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PR01424

Identifier
TGFBETA1  [View Relations]  [View Alignment]  
Accession
PR01424
No. of Motifs
6
Creation Date
31-OCT-2000
Title
Transforming growth factor beta 1 precursor signature
Database References
PRINTS; PR01423 TGFBETA
PDB; 1KLA; 1KLC; 1KLD
SCOP; 1KLA; 1KLC; 1KLD
CATH; 1KLA; 1KLC; 1KLD
MIM; 190180
Literature References
1. ARCHER, S.J., BAX, A., ROBERTS, A.B., SPORN, M.B., OGAWA, Y., PIEZ, K.A.,
WEATHERBEE, J.A., TSANG, M.L., LUCAS, R. AND ZHENG, B.L.
Transforming growth factor beta 1: NMR signal assignments of the recombinant
protein expressed and isotopically enriched using Chinese hamster ovary cells.
BIOCHEMISTRY 32 1152-1163 (1993). 
 
2. CHEIFETZ, S., WEATHERBEE, J.A., TSANG, M.L.S., ANDERSON, J.K.,
MOLE, J.E., LUCAS, R. AND MASSAGUE, J. 
The transforming growth factor-beta system, a complex pattern of 
cross-reactive ligands and receptors. 
CELL 48 409-415 (1987).
 
3. SUTTON, R., WARD, W.G., RAPHAEL, K.A. AND CAM, G.R. 
Growth factor expression in skin during wool follicle development. 
COMP.BIOCHEM.PHYSIOL. 110B 697-705 (1995).
 
4. DERYNCK, R. AND RHEE, L. 
Sequence of the porcine transforming growth factor-beta precursor. 
NUCLEIC ACIDS RES. 15 3187-3187 (1987).
 
5. MASSAGUE, J. AND LIKE, B. 
Cellular receptors for type beta transforming growth factor. Ligand 
binding and affinity labeling in human and rodent cell lines. 
J.BIOL.CHEM. 260 2636-2645 (1985).
 
6. HINCK, A.P., ARCHER, S.J., QIAN, S.W., ROBERTS, A.B.,
SPORN, M.B., WEATHERBEE, J.A., TSANG, M.L.-S., LUCAS, R.,
ZHENG, B.-L., WENKER, J. AND TORCHIA, D.A. 
Transforming growth factor beta 1: three-dimensional structure in
solution and comparison with the X-ray structure of transforming 
growth factor beta 2. 
BIOCHEMISTRY 35 8517-8534 (1996).
 
7. MILLER, D.A., LEE, A., MATSUI, Y., CHEN, E.Y., MOSES H.L. AND DERYNCK, R.
Complementary DNA cloning of the murine transforming growth factor-beta 3
beta 1 messenger RNA in murine embryos and adult tissues.
MOL.ENDOCRINOL. 3 1926-1934 (1989). 

Documentation
The transforming growth factors-beta (TGF-beta 1-5) constitute a family of
multi-functional cytokines that regulate cell growth and differentiation [1].
Many cells synthesise TGF-beta, and essentially all have specific receptors 
for this peptide [2]. TGF-beta regulates the actions of many other peptide
growth factors and determines a positive or negative direction of their 
effects. The protein functions as a disulphide-linked homodimer. Its
sequence is characterised by the presence of several C-terminal cysteine
residues, which form interlocking disulphide links arranged in a knot-like
topology. A similar "cystine-knot" arrangement has been noted in the
structures of some enzyme inhibitors and neurotoxins that bind to voltage-
gated Ca2+ channels, although the precise topology here differs. 
 
The three-dimensional structures of several members of the TGF-beta super-
family have been deduced. The solution structure of human TGF-beta 1 has
been determined using multinuclear magnetic resonance spectroscopy with
hybrid distance geometry/simulated annealing [6]. The structure shows a high
degree of similarity to that of TGF-beta 2, but there are several notable
differences in structure and flexibility, which might relate to function [6].
 
TGF-beta genes are expressed differentially, suggesting that the various TGF-
beta species may have distinct physiological roles in vivo. Examination of
TGF-beta 1 mRNA levels in adult murine tissues indicates that expression is
predominant in spleen, lung and placenta [7]. TGF-beta 1 is believed to play
important roles in pathologic processes.
 
