Ratn1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005576 extracellular region	IBA GO_REF:0000033	ACCEPT	Summary: Secreted lipocalin shed in urine/dander; extracellular localization is correct and central. Reason: Secretory protein acting in the extracellular space. Supporting Evidence: file:rat/Ratn1/Ratn1-uniprot.txt SUBCELLULAR LOCATION: Secreted
GO:0005549 odorant binding	IBA GO_REF:0000033	ACCEPT	Summary: Binds small hydrophobic odorant/pheromone ligands in the lipocalin calyx. Reason: Core lipocalin ligand-binding function. Supporting Evidence: file:rat/Ratn1/Ratn1-uniprot.txt Major urinary proteins (Mups) bind and release pheromones.
GO:0005576 extracellular region	IEA GO_REF:0000044	ACCEPT	Summary: Secreted lipocalin shed in urine/dander; extracellular localization is correct and central. Reason: Secretory protein acting in the extracellular space. Supporting Evidence: file:rat/Ratn1/Ratn1-uniprot.txt SUBCELLULAR LOCATION: Secreted
GO:0005829 cytosol	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Cytosol, mapped from the UniProt subcellular location of the processed 15.5 kDa fatty acid-binding protein form. Reason: UniProt places a 15.5 kDa processed form of the protein in the cytosol, probably after endocytic uptake from the urinary lumen in the kidney. This location reflects degradation and reuptake after secretion, not the site where the protein acts as a pheromone carrier, so it is kept as non-core. (Earlier review text attributed the cytosolic signal to the biosynthetic route, which is not correct for a secreted protein.) Supporting Evidence: file:rat/Ratn1/Ratn1-uniprot.txt Cytoplasm, cytosol. Note=It is probably taken up from the urinary lumen by endocytosis.
GO:0008286 insulin receptor signaling pathway	IEA GO_REF:0000108	REMOVE	Summary: Insulin receptor signaling pathway, inferred automatically from the insulin receptor activity (GO:0005009) row through an inter-ontology link. Reason: This row only restates the transferred insulin receptor activity, which is removed: a secreted lipocalin cannot be an insulin receptor, and the mouse source study found no effect of MUP1 on insulin receptor phosphorylation. With its premise removed, the derived process annotation has no support (earlier review: MARK_AS_OVER_ANNOTATED). Supporting Evidence: PMID:19258313 Therefore, it is unlikely that MUP1 inhibits the hepatic gluconeogenic program by increasing insulin sensitivity in the liver.
GO:0036094 small molecule binding	IEA GO_REF:0000002	MODIFY	Summary: Small molecule binding mapped from the lipocalin family signature (InterPro:IPR002345). Reason: Correct but uninformative: the lipocalin calyx binds small hydrophobic pheromones. The specific, supported activity is pheromone binding, which the gene already carries; replace with that term (earlier review: MARK_AS_OVER_ANNOTATED, but the term is not wrong, only too general). Proposed replacements: pheromone binding Supporting Evidence: file:rat/Ratn1/Ratn1-uniprot.txt Major urinary proteins (Mups) bind and release pheromones.
GO:0005009 insulin receptor activity	ISS GO_REF:0000024	REMOVE	Summary: Insulin receptor activity transferred by sequence similarity from mouse MUP1 (UniProtKB:P11588). Reason: A secreted lipocalin of about 19 kDa has no transmembrane or tyrosine kinase domain and cannot carry out insulin receptor activity. The mouse source study itself (PMID:19258313) found that MUP1 overexpression did not change insulin-stimulated insulin receptor phosphorylation, and concluded that MUP1 does not act through hepatic insulin sensitivity. The transferred activity is contradicted, so the row is removed (earlier review: MARK_AS_OVER_ANNOTATED). Supporting Evidence: PMID:19258313 Therefore, it is unlikely that MUP1 inhibits the hepatic gluconeogenic program by increasing insulin sensitivity in the liver. file:rat/Ratn1/Ratn1-uniprot.txt Belongs to the calycin superfamily. Lipocalin family.
GO:0005550 pheromone binding	ISS GO_REF:0000024	ACCEPT	Summary: MUPs bind and release volatile pheromones; the defining molecular function of Mus m 1 / Rat n 1. Reason: Core, experimentally/curated pheromone-binding function of the protein. Supporting Evidence: file:rat/Ratn1/Ratn1-uniprot.txt Major urinary proteins (Mups) bind and release pheromones.
