# HISTORY 24 Mar 2016: Updated by: TOUCHUP-v1.15 14 Mar 2016: Updated by: TOUCHUP-v1.12 # molecular_function 20110715: Bilateria_PTN000056248 has function Wnt-activated receptor activity (GO:0042813) 20110715: Bilateria_PTN000056248 has function Wnt-protein binding (GO:0017147) 20110715: Tetrapoda_PTN000056284 has function low-density lipoprotein receptor activity (GO:0005041) 20110715: Tetrapoda_PTN000056284 has function apolipoprotein binding (GO:0034185) # cellular_component 20110718: Deuterostomia_PTN000056261 is found in receptor complex (GO:0043235) 20110718: Deuterostomia_PTN000056261 is found in plasma membrane (GO:0005886) 20110718: Tetrapoda_PTN000056284 is found in caveola (GO:0005901) 20110718: Tetrapoda_PTN000056284 is found in synapse (GO:0045202) 20110718: Tetrapoda_PTN000056284 is found in neuronal cell body (GO:0043025) 20110718: Tetrapoda_PTN000056284 is found in cell surface (GO:0009986) # biological_process 20110721: Bilateria_PTN000056248 participates in Wnt signaling pathway involved in dorsal/ventral axis specification (GO:0044332) 20110720: Bilateria_PTN000056248 participates in canonical Wnt signaling pathway (GO:0060070) 20110721: Tetrapoda_PTN000056265 participates in adipose tissue development (GO:0060612) 20110722: Tetrapoda_PTN000056265 participates in cholesterol homeostasis (GO:0042632) 20110720: Tetrapoda_PTN000056265 participates in bone marrow development (GO:0048539) 20110720: Tetrapoda_PTN000056265 participates in retinal blood vessel morphogenesis (GO:0061304) 20110722: Tetrapoda_PTN000056265 participates in regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0061178) 20110721: Tetrapoda_PTN000056265 participates in osteoblast development (GO:0002076) 20110722: Euteleostomi_PTN000056263 participates in embryonic retina morphogenesis in camera-type eye (GO:0060059) 20110722: Tetrapoda_PTN000056284 participates in cerebral cortex development (GO:0021987) 20110722: Tetrapoda_PTN000056284 participates in odontogenesis of dentin-containing tooth (GO:0042475) 20110722: Tetrapoda_PTN000056284 participates in trachea cartilage morphogenesis (GO:0060535) 20110722: Tetrapoda_PTN000056284 participates in axis elongation involved in somitogenesis (GO:0090245) 20110722: Tetrapoda_PTN000056284 participates in neural crest formation (GO:0014029) 20110722: Tetrapoda_PTN000056284 participates in receptor-mediated endocytosis of low-density lipoprotein particle involved in cholesterol transport (GO:0090118) 20110722: Tetrapoda_PTN000056284 participates in Wnt signaling pathway involved in somitogenesis (GO:0090244) 20110721: Tetrapoda_PTN000056284 participates in neural tube closure (GO:0001843) 20110722: Tetrapoda_PTN000056284 participates in external genitalia morphogenesis (GO:0035261) 20110722: Tetrapoda_PTN000056284 participates in embryonic pattern specification (GO:0009880) 20110721: Tetrapoda_PTN000056284 participates in midbrain-hindbrain boundary development (GO:0030917) 20110720: Tetrapoda_PTN000056284 participates in positive regulation of sequence-specific DNA binding transcription factor activity (GO:0051091) 20110722: Tetrapoda_PTN000056284 participates in midbrain development (GO:0030901) 20110722: Tetrapoda_PTN000056284 participates in neural crest cell differentiation (GO:0014033) 20110721: Tetrapoda_PTN000056284 participates in synaptic transmission (GO:0007268) 20110721: Tetrapoda_PTN000056284 participates in cerebellum morphogenesis (GO:0021587) 20110721: Tetrapoda_PTN000056284 participates in thalamus development (GO:0021794) 20110722: Tetrapoda_PTN000056284 participates in primitive streak formation (GO:0090009) 20110722: Tetrapoda_PTN000056284 participates in palate development (GO:0060021) 20110722: Tetrapoda_PTN000056284 participates in face morphogenesis (GO:0060325) 