Affinage

AZGP1

Zinc-alpha-2-glycoprotein · UniProt P25311

Length
298 aa
Mass
34.3 kDa
Annotated
2026-06-09
100 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AZGP1 (zinc-alpha-2-glycoprotein, ZAG) is a secreted MHC class I-like glycoprotein, structurally resembling a class I MHC heavy chain but lacking beta2-microglobulin binding, whose groove accommodates a nonpeptidic lipid-related ligand consistent with a role in lipid catabolism (PMID:10206894). It is encoded on chromosome 7q22, distinct from classical MHC genes (PMID:8162703). As a metabolic effector, ZAG binds beta3- and beta2-adrenergic receptors (but not beta1-AR) with nanomolar affinity to stimulate cAMP production, and its anti-obesity, lipolytic, and insulin-sensitizing actions are abolished by propranolol, establishing a beta-AR-mediated mechanism (PMID:22227600, PMID:21245862). Through this axis ZAG induces uncoupling proteins (UCP-1, UCP-2 via beta3-AR/cAMP; UCP-3 via MAPK) (PMID:15246563) and drives white adipose tissue browning by promoting PPARgamma/EBF2 recruitment to the Prdm16 promoter and PPARgamma/PGC-1alpha recruitment to the Ucp1 promoter (PMID:29570397). In hypothalamic POMC neurons, AZGP1 enhances leptin-JAK2-STAT3 signaling by binding acylglycerol kinase (AGK) and blocking its ubiquitination, increasing neuronal excitability and regulating whole-body energy homeostasis (PMID:38643150). AZGP1 also acts broadly as a tumor suppressor and anti-fibrotic factor: it blocks TGF-beta1-mediated ERK2 phosphorylation to suppress epithelial-mesenchymal transition in pancreatic and hepatocellular carcinoma (PMID:20581862, PMID:26902423), inhibits proliferation, glycolysis, and angiogenesis (PMID:24918753, PMID:38659028, PMID:41535762), and signals additionally through PTEN/Akt, mTOR/FASN, TGF-beta1/Smad3, and PI3K/AKT pathways (PMID:27993894, PMID:24918753, PMID:37669935, PMID:40305469). Its expression is tightly controlled at multiple levels: transcriptionally by the androgen receptor and Ikaros (PMID:30820960, PMID:27993894), epigenetically by histone deacetylation and promoter methylation (PMID:18978557, PMID:41535762), post-transcriptionally by the MIR155HG/miR-155 axis (PMID:38729323), and post-translationally by TRIM25-mediated ubiquitination and proteasomal degradation (PMID:38183356, PMID:37927217).

Mechanistic history

Synthesis pass · year-by-year structured walk · 26 steps
  1. 1994 High

    Establishing the genomic location of AZGP1 separated it from the classical MHC locus despite structural similarity, framing it as an evolutionarily transposed MHC-like gene.

    Evidence Fluorescent in situ hybridization mapping to chromosome 7q22

    PMID:8162703

    Open questions at the time
    • Does not address protein function
    • No regulatory or expression context
  2. 1999 High

    The crystal structure answered what kind of molecule ZAG is, revealing an MHC class I-like fold with a groove holding a nonpeptidic ligand and no beta2-microglobulin, pointing toward a lipid-handling rather than antigen-presenting role.

    Evidence X-ray crystallography at 2.8 Å resolution

    PMID:10206894

    Open questions at the time
    • Identity of the bound nonpeptidic ligand not determined
    • No cellular receptor or pathway established
    • Functional link to lipid catabolism inferred, not demonstrated
  3. 2004 Medium

    Linked ZAG to thermogenic effector output by showing it induces distinct uncoupling proteins through separable beta3-AR/cAMP and MAPK pathways.

    Evidence In vitro adipocyte/myotube assays with pharmacological receptor antagonism

    PMID:15246563

    Open questions at the time
    • Direct ZAG-receptor binding not shown here
    • Single lab, in vitro only
  4. 2008 High

    Defined the ZAG-PIP physical interaction at atomic resolution, identifying a direct protein binding partner via the alpha3 domain.

    Evidence X-ray crystallography of the complex purified from seminal plasma

    PMID:18930737

    Open questions at the time
    • Functional consequence of ZAG-PIP binding not established
    • Physiological context of the interaction unclear
  5. 2008 High

    Showed ZAG suppresses epithelial cell proliferation in kidney and that its loss alters tissue repair, an early indication of a growth-suppressive role.