GO:0005576 extracellular region	IDA PMID:6886376 Male urinary protein-1 (Mup-1) expression in the female rat.	ACCEPT	Summary: Extracellular region, from detection of the Mup-1 protein in male and female rat urine (PMID:6886376). Reason: The protein is secreted by the liver and excreted in urine, where it carries pheromones. Its detection in urine directly supports the extracellular location, which is where it functions. Supporting Evidence: PMID:6886376 the Mup-1 gene was clearly detected on agarose gel electrophorograms of not only intact male but also intact female urine. file:rat/Ratn1/Ratn1-uniprot.txt SUBCELLULAR LOCATION: Secreted.
GO:0005634 nucleus	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Nucleus, transferred by sequence similarity from mouse MUP1 (UniProtKB:P11588). Reason: The rat protein is a secreted lipocalin. UniProt records it as secreted, with a processed form in the cytosol, and does not list a nuclear location. No nuclear function is known for it, and the mouse source record (PMID:6643987) is an electrophoretic survey of urinary, serum and liver MUPs whose abstract does not address nuclear localization. Transferring a nuclear location overstates the evidence. Supporting Evidence: file:rat/Ratn1/Ratn1-uniprot.txt SUBCELLULAR LOCATION: Secreted.
GO:0005829 cytosol	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Cytosol, transferred by sequence similarity from mouse MUP1 (UniProtKB:P11588). Reason: Consistent with UniProt placing the processed 15.5 kDa form of the rat protein in the cytosol after probable endocytic uptake from urine. A post-secretion location, not the functional one; kept as non-core. Supporting Evidence: file:rat/Ratn1/Ratn1-uniprot.txt Cytoplasm, cytosol. Note=It is probably taken up from the urinary lumen by endocytosis.
GO:0006112 energy reserve metabolic process	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Energy reserve metabolic process transferred by sequence similarity from mouse MUP1 (UniProtKB:P11588), whose source annotation comes from systemic delivery of recombinant MUP1 to diabetic mice (PMID:19336396). Reason: The mouse experiments raised circulating MUP1 by adenovirus or osmotic pump in obese or diabetic mice and measured downstream metabolic outcomes. Even for mouse MUP1 these are systemic effects of a pharmacologically raised protein, not an activity of the lipocalin itself. Rodent MUP genes form species-specific clusters, so the mouse donor is a family member rather than a demonstrated one-to-one ortholog of rat P02761, and no comparable metabolic role has been shown for the rat urinary protein. The transfer overstates what is known for this protein, whose established function is pheromone binding and transport. Supporting Evidence: PMID:19336396 Chronic elevation of circulating MUP-1 in db/db mice, using an osmotic pump-based protein delivery system, increased energy expenditure and locomotor activity, raised core body temperature, and decreased glucose intolerance as well as insulin resistance.
GO:0007005 mitochondrion organization	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Mitochondrion organization transferred by sequence similarity from mouse MUP1 (UniProtKB:P11588), whose source annotation comes from systemic delivery of recombinant MUP1 to diabetic mice (PMID:19336396). Reason: The mouse experiments raised circulating MUP1 by adenovirus or osmotic pump in obese or diabetic mice and measured downstream metabolic outcomes. Even for mouse MUP1 these are systemic effects of a pharmacologically raised protein, not an activity of the lipocalin itself. Rodent MUP genes form species-specific clusters, so the mouse donor is a family member rather than a demonstrated one-to-one ortholog of rat P02761, and no comparable metabolic role has been shown for the rat urinary protein. The transfer overstates what is known for this protein, whose established function is pheromone binding and transport. Supporting Evidence: PMID:19336396 Chronic elevation of circulating MUP-1 in db/db mice, using an osmotic pump-based protein delivery system, increased energy expenditure and locomotor activity, raised core body temperature, and decreased glucose intolerance as well as insulin resistance.
GO:0009060 aerobic respiration	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Aerobic respiration transferred by sequence similarity from mouse MUP1 (UniProtKB:P11588), whose source annotation comes from systemic delivery of recombinant MUP1 to diabetic mice (PMID:19336396). Reason: The mouse experiments raised circulating MUP1 by adenovirus or osmotic pump in obese or diabetic mice and measured downstream metabolic outcomes. Even for mouse MUP1 these are systemic effects of a pharmacologically raised protein, not an activity of the lipocalin itself. Rodent MUP genes form species-specific clusters, so the mouse donor is a family member rather than a demonstrated one-to-one ortholog of rat P02761, and no comparable metabolic role has been shown for the rat urinary protein. The transfer overstates what is known for this protein, whose established function is pheromone binding and transport. Supporting Evidence: PMID:19336396 Chronic elevation of circulating MUP-1 in db/db mice, using an osmotic pump-based protein delivery system, increased energy expenditure and locomotor activity, raised core body temperature, and decreased glucose intolerance as well as insulin resistance.
