# HISTORY 24 Mar 2016: Updated by: TOUCHUP-v1.15 14 Mar 2016: Updated by: TOUCHUP-v1.14 # molecular_function # cellular_component 20110217: Eukaryota_PTN000104831 is found in integral component of organelle membrane (GO:0031301) 20110217: Eukaryota_PTN000104831 is found in vacuole (GO:0005773) 20110217: Bilateria_PTN000104834 is found in lysosome (GO:0005764) # biological_process 20110217: Eukaryota_PTN000104831 participates in arginine transport (GO:0015809) 20110217: Eukaryota_PTN000104831 participates in regulation of intracellular pH (GO:0051453) 20110217: Eukaryota_PTN000104831 participates in vacuolar transport (GO:0007034) 20110217: Eukaryota_PTN000104831 participates in vacuole organization (GO:0007033) 20110217: Bilateria_PTN000104834 participates in lysosome organization (GO:0007040) 20110217: Mammalia_PTN000104838 participates in lysosomal lumen acidification (GO:0007042) # WARNINGS - THE FOLLOWING HAVE BEEN REMOVED FOR THE REASONS NOTED # NOTES . Fast-pass curation of the PTHR10981 (CLN3/Battenin) family of proteins involved with lysosomal function. Mutations in human CLN3 cause the neurodegenerative disorder Batten disease (OMIM 204200). Batten disease is a neuronal ceroid lipofuscinosis, a storage disease marked by abnormal accumulation of lipofuscins, brown pigments similar to melanin that are products of oxidation of lipids and lipoproteins. Phylogeny This family consists of a single clade stretching from Leishmania (trypanosomes) to humans. Other than a triplication among the worms, there are no significant polytomies. There are also vey few annotations, especially in MF. MF -There is only 1 term, annotated to mouse Cln3, GO:0048306 "calcium-dependent protein binding." Cannot propagate "protein binding," and unable to corroborate the calcium dependence in any other protein. Do not propagate. -UniProt mentions 1 TAS to GO:0051082 "unfolded protein binding" (PMID 8980123) and a couple of IEA's to 48306 among the mammals, but otherwise there are no MF annotations. CC -Make sure to capture lysosome/vacuole aspect. Propagate "vacuole" (parental term) to AN0, "lysosome" to the animals (AN3), and GO:0000329 "fungal-type vacuole membrane" to the fungi (AN47). -Propagate GO:0031301 "integral to organelle membrane" to AN0. There are no annotations to "integral to" vacuole or lysosome membranes, just ER. -All Golgi annotations are found in the human protein, but the primate clade as a whole is slightly divergent from the rest of the family, so do not propagate unique annotations solely from descendants of AN11. -Remaining terms should not be propagated. BP -Propagate GO:0051453 "regulation of intracellular pH" to AN0, but note that it is lysosomal pH elevation in humans (PMID 10924275) and more complicated regulation of vacuolar pH in fungi (3 annotations in cerevisiae, 1 in pombe). Propagate GO:0007042 "lysosomal lumen acidification" from human CLN3 just to the mammals (AN7). -To capture and portray this complexity with the terms available, propagate GO:0007034 "vacuolar transport" to AN0. This term, defined as "The directed movement of substances into, out of or within a vacuole," covers pH changes accomplished by pumping protons or other chemicals in/out of a vacuole/lysosome. Supporting annotations include: Human: PMID 16251196, "Defective lysosomal arginine transport in juvenile Batten disease," annotated to GO:0015809 "arginine transport." Yeast: PMID 14660799, "A role in vacuolar arginine transport for yeast Btn1p and for human CLN3, the protein defective in Batten disease," annotated to GO:0015809 "arginine transport." -Propagate GO:0015809 "arginine transport" to AN0 based on annotations in human and yeast. -Propagate GO:0007033 "vacuole organization" to AN0 and GO:0007040 "lysosome organization" to the animals. =Questions for MOD curators= ==Cellular component== ===All organisms=== *'''Question: '''Organisms that annotate to "lysosome" or other membrane-bound compartments: Can you specify "membrane" or "integral to membrane" in these compartments? **'''Curator answer:''' Insert answer here. ***FlyBase: On reviewing this I managed to add a new experimental lysosome annotation for Drosophila from PMID:19028667 but could not specify "membrane" or "integral to membrane" terms from this paper. The authors in this 2009 paper comment, "The exact localization of CLN3 remains undefined despite examination of its distribution in a number of studies." Susan ***GOA (Human): I have updated the annotation to lysosomal membrane after re-reading PMID:9384607 ==Biological Process== ===Human=== *'''Question: '''Is there a more specific term than GO:0051453 "regulation of intracellular pH" that can be used based on PMID 10924275, "CLN3 protein regulates lysosomal pH and alters intracellular processing..." which states, "CLN3 protein increases lysosomal pH in cultured human embryonal kidney cells." Should there be a new term? **'''Curator answer:''' Have requested new terms for 'regulation of lysosomal pH', 'lysosomal pH reduction' and 'lysosomal pH elevation' with a view to annotate CLN3 with the 'lysosomal pH elevation' term. MSL, 17 Feb 2011: Submitted MSL, 26 Aug 2011: Updated with answers from wiki HM, reviewed May 21 2014 # 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).