WORKLIST ENTRIES (1): PRESENILNSEL View alignment C.elegans Sel-12 (presenilin) signature Type of fingerprint: COMPOUND with 4 elements Links: PRINTS; PR01072 PRESENILIN; PR01073 PRESENILIN1; PR01074 PRESENILIN2 INTERPRO; IPR001686 Creation date 01-MAR-1999; UPDATE 07-JUN-1999 1. CRUTS, M. AND VAN BROECKHOVEN, C. Presenilin mutations in Alzheimer's disease. HUM.MUTAT. 11 183-190 (1998). 2. LEVITAN, D. AND GREENWALD, I. Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer's disease gene. NATURE 377 351-354 (1995). Presenilins are polytopic transmembrane (TM) proteins, mutations in which are associated with the occurrence of early-onset familial Alzheimer's disease, a rare form of the disease that results from a single-gene mutation . While the aetiology of Alzheimer's disease is unresolved, all forms are typified by a global cognitive decline and the occurrence of characteristic neuropathological changes. Invariably, post-mortem brains from Alzheimer's patients contain abundant neurofibrillary tangles, together with depositions of beta-amyloid protein as senile plaques. The physiological functions of presenilins are unknown, but they may be related to developmental signalling, apoptotic signal transduction, or processing of selected proteins, such as the beta-amyloid precursor protein (beta-APP). That presenilin homologues have been identified in species that do not have an Alzhemier's disease correlate suggests that they may have functions unrelated to the disease, homologues having been identified in mouse, Drosophila and C.elegans. In humans, there are two presenilin genes (PS1 and PS2), encoding proteins of 467 and 448 amino acids respectively. They share 67% amino acid identity, the greatest divergence between the two falling in the N-terminus and in the large hydrophilic loop towards the C-terminal part of each molecule. Six to nine TM domains are predicted for each, and biochemical analysis has demonstrated that their C-termini are cytoplasmic; but the orientation of their N-termini and large hydrophilic loops remains to be resolved. They are expressed in almost all tissues, including the brain and, at a cellular level, they have been localised to the nuclear envelope, endoplasmic reticulum and Golgi apparatus. Sel-12, a worm homologue of the mammalian presenilins (with which it shares ~50% amino acid identity), has been shown to facilitate the function of the Notch receptor (LIN-12 protein), which plays a role in cell-cell signalling during cell differentiation in development. Intriguingly, presenilin 1 is able to restore function in a C.elegans mutant lacking sel-12, suggesting presenilin may also be involved in cell-cell signalling in higher species . PRESENILNSEL is a 4-element fingerprint that provides a signature for the C.elegans presenilin homologue, sel-12, and related C.elegans proteins. The fingerprint was derived from an initial alignment of 2 sequences: the motifs were drawn from conserved regions spanning ~two thirds of the alignment, focusing on those sections that characterise sel-12 but distinguish it from other presenilin isoforms - motif 1 encodes ~half the N-terminal hydrophilic region; and motifs 3-4 reside within the hydrophilic region between putative TM domains 7 and 8. A single iteration on OWL31.1 was required to reach convergence, no further sequences being identified beyond the starting set. An update on SPTR37_9f identified a true set of 2 sequences. SUMMARY INFORMATION 2 codes involving 4 elements 0 codes involving 3 elements 0 codes involving 2 elements COMPOSITE FINGERPRINT INDEX 4| 2 2 2 2 3| 0 0 0 0 2| 0 0 0 0 --+--------------------- | 1 2 3 4 True positives.. Q20076 SE12_CAEEL PROTEIN TITLES Q20076 HYPOTHETICAL 94.6 KD PROTEIN F35H12.3 IN CHROMOSOME X - CAEN SE12_CAEEL INTEGRAL MEMBRANE PROTEIN SEL-12 - CAENORHABDITIS ELEGANS.
SCAN HISTORY OWL31_1 1 300 NSINGLE SPTR37_9f 2 3 NSINGLE INITIAL MOTIF SETS PRESENILNSEL1 Length of motif = 19 Motif number = 1 C.elegans Sel-12 (presenilin) motif I - 1 PCODE ST INT NLITNRNSQEDENVVEEAE CELF35H12 24 24 NLITNRNSQEDENVVEEAE SE12_CAEEL 24 24 PRESENILNSEL2 Length of motif = 17 Motif number = 2 C.elegans Sel-12 (presenilin) motif II - 1 PCODE ST INT SCSSETPKRPKVKRIPQ CELF35H12 296 253 SCSSETPKRPKVKRIPQ SE12_CAEEL 296 253 PRESENILNSEL3 Length of motif = 22 Motif number = 3 C.elegans Sel-12 (presenilin) motif III - 1 PCODE ST INT KVQIESNTTASTTQNSGVRVER CELF35H12 313 0 KVQIESNTTASTTQNSGVRVER SE12_CAEEL 313 0 PRESENILNSEL4 Length of motif = 19 Motif number = 4 C.elegans Sel-12 (presenilin) motif IV - 1 PCODE ST INT ELAAERPTVQDANFHRHEE CELF35H12 335 0 ELAAERPTVQDANFHRHEE SE12_CAEEL 335 0 FINAL MOTIF SETS PRESENILNSEL1 Length of motif = 19 Motif number = 1 C.elegans Sel-12 (presenilin) motif I - 2 PCODE ST INT NLITNRNSQEDENVVEEAE Q20076 24 24 NLITNRNSQEDENVVEEAE SE12_CAEEL 24 24 PRESENILNSEL2 Length of motif = 17 Motif number = 2 C.elegans Sel-12 (presenilin) motif II - 2 PCODE ST INT SCSSETPKRPKVKRIPQ Q20076 296 253 SCSSETPKRPKVKRIPQ SE12_CAEEL 296 253 PRESENILNSEL3 Length of motif = 22 Motif number = 3 C.elegans Sel-12 (presenilin) motif III - 2 PCODE ST INT KVQIESNTTASTTQNSGVRVER Q20076 313 0 KVQIESNTTASTTQNSGVRVER SE12_CAEEL 313 0 PRESENILNSEL4 Length of motif = 19 Motif number = 4 C.elegans Sel-12 (presenilin) motif IV - 2 PCODE ST INT ELAAERPTVQDANFHRHEE Q20076 335 0 ELAAERPTVQDANFHRHEE SE12_CAEEL 335 0
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