20110722: Tetrapoda_PTN000056284 participates in convergent extension (GO:0060026) 20110721: Tetrapoda_PTN000056284 participates in pericardium morphogenesis (GO:0003344) # WARNINGS - THE FOLLOWING HAVE BEEN REMOVED FOR THE REASONS NOTED # NOTES PAINTing SF108 and SF109 for the Wnt project Phylogeny These two subfamilies contain the human and mouse LRP5 and -6 proteins (low-density lipoprotein receptor-related proteins) descended from AN416. There are consecutive fish, Ciona, and urchin outgroups; I will probably confine propagation to this clade (AN413) and possibly just to AN416. There is an LRP5L clade (AN402) paralogous to AN413, but AN402 is unannotated, so I will propagate only the most conserved and widely-annotated functions beyond AN413. MF -Propagate GO:0042813 "Wnt receptor activity" to AN400 to span the entire metazoan clade, BUT NO FARTHER! -Same with GO:0017147 "Wnt-protein binding" and GO:0034185 "apolipoprotein binding." -Do not propagate GO:0019534 "toxin transporter activity" as there are both positive and negative annotations to it, and "toxin" isn't really an informative term in this context. -Can't find any evidence outside the LRP6 clade (AN436) for GO:0005041 "low-density lipoprotein receptor activity," so propagate to AN436 only. -Based on UniProt descriptions, propagate GO:0015026 "coreceptor activity" to AN416 to cover both the LRP5 and LRP6 clades. For additional corroborating info, see http://www.stanford.edu/group/nusselab/cgi-bin/wnt/arrow_LRP and http://www.sabiosciences.com/pathway.php?sn=WNT_Signaling. -Do not propagate GO:0005109 "frizzled binding" as the paper (PMID 11029007) is old (2000) and the binding may be indirect based on the abstract. ("The extracellular domain of LRP6 bound Wnt-1 and associated with Fz in a __Wnt-dependent__ manner.") Also, the idea is addressed by "coreceptor activity" (above). CC -Propagate GO:0005886 "plasma membrane" to AN413. Cannot use a more specific term like "integral to..." until there is an experimental annotation to it. -Propagate GO:0009986 "cell surface" to the LRP6 clade (AN436). -Propagate GO:0005901 "caveola" to LRP6 clade even though both annotations have a colocolizes_with qualifier. -Ignore "mitochondrion" from HTP mouse paper. -Propagate GO:0043235 "receptor complex" to AN413. -Propagate GO:0043025 "neuronal cell body" and GO:0045202 "synapse" from rat to LRP6 clade based on PMID 20404321. BP Signaling terms -Propagate GO:0016055 "Wnt receptor signaling pathway" to AN400 based on annotations throughout the LRP5/6 subfamily, including in fly. Although this is a basic function of this family, it is not found widely or frequently enough in PTHR10529 overall to justify propagating beyond this clade. -Also propagate GO:0060070 "canonical Wnt receptor signaling pathway" to AN400 based on same annotation pattern, even though this will subsume the annotation to 16055, above. -Do not propagate "regulation" terms in signaling pathways; the subtlety of "regulation of" signaling is lost in the transfer process. -GO:0044332 "Wnt receptor signaling pathway involved in dorsal/ventral axis specification" appears only in annotations from PMID 11029007. However, there is an additional annotation to GO:0009950 "dorsal/ventral axis specification" from LRP6 (PMID 18985738), and we have already propagated 16055 to AN400. Propagate 44332 to AN400. -Propagate GO:0007268 "synaptic transmission" from rat to LRP6 clade; seems to proceed through a Wnt pathway. Transcription as a target of signaling -There are multiple annotations to GO:0006355 "regulation of transcription, DNA-dependent" and its children across both the LRP5 and -6 clades. The child term GO:0045944 "positive regulation of transcription from RNA polymerase II promoter" is found in both, so