# HISTORY
26 Mar 2016: Updated by: TOUCHUP-v1.15
16 Mar 2016: Updated by: TOUCHUP-v1.14

# molecular_function
20140301: root_PTN000432607 has function protein disulfide isomerase activity (GO:0003756) 
20140301: Eumetazoa_PTN001053176 contributes to function peptidyl-proline 4-dioxygenase activity (GO:0031545) 

# cellular_component
20140301: root_PTN000432607 is found in endoplasmic reticulum (GO:0005783) 
20140301: Chordata_PTN001053285 is found in cell surface (GO:0009986) 
20140301: Chordata_PTN001448745 is found in cell surface (GO:0009986) 

# biological_process
20140301: root_PTN000432607 participates in protein folding (GO:0006457) 
20140301: root_PTN000432607 participates in response to endoplasmic reticulum stress (GO:0034976) 
20140301: Eumetazoa_PTN001053176 participates in regulation of oxidative stress-induced intrinsic apoptotic signaling pathway (GO:1902175) 
20140301: Eumetazoa_PTN001053302 participates in apoptotic cell clearance (GO:0043277) 
20140301: Eumetazoa_PTN001053251 participates in apoptotic cell clearance (GO:0043277) 
20140301: Tetrapoda_PTN001053181 does NOT participate in response to endoplasmic reticulum stress (GO:0034976) 

# WARNINGS - THE FOLLOWING HAVE BEEN REMOVED FOR THE REASONS NOTED

# NOTES
Overall, the ancestral function is likely to be PDI, BP protein folding.  In eukaryotes BP of response to ER stress, as it is upregulated during stress.
MOLECULAR FUNCTION
Many annotations to protein disulfide reductase, but this reflects the problem that there is no relation in the ontology between PDI activity and protein disulfide oxidoreductase, which is the mechanism (by definition) of disulfide rearrangement (breaking and forming disulfides).  Suggest change to ontology.
MSA indicates several clades missing key aligned residues:
- outgroup archae and eubacterial genes: propagated PDI only to eukaryote ancestor
- tetrapod clades containing human ERP27 and PDILT (confirmed in SwissProt entries): loss of MF for these clades
Human and C. elegans P4HB is annotated to peptidyl-proline-4-dioxygenase, but it is only in a heteromeric complex that it has this activity, so suggest adding contributes_to qualifier to annot of human procollagen-proline....  Propagate to metazoan ancestor as this is age of P4HA genes (cf PTHR10869)
No evidence for arsenate reductase activity for human TMX1, suggest removing annotation
Transglutaminase activity in C. elegans pdi-1, -2, -3, so also likely ancestral, but what is biological significance? Do not propagate now.
CELLULAR COMPONENT
PDI-3, TMX3 location at cell surface is in platelets during clotting response; only chordates have platelets.
D. mel ERp60 annotations to lipid particle and microtubule are from HT experiments, do not propagate
BIOLOGICAL PROCESS
propagate only two apoptosis-related terms (one of them the downstream process of apoptotic cell clearance-- PDI from dead cells accumulates on cell surface and triggers phagocytic action), to base of metazoa as this is where apoptosis evolved.
Don't propagate any higher processes, as PDI's perform protein folding, and effects of mutants are likely to be very indirect.  Propagate only those effects with some established mechanism.
PT, Nov 2013

# REFERENCE
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).