    Evidence Primary cell culture, siRNA knockdown in vitro and in vivo, ischemia/reperfusion model

    PMID:18815245

    Open questions at the time
    • Molecular mediator of anti-proliferative effect not identified
    • Receptor dependence not tested
  6. 2008 Medium

    Identified histone deacetylation, rather than DNA methylation, as the dominant epigenetic mechanism silencing AZGP1 in lung adenocarcinoma.

    Evidence HDAC inhibitor (TSA) and demethylating agent treatment with qPCR in two cell lines

    PMID:18978557

    Open questions at the time
    • Specific HDAC/transcription factor not identified
    • Two cell lines only
  7. 2010 High

    Established AZGP1 as a tumor suppressor that blocks TGF-beta-mediated ERK2 phosphorylation to suppress EMT, providing the first mechanistic anti-cancer pathway.

    Evidence siRNA knockdown, recombinant protein rescue, TGF-beta blockade, EMT marker and invasion assays in pancreatic cancer cells

    PMID:20581862

    Open questions at the time
    • How secreted AZGP1 signals to block ERK2 not defined
    • Receptor mediating the effect unknown
  8. 2010 Medium

    Showed adipocytes are the primary cellular source of ZAG and that inflammatory cytokines suppress its production, defining inflammatory control of ZAG in adipose tissue.

    Evidence Macrophage-conditioned medium and TNF-alpha treatment with RT-PCR, Western, ELISA

    PMID:20595026

    Open questions at the time
    • Transcriptional mediators of cytokine suppression not defined
    • Single lab
  9. 2011 High

    Identified the beta3- and beta2-adrenergic receptors as direct ZAG receptors and confirmed beta-AR dependence of its metabolic effects in vivo, providing the central signaling mechanism.

    Evidence Radioligand binding with Kd determination, cAMP assay in transfected CHO-K1 cells, propranolol antagonism in ob/ob mice

    PMID:22227600

    Open questions at the time
    • Structural basis of ZAG-beta-AR binding not resolved
    • Relationship between the groove ligand and receptor binding unclear
  10. 2011 Medium

    Demonstrated ZAG directly stimulates adipocyte lipolysis and correlated elevated ZAG with cancer cachexia, linking molecular activity to a wasting phenotype.

    Evidence In vitro lipolysis assay with recombinant ZAG and ex vivo tissue secretion measurement

    PMID:21245862

    Open questions at the time
    • Causality in human cachexia not established
    • Single lab
  11. 2012 Medium

    Localized a beta-AR-mediated site of oral ZAG action to the gastrointestinal tract and showed ZAG can amplify endogenous ZAG levels.

    Evidence Oral ZAG administration in ob/ob mice with propranolol antagonism and GI gene expression

    PMID:22903615

    Open questions at the time
    • Mechanism of endogenous ZAG induction not defined
    • Single lab
  12. 2014 Medium

    Connected AZGP1 tumor suppression to metabolic reprogramming, showing it suppresses mTOR signaling and FASN-driven fatty acid synthesis.

    Evidence Overexpression with mTOR/FASN pathway Westerns, proliferation, cell cycle, and migration assays in colorectal cancer cells

    PMID:24918753

    Open questions at the time
    • No endogenous rescue experiment
    • Upstream link to receptor signaling not shown
  13. 2016 Medium

    Independently replicated the TGF-beta1/ERK2/EMT tumor suppressor axis in hepatocellular carcinoma and demonstrated anti-metastatic activity in vivo.

    Evidence Overexpression/knockdown, phospho-ERK2 Western, invasion assay, xenograft metastasis model

    PMID:26902423

    Open questions at the time
    • Receptor/signaling intermediary upstream of ERK2 not defined
    • Single lab
  14. 2017 Medium

    Identified Ikaros as a transcriptional activator of AZGP1 via a histone-acetylation feedback loop and extended its anti-invasive signaling to PTEN/Akt and CD44s pathways.

    Evidence ChIP, promoter reporter, HDAC inhibitor treatment, overexpression/knockdown in HCC

    PMID:27993894

    Open questions at the time
    • Direct vs indirect regulation of PTEN/Akt not resolved
    • Single lab
  15. 2018 High

    Defined the transcriptional program of ZAG-induced adipose browning, showing recruitment of PPARgamma/EBF2 and PPARgamma/PGC-1alpha to the Prdm16 and Ucp1 promoters.

    Evidence ChIP, MEF differentiation, recombinant protein treatment, in vivo tumor model

    PMID:29570397

    Open questions at the time
    • Link from beta-AR/cAMP signaling to these transcription factors not fully traced
    • Single lab
  16. 2019 High

    Established AZGP1 as a direct androgen receptor target through functional AREs, and showed it promotes G1/S transition via cyclin D1, adding a context-dependent proliferative role.

