Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on curation of immunofluorescence data
Combined Automated Annotation using Multiple IEA Methods
Large-scale proteomics and phosphoproteomics of urinary exosomes.
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Profiles the proteome of exosomes from normal human urine and identifies 1132 proteins; ADIRF is one of the 1016 gene products GOA annotates to extracellular exosome from this study, from the supplementary identification list rather than from any ADIRF-specific result.
"Overall, the analysis identified 1132 proteins unambiguously, including 177 that are represented on the Online Mendelian Inheritance in Man database of disease-related genes, suggesting that exosome analysis is a potential approach to discover urinary biomarkers."
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Defines the vesicle population being sampled, which is what makes GO:0070062 rather than a generic extracellular term the assigned annotation.
"Normal human urine contains large numbers of exosomes, which are 40- to 100-nm vesicles that originate as the internal vesicles in multivesicular bodies from every renal epithelial cell type facing the urinary space."
A Novel pro-adipogenesis factor abundant in adipose tissues and over-expressed in obesity acts upstream of PPARγ and C/EBPα.
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The only functional characterisation of ADIRF in the nucleus, and the source of three of the eleven GOA rows. The assay is explicitly over-expression, which is why the two process rows should carry IMP rather than IDA.
"Over-expression studies in 3T3-L1 cells indicated that it up-regulates the levels of CCAAT/enhancer binding protein α (C/EBPα) and PPARγ and promotes adipogenic differentiation starting from the early stage of adipogenesis."
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Direct observation of nuclear localisation, supporting the GO:0005634 IDA row; this observation is a direct assay and IDA is correct for it.
"Our data demonstrated that C10orf116 is highly expressed in adipose tissue and is localized primarily within the nucleus."
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The authors' own summary of the inference, which is the basis for the GO:0045944 annotation; note it is framed as characteristics rather than a demonstrated mechanism.
"C10orf16 manifested the characteristics of an adipocyte lineage-specific nuclear factor that can modulate the master adipogenesis transcription factors early during differentiation."
In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
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The authors caution that abundant contaminating proteins in these preparations require verification before their presence is generalised - directly relevant to a small, very abundant protein like ADIRF being detected in a urogenital-tract exosome preparation.
"Certainly the presence of high abundant contaminating proteins, in exosome preparations from cancer-related biofluids such as EPS-urine, must be taken into account and further verified before generalizing their presence to a clinical association with the cancerous condition."
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The paper's own protein count, which does not reconcile with the 1046 gene products GOA annotates from it; the identifications are in a supplemental table absent from the cached text, so the difference is recorded as unresolved.
"in total, close to 900 proteins were identified in the two EPS-urine exosome pools"
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The authors note that proteins recovered in urine exosome preparations are often simply abundant, or may exist in soluble form - a further reason the exosome-specific claim is weaker than the extracellular one.
"This evidence suggests that, proteins found in urine exosome preparations are relatively abundant and thus also detected when the whole fluid is analyzed, or alternatively, some of these proteins could also exist as a soluble form."
A reference map of the human binary protein interactome.
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Establishes that the HuRI dataset screened with three Y2H assay versions, which is why IntAct logs the single ADIRF-IL18 interaction under three sub-methods and UniProt reports NbExp=3 for what is one screen.
"We screened this search space a total of nine times with a panel of three Y2H assay versions"
Tripartite factors leading to molecular divergence between human and murine smooth muscle.
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Identifies the genomic basis of ADIRF's absence in the mouse lineage: a 43-kb deletion removing the promoter and first exon, which encodes the first 42 of the protein's 76 residues.
"The mouse locus corresponding to human ADIRF harbors a deletion of close to 43 kb (Fig 5A). This deletion is predicted to remove the promoter and first exon of ADIRF, a sequence that encodes the first 42 amino acids of the 76 amino acid gene product."
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Places the loss in the common ancestor of mouse, rat and hamster, which matches the independently measured absence of ADIRF across all of Muroidea.
"deletion of this segment (and loss of ADIRF expression) occurred in the evolutionary predecessor to mouse, rat, and hamster."
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ADIRF is more abundant in arterial tissue than in the adipose tissue that gave it its name - relevant because all eleven GOA rows are adipogenesis or localisation and none is vascular.
