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PR01425

Identifier
TGFBETA2  [View Relations]  [View Alignment]  
Accession
PR01425
No. of Motifs
8
Creation Date
31-OCT-2000
Title
Transforming growth factor beta 2 precursor signature
Database References
PRINTS; PR01423 TGFBETA
PDB; 1TFG; 2TGI
SCOP; 1TFG; 2TGI
CATH; 1TFG; 2TGI
MIM; 190220
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. MARQUARDT, H., LIOUBIN, M.N. AND IKEDA, T. 
Complete amino acid sequence of human transforming growth factor 
type beta 2. 
J.BIOL.CHEM. 262 12127-12131 (1987).
 
4. BURT, D.W. AND PATON, I.R. 
Molecular cloning and primary structure of the chicken transforming 
growth factor-beta 2 gene. 
DNA CELL BIOL. 10 723-734 (1991).
 
5. DAOPIN, S., PIEZ, K.A., OGAWA, Y. AND DAVIES, D.R. 
Crystal structure of transforming growth factor-beta 2: an unusual 
fold for the superfamily. 
SCIENCE 257 369-373 (1992).

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 complete amino acid sequence of human beta 2 transforming growth factor
(hTGF-beta 2) has been determined by automated Edman degradation [3]. Human
TGF-beta 2 consists of 2 identical disulphide-linked subunits that share a
high degree of similarity with the functionally related TGF-beta 1, and 
reveal lower levels of similarity to porcine inhibins and activins, the 
C-terminal regions of human Mullerian inhibiting substance, and the putative
decapentaplegic gene complex protein of Drosophila [3]. 
 
The three-dimensional structures of several members of the TGF-beta super-
family have been deduced. The crystal structure of the TGF-beta 2 monomer 
lacks a well-defined hydrophobic core and displays an unusual elongated 
non-globular fold [5]. Eight cysteine residues form 4 intra-chain disulphide
bonds, creating the characteristic knotted arrangement. The dimer is 
stabilised by a ninth cysteine, which forms an inter-chain disulphide bond,
and by 2 identical hydrophobic interfaces. Other members of the TGF-beta
superfamily, including activins, inhibins and various developmental factors,
are also likely to adopt the TGF-beta fold. 
 
TGFBETA2 is an 8-element fingerprint that provides a signature for the 
transforming growth factor beta 2 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 2 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 10 
sequences was identified. Two partial matches were also found, TGF3_RAT and
TGF3_MOUSE, both of which are TGF-beta 3 proteins that match motifs 1 and 3.
Summary Information
  10 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
81010101010101010
700000000
600000000
500000000
400000000
300000000
220200000
12345678
True Positives
Q15579        Q9R281        Q9R298        Q9R2B8        
Q9WUQ8 TGF2_CHICK TGF2_HUMAN TGF2_MOUSE
TGF2_PIG TGF2_XENLA
True Positive Partials
Codes involving 2 elements
TGF3_MOUSE TGF3_RAT
Sequence Titles
Q15579      TRANSFORMING GROWTH FACTOR-BETA-2 PRECURSOR - Homo sapiens (Human). 
Q9R281 TRANSFORMING GROWTH FACTOR BETA 2 PRECURSOR - Rattus norvegicus (Rat).
Q9R298 TGF-BETA 2 SHORT FORM PRECURSOR - Rattus norvegicus (Rat).
Q9R2B8 TGF-BETA2 PROTEIN - Rattus norvegicus (Rat).
Q9WUQ8 TGF-BETA 2 LONG FORM PRECURSOR - Rattus norvegicus (Rat).
TGF2_CHICK TRANSFORMING GROWTH FACTOR BETA 2 PRECURSOR (TGF-BETA 2) - Gallus gallus (Chicken).
TGF2_HUMAN TRANSFORMING GROWTH FACTOR BETA 2 PRECURSOR (TGF-BETA 2) (GLIOBLASTOMA -DERIVED T-CELL SUPPRESSOR FACTOR) (G-TSF) (BSC-1 CELL GROWTH INHIBITOR) (POLYERGIN) (CETERMIN) - Homo sapiens (Human), and Cercopithecus aethiops (Green monkey) (Grivet).
TGF2_MOUSE TRANSFORMING GROWTH FACTOR BETA 2 PRECURSOR (TGF-BETA 2) - Mus musculus (Mouse).
TGF2_PIG TRANSFORMING GROWTH FACTOR BETA 2 PRECURSOR (TGF-BETA 2) - Sus scrofa (Pig).
TGF2_XENLA TRANSFORMING GROWTH FACTOR BETA 2 PRECURSOR (TGF-BETA 2) - Xenopus laevis (African clawed frog).

