id: P02761
gene_symbol: Ratn1
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:10116
  label: Rattus norvegicus
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:
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Secreted lipocalin shed in urine/dander; extracellular localization is correct and central.
    action: ACCEPT
    reason: Secretory protein acting in the extracellular space.
    supported_by:
    - reference_id: file:rat/Ratn1/Ratn1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Secreted'
- term:
    id: GO:0005549
    label: odorant binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Binds small hydrophobic odorant/pheromone ligands in the lipocalin calyx.
    action: ACCEPT
    reason: Core lipocalin ligand-binding function.
    supported_by:
    - reference_id: file:rat/Ratn1/Ratn1-uniprot.txt
      supporting_text: Major urinary proteins (Mups) bind and release pheromones.
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Secreted lipocalin shed in urine/dander; extracellular localization is correct and central.
    action: ACCEPT
    reason: Secretory protein acting in the extracellular space.
    supported_by:
    - reference_id: file:rat/Ratn1/Ratn1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Secreted'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Cytosolic signal reflects the biosynthetic route of this secreted protein, not a functional
      compartment.
    action: KEEP_AS_NON_CORE
    reason: Biosynthetic/transit localization; functional compartment is extracellular.
- term:
    id: GO:0008286
    label: insulin receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Depends on the implausible insulin-receptor-activity call; not demonstrated for this protein.
- term:
    id: GO:0036094
    label: small molecule binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: Generic parent of the specific odorant/pheromone binding already annotated.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative broad parent; specific ligand-binding is captured.
- term:
    id: GO:0005009
    label: insulin receptor activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    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.'
    action: MARK_AS_OVER_ANNOTATED
    reason: A secreted ~19 kDa lipocalin cannot be the insulin receptor (a transmembrane receptor tyrosine
      kinase); clear fold/architecture mismatch from ISS over-propagation.
- term:
    id: GO:0005550
    label: pheromone binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: MUPs bind and release volatile pheromones; the defining molecular function of Mus m 1 / Rat
      n 1.
    action: ACCEPT
    reason: Core, experimentally/curated pheromone-binding function of the protein.
    supported_by:
    - reference_id: file:rat/Ratn1/Ratn1-uniprot.txt
      supporting_text: Major urinary proteins (Mups) bind and release pheromones.
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IDA
  original_reference_id: PMID:6886376
  qualifier: located_in
  review:
    summary: Secreted lipocalin shed in urine/dander; extracellular localization is correct and central.
    action: ACCEPT
    reason: Secretory protein acting in the extracellular space.
    supported_by:
    - reference_id: file:rat/Ratn1/Ratn1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Secreted'
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Nuclear localization contradicts the protein's signal-peptide-driven secretion (extracellular
      pheromone carrier); it accompanies the ISS-propagated intracellular metabolic-signalling hypothesis.
    action: MARK_AS_OVER_ANNOTATED
    reason: Inconsistent with the secreted localization of this lipocalin; over-propagated with the metabolic
      cluster.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Cytosolic signal reflects the biosynthetic route of this secreted protein, not a functional
      compartment.
    action: KEEP_AS_NON_CORE
    reason: Biosynthetic/transit localization; functional compartment is extracellular.
- term:
    id: GO:0006112
    label: energy reserve metabolic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for
      this protein, whose evidenced function is pheromone/odorant binding.
- term:
    id: GO:0007005
    label: mitochondrion organization
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for
      this protein, whose evidenced function is pheromone/odorant binding.
- term:
    id: GO:0009060
    label: aerobic respiration
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for
      this protein, whose evidenced function is pheromone/odorant binding.
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for
      this protein, whose evidenced function is pheromone/odorant binding.
- term:
    id: GO:0010888
    label: negative regulation of lipid storage
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for
      this protein, whose evidenced function is pheromone/odorant binding.
- term:
    id: GO:0010907
    label: positive regulation of glucose metabolic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for
      this protein, whose evidenced function is pheromone/odorant binding.
- term:
    id: GO:0031649
    label: heat generation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for
      this protein, whose evidenced function is pheromone/odorant binding.