TGFBETA1 is a 6-element fingerprint that provides a signature for the
transforming growth factor beta 1 precursor proteins. The fingerprint was
derived from an initial alignment of 8 sequences: the motifs were drawn from
conserved regions spanning the N-terminal half of the alignment, focusing on
those sections that characterise TGF-beta 1 proteins but distinguish them
from the rest of the TGF-beta superfamily. Two iterations on SPTR39_14f were
required to reach convergence, at which point a true set comprising 11 
sequences was identified. A single partial match was also found, O93449,
a transforming growth factor beta precursor from Oncorhynchus mykiss
(Rainbow trout) that only matches motifs 2, 3 and 5.
Summary Information
  11 codes involving  6 elements
0 codes involving 5 elements
0 codes involving 4 elements
1 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
6111111111111
5000000
4000000
3011010
2000000
123456
True Positives
Q9TUM8        Q9Z1Y6        TGB1_SHEEP    TGF1_CANFA    
TGF1_CERAE TGF1_HORSE TGF1_HUMAN TGF1_MOUSE
TGF1_PIG TGF1_RAT TGF1_XENLA
True Positive Partials
Codes involving 3 elements
O93449
Sequence Titles
Q9TUM8      TRANSFORMING GROWTH FACTOR BETA 1 - Equus caballus (Horse). 
Q9Z1Y6 TRANSFORMING GROWTH FACTOR BETA 1 PRECURSOR (TGF-BETA 1) (INTERLEUKIN TGF BETA) - Cavia porcellus (Guinea pig).
TGB1_SHEEP TRANSFORMING GROWTH FACTOR BETA 1 PRECURSOR (TGF-BETA 1) - OVIS ARIES (SHEEP).
TGF1_CANFA TRANSFORMING GROWTH FACTOR BETA 1 PRECURSOR (TGF-BETA 1) - Canis familiaris (Dog).
TGF1_CERAE TRANSFORMING GROWTH FACTOR BETA 1 PRECURSOR (TGF-BETA 1) - Cercopithecus aethiops (Green monkey) (Grivet).
TGF1_HORSE TRANSFORMING GROWTH FACTOR BETA 1 PRECURSOR (TGF-BETA 1) - Equus caballus (Horse).
TGF1_HUMAN TRANSFORMING GROWTH FACTOR BETA 1 PRECURSOR (TGF-BETA 1) - Homo sapiens (Human).
TGF1_MOUSE TRANSFORMING GROWTH FACTOR BETA 1 PRECURSOR (TGF-BETA 1) - Mus musculus (Mouse).
TGF1_PIG TRANSFORMING GROWTH FACTOR BETA 1 PRECURSOR (TGF-BETA 1) - Sus scrofa (Pig).
TGF1_RAT TRANSFORMING GROWTH FACTOR BETA 1 PRECURSOR (TGF-BETA 1) - Rattus norvegicus (Rat).
TGF1_XENLA TRANSFORMING GROWTH FACTOR BETA 1 PRECURSOR (TGF-BETA 1) (TGF-BETA 5) - Xenopus laevis (African clawed frog).

O93449 TRANSFORMING GROWTH FACTOR BETA PRECURSOR - Oncorhynchus mykiss (Rainbow trout) (Salmo gairdneri).
Scan History
SPTR39_14f 2  50   NSINGLE    
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
LLPLLWLLVLTPGRPAAGLS TGF1_HUMAN 12 12 -
LLPLLWLLVLTPSRPAAGLS TGF1_CERAE 12 12 -
LLPLLRLLVLTPGRPAAGLS TGF1_CANFA 12 12 -
LLPLLWLLVLTPGRPAAGLS TGF1_HORSE 12 12 -
LLPLLWLLVLTPGRPAAGLS TGF1_PIG 12 12 -
LLPLPWLLVLTPGRPAAGLS TGF1_MOUSE 12 12 -
LLPLPWLLVLTPGRPAAGLS TGF1_RAT 12 12 -
LWMLLVLLVLHLSSLAMSLS TGF1_XENLA 4 4 -

