Presentation is loading. Please wait.

Presentation is loading. Please wait.

Protein Ontology: Addressing the need for precision in representing protein networks Darren A. Natale, Ph.D. Protein Science Team Lead, PIR Research Assistant.

Published by Modified over 8 years ago

Similar presentations

Presentation on theme: "Protein Ontology: Addressing the need for precision in representing protein networks Darren A. Natale, Ph.D. Protein Science Team Lead, PIR Research Assistant."— Presentation transcript:

1 Protein Ontology: Addressing the need for precision in representing protein networks Darren A. Natale, Ph.D. Protein Science Team Lead, PIR Research Assistant Professor, GUMC Workshop on Ontologies of Cellular Networks March 2008

2 IEV_0000090 part_of IEV_0000156 IEV_0000159 IEV_0000155 IEV_0000157 IEV_0000158 4 Binding of R-smad:smad4 complex and responsive element 2 Complex formation of R-smad and Smad4 5 Transcription by R-smad:smad4 1 Phosphorylation of R-smad by TGF beta receptor I 3 Nuclear import of R-smad:smad4 TGF-  signaling pathway Example from: INOH Event Ontology R-smad R-smad: Smad4 smad4 TGF beta receptor I responsive element ActionsLocations Nucleus Cytoplasm nuc lear me m b rane Roles

3 IMR_0000369 Txn regulator IMR_0000370 SMAD IMR_0000372 Co-Smad IMR_0000371 R-Smad IMR_0000373 I-Smad IMR_0100312 Smad3 IMR_0100311 Smad2 IMR_0100313 Smad5 IMR_0100310 Smad1 IMR_0100314 Smad8 is_a Example from: INOH Molecule Role Ontology IMR_0100315 Smad4 The Roles Played IMR_0704004 SMAD2_HUMAN sequence_of

4 Cellular Component: - nucleus Molecular Function: - protein binding Biological Process: - signal transduction - regulation of transcription, DNA-dependent Mothers against decapentaplegic homolog 2 Smad 2 GO annotation of SMAD2_HUMAN:

5 II I TGF-  TGF-beta receptor PP Smad 4 4 DNA binding 1 phosphorylation 2 complex formation Nucleus Cytoplasm Smad 2 PP Smad 4 5 Transcription Regulation PP Smad 2 Smad 4 3 nuclear translocation PP Smad 2 P P P ++ ERK1 CAMK2 P P

6 “normal”Cytoplasmic PRO:00000011 REACT_7257.1 TGF-  receptor phosphorylated Forms complex Nuclear Txn upregulation PRO:00000013 REACT_7563.1 ERK1 phosphorylatedForms complex Nuclear Txn upregulation++ PRO:00000014 CAMK2 phosphorylated Forms complex Cytoplasmic No Txn upregulation PRO:00000015 alternatively spliced short form Cytoplasmic PRO:00000016 REACT_7906.1 phosphorylated short form Nuclear Txn upregulationPRO:00000018 REACT_7100.1 point mutation (causative agent: large intestine carcinoma) Doesn’t form complex Cytoplasmic No Txn upregulation PRO:00000019 Smad 2 PP PP P PP P x PP SMAD2_HUMAN

7 %PRO:00000010 Smad2 %PRO:00000011 Smad2 isoform 1 (long form) %PRO:00000012 Smad2 isoform 1 phosphorylated form %PRO:00000013 Smad2 isoform 1, TGF-  receptor I-phosphorylated %PRO:00000014 Smad2 isoform 1, TGF-  receptor I and ERK1-phosphorylated arises_from SO: amino_acid_substitution NOT has_modification MOD: phosphorylated residue NOT has_function GO: transcription coactivator activity gives_rise_to DO: carcinoma of the large intestine %PRO:00000015 Smad2 sequence 1, TGF-  receptor I and CAMK2-phosphorylated %PRO:00000016 Smad2 sequence 2 (short form) - splice variant %PRO:00000017 Smad2 sequence 2 phosphorylated form %PRO:00000018 Smad2 sequence 2, TGF-  receptor I-phosphorylated %PRO:00000019 Smad2 sequence 3 - genetic variant related to colorectal carcinoma %PRO:00000015 Smad2 isoform 1, TGF-  receptor I and CAMK2-phosphorylated %PRO:00000016 Smad2 isoform 2 (short form) - splice variant %PRO:00000017 Smad2 isoform 2 phosphorylated form %PRO:00000018 Smad2 isoform 2, TGF-  receptor I-phosphorylated %PRO:00000019 Smad2 isoform 3 - genetic variant related to colorectal carcinoma has_modification MOD:O-phosphorylated L-serine has_modification MOD:O-phosphorylated L-threonine has_function GO: TGF-  receptor, pathway-specific cytoplasmic mediator activity has_function GO:SMAD binding has_function GO:transcription coactivator activity participates_in GO:signal transduction participates_in GO:SMAD protein heteromerization participates_in GO:regulation of transcription, DNA-dependent located_in GO:nucleus part_of GO:transcription factor complex

