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PR01426

Identifier
TGFBETA3  [View Relations]  [View Alignment]  
Accession
PR01426
No. of Motifs
10
Creation Date
31-OCT-2000
Title
Transforming growth factor beta 3 precursor signature
Database References
PRINTS; PR01423 TGFBETA
PDB; 1TGJ; 1TGK
SCOP; 1TGJ; 1TGK
CATH; 1TGJ; 1TGK
MIM; 190230
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. DERYNCK, R., LINDQUIST, P.B., LEE, A., WEN, D.,
TAMM, J., GRAYCAR, J.L., RHEE, L., MASON, A.J.,
MILLER, D.A., COFFEY, R.J., MOSES, H.L. AND CHEN, E.Y. 
A new type of transforming growth factor-beta, TGF-beta 3. 
EMBO J. 7 3737-3743 (1988).
 
4. WANG, J., KULISZEWSKI, M., YEE, W., SEDLACKOVA, L.,
XU, J., TSEU, I. AND POST, M. 
Cloning and expression of glucocorticoid-induced genes in fetal rat 
lung fibroblasts. Transforming growth factor-beta 3. 
J.BIOL.CHEM. 270 2722-2728 (1995).
 
5. MITTL, P.R., PRIESTLE, J.P., COX, D.A., MCMASTER, G.,
CERLETTI, N. AND GRUTTER, M.G. 
The crystal structure of TGF-beta 3 and comparison to 
TGF-beta 2: implications for receptor binding. 
PROTEIN SCI. 5 1261-1271 (1996).
 
6. 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 differs. 
 
TGF-beta genes are expressed differentially, suggesting that the various TGF-
beta species may have distinct physiological roles in vivo. Examination of
TGF-beta 3 mRNA levels in adult murine tissues indicated that expression is 
predominant in brain, heart, adipose tissue and testis [6]. TGF beta-3 mRNA
is also observed in adult mouse lung and placenta [6]. Research on rat
foetal lung fibroblasts has shown that exposure to cortisol increases TGF-
beta 3 mRNA expression in a time- and dose-dependent manner, suggesting that
glucocorticoids may mediate their stimulatory effect on lung maturation by
inducing TGF-beta 3 expression in foetal lung fibroblasts [4]. 
 
The three-dimensional structures of several members of the TGF-beta super-
family have been deduced. The crystal structure of TGF-beta 3 reveals a near
identical central core to that of TGF-beta 2 [5]. The principal differences 
are witnessed in the conformations of the N-terminal alpha-helix and in the
beta-sheet loops [5], which could account for the individual cellular
responses, if these differences are recognised by the TGF-beta receptors.
 
TGFBETA3 is a 10-element fingerprint that provides a signature for the 
transforming growth factor beta 3 precursor proteins. The fingerprint was
derived from an initial alignment of 5 sequences: the motifs were drawn from
conserved regions spanning the N-terminal half of the alignment, focusing on
those sections that characterise TGF-beta 3 proteins but distinguish them
from the rest of the TGF-beta superfamily. A single iteration on SPTR39_14f 
was required to reach convergence, no further sequences being identified
beyond the starting set.
Summary Information
5 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
0 codes involving 2 elements
Composite Feature Index
105555555555
90000000000
80000000000
70000000000
60000000000
50000000000
40000000000
30000000000
20000000000
12345678910
True Positives
TGF3_CHICK    TGF3_HUMAN    TGF3_MOUSE    TGF3_PIG      
TGF3_RAT
Sequence Titles
TGF3_CHICK  TRANSFORMING GROWTH FACTOR BETA 3 PRECURSOR (TGF-BETA 3) - Gallus gallus (Chicken). 
TGF3_HUMAN TRANSFORMING GROWTH FACTOR BETA 3 PRECURSOR (TGF-BETA 3) - Homo sapiens (Human).
TGF3_MOUSE TRANSFORMING GROWTH FACTOR BETA 3 PRECURSOR (TGF-BETA 3) - Mus musculus (Mouse).
TGF3_PIG TRANSFORMING GROWTH FACTOR BETA 3 PRECURSOR (TGF-BETA 3) - Sus scrofa (Pig).
TGF3_RAT TRANSFORMING GROWTH FACTOR BETA 3 PRECURSOR (TGF-BETA 3) - Rattus norvegicus (Rat).
Scan History
SPTR39_14f 1  25   NSINGLE    
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
QRALVVLALLNLATVSLSLS TGF3_RAT 6 6 -
QRALVVLALLNFATVSLSLS TGF3_HUMAN 6 6 -
QRALVVLALLNLATISLSLS TGF3_MOUSE 4 4 -
QRALVVLALLNFATVSLSMS TGF3_PIG 4 4 -
QRALVLLSLLSFATVSLALS TGF3_CHICK 6 6 -