    Evidence ChIP-Seq, dual-luciferase reporter with ARE mutagenesis, cell cycle analysis, xenotransplantation

    PMID:30820960

    Open questions at the time
    • Reconciliation with anti-proliferative roles in other tissues unresolved
    • Mechanism of cyclin D1 induction not defined
  17. 2022 Medium

    Demonstrated anti-fibrotic protection in kidney disease linked to improved lipid metabolism and fatty acid oxidation, extending AZGP1 function to tissue fibrosis.

    Evidence Recombinant AZGP1 treatment and proximal-tubule transgenic overexpression in a UUO fibrosis model

    PMID:35054830

    Open questions at the time
    • Receptor/signaling pathway mediating anti-fibrotic effect not defined
    • Single lab
  18. 2023 Medium

    Showed lenvatinib upregulates AZGP1 via promoter H3K27 acetylation and that AZGP1 mediates EMT inhibition through TGF-beta1/Smad3, integrating drug response with the tumor suppressor axis.

    Evidence Drug target identification, ChIP for H3K27Ac, AZGP1-dependent rescue, Smad3 phospho-Westerns in cholangiocarcinoma

    PMID:37669935

    Open questions at the time
    • Whether lenvatinib effect is fully AZGP1-dependent in vivo not resolved
    • Single lab
  19. 2024 Medium

    Identified TRIM25 as the E3 ligase driving AZGP1 ubiquitination and proteasomal degradation, providing post-translational control of AZGP1 abundance, replicated across cholangiocarcinoma and breast cancer.

    Evidence Co-immunoprecipitation, ubiquitination assays, TRIM25 knockdown, and functional reversal in two cancer types

    PMID:37927217 PMID:38183356

    Open questions at the time
    • Ubiquitination site(s) on AZGP1 not mapped
    • Single Co-IP-based interaction per study
    • Regulation of TRIM25 activity not addressed
  20. 2024 High

    Defined a central mechanism for AZGP1 in energy homeostasis, showing it stabilizes acylglycerol kinase to enhance leptin-JAK2-STAT3 signaling in POMC neurons.

    Evidence POMC-specific conditional KO/OE, Co-IP of AZGP1-AGK, STAT3 phosphorylation, electrophysiology, metabolic phenotyping

    PMID:38643150

    Open questions at the time
    • How extracellular/secreted AZGP1 acts intracellularly on AGK not reconciled
    • Relationship to beta-AR signaling unclear
  21. 2024 High

    Showed AZGP1 directly inhibits angiogenesis, with deficiency increasing prostate vessel density and overexpression suppressing endothelial function and microvessel density.

    Evidence AZGP1 KO mice, xenograft overexpression, HUVEC functional assays, proteomics

    PMID:38659028

    Open questions at the time
    • Direct molecular target on endothelial cells not identified
    • Causal role of proteomic hits not tested
  22. 2024 High

    Revealed a context-dependent pro-inflammatory role, where AZGP1 aggravates macrophage M1 polarization and pyroptosis via NLRP3/caspase-1 in periodontitis.

    Evidence AAV overexpression and Azgp1-/- mice, BMDM assays, NLRP3/caspase-1 inhibitor rescue

    PMID:38491721

    Open questions at the time
    • Mechanism connecting AZGP1 to NLRP3 activation not defined
    • Apparent contradiction with anti-inflammatory roles elsewhere unresolved
  23. 2024 Medium

    Added post-transcriptional control, showing the MIR155HG/miR-155 axis directly targets the AZGP1 3'UTR to regulate inflammatory and fibrotic output.

    Evidence Dual-luciferase 3'UTR assay, miR-155 overexpression, AZGP1 rescue in hypertrophic scar fibroblasts

    PMID:38729323

    Open questions at the time
    • In vivo relevance of the axis not established
    • Single lab
  24. 2025 Medium

    Extended anti-fibrotic/anti-EMT function to retinal pigment epithelium via PI3K/AKT regulation and demonstrated in vivo efficacy of recombinant AZGP1.

    Evidence RNA-seq, AZGP1 KD/OE in ARPE-19 cells, PI3K/AKT Westerns, intravitreal rAZGP1 in laser-induced SRF model

    PMID:40305469

    Open questions at the time
    • Receptor coupling AZGP1 to PI3K/AKT not identified
    • Single lab
  25. 2025 Medium

    Connected adipocyte AZGP1 to metabolic-immune crosstalk, showing its loss aggravates insulin resistance and M1 polarization, with ZAG acting via beta3-AR/PKA/STAT3 in macrophages.

