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Copyright OpenHelix. No use or reproduction without express written consent1

Version 3 Copyright OpenHelix. No use or reproduction without express written consent 2 SMART Simple Modular Architecture Research Tool Evolution of Function within Multi-domain Proteins Materials prepared by: Mary Mangan PhD Updated: Q1 2011

Copyright OpenHelix. No use or reproduction without express written consent3 SMART Agenda Introduction and Credits Sequence or ID Searches Architecture Searches Domains by Name or Browsing Advanced Query Summary Exercises Introduction and Credits

Copyright OpenHelix. No use or reproduction without express written consent4 Protein Domains as Keys to Function Domain structure of proteins is modular Evolution has generated new combinations of domains Understanding domains can elucidate functions Predicted gene Known gene

Copyright OpenHelix. No use or reproduction without express written consent5 SMART brings Data Sources Together SMART RDBMS (relational database) HMMer Hidden Markov Models PFAM (Protein Family) SCOP and Superfamily Swiss-Prot, Trembl, all Ensembl proteomes GO (Gene Ontology) InterPro One interface for access to many types of data

Copyright OpenHelix. No use or reproduction without express written consent6 SMART Credits Developed and maintained by the lab of Peer Bork, EMBL SMART 1.0, Schultz et al. PNAS USA 95, SMART 4.0, Letunic et al. NAR 30, SMART 5.0, Letunic et al. NAR 34, D257-D260

Copyright OpenHelix. No use or reproduction without express written consent7 SMART Modes: Genomic, Normal On first arrival, SMART mode choice Normal: all proteins in Ensembl Genomic: completed genomes only Color code will signify your current mode Later, change mode at SETUP or MODE box Normal Genomic

Copyright OpenHelix. No use or reproduction without express written consent8 SMART Searches: start with domains help and documentation start with a sequence or ID start with architecture

Copyright OpenHelix. No use or reproduction without express written consent9 SMART Agenda Introduction and Credits Sequence or ID Searches Architecture Searches Domains by Names or Browsing Advanced Query Summary Exercises

Copyright OpenHelix. No use or reproduction without express written consent10 SMART Sequence or ID Searches start with a sequence or ID

Copyright OpenHelix. No use or reproduction without express written consent11 Start with a Sequence Known proteins or predictions IDs A known protein or prediction as amino acid sequence Run the search Supplement the default search Use batch access for multiple sequences Here, you must start with an ID. Do not use a gene name or symbol. Look up the ID in UniProt, for example Or, you can begin with a protein sequence

Copyright OpenHelix. No use or reproduction without express written consent12 Perform a Sample Sequence Search Paste sequence Decide if you want extras Click Sequence SMART

Copyright OpenHelix. No use or reproduction without express written consent13 Results of a Sequence Search Domain structure shown Access to similar proteins Domain details Some domains not shown not displayed

Copyright OpenHelix. No use or reproduction without express written consent14 SMART Agenda Introduction and Credits Sequence or ID Searches Architecture Searches Domains by Name or Browsing Advanced Query Summary Exercises

Copyright OpenHelix. No use or reproduction without express written consent15 SMART Architecture Search start with architecture

Copyright OpenHelix. No use or reproduction without express written consent16 Start with Architecture: Domain Combinations My sample search: Rgs AND S_Tkc, all species We’ll try GO later find names

Copyright OpenHelix. No use or reproduction without express written consent17 Architecture: Results Some representative proteins All would be available… Links to protein descriptions more…

Copyright OpenHelix. No use or reproduction without express written consent18 Start with Architecture: GO Terms My sample GO search: transmembrane receptor More on GO: Tar homologs Toll-IL1

Copyright OpenHelix. No use or reproduction without express written consent19 GO Architecture Search Results

Copyright OpenHelix. No use or reproduction without express written consent20 Domain Diagrams Details Shown are 2 sample proteins with multiple domains Intron positions display as lines: amino acid number (top) Intron phase (based on Ensembl predictions) (below) Intron position Intron phase click domains for details

Copyright OpenHelix. No use or reproduction without express written consent21 SMART Agenda Introduction and Credits Sequence or ID Searches Architecture Searches Domains by Name or Browsing Advanced Query Summary Exercises

Copyright OpenHelix. No use or reproduction without express written consent22 SMART Domains Detected start with domains

Copyright OpenHelix. No use or reproduction without express written consent23 Start with a Domain Several search options here Keyword search: kinase, cell cycle, helix turn Domain name or ID: Ras Browse: get a page with all domains, look around Sample search: kinase as keyword click kinase

Copyright OpenHelix. No use or reproduction without express written consent24 Keyword or Name Search Result Click to get the list of proteins with this domain

Copyright OpenHelix. No use or reproduction without express written consent25 Domain Name/ID Search: RAS If only one result, you go directly to that domain page ras

Copyright OpenHelix. No use or reproduction without express written consent26 Browse the Domains Click domain link to go to the detail pages. download news suggest

Copyright OpenHelix. No use or reproduction without express written consent27 SMART Agenda Introduction and Credits Sequence or ID Searches Architecture Searches Domains by Name or Browsing Advanced Query Summary Exercises

Copyright OpenHelix. No use or reproduction without express written consent28 Advanced Query: only if you know SQL!

Copyright OpenHelix. No use or reproduction without express written consent29 SMART Agenda Introduction and Credits Sequence or ID Searches Architecture Searches Domains by Name or Browsing Advanced Query Summary Exercises

Copyright OpenHelix. No use or reproduction without express written consent30 SMART start with domains start with a sequence or ID start with architecture

Copyright OpenHelix. No use or reproduction without express written consent31 SMART Agenda Introduction and Credits Sequence or ID Searches Architecture Searches Domains by Name or Browsing Advanced Query Summary Exercises

Copyright OpenHelix. No use or reproduction without express written consent32