Family Curator Notes

Annotation inferences using phylogenetic trees
The goal of the GO Reference Genome Project, described in PMID 19578431, is to provide accurate, complete and consistent GO annotations for all genes in twelve model organism genomes.To this end, GO curators are annotating evolutionary trees from the PANTHER database with GO terms describing molecular function, biological process and cellular component. GO terms based on experimental data from the scientific literature are used to annotate ancestral genes in the phylogenetic tree by sequence similarity (ISS), and unannotated descendants of these ancestral genes are inferred to have inherited these same GO annotations by descent. The annotations are done using a tool called PAINT (Phylogenetic Annotation and INference Tool).

Description of phylogeny

This family consists of 81 proteins. kch from aquifex is an outgroup. The clades are:

AN2: animal (AN3) and fungi (AN125), no plant members
AN130: protozoan
AN139: protozoan
A8JOX8 from the green algae chlamydomonas


KCNMA1 from human, mouse, rat and cattle are well characterized. The key biological role for this protein family is to function as calcium activated potassium channel.

-There are widespread annotations in clade AN3 to GO:0015269 ?calcium activated potassium channel activity?. Branch length between AN2 and AN3 is very short; therefore I propagated GO:0015269 to AN2. None of the proteins outside AN2 is from RefGenome organism and none of them have existing annotations. Without looking into relevant literature, I annotated conservatively here to AN2 instead of AN0.
-Based on similar reasoning, propagate GO:0005249 (voltage gated potassium channel activity) to AN2. Worm slo-2 has an annotation to GO:0015271 (outward rectifier potassium channel activity) which is a child of GO:0005249.
- propagate GO:0060072 "large conductance calcium-activated potassium channel activity" to AN4.
-Propagate GO:0005267 (potassium channel activity) to AN0. GO:0005267 is a parent term of GO:0005249.
-Protein binding and actin binding terms annotated to KCNMA1 were not propagated.

NOTE: There are some proteins with longer branch distance, for example the LOC clade AN113. Based on discussions with Mike and Pscale, these were not excluded from annotation propagation (Mike: I don't think I would bother. The descriptions for these indicate that they are predicted to be potassium channels, and we don't have any better information on them. There are a number of singletons above those guys with comparable branch lengths; some are annotated as predicted potassium channels, and some have no comment, but none says that it is actually something else, so I would just let the annotation stand).


-Calcium activated potassium channel are located in the plasma membrane of a variety of different cell types (PMID: 8973172). Members of this family that have been annotated to ?plasma membrane? include those from rat, worm, fly, human, mouse. Propagate GO:0005886 (plasma membrane) to AN2. Again I am annotating conservatively here to AN2 instead of AN0. However, for GO:0016021 (integral to membrane), I propagated to AN0.
-There are also several annotations to GO:0008076 (voltage-gated potassium channel complex); this was propagated to AN2 (consistent with propagating GO:0005249 ?voltage gated potassium channel activity? to AN2). Note that GO:0008076 "voltage-gated potassium channel complex" is a child of "integral to plasma membrane".
- propagate GO:0016324 apical plasma membrane to KCNMA1 mamal clade AN22 (this is being conservative here, not propagated to AN11: AN11 and AN22 arise from gene duplication. AN11 has longer branch distance).


-Propagate GO:0071805 potassium ion transmembrane transport to AN0

PMID: 8973172

Submitted 2011 Jan 24, DHL
Revised 2011-01-28, DHL