WORKLIST ENTRIES (1):

LNOTCHREPEAT View alignment     LIN-12/notch repeat (LNR) signature
 Type of fingerprint: COMPOUND with 3  elements
Links:
   PRINTS; PR01983 NOTCH
   PFAM; PF00066 notch
   INTERPRO; IPR000800

 Creation date 01-DEC-2000

   1. KIMBLE, J., HENDERSON, S. AND CRITTENDEN, S.
   Notch/LIN-12 signalling: transduction by regulated protein splicing.
   TRENDS BIOCHEM.SCI. 23 353-357 (1998).

   2. BRAY, S.
   Notch.
   CURR.BIOL. 10 R433-R435 (2000).

   3. KIMBLE, J. AND SIMPSON, P.
   The LIN-12/Notch signalling pathway and its regulation.
   ANNU.REV.CELL DEV.BIOL. 13 333-361 (1997).

   LIN-12/notch proteins function as receptors for intercellular signals during
   development in a diverse range of species, from human through to C.elegans.
   The LIN-12/notch family is characterised by a repeat region (termed LNR),
   and members also share a number of other features, such as extracellular EGF 
   repeats and intracellular ankyrin repeats. Notch is involved in many
   developmental processes, including limb and appendage development, lymphoid
   lineage selection, axon pathfinding and dendritic sprouting. Dysfunction of
   the notch/LIN-12 signalling pathway has been implicated in several human
   diseases, including leukaemia, cervical and colon cancer, Alzheimer's
   disease, cerebral ischaemia and alagille syndrome [1].  
  
   The notch protein can be divided into 3 main regions: a large extracellular
   domain (ECD), which is composed largely of EGF repeats (between 10 and 36)
   and also contains the triplet cysteine-rich LIN-12/Notch repeat; a single
   transmembrane (TM) domain; and an intracellular domain (ICD), which contains
   6 ankyrin repeats that form the binding site for cytoplasmic regulators of
   notch activity [2]. Three components appear to be essential for LIN-12/notch
   signalling: the Delta/Serrate/LAG-2 (DSL) ligand; the LIN-12/notch receptor
   itself; and the CBF1/Su(H)/LAG-1 (CSL) transcription factor. While 2 EGF-
   like repeats (11 and 12 in Drosophila) appear to be sufficient and necessary
   for DSL ligand binding, the LNR region appears to be involved in receptor
   regulation. Currently, 2 possible methods of CSL factor regulation are
   proposed: receptor-mediated transport of the CSL factor from cytoplasm
   to nucleus; and cleavage of the ICD upon receptor activation, followed by
   entry of the ICD into the nucleus, where it acts as a co-activator of
   transcription with the CSL factor [3].
  
   LNOTCHREPEAT is a 3-element fingerprint that provides a signature for the
   LIN-12/notch (LNR) repeat. The fingerprint was derived from an initial alignment
   of 10 sequences: the motifs were drawn from conserved regions within the 
   repeat, successively encoding the C-termini of repeats 1, 2 and 3 
   respectively. Two iterations on SPTR39_14f were required to reach 
   convergence, at which point a true set comprising 23 sequences was identified.

  SUMMARY INFORMATION
     23 codes involving  3 elements
      0 codes involving  2 elements

   COMPOSITE FINGERPRINT INDEX
  
    3|  23   23   23  
    2|   0    0    0  
   --+----------------
     |   1    2    3  

True positives..
 NTC1_MOUSE     NTC1_RAT       NOTC_XENLA     NOTC_BRARE     
 Q9QW58         NTC3_MOUSE     Q9R172         Q9UM47         
 Q9Y6L8         Q25253         Q9QW30         O35516         
 NOTC_DROME     O97458         Q9W4T8         O00306         
 Q99940         NTC4_MOUSE     O35442         O61240         
 LI12_CAEEL     O16004         GLP1_CAEEL     


