protein ontology: addressing the need for precision in representing protein networks
DESCRIPTION
Protein Ontology: Addressing the need for precision in representing protein networks. Workshop on Ontologies of Cellular Networks March 2008. Darren A. Natale, Ph.D. Protein Science Team Lead, PIR Research Assistant Professor, GUMC. TGF- b signaling pathway. - PowerPoint PPT PresentationTRANSCRIPT
Protein Ontology:
Addressing the need for precision in representing protein networks
Darren A. Natale, Ph.D.Protein Science Team Lead, PIRResearch Assistant Professor, GUMC
Workshop on Ontologies of Cellular NetworksMarch 2008
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 pathwayExample from: INOH Event Ontology
R-smad
R-smad
R-smad:
R-smad:
R-smad:
Smad4
smad4
smad4
smad4
TGF beta receptor I
responsive element
Actions Locations
Nucleus
Cytoplasm
nuclear membrane
Roles
IMR_0000369Txn regulator
IMR_0000370SMAD
IMR_0000372Co-Smad
IMR_0000371R-Smad
IMR_0000373I-Smad
IMR_0100312Smad3
IMR_0100311Smad2
IMR_0100313Smad5
IMR_0100310Smad1
IMR_0100314Smad8
is_a
Example from: INOH Molecule Role Ontology
IMR_0100315Smad4
The Roles Played
IMR_0704004SMAD2_HUMAN
sequence_of
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:
II I
TGF-TGF-beta receptor
PP Smad 4
4 DNA binding
1 phosphorylation
2 complex formation
Nucleus
Cytoplasm
Smad 2
Smad 2
PPSmad 2
Smad 4
5 Transcription Regulation
PPSmad 2
Smad 4
3 nuclear translocation
PPSmad 2PP
P
++
ERK1CAMK2
PP
“normal” •Cytoplasmic PRO:00000011 REACT_7257.1
TGF- receptor phosphorylated
•Forms complex•Nuclear•Txn upregulation
PRO:00000013REACT_7563.1
ERK1 phosphorylated •Forms complex•Nuclear•Txn upregulation++
PRO:00000014
CAMK2 phosphorylated
•Forms complex•Cytoplasmic•No Txn upregulation
PRO:00000015
alternatively spliced short form
•Cytoplasmic
PRO:00000016REACT_7906.1
phosphorylated short form
•Nuclear•Txn upregulation PRO:00000018
REACT_7100.1
point mutation (causative agent: large intestine carcinoma)
•Doesn’t form complex•Cytoplasmic•No Txn upregulation
PRO:00000019
Smad 2
PPSmad 2
PPSmad 2P
PPSmad 2 P
Smad 2 x
Smad 2
Smad 2 PP
SMAD2_HUMAN
SMAD2_HUMAN
SMAD2_HUMAN
SMAD2_HUMAN
SMAD2_HUMAN
SMAD2_HUMAN
SMAD2_HUMAN
%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_substitutionNOT has_modification MOD: phosphorylated residueNOT has_function GO: transcription coactivator activitygives_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-serinehas_modification MOD:O-phosphorylated L-threoninehas_function GO: TGF- receptor, pathway-specific cytoplasmic mediator activityhas_function GO:SMAD bindinghas_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
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/proprotein
Root Levelis_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 geneGene-Level Distinction• In common: specific gene• Sources: PIRSF subfamily, Panther subfamily
is_a
Gene Level
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 pathwayExample from: INOH Event Ontology
R-smad
R-smad
R-smad:
R-smad:
R-smad:
Smad4
smad4
smad4
smad4
TGF beta receptor I
responsive element
Actions Locations
Nucleusnuclear membrane
Roles
Actors
smad2
smad2
smad2:
smad2:
smad2:
P P
P P
P P
P P
P P
has_participant PRO:smad4has_participant PRO:TGF- receptor-phosphorylated smad2
P
P
P
P
P
Transcription
has_participant PRO:smad4has_participant PRO:TGF- receptor & ERK1-phosphorylated smad2
Cytoplasm
PRO Team (so far…)•Principle Investigators
Cathy Wu (PIR at GUMC)Judith Blake (The Jackson Laboratory)Barry Smith (SUNY Buffalo)
•Curators & DevelopersCecilia 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