Annotation Conf. Call 2016-09-27

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Bluejeans URL: https://bluejeans.com/993661940

Agenda

Meetings

Next GOC Meeting - USC, Los Angeles, CA, November 4-6, 2016

  • Please indicate on the Meeting Logistics Page if you plan to come.
  • There is now a column for attending the GO dinner on Friday night. Please add your intention.
  • There will be a one-day Noctua/LEGO training session for the Monday (November 7th) following the general consortium meeting. Please indicate on the logistics page if you are definitely staying for that so Paul T. can arrange for a meeting room.

GO Group Contacts

  • Google spreadsheet sent out by ontology editors
  • List of GO group members on github under people directory
    • Does everyone have a github account?
    • What is required for someone to be listed under People for the GO project?
    • What is required to see everyone listed under People for the GO project?

Annotation Consistency Exercise

Abstract Chemotaxis, or directional movement toward extracellular chemical gradients, is an important property of cells that is mediated through G-protein-coupled receptors (GPCRs). Although many chemotaxis pathways downstream of Gβγ have been identified, few Gα effectors are known. Gα effectors are of particular importance because they allow the cell to distinguish signals downstream of distinct chemoattractant GPCRs. Here we identify GflB, a Gα2 binding partner that directly couples the Dictyostelium cyclic AMP GPCR to Rap1. GflB localizes to the leading edge and functions as a Gα-stimulated, Rap1-specific guanine nucleotide exchange factor required to balance Ras and Rap signaling. The kinetics of GflB translocation are fine-tuned by GSK-3 phosphorylation. Cells lacking GflB display impaired Rap1/Ras signaling and actin and myosin dynamics, resulting in defective chemotaxis. Our observations demonstrate that GflB is an essential upstream regulator of chemoattractant-mediated cell polarity and cytoskeletal reorganization functioning to directly link Gα activation to monomeric G-protein signalling.

Discussion Points

  1. What is the most appropriate annotation to describe how GflB binds to Rap1 (rapA), in the presence of ACTIVATED galpha2(gpaB)?
    • BP Annotations
    gpaB: GO:0032092 positive regulation of protein binding IDA, has_regulation_target GflB,rapA
    gpaB: GO:1905099 positive regulation of guanyl-nucleotide exchange factor activity IDA “request a PRO term for the active form?”
    • MF annotations
    gflB: protein binding RapA happens_during GO:0001965 G-protein alpha-subunit binding
    gflB: small GTPase binding RapA happens_during activation of GTPase activity, has_direct_input gpaB
    rapA: GO:0005515 protein binding GflB happens_during GO:0001965 G-protein alpha-subunit binding
    rapA: GO:0005515 protein binding (gflB) happens_during activation of GTPase activity
  2. Do we need a new term ‘positive regulation of myosin II assembly’ Or is the current ‘regulation of myosin II assembly’ the positive regulation term as there is also ‘regulation of myosin II disassembly’, which is negative regulation of assembly?
  3. Ras protein specificity with Pan antibody assays. Use rasB, rasC, rasG in extension or not?
  4. Use of SO term to define where a protein binds another, but is extension occurs_at appropriate? Does it refer to first or second protein? Do we need a different relation, interacts_with?
    • Annotation: gflB: GO:0001965 G-protein alpha-subunit binding IPI gpaB occurs_at SO:0100014 n_terminal_region
  5. Possible other new terms
    • guanylyl-nucleotide exchange factor binding
    • nucleitide exchange factor binding
    • Rap GTPase binding as another child of 'Ras GTPase binding/', which has many other children
  6. LEGO