    Evidence Adipocyte-specific KO mice on high-fat diet, in vitro macrophage polarization with pharmacological dissection

    PMID:40068519

    Open questions at the time
    • Reconciliation with pro-M1 role in periodontitis not addressed
    • Single lab
  26. 2026 Medium

    Showed promoter methylation silences AZGP1 in prostate cancer and that AZGP1 suppresses aerobic glycolysis, linking epigenetic loss to metabolic reprogramming and metastasis.

    Evidence Methylation-specific PCR, Seahorse ECAR/OCR, lactate assays, transcriptomics, metastasis models

    PMID:41535762

    Open questions at the time
    • Direct molecular link between AZGP1 and glycolytic enzymes not defined
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How AZGP1's structural groove ligand, its secreted-protein status, and its beta-AR receptor binding are mechanistically unified across its disparate metabolic, tumor-suppressive, anti-fibrotic, and pro-inflammatory roles remains unresolved, as does how a secreted protein acts on intracellular partners such as AGK.
  • Identity of the native groove ligand unknown
  • Tissue-context determinants of opposing inflammatory roles undefined
  • Mechanism of intracellular action by a secreted protein unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 2 GO:0098772 molecular function regulator activity 2 GO:0008289 lipid binding 1
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 2
Partners
ADRB2ADRB3AGKPIPTRIM25

