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PR01984

Identifier
NOTCH1  [View Relations]  [View Alignment]  
Accession
PR01984
No. of Motifs
5
Creation Date
11-JUN-2009
Title
Neurogenic locus Notch protein 1 signature 
Database References
PRINTS; PR01983 NOTCH
PROSITE; PS50258 LNR
PFAM; PF00066 Notch; PF06816 NOD; PF07684 NODP

SMART; SM00004 NL
INTERPRO; IPR000800; IPR008297; IPR010660; IPR011656
PDB; 2FO1; 1PB5; 1TOZ; 2F8X; 2VJ3; 3ETO
SCOP; 2FO1; 1PB5; 1TOZ; 2F8X; 2VJ3; 3ETO
CATH; 2FO1; 1PB5; 1TOZ; 2F8X; 2VJ3; 3ETO
MIM; 109730; 190198
Literature References
1. KOPAN, R. AND ILAGAN, M.
The canonical notch signaling pathway: unfolding the activation mechanism. 
CELL 137 216-233 (2009).
 
2. ARTAVANIS-TSAKONAS, S., RAND, M.D. AND LAKE, R.J.
Notch signaling: cell fate control and signal integration in development. 
SCIENCE 284 770-776 (1999).
 
3. HARTMANN, D., DE STROOPER, B., SERNEELS. L., CRAESSAERTS, K., 
HERREMAN, A., ANNAERT, W., UMANS, L., LUBKE, T., LENA ILLERT, A., 
VON FIGURA, K. AND SAFTIG, P. 
The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling
but not for alpha-secretase activity in fibroblasts.
HUM.MOL.GENET. 11 2615-2624 (2002).
 
4. DE STROOPER, B., ANNAERT, W., CUPERS, P., SAFTIG, P., CRAESSAERTS, K.,
MUMM, J.S., SCHROETER, E.H., SCHRIJVERS, V., WOLFE, M.S., RAY, W.J., 
GOATE, A.AND KOPAN, R.
A presenilin-1-dependent gamma-secretase-like protease mediates release of 
Notch intracellular domain. 
NATURE 398 518-522 (1999).
 
5. WU, L., ASTER, J.C., BLACKLOW, S.C., LAKE, R., ARTAVANIS-TSAKONAS, S.,
AND GRIFFIN, J.D.
MAML1, a human homologue of Drosophila mastermind, is a transcriptional
co-activator for NOTCH receptors.
NAT.GENET. 26 484-489 (2000).
 
6. GRIDLEY, T. 
Notch signaling and inherited disease syndromes. 
HUM.MOL.GENET. 1 R9-R13 (2003).
 
7. LOUVI, A. AND ARTAVANIS-TSAKONAS, S.
Notch signalling in vertebrate neural development. 
NAT.REV.NEUROSCI. 7 93-102 (2006).
 
8. BALDI, A., DE FALCO, M., DE LUCA, L., COTTONE, G., PAGGI, M.G.,
NICKOLOFF, B.J., MIELE, L. AND DE LUCA, A. 
Characterization of tissue specific expression of Notch-1 in human tissues.
BIOL.CELL. 96 303-311 (2004).

Documentation
Notch cell surface receptors are large, single-pass type-1 transmembrane
proteins found in a diverse range of metazoan species, from human to
Caenorhabditis species. The fruit fly, Drosophila melanogaster, possesses
only one Notch protein, whereas in C.elegans, two receptors have been found;
by contrast, four Notch paralogues (designated N1-4) have been identified in
mammals, playing both unique and redundant roles.
 
The hetero-oligomer Notch comprises a large extracellular domain (ECD),
containing 10-36 tandem Epidermal Growth Factor (EFG)-like repeats, which
are involved in ligand interactions; a negative regulatory region,
including three cysteine-rich Lin12-Notch Repeats (LNR); a single trans-
membrane domain (TM); a small intracellular domain (ICD), which includes a
RAM (RBPjk-association module) domain; six ankyrin repeats (ANK), which are
involved in protein-protein interactions; and a PEST domain. Drosophila 
Notch also contains an OPA domain [1]. 	 
 