Annotations

Gene/Marker Name Qualifier GO ID/term Evidence Code With/From Annotation Extension Comment
Biological Process
gflB GO:0014066 regulation of phosphatidylinositol 3-kinase signaling IMP part_of GO:0050920 regulation of chemotaxis? will be clearer in LEGO
gflB GO:0030837 negative regulation of actin polymerization IMP part_of GO:0050920 regulation of chemotaxis? presumably indirect, via effect on rapA activity; will be clearer in LEGO
gflB GO:new (cf. GO:0043520) positive regulation of myosin II filament assembly IMP part_of GO:0050920 regulation of chemotaxis? presumably indirect, via effect on rapA activity; will be clearer in LEGO
gflB GO:0046580 negative regulation of Ras protein signal transduction IMP part_of GO:0071320 cellular response to cAMP 2e, 2f
gflB GO:0030010 establishment of cell polarity IMP part_of GO:0071320 cellular response to cAMP s3b, 3a, s4a
gflB NTR: negative regulation of Akt/PKB singalling IMP 3b, 3c, s4b
gflB NTR: negative regulation of actin polimerization IMP happens_during GO:0043327 chemotaxis to cAMP 4a-c
gflB NTR: positive regulation of myosin II polimerization IMP happens_during GO:0043327 chemotaxis to cAMP 4a-c
gflB GO:0043327 chemotaxis to cAMP IMP The observed developmental defects seem to be downstream of the cAMP signaling, so maybe in a LEGO diagram the process of chemotaxis to cAMP would have a positive causal relationship to the developmentl processes? Also, 'chemotaxis to cAMP' does not seem to have a relationship to 'response to cAMP' in the ontology. Should it?
gflB GO:0071320 cellular response to cAMP IMP
gflB GO:0043547 positive regulation of GTPase activity IMP has_regulation_target Rap1
gflB GO:0034260 negative regulation of GTPase activity IMP RasB|RasC I'm not sure if it's okay to put all of these specific Ras targets when a pan-Ras antibody was used.
gflB GO:0007264 small GTPase mediated signal transduction IMP
gflB GO:0030836 negative regulation of actin filament polymerization IMP I'm not sure about making this annotation; if I'm understanding the model correctly, the regulation would be indirect.
gflB GO:new positive regulation of myosin II filament assembly IMP
gflB GO:0090630 activation of GTPase activity IMP has_regulation_target, happens_during, occurs_at rapA, response to cAMP, cell leading edge as rap is in ras superfamily, this is the most specific term
gflB GO:0046580 negative regulation of Ras protein signal transduction IMP happens_during rasC, rasG, rasB , response to cAMP, cell leading edge | asexual reproduction alternative term: negative regulation of GTPase activity
gflB GO:0061118 regulation of positive chemotaxis to cAMP IMP
gflB GO:0030837 negative regulation of actin filament polymerization IMP happens_during(GO:0051591) response to cAMP ,occurs_at(GO:0005886) plasma membrane
gflB GO:0043520 regulation of myosin II filament assembly IMP happens_during(GO:0051591 response to cAMP ,occurs_at(GO:0005886) plasma membrane
gflB GO:0030010 establishment of cell polarity IMP
gflB GO:0071901 negative regulation of protein serine/threonine kinase activity IMP has_input gflB
gflB GO:0007264 small GTPase mediated signal transductions IMP has_regulation_target pkbA, pkgA
gflB GO:0030837 negative regulation of actin filament polymerisation IMP
gflB GO:0043520 regulation of myosin II filament assembly IMP
gflB GO:0006935 chemotaxis IMP
gflB GO:0046579 positive regulation of Ras protein signal transduction IMP
gflB GO:0061122 positive regulation of positive chemotaxis to cAMP IMP pg 460 right column
gflB GO:0032487 regulation of Rap protein signal transduction IMP has input: rapA GO:0071320|UniProt: P18613 may need to request "positive regulation of Rap signal transduction; pg 461 right column
gflB GO:0046580 negative regulation of Ras protein signal transduction IMP happens during: cellular response to cAMP GO:0071320 no input here as it could be RasG, RasB and or RasC; pg 461 right column
gflB GO:0030838 positive regulation of actin filament polymerisation IMP occurs at: cell leading GO:0071320|GO:0031252 pg 462 right column
gflB GO:0043520 regulation of myosin II filament assembly IMP occurs at: cell leading GO:0071320|GO:0031252 may need to request "positive regulation of myosin II filament assembly; pg 462 right column
gflB GO:0043327 chemotaxis to cAMP IMP
gflB GO:0046580 negative regulation of Ras protein signal transduction IMP regulates_o_has_participant RasG
