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PR01452

Identifier
LNOTCHREPEAT  [View Relations]  [View Alignment]  
Accession
PR01452
No. of Motifs
3
Creation Date
01-DEC-2000
Title
LIN-12/notch repeat (LNR) signature
Database References

PFAM; PF00066 notch
INTERPRO; IPR000800
Literature References
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).

Documentation
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 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 Feature Index
3232323
2000
123
True Positives
GLP1_CAEEL    LI12_CAEEL    NOTC_BRARE    NOTC_DROME    
NOTC_XENLA NTC1_MOUSE NTC1_RAT NTC3_MOUSE
NTC4_MOUSE O00306 O16004 O35442
O35516 O61240 O97458 Q25253
Q99940 Q9QW30 Q9QW58 Q9R172
Q9UM47 Q9W4T8 Q9Y6L8
Sequence Titles
GLP1_CAEEL  GLP-1 PROTEIN PRECURSOR - Caenorhabditis elegans. 
LI12_CAEEL LIN-12 PROTEIN PRECURSOR - Caenorhabditis elegans.
NOTC_BRARE NEUROGENIC LOCUS NOTCH HOMOLOG PROTEIN PRECURSOR - Brachydanio rerio (Zebrafish) (Zebra danio).
NOTC_DROME NEUROGENIC LOCUS NOTCH PROTEIN PRECURSOR - Drosophila melanogaster (Fruit fly).
NOTC_XENLA NEUROGENIC LOCUS NOTCH PROTEIN HOMOLOG PRECURSOR (XOTCH PROTEIN) - Xenopus laevis (African clawed frog).
NTC1_MOUSE NEUROGENIC LOCUS NOTCH HOMOLOG PROTEIN 1 PRECURSOR (MOTCH PROTEIN) - Mus musculus (Mouse).
NTC1_RAT NEUROGENIC LOCUS NOTCH HOMOLOG PROTEIN 1 PRECURSOR - Rattus norvegicus (Rat).
NTC3_MOUSE NEUROGENIC LOCUS NOTCH 3 PROTEIN - Mus musculus (Mouse).
NTC4_MOUSE NEUROGENIC LOCUS NOTCH HOMOLOG PROTEIN 4 PRECURSOR (TRANSFORMING PROTEIN INT-3) - Mus musculus (Mouse).
O00306 NOTCH4 - Homo sapiens (Human).
O16004 NOTCH HOMOLOG - Lytechinus variegatus (Sea urchin).
O35442 NOTCH4 - Mus musculus (Mouse).
O35516 CELL SURFACE PROTEIN - Mus musculus (Mouse).
O61240 HRNOTCH PROTEIN - Halocynthia roretzi (Sea squirt).
O97458 EG:163A10.2 PROTEIN - Drosophila melanogaster (Fruit fly).
Q25253 NOTCH HOMOLOG SCALLOPED WINGS (SCL) - Lucilia cuprina (Greenbottle fly) (Australian sheep blowfly).
Q99940 NOTCH4 - Homo sapiens (Human).
Q9QW30 NOTCH2 PROTEIN - Rattus sp.
Q9QW58 MOTCH=NOTCH PRODUCT HOMOLOG - Mus sp.
Q9R172 NOTCH 3 PROTEIN - Rattus norvegicus (Rat).
Q9UM47 NOTCH3 - Homo sapiens (Human).
Q9W4T8 N GENE PRODUCT - Drosophila melanogaster (Fruit fly).
Q9Y6L8 NOTCH3 - Homo sapiens (Human).
Scan History
SPTR39_14f 2  50   NSINGLE    
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
CNNHACGWDGGDCS NTC1_RAT 1467 1467 -
CNNHACGWDGGDCS NOTC_XENLA 1465 1465 -
CNTPGCGWDGGDCS NTC3_MOUSE 1406 1406 -
CNSHACQWDGGDCS O35516 1441 1441 -
CNTYACNFDGNDCS NOTC_DROME 1500 1500 -
CSGPGGDWDGGDCS NTC4_MOUSE 1187 1187 -
CNVHECEFDGGDCS O61240 1327 1327 -
CNYAACKFDGGDCS LI12_CAEEL 656 656 -
CNTHLCEWDGKDCS O16004 1458 1458 -
CNLEECNFDGGDCS GLP1_CAEEL 514 514 -

Motif 2 width=13
Element Seqn Id St Int Rpt
CNSAGCLFDGFDC NTC1_RAT 1509 28 -
CNNTGCLYDGFDC NOTC_XENLA 1507 28 -
CSSPACLYDNFDC NTC3_MOUSE 1447 27 -
CNTAECLFDNFEC O35516 1482 27 -
CNNAACHYDGHDC NOTC_DROME 1540 26 -
CDSEECLFDGYDC NTC4_MOUSE 1229 28 -
CNNEDCLHDGMDC O61240 1369 28 -
CNNEECLYDGMDC LI12_CAEEL 697 27 -
CNNHGCLFDGFDC O16004 1500 28 -
CNNEECLYDGLDC GLP1_CAEEL 555 27 -

Motif 3 width=13
Element Seqn Id St Int Rpt
CNSAECEWDGLDC NTC1_RAT 1549 27 -
CNNAECEWDGLDC NOTC_XENLA 1547 27 -
CNTEECGWDGLDC NTC3_MOUSE 1489 29 -
CNSEECGWDGLDC O35516 1520 25 -
CNNAECSWDGLDC NOTC_DROME 1580 27 -
CNNAECGWDGGDC NTC4_MOUSE 1268 26 -
CNNANCGWDGADC O61240 1409 27 -
CNTNGCGFDGGDC LI12_CAEEL 737 27 -
CNNIGCLYDGLDC O16004 1539 26 -
CSFIGCGFDGGDC GLP1_CAEEL 595 27 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
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 -

Motif 2 width=13
Element Seqn Id St Int Rpt
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 -

Motif 3 width=13
Element Seqn Id St Int Rpt
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 -