Notch signalling is an evolutionarily conserved pathway involved in a wide
variety of developmental processes, including adult homeostasis and stem 
cell maintainance, cell proliferation and apoptosis [2]. Notch is activated
by a range of ligands - the so-called DSL ligands (Delta/Seratte/LAG-2). 
Activation is also mediated by a sequence of proteolytic events: ligand
binding leads to cleavage of Notch by ADAM proteases [3] at site 2 (S2) and
presenilin-1/g-secretase at sites 3 (S3)and 4 (S4) [4].The last cleavage
releases the Notch intracellular part of the protein (NICD) from the
membrane and, upon release, the NICD translocates to the nucleus where it
associates with a CBF1/RBJk/Su(H)/Lag1 (CSL) family of DNA-binding proteins.
The subsequent recruitment of a co-activator mastermind like (MAML1) protein
[5] promotes transcriptional activation of Notch target genes: well 
established Notch targets are the Hes and Hey gene families.  
     
Aberrant Notch function and signalling has been associated with a number of
human disorders, including Allagile syndrome, spondylocostal dysostosis,
aortic valve disease, CADASIL (Cerebral Autosomal Dominant Arteriopathy with
Subcortical Infarcts and Leukoencephalopathy), and T-cell Acute Lympho-
blastic Leukemia (T-ALL); it has also been implicated in various human
carcinomas [6,7].
 
Notch 1 has a widespread pattern of expression and has been demonstrated
to be involved in several processes such as mesenchymal cell differentiation,
spermatogenesis, and osteoblastic cell differentiation. The pattern of 
expression of Notch 1 in adult human tissues reveals that this receptor
may play multiple roles in several cell types, including neurons, lymphoid
cells and skeletal muscle cells, as well as suprabasal cells in stratified
epithelia [8]. 
 
NOTCH1 is a 5-element fingerprint that provides a signature for neurogenic
locus Notch protein 1. The fingerprint was derived from an initial alignment 
of 8 sequences: the motifs were drawn from conserved regions spanning 
virtually the full alignment length - motif 1 lies between the EGF repeat 
and LNR regions and is unique to Notch 1 proteins; motif 2 lies in a
conserved area C-terminal to the LNR region; motif 3 lies N-terminal to the 
TM domain; motif 4 resides in an area C-terminal to the ankyrin repeat
region; and motif 5 is close to the protein C-terminus. Two iterations on
SPTR57_40f were required to reach convergence, at which point a true set
comprising 14 sequences was identified. Two partial matches were also 
identified: B5UQW5_ONCMY and 093616_DANRE, which are Notch protein fragments
that are missing parts of the sequence bearing 2 or 3 motifs.
Summary Information
  14 codes involving  5 elements
0 codes involving 4 elements
1 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
51414141414
400000
311010
200011
12345
True Positives
A0PGH6_DANRE  A2RUV0_XENTR  A5WUN6_DANRE  B7WP15_HUMAN  
NOTC1_HUMAN NOTC_BRARE NOTC_XENLA NTC1_MOUSE
NTC1_RAT Q7TQ50_MOUSE Q7TQ51_MOUSE Q7TQ52_MOUSE
Q8AXP0_CYNPY Q8K428_MOUSE
True Positive Partials
Codes involving 3 elements
B5U9W5_ONCMY
Codes involving 2 elements
O93616_DANRE
Sequence Titles
A0PGH6_DANRE Notch1b - Danio rerio (Zebrafish) (Brachydanio rerio). 
A2RUV0_XENTR Notch1 protein - Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
A5WUN6_DANRE Notch homolog 1b - Danio rerio (Zebrafish) (Brachydanio rerio).
B7WP15_HUMAN Putative uncharacterized protein NOTCH1; - Homo sapiens (Human).
NOTC1_HUMAN Neurogenic locus notch homolog protein 1; Notch 1; hN1; Translocation-associated notch protein TAN-1; Contains: Notch 1 extracellular truncation; Contains: Notch 1 intracellular domain; Precursor; - Homo sapiens (Human).
NOTC_BRARE NEUROGENIC LOCUS NOTCH HOMOLOG PROTEIN PRECURSOR - Brachydanio rerio (Zebrafish) (Zebra danio).
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).
Q7TQ50_MOUSE Notch gene homolog 1 (Drosophila); Transmembrane receptor Notch1; - Mus musculus (Mouse).
Q7TQ51_MOUSE Transmembrane receptor Notch1 D; - Mus musculus (Mouse).
Q7TQ52_MOUSE Transmembrane receptor Notch1 B; - Mus musculus (Mouse).
Q8AXP0_CYNPY Receptor protein Notch1 - Cynops pyrrhogaster (Japanese common newt).
Q8K428_MOUSE Notch 1 protein; - Mus musculus (Mouse).