gflB GO:0046579 positive regulation of Ras protein signal transduction IMP regulates_o_has_participant Rap1
gflB GO:0030837 negative regulation of actin filament polymerisation IMP
gflB GO:0043520 regulation of myosin II filament assembly IMP ask for positive regulation term
gflB GO:0061339 establishment or maintenance of monopolar cell polarity
gflB GO:0060326 cell chemotaxis IMP
gflB GO:0046580 negative regulation of Ras protein signal transduction happens_during GO:0060326 cell chemotaxis
gflB GO:0032487 regulation of Rap protein signal transduction IMP happens_during GO:0060326 cell chemotaxis
gflB GO:0032487 regulation of Rap protein signal transduction IMP has_regulation_target UniProtKB:P18613 RAP1 is target
gpaB GO:0043327 chemotaxis to cAMP IMP Table 1, Figure 1, Movies S1-S3.
gpaB GO:0048468 cell development IMP S1e
gpaB GO:0032092 positive regulation of protein binding IDA has_regulation_target GflB,rapA I'm not sure the exact meaning of this annotation is clear, i.e. that gpaB is regulating the binding of GflB to rapA.
gpaB GO:1905099 positive regulation of guanyl-nucleotide exchange factor activity IDA has_regulation_target, occurs_at gflB, GO:1904269 cell leading edge cell cortex
gpaB GO:1905099 positive regulation of guanyl-nucleotide exchange factor activity IDA has regul;ation target: gflB UniProt: Q54L90 pg 461 left column
gpaB GO:1905099 positive regulation of guanyl-nucleotide exchange factor activity IDA request a PRO term for the active form?
gskA GO:0006468 protein phosphorylation IDA has_input AND negatively_regulates gflB (DDB_G0286773) AND GO:0072697 protein localization to cell cortex 5d, 5e
gskA GO:1904777 negative regulation of protein localization to cell cortex IMP has_regulation_target gflB (DDB_G0286773) 5e
gskA GO:0018105 peptidyl serine phosphorylation IMP
gskA GO:0018107 peptidyl threonine phosphorylation IMP
gskA GO:1904776 regulation of protein localization to cell cortex IMP has_regulation_target GflB
gskA GO:0006468 protein phosphorylation IDA has_input gflB
gskA GO:1904776 regulation of protein localization to cell cortex IMP has_regulation_target, occurs_at gflB, leading edge
gskA GO:0018105 peptidyl-serine phosphorylation IMP has input: gflB UniProt: Q54L90 pg 464 right column
gskA GO:0018107 peptidyl-threonine phosphorylation IMP has input: gflB UniProt: Q54L90 pg 464 right column
gskA GO:1904777 negative regulation of protein localization to cell cortex IMP happens during: cellular response to cAMP UniProt: Q54L90|GO:0071320 pg 464 right column
gskA GO:0006468 protein phosphorylation IMP has_input GflB
gskA GO:1902463 protein localization to cell leading edge transports or maintains localization of GflB
rapA GO:0071320 cellular response to cAMP IEP
rasB GO:0071320 cellular response to cAMP IEP See above comment on pan-Ras antibody.
rasC GO:0071320 cellular response to cAMP IEP See above comment on pan-Ras antibody.
rasG GO:0071320 cellular response to cAMP IEP See above comment on pan-Ras antibody.
Molecular Function
gflB GO:0017034 Rap guanyl-nucleotide exchange factor activity IDA has_regulation_target Rap1
gflB GO:0005515 protein binding IDA Ga2
gflB GO:0005515 protein binding IPI Rap1 how to capture "requires presence of active Ga2" in conventional annotation? (I'm not even sure how to do it in LEGO)
gflB NOT NTR: Rho GTPase activator activity IDA S2b-d
gflB GO:0005088 Ras guanyl-nucleotide exchange factor activity IMP 2a
gflB GO:0001965 G-protein alpha-subunit binding IPI gpaB (DDB_G0276267) 1b
gflB GO:0005515 protein binding IPI rapA (DDB_G0291237) happens_during GO:0001965 G-protein alpha-subunit binding s2e + 2b
gflB NTR: activation of Rap1 GTPase activity IMP part_of GO:0071320 cellular response to cAMP
gflB GO:0001965 G-protein alpha-subunit binding IPI gpaB occurs_at SO:0100014 n_terminal_region SO term is defining where gflB binds to gpaB - need new relation?
gflB GO:0031267 small GTPase binding IPI RapA happens_during, has_direct_input activation of GTPase activity, gpaB maybe Rap GTPase binding should be added as child, all others are there
gflB GO:0017034 Rap guanyl-nucleotide exchange factor activity IDA has_input, happens_during, occurs_at rapA,activation of GTPase activity, cell cortex
gflB GO:0005543 phospholipid binding IDA occurs_at SO:0100014 n_terminal_region Fig.5SA
