Affinage mechanistic annotation for ADISSP (human) Affinage Affinage (Claude Sonnet reading pass + Opus synthesis pass) 5 citations

Affinage mechanistic annotation for ADISSP (human)

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Current model (mechanistic narrative)

ADISSP (C20orf27) is an adipose-specific secreted signaling protein that functions as an adipokine coupling adrenergic input to thermogenesis and glucose homeostasis PMID:36496438. Its expression is enriched in brown adipose tissue and its secretion is stimulated by β3-adrenergic activation PMID:36496438; once released, it binds a surface receptor on adipocytes and activates protein kinase A independently of β-adrenergic signaling to drive white adipose tissue browning PMID:36496438. Adipose-specific knockout impairs WAT browning and renders mice susceptible to high-fat diet-induced obesity and hyperglycemia, establishing ADISSP as a required upstream regulator of thermogenesis and glucose handling PMID:36496438. Recombinant ADISSP additionally activates insulin-independent Akt signaling in white fat to promote glucose disposal and normalize hyperglycemia in type 1 and type 2 diabetic models PMID:42030391. In cancer settings, ADISSP interacts with the catalytic subunit of protein phosphatase 1 (PP1c) and promotes colorectal cancer cell proliferation through activation of the TGFβR-TAK1-NFκB cascade PMID:32024300. The identity of its adipocyte surface receptor and the molecular route from receptor engagement to PKA and Akt activation have not been characterized in the available corpus.

Affinage mechanism profile (its own GO/Reactome grounding)

Recorded for reference. The AIGR evaluation found this grounding is coarse (collapses to general parents) and can contradict the narrative — do not import these GO ids directly; re-ground from the narrative + PMIDs.

Dated findings (citation-anchored)

Year Confidence Finding PMIDs Journal
2022 Medium Adissp (C20orf27/FLJ20550) is an adipose-secreted signaling protein whose expression is adipose-specific and highly enriched in brown adipose tissue (BAT); its secretion is stimulated by β3-adrenergic activation. PMID:36496438 Nature Communications
2022 Medium Adissp binds to a putative receptor on the adipocyte surface and activates protein kinase A (PKA) independently of β-adrenergic signaling, promoting white adipose tissue (WAT) browning/thermogenesis. PMID:36496438 Nature Communications
2022 High Adipose-specific Adissp knockout mice are defective in WAT browning and are susceptible to high-fat diet-induced obesity and hyperglycemia, establishing Adissp as a required upstream regulator of thermogenesis and glucose homeostasis. PMID:36496438 Nature Communications
2026 Medium Recombinant Adissp (rAdissp) protein activates insulin-independent Akt signaling in white fat to stimulate glucose disposal, normalizing hyperglycemia in both type 1 and type 2 diabetic mouse models. PMID:42030391 Science Advances
2020 Medium C20orf27 (ADISSP) promotes colorectal cancer cell growth and proliferation by interacting with PP1c (the catalytic subunit of type 1 phosphatase) and activating the TGFβR-TAK1-NFκB signaling cascade; NFκB inhibition reverses this effect. PMID:32024300 Cancers
2025 Low C20orf27 (ADISSP) promotes hepatocellular carcinoma cell proliferation and migration by regulating cyclin-related proteins (MDM2, PCNA, Cyclin E1, CDK2, p-Rb) and acts upstream of NT5E as a downstream target. PMID:40690096 Discover Oncology
2025 Low C20orf27 (ADISSP) mediates colorectal cancer cell proliferation through XBP1 signaling under normal lipid conditions, but switches to promoting metastasis via MST1 signaling under high-lipid conditions, demonstrating context-dependent pathway utilization. PMID:40876696 Cellular Signalling

Citations