B5U9W5_ONCMY Notch1; - Oncorhynchus mykiss (Rainbow trout) (Salmo gairdneri).

O93616_DANRE Notch homologue 1a - Danio rerio (Zebrafish) (Brachydanio rerio).
Scan History
SPTR57_40f 2  100  NSINGLE    
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
HILDYSFTGGAGPDIPP NTC1_MOUSE 1426 1426 -
HILDYSFGGGAGRDIPP NOTC1_HUMAN 1426 1426 -
HILDYSFTGAAGRDIPP NTC1_RAT 1426 1426 -
HILDYEFNGGVGQDIIP Q8AXP0_CYNPY 1424 1424 -
HILDYGFIGGLGKNITP A2RUV0_XENTR 1424 1424 -
HILDWSFPGGTGQDITP A5WUN6_DANRE 1373 1373 -
HILDYEFPGGLGKNITP NOTC_XENLA 1424 1424 -
HILDYSFSGGQGRDIAP NOTC_BRARE 1423 1423 -

Motif 2 width=13
Element Seqn Id St Int Rpt
RNNSFHFLRELSH NTC1_MOUSE 1586 143 -
RNSSFHFLRELSR NOTC1_HUMAN 1586 143 -
RNNSFHFLRDVSH NTC1_RAT 1586 143 -
KNNSFNFLRELSR Q8AXP0_CYNPY 1584 143 -
KNNSVNFLRELSR A2RUV0_XENTR 1583 142 -
RNNSFGFLRELSR A5WUN6_DANRE 1534 144 -
KNNSVNFLRELSR NOTC_XENLA 1583 142 -
RNRSSSFLRELSS NOTC_BRARE 1584 144 -

Motif 3 width=11
Element Seqn Id St Int Rpt
IPYKIEAVKSE NTC1_MOUSE 1704 105 -
IPYKIEAVQSE NOTC1_HUMAN 1714 115 -
IPYKIEAVKSE NTC1_RAT 1704 105 -
IPYKIEAVKSE Q8AXP0_CYNPY 1711 114 -
IPYKIEAVKSE A2RUV0_XENTR 1708 112 -
MPYVIEAVTSE A5WUN6_DANRE 1663 116 -
LSYKIEAVKSE NOTC_XENLA 1708 112 -
VPYIIEAVTSE NOTC_BRARE 1706 109 -