GO:0010628 positive regulation of gene expression	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Positive regulation of gene expression transferred by sequence similarity from mouse MUP1 (UniProtKB:P11588), whose source annotation comes from systemic delivery of recombinant MUP1 to diabetic mice (PMID:19336396). Reason: The mouse experiments raised circulating MUP1 by adenovirus or osmotic pump in obese or diabetic mice and measured downstream metabolic outcomes. Even for mouse MUP1 these are systemic effects of a pharmacologically raised protein, not an activity of the lipocalin itself. Rodent MUP genes form species-specific clusters, so the mouse donor is a family member rather than a demonstrated one-to-one ortholog of rat P02761, and no comparable metabolic role has been shown for the rat urinary protein. The transfer overstates what is known for this protein, whose established function is pheromone binding and transport. Supporting Evidence: PMID:19336396 Chronic elevation of circulating MUP-1 in db/db mice, using an osmotic pump-based protein delivery system, increased energy expenditure and locomotor activity, raised core body temperature, and decreased glucose intolerance as well as insulin resistance.
GO:0010888 negative regulation of lipid storage	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Negative regulation of lipid storage transferred by sequence similarity from mouse MUP1 (UniProtKB:P11588), whose source annotation comes from systemic delivery of recombinant MUP1 to diabetic mice (PMID:19336396). Reason: The mouse experiments raised circulating MUP1 by adenovirus or osmotic pump in obese or diabetic mice and measured downstream metabolic outcomes. Even for mouse MUP1 these are systemic effects of a pharmacologically raised protein, not an activity of the lipocalin itself. Rodent MUP genes form species-specific clusters, so the mouse donor is a family member rather than a demonstrated one-to-one ortholog of rat P02761, and no comparable metabolic role has been shown for the rat urinary protein. The transfer overstates what is known for this protein, whose established function is pheromone binding and transport. Supporting Evidence: PMID:19336396 Chronic elevation of circulating MUP-1 in db/db mice, using an osmotic pump-based protein delivery system, increased energy expenditure and locomotor activity, raised core body temperature, and decreased glucose intolerance as well as insulin resistance.
GO:0010907 positive regulation of glucose metabolic process	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Positive regulation of glucose metabolic process transferred by sequence similarity from mouse MUP1 (UniProtKB:P11588), whose source annotation comes from systemic delivery of recombinant MUP1 to diabetic mice (PMID:19258313 and PMID:19336396). Reason: The mouse experiments raised circulating MUP1 by adenovirus or osmotic pump in obese or diabetic mice and measured downstream metabolic outcomes. Even for mouse MUP1 these are systemic effects of a pharmacologically raised protein, not an activity of the lipocalin itself. Rodent MUP genes form species-specific clusters, so the mouse donor is a family member rather than a demonstrated one-to-one ortholog of rat P02761, and no comparable metabolic role has been shown for the rat urinary protein. The transfer overstates what is known for this protein, whose established function is pheromone binding and transport. Supporting Evidence: PMID:19258313 Recombinant MUP1 markedly attenuated hyperglycemia and glucose intolerance in genetic (db/db) and dietary fat-induced type 2 diabetic mice as well as in streptozotocin-induced type 1 diabetic mice. PMID:19336396 Chronic elevation of circulating MUP-1 in db/db mice, using an osmotic pump-based protein delivery system, increased energy expenditure and locomotor activity, raised core body temperature, and decreased glucose intolerance as well as insulin resistance.
GO:0031649 heat generation	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Heat generation transferred by sequence similarity from mouse MUP1 (UniProtKB:P11588), whose source annotation comes from systemic delivery of recombinant MUP1 to diabetic mice (PMID:19336396). Reason: The mouse experiments raised circulating MUP1 by adenovirus or osmotic pump in obese or diabetic mice and measured downstream metabolic outcomes. Even for mouse MUP1 these are systemic effects of a pharmacologically raised protein, not an activity of the lipocalin itself. Rodent MUP genes form species-specific clusters, so the mouse donor is a family member rather than a demonstrated one-to-one ortholog of rat P02761, and no comparable metabolic role has been shown for the rat urinary protein. The transfer overstates what is known for this protein, whose established function is pheromone binding and transport. Supporting Evidence: PMID:19336396 Chronic elevation of circulating MUP-1 in db/db mice, using an osmotic pump-based protein delivery system, increased energy expenditure and locomotor activity, raised core body temperature, and decreased glucose intolerance as well as insulin resistance.
