Conserve Fibroblast growth factor 8 (fgf 8) domains

1
Conserve Fibroblast growth factor 8 (fgf 8)
domains

• Ana Tomas
• Judith Paridaen
• Susana Domingues

2
Fibroblast growth factor 8

• Member of the FGF family

• Function
• Mitogenic
• Chemotactic
• Angiogenic activity
• Promoting cell growth, differentiation and
  motility

3
Some Fgf 8 characteristics

• Estimated half-life
• The N-terminal of the sequence considered is M
  (Met)
• The estimated half-life is
• ? 30 hours (mammalian)
• Instability index
• The instability index (II) is computed to be
  47.80
• Unstable protein

• N.º of a.a. 233
• Molecular weight 26525.4
• Theoretical p.i. 10.44
• Total n.º of negatively charged residues (Asp
  Glu) 19
• Total n.º of positively charged residues (Arg
  Lys) 40
• Formula C1164H1877N363O330S9
• Total n.º of atoms 3743
• Grand average of hydropathicity -0.651 (soluble)

ProtParam tool - ExPASy
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Structure

• 6 chains present
• 913 residues

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Structure and active sites
ProSAT - Protein Structure Annotation Tool
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Models

• Axolotl
• Chicken
• Ciona S.
• Cow
• Dog
• Drosophila
• Fugu
• Houseshrew
• Human

• Japanese lamprey
• Mouse
• Opossum
• Oryzias
• Rabbit
• Rat
• Rhesus macaque
• Shell turtle
• Tetraodon
• Zebrafish

Ciona
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Phylogenetic tree
Cluster algorithm
8
Consensus domains
Multalin Multi alignment program
9
3D structure and consensus domains
Rasmol
10
Fgf8 structure with receptor
Rasmol
11
Common regulatory elements in Fgf8 downstream
targets

• Anna Ferrer-Vaquer
• Alisa Fuchs

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Fgf8 signaling pathway

• Elk
• Ets
• cJun
• Fos
• Myc
• ...

13
Fgf8 inducible genes

• Sprouty1
• Pax3
• Otx2
• Tbx2
• Erm
• Pea3
• Ptx1
• Lhx6
• Sef
• AP2
• Flrt3 .... Many more

• Sprouty1 gt Mm, Gg, Dr
• Pax3 gt Mm, Gg, Dr
• Otx2 gt Mm, Gg, Dr
• Tbx2 gt Mm, Gg, Dr
• Erm
• Pea3
• Ptx1
• Lhx6
• Sef
• AP2
• Flrt3 .... Many more

• Limitation
• 1Kb of 5UTR

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Alignment
Alignment of sequences from different genes to
find consensus blocks Not reliable
15
Promoter analysis
16
Results of promoter analysis
Promotor/TF Elk vMyb ZBP-89
mSprouty1
mPax3
mOtx2
mTbx2
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Conclusion
Analysis of nucleotide sequences is much more
difficult than amino acids