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PR01841

Identifier
WNT1PROTEIN  [View Relations]  [View Alignment]  
Accession
PR01841
No. of Motifs
5
Creation Date
06-JAN-2003
Title
Wnt-1 protein signature
Database References
PRINTS; PR01349 WNTPROTEIN
MIM; 164820
Literature References
1. WODARZ, A. AND NUSSE, R.
Mechanisms of Wnt signal transduction.
ANNU.REV.CELL DEV.BIOL. 14 59-88 (1998).
 
2. BEJSOVEC, A.
Signal transduction: Wnt signalling shows its versatility.
CURR.BIOL. 9 R684-R687 (1999).
 
3. DE FERRARI, G.V. AND INESTROSA, N.C.
Wnt signaling function in Alzheimer's disease.
BRAIN RES.BRAIN RES.REV. 33 1-12 (2000).
 
4. SEMENOV, M.V. AND SNYDER, M.
Human dishevelled genes constitute a DHR-containing multigene family.
GENOMICS 42 302-310 (1997).
 
5. PEIFER, M. AND POLAKIS, P.
Wnt signalling in oncogenesis and embryogenesis - a look outside the
nucleus.
SCIENCE 287 1606-1609 (2000).
 
6. MOON, R.T.
An introduction to non-canonical Wnt and Frizzled signaling.
SEMIN.CELL DEV.BIOL. 13 215 (2002).

Documentation
Wnt proteins constitute a large family of secreted molecules that are
involved in intercellular signalling during development. The name derives
from the first 2 members of the family to be discovered: int-1 (mouse) and
wingless (Drosophila) [1]. It is now recognised that Wnt signalling controls
many cell fate decisions in a variety of different organisms, including
mammals [2]. Wnt signalling has been implicated in tumorigenesis, early
mesodermal patterning of the embryo, morphogenesis of the brain and kidneys,
regulation of mammary gland proliferation and Alzheimer's disease [3,4].
 
Wnt-mediated signalling is believed to proceed initially through binding to
cell surface receptors of the frizzled family; the signal is subsequently
transduced through several cytoplasmic components to B-catenin, which enters
the nucleus and activates the transcription of several genes important in
development [5]. More recently, however, several non-canonical Wnt
signalling pathways have been elucidated that act independently of
B-catenin [6]. Members of the Wnt gene family are defined by their sequence
similarity to mouse Wnt-1 and Wingless in Drosophila. They encode proteins
of ~350-400 residues in length, with orthologues identified in several,
mostly vertebrate, species. Very little is known about the structure of 
Wnts as they are notoriously insoluble; in terms of primary structure, the
family is characterised by a signal sequence and an almost invariant pattern
of 23-24 conserved cysteines [1]. Fifteen major Wnt gene families have been 
identified in vertebrates, with multiple subtypes within some classes.
 
The Wnt-1 gene was first identified in 1982 as a proto-oncogene activated by
the integration of mouse mammary tumour virus (MMTV) in mammary tumours.
With the identification of Drosophila wingless, however, it became clear
that Wnt genes are important regulators of many developmental decisions.
Mutation of the embryonic mouse Wnt-1 gene leads to loss of the midbrain and
cerebellum; and a number of processes including segment polarity and limb
development are interrupted in Drosophila wingless mutants [1].
 
WNT1PROTEIN is a 5-element fingerprint that provides a signature for Wnt-1
proteins. The fingerprint was derived from an initial alignment of 5
sequences: the motifs were drawn from conserved regions spanning the full
alignment length, focusing on those sections that characterise Wnt-1
proteins but distinguish them from related Wnt subtypes - motifs 1 and 2 lie
towards the N-terminus, between the putative signal peptide and the first
conserved cysteine residue; and motifs 3-5 reside between conserved 
cysteines in the C-terminal portion. Two iterations on SPTR40_20f were 
required to reach convergence, at which point a true set comprising 6 
sequences was identified.
Summary Information
6 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
566666
400000
300000
200000
12345
True Positives
P79752        WNT1_AMBME    WNT1_BRARE    WNT1_HUMAN    
WNT1_MOUSE WNT1_XENLA
Sequence Titles
P79752      WNT1 - Fugu rubripes (Japanese pufferfish) (Takifugu rubripes). 
WNT1_AMBME WNT-1 protein precursor - Ambystoma mexicanum (Axolotl).
WNT1_BRARE WNT-1 protein precursor - Brachydanio rerio (Zebrafish) (Zebra danio).
WNT1_HUMAN WNT-1 proto-oncogene protein precursor - Homo sapiens (Human).
WNT1_MOUSE WNT-1 proto-oncogene protein precursor - Mus musculus (Mouse).
WNT1_XENLA WNT-1 protein precursor (XWNT-1) (XINT-1) - Xenopus laevis (African clawed frog).
Scan History
SPTR40_20f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
AVNNSGRWWGI WNT1_BRARE 26 26 -
AVNNSGRWWGV WNT1_AMBME 26 26 -
AANSSGRWWGI WNT1_HUMAN 27 27 -
AANSSGRWWGI WNT1_MOUSE 27 27 -
AVNNSGKWWGI WNT1_XENLA 26 26 -