Motif 2 width=10
Element Seqn Id St Int Rpt
KTIDMELVKR TGF1_HUMAN 34 2 -
KTIDMELVKR TGF1_CERAE 34 2 -
KTIDMELVKR TGF1_CANFA 34 2 -
KTIDMELVKR TGF1_HORSE 34 2 -
KTIDMELVKR TGF1_PIG 34 2 -
KTIDMELVKR TGF1_MOUSE 34 2 -
KTIDMELVKR TGF1_RAT 34 2 -
KAVDMEEVRK TGF1_XENLA 26 2 -

Motif 3 width=20
Element Seqn Id St Int Rpt
FNTSELREAVPEPVLLSRAE TGF1_HUMAN 135 91 -
FNTSELREAVPEPVLLSRAE TGF1_CERAE 135 91 -
FNTSELREAVPEPVLLSRAE TGF1_CANFA 135 91 -
FNTSELRAAVPDPMLLSRAE TGF1_HORSE 135 91 -
FNTSELREAVPEPVLLSRAE TGF1_PIG 135 91 -
FNTSDIREAVPEPPLLSRAE TGF1_MOUSE 135 91 -
FNTSDIREAVPEPPLLSRAE TGF1_RAT 135 91 -
FNASHVRENVGMNSLLHHAE TGF1_XENLA 122 86 -

Motif 4 width=12
Element Seqn Id St Int Rpt
QHVELYQKYSNN TGF1_HUMAN 166 11 -
QHVELYQKYSNN TGF1_CERAE 166 11 -
QHVELYQKYSND TGF1_CANFA 166 11 -
QHVELYQKYSNN TGF1_HORSE 166 11 -
QHVELYQKYSND TGF1_PIG 166 11 -
QHVELYQKYSNN TGF1_MOUSE 166 11 -
QHVELYQKYSNN TGF1_RAT 166 11 -
QRMELFWKYQEN TGF1_XENLA 155 13 -

Motif 5 width=13
Element Seqn Id St Int Rpt
WLSRGGEIEGFRL TGF1_HUMAN 207 29 -
WLSRGGEIEGFRL TGF1_CERAE 207 29 -
WLSHGGEVEGFRL TGF1_CANFA 207 29 -
WLSQGGAMEGFRL TGF1_HORSE 207 29 -
WLTRREAIEGFRL TGF1_PIG 207 29 -
WLNQGDGIQGFRF TGF1_MOUSE 207 29 -
WLNQGDGIQGFRF TGF1_RAT 207 29 -
WLKRAEENEQFGL TGF1_XENLA 199 32 -

Motif 6 width=12
Element Seqn Id St Int Rpt
PLERAQHLQSSR TGF1_HUMAN 264 44 -
PLERAQHLQSSR TGF1_CERAE 264 44 -
PLERAQHLHSSR TGF1_CANFA 264 44 -
PLERAQQLHSSR TGF1_HORSE 264 44 -
PLERAQHLHSSR TGF1_PIG 264 44 -
PLERAQHLHSSR TGF1_MOUSE 264 44 -
PLERAQHLHSSR TGF1_RAT 264 44 -
PAERIDTVTSSR TGF1_XENLA 256 44 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
LLPLLWLLVLTPGRPAAGLS TGF1_HUMAN 12 12 -
LLPLLWLLVLTPSRPAAGLS TGF1_CERAE 12 12 -
LLPLLRLLVLTPGRPAAGLS TGF1_CANFA 12 12 -
LLPLLWLLVLTPGRPAAGLS TGF1_HORSE 12 12 -
LLPLLWLLVLTPGRPAAGLS TGF1_PIG 12 12 -
LLPLLWLLVLAPGRPASGLS Q9Z1Y6 12 12 -
LLPLLWLLMLTPGRPVAGLS TGB1_SHEEP 12 12 -
LLPLLWLLVLTPGRPAAGLS Q9TUM8 12 12 -
LLPLPWLLVLTPGRPAAGLS TGF1_MOUSE 12 12 -
LLPLPWLLVLTPGRPAAGLS TGF1_RAT 12 12 -
LWMLLVLLVLHLSSLAMSLS TGF1_XENLA 4 4 -