Motif 2 width=18
Element Seqn Id St Int Rpt
SPPEPSVMTHVPYQVLAL TGF3_RAT 55 29 -
SPPEPTVMTHVPYQVLAL TGF3_HUMAN 55 29 -
SPPEPSVMTHVPYQVLAL TGF3_MOUSE 53 29 -
SPPDPSMLANIPTQVLDL TGF3_PIG 53 29 -
SPPESVGPAHVPYQILAL TGF3_CHICK 55 29 -

Motif 3 width=18
Element Seqn Id St Int Rpt
ELLEEMHGEREEGCTQET TGF3_RAT 78 5 -
ELLEEMHGEREEGCTQEN TGF3_HUMAN 78 5 -
ELLEEMHGEREEGCTQET TGF3_MOUSE 76 5 -
ELLEEVHGERGDDCTQEN TGF3_PIG 76 5 -
ELLEEMEEEKEESCSQEN TGF3_CHICK 78 5 -

Motif 4 width=19
Element Seqn Id St Int Rpt
IHKFDMIQGLAEHNELAVC TGF3_RAT 105 9 -
IHKFDMIQGLAEHNELAVC TGF3_HUMAN 105 9 -
IHKFDMIQGLAEHNELAVC TGF3_MOUSE 103 9 -
IYKFDMIQGLEEHNDLAVC TGF3_PIG 103 9 -
IHKFDMIQGLPEHNELGIC TGF3_CHICK 105 9 -

Motif 5 width=18
Element Seqn Id St Int Rpt
CPKGITSKVFRFNVSSVE TGF3_RAT 123 -1 -
CPKGITSKVFRFNVSSVE TGF3_HUMAN 123 -1 -
CPKGITSKVFRFNVSSVE TGF3_MOUSE 121 -1 -
CPKGITSKIFRFNVSSVE TGF3_PIG 121 -1 -
CPKGVTSNVFRFNVSSAE TGF3_CHICK 123 -1 -

Motif 6 width=13
Element Seqn Id St Int Rpt
VLRVPNPSSKRTE TGF3_RAT 153 12 -
VLRVPNPSSKRNE TGF3_HUMAN 153 12 -
VLRVPNPSSKRTE TGF3_MOUSE 151 12 -
VLRMPNPSSKRSE TGF3_PIG 151 12 -
VLRVPNPSSKRSE TGF3_CHICK 153 12 -

Motif 7 width=20
Element Seqn Id St Int Rpt
PDEHIAKQRYIGGKNLPTRG TGF3_RAT 176 10 -
PDEHIAKQRYIGGKNLPTRG TGF3_HUMAN 176 10 -
PDEHIAKQRYIGGKNLPTRG TGF3_MOUSE 174 10 -
PDEHIAKQRYIDGKNLPTRG TGF3_PIG 174 10 -
PDEHIAKQRYLSGRNVQTRG TGF3_CHICK 176 10 -

Motif 8 width=15
Element Seqn Id St Int Rpt
LLRRESNLGLEISIH TGF3_RAT 212 16 -
LLRRESNLGLEISIH TGF3_HUMAN 212 16 -
LLRRESNLGLEISIH TGF3_MOUSE 210 16 -
LLRRESNLGLEISIH TGF3_PIG 210 16 -
LLHRESNLGLEISIH TGF3_CHICK 212 16 -

Motif 9 width=18
Element Seqn Id St Int Rpt
DNEDDHGRGDLGRLKKQK TGF3_RAT 254 27 -
DNEDDHGRGDLGRLKKQK TGF3_HUMAN 254 27 -
DNEDDHGRGDLGRLKKQK TGF3_MOUSE 252 27 -
DSEDDPGRGDLGRLKKKK TGF3_PIG 252 27 -
DSEDDYGRGDLGRLKKQK TGF3_CHICK 254 27 -

Motif 10 width=15
Element Seqn Id St Int Rpt
PPHRLDSPGQGGQRK TGF3_RAT 284 12 -
PPHRLDNPGQGGQRK TGF3_HUMAN 284 12 -
PPHRLDSPGQGSQRK TGF3_MOUSE 282 12 -
PPDRLDNPGLGAQRK TGF3_PIG 281 11 -
PPHRLESPTLGGQRK TGF3_CHICK 284 12 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
QRALVVLALLNLATVSLSLS TGF3_RAT 6 6 -
QRALVVLALLNFATVSLSLS TGF3_HUMAN 6 6 -
QRALVVLALLNLATISLSLS TGF3_MOUSE 4 4 -
QRALVVLALLNFATVSLSMS TGF3_PIG 4 4 -
QRALVLLSLLSFATVSLALS TGF3_CHICK 6 6 -

