1. A brief on: Domain Families & Classification

2. Classification to Families
We can classify proteins into families by:
A. Sequence
B. Structure
C. Function (annotation)
D. Evolution

3. Used Terms: Motif = Domain = Signature = Profile = Seed Family = Cluster
These terms are used interchangeably,
They are very (too) flexible

4. Motif = Domain = Function ???
A motif is a sequence signature.
Structural definition of a domain: an independently folding structural unit.
A protein family is not well-defined.
Protein function is not well-defined (some proteins can have several functions).
Conclusion: these terms are used interchangeably, but they are very flexible.

6. Protein folds Toxin binding protein (TolB) Glucose dehydrogenase
Di-isopropyl-fluorophosphatase

7. Dominant domain fold types.
Holm and Sander. PROTEINS: Structure, Function, and Genetics 33:88–96 (1998)

8. Why Research Protein Families?
Function prediction and annotation.
Evolutionary research - finding orthologs and paralogs.
Search for new protein folds.
Functional research by similarity in characteristics.

9. Domains are the building blocks of evolution: some facts..
Each occurs in diverse sets of protein families
Number of domains in proteins ranges
from 1 up to tens
Structural based domain are ~ 150 aa
Length varies: some are very short
30-40 aa, other are long > 500 aa
Domain definition is somewhat blurred
Domain boundary is an unsolved problem
Pyruvate kinase, PDB:1pkn

10. How is a novel gene born?
Domains are the evolutionary units of sequence that comprise the gene coding regions.
Most genes are built from more than one domain.
Novel genes can be created by recombination of domains into new domain arrangements.

11. Correspondence between functional associations and genes linked by the fusion method
From Glycolysis:
M. genitalium PGK
Glycerone-P
M. genitalium TIM
PGK1
M. genitalium GAPDH
Glyceraldehyde-3P
GAPDH
Glycerate-1,3P2
Thermotoga Maritima
PGK+TIM
TIM
Strart with this one
Lines coming out
Glycerate-3P
Phytophthora infestans
TIM+GAPDH

12. What is a Protein Family?
Protein family: A group of proteins that have a common protein ancestor.
Is it that simple?
Domains: non-linear evolution
Who is in this family?

13. A protein can have several same or different domains
Fibronectin protein–1fnf

14. The Power of Integration Pfam, Prosite, SMART, PRINTS, tigrFam, ProDom
SCOP
CATH
FSSP GO
KEGG
Pfam, Prosite, SMART, PRINTS, tigrFam, ProDom
InterPro