PTHR43444 PANTHER:PTN000111103 (inferring transcriptional regulation for all glyoxylase family from PARK7)

[ValWood]

https://www.pombase.org/gene/SPAC1F7.06 is a member of https://www.pombase.org/gene_subset/interpro:IPR002818

the transcriptional regulation comes from from PARK7 Q99497 Q99LX0

this is park7 ortholog https://www.pombase.org/gene/SPAC22E12.03c

I don't think we can say that all glyoxylase are involved in transcriptional regulation?

[RLovering]

Rebecca created multiple annotations confirming PARK7 acts as a transcription co-factor eg: https://www.ncbi.nlm.nih.gov/pubmed/16731528 Abstract: Previously, we have reported that DJ-1 is a neuroprotective transcriptional co-activator interacting with the transcriptional co-repressor pyrimidine tract-binding protein-associated splicing factor (PSF). Here we show that DJ-1 and PSF bind and regulate the human tyrosine hydroxylase (TH) promoter. Inactivation of DJ-1 by small interference RNA (siRNA) results in decreased TH expression and l-DOPA production in human dopaminergic cell lines. Consistent with its role as a transcriptional regulator, DJ-1 specifically suppresses the global SUMO-1 modification. High molecular weight sumoylated protein species, including PSF, accumulate in the lymphoblast cells from the patients carrying pathogenic DJ-1 mutations. DJ-1 elevates the TH expression by inhibiting the sumoylation of PSF and preventing its sumoylation-dependent recruitment of histone deacetylase 1. Furthermore, siRNA silencing of DJ-1 decreases the acetylation of TH promoter-bound histones, and histone deacetylase inhibitors restore the DJ-1 siRNA-induced repression of TH. Therefore, our results suggest DJ-1 as a regulator of protein sumoylation and directly link the loss of DJ-1 expression and transcriptional dysfunction to impaired dopamine synthesis.

[ValWood]

I'm not objecting to the ortholog of PARK7 (SPAC22E12.03c) having this annotation (although I'm not convinced that it should be transferred to fungi, if this particular function is neurone specific....)

I'm objecting to the transfer to other family members (which have no identifiable human orthologs....like SPAC1F7.06)

The primary function of these glyoxylases is detoxification.... I don't think we should blanket annotate them as transcriptional repressors....

[pgaudet]

We reannotated the tree. We removed the propagation to transcriptional regulation.

New annotations:

• protein deglycase activity
• protein deglycation, glyoxal removal
• guanine deglycation, glyoxal removal
• cytosol & nucleus in eukaryotes.

Thanks, Pascale

[pgaudet]

We did not propagate the other BPs which may be indirect effects :

GO - Biological process:

activation of protein kinase B activity Source: ParkinsonsUK-UCL
adult locomotory behavior Source: Ensembl
autophagy Source: UniProtKB-KW
cellular response to glyoxal Source: ParkinsonsUK-UCL
cellular response to hydrogen peroxide Source: UniProtKB
cellular response to oxidative stress Source: ParkinsonsUK-UCL
detoxification of copper ion Source: UniProtKB
detoxification of mercury ion Source: UniProtKB
DNA repair Source: UniProtKB
dopamine uptake involved in synaptic transmission Source: Ensembl
enzyme active site formation via L-cysteine sulfinic acid Source: Ensembl
glucose homeostasis Source: UniProtKB
glutathione deglycation Source: ParkinsonsUK-UCL
glycolate biosynthetic process Source: ParkinsonsUK-UCL
glyoxal metabolic process Source: ParkinsonsUK-UCL
guanine deglycation Source: UniProtKB
guanine deglycation, glyoxal removal Source: UniProtKB
guanine deglycation, methylglyoxal removal Source: UniProtKB
hydrogen peroxide metabolic process Source: ParkinsonsUK-UCL
inflammatory response Source: UniProtKB-KW
insulin secretion Source: UniProtKB
lactate biosynthetic process Source: ParkinsonsUK-UCL
membrane depolarization Source: Ensembl
membrane hyperpolarization Source: Ensembl
methylglyoxal metabolic process Source: ParkinsonsUK-UCL
mitochondrion organization Source: UniProtKB
negative regulation of apoptotic process Source: ParkinsonsUK-UCL
negative regulation of cell death Source: UniProtKB
negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway Source: ParkinsonsUK-UCL
negative regulation of death-inducing signaling complex assembly Source: ParkinsonsUK-UCL
negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
negative regulation of extrinsic apoptotic signaling pathway Source: UniProtKB
negative regulation of gene expression Source: ParkinsonsUK-UCL
negative regulation of hydrogen peroxide-induced cell death Source: ParkinsonsUK-UCL
negative regulation of hydrogen peroxide-induced neuron death Source: ParkinsonsUK-UCL
negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
negative regulation of neuron apoptotic process Source: BHF-UCL
negative regulation of neuron death Source: ParkinsonsUK-UCL
negative regulation of nitrosative stress-induced intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
negative regulation of oxidative stress-induced cell death Source: ParkinsonsUK-UCL
negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
negative regulation of proteasomal ubiquitin-dependent protein catabolic process Source: ParkinsonsUK-UCL
negative regulation of protein acetylation Source: ParkinsonsUK-UCL
negative regulation of protein binding Source: UniProtKB
negative regulation of protein export from nucleus Source: ParkinsonsUK-UCL
negative regulation of protein K48-linked deubiquitination Source: ParkinsonsUK-UCL
negative regulation of protein kinase activity Source: ParkinsonsUK-UCL
negative regulation of protein phosphorylation Source: ParkinsonsUK-UCL
negative regulation of protein sumoylation Source: ParkinsonsUK-UCL
negative regulation of protein ubiquitination Source: ParkinsonsUK-UCL
negative regulation of reactive oxygen species biosynthetic process Source: UniProtKB
negative regulation of TRAIL-activated apoptotic signaling pathway Source: ParkinsonsUK-UCL
negative regulation of ubiquitin-protein transferase activity Source: ParkinsonsUK-UCL
negative regulation of ubiquitin-specific protease activity Source: ParkinsonsUK-UCL
peptidyl-arginine deglycation Source: ParkinsonsUK-UCL
peptidyl-cysteine deglycation Source: ParkinsonsUK-UCL
peptidyl-lysine deglycation Source: ParkinsonsUK-UCL
positive regulation of acute inflammatory response to antigenic stimulus Source: UniProtKB
positive regulation of androgen receptor activity Source: ParkinsonsUK-UCL
positive regulation of autophagy of mitochondrion Source: ParkinsonsUK-UCL
positive regulation of DNA binding transcription factor activity Source: ParkinsonsUK-UCL
positive regulation of dopamine biosynthetic process Source: ParkinsonsUK-UCL
positive regulation of gene expression Source: ParkinsonsUK-UCL
positive regulation of interleukin-8 production Source: ParkinsonsUK-UCL
positive regulation of L-dopa biosynthetic process Source: ParkinsonsUK-UCL
positive regulation of L-dopa decarboxylase activity Source: ParkinsonsUK-UCL
positive regulation of mitochondrial electron transport, NADH to ubiquinone Source: ParkinsonsUK-UCL
positive regulation of NAD(P)H oxidase activity Source: UniProtKB
positive regulation of oxidative phosphorylation uncoupler activity Source: Ensembl
positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway Source: Ensembl
positive regulation of peptidyl-serine phosphorylation Source: ParkinsonsUK-UCL
positive regulation of protein homodimerization activity Source: ParkinsonsUK-UCL
positive regulation of protein kinase B signaling Source: ParkinsonsUK-UCL
positive regulation of protein localization to nucleus Source: ParkinsonsUK-UCL
positive regulation of pyrroline-5-carboxylate reductase activity Source: ParkinsonsUK-UCL
positive regulation of reactive oxygen species biosynthetic process Source: Ensembl
positive regulation of superoxide dismutase activity Source: ParkinsonsUK-UCL
positive regulation of transcription by RNA polymerase II Source: ParkinsonsUK-UCL
positive regulation of transcription regulatory region DNA binding Source: ParkinsonsUK-UCL
positive regulation of tyrosine 3-monooxygenase activity Source: ParkinsonsUK-UCL
protein deglycation, glyoxal removal Source: ParkinsonsUK-UCL
protein deglycation, methylglyoxal removal Source: ParkinsonsUK-UCL
protein deglycosylation Source: UniProtKB
protein stabilization Source: ParkinsonsUK-UCL
Ras protein signal transduction Source: ParkinsonsUK-UCL
regulation of androgen receptor signaling pathway Source: UniProtKB
regulation of inflammatory response Source: UniProtKB
regulation of mitochondrial membrane potential Source: ParkinsonsUK-UCL
regulation of neuron apoptotic process Source: UniProtKB
regulation of supramolecular fiber organization Source: ParkinsonsUK-UCL
single fertilization Source: UniProtKB-KW

[ValWood]

Agreed, most of these 'phenotypes' (disease symptoms) predate the knowledge that this is a protein deglycase activity http://www.uniprot.org/citations/25416785

and the true function becomes somewhat buried....

[ValWood]

There are 12 pages of annotations for PARK7 in QuickGO! Including 4 to extracellular exosome ;)

[ValWood]

I don't even think we can be sure these are OK for all members?

protein deglycase activity protein deglycation, glyoxal removal guanine deglycation, glyoxal removal cytosol & nucleus in eukaryotes.

I would be wary of transeferring to all members from https://www.pombase.org/gene_subset/interpro:IPR002818 (especially the specificity guanine deglycation, glyoxal removal)

could this be confined to PARK7 family orthologs?

[pgaudet]

We certainly have evidence all the way to E. coli. So unless there is evidence that the function was lost in a specific branch, we normally infer that it the function was inherited from the ancestor. Does that sound OK ?

Thanks, Pascale

[ValWood]

GO:0036524 protein deglycase activity

is probably OK, but I suspect these could have different specificities:

Our previous and current data suggest that S. pombe DJ-1 homologs are involved in the stationary-phase stress responses. This conclusion is based on the following observations. First, S. pombe Hsp3101 and Hsp3102 are the major GSH-independent glyoxalase III that may have some role in protecting cells from reactive carbonyl species toxicity accumulated during the stationary phase of yeast growth [19]. Second, S. pombe DJ-1 homologs appear to be involved but not essential for autophagy in stationary phase. Third, Sdj1 is likely to play a role in defense against oxidative stress during stationary phase. Fourth, expression of S. pombe DJ-1 homologs are induced in stationary phase in a Sty1-dependent manner. Interestingly, S. pombe DJ-1 homologs exhibit different patterns of subcellular localization [19]. Moreover, induction of S. pombe DJ-1 homologs may involve different transcription factors. Based on these observations, we speculate that S. pombe DJ-1 homologs may play overlapping yet distinct roles in stress responses.