Motif 2 width=18
Element Seqn Id St Int Rpt
SPPEPSVMTHVPYQVLAL TGF3_RAT 55 29 -
SPPEPTVMTHVPYQVLAL TGF3_HUMAN 55 29 -
SPPEPSVMTHVPYQVLAL TGF3_MOUSE 53 29 -
SPPDPSMLANIPTQVLDL TGF3_PIG 53 29 -
SPPESVGPAHVPYQILAL TGF3_CHICK 55 29 -

Motif 3 width=18
Element Seqn Id St Int Rpt
ELLEEMHGEREEGCTQET TGF3_RAT 78 5 -
ELLEEMHGEREEGCTQEN TGF3_HUMAN 78 5 -
ELLEEMHGEREEGCTQET TGF3_MOUSE 76 5 -
ELLEEVHGERGDDCTQEN TGF3_PIG 76 5 -
ELLEEMEEEKEESCSQEN TGF3_CHICK 78 5 -

Motif 4 width=19
Element Seqn Id St Int Rpt
IHKFDMIQGLAEHNELAVC TGF3_RAT 105 9 -
IHKFDMIQGLAEHNELAVC TGF3_HUMAN 105 9 -
IHKFDMIQGLAEHNELAVC TGF3_MOUSE 103 9 -
IYKFDMIQGLEEHNDLAVC TGF3_PIG 103 9 -
IHKFDMIQGLPEHNELGIC TGF3_CHICK 105 9 -

Motif 5 width=18
Element Seqn Id St Int Rpt
CPKGITSKVFRFNVSSVE TGF3_RAT 123 -1 -
CPKGITSKVFRFNVSSVE TGF3_HUMAN 123 -1 -
CPKGITSKVFRFNVSSVE TGF3_MOUSE 121 -1 -
CPKGITSKIFRFNVSSVE TGF3_PIG 121 -1 -
CPKGVTSNVFRFNVSSAE TGF3_CHICK 123 -1 -

Motif 6 width=13
Element Seqn Id St Int Rpt
VLRVPNPSSKRTE TGF3_RAT 153 12 -
VLRVPNPSSKRNE TGF3_HUMAN 153 12 -
VLRVPNPSSKRTE TGF3_MOUSE 151 12 -
VLRMPNPSSKRSE TGF3_PIG 151 12 -
VLRVPNPSSKRSE TGF3_CHICK 153 12 -

Motif 7 width=20
Element Seqn Id St Int Rpt
PDEHIAKQRYIGGKNLPTRG TGF3_RAT 176 10 -
PDEHIAKQRYIGGKNLPTRG TGF3_HUMAN 176 10 -
PDEHIAKQRYIGGKNLPTRG TGF3_MOUSE 174 10 -
PDEHIAKQRYIDGKNLPTRG TGF3_PIG 174 10 -
PDEHIAKQRYLSGRNVQTRG TGF3_CHICK 176 10 -

Motif 8 width=15
Element Seqn Id St Int Rpt
LLRRESNLGLEISIH TGF3_RAT 212 16 -
LLRRESNLGLEISIH TGF3_HUMAN 212 16 -
LLRRESNLGLEISIH TGF3_MOUSE 210 16 -
LLRRESNLGLEISIH TGF3_PIG 210 16 -
LLHRESNLGLEISIH TGF3_CHICK 212 16 -

Motif 9 width=18
Element Seqn Id St Int Rpt
DNEDDHGRGDLGRLKKQK TGF3_RAT 254 27 -
DNEDDHGRGDLGRLKKQK TGF3_HUMAN 254 27 -
DNEDDHGRGDLGRLKKQK TGF3_MOUSE 252 27 -
DSEDDPGRGDLGRLKKKK TGF3_PIG 252 27 -
DSEDDYGRGDLGRLKKQK TGF3_CHICK 254 27 -

Motif 10 width=15
Element Seqn Id St Int Rpt
PPHRLDSPGQGGQRK TGF3_RAT 284 12 -
PPHRLDNPGQGGQRK TGF3_HUMAN 284 12 -
PPHRLDSPGQGSQRK TGF3_MOUSE 282 12 -
PPDRLDNPGLGAQRK TGF3_PIG 281 11 -
PPHRLESPTLGGQRK TGF3_CHICK 284 12 -