8 ProEvo ProForm GO Gene Ontology molecular function cellular component biological process participates_in part_of (for complexes) located _in (for compartments) has_function PRO http://pir.georgetown.edu/pro protein Root Level is_a translation product of an evolutionarily-related gene translation product of a specific mRNA Family-Level Distinction In common: specific ancestor Source: PIRSF family Modification-Level Distinction In common: specific translation product Source: UniProtKB Sequence-Level Distinction In common: specific allele or splice variant Source: UniProtKB cleaved/modified translation product disease DO/UMLS Disease agent_of is_a protein modification has_modification PSI-MOD Modification SO Sequence Ontology sequence change arises_from (sequence change) gives_rise_to (effect on function) is_a protein domain has_part Pfam Domain Example: TGF-  receptor phosphorylated smad2 isoform1 is a phosphorylated smad2 isoform1 is a smad2 isoform 1 is a smad2 is a TGF-  receptor-regulated smad is a smad is a protein Modification Level Sequence Level Family Level Root Level translation product of a specific gene Gene-Level Distinction In common: specific gene Sources: PIRSF subfamily, Panther subfamily is_a Gene Level

9 IEV_0000090 part_of IEV_0000156 IEV_0000159 IEV_0000155 IEV_0000157 IEV_0000158 4 Binding of R-smad:smad4 complex and responsive element 2 Complex formation of R-smad and Smad4 5 Transcription by R-smad:smad4 1 Phosphorylation of R-smad by TGF beta receptor I 3 Nuclear import of R-smad:smad4 TGF-  signaling pathway Example from: INOH Event Ontology R-smad R-smad: Smad4 smad4 TGF beta receptor I responsive element ActionsLocations Nucleus nuc lear me m b rane Roles Actors smad2 smad2: PP PP PP PP PP has_participant PRO:smad4 has_participant PRO:TGF-  receptor-phosphorylated smad2 P P P P P Transcription has_participant PRO:smad4 has_participant PRO:TGF-  receptor & ERK1-phosphorylated smad2 Cytoplasm

10 PRO Team (so far…) Principle Investigators Cathy Wu (PIR at GUMC) Judith Blake (The Jackson Laboratory) Barry Smith (SUNY Buffalo) Curators & Developers Cecilia Arighi (PIR at GUMC) Winona Barker (PIR at GUMC) Harold Drabkin (The Jackson Laboratory) Zhang-zhi Hu (PIR at GUMC) Hongfang Liu (GUMC) Darren Natale (PIR at GUMC) Official Launch: March 31, 2008 http://pir.georgetown.edu/pro

11 IMR_0000369 Txn regulator IMR_0000370 SMAD IMR_0000371 R-Smad IMR_0100311 Smad2 Smad2 vs c-Myc in INOH and PRO IMR_0000368 Txn factor IMR_0000949 protein IMR_0000383 Myc IMR_0100401 c-Myc PRO:00000006 smad PRO:00000009 R-Smad PRO:00000010 smad2 is_a PRO:0000003 protein PRO:00100020 myc PRO:00000328 c-myc

12 cytoskeleton component EPB42 Hypothetical example: TGM3 vs EPB42 structural protein IMR_0000949 protein TGM3 is_a PRO:0000003 protein transglutaminaseEPB42protease TGM3 protein modifier enzyme

Download ppt "Protein Ontology: Addressing the need for precision in representing protein networks Darren A. Natale, Ph.D. Protein Science Team Lead, PIR Research Assistant."