GO:0042593 glucose homeostasis	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Glucose homeostasis transferred by sequence similarity from mouse MUP1 (UniProtKB:P11588), whose source annotation comes from systemic delivery of recombinant MUP1 to diabetic mice (PMID:19258313). Reason: The mouse experiments raised circulating MUP1 by adenovirus or osmotic pump in obese or diabetic mice and measured downstream metabolic outcomes. Even for mouse MUP1 these are systemic effects of a pharmacologically raised protein, not an activity of the lipocalin itself. Rodent MUP genes form species-specific clusters, so the mouse donor is a family member rather than a demonstrated one-to-one ortholog of rat P02761, and no comparable metabolic role has been shown for the rat urinary protein. The transfer overstates what is known for this protein, whose established function is pheromone binding and transport. Supporting Evidence: PMID:19258313 Recombinant MUP1 markedly attenuated hyperglycemia and glucose intolerance in genetic (db/db) and dietary fat-induced type 2 diabetic mice as well as in streptozotocin-induced type 1 diabetic mice.
GO:0045475 locomotor rhythm	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Locomotor rhythm transferred by sequence similarity from mouse MUP1 (UniProtKB:P11588), whose source annotation comes from systemic delivery of recombinant MUP1 to diabetic mice (PMID:19336396). Reason: The mouse experiments raised circulating MUP1 by adenovirus or osmotic pump in obese or diabetic mice and measured downstream metabolic outcomes. Even for mouse MUP1 these are systemic effects of a pharmacologically raised protein, not an activity of the lipocalin itself. Rodent MUP genes form species-specific clusters, so the mouse donor is a family member rather than a demonstrated one-to-one ortholog of rat P02761, and no comparable metabolic role has been shown for the rat urinary protein. The transfer overstates what is known for this protein, whose established function is pheromone binding and transport. Supporting Evidence: PMID:19336396 Chronic elevation of circulating MUP-1 in db/db mice, using an osmotic pump-based protein delivery system, increased energy expenditure and locomotor activity, raised core body temperature, and decreased glucose intolerance as well as insulin resistance.
GO:0045721 negative regulation of gluconeogenesis	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Negative regulation of gluconeogenesis transferred by sequence similarity from mouse MUP1 (UniProtKB:P11588), whose source annotation comes from systemic delivery of recombinant MUP1 to diabetic mice (PMID:19258313). Reason: The mouse experiments raised circulating MUP1 by adenovirus or osmotic pump in obese or diabetic mice and measured downstream metabolic outcomes. Even for mouse MUP1 these are systemic effects of a pharmacologically raised protein, not an activity of the lipocalin itself. Rodent MUP genes form species-specific clusters, so the mouse donor is a family member rather than a demonstrated one-to-one ortholog of rat P02761, and no comparable metabolic role has been shown for the rat urinary protein. The transfer overstates what is known for this protein, whose established function is pheromone binding and transport. Supporting Evidence: PMID:19258313 MUP1 inhibited the expression of both gluconeogenic genes and lipogenic genes in the liver.
GO:0045834 positive regulation of lipid metabolic process	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Positive regulation of lipid metabolic process transferred by sequence similarity from mouse MUP1 (UniProtKB:P11588), whose source annotation comes from systemic delivery of recombinant MUP1 to diabetic mice (PMID:19336396). Reason: The mouse experiments raised circulating MUP1 by adenovirus or osmotic pump in obese or diabetic mice and measured downstream metabolic outcomes. Even for mouse MUP1 these are systemic effects of a pharmacologically raised protein, not an activity of the lipocalin itself. Rodent MUP genes form species-specific clusters, so the mouse donor is a family member rather than a demonstrated one-to-one ortholog of rat P02761, and no comparable metabolic role has been shown for the rat urinary protein. The transfer overstates what is known for this protein, whose established function is pheromone binding and transport. Supporting Evidence: PMID:19336396 Chronic elevation of circulating MUP-1 in db/db mice, using an osmotic pump-based protein delivery system, increased energy expenditure and locomotor activity, raised core body temperature, and decreased glucose intolerance as well as insulin resistance.
GO:0045892 negative regulation of DNA-templated transcription	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Negative regulation of DNA-templated transcription transferred by sequence similarity from mouse MUP1 (UniProtKB:P11588), based on reduced hepatic gluconeogenic and lipogenic gene expression after MUP1 overexpression. Reason: The donor observation is a change in liver mRNA levels after raising circulating MUP1. It does not show that the secreted lipocalin acts on transcription, which would require nuclear action by a protein that functions in plasma and urine. Transferring this to the rat urinary protein overstates the evidence. Supporting Evidence: PMID:19258313 MUP1 inhibited the expression of both gluconeogenic genes and lipogenic genes in the liver.