Motif 2 width=10
Element Seqn Id St Int Rpt
KTIDMELVKR TGF1_HUMAN 34 2 -
KTIDMELVKR TGF1_CERAE 34 2 -
KTIDMELVKR TGF1_CANFA 34 2 -
KTIDMELVKR TGF1_HORSE 34 2 -
KTIDMELVKR TGF1_PIG 34 2 -
KTIDMELVKR Q9Z1Y6 34 2 -
KTIDMELVKR TGB1_SHEEP 34 2 -
KTIDMELVKR Q9TUM8 34 2 -
KTIDMELVKR TGF1_MOUSE 34 2 -
KTIDMELVKR TGF1_RAT 34 2 -
KAVDMEEVRK TGF1_XENLA 26 2 -

Motif 3 width=20
Element Seqn Id St Int Rpt
FNTSELREAVPEPVLLSRAE TGF1_HUMAN 135 91 -
FNTSELREAVPEPVLLSRAE TGF1_CERAE 135 91 -
FNTSELREAVPEPVLLSRAE TGF1_CANFA 135 91 -
FNTSELRAAVPDPMLLSRAE TGF1_HORSE 135 91 -
FNTSELREAVPEPVLLSRAE TGF1_PIG 135 91 -
FNTSELREAVPDPLLLSRAE Q9Z1Y6 135 91 -
FNTSELREAVPEPVLLSRAD TGB1_SHEEP 135 91 -
FNASELRAAVPDPMLLSRAE Q9TUM8 135 91 -
FNTSDIREAVPEPPLLSRAE TGF1_MOUSE 135 91 -
FNTSDIREAVPEPPLLSRAE TGF1_RAT 135 91 -
FNASHVRENVGMNSLLHHAE TGF1_XENLA 122 86 -

Motif 4 width=12
Element Seqn Id St Int Rpt
QHVELYQKYSNN TGF1_HUMAN 166 11 -
QHVELYQKYSNN TGF1_CERAE 166 11 -
QHVELYQKYSND TGF1_CANFA 166 11 -
QHVELYQKYSNN TGF1_HORSE 166 11 -
QHVELYQKYSND TGF1_PIG 166 11 -
QHVELYQKYSNN Q9Z1Y6 166 11 -
QHVELYQKYSNN TGB1_SHEEP 166 11 -
QHVELYQKYSNN Q9TUM8 166 11 -
QHVELYQKYSNN TGF1_MOUSE 166 11 -
QHVELYQKYSNN TGF1_RAT 166 11 -
QRMELFWKYQEN TGF1_XENLA 155 13 -

Motif 5 width=13
Element Seqn Id St Int Rpt
WLSRGGEIEGFRL TGF1_HUMAN 207 29 -
WLSRGGEIEGFRL TGF1_CERAE 207 29 -
WLSHGGEVEGFRL TGF1_CANFA 207 29 -
WLSQGGAMEGFRL TGF1_HORSE 207 29 -
WLTRREAIEGFRL TGF1_PIG 207 29 -
WLSQGEELEGFRF Q9Z1Y6 207 29 -
WLTHREEIEGFRL TGB1_SHEEP 207 29 -
WLSQGGAMEGLRL Q9TUM8 207 29 -
WLNQGDGIQGFRF TGF1_MOUSE 207 29 -
WLNQGDGIQGFRF TGF1_RAT 207 29 -
WLKRAEENEQFGL TGF1_XENLA 199 32 -

Motif 6 width=12
Element Seqn Id St Int Rpt
PLERAQHLQSSR TGF1_HUMAN 264 44 -
PLERAQHLQSSR TGF1_CERAE 264 44 -
PLERAQHLHSSR TGF1_CANFA 264 44 -
PLERAQQLHSSR TGF1_HORSE 264 44 -
PLERAQHLHSSR TGF1_PIG 264 44 -
PLERAQHLHSSR Q9Z1Y6 264 44 -
PLERAQHLHSSR TGB1_SHEEP 264 44 -
PLERAQQLHSSR Q9TUM8 264 44 -
PLERAQHLHSSR TGF1_MOUSE 264 44 -
PLERAQHLHSSR TGF1_RAT 264 44 -
PAERIDTVTSSR TGF1_XENLA 256 44 -