Download Gene Ontology (GO)

Sequence-Structure-Function
Sequence
Threading
Structure
BLAST
Function
Folding: impossible
but for the smallest
structures
Ab initio
Function prediction
from structure –
very difficult
Experimental
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Structural genomics
Functional genomics
Protein-protein interaction
Metabolic pathways
• Expression data
Protein function groups
• Catalysis (enzymes)
• Binding – transport (active/passive)
– Protein-DNA/RNA binding (e.g. histones, transcription factors)
– Protein-protein interactions (e.g. antibody-lysozyme)
– Protein-fatty acid binding (e.g. apolipoproteins)
– Protein – small molecules (drug interaction, structure decoding)
• Structural component (e.g. -crystallin)
• Regulation
• Signalling
• Transcription regulation
• Immune system
• Motor proteins (actin/myosin)
Energy difference upon binding
Examples of protein interactions (and functional importance) include:
• Protein – protein (pathway analysis);
• Protein – small molecules (drug interaction, structure decoding);
• Protein – peptides, DNA/RNA (function analysis)
The change in Gibb’s Free Energy of the protein-ligand binding interaction can be monitored
and expressed by the following;
G =  H - T x S
(H=Enthalpy, S=Entropy and T=Temperature)
Protein function
• Many proteins combine functions
• Some immunoglobulin structures are thought to have more than 100
different functions (and active/binding sites)
• Alternative splicing can generate (partially) alternative structures
Protein function
Protein-protein interaction
Active site / binding cleft
Shape complementarity
Protein function evolution
Chymotrypsin
How to infer function
• Experiment
• Deduction from sequence
– Multiple sequence alignment – conservation patterns
– Homology searching
• Deduction from structure
– Threading
– Structure-structure comparison
– Homology modelling
Mevalonate plays a role in
epithelial cancers: it can inhibit
EGFR
Metabolic
networks
Glycolysis
and
Gluconeogenesis
Kegg database (Japan)
Gene Ontology (GO)
• Not a genome sequence database
• Developing three structured, controlled vocabularies (ontologies) to describe gene products
in terms of:
– biological process
– cellular component
– molecular function
in a species-independent manner
The GO ontology
Gene Ontology Members
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FlyBase - database for the fruitfly Drosophila melanogaster
Berkeley Drosophila Genome Project (BDGP) - Drosophila informatics; GO database & software, Sequence Ontology development
Saccharomyces Genome Database (SGD) - database for the budding yeast Saccharomyces cerevisiae
Mouse Genome Database (MGD) & Gene Expression Database (GXD) - databases for the mouse Mus musculus
The Arabidopsis Information Resource (TAIR) - database for the brassica family plant Arabidopsis thaliana
WormBase - database for the nematode Caenorhabditis elegans
EBI GOA project : annotation of UniProt (Swiss-Prot/TrEMBL/PIR) and InterPro databases
Rat Genome Database (RGD) - database for the rat Rattus norvegicus
DictyBase - informatics resource for the slime mold Dictyostelium discoideum
GeneDB S. pombe - database for the fission yeast Schizosaccharomyces pombe (part of the Pathogen Sequencing Unit at the Wellcome Trust Sanger Institute)
GeneDB for protozoa - databases for Plasmodium falciparum, Leishmania major, Trypanosoma brucei, and several other protozoan parasites (part of the Pathogen Sequencing Unit at the Wellcome Trust Sanger Institute)
Genome Knowledge Base (GK) - a collaboration between Cold Spring Harbor Laboratory and EBI)
TIGR - The Institute for Genomic Research
Gramene - A Comparative Mapping Resource for Monocots
Compugen (with its Internet Research Engine)
The Zebrafish Information Network (ZFIN) - reference datasets and information on Danio rerio