gflB GO:0001965 G-protein alpha-subunit binding IPI gpaB activated by GppNHp (CHEBI:78408) or should this be GTP (CHEBI:15996); pg 460 left column
gflB GO:0017034 Rap guanyl-nucleotide exchange factor activity IDA has regulation target: rapA UniProt: P18613 pg 461 left column
GflB GO:0005515 protein binding IPI GpaB
GflB GO:0005085 guanyl-nucleotide exchange factor activity IMP
GflB GO:0005085 guanyl-nucleotide exchange factor activity IDA has_input Rap1
GflB GO:0005515 protein binding IPI Rap1 has_participant GpaB depends on Ga2 being bound to GPPnHp
GflB GO:0005515 protein binding IPI GpaB
GflB GO:0005515 protein binding IPI RACB, RACL
GflB GO:0005085 guanyl-nucleotide exchange factor activity IDA has_direct_input UniProtKB:P18613 RAP1 is target
gpaB GO:0005515 protein binding IPI gflB (DDB_G0286773) 1b
gpaB NTR: Ras guanyl-nucleotide exchange factor binding IC GO:0005515 protein binding 1
gpaB GO:0032092 positive regulation of protein binding IDA has_regulation_target AND has_regulation_target gflB (DDB_G0286773) AND rapA (DDB_G0291237 2b
gpaB GO:0005515 protein binding IPI GflB Possibly a new term for guanylyl-nucleotide exchange factor binding? Also, see above.
gpaB GO:0005515 protein binding IPI gflB part_of GO:0007186 G-protein coupled receptor signaling pathway maybe new term 'nucleitide exchange factor binding? Cannot easily annotate that only activated (GTP bound) gpbA binds to gflB
GpaB GO:0005515 protein binding IPI GflB
GskA GO:0004674 protein serine/threonine kinase activity IDA has_direct_input GflB
GskA GO:0004674 protein serine/threonine kinase activity IMP happens_during, part_of, has_regulation_target GO:0071320, GO:1905097, GflB full extension: happens_during GO:0071320, part_of GO:1905097, has_regulation_target GflB (GO:0071320 = cellular response to cAMP; GO:1905097 = regulation of guanyl-nucleotide exchange factor activity)
gskA GO:0004674 protein serine/threonine kinase activity IDA has_input gflB (DDB_G0286773) 5d
GskA GO:0004674 protein serine/threonine kinase activity ISS human GSK3b has input GflB
GskA GO:0004674 protein serine/threonine kinase activity IDA has_direct_input UniProtKB:Q54L90
RACB GO:0005515 protein binding IPI GflB Fig. S1
RACL GO:0005515 protein binding IPI GflB Fig. S1
rapA GO:0005515 protein binding IPI gflB (DDB_G0286773) happens_during GO:0001965 G-protein alpha-subunit binding s2e + 2b
rapA GO:0005515 protein binding IPI GflB
rapA GO:0005515 protein binding IPI GflB happens_during activation of GTPase activity new term 'nucleitide exchange factor binding?
Cellular Component
gflB GO:0005737 cytoplasm IDA unstimulated cells
gflB GO:1904269 cell leading edge cell cortex IDA unstimulated cells
gflB GO:0005938 cell cortex IDA exists_during GO:0071320 GO:0071320 = cellular response to cAMP; not sure how to capture cytoskeleton dependency, in conventional annotation extensions or LEGO; does the experiment with GflBP1 and LatA show plasma membrane GO:0005886?
gflB GO:0005737 cytoplasm IDA 5a
gflB GO:0005737 cytoplasm IDA exists_during asexual reproduction
gflB GO:0005938 cell cortex IDA exists_during response to cAMP
gflB GO:0031252 cell leading edge IDA exists_during chemotaxis to cAMP
gflB GO:0005886 plasma membrane IDA exists_during chemotaxis to cAMP annotated 'plasma membrane' because of latA + domain expression experiments, also Supp Fig. 5A shows Phospholipid binding (see MF)
GflB GO:0005938 cell cortex IDA
GflB GO:0031252 cell leading edge IDA exists_during chemotaxis (GO:0006935)
gflB GO:0005737 cytoplasm IDA pg 462 right column
gflB GO:0031252 cell leading edge IDA exists during: cell chemotaxis GO:0060326 gradient treatment to induce chemotaxis; pg 462 right column
gflB GO:0005938 cell cortex IDA happens during: cellular response to cAMP GO:0071320 uniform or global treatment with cAMP; pg 462 right column
gflB GO:0031256 leading edge membrane IDA
gflB GO:0031252 cell leading edge IDA
gflB GO:1904269  cell leading edge cell cortex IDA localization_dependent_on ?Galpha2 requires binding of active Galpha
Raf1 GO:1904269 cell leading edge cell cortex IDA
Ral GO:1904269 cell leading edge cell cortex IDA
Rap1 GO:0009279 cell outer membrane IDA
Rap1 GO:0005886 plasma membrane IDA
rapA GO:0005886 plasma membrane IDA 3a
rapA GO:0005886 plasma membrane IDA
rasG GO:0005886 plasma membrane IDA 3a
RasG GO:0005886 plasma membrane IDA
RasG GO:0009279 cell outer membrane IDA
RasG GO:0005886 plasma membrane IDA