TGF3_MOUSE TRANSFORMING GROWTH FACTOR BETA 3 PRECURSOR (TGF-BETA 3) - Mus musculus (Mouse).
TGF3_RAT TRANSFORMING GROWTH FACTOR BETA 3 PRECURSOR (TGF-BETA 3) - Rattus norvegicus (Rat).
Scan History
SPTR39_14f 2  50   NSINGLE    
Initial Motifs
Motif 1  width=22
Element Seqn Id St Int Rpt
HYCVLSAFLLLHLVTVALSLST TGF2_PIG 2 2 -
HYCVLSTFLLLHLVPVALSLST TGF2_MOUSE 2 2 -
HYCVLSAFLILHLVTVALSLST TGF2_HUMAN 2 2 -
HCYLLSVFLTLDLAAVALSLST TGF2_CHICK 2 2 -
HYYVLFTFLTLDLAPVALSLST TGF2_XENLA 2 2 -

Motif 2 width=20
Element Seqn Id St Int Rpt
LTSPPEDYPEPEEVPPEVIS TGF2_PIG 50 26 -
LTSPPEDYPEPDEVPPEVIS TGF2_MOUSE 50 26 -
LTSPPEDYPEPEEVPPEVIS TGF2_HUMAN 50 26 -
LTSPPDEYPEPEEVPPEVIS TGF2_CHICK 50 26 -
LNSPPEDYPEPGEVSQDVIS TGF2_XENLA 50 26 -

Motif 3 width=23
Element Seqn Id St Int Rpt
DLLQEKASRRAAACERERSDEEY TGF2_PIG 76 6 -
DLLQEKASRRAAACERERSEQEY TGF2_MOUSE 76 6 -
DLLQEKASRRAAACERERSDEEY TGF2_HUMAN 76 6 -
DLLQEKANHRAATCERERSDEEY TGF2_CHICK 76 6 -
DLLQEKANERATSCERERSEDEY TGF2_XENLA 76 6 -

Motif 4 width=16
Element Seqn Id St Int Rpt
NAIPPTFYRPYFRIVR TGF2_PIG 116 17 -
NAIPPTFYRPYFRIVR TGF2_MOUSE 116 17 -
NAIPPTFYRPYFRIVR TGF2_HUMAN 116 17 -
NAIPPSYYSLYFRIVR TGF2_CHICK 115 16 -
NVIPPSYTTPYFRIVR TGF2_XENLA 116 17 -

Motif 5 width=12
Element Seqn Id St Int Rpt
FRLQNPKARVAE TGF2_PIG 152 20 -
FRLQNPKARVAE TGF2_MOUSE 152 20 -
FRLQNPKARVPE TGF2_HUMAN 152 20 -
FRLQNSKARVSE TGF2_CHICK 151 20 -
FRLMNTKARVSE TGF2_XENLA 152 20 -

Motif 6 width=13
Element Seqn Id St Int Rpt
LKSKDLTSPTQRY TGF2_PIG 172 8 -
LKSKDLTSPTQRY TGF2_MOUSE 172 8 -
LKSKDLTSPTQRY TGF2_HUMAN 172 8 -
LKSKELSSPGQRY TGF2_CHICK 171 8 -
LKSKDLASPTQRY TGF2_XENLA 172 8 -