Motif 4 width=31
Element Seqn Id St Int Rpt
YLSDVASHPLLPSPFQQSPSMPLSHLPGMPD NTC1_MOUSE 2199 484 -
YLSDVASPPLLPSPFQQSPSVPLNHLPGMPD NOTC1_HUMAN 2209 484 -
YLSDVASPPLLPSPFQQSPSMPLSHLPGMPD NTC1_RAT 2199 484 -
YISDVASPPLMTSPFQQSPSMALNLLPGMTD Q8AXP0_CYNPY 2203 481 -
YLSDVASPPLMTSPFQQSPSMPLNHLTSMQD A2RUV0_XENTR 2206 487 -
YISDIASPPQMTSPFQQSPSMSLNQLQGMSD A5WUN6_DANRE 2154 480 -
YLSDVSSPPLMTSPFQQSPSMPLNHLTSMPE NOTC_XENLA 2205 486 -
YLSDVSSPPMMTSPFQQSPPISLNQLQGLAD NOTC_BRARE 2191 474 -

Motif 5 width=12
Element Seqn Id St Int Rpt
NGQCEWLPRLQN NTC1_MOUSE 2295 65 -
NGQCEWLSRLQS NOTC1_HUMAN 2305 65 -
NGQCEWLPRLQN NTC1_RAT 2295 65 -
NGQCDWLSRLQN Q8AXP0_CYNPY 2294 60 -
NGQCDWFARLQN A2RUV0_XENTR 2294 57 -
NGQCEWLGRMHG A5WUN6_DANRE 2227 42 -
NSQCDWLARLQN NOTC_XENLA 2295 59 -
AGACDWLQRVQQ NOTC_BRARE 2255 33 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
HILDYSFTGGAGRDIPP Q7TQ50_MOUSE 1426 1426 -
HILDYSFTGGAGRDIPP Q8K428_MOUSE 1426 1426 -
HILDYSFTGGAGRDIPP Q7TQ52_MOUSE 1411 1411 -
HILDYSFTGGAGRDIPP Q7TQ51_MOUSE 1421 1421 -
HILDYSFTGGAGPDIPP NTC1_MOUSE 1426 1426 -
HILDYSFGGGAGRDIPP B7WP15_HUMAN 1427 1427 -
HILDYSFGGGAGRDIPP NOTC1_HUMAN 1426 1426 -
HILDYSFTGAAGRDIPP NTC1_RAT 1426 1426 -
HILDYEFNGGVGQDIIP Q8AXP0_CYNPY 1424 1424 -
HILDYGFIGGLGKNITP A2RUV0_XENTR 1424 1424 -
HILDWSFPGGTGQDITP A0PGH6_DANRE 1402 1402 -
HILDWSFPGGTGQDITP A5WUN6_DANRE 1373 1373 -
HILDYEFPGGLGKNITP NOTC_XENLA 1424 1424 -
HILDYSFSGGQGRDIAP NOTC_BRARE 1423 1423 -

Motif 2 width=13
Element Seqn Id St Int Rpt
RNNSFHFLRELSH Q7TQ50_MOUSE 1586 143 -
RNNSFHFLRELSH Q8K428_MOUSE 1586 143 -
RNNSFHFLRELSH Q7TQ52_MOUSE 1571 143 -
RNNSFHFLRELSH Q7TQ51_MOUSE 1581 143 -
RNNSFHFLRELSH NTC1_MOUSE 1586 143 -
RNSSFHFLRELSR B7WP15_HUMAN 1587 143 -
RNSSFHFLRELSR NOTC1_HUMAN 1586 143 -
RNNSFHFLRDVSH NTC1_RAT 1586 143 -
KNNSFNFLRELSR Q8AXP0_CYNPY 1584 143 -
KNNSVNFLRELSR A2RUV0_XENTR 1583 142 -
RNNSFGFLRELSR A0PGH6_DANRE 1563 144 -
RNNSFGFLRELSR A5WUN6_DANRE 1534 144 -
KNNSVNFLRELSR NOTC_XENLA 1583 142 -
RNRSSSFLRELSS NOTC_BRARE 1584 144 -