- term:
    id: GO:0042593
    label: glucose homeostasis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for
      this protein, whose evidenced function is pheromone/odorant binding.
- term:
    id: GO:0045475
    label: locomotor rhythm
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for
      this protein, whose evidenced function is pheromone/odorant binding.
- term:
    id: GO:0045721
    label: negative regulation of gluconeogenesis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for
      this protein, whose evidenced function is pheromone/odorant binding.
- term:
    id: GO:0045834
    label: positive regulation of lipid metabolic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for
      this protein, whose evidenced function is pheromone/odorant binding.
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Transcriptional regulation requires nuclear/chromatin action, incompatible with a secreted
      extracellular lipocalin; ISS-propagated with the MUP metabolic-signalling cluster.
    action: MARK_AS_OVER_ANNOTATED
    reason: Requires intranuclear action incompatible with a secreted protein; ISS over-propagation.
- term:
    id: GO:0051055
    label: negative regulation of lipid biosynthetic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for
      this protein, whose evidenced function is pheromone/odorant binding.
- term:
    id: GO:0051897
    label: positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for
      this protein, whose evidenced function is pheromone/odorant binding.
- term:
    id: GO:0061179
    label: negative regulation of insulin secretion involved in cellular response to glucose stimulus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for
      this protein, whose evidenced function is pheromone/odorant binding.
- term:
    id: GO:0071396
    label: cellular response to lipid
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-propagated similarity annotation from MUP metabolic literature; not demonstrated for
      this protein, whose evidenced function is pheromone/odorant binding.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator
    judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping,
    accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000108
  title: Automatic assignment of GO terms using logical inference, based on on inter-ontology links
  findings: []
- id: PMID:6886376
  title: Male urinary protein-1 (Mup-1) expression in the female rat.
  findings: []
- id: file:rat/Ratn1/Ratn1-uniprot.txt
  title: UniProt entry P02761 (Ratn1), Rattus norvegicus
  findings:
  - statement: Secreted MUP lipocalin that binds/releases pheromones; major rodent allergen.
    supporting_text: Major urinary proteins (Mups) bind and release pheromones.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Curated UniProt record; source for the pheromone/odorant-binding core function. Metabolic
      annotations are ISS over-propagation.
core_functions:
- description: 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:
    id: GO:0005550
    label: pheromone binding
  supported_by:
  - reference_id: file:rat/Ratn1/Ratn1-uniprot.txt
    supporting_text: Major urinary proteins (Mups) bind and release pheromones.
  locations:
  - id: GO:0005576
    label: extracellular region
  knowledge_gaps:
  - gap_statement: Whether this MUP allergen has any genuine endocrine/metabolic function (as ISS-propagated
      from MUP metabolic studies) is unresolved and probably spurious for this protein.
    boundary: 'Established: pheromone/odorant binding by the secreted lipocalin. Unknown/disputed: the
      insulin-receptor / glucose-lipid-metabolism roles transferred by similarity across the MUP family.'
    gap_kind:
    - BIOLOGY
    - CURATION
    provenance:
    - reference_id: file:rat/Ratn1/Ratn1-uniprot.txt
      supporting_text: Major urinary proteins (Mups) bind and release pheromones.
proposed_new_terms: []
suggested_questions:
- question: What is the specific volatile pheromone/odorant carried by this MUP, and how does ligand identity
    relate to its behavioural (and kairomone) effects?
  experts: []
- question: 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.
  experts: []
suggested_experiments:
- hypothesis: This MUP binds and slowly releases a specific volatile pheromone in its lipocalin calyx.
  description: 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.
  experiment_type: ligand identification / biophysical binding assay
- hypothesis: The metabolic phenotypes attributed to MUPs are not a function of this secreted lipocalin.
  description: Test recombinant protein for direct insulin-receptor engagement and for effects on hepatocyte
    glucose/lipid metabolism, with appropriate paralog and endotoxin controls.
  experiment_type: receptor-binding / cell-based metabolic assay