Motif 7 width=17
Element Seqn Id St Int Rpt
PSNNYIIPNKSEELEAR TGF2_PIG 233 48 -
PSNNYIIPNKSEELEAR TGF2_MOUSE 233 48 -
PSNNYIIPNKSEELEAR TGF2_HUMAN 233 48 -
PSNNYIIPNKSEEPEAR TGF2_CHICK 232 48 -
PSNNYIIPNKSEELETR TGF2_XENLA 233 48 -

Motif 8 width=13
Element Seqn Id St Int Rpt
KSTRKKNSGKTPH TGF2_PIG 268 18 -
KSTRKKTSGKTPH TGF2_MOUSE 268 18 -
KSTRKKNSGKTPH TGF2_HUMAN 268 18 -
KSNRKKYSGKTPH TGF2_CHICK 266 17 -
KTGRKKHTGRTPH TGF2_XENLA 267 17 -
Final Motifs
Motif 1  width=22
Element Seqn Id St Int Rpt
HYCVLRTFLLLHLVPVALSLST Q9R281 2 2 -
HYCVLRTFLLLHLVPVALSLST Q9R2B8 2 2 -
HYCVLRTFLLLHLVPVALSLST Q9R298 2 2 -
HYCVLSAFLLLHLVTVALSLST TGF2_PIG 2 2 -
HYCVLRTFLLLHLVPVALSLST Q9WUQ8 2 2 -
HYCVLSTFLLLHLVPVALSLST TGF2_MOUSE 2 2 -
HYCVLSAFLILHLVTVALSLST TGF2_HUMAN 2 2 -
HYCVLSAFLILHLVTVALSLST Q15579 2 2 -
HCYLLSVFLTLDLAAVALSLST TGF2_CHICK 2 2 -
HYYVLFTFLTLDLAPVALSLST TGF2_XENLA 2 2 -

Motif 2 width=20
Element Seqn Id St Int Rpt
LTSPPEDYPEPDEVPPEVIS Q9R281 50 26 -
LTSPPEDYPEPDEVPPEVIS Q9R2B8 50 26 -
LTSPPEDYPEPDEVPPEVIS Q9R298 50 26 -
LTSPPEDYPEPEEVPPEVIS TGF2_PIG 50 26 -
LTSPPEDYPEPDEVPPEVIS Q9WUQ8 50 26 -
LTSPPEDYPEPDEVPPEVIS TGF2_MOUSE 50 26 -
LTSPPEDYPEPEEVPPEVIS TGF2_HUMAN 50 26 -
LTSPPEDYPEPEEVPPEVIS Q15579 50 26 -
LTSPPDEYPEPEEVPPEVIS TGF2_CHICK 50 26 -
LNSPPEDYPEPGEVSQDVIS TGF2_XENLA 50 26 -

Motif 3 width=23
Element Seqn Id St Int Rpt
DLLQEKASRRAAACERERSDEEY Q9R281 76 6 -
DLLQEKASRRAAACERERSDEEY Q9R2B8 76 6 -
DLLQEKASRRAAACERERSDEEY Q9R298 76 6 -
DLLQEKASRRAAACERERSDEEY TGF2_PIG 76 6 -
DLLQEKASRRAAACERERSDEEY Q9WUQ8 76 6 -
DLLQEKASRRAAACERERSEQEY TGF2_MOUSE 76 6 -
DLLQEKASRRAAACERERSDEEY TGF2_HUMAN 76 6 -
DLLQEKASRRAAACERERSDEEY Q15579 76 6 -
DLLQEKANHRAATCERERSDEEY TGF2_CHICK 76 6 -
DLLQEKANERATSCERERSEDEY TGF2_XENLA 76 6 -

