Gene Ontology annotation through association of InterPro records with GO terms

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

PMID:15567149

Cloning, expression, and differentiation-dependent regulation of SMAF1 in adipogenesis.

The nuclear localization that seeded ADIG's nucleus annotations comes from an overexpressed SMAF1-EGFP fusion and was presented by the authors as suggestive only.

"Transfection and localization studies of a SMAF1-EGFP fusion construct indicate nuclear localization, suggestive of a possible regulatory role."
SMAF1 transcript accompanies both brown and white adipogenic conversion, establishing co-regulation with the adipocyte program rather than a demonstrated regulatory role.

"Northern blot analysis of brown and white adipogenic conversion reveals that expression of SMAF1 closely parallels emergence of an adipocyte phenotype"

PMID:26427354

Expression, regulation and functional assessment of the 80 amino acid Small Adipocyte Factor 1 (Smaf1) protein in adipocytes.

Adipogenin protein expression in adipocytes is wholly dependent on PPAR-gamma.

"siRNA studies reveal that expression of Smaf1 in adipocytes is wholly dependent on PPARγ"
The lipid droplet localization of adipogenin rests on immunolocalization of an overexpressed HA-tagged construct.

"immunolocalization studies using HA-tagged Smaf1 reveal enrichment at adipocyte lipid droplets"
Acute siRNA knockdown did not produce a triglyceride storage phenotype, in tension with the later knockout and structural work.

"Smaf1 does not have a major role in adipocyte triglyceride accumulation, lipolysis or insulin-stimulated pAkt induction"

PMID:33691105

Phenotypic characterization of Adig null mice suggests roles for adipogenin in the regulation of fat mass accrual and leptin secretion.

Adipogenin is required for adipogenesis in cultured adipocytes and for normal fat mass accrual in vivo.

"Data from Adig-deficient cells suggest that Adig is required for adipogenesis."
Adig null mice are leaner on a high-fat diet and in the ob/ob background.

"Adig-/- mice are leaner than wild-type mice when fed a high-fat diet and when crossed with Ob/Ob hyperphagic mice"
Adipogenin deficiency reduces fat-mass-adjusted plasma leptin and impairs leptin secretion from adipose explants.

"Adig deficiency also reduces fat-mass-adjusted plasma leptin levels and impairs leptin secretion from adipose explants"
Adipogenin is a transmembrane protein, not a soluble nuclear factor.

"Adipogenin (Adig) is an adipocyte-enriched transmembrane protein."

PMID:39211078

Adipogenin Dictates Adipose Tissue Expansion by Facilitating the Assembly of a Dodecameric Seipin Complex.

The preprint reported a thermogenic phenotype that does not appear in the published version: Adig overexpression elevating thermogenesis during cold exposure.

"It also elevates thermogenesis during cold exposure."
The preprint also reported impaired cold tolerance in adipocyte-specific Adig knockout mice, again absent from the published paper.

"In contrast, inducible adipocyte-specific Adig knockout mice manifest aberrant lipid droplet formation in brown adipose tissues and impaired cold tolerance."

PMID:37249025

Transcriptional regulation of adipogenin expression in liver steatosis by hepatic peroxisome proliferator-activated receptor gamma.

Hepatic PPAR-gamma binds a functional PPRE in the Adig promoter and drives Adig expression in liver steatosis, supporting the description's statement that ADIG is induced in steatotic liver.

"Adig was found to be highly expressed in various fatty liver mouse models."

PMID:27766294

Data on regulation of the gene for the adipocyte-enriched micropeptide Adig/Smaf1 by qPCR analysis and luciferase reporter assay.

Reporter and qPCR data establish PPAR-gamma/RXR-alpha regulation of the Adig promoter, supporting the PPAR-gamma-target framing used in the description.

"Luciferase reporter assays provide data for regulation of an ~ 2 kb fragment of the 5' flanking region of Adig/Smaf1 gene by PPARγ/RXRα."

PMID:42005040

Adipogenin-seipin, lipid droplet architecture and the expanding metabolic frontier: Implications for metabolic disorders and cancer.

A 2026 review of adipogenin-seipin and lipid droplet architecture, directly on the topic of this gene.

"By stabilizing a dodecameric seipin complex, adipogenin redirects triacylglycerol flux from LD nucleation to droplet expansion, thereby promoting LD enlargement, adipocyte hypertrophy and adipose tissue growth."

file:genes/human/ADIG/ADIG-deep-research-affinage.md

Affinage mechanistic annotation for ADIG (human)

Affinage's own mechanism profile assigns ADIG a regulator-type molecular activity and a lipid droplet location, and names seipin as its sole partner.

"**molecular_activity:** GO:0098772 molecular function regulator activity"
Affinage captured the seipin dodecamer mechanism only as an unpublished bioRxiv entry with no PMID, so the record understates the strength of the evidence now available.

"Adig directly interacts with seipin to form a rigid complex"

PMID:41196993

Adipogenin promotes the development of lipid droplets by binding a dodecameric seipin complex.

Adipogenin is a single-pass endoplasmic reticulum membrane protein with a cytosolic C-terminus, determined by ER-marker colocalization, APEX2 electron microscopy at near-endogenous levels, and protease protection.

"Thus, Adig is a single-pass ER protein with a cytosolic C-terminal tail"
The study explicitly set out to adjudicate the conflicting plasma membrane, nuclear and lipid droplet localizations reported previously.

"We next assessed the subcellular location of Adig because previous reports suggest different locations, including the plasma membrane (2), nuclei (3), and the surface of LDs (4)."
Seipin is the principal adipogenin interactor, identified as the top hit in unbiased pulldown mass spectrometry.

"The most enriched protein with substantial sequence coverage was seipin"
Adipogenin selectively binds the dodecameric seipin oligomer and promotes its assembly by bridging and stabilizing adjacent subunits.

"Adig selectively bound to the dodecameric form and enhanced seipin assembly by bridging and stabilizing adjacent subunits."
Adipogenin prevents seipin from aggregating, favouring functional complexes instead.

"Thus, when expressed with Adig, seipin appeared to form functional seipin-Adig complexes rather than seipin aggregates."
Adig-bound seipin complexes are mobile and do not form stable contacts with nascent lipid droplets, unlike Adig-free seipin complexes.

"they formed stable contacts with seipin complexes without Adig, while seipin-Adig complexes moved rapidly through their vicinity"
The seipin-adipogenin complex promotes lipid droplet development at early and late stages.

"Functionally, this complex promoted lipid droplet development at both early and late stages."
Adipocyte-specific Adig overexpression increases fat mass and enlarges droplets; Adig deletion disrupts triglyceride accumulation in brown adipose tissue.

"In transgenic mice, adipocyte-specific overexpression of Adig increased fat mass and enlarged lipid droplets, whereas Adig deletion disrupted triglyceride accumulation in brown adipose tissues."