propagate 45944 to AN416. -GO:0051091 "positive regulation of sequence-specific DNA binding transcription factor activity" is found on human and mouse LRP6, so propagate to LRP6 clade (AN436) Developmental terms -Propagate GO:0060349 "bone morphogenesis" to AN416 based on multiple osteoporosis papers for LRP5 and an IMP on LRP6. -Propagate GO:0048539 "bone marrow development" from PMID 17680723 to the rest of the LRP5 clade. This paper also has annotations to GO:0045600 "positive regulation of fat cell differentiation," GO:0060612 "adipose tissue development," and GO:0045668 "negative regulation of osteoblast differentiation." -Propagate GO:0045598 "regulation of fat cell differentiation" to AN416 based on annotations to the positive (human LRP5, PMID 17680723) and negative (mouse Lrp6, PMID 17888405) child terms. Also propagate GO:0060612 "adipose tissue development" from human to the LRP5 clade. -Propagate GO:0061304 "retinal blood vessel morphogenesis" to the LRP5 clade based on multiple annotations to this and the parent term GO:0061299 "retina vasculature morphogenesis in camera-type eye" in mouse and human. Note that 61304 specifies camera-type eyes, but only by parentage. Propagate parent term GO:0048596 "embryonic camera-type eye morphogenesis" to AN416 based on additional annotations in LRP6 clade. -Propagate GO:0060042 "retina morphogenesis in camera-type eye" to AN415 to cover vertebrates from annotations in both LRP5 and -6 clades. Actually, specify GO:0060059 "embryonic retina morphogenesis in camera-type eye" based on mouse Lrp6. -Propagate GO:0030900 "forebrain development" to LRP6 clade based on annotations to this and several child terms from at least 2 papers. -Propagate GO:0030326 "embryonic limb morphogenesis" to LRP6 clade based on multiple mouse annotations to this term, a parental term ("limb morphogenesis") and 2 child terms (forelimb, hindlimb, and digit). Expand to LRP5 clade based on limb and digit annotations. Don't specify "digit" for now, even with annotations to both LRP5 and -6. -Propagate GO:0046849 "bone remodeling" to AN416 based on multiple annotations to mouse Lrp5 and -6, plus related bone-type annotations. -Propagate GO:0060444 "branching involved in mammary gland duct morphogenesis" to AN416 based on multiple annotations to this term and its parent. -Propagate GO:0042475 "odontogenesis of dentine-containing tooth" to LRP6 clade based on 4 annotations from very old mouse papers. Receptor and transport processes -Based on PMID 12509515 (mouse), propagate GO:0061178 "regulation of insulin secretion involved in cellular response to glucose stimulus" and GO:0042632 "cholesterol homeostasis" (with 2 additional human citations) to LRP5 clade. -Propagate GO:0090118 "receptor-mediated endocytosis of low-density lipoprotein particle involved in cholesterol transport" from mouse to Lrp6 clade. Ignore all "protein phosphorylation"-type processes as too nebulous. =Questions for MOD curators= ==Cellular Component== ===All organisms=== * '''Critical: '''LRP5 and LRP6 are believed to be single-pass transmembrane proteins due to sequence similarity. Can anyone justify this with an experimental annotation? **'''Curator answer: '''Insert answer here. =Questions for ontology curators= ==Cellular Component== *Should GO:0005768 "endosome" ("a membrane-bounded organelle to which materials ingested by endocytosis are delivered") be an is_a child of GO:0031410 "cytoplasmic vesicle" ("a vesicle formed of membrane or protein, found in the cytoplasm of a cell")? ==Biological Process== *GO:0048069 "eye pigmentation" is_a GO:0032502 "developmental process," but it isn't a child of GO:0001654 "eye development." Is this right? MSL, submitted 22 July 2011 # 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).