Motif 4 width=16
Element Seqn Id St Int Rpt
NAIPPTFYRPYFRIVR Q9R281 116 17 -
NAIPPTFYRPYFRIVR Q9R2B8 116 17 -
NAIPPTFYRPYFRIVR Q9R298 116 17 -
NAIPPTFYRPYFRIVR TGF2_PIG 116 17 -
DAIPPTFYRPYFRIVR Q9WUQ8 144 45 -
NAIPPTFYRPYFRIVR TGF2_MOUSE 116 17 -
NAIPPTFYRPYFRIVR TGF2_HUMAN 116 17 -
DAIPPTFYRPYFRIVR Q15579 144 45 -
NAIPPSYYSLYFRIVR TGF2_CHICK 115 16 -
NVIPPSYTTPYFRIVR TGF2_XENLA 116 17 -

Motif 5 width=12
Element Seqn Id St Int Rpt
FRLQNPKARVAE Q9R281 152 20 -
FRLQNPKARVAE Q9R2B8 152 20 -
FRLQNPKARVAE Q9R298 152 20 -
FRLQNPKARVAE TGF2_PIG 152 20 -
FRLQNPKARVAE Q9WUQ8 180 20 -
FRLQNPKARVAE TGF2_MOUSE 152 20 -
FRLQNPKARVPE TGF2_HUMAN 152 20 -
FRLQNPKARVPE Q15579 180 20 -
FRLQNSKARVSE TGF2_CHICK 151 20 -
FRLMNTKARVSE TGF2_XENLA 152 20 -

Motif 6 width=13
Element Seqn Id St Int Rpt
LKSKDLTSPTQRY Q9R281 172 8 -
LKSKDLTSPTQRY Q9R2B8 172 8 -
LKSKDLTSPTQRY Q9R298 172 8 -
LKSKDLTSPTQRY TGF2_PIG 172 8 -
LKSKDLTSPTQRY Q9WUQ8 200 8 -
LKSKDLTSPTQRY TGF2_MOUSE 172 8 -
LKSKDLTSPTQRY TGF2_HUMAN 172 8 -
LKSKDLTSPTQRY Q15579 200 8 -
LKSKELSSPGQRY TGF2_CHICK 171 8 -
LKSKDLASPTQRY TGF2_XENLA 172 8 -

Motif 7 width=17
Element Seqn Id St Int Rpt
PSNNYIIPNKSQELEAR Q9R281 233 48 -
PSNNYIIPNKSQELEAR Q9R2B8 233 48 -
PSNNYIIPNKSQELEAR Q9R298 233 48 -
PSNNYIIPNKSEELEAR TGF2_PIG 233 48 -
PSNNYIIPNKSQELEAR Q9WUQ8 261 48 -
PSNNYIIPNKSEELEAR TGF2_MOUSE 233 48 -
PSNNYIIPNKSEELEAR TGF2_HUMAN 233 48 -
PSNNYIIPNKSEELEAR Q15579 261 48 -
PSNNYIIPNKSEEPEAR TGF2_CHICK 232 48 -
PSNNYIIPNKSEELETR TGF2_XENLA 233 48 -

Motif 8 width=13
Element Seqn Id St Int Rpt
KSTRKKSSGKTPH Q9R281 268 18 -
KSTRKKSSGKTPH Q9R2B8 268 18 -
KSTRKKSSGKTPH Q9R298 268 18 -
KSTRKKNSGKTPH TGF2_PIG 268 18 -
KSTRKKSSGKTPH Q9WUQ8 296 18 -
KSTRKKTSGKTPH TGF2_MOUSE 268 18 -
KSTRKKNSGKTPH TGF2_HUMAN 268 18 -
KSTRKKNSGKTPH Q15579 296 18 -
KSNRKKYSGKTPH TGF2_CHICK 266 17 -
KTGRKKHTGRTPH TGF2_XENLA 267 17 -