WORKLIST ENTRIES (1): WNT2PROTEIN View alignment Wnt-2 protein signature Type of fingerprint: COMPOUND with 3 elements Links: PRINTS; PR01349 WNTPROTEIN PRINTS; PR01841 WNT1PROTEIN; PR01843 WNT3PROTEIN; PR01844 WNT4PROTEIN PRINTS; PR01845 WNT6PROTEIN; PR01891 WNT7PROTEIN; PR01892 WNT8PROTEIN PRINTS; PR01893 WNT10PROTEIN; PR01894 WNT14PROTEIN; PR01895 WNT16PROTEIN MIM; 147870 Creation date 07-JAN-2003 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). 7. WAINWRIGHT, B.J., SCAMBLER, P.J., STANIER, P., WATSON, E.K., BELL, G., WICKING, C., ESTIVILL, X., COURTNEY, M., BOUE, A. AND PEDERSEN, P.S. Isolation of a human gene with protein sequence similarity to human and murine int-1 and the Drosophila segment polarity mutant wingless. EMBO J. 7 1743-1748 (1988). 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) . It is now recognised that Wnt signalling controls many cell fate decisions in a variety of different organisms, including mammals . 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 . More recently, however, several non-canonical Wnt signalling pathways have been elucidated that act independently of B-catenin . 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 . Fifteen major Wnt gene families have been identified in vertebrates, with multiple subtypes within some classes. The Wnt-2 gene was isolated from a human lung cDNA library in 1988 . The protein was initially named IRP for Int-1 Related Protein and later termed Wnt-2. Northern blot analysis from a range of embryonic and adult tissues revealed that the gene was expressed almost exclusively in placenta and lung. Mutation of the mouse Wnt-2 gene leads to placental defects. WNT2PROTEIN is a 3-element fingerprint that provides a signature for Wnt-2 proteins. The fingerprint was derived from an initial alignment of 3 sequences: the motifs were drawn from conserved regions spanning the N- terminal half of the alignment, focusing on those sections that characterise Wnt-2 proteins but distinguish them from related Wnt subtypes - motif 1 includes the first conserved cysteine; and motif 3 lies in the central portion of the protein. Two iterations on SPTR40_20f were required to reach convergence, at which point a true set comprising 9 sequences was identified. SUMMARY INFORMATION 9 codes involving 3 elements 0 codes involving 2 elements COMPOSITE FINGERPRINT INDEX 3| 9 9 9 2| 0 0 0 --+---------------- | 1 2 3 True positives.. WNT2_MOUSE WNT2_HUMAN Q9CZW3 Q98SN7 WN2B_HUMAN WN2B_MOUSE WN2B_XENLA Q8UW39 WNT2_BRARE PROTEIN TITLES WNT2_MOUSE WNT-2 protein precursor (IRP protein) (INT-1 related protein WNT2_HUMAN WNT-2 protein precursor (IRP protein) (Int-1 related protein Q9CZW3 2610510E18RIK PROTEIN - Mus musculus (Mouse). Q98SN7 WG/INT-1 RELATED GENE PRODUCT WNT-2B - Gallus gallus (Chicke WN2B_HUMAN WNT-2B protein precursor (WNT-13) - Homo sapiens (Human). WN2B_MOUSE WNT-2B protein precursor (WNT-13) - Mus musculus (Mouse). WN2B_XENLA WNT-2B protein precursor (Xwnt-2b) - Xenopus laevis (African Q8UW39 WNT2 PROTEIN - Fugu rubripes (Japanese pufferfish) (Takifugu WNT2_BRARE WNT-2 protein precursor - Brachydanio rerio (Zebrafish) (Zeb
SCAN HISTORY SPTR40_20f 2 300 NSINGLE INITIAL MOTIF SETS WNT2PROTEIN1 Length of motif = 12 Motif number = 1 Wnt-2 protein motif I - 1 PCODE ST INT SQVMCDNIPGLI WNT2_BRARE 35 35 SRVMCDNVPGLV WNT2_HUMAN 37 37 SRVMCDNVPGLV WNT2_MOUSE 37 37 WNT2PROTEIN2 Length of motif = 11 Motif number = 2 Wnt-2 protein motif II - 1 PCODE ST INT TMAREHNLFGR WNT2_BRARE 87 40 TLDRDHSLFGR WNT2_HUMAN 89 40 TLDRDHSLFGR WNT2_MOUSE 89 40 WNT2PROTEIN3 Length of motif = 10 Motif number = 3 Wnt-2 protein motif III - 1 PCODE ST INT RKERDARALM WNT2_BRARE 175 77 RKGKDARALM WNT2_HUMAN 177 77 RKGKDARALM WNT2_MOUSE 177 77 FINAL MOTIF SETS WNT2PROTEIN1 Length of motif = 12 Motif number = 1 Wnt-2 protein motif I - 2 PCODE ST INT SRVMCDNVPGLV Q9CZW3 37 37 SRVMCDNVPGLV WNT2_HUMAN 37 37 SRVMCDNVPGLV WNT2_MOUSE 37 37 ARVICDNIPGLV Q98SN7 62 62 ARVICDNIPGLV WN2B_HUMAN 68 68 ARVICDNIPGLV WN2B_MOUSE 66 66 ARVICDNIPGLV WN2B_XENLA 28 28 SQVMCDNIPGLV Q8UW39 35 35 SQVMCDNIPGLI WNT2_BRARE 35 35 WNT2PROTEIN2 Length of motif = 11 Motif number = 2 Wnt-2 protein motif II - 2 PCODE ST INT TLDRDHSLFGR Q9CZW3 89 40 TLDRDHSLFGR WNT2_HUMAN 89 40 TLDRDHSLFGR WNT2_MOUSE 89 40 TLDRDHTVFGR Q98SN7 114 40 TLDRDHTVFGR WN2B_HUMAN 120 40 TLDRDHTVFGR WN2B_MOUSE 118 40 TLDRDHTVFGR WN2B_XENLA 80 40 TTARDHNLFGR Q8UW39 87 40 TMAREHNLFGR WNT2_BRARE 87 40 WNT2PROTEIN3 Length of motif = 10 Motif number = 3 Wnt-2 protein motif III - 2 PCODE ST INT RKGKDARALM Q9CZW3 177 77 RKGKDARALM WNT2_HUMAN 177 77 RKGKDARALM WNT2_MOUSE 177 77 KKVKDARALM Q98SN7 202 77 KRLKDARALM WN2B_HUMAN 208 77 KRLKDARALM WN2B_MOUSE 206 77 KRLKDARALM WN2B_XENLA 168 77 RKERDARALM Q8UW39 175 77 RKERDARALM WNT2_BRARE 175 77
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