  PROTEIN TITLES
   NTC1_MOUSE       NEUROGENIC LOCUS NOTCH HOMOLOG PROTEIN 1 PRECURSOR (MOTCH PR
   NTC1_RAT         NEUROGENIC LOCUS NOTCH HOMOLOG PROTEIN 1 PRECURSOR - Rattus 
   NOTC_XENLA       NEUROGENIC LOCUS NOTCH PROTEIN HOMOLOG PRECURSOR (XOTCH PROT
   NOTC_BRARE       NEUROGENIC LOCUS NOTCH HOMOLOG PROTEIN PRECURSOR - Brachydan
   Q9QW58           MOTCH=NOTCH PRODUCT HOMOLOG - Mus sp.
   NTC3_MOUSE       NEUROGENIC LOCUS NOTCH 3 PROTEIN - Mus musculus (Mouse).
   Q9R172           NOTCH 3 PROTEIN - Rattus norvegicus (Rat).
   Q9UM47           NOTCH3 - Homo sapiens (Human).
   Q9Y6L8           NOTCH3 - Homo sapiens (Human).
   Q25253           NOTCH HOMOLOG SCALLOPED WINGS (SCL) - Lucilia cuprina (Green
   Q9QW30           NOTCH2 PROTEIN - Rattus sp.
   O35516           CELL SURFACE PROTEIN - Mus musculus (Mouse).
   NOTC_DROME       NEUROGENIC LOCUS NOTCH PROTEIN PRECURSOR - Drosophila melano
   O97458           EG:163A10.2 PROTEIN - Drosophila melanogaster (Fruit fly).
   Q9W4T8           N GENE PRODUCT - Drosophila melanogaster (Fruit fly).
   O00306           NOTCH4 - Homo sapiens (Human).
   Q99940           NOTCH4 - Homo sapiens (Human).
   NTC4_MOUSE       NEUROGENIC LOCUS NOTCH HOMOLOG PROTEIN 4 PRECURSOR (TRANSFOR
   O35442           NOTCH4 - Mus musculus (Mouse).
   O61240           HRNOTCH PROTEIN - Halocynthia roretzi (Sea squirt).
   LI12_CAEEL       LIN-12 PROTEIN PRECURSOR - Caenorhabditis elegans.
   O16004           NOTCH HOMOLOG - Lytechinus variegatus (Sea urchin).
   GLP1_CAEEL       GLP-1 PROTEIN PRECURSOR - Caenorhabditis elegans.

