* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Gene Ontology (GO)
Ribosomally synthesized and post-translationally modified peptides wikipedia , lookup
Gene regulatory network wikipedia , lookup
Paracrine signalling wikipedia , lookup
Signal transduction wikipedia , lookup
Gene nomenclature wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Silencer (genetics) wikipedia , lookup
Point mutation wikipedia , lookup
Metalloprotein wikipedia , lookup
Gene expression wikipedia , lookup
G protein–coupled receptor wikipedia , lookup
Ancestral sequence reconstruction wikipedia , lookup
Expression vector wikipedia , lookup
Bimolecular fluorescence complementation wikipedia , lookup
Homology modeling wikipedia , lookup
Interactome wikipedia , lookup
Magnesium transporter wikipedia , lookup
Western blot wikipedia , lookup
Protein structure prediction wikipedia , lookup
Protein purification wikipedia , lookup
Nuclear magnetic resonance spectroscopy of proteins wikipedia , lookup
Anthrax toxin wikipedia , lookup
Proteolysis wikipedia , lookup
Protein Structure & Analysis Biology 224 Instructor: Tom Peavy Feb 21 & 26, 2008 <Images from Bioinformatics and Functional Genomics by Jonathan Pevsner> Protein families Protein localization protein Protein function Gene ontology (GO): --cellular component --biological process --molecular function Physical properties Protein domains, motifs & signatures Definitions Signature: • a protein category such as a domain or motif Domain: • a region of a protein that can adopt a 3D structure • a fold • a family is a group of proteins that share a domain • examples: zinc finger domain immunoglobulin domain Motif (or fingerprint): • a short, conserved region of a protein • typically 10 to 20 contiguous amino acid residues Definition of a domain According to InterPro at EBI (http://www.ebi.ac.uk/interpro/): A domain is an independent structural unit, found alone or in conjunction with other domains or repeats. Domains are evolutionarily related. According to SMART (http://smart.embl-heidelberg.de): A domain is a conserved structural entity with distinctive secondary structure content and a hydrophobic core. Homologous domains with common functions usually show sequence similarities. 15 most common domains (human) Zn finger, C2H2 type Immunoglobulin EGF-like Zn-finger, RING Homeobox Pleckstrin-like RNA-binding region RNP-1 SH3 Calcium-binding EF-hand Fibronectin, type III PDZ/DHR/GLGF Small GTP-binding protein BTB/POZ bHLH Cadherin 1093 proteins 1032 471 458 417 405 400 394 392 300 280 261 236 226 226 Varieties of protein domains Extending along the length of a protein Occupying a subset of a protein sequence Occurring one or more times Example of a protein with domains: Methyl CpG binding protein 2 (MeCP2) MBD TRD The protein includes a methylated DNA binding domain (MBD) and a transcriptional repression domain (TRD). MeCP2 is a transcriptional repressor. Mutations in the gene encoding MeCP2 cause Rett Syndrome, a neurological disorder affecting girls primarily. Result of an MeCP2 blastp search: A methyl-binding domain shared by several proteins Are proteins that share only a domain homologous? Proteins can have both domains and patterns (motifs) Pattern Pattern (several (several residues) residues) Domain (aspartyl protease) Domain (reverse transcriptase) SwissProt entry for HIV-1 pol links to many databases http://www.ebi.ac.uk/Databases/ InterPro InterPro is a database of protein families, domains and functional sites in which identifiable features found in known proteins can be applied to unknown protein sequences. http://www.ebi.ac.uk/interpro/ ExPASy Proteomics Server The ExPASy (Expert Protein Analysis System) proteomics server of the Swiss Institute of Bioinformatics (SIB) is dedicated to the analysis of protein sequences and structures as well as 2-D PAGE (Disclaimer / References). http://ca.expasy.org/ PROSITE Database of protein families and domains http://ca.expasy.org/prosite/ Pfam is a large collection of multiple sequence alignments and hidden Markov models covering many common protein domains. http://www.sanger.ac.uk/Software/Pfam/index.shtml PRINTS is a compendium of protein fingerprints http://umber.sbs.man.ac.uk/dbbrowser/PRINTS/ The ProDom protein domain database consists of an automatic compilation of homologous domains. http://prodes.toulouse.inra.fr/prodom/current/html/home.php SMART (a Simple Modular Architecture Research Tool) allows the identification and annotation of genetically mobile domains and the analysis of domain architectures. http://smart.embl-heidelberg.de/ The ProDom protein domain database consists of an automatic compilation of homologous domains. http://prodes.toulouse.inra.fr/prodom/current/html/home.php Houses the PIRSF, ProClass and ProLINK databases http://pir.georgetown.edu/ Protein family classification and databases TIGRFAMs http://www.tigr.org/TIGRFAMs/index.shtml SUPERFAMILY http://supfam.mrc-lmb.cam.ac.uk/SUPERFAMILY/ PANTHER http://www.pantherdb.org/ PIRSF http://pir.georgetown.edu/iproclass/ Gene3D http://www.biochem.ucl.ac.uk/bsm/cath/Gene3D/ Definition of a motif A motif (or fingerprint) is a short, conserved region of a protein. Its size is often 10 to 20 amino acids. Simple motifs include transmembrane domains and phosphorylation sites. These do not imply homology when found in a group of proteins. In PROSITE,a pattern is a qualitative motif description (a protein either matches a pattern, or not). Gene Ontology (GO) Consortium The Gene Ontology Consortium An ontology is a description of concepts. The GO Consortium compiles a dynamic, controlled vocabulary of terms related to gene products. There are three organizing principles: Molecular function Biological process Cellular component Example Gene product cytochrome c GO entry terms: molecular function = electron transporter activity, the biological process = oxidative phosphorylation and induction of cell death the cellular component = mitochondrial matrix and mitochondrial inner membrane. GO consortium (http://www.geneontology.org) No centralized GO database. Instead, curators of organism-specific databases assign GO terms to gene products for each organism. AmiGO is the searchable portion of the GO --Gene Symbol, name, UniProt access numbers, and Text searches can be used to find GO entries The Gene Ontology Consortium: Evidence Codes IC IDA IEA IEP IGI IMP IPI ISS NAS ND TAS Inferred by curator Inferred from direct assay Inferred from electronic annotation Inferred from expression pattern Inferred from genetic interaction Inferred from mutant phenotype Inferred from physical interaction Inferred from sequence or structural similarity Non-traceable author statement No biological data Traceable author statement