Minutes

  • On call: Bob, David H, Helen, George, Kimberly, Li, Midori, Olivia, Paola, Paul T, Petra, Sabrina, Sage, Stan, Suzi

USC Meeting

  • Please double-check the table and fill in for meeting, dinner, and the Noctua workshop.
  • Let Seth know if you need access to the Noctua tool
  • Also check Quick Start Guide linked from Noctua homepage for instructions on how to login

Contact Information

  • GO editors sent out a Google spreadsheet for contact information for each group
    • Most groups on this call have filled this sheet out
    • Paola will try to find contacts for the other groups on the spreadsheet who no longer regularly attend the annotation calls
  • Please get a github account if you'd like to contribute to any of the GO repositories, e.g. ontology requests
    • Users will need to be invited to a repository in order to have their name on the autocomplete list for a repository
    • PomBase is trying to set up a generic username for them to allow relevant notices sent to their helpdesk

Annotation Consistency Exercise

  • Try to get wiki table and spreadsheet better aligned
    • Action: Send wiki compatible table to all - DONE
  • Biggest question: How do we annotate that the binding bewteen GflB is dependent on the active (GTP-bound) form of the Galpha2 protein?
    • Possibly use PRO identifiers for capturing the active forms of entities like G proteins that are active when bound to a nucleotide
    • How to capture the effect of Galpha2 on the activity of GflB? One possible solution: Galpha2 positive regulation of protein binding has_regulation_targets GflB and RapA
    • DH: Use of happens_during does not capture the causal relation between the processes
    • Action: Investigate if PRO (Prosite?? - not in P2GO and didn't get impression on first sight they add active form of a protein..)
  • Questions about annotation to regulation of myosin II assembly/disassembly
    • Do we need separate terms?
    • Are these exactly opposite processes? If not, then keeping the terms separate would be best and we will need to add new terms.
    • Action: Create new term 'positive regulation of myosin II assembly'
  • Pan-ras antibody results
    • Older references support use of the specific Ras proteins based on use of the pan-ras antibody
    • Maybe a PRO term for Ras family proteins would be appropriate here, too
    • Action Keep specific ras extensions for this paper annotation - petra
  • Using SO identifiers to capture more granular information about sites of protein binding
    • for example, occurs_at N-terminal region
    • Groups may differ on this point - some curators might want to add this, others would not go into this much detail
    • Is SO the appropriate ontology for capturing this information?
      • SO has both amino acid and nucleotide sequence terms
    • Midori: We do an analogous thing for some DNA binding annotations but in these cases it's clear that the extension refers to the nucleotide
    • With protein binding annotations, it could be ambiguous as to which N-terminal region the annotation extension refers to
    • If we could do nested expressions in annotation extensions, the meaning of this extension would be clearer
    • In a Noctua model, though, you could say that the N-terminal region is part_of the relevant entity
    • Action: Delete this extension in linear annotation?
  • Other new term requests
    • Children of RasGTPase binding - need Rap GTPase binding
    • Guanylyl nucleotide exchange factor binding
    • Ontology editors are shying away from adding more of these binding terms as it is not sustainable
    • Preference would be given to allowing users to get this information by more sophisticated searches
    • There are currently so many binding terms, so even though we may not want more, then how do we justify not having a specific binding term when related binding terms are already there, e.g. Rap GTPase binding when Rac, Ras, Rho, etc. GTPase binding terms exist?
    • Discuss this at the November meeting - formal plan for modified form binding as well as specific protein terms
      • We need to make sure we don't lose information about who is binding whom
      • We want to support the search functionality that allows users to look for binding to specific types of proteins, but we don't necessarily want these terms in the ontology
      • Could we mine the information about the interacting partner's MF to inform the search
      • There are also annotation consistency issues wrt whether use of protein domain binding
    • Action Request no new binding term!
  • Will try to work on a LEGO model for this paper
    • Would be good to have a generic G protein signaling template