Motif 2 width=12
Element Seqn Id St Int Rpt
SKNVQLVLDPSL WNT1_BRARE 49 12 -
TKNVQLVLDPSL WNT1_AMBME 49 12 -
SKSLQLVLEPSL WNT1_HUMAN 50 12 -
SKSLQLVLEPSL WNT1_MOUSE 50 12 -
ARPVPLVLDPSL WNT1_XENLA 51 14 -

Motif 3 width=10
Element Seqn Id St Int Rpt
SSERGRDLRY WNT1_BRARE 186 125 -
SSERGRDLRY WNT1_AMBME 186 125 -
SGEKGRDLRF WNT1_HUMAN 187 125 -
SGEKGRDLRF WNT1_MOUSE 187 125 -
SSERGRDLKY WNT1_XENLA 187 124 -

Motif 4 width=11
Element Seqn Id St Int Rpt
RADPRHLEPEN WNT1_BRARE 268 72 -
RVQTHHLEPEN WNT1_AMBME 267 71 -
RAELLRLEPED WNT1_HUMAN 268 71 -
RAELLRLEPED WNT1_MOUSE 268 71 -
RSDPPHLEPEN WNT1_XENLA 269 72 -

Motif 5 width=10
Element Seqn Id St Int Rpt
KTGTHGTSGR WNT1_BRARE 304 25 -
KTGTSGTSGR WNT1_AMBME 303 25 -
RLGTAGTAGR WNT1_HUMAN 304 25 -
RLGTAGTAGR WNT1_MOUSE 304 25 -
KNGTPGTTGR WNT1_XENLA 305 25 -
Final Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
AVNNSGRWWGI WNT1_BRARE 26 26 -
AVNNSGRWWGI P79752 26 26 -
AVNNSGRWWGV WNT1_AMBME 26 26 -
AANSSGRWWGI WNT1_HUMAN 27 27 -
AANSSGRWWGI WNT1_MOUSE 27 27 -
AVNNSGKWWGI WNT1_XENLA 26 26 -

Motif 2 width=12
Element Seqn Id St Int Rpt
SKNVQLVLDPSL WNT1_BRARE 49 12 -
SKNVQLVLDPSL P79752 49 12 -
TKNVQLVLDPSL WNT1_AMBME 49 12 -
SKSLQLVLEPSL WNT1_HUMAN 50 12 -
SKSLQLVLEPSL WNT1_MOUSE 50 12 -
ARPVPLVLDPSL WNT1_XENLA 51 14 -

Motif 3 width=10
Element Seqn Id St Int Rpt
SSERGRDLRY WNT1_BRARE 186 125 -
SSERGRDLRY P79752 186 125 -
SSERGRDLRY WNT1_AMBME 186 125 -
SGEKGRDLRF WNT1_HUMAN 187 125 -
SGEKGRDLRF WNT1_MOUSE 187 125 -
SSERGRDLKY WNT1_XENLA 187 124 -

Motif 4 width=11
Element Seqn Id St Int Rpt
RADPRHLEPEN WNT1_BRARE 268 72 -
RAHPRHLEPEN P79752 268 72 -
RVQTHHLEPEN WNT1_AMBME 267 71 -
RAELLRLEPED WNT1_HUMAN 268 71 -
RAELLRLEPED WNT1_MOUSE 268 71 -
RSDPPHLEPEN WNT1_XENLA 269 72 -

Motif 5 width=10
Element Seqn Id St Int Rpt
KTGTHGTSGR WNT1_BRARE 304 25 -
KTGTLGTSGR P79752 304 25 -
KTGTSGTSGR WNT1_AMBME 303 25 -
RLGTAGTAGR WNT1_HUMAN 304 25 -
RLGTAGTAGR WNT1_MOUSE 304 25 -
KNGTPGTTGR WNT1_XENLA 305 25 -