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PR01431

Identifier
TUBERIN  [View Relations]  [View Alignment]  
Accession
PR01431
No. of Motifs
10
Creation Date
31-OCT-2000
Title
Tuberin signature
Database References
Literature References
1. VAN SLEGTENHORST, M., NELLIST, M., NAGELKERKEN, B., CHEADLE, J.,
SNELL, R., VAN DEN OUWELAND, A., REUSER, A., SAMPSON, J., HALLEY, D.
AND VAN DER SLUIJS, P.
Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products.
HUM.MOL.GENET. 7 1053-1057 (1998). 
 
2. XU, L., STERNER, C., MAHESHWAR, M.M., WILSON, P.J., NELLIST, M.,
SHORT, P.M., HAINES, J.L., SAMPSON, J.R. AND RAMESH, V.
Alternative splicing of the tuberous sclerosis 2 (TSC2) gene in human and
mouse tissues.
GENOMICS 27 475-480 (1995). 
 
3. XIAO, G.H., SHOARINEJAD, F., JIN, F., GOLEMIS, E.A. AND YEUNG, R.S.
The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5 GTPase
activating protein (GAP) in modulating endocytosis.
J.BIOL.CHEM. 272 6097-6100 (1997). 

Documentation
Tuberous sclerosis (TSC) is an autosomal dominant disorder caused by a 
mutation in either the TSC1 or TSC2 tumour suppressor genes. The disease is
characterised by hamartomas in one or more organs (including brain, skin,
heart and kidney) giving rise to a broad phenotypic spectrum (including 
seizures, mental retardation, renal dysfunction and dermatological 
abnormalities [1]. TSC2 encodes tuberin, a putative GTPase activating
protein for rap1 and rab5. The TSC1 gene was recently identified and codes
for hamartin, a novel protein with no significant similarity to tuberin or
any other known vertebrate protein [1]. Hamartin and tuberin have been shown
to associate physically in vivo, their interaction being mediated by
predicted coiled-coil domains [1]. It is thought that hamartin and tuberin
function in the same complex, rather than in separate pathways [1].
Moreover, because oligomerisation of the hamartin C-terminal coiled coil
domain is inhibited by the presence of tuberin, it is possible that tuberin
acts as a chaperone, preventing hamartin self-aggregation. 
 
Tuberin, is a widely expressed 1784-amino-acid protein [2]. Expression of 
the wild-type gene in TSC2 mutant tumour cells inhibits proliferation and
tumorigenicity. This "suppressor" activity is encoded by a functional
domain in the C-terminus that shares similarity with the GTPase activating
protein Rap1GAP [2]. Using a yeast two-hybrid assay, the cytosolic factor,
rabaptin-5, was found to associate with a distinct domain lying adjacent
to the TSC2 GAP similarity region [2]. Rabaptin-5 also binds the active form
of GTPase Rab5. It is thought that tuberin may function as a Rab5GAP in vivo 
to negatively regulate Rab5-GTP activity in endocytosis [3]. 
 
TUBERIN is a 10-element fingerprint that provides a signature for tuberins.
The fingerprint was derived from an initial alignment of 2 sequences: the
motifs were drawn largely from hydrophobic segments spanning virtually the
full alignment length. Two iterations on SPTR39_14f were required to reach
convergence, at which point a true set comprising 3 sequences was identified.
Two partial matches were also found, Q9VW83 and  Q9U9B0, both of which are
Drosophila gigas proteins (which belong to the GTPase activating protein
rap1GAP family) that match motifs 3 and 10.
Summary Information
   3 codes involving 10 elements
0 codes involving 9 elements
0 codes involving 8 elements
0 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
2 codes involving 2 elements
Composite Feature Index
103333333333
90000000000
80000000000
70000000000
60000000000
50000000000
40000000000
30000000000
20020000002
12345678910
True Positives
TSC2_HUMAN    TSC2_MOUSE    TSC2_RAT      
True Positive Partials
Codes involving 2 elements
Q9U9B0 Q9VW83
Sequence Titles
TSC2_HUMAN  TUBERIN (TUBEROUS SCLEROSIS 2 PROTEIN) - Homo sapiens (Human). 
TSC2_MOUSE TUBERIN (TUBEROUS SCLEROSIS 2 HOMOLOG PROTEIN) - Mus musculus (Mouse).
TSC2_RAT TUBERIN (TUBEROUS SCLEROSIS 2 HOMOLOG PROTEIN) - Rattus norvegicus (Rat).

Q9U9B0 GIGAS PROTEIN - Drosophila melanogaster (Fruit fly).
Q9VW83 GIG PROTEIN - Drosophila melanogaster (Fruit fly).
Scan History
SPTR39_14f 1  50   NSINGLE    
Initial Motifs
Motif 1  width=24
Element Seqn Id St Int Rpt
FVLQWMDVGLSSEFLLVLVNLVKF TSC2_HUMAN 163 163 -
FVLQWMDVGLSSEFLLVLVNLVKF TSC2_RAT 163 163 -

Motif 2 width=20
Element Seqn Id St Int Rpt
TASSVDIEVSLQVLDAVVCY TSC2_HUMAN 209 22 -
TVSSVDIEVSLQVLDAVVCY TSC2_RAT 209 22 -