GO:0051055 negative regulation of lipid biosynthetic process	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Negative regulation of lipid biosynthetic process transferred by sequence similarity from mouse MUP1 (UniProtKB:P11588), whose source annotation comes from systemic delivery of recombinant MUP1 to diabetic mice (PMID:19258313). Reason: The mouse experiments raised circulating MUP1 by adenovirus or osmotic pump in obese or diabetic mice and measured downstream metabolic outcomes. Even for mouse MUP1 these are systemic effects of a pharmacologically raised protein, not an activity of the lipocalin itself. Rodent MUP genes form species-specific clusters, so the mouse donor is a family member rather than a demonstrated one-to-one ortholog of rat P02761, and no comparable metabolic role has been shown for the rat urinary protein. The transfer overstates what is known for this protein, whose established function is pheromone binding and transport. Supporting Evidence: PMID:19258313 MUP1 inhibited the expression of both gluconeogenic genes and lipogenic genes in the liver.
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction transferred by sequence similarity from mouse MUP1 (UniProtKB:P11588), whose source annotation comes from systemic delivery of recombinant MUP1 to diabetic mice (PMID:19336396). Reason: The mouse experiments raised circulating MUP1 by adenovirus or osmotic pump in obese or diabetic mice and measured downstream metabolic outcomes. Even for mouse MUP1 these are systemic effects of a pharmacologically raised protein, not an activity of the lipocalin itself. Rodent MUP genes form species-specific clusters, so the mouse donor is a family member rather than a demonstrated one-to-one ortholog of rat P02761, and no comparable metabolic role has been shown for the rat urinary protein. The transfer overstates what is known for this protein, whose established function is pheromone binding and transport. Supporting Evidence: PMID:19336396 Chronic elevation of circulating MUP-1 in db/db mice, using an osmotic pump-based protein delivery system, increased energy expenditure and locomotor activity, raised core body temperature, and decreased glucose intolerance as well as insulin resistance.
GO:0061179 negative regulation of insulin secretion involved in cellular response to glucose stimulus	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Negative regulation of insulin secretion involved in cellular response to glucose stimulus transferred by sequence similarity from mouse MUP1 (UniProtKB:P11588), whose source annotation comes from systemic delivery of recombinant MUP1 to diabetic mice (PMID:19336396). Reason: The mouse experiments raised circulating MUP1 by adenovirus or osmotic pump in obese or diabetic mice and measured downstream metabolic outcomes. Even for mouse MUP1 these are systemic effects of a pharmacologically raised protein, not an activity of the lipocalin itself. Rodent MUP genes form species-specific clusters, so the mouse donor is a family member rather than a demonstrated one-to-one ortholog of rat P02761, and no comparable metabolic role has been shown for the rat urinary protein. The transfer overstates what is known for this protein, whose established function is pheromone binding and transport. Supporting Evidence: PMID:19336396 Chronic elevation of circulating MUP-1 in db/db mice, using an osmotic pump-based protein delivery system, increased energy expenditure and locomotor activity, raised core body temperature, and decreased glucose intolerance as well as insulin resistance.
GO:0071396 cellular response to lipid	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Cellular response to lipid transferred by sequence similarity from mouse MUP1 (UniProtKB:P11588), whose source annotation comes from systemic delivery of recombinant MUP1 to diabetic mice (PMID:19258313). Reason: The mouse experiments raised circulating MUP1 by adenovirus or osmotic pump in obese or diabetic mice and measured downstream metabolic outcomes. Even for mouse MUP1 these are systemic effects of a pharmacologically raised protein, not an activity of the lipocalin itself. Rodent MUP genes form species-specific clusters, so the mouse donor is a family member rather than a demonstrated one-to-one ortholog of rat P02761, and no comparable metabolic role has been shown for the rat urinary protein. The transfer overstates what is known for this protein, whose established function is pheromone binding and transport. Supporting Evidence: PMID:19258313 Recombinant MUP1 markedly attenuated hyperglycemia and glucose intolerance in genetic (db/db) and dietary fat-induced type 2 diabetic mice as well as in streptozotocin-induced type 1 diabetic mice.

Gene Description

Existing Annotations Review

Core Functions

Secreted lipocalin that binds and releases volatile pheromones/odorants in its beta-barrel calyx, mediating chemical communication; shed in urine and dander (major rodent inhalant allergen).

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

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