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PR01985

Identifier
NOTCH2  [View Relations]  [View Alignment]  
Accession
PR01985
No. of Motifs
4
Creation Date
11-JUN-2009
Title
Neurogenic locus Notch protein 2 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; 2004
SCOP; 2004
CATH; 2004
MIM; 600275; 610205
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).

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 2 has a widespread expression pattern. It is expressed in a number of
tissues, including brain, heart, kidney, lung, teeth, skeletal muscle and
liver.
 
NOTCH2 is a 4-element fingerprint that provides a signature for neurogenic
locus Notch protein 2. The fingerprint was derived from an initial alignment
of 5 sequences: the motifs were drawn from conserved regions spanning
virtually the full alignment length - motif 1 lies in a conserved area
C-terminal to the LNR region; motif 2 lies in a conserved section N-terminal 
to the TM domain; motif 3 resides in a region C-terminal to the ankyrin 
repeats; and motif 4 resides in a region N-terminal to the PEST domain. Two 
iterations on SPTR57_40f were required to reach convergence, at which point
a true set comprising 3 sequences was identified. Two partial matches were
also found, both Notch 2 sequences that are missing parts of the sequence
bearing the first 2 motifs.
Summary Information
   3 codes involving  4 elements
0 codes involving 3 elements
2 codes involving 2 elements
Composite Feature Index
43333
30000
20022
1234
True Positives
NOTC2_HUMAN   O35516        Q9QW30        
True Positive Partials
Codes involving 2 elements
Q6PCM9_MOUSE Q96JU8_HUMAN
Sequence Titles
NOTC2_HUMAN Neurogenic locus notch homolog protein 2; Notch 2; hN2; Contains:   Notch 2 extracellular truncation; Contains:   Notch 2 intracellular domain;  Precursor; - Homo sapiens (Human). 
O35516 CELL SURFACE PROTEIN - Mus musculus (Mouse).
Q9QW30 NOTCH2 PROTEIN - Rattus sp.

Q6PCM9_MOUSE Notch2 protein; - Mus musculus (Mouse).
Q96JU8_HUMAN cDNA FLJ14963 fis, clone PLACE4000522, weakly similar to NEUROGENIC LOCUS NOTCH PROTEIN; - Homo sapiens (Human).
Scan History
SPTR57_40f 2  100  NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
LQDSRSFLRALGT Q9QW30 1559 1559 -
LQDARSFLRALGT NOTC2_HUMAN 1559 1559 -
LQDSRSFLRALGT O35516 1557 1557 -

Motif 2 width=10
Element Seqn Id St Int Rpt
LSYPLVSVVS Q9QW30 1659 87 -
LSYPLVSVVS NOTC2_HUMAN 1659 87 -
LSYPLVSVFS O35516 1659 89 -

Motif 3 width=13
Element Seqn Id St Int Rpt
VLPSVSQLLSHHH Q9QW30 2216 547 -
VLPSVSQLLSHHH NOTC2_HUMAN 2217 548 -
VLPSVSQLLSHHH O35516 2215 546 -

Motif 4 width=22
Element Seqn Id St Int Rpt
EGKPIPTQREPLPPIVTFQLIP Q9QW30 2290 61 -
EGKHITTPREPLPPIVTFQLIP NOTC2_HUMAN 2290 60 -
EGKHMSTQREPLPPIVTFQLIP O35516 2289 61 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
LQDSRSFLRALGT Q9QW30 1559 1559 -
LQDARSFLRALGT NOTC2_HUMAN 1559 1559 -
LQDSRSFLRALGT O35516 1557 1557 -

Motif 2 width=10
Element Seqn Id St Int Rpt
LSYPLVSVVS Q9QW30 1659 87 -
LSYPLVSVVS NOTC2_HUMAN 1659 87 -
LSYPLVSVFS O35516 1659 89 -

Motif 3 width=13
Element Seqn Id St Int Rpt
VLPSVSQLLSHHH Q9QW30 2216 547 -
VLPSVSQLLSHHH NOTC2_HUMAN 2217 548 -
VLPSVSQLLSHHH O35516 2215 546 -

Motif 4 width=22
Element Seqn Id St Int Rpt
EGKPIPTQREPLPPIVTFQLIP Q9QW30 2290 61 -
EGKHITTPREPLPPIVTFQLIP NOTC2_HUMAN 2290 60 -
EGKHMSTQREPLPPIVTFQLIP O35516 2289 61 -