Similar presentations

Annotation of Gene Function …and how thats useful to you.

Annotation of Gene Function …and how thats useful to you.
Chapter 11 Cell Communication

Chapter 11 Cell Communication
Ch 17 Gene Expression I: Transcription

Ch 17 Gene Expression I: Transcription
Molecular Basis for Relationship between Genotype and Phenotype DNA RNA protein genotype function organism phenotype DNA sequence amino acid sequence transcription.

Molecular Basis for Relationship between Genotype and Phenotype DNA RNA protein genotype function organism phenotype DNA sequence amino acid sequence transcription.
Lecture 4: DNA transcription

Lecture 4: DNA transcription
SIGNALING FROM THE CELL SURFACE TO THE NUCLEUS

SIGNALING FROM THE CELL SURFACE TO THE NUCLEUS
Endo. 4 Detecting and signalling Cell surface receptors: G protein linked and tyrosine kinase receptors: second messengers, phosphorylating kinases, activation.

Endo. 4 Detecting and signalling Cell surface receptors: G protein linked and tyrosine kinase receptors: second messengers, phosphorylating kinases, activation.
Chapter 5 Ligand gated ion channels, intracellular receptors and phosphorylation cascades.

Chapter 5 Ligand gated ion channels, intracellular receptors and phosphorylation cascades.
Relationship between Genotype and Phenotype

Relationship between Genotype and Phenotype
A tumor suppressor gene

A tumor suppressor gene
Developing a protein-interactions ontology Esther Ratsch European Media Laboratory.

Developing a protein-interactions ontology Esther Ratsch European Media Laboratory.
Transforming Growth Factor-Beta Receptor 2 TGF-β receptor 2

Transforming Growth Factor-Beta Receptor 2 TGF-β receptor 2
EBI is an Outstation of the European Molecular Biology Laboratory. UniProt Jennifer McDowall, Ph.D. Senior InterPro Curator Protein Sequence Database:

EBI is an Outstation of the European Molecular Biology Laboratory. UniProt Jennifer McDowall, Ph.D. Senior InterPro Curator Protein Sequence Database:
Step 1 of Protein Synthesis

Step 1 of Protein Synthesis
Colinearity of Gene and Protein DNA RNA protein genotype function organism phenotype DNA sequence amino acid sequence transcription translation.

Colinearity of Gene and Protein DNA RNA protein genotype function organism phenotype DNA sequence amino acid sequence transcription translation.
DNA and Chromosome Structure. Chromosomal Structure of the Genetic Material.

DNA and Chromosome Structure. Chromosomal Structure of the Genetic Material.
Express yourself That darn ribosome Mighty Mighty Proteins Mutants RNA to the Rescue 500 400 300 200 100 200 300 400 500 100 200 300 400 500 100 200 300.

Express yourself That darn ribosome Mighty Mighty Proteins Mutants RNA to the Rescue
Cell Signaling A __________________________is a series of steps by which a signal on a cell’s surface is converted into a ________________________________________________.

Cell Signaling A __________________________is a series of steps by which a signal on a cell’s surface is converted into a ________________________________________________.
Cell signaling Lecture 8. Transforming growth factor (TGF β) Receptors/Smad pathway BMP7 TGF β1, TGF β2, TGF β3 Dpp Inhibins Activins TGF β receptors.

Cell signaling Lecture 8. Transforming growth factor (TGF β) Receptors/Smad pathway BMP7 TGF β1, TGF β2, TGF β3 Dpp Inhibins Activins TGF β receptors.
Control of Gene Expression Eukaryotes. Eukaryotic Gene Expression Some genes are expressed in all cells all the time. These so-called housekeeping genes.

Control of Gene Expression Eukaryotes. Eukaryotic Gene Expression Some genes are expressed in all cells all the time. These so-called housekeeping genes.

Similar presentations

Ads by Google