"The ADIRF gene is relatively highly expressed (over 700 RKMP in tibial artery in GTEx [Release V6]) and more abundant in arterial than adipose tissue where it was initially characterized."
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Provides a specificity control for antibody Sigma HPA026810, the same antibody behind HPA's immunofluorescence call and therefore behind the GO:0005654 IDA row: it gives no signal in any mouse tissue, the species lacking the gene.
"Finally, mouse did not stain for LPHN2/ADGRL2 in lung non-vascular SMC or for ADIRF in any tissue."
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ADIRF has no clear paralogue, so no functional redundancy can compensate for its absence in the mouse lineage - independently confirmed here, since the only other human PTHR39227 entry, Q5TBU5, is an unreviewed TrEMBL duplicate with the identical 76-aa sequence.
"The chances that ADIRF could result in functional changes is increased because it appears to encode a protein with no clear paralogs."
Adipose most abundant 2 protein is a predictive marker for cisplatin sensitivity in cancers.
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Measures ADIRF/APM2 in human serum by ELISA at microgram-per-millilitre concentrations in 139 patients, independently corroborating that the protein reaches an extracellular fluid - a route absent from GOA.
"cut-off value was determined as 18.7 µg/mL, with a sensitivity and specificity of 84.0% and 71.7%, respectively"
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The authors treat secretion into the blood as a premise for their assay design rather than demonstrating it, so this paper establishes that ADIRF is present in serum but not how it gets there - and the protein has no signal peptide or transmembrane segment.
"To determine serum APM2 concentration as a potential biomarker of CDDP sensitivity, as it is secreted into the blood stream, the APM2 serum level was tested with ELISA in 71 HCC patients who were treated with CDDP intra-arterial infusion"
Lipoaspirate fluid proteome: A preliminary investigation by LC-MS top-down/bottom-up integrated platform of a high potential biofluid in regenerative medicine.
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Detects intact ADIRF by top-down mass spectrometry in the acid-soluble fraction of lipoaspirate fluid, a third independent extracellular detection route and one from adipose tissue itself.
"adipogenesis regulatory factor, perilipin-1 fragments, and S100A6, along with their PTMs"
APM2 is a novel mediator of cisplatin resistance in a variety of cancer cell types regardless of p53 or MMR status.
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The second phenotype attributed to ADIRF: over-expression confers cisplatin resistance and silencing sensitises cancer cell lines. No molecular mechanism is identified, and no GO annotation exists or is proposed for it, because a drug-resistance phenotype is not a molecular function or a biological process the gene participates in.
"APM2 is a novel mediator of cisplatin resistance in a variety of cancer cell types regardless of p53 or MMR status."
Overexpression of C10orf116 promotes proliferation, inhibits apoptosis and enhances glucose transport in 3T3-L1 adipocytes.
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A third over-expression study in the same mouse 3T3-L1 line, reporting effects on proliferation, apoptosis and insulin-stimulated glucose uptake. No GO annotation is proposed from it: it shares the interpretive limit of PMID:23239344, being ectopic expression in a lineage with no ADIRF gene, and the reported effects are cellular phenotypes rather than the protein's own activity.
"Overexpression of C10orf116 promotes proliferation, inhibits apoptosis and enhances glucose transport in 3T3-L1 adipocytes."
Characterization of microRNA expression profiles in 3T3-L1 adipocytes overexpressing C10orf116.
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A fourth study, again over-expression in mouse 3T3-L1. Cited to establish the completeness of the claim that every functional experiment on ADIRF used this one heterologous system; no annotation is drawn from it.
"Characterization of microRNA expression profiles in 3T3-L1 adipocytes overexpressing C10orf116."
Circadian lncRNA ADIRF-AS1 binds PBAF and regulates renal clear cell tumorigenesis.
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Concerns ADIRF-AS1, a distinct antisense lncRNA gene at the ADIRF locus, not the ADIRF protein. Recorded to make the boundary explicit: 10 of the 37 PubMed records matching ADIRF in title or abstract are about this lncRNA, and none of ADIRF's eleven GOA rows cites any of them.
"Circadian lncRNA ADIRF-AS1 binds PBAF and regulates renal clear cell tumorigenesis."
Affinage mechanistic annotation for ADIRF (human)
ADIRF (Q15847) bioinformatics results
UniProtKB entry Q15847 (ADIRF_HUMAN)