Motif 3 width=19
Element Seqn Id St Int Rpt
APLLRGAVFFVGMALWGAH TSC2_HUMAN 289 60 -
APLLRGAVFFVGMALWGAH TSC2_RAT 289 60 -

Motif 4 width=21
Element Seqn Id St Int Rpt
ELQVVAWDILLNIIERLLQQL TSC2_HUMAN 352 44 -
ELQAVTWDILLDIIERLLQQL TSC2_RAT 352 44 -

Motif 5 width=22
Element Seqn Id St Int Rpt
VKTAVLGLLVILQTKLYTLPAS TSC2_HUMAN 560 187 -
VKTAVLGLLVILQTKLYTLPAS TSC2_RAT 560 187 -

Motif 6 width=26
Element Seqn Id St Int Rpt
YTLPIASSIRLQAFDFLFLLRADSLH TSC2_HUMAN 602 20 -
YSLPIASSIRLQAFDFLLLLRADSLH TSC2_RAT 602 20 -

Motif 7 width=21
Element Seqn Id St Int Rpt
AVRLGSVPYSLLFRVLLQCLK TSC2_HUMAN 678 50 -
AVRLGHLPYSLLFRVLLQCLK TSC2_RAT 678 50 -

Motif 8 width=22
Element Seqn Id St Int Rpt
WKVLKLVLGRLPESLRYKVLIF TSC2_HUMAN 703 4 -
WKVLKLVLSKLPESLRYKVLIF TSC2_RAT 703 4 -

Motif 9 width=21
Element Seqn Id St Int Rpt
SMAVPLLEFLSTLARLPHLYR TSC2_HUMAN 838 113 -
SMAIPLLEFLSTLARLPHLYR TSC2_RAT 838 113 -

Motif 10 width=21
Element Seqn Id St Int Rpt
YIVCLAHHVIAMWFIRCRLPF TSC2_HUMAN 884 25 -
YIVCLAHHVIAMWFIRCRLPF TSC2_RAT 884 25 -
Final Motifs
Motif 1  width=24
Element Seqn Id St Int Rpt
FVLQWMDVGLSSEFLLVLVNLVKF TSC2_MOUSE 163 163 -
FVLQWMDVGLSSEFLLVLVNLVKF TSC2_HUMAN 163 163 -
FVLQWMDVGLSSEFLLVLVNLVKF TSC2_RAT 163 163 -

Motif 2 width=20
Element Seqn Id St Int Rpt
TVSSVDIEVSLQVLDAVVCY TSC2_MOUSE 209 22 -
TASSVDIEVSLQVLDAVVCY TSC2_HUMAN 209 22 -
TVSSVDIEVSLQVLDAVVCY TSC2_RAT 209 22 -

Motif 3 width=19
Element Seqn Id St Int Rpt
APLLRGAVFFVGMALWGAH TSC2_MOUSE 289 60 -
APLLRGAVFFVGMALWGAH TSC2_HUMAN 289 60 -
APLLRGAVFFVGMALWGAH TSC2_RAT 289 60 -

Motif 4 width=21
Element Seqn Id St Int Rpt
ELQAVTWDILLDIIERLLQQL TSC2_MOUSE 352 44 -
ELQVVAWDILLNIIERLLQQL TSC2_HUMAN 352 44 -
ELQAVTWDILLDIIERLLQQL TSC2_RAT 352 44 -

Motif 5 width=22
Element Seqn Id St Int Rpt
VKTAVLGLLVILQTKLYTLPAS TSC2_MOUSE 560 187 -
VKTAVLGLLVILQTKLYTLPAS TSC2_HUMAN 560 187 -
VKTAVLGLLVILQTKLYTLPAS TSC2_RAT 560 187 -

Motif 6 width=26
Element Seqn Id St Int Rpt
YSLPIASSIRLQAFDFLLLLRADSLH TSC2_MOUSE 602 20 -
YTLPIASSIRLQAFDFLFLLRADSLH TSC2_HUMAN 602 20 -
YSLPIASSIRLQAFDFLLLLRADSLH TSC2_RAT 602 20 -

Motif 7 width=21
Element Seqn Id St Int Rpt
AVRLGYLPYSLLFRVLLQCLK TSC2_MOUSE 678 50 -
AVRLGSVPYSLLFRVLLQCLK TSC2_HUMAN 678 50 -
AVRLGHLPYSLLFRVLLQCLK TSC2_RAT 678 50 -

Motif 8 width=22
Element Seqn Id St Int Rpt
WKVLKLVLSRLPESLRYKVLIF TSC2_MOUSE 703 4 -
WKVLKLVLGRLPESLRYKVLIF TSC2_HUMAN 703 4 -
WKVLKLVLSKLPESLRYKVLIF TSC2_RAT 703 4 -

Motif 9 width=21
Element Seqn Id St Int Rpt
SMAIPLLEFLSTLARLPHLYR TSC2_MOUSE 838 113 -
SMAVPLLEFLSTLARLPHLYR TSC2_HUMAN 838 113 -
SMAIPLLEFLSTLARLPHLYR TSC2_RAT 838 113 -

Motif 10 width=21
Element Seqn Id St Int Rpt
YIVCLAHHVIAMWFIRCRLPF TSC2_MOUSE 884 25 -
YIVCLAHHVIAMWFIRCRLPF TSC2_HUMAN 884 25 -
YIVCLAHHVIAMWFIRCRLPF TSC2_RAT 884 25 -