SCAN HISTORY SPTR39_14f 2 50 NSINGLE INITIAL MOTIF SETS LNOTCHREPEAT1 Length of motif = 14 Motif number = 1 LIN-12/notch repeat (LNR) motif I - 1 PCODE ST INT CNTYACNFDGNDCS NOTC_DROME 1500 1500 CNNHACGWDGGDCS NOTC_XENLA 1465 1465 CNNHACGWDGGDCS NTC1_RAT 1467 1467 CNTHLCEWDGKDCS O16004 1458 1458 CNSHACQWDGGDCS O35516 1441 1441 CNTPGCGWDGGDCS NTC3_MOUSE 1406 1406 CSGPGGDWDGGDCS NTC4_MOUSE 1187 1187 CNVHECEFDGGDCS O61240 1327 1327 CNYAACKFDGGDCS LI12_CAEEL 656 656 CNLEECNFDGGDCS GLP1_CAEEL 514 514 LNOTCHREPEAT2 Length of motif = 13 Motif number = 2 LIN-12/notch repeat (LNR) motif II - 1 PCODE ST INT CNNAACHYDGHDC NOTC_DROME 1540 26 CNNTGCLYDGFDC NOTC_XENLA 1507 28 CNSAGCLFDGFDC NTC1_RAT 1509 28 CNNHGCLFDGFDC O16004 1500 28 CNTAECLFDNFEC O35516 1482 27 CSSPACLYDNFDC NTC3_MOUSE 1447 27 CDSEECLFDGYDC NTC4_MOUSE 1229 28 CNNEDCLHDGMDC O61240 1369 28 CNNEECLYDGMDC LI12_CAEEL 697 27 CNNEECLYDGLDC GLP1_CAEEL 555 27 LNOTCHREPEAT3 Length of motif = 13 Motif number = 3 LIN-12/notch repeat (LNR) motif III - 1 PCODE ST INT CNNAECSWDGLDC NOTC_DROME 1580 27 CNNAECEWDGLDC NOTC_XENLA 1547 27 CNSAECEWDGLDC NTC1_RAT 1549 27 CNNIGCLYDGLDC O16004 1539 26 CNSEECGWDGLDC O35516 1520 25 CNTEECGWDGLDC NTC3_MOUSE 1489 29 CNNAECGWDGGDC NTC4_MOUSE 1268 26 CNNANCGWDGADC O61240 1409 27 CNTNGCGFDGGDC LI12_CAEEL 737 27 CSFIGCGFDGGDC GLP1_CAEEL 595 27 FINAL MOTIF SETS LNOTCHREPEAT1 Length of motif = 14 Motif number = 1 LIN-12/notch repeat (LNR) motif I - 2 PCODE ST INT CNNHACGWDGGDCS NTC1_MOUSE 1467 1467 CNNHACGWDGGDCS NTC1_RAT 1467 1467 CNNHACGWDGGDCS NOTC_XENLA 1465 1465 CNNHACGWDGGDCS NOTC_BRARE 1465 1465 CNNHACGWDGGDCS Q9QW58 648 648 CNTPGCGWDGGDCS NTC3_MOUSE 1406 1406 CNSPGCGWDGGDCS Q9R172 1407 1407 CNSPGCGWDGGDCS Q9UM47 1405 1405 CNSPGCGWDGGDCS Q9Y6L8 1405 1405 CNTYACNFDGNDCS Q25253 1481 1481 CNSHACQWDGGDCS Q9QW30 1443 1443 CNSHACQWDGGDCS O35516 1441 1441 CNTYACNFDGNDCS NOTC_DROME 1500 1500 CNTYACNFDGNDCS O97458 1500 1500 CNTYACNFDGNDCS Q9W4T8 1500 1500 CSGPGGNWDGGDCS O00306 1191 1191 CSGPGGNWDGGDCS Q99940 1190 1190 CSGPGGDWDGGDCS NTC4_MOUSE 1187 1187 CSGPGGDWDGGDCS O35442 1187 1187 CNVHECEFDGGDCS O61240 1327 1327 CNYAACKFDGGDCS LI12_CAEEL 656 656 CNTHLCEWDGKDCS O16004 1458 1458 CNLEECNFDGGDCS GLP1_CAEEL 514 514 LNOTCHREPEAT2 Length of motif = 13 Motif number = 2 LIN-12/notch repeat (LNR) motif II - 2 PCODE ST INT CNSAGCLFDGFDC NTC1_MOUSE 1509 28 CNSAGCLFDGFDC NTC1_RAT 1509 28 CNNTGCLYDGFDC NOTC_XENLA 1507 28 CATAGCLYDGFDC NOTC_BRARE 1507 28 CNSAGCLFDGFDC Q9QW58 690 28 CSSPACLYDNFDC NTC3_MOUSE 1447 27 CSSPACLYDNFDC Q9R172 1448 27 CSSPACLYDNFDC Q9UM47 1446 27 CSSPACLYDNFDC Q9Y6L8 1446 27 CNNAACLFDGRDC Q25253 1522 27 CNTAECLFDNFEC Q9QW30 1484 27 CNTAECLFDNFEC O35516 1482 27 CNNAACHYDGHDC NOTC_DROME 1540 26 CNNAACHYDGHDC O97458 1540 26 CNNAACHYDGHDC Q9W4T8 1540 26 CDSEECLFDGYDC O00306 1233 28 CDSEECLFDGYDC Q99940 1232 28 CDSEECLFDGYDC NTC4_MOUSE 1229 28 CDSEECLFDGYDC O35442 1229 28 CNNEDCLHDGMDC O61240 1369 28 CNNEECLYDGMDC LI12_CAEEL 697 27 CNNHGCLFDGFDC O16004 1500 28 CNNEECLYDGLDC GLP1_CAEEL 555 27 LNOTCHREPEAT3 Length of motif = 13 Motif number = 3 LIN-12/notch repeat (LNR) motif III - 2 PCODE ST INT CNSAECEWDGLDC NTC1_MOUSE 1549 27 CNSAECEWDGLDC NTC1_RAT 1549 27 CNNAECEWDGLDC NOTC_XENLA 1547 27 CNNAECEWDGLDC NOTC_BRARE 1547 27 CNSAECERDGLDC Q9QW58 730 27 CNTEECGWDGLDC NTC3_MOUSE 1489 29 CNTEECGWDGLDC Q9R172 1490 29 CNTEECGWDGLDC Q9UM47 1488 29 CNTEECGWDGLDC Q9Y6L8 1488 29 CNNAECNWDGLDC Q25253 1562 27 CNNEECGWDGLDC Q9QW30 1522 25 CNSEECGWDGLDC O35516 1520 25 CNNAECSWDGLDC NOTC_DROME 1580 27 CNNAECSWDGLDC O97458 1580 27 CNNAECSWDGLDC Q9W4T8 1580 27 CNTAECGWDGGDC O00306 1272 26 CNTAECGWDGGDC Q99940 1271 26 CNNAECGWDGGDC NTC4_MOUSE 1268 26 CNNAECGWDGGDC O35442 1268 26 CNNANCGWDGADC O61240 1409 27 CNTNGCGFDGGDC LI12_CAEEL 737 27 CNNIGCLYDGLDC O16004 1539 26 CSFIGCGFDGGDC GLP1_CAEEL 595 27

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