MOUSE 114 1
IPKTDYDNFLMAHLIN Q61921 108 1
ILKTDYDNYIMFHLIN MUP4_MOUSE 108 1
MAJORURINARY6 Length of motif = 22 Motif number = 6
Rodent urinary protein motif VI - 1
PCODE ST INT
TFQLMELYGRTKDLSSDIKEKF Q63213 132 5
TFQLMELYGREPDLSLDIKEKF MUPM_MOUSE 135 5
TFQLMGLYGREPDLSSDIKERF Q61921 129 5
TFQLMELYGRKADLNSDIKEKF MUP4_MOUSE 129 5
MAJORURINARY7 Length of motif = 18 Motif number = 7
Rodent urinary protein motif VII - 1
PCODE ST INT
HGITRDNIIDLTKTDRCL Q63213 160 6
HGIIRENIIDLTNVNRCL MUPM_MOUSE 163 6
HGILRENIIDLSNANRCL Q61921 157 6
HGIIKENIIDLTKTNRCL MUP4_MOUSE 157 6
FINAL MOTIF SETS
MAJORURINARY1 Length of motif = 15 Motif number = 1
Rodent urinary protein motif I - 2
PCODE ST INT
HAEEASSTGRNFNVE MUP1_MOUSE 17 17
HAEEASSTGRNFNVE MUP6_MOUSE 17 17
HAEEASSTGRNFNVE MUP2_MOUSE 17 17
HAEEASSTGRNFNVE Q61921 15 15
HAEEASSERQNFNVE MUP5_MOUSE 17 17
HAEEASSTRGNLDVA MUP_RAT 18 18
HAEEASSTRGNLDVD Q63024 18 18
HAEEASSTRGNLDVD Q63025 18 18
HAEEATSKGQNLNVE MUP4_MOUSE 15 15
HAEEASFERGNLDVD Q63213 18 18
HAEESSSMERNFNVE MUPM_MOUSE 21 21
MAJORURINARY2 Length of motif = 19 Motif number = 2
Rodent urinary protein motif II - 2
PCODE ST INT
NGEWHTIILASDKREKIED MUP1_MOUSE 34 2
NGEWHTIILASDKREKIED MUP6_MOUSE 34 2
NGEWHTIILASDKREKIED MUP2_MOUSE 34 2
NGEWHTIILAFDKREKIED Q61921 32 2
NGKWFSILLASDKREKIEE MUP5_MOUSE 34 2
NGDWFSIVVASNKREKIEE MUP_RAT 35 2
NGDWFSIVVASDKREKIEE Q63024 35 2
NGDWFSIVVASDKREKIEE Q63025 35 2
NGEWFSILLASDKREKIEE MUP4_MOUSE 32 2
NGDWFSIVVASDKREKIEE Q63213 35 2
SGYWFSIAEASYEREKIEE MUPM_MOUSE 38 2
MAJORURINARY3 Length of motif = 22 Motif number = 3
Rodent urinary protein motif III - 2
PCODE ST INT
IHVLENSLVLKFHTVRDEECSE MUP1_MOUSE 63 10
IHVLENSLVLKFHTVRDEECSE MUP6_MOUSE 63 10
IHVLEKSLVLKFHTVRDEECSE MUP2_MOUSE 63 10
IHVLENSLVLKFHTVRDEECSE Q61921 61 10
IDVLENSLAFKFHTVIDEECTE MUP5_MOUSE 63 10
IDVLENSLGFKFRIKENGECRE MUP_RAT 64 10
IDVLENSLGFKFRIKENGECRE Q63024 64 10
IDVLENSLGFKFRIKENGECRE Q63025 64 10
IHVLENSLAFKFHTVIDGECSE MUP4_MOUSE 61 10
IDVLENSLGFTFRIKENGVCTE Q63213 64 10
ITVLENSLVFKFHLIVNEECTE MUPM_MOUSE 67 10
MAJORURINARY4 Length of motif = 13 Motif number = 4
Rodent urinary protein motif IV - 2
PCODE ST INT
GEYSVTYDGFNTF MUP1_MOUSE 96 11
GEYSVTYDGFNTF MUP6_MOUSE 96 11
GEYSVTYDGFNTF MUP2_MOUSE 96 11
GEYSVTYDGFNTF Q61921 94 11
GEYSVTYDGFNTF MUP5_MOUSE 96 11
GEYFVEYDGGNTF MUP_RAT 97 11
GEYFVEYDGGNTF Q63024 97 11
GEYFVEYDGGNTF Q63025 97 11
GEYSVMYDGFNTF MUP4_MOUSE 94 11
GEYFVEYDGENTF Q63213 97 11
GIYYMNYDGFNTF MUPM_MOUSE 100 11
MAJORURINARY5 Length of motif = 16 Motif number = 5
Rodent urinary protein motif V - 2
PCODE ST INT
IPKTDYDNFLMAHLIN MUP1_MOUSE 110 1
IPKTDYDNFLMAHLIN MUP6_MOUSE 110 1
IPKTDYDNFLMAHLIN MUP2_MOUSE 110 1
IPKTDYDNFLMAHLIN Q61921 108 1
ILKTDYDNYIMFHLIN MUP5_MOUSE 110 1
ILKTDYDRYVMFHLIN MUP_RAT 111 1
ILKTDYDRYVMFHLIN Q63024 111 1
ILKTDYDRYVMFHLIN Q63025 111 1
ILKTDYDNYIMFHLIN MUP4_MOUSE 108 1
ILKTDYDNYVMFHLVN Q63213 111 1
ILKTDYDNYIMIHLIN MUPM_MOUSE 114 1
MAJORURINARY6 Length of motif = 22 Motif number = 6
Rodent urinary protein motif VI - 2
PCODE ST INT
TFQLMGLYGREPDLSSDIKERF MUP1_MOUSE 131 5
TFQLMGLYGREPDLMSDIKERF MUP6_MOUSE 131 5
TFQLMGLYGREPDLSSDIKERF MUP2_MOUSE 131 5
TFQLMGLYGREPDLSSDIKERF Q61921 129 5
NFQLMELFGREPDLSSDIKEKF MUP5_MOUSE 131 5
TFQLMVLYGRTKDLSSDIKEKF MUP_RAT 132 5
TFQAMVLYGRTKDLSSDIKEKF Q63024 132 5
TFQAMVLYGRTKDLSSDIKEKF Q63025 132 5
TFQLMELYGRKADLNSDIKEKF MUP4_MOUSE 129 5
TFQLMELYGRTKDLSSDIKEKF Q63213 132 5
TFQLMELYGREPDLSLDIKEKF MUPM_MOUSE 135 5
MAJORURINARY7 Length of motif = 18 Motif number = 7
Rodent urinary protein motif VII - 2
PCODE ST INT
HGILRENIIDLSNANRCL MUP1_MOUSE 159 6
HGILRENIIDLSNANRCL MUP6_MOUSE 159 6
HGILRENIIDLSNANRCL MUP2_MOUSE 159 6
HGILRENIIDLSNANRCL Q61921 157 6
HGIVRENIIDLSNANRCL MUP5_MOUSE 159 6
HGITRDNIIDLTKTDRCL MUP_RAT 160 6
HGITRDNIIDLTKTDHCL Q63024 160 6
HGITRDNIIDLTKTDHCL Q63025 160 6
HGIIKENIIDLTKTNRCL MUP4_MOUSE 157 6
HGITRDNIIDLTKTDRCL Q63213 160 6
HGIIRENIIDLTNVNRCL MUPM_MOUSE 163 6
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