Motif 3 width=11
Element Seqn Id St Int Rpt
IPYKIEAVKSE Q7TQ50_MOUSE 1704 105 -
IPYKIEAVKSE Q8K428_MOUSE 1704 105 -
IPYKIEAVKSE Q7TQ52_MOUSE 1689 105 -
IPYKIEAVKSE Q7TQ51_MOUSE 1699 105 -
IPYKIEAVKSE NTC1_MOUSE 1704 105 -
IPYKIEAVQSE B7WP15_HUMAN 1715 115 -
IPYKIEAVQSE NOTC1_HUMAN 1714 115 -
IPYKIEAVKSE NTC1_RAT 1704 105 -
IPYKIEAVKSE Q8AXP0_CYNPY 1711 114 -
IPYKIEAVKSE A2RUV0_XENTR 1708 112 -
MPYVIEAVTSE A0PGH6_DANRE 1692 116 -
MPYVIEAVTSE A5WUN6_DANRE 1663 116 -
LSYKIEAVKSE NOTC_XENLA 1708 112 -
VPYIIEAVTSE NOTC_BRARE 1706 109 -

Motif 4 width=31
Element Seqn Id St Int Rpt
YLSDVASPPLLPSPFQQSPSMPLSHLPGMPD Q7TQ50_MOUSE 2199 484 -
YLSDVASPPLLPSPFQQSPSMPLSHLPGMPD Q8K428_MOUSE 2199 484 -
YLSDVASPPLLPSPFQQSPSMPLSHLPGMPD Q7TQ52_MOUSE 2184 484 -
YLSDVASPPLLPSPFQQSPSMPLSHLPGMPD Q7TQ51_MOUSE 2194 484 -
YLSDVASHPLLPSPFQQSPSMPLSHLPGMPD NTC1_MOUSE 2199 484 -
YLSDVASPPLLPSPFQQSPSVPLNHLPGMPD B7WP15_HUMAN 2210 484 -
YLSDVASPPLLPSPFQQSPSVPLNHLPGMPD NOTC1_HUMAN 2209 484 -
YLSDVASPPLLPSPFQQSPSMPLSHLPGMPD NTC1_RAT 2199 484 -
YISDVASPPLMTSPFQQSPSMALNLLPGMTD Q8AXP0_CYNPY 2203 481 -
YLSDVASPPLMTSPFQQSPSMPLNHLTSMQD A2RUV0_XENTR 2206 487 -
YISDIASPPQMTSPFQQSPSMSLNQLQGMSD A0PGH6_DANRE 2183 480 -
YISDIASPPQMTSPFQQSPSMSLNQLQGMSD A5WUN6_DANRE 2154 480 -
YLSDVSSPPLMTSPFQQSPSMPLNHLTSMPE NOTC_XENLA 2205 486 -
YLSDVSSPPMMTSPFQQSPPISLNQLQGLAD NOTC_BRARE 2191 474 -

Motif 5 width=12
Element Seqn Id St Int Rpt
NGQCEWLPRLQN Q7TQ50_MOUSE 2295 65 -
NGQCEWLPRLQN Q8K428_MOUSE 2295 65 -
NGQCEWLPRLQN Q7TQ52_MOUSE 2280 65 -
NGQCEWLPRLQN Q7TQ51_MOUSE 2290 65 -
NGQCEWLPRLQN NTC1_MOUSE 2295 65 -
NGQCEWLSRLQS B7WP15_HUMAN 2306 65 -
NGQCEWLSRLQS NOTC1_HUMAN 2305 65 -
NGQCEWLPRLQN NTC1_RAT 2295 65 -
NGQCDWLSRLQN Q8AXP0_CYNPY 2294 60 -
NGQCDWFARLQN A2RUV0_XENTR 2294 57 -
NGQCEWLERMHG A0PGH6_DANRE 2256 42 -
NGQCEWLGRMHG A5WUN6_DANRE 2227 42 -
NSQCDWLARLQN NOTC_XENLA 2295 59 -
AGACDWLQRVQQ NOTC_BRARE 2255 33 -