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Crystal structure of ZAG solved at 2.8 Å resolution, revealing it resembles a class I MHC heavy chain but does not bind beta2-microglobulin. The ZAG groove (analogous to MHC peptide-binding groove) contains a nonpeptidic compound, suggesting a role in lipid catabolism. X-ray crystallography Science High 10206894
2008 Crystal structure of the ZAG–PIP (prolactin-inducible protein) complex purified from human seminal plasma determined by X-ray crystallography; PIP's beta-structure aligns with the alpha3 domain of ZAG forming a long interface stabilized by 12 hydrogen bonds and 3 salt bridges, with a buried area of ~914 Ų. X-ray crystallography; protein purification from seminal plasma Journal of Molecular Biology High 18930737
2004 ZAG induces uncoupling protein (UCP) expression in adipose and muscle cells: UCP-1 in brown adipose tissue via beta3-adrenergic receptor (beta3-AR)/cAMP pathway; UCP-2 in C2C12 myotubes via beta3-AR/cAMP; UCP-3 in myotubes via MAPK (not beta3-AR). In vitro cell culture assays; pharmacological receptor antagonism (SR59230A, IBMX); concentration-response Cancer Letters Medium 15246563
2010 AZGP1 suppresses TGF-beta-mediated EMT in pancreatic cancer cells by blocking TGF-beta-mediated ERK2 phosphorylation. Silencing AZGP1 increases invasiveness and induces mesenchymal markers (vimentin, integrin-alpha5) while reducing epithelial markers (CDH1, desmoplakin, keratin-19). AZGP1 expression is epigenetically silenced by histone deacetylation. siRNA knockdown; recombinant ZAG treatment; Western blot for EMT markers; invasion assay; TGF-beta blockade; PCR array Oncogene High 20581862
2011 ZAG binds to the beta3-adrenergic receptor (Kd 46 nM) and beta2-AR (Kd 71 nM) but not beta1-AR in CHO-K1 cells transfected with human beta-ARs, and stimulates cAMP production. Anti-obesity and anti-diabetic effects of ZAG in ob/ob mice (weight loss, improved glucose tolerance, insulin sensitivity, glucose transport) are abolished by propranolol, confirming beta-AR-mediated mechanism. Radioligand binding assay; cAMP assay in transfected CHO-K1 cells; pharmacological antagonism in ob/ob mice; oral glucose tolerance test Biochimica et Biophysica Acta High 22227600
2008 Recombinant Zag suppresses proliferation of primary renal epithelial cells, while siRNA knockdown of Zag increases proliferation. In vivo siRNA-mediated Zag suppression in aged mice increases epithelial cell proliferation after renal ischemia/reperfusion but also increases parenchymal fibrosis. Primary cell culture; siRNA knockdown in vitro and in vivo; ischemia/reperfusion model; BrdU proliferation assay Journal of the American Society of Nephrology High 18815245
2018 ZAG induces white adipose tissue (WAT) browning in mice by stimulating PPARgamma and EBF2 expression, promoting their recruitment to the Prdm16 promoter, inducing Prdm16 expression. In brown adipose tissue, ZAG promotes PPARgamma and PGC-1alpha and their recruitment to the Ucp1 promoter, increasing Ucp1 expression. Cell implantation tumor model; MEF differentiation; ChIP assay; recombinant protein treatment; gene expression analysis FASEB Journal High 29570397
2016 AZGP1 suppresses EMT and hepatic carcinogenesis by blocking TGF-beta1-mediated ERK2 phosphorylation in hepatocellular carcinoma cells, reducing mesenchymal markers and inhibiting cell invasion in vitro; local AZGP1 injection in vivo significantly inhibits lung metastasis. In vitro overexpression/knockdown; phospho-ERK2 Western blot; invasion assay; in vivo xenograft metastasis model Cancer Letters Medium 26902423
2017 Transcription factor Ikaros binds to the AZGP1 promoter and transactivates its expression in HCC cells. Downregulation of AZGP1 in HCC is associated with histone deacetylation. Positive feedback between H4 acetylation-mediated Ikaros transactivation and Ikaros-mediated H4 acetylation regulates AZGP1 expression. AZGP1 inhibits HCC cell migration and invasion through regulation of PTEN/Akt and CD44s pathways. ChIP assay; promoter reporter assay; histone deacetylase inhibitor treatment; overexpression/knockdown; in vitro and in vivo functional assays Carcinogenesis Medium 27993894
2019 AZGP1 is an androgen-responsive gene regulated by the androgen receptor (AR): ChIP-Seq identifies canonical androgen-responsive elements (AREs) at the AZGP1 enhancer, and dual-luciferase reporter assays show AREs are highly responsive to androgen; mutations in AREs abolish reporter activity. AZGP1 promotes G1/S phase transition by increasing cyclin D1 levels. ChIP-Seq; dual-luciferase reporter assay with ARE mutagenesis; RT-PCR and Western blot; flow cytometry cell cycle analysis; xenotransplantation Journal of Cellular Physiology High 30820960
