RECEPTORS: Difference between revisions

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**<font color="orange">Q: Do we need to create 'apolipoprotein cargo receptor' and 'apolipoprotein signaling receptor' terms.</font color>
**<font color="orange">Q: Do we need to create 'apolipoprotein cargo receptor' and 'apolipoprotein signaling receptor' terms.</font color>


==<font color="navy">X-ACTIVATED RECEPTORS</font color>==
==<font color="navy">X-ACTIVATED RECEPTORS</font color>==

Revision as of 10:16, 2 August 2011

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RECEPTORS AND HAS_PART

There is a proposal to change the binding relationships, and kinase activities of the receptors to HAS_PART relationships.

  • Currently the receptors are linked to the ligand-binding GO term via an is_a relationship. This is incorrect. For example, epidermal growth factor receptor activity ; GO:0005006' is described as 'combining with EGF to initiate a change in cell activity'. The kinase activity of the receptor is separate to the EGF-binding activity and thus creates TPV having the receptor as is_a kinase activity.
  • The problem is that a receptor molecule has multiple 'activities' (bind the ligand and passing the signal on). Therefore the option of moving receptors to the process ontology was discussed at length but was decided against.
  • We need to separate the name of a gene product (EGFR) with the activities of the gene product.

For an overview of how the HAS_PART receptor proposal, see slide 35 of the following presentation from the LA GOC meeting, May 2011.


Related receptor SF item:


TRANSMEMBRANE RECEPTORS : DONE

There was a proposal (January 2011) to clean up the transmembrane receptor terms. The proposal was 2 fold:

  • 1. Remove the cellular component (transmembrane) information from the term name.
  • 2. Update the definitions of terms to show it’s a receptor that possesses kinase activity, and NOT phosphorylation of a receptor.

After describing the proposal via an annotation call on January 10th 2011, it was decided that:

  • The membrane localization of the receptor was integral to its activity (transmitting a signal from one side of the membrane to the other). Therefore the 'transmembrane' information should stay in the term name, but the definitions should be updated to make this clearer.

UPDATE FROM MAY 2011:

  • The definitions of the TM receptor terms have been updated to show that it is a receptor that possesses kinase activity (for example), and transmits a signal across a membrane.


SIGNALING RECEPTORS== DONE

BACKGROUND

  • Many receptors don't signal but instead internalize their ligand by receptor-mediated endocytosis. The old structure of GO did not account for this and all receptor terms were under 'signal transducer activity'. Initially there was discussion about whether endocytic receptors signal when they respond to their ligand to internalize. However, it was decided that in GO, it would be simplest to use signaling receptor to describe receptors that are coupled to a signal transduction cascade.
  • It's complicated by the fact that some signaling receptors (eg EGFR) internalize with their ligand. For these, I created 'rregulation of signal transduction by receptor internalization ; GO:0038009' process terms, along with 'endosomal signal transduction ; GO:2000803'.
  • The options were discussed at the signaling call on July 18th 2011. Based on the existing mappings for 'receptor activity', it was decided to move 'receptor activity' to be directly under 'molecular function' and create new terms for 'signaling receptors' and 'cargo/endocytic receptors' (OPTION 1 in the discussion discussion section). These edits were added to the ontology on AUGUST 2nd 2011 (revision 2.2140).
  • PLEASE COULD THE SIGNALING WG CHECK TO SEE IF ANY RECEPTOR TERMS LOOK IN THE WRONG PLACE !!


Some Notes/Outstanding Questions:

  • PATTERN RECOGNITION RECEPTORS: I haven't assigned pattern recognition receptors to cargo or signaling because they can be split into those that internalize their ligand without transducing a signal, and those that act via a signal transduction pathway (see http://en.wikipedia.org/wiki/Pattern_recognition_receptor).

However, given GO:0002221

pattern recognition receptor signaling pathway ; GO:0002221
--[partof]pattern recognition receptor activity ; GO:0008329
    • Q1: Do we want a term 'signaling pattern recognition receptor activity ; GO:NEW'? to be under GO:0002221 instead?
    • Q2: Are any of the current children of GO:0008329 signaling receptors?


  • LIPOPROTEIN PARTICLE RECEPTORS. I moved the lipoprotein particle receptor terms to be cargo receptors. Although members of the LDLR family are involved in signal transduction, they appear to do this by binding non-LDL ligands (eg reelin, PDGF etc). I've made a term 'reelin receptor activity ; GO:0038025' to cover the former. For the LRP1 protein that may transduce a signal by being proteolytically cleaved and the intracellular domain translocating to the nucleus, it's not clear what ligand is being bound, so 'signaling receptor activity ; GO:0038023' would be the most accurate term for annotation.


  • APOLIPOPROTEIN RECEPTORS. Not sure about apolipoprotein receptor activity ; GO:0030226. It's child 'apolipoprotein A-I receptor activity ; GO:0034188' has been used to annotate a clear signaling receptor. I've given GO:0034188 a signaling receptor parent, but kept GO:0030226 directly under receptor activity for now.
    • Q: Do we need to create 'apolipoprotein cargo receptor' and 'apolipoprotein signaling receptor' terms.


X-ACTIVATED RECEPTORS

At the February 2011 signaling workshop, it was agreed that, to distinguish the activity of the receptor from the gene product name, we should change receptors to 'x-activated receptor activity'. This fits in with the HAS_PART proposal, since 'epidermal growth factor-activated receptor activity' would HAS_PART 'epidermal growth factor binding'.

  E.g:
  epidermal growth factor receptor activity TO epidermal growth factor-activated receptor activity
  Wnt receptor activity TO Wnt-activated receptor activity
  activin receptor activity TO activin-activated receptor activity


LIGAND-GATED ION CHANNELS

Q: Are ligand-gated ion channels, receptors, and if so should they be in the receptor node?

At the moment (June 2011), ligand-gated ion channels are separate from 'receptor activity'. There are ligand-gated ion channel terms with 'receptor' synonyms:

ligand-gated ion channel activity ; GO:0015276 (synonym [NARROW] :ionotropic neurotransmitter receptor extracellular ATP-gated cation channel activity ; GO:0004931 (synonym [RELATED]: P2X receptor) inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity ; GO:0005220 (see below)


IP3 RECEPTOR

There was discussion (June 2011) within the signaling WG about whether 'inositol-1,4,5-trisphosphate receptor activity ; GO:0008095' and 'inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity ; GO:0005220' are synonymous. It was agreed they are, so the terms were merged by Becky (June 2011).


IONOTROPIC RECEPTORS

Are 'ionotropic receptors' just ligand-gated ion channels? If so, there is redundancy between:

  glutamate-gated calcium ion channel activity ; GO:0022849
  &
  ionotropic glutamate receptor activity ; GO:0004970

For a background, see http://www.sinauer.com/neuroscience4e/animations5.3.html.