Ratn1

UniProt ID: P02761
Organism: Rattus norvegicus
Review Status: DRAFT
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Gene Description

Rat n 1 (major urinary protein), a secreted lipocalin (calycin superfamily, lipocalin family) and the major rat allergen. MUPs bind and release volatile pheromones in their beta-barrel calyx and may protect them from oxidation, regulating social behaviours (aggression, mating, territory) and acting as kairomones. Rat n 1 is shed in urine and dander and is the dominant rat inhalant allergen (laboratory-animal allergy).

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: Cytosolic signal reflects the biosynthetic route of this secreted protein, not a functional compartment.
Reason: Biosynthetic/transit localization; functional compartment is extracellular.
GO:0008286 insulin receptor signaling pathway
IEA
GO_REF:0000108
MARK AS OVER ANNOTATED
Summary: Insulin-receptor-signaling involvement is ISS-propagated from MUP metabolic studies; not shown for this allergen and downstream of the implausible insulin-receptor-activity assignment.
Reason: Depends on the implausible insulin-receptor-activity call; not demonstrated for this protein.
GO:0036094 small molecule binding
IEA
GO_REF:0000002
MARK AS OVER ANNOTATED
Summary: Generic parent of the specific odorant/pheromone binding already annotated.
Reason: Uninformative broad parent; specific ligand-binding is captured.
GO:0005009 insulin receptor activity
ISS
GO_REF:0000024
MARK AS OVER ANNOTATED
Summary: Insulin receptor activity is implausible for a small secreted extracellular lipocalin: it has no transmembrane/tyrosine-kinase receptor architecture. ISS-propagated from MUP metabolic reports.
Reason: A secreted ~19 kDa lipocalin cannot be the insulin receptor (a transmembrane receptor tyrosine kinase); clear fold/architecture mismatch from ISS over-propagation.
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: 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:0005634 nucleus
ISS
GO_REF:0000024
MARK AS OVER ANNOTATED
Summary: Nuclear localization contradicts the protein's signal-peptide-driven secretion (extracellular pheromone carrier); it accompanies the ISS-propagated intracellular metabolic-signalling hypothesis.
Reason: Inconsistent with the secreted localization of this lipocalin; over-propagated with the metabolic cluster.
GO:0005829 cytosol
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: Cytosolic signal reflects the biosynthetic route of this secreted protein, not a functional compartment.
Reason: Biosynthetic/transit localization; functional compartment is extracellular.
GO:0006112 energy reserve metabolic process
ISS
GO_REF:0000024
MARK AS OVER ANNOTATED
Summary: ISS-propagated from major-urinary-protein endocrine/metabolic studies (a hormone-like role reported for specific MUPs) and transferred across the whole MUP family. This metabolic function is not established for this secreted lipocalin allergen and conflicts with its characterized role as a pheromone carrier.
Reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for this protein, whose evidenced function is pheromone/odorant binding.
GO:0007005 mitochondrion organization
ISS
GO_REF:0000024
MARK AS OVER ANNOTATED
Summary: ISS-propagated from major-urinary-protein endocrine/metabolic studies (a hormone-like role reported for specific MUPs) and transferred across the whole MUP family. This metabolic function is not established for this secreted lipocalin allergen and conflicts with its characterized role as a pheromone carrier.
Reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for this protein, whose evidenced function is pheromone/odorant binding.
GO:0009060 aerobic respiration
ISS
GO_REF:0000024
MARK AS OVER ANNOTATED
Summary: ISS-propagated from major-urinary-protein endocrine/metabolic studies (a hormone-like role reported for specific MUPs) and transferred across the whole MUP family. This metabolic function is not established for this secreted lipocalin allergen and conflicts with its characterized role as a pheromone carrier.
Reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for this protein, whose evidenced function is pheromone/odorant binding.
GO:0010628 positive regulation of gene expression
ISS
GO_REF:0000024
MARK AS OVER ANNOTATED
Summary: ISS-propagated from major-urinary-protein endocrine/metabolic studies (a hormone-like role reported for specific MUPs) and transferred across the whole MUP family. This metabolic function is not established for this secreted lipocalin allergen and conflicts with its characterized role as a pheromone carrier.
Reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for this protein, whose evidenced function is pheromone/odorant binding.
GO:0010888 negative regulation of lipid storage
ISS
GO_REF:0000024
MARK AS OVER ANNOTATED
Summary: ISS-propagated from major-urinary-protein endocrine/metabolic studies (a hormone-like role reported for specific MUPs) and transferred across the whole MUP family. This metabolic function is not established for this secreted lipocalin allergen and conflicts with its characterized role as a pheromone carrier.
Reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for this protein, whose evidenced function is pheromone/odorant binding.
GO:0010907 positive regulation of glucose metabolic process
ISS
GO_REF:0000024
MARK AS OVER ANNOTATED
Summary: ISS-propagated from major-urinary-protein endocrine/metabolic studies (a hormone-like role reported for specific MUPs) and transferred across the whole MUP family. This metabolic function is not established for this secreted lipocalin allergen and conflicts with its characterized role as a pheromone carrier.
Reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for this protein, whose evidenced function is pheromone/odorant binding.
GO:0031649 heat generation
ISS
GO_REF:0000024
MARK AS OVER ANNOTATED
Summary: ISS-propagated from major-urinary-protein endocrine/metabolic studies (a hormone-like role reported for specific MUPs) and transferred across the whole MUP family. This metabolic function is not established for this secreted lipocalin allergen and conflicts with its characterized role as a pheromone carrier.
Reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for this protein, whose evidenced function is pheromone/odorant binding.
GO:0042593 glucose homeostasis
ISS
GO_REF:0000024
MARK AS OVER ANNOTATED
Summary: ISS-propagated from major-urinary-protein endocrine/metabolic studies (a hormone-like role reported for specific MUPs) and transferred across the whole MUP family. This metabolic function is not established for this secreted lipocalin allergen and conflicts with its characterized role as a pheromone carrier.
Reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for this protein, whose evidenced function is pheromone/odorant binding.
GO:0045475 locomotor rhythm
ISS
GO_REF:0000024
MARK AS OVER ANNOTATED
Summary: ISS-propagated from major-urinary-protein endocrine/metabolic studies (a hormone-like role reported for specific MUPs) and transferred across the whole MUP family. This metabolic function is not established for this secreted lipocalin allergen and conflicts with its characterized role as a pheromone carrier.
Reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for this protein, whose evidenced function is pheromone/odorant binding.
GO:0045721 negative regulation of gluconeogenesis
ISS
GO_REF:0000024
MARK AS OVER ANNOTATED
Summary: ISS-propagated from major-urinary-protein endocrine/metabolic studies (a hormone-like role reported for specific MUPs) and transferred across the whole MUP family. This metabolic function is not established for this secreted lipocalin allergen and conflicts with its characterized role as a pheromone carrier.
Reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for this protein, whose evidenced function is pheromone/odorant binding.
GO:0045834 positive regulation of lipid metabolic process
ISS
GO_REF:0000024
MARK AS OVER ANNOTATED
Summary: ISS-propagated from major-urinary-protein endocrine/metabolic studies (a hormone-like role reported for specific MUPs) and transferred across the whole MUP family. This metabolic function is not established for this secreted lipocalin allergen and conflicts with its characterized role as a pheromone carrier.
Reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for this protein, whose evidenced function is pheromone/odorant binding.
GO:0045892 negative regulation of DNA-templated transcription
ISS
GO_REF:0000024
MARK AS OVER ANNOTATED
Summary: Transcriptional regulation requires nuclear/chromatin action, incompatible with a secreted extracellular lipocalin; ISS-propagated with the MUP metabolic-signalling cluster.
Reason: Requires intranuclear action incompatible with a secreted protein; ISS over-propagation.
GO:0051055 negative regulation of lipid biosynthetic process
ISS
GO_REF:0000024
MARK AS OVER ANNOTATED
Summary: ISS-propagated from major-urinary-protein endocrine/metabolic studies (a hormone-like role reported for specific MUPs) and transferred across the whole MUP family. This metabolic function is not established for this secreted lipocalin allergen and conflicts with its characterized role as a pheromone carrier.
Reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for this protein, whose evidenced function is pheromone/odorant binding.
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
ISS
GO_REF:0000024
MARK AS OVER ANNOTATED
Summary: ISS-propagated from major-urinary-protein endocrine/metabolic studies (a hormone-like role reported for specific MUPs) and transferred across the whole MUP family. This metabolic function is not established for this secreted lipocalin allergen and conflicts with its characterized role as a pheromone carrier.
Reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for this protein, whose evidenced function is pheromone/odorant binding.
GO:0061179 negative regulation of insulin secretion involved in cellular response to glucose stimulus
ISS
GO_REF:0000024
MARK AS OVER ANNOTATED
Summary: ISS-propagated from major-urinary-protein endocrine/metabolic studies (a hormone-like role reported for specific MUPs) and transferred across the whole MUP family. This metabolic function is not established for this secreted lipocalin allergen and conflicts with its characterized role as a pheromone carrier.
Reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for this protein, whose evidenced function is pheromone/odorant binding.
GO:0071396 cellular response to lipid
ISS
GO_REF:0000024
MARK AS OVER ANNOTATED
Summary: ISS-propagated from major-urinary-protein endocrine/metabolic studies (a hormone-like role reported for specific MUPs) and transferred across the whole MUP family. This metabolic function is not established for this secreted lipocalin allergen and conflicts with its characterized role as a pheromone carrier.
Reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for this protein, whose evidenced function is pheromone/odorant binding.

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).

Molecular Function:
pheromone binding
Cellular Locations:
Supporting Evidence:
  • file:rat/Ratn1/Ratn1-uniprot.txt
    Major urinary proteins (Mups) bind and release pheromones.

References

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Suggested Questions for Experts

Q: What is the specific volatile pheromone/odorant carried by this MUP, and how does ligand identity relate to its behavioural (and kairomone) effects?

Q: Are the ISS-propagated metabolic roles (insulin-receptor/glucose-lipid regulation) genuine for any MUP, or an artifact of family-level transfer from one studied paralog? They are not supported for this secreted lipocalin.

Suggested Experiments

Experiment: Identify endogenous ligands co-purifying with the native protein by GC-MS and confirm binding/release kinetics of candidate volatiles to the recombinant protein by fluorescent-probe displacement.

Hypothesis: This MUP binds and slowly releases a specific volatile pheromone in its lipocalin calyx.

Type: ligand identification / biophysical binding assay

Experiment: Test recombinant protein for direct insulin-receptor engagement and for effects on hepatocyte glucose/lipid metabolism, with appropriate paralog and endotoxin controls.

Hypothesis: The metabolic phenotypes attributed to MUPs are not a function of this secreted lipocalin.

Type: receptor-binding / cell-based metabolic assay

πŸ“š Additional Documentation

Notes

(Ratn1-notes.md)

Ratn1 β€” curation notes (ALLERGENS backlog, mammalian inhalant cohort)

Rat n 1 = major urinary protein; secreted pheromone-binding lipocalin (major rat allergen). Same curation as Mus m 1 incl. IDA extracellular (PMID:6886376) ACCEPT; metabolic ISS cluster over-annotated.

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