2014 AZGP1 overexpression in LoVo colorectal cancer cells suppresses mTOR pathway activation and FASN-regulated endogenous fatty acid synthesis, reducing proliferation, inducing G2 arrest and apoptosis, and decreasing migration. Plasmid transfection; Western blot for p-mTOR, p-S6, S6K1, eIF4E, FASN; MTT assay; flow cytometry; Transwell migration assay PLoS One Medium 24918753
2010 Macrophage-conditioned medium and TNF-alpha suppress ZAG mRNA expression and protein secretion by human adipocytes, while ZAG is produced primarily by mature adipocytes (not preadipocytes or macrophages), identifying macrophage-associated inflammation as a regulator of ZAG in adipose tissue. Macrophage-conditioned medium treatment; TNF-alpha treatment; RT-PCR; Western blot; ELISA Molecular and Cellular Endocrinology Medium 20595026
2024 AZGP1 in hypothalamic POMC neurons regulates whole-body energy homeostasis: POMC-specific overexpression of Azgp1 reduces food intake, raises energy expenditure, improves leptin and insulin sensitivity, reduces liver steatosis, and promotes adipose browning under high-fat diet. Mechanistically, AZGP1 enhances leptin-JAK2-STAT3 signaling by interacting with acylglycerol kinase (AGK) to block its ubiquitination and degradation, increasing POMC neuron excitability. POMC neuron-specific conditional knockout and overexpression (inducible); co-immunoprecipitation (AZGP1-AGK interaction); STAT3 phosphorylation assay; electrophysiology; metabolic phenotyping Nature Communications High 38643150
2024 AZGP1 interacts with TRIM25 (tripartite motif-containing protein 25) via co-immunoprecipitation. TRIM25 catalyzes ubiquitination of AZGP1, promoting its proteasomal degradation. TRIM25 knockdown leads to AZGP1 upregulation and induces cholangiocarcinoma cell apoptosis. AZGP1 overexpression suppresses tumor growth in xenograft models. Co-immunoprecipitation; ubiquitination assay; TRIM25 knockdown; overexpression; xenograft mouse model; tissue microarray Journal of Cellular and Molecular Medicine Medium 38183356
2024 AZGP1 deficiency in mouse prostate promotes angiogenesis in vivo (increased vessel density by 6 months in AZGP1-/- mice). AZGP1 overexpression in xenograft tumors decreases microvessel density. AZGP1 directly inhibits human umbilical vein endothelial cell proliferation, migration, tubular formation, and branching in vitro. Proteomics of AZGP1-overexpressing xenografts identifies enrichment of angiogenesis pathway proteins (YWHAZ, EPHA2, SERPINE1, PDCD6, MMP9, etc.). AZGP1 KO mice (histological analysis); lentiviral overexpression in xenografts; in vitro HUVEC functional assays; proteomics; tissue microarray Journal of Translational Medicine High 38659028
2023 AZGP1 interacts with lenvatinib as a key target in intrahepatic cholangiocarcinoma (ICC). Lenvatinib increases H3K27Ac acetylation at the AZGP1 promoter to upregulate AZGP1 expression. AZGP1, in turn, inhibits ICC EMT by regulating the TGF-beta1/Smad3 signaling pathway in an AZGP1-dependent manner. Drug target identification; ChIP for H3K27Ac at AZGP1 promoter; AZGP1 knockdown rescue experiments; Western blot for Smad3 phosphorylation; in vitro and in vivo models Cell Death & Disease Medium 37669935
2008 AZGP1 expression in lung adenocarcinoma cell lines is regulated by histone deacetylation: treatment with trichostatin A (TSA, HDAC inhibitor) induced 713-fold and 169-fold increase in AZGP1 mRNA in A549 and SKLU1 cells, respectively, while 5-aza-2'-deoxycytidine (demethylating agent) had minimal effect. Cell line treatment with TSA and 5-AZA; real-time PCR; Western blot Journal of Thoracic Oncology Medium 18978557
2011 Recombinant ZAG stimulates lipolysis in human adipocytes in vitro, and ZAG expression and secretion by subcutaneous adipose tissue is elevated in cachectic cancer patients correlating with weight loss and serum glycerol levels. In vitro lipolysis assay with recombinant ZAG; ZAG secretion measurement from ex vivo adipose tissue; correlation analysis British Journal of Cancer Medium 21245862
2012 Oral ZAG administration in ob/ob mice increases endogenous murine ZAG serum levels through interaction with beta-adrenergic receptors in the gastrointestinal tract (particularly esophagus), as effects on body weight, temperature, urinary glucose, and insulin sensitivity are abolished by co-administration of propranolol. Tryptic digestion inactivates ZAG. Oral ZAG administration in ob/ob mice; pharmacological antagonism (propranolol); ELISA for serum ZAG; gene expression in GI tissues Endocrinology Medium 22903615
2024 AZGP1 aggravates macrophage M1 polarization and pyroptosis in periodontitis through NLRP3/caspase-1 signaling. AAV-mediated Azgp1 overexpression in the periodontium enhances M1 macrophage proportion and pyroptosis markers; Azgp1-/- mice show opposite effects. NLRP3 or caspase-1 inhibition rescues the effects of Azgp1 overexpression. AAV overexpression in vivo; Azgp1-/- knockout mice; BMDM cell assays (LPS and PA stimulation); NLRP3/caspase-1 inhibitor rescue; conditioned medium on hPDLSCs Journal of Dental Research High 38491721
2025 AZGP1 inhibits EMT in retinal pigment epithelial (RPE) cells and subretinal fibrosis by regulating the PI3K/AKT signaling pathway. Knockdown and overexpression studies in ARPE-19 cells confirm AZGP1 modulates PI3K/AKT activity. Intravitreal injection of recombinant AZGP1 in a laser-induced SRF mouse model reduces collagen I, CD31-positive area, and fibrosis markers. RNA-seq of RPE/choroid; AZGP1 KD and OE in ARPE-19 cells; Western blot for PI3K/AKT; intravitreal rAZGP1 injection in mice; immunofluorescence Investigative Ophthalmology & Visual Science Medium 40305469
2022 AZGP1 has protective anti-fibrotic effects in kidney disease: recombinant AZGP1 treatment in mice with unilateral ureteric obstruction preserves tubular integrity, reduces collagen deposition and fibrosis markers, and reduces stress-induced tubular lipid droplet accumulation by improving lipid metabolism/fatty acid oxidation gene expression. Recombinant AZGP1 systemic treatment; conditional transgenic AZGP1 overexpression in proximal tubular cells; UUO fibrosis model; histology; gene expression International Journal of Molecular Sciences Medium 35054830
2024 TRIM25 promotes ubiquitination and degradation of AZGP1 in breast cancer, identified through co-immunoprecipitation. AZGP1 knockdown promotes breast cancer cell proliferation, migration, and invasion in vitro and in vivo. TRIM25 overexpression partially reverses the pro-tumorigenic effects of AZGP1 overexpression. Co-immunoprecipitation; ubiquitination assay; AZGP1 knockdown and overexpression; in vitro and in vivo functional assays Environmental Toxicology Medium 37927217
2026 Promoter methylation (at cg26429636 region) silences AZGP1 transcription in prostate cancer cells, and low AZGP1 expression is associated with upregulated glycolysis (elevated L-lactic acid production, higher ECAR, reduced OCR). AZGP1 overexpression reduces glycolysis, suggesting AZGP1 suppresses aerobic glycolysis to inhibit metastasis. Methylation-specific PCR (MSP); ECAR/OCR measurement (Seahorse); L-lactic acid assay; single-cell and bulk transcriptomics; in vitro and in vivo metastasis models Cellular & Molecular Biology Letters Medium 41535762
2025 Adipocyte-specific AZGP1 ablation aggravates insulin resistance and adipose tissue inflammation by increasing M1 macrophage proportion and inhibiting AKT signaling in mice on high-fat diet. Exogenous ZAG inhibits palmitic acid-induced M1 macrophage polarization via beta3-AR/PKA/STAT3 signaling in RAW264.7 macrophages. Adipocyte-specific AZGP1 KO mice; high-fat diet metabolic phenotyping; in vitro macrophage polarization assay with pharmacological dissection; Western blot for AKT/STAT3 phosphorylation International Immunopharmacology Medium 40068519
2024 MIR155HG/miR-155-5p/-3p axis targets AZGP1 through direct binding to the AZGP1 3'UTR (confirmed by dual-luciferase assay). miR-155-5p/-3p suppress AZGP1, and AZGP1 overexpression rescues inhibition of inflammatory cytokine production (IL-1beta, IL-6) and alpha-SMA expression induced by miR-155 overexpression in hypertrophic scar fibroblasts. Dual-luciferase reporter assay; miR-155 overexpression; AZGP1 plasmid rescue; qRT-PCR; Western blot Cellular Signalling Medium 38729323
1994 The human AZGP1 gene was mapped to chromosome 7q22 by fluorescent in situ hybridization (FISH), distinct from classical MHC genes on chromosome 6, indicating evolutionary transposition events. Fluorescent in situ hybridization (FISH) Cytogenetics and Cell Genetics High 8162703
2024 ZAG promotes white adipose tissue progenitor cell differentiation toward fibrosis (not adipogenesis) in triple-negative breast cancer: TNBC-secreted ZAG inhibits adipogenesis and instead induces fibrotic gene expression in adipose stem and progenitor cells (ASPCs). ZAG depletion in TNBC cells attenuates fibrosis in white adipose tissue and inhibits tumor growth. Secretome screen of 10 breast cancer cell lines; ASPC differentiation assay; ZAG knockdown; gene expression analysis; in vivo tumor growth assay bioRxivpreprint Medium 38496643
2009 Recombinant ZAG stimulates adiponectin release from human differentiated adipocytes in vitro, establishing a functional link between ZAG and adiponectin production. Recombinant ZAG treatment of SGBS human adipocytes; ELISA for adiponectin Clinical Endocrinology Low 19549246
2024 AZGP1 functions as an RNA-binding protein (RBP) in lung epithelial cells, regulating alternative splicing events (including DDAH1 and SFRP1) and inhibiting AT2 cell proliferation by modulating expression of SAMD5, DNER, DPYSL3, GBP5, GBP3, and KCNJ2, as identified through scRNA-seq and bulk RNA-seq analyses in COPD. scRNA-seq (GSE173896); bulk RNA-seq (GSE124180); alternative splicing identification; differential gene expression analysis Gene Low 38950687

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2022 Thirty years of resistance: Zig-zag through the plant immune system. The Plant cell 637 35167697
1994 The three-dimensional architecture of chromatin in situ: electron tomography reveals fibers composed of a continuously variable zig-zag nucleosomal ribbon. The Journal of cell biology 179 8138564
2003 C. elegans ZAG-1, a Zn-finger-homeodomain protein, regulates axonal development and neuronal differentiation. Development (Cambridge, England) 114 12835394
1999 Crystal structure of human ZAG, a fat-depleting factor related to MHC molecules. Science (New York, N.Y.) 110 10206894
2009 The adipokine zinc-alpha2-glycoprotein (ZAG) is downregulated with fat mass expansion in obesity. Clinical endocrinology 97 19549246
2011 Enhanced ZAG production by subcutaneous adipose tissue is linked to weight loss in gastrointestinal cancer patients. British journal of cancer 95 21245862
1998 Chromatin conformation in living cells: support for a zig-zag model of the 30 nm chromatin fiber. Journal of molecular biology 92 9811543
2010 AZGP1 is a tumor suppressor in pancreatic cancer inducing mesenchymal-to-epithelial transdifferentiation by inhibiting TGF-β-mediated ERK signaling. Oncogene 87 20581862
2008 Zag expression during aging suppresses proliferation after kidney injury. Journal of the American Society of Nephrology : JASN 86 18815245
2018 The tumor secretory factor ZAG promotes white adipose tissue browning and energy wasting. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 75 29570397
2016 Small RNAs Add Zing to the Zig-Zag-Zig Model of Plant Defenses. Molecular plant-microbe interactions : MPMI 74 26867095
2008 ZAG, a lipid mobilizing adipokine, is downregulated in human obesity. Journal of physiology and biochemistry 64 18663996
2013 Additive effect of the AZGP1, PIP, S100A8 and UBE2C molecular biomarkers improves outcome prediction in breast carcinoma. International journal of cancer 60 24114735
2004 Effect of zinc-alpha2-glycoprotein (ZAG) on expression of uncoupling proteins in skeletal muscle and adipose tissue. Cancer letters 57 15246563
2008 Crystal structure of the novel complex formed between zinc alpha2-glycoprotein (ZAG) and prolactin-inducible protein (PIP) from human seminal plasma. Journal of molecular biology 56 18930737
2008 AZGP1 autoantibody predicts survival and histone deacetylase inhibitors increase expression in lung adenocarcinoma. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 50 18978557
2011 Role of β-adrenergic receptors in the anti-obesity and anti-diabetic effects of zinc-α2-glycoprotien (ZAG). Biochimica et biophysica acta 46 22227600
2010 Macrophage-secreted factors inhibit ZAG expression and secretion by human adipocytes. Molecular and cellular endocrinology 46 20595026
2016 AZGP1 suppresses epithelial-to-mesenchymal transition and hepatic carcinogenesis by blocking TGFβ1-ERK2 pathways. Cancer letters 44 26902423
2003 zag-1, a Zn-finger homeodomain transcription factor controlling neuronal differentiation and axon outgrowth in C. elegans. Development (Cambridge, England) 44 12835395
2017 Downregulation of AZGP1 by Ikaros and histone deacetylase promotes tumor progression through the PTEN/Akt and CD44s pathways in hepatocellular carcinoma. Carcinogenesis 37 27993894
2011 Low AZGP1 expression predicts for recurrence in margin-positive, localized prostate cancer. The Prostate 37 21432866
2023 CircNOLC1 Promotes Colorectal Cancer Liver Metastasis by Interacting with AZGP1 and Sponging miR-212-5p to Regulate Reprogramming of the Oxidative Pentose Phosphate Pathway. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 34 37870214
2017 Th17 and IL-17 Cause Acceleration of Inflammation and Fat Loss by Inducing α2-Glycoprotein 1 (AZGP1) in Rheumatoid Arthritis with High-Fat Diet. The American journal of pathology 34 28284716
2015 Reduced AZGP1 expression is an independent predictor of early PSA recurrence and associated with ERG-fusion positive and PTEN deleted prostate cancers. International journal of cancer 34 26383228
2012 A "zig-zag" naphthodithiophene core for increased efficiency in solution-processed small molecule solar cells. Chemical communications (Cambridge, England) 34 22822480
2009 Cigarette smoking induces overexpression of a fat-depleting gene AZGP1 in the human. Chest 34 19188554
2024 AZGP1 Aggravates Macrophage M1 Polarization and Pyroptosis in Periodontitis. Journal of dental research 28 38491721
2014 Circulating anti-inflammatory adipokines High Molecular Weight Adiponectin and Zinc-α2-glycoprotein (ZAG) are inhibited in early sepsis, but increase with clinical recovery: a pilot study. BMC anesthesiology 28 25580089
2019 AZGP1 is androgen responsive and involved in AR-induced prostate cancer cell proliferation and metastasis. Journal of cellular physiology 27 30820960
2024 AZGP1 in POMC neurons modulates energy homeostasis and metabolism through leptin-mediated STAT3 phosphorylation. Nature communications 26 38643150
1994 Mapping of the human Zn-alpha 2-glycoprotein gene (AZGP1) to chromosome 7q22 by in situ hybridization. Cytogenetics and cell genetics 26 8162703
2019 ZAG Regulates the Skin Barrier and Immunity in Atopic Dermatitis. The Journal of investigative dermatology 25 30738053
2016 Loss of Expression of AZGP1 Is Associated With Worse Clinical Outcomes in a Multi-Institutional Radical Prostatectomy Cohort. The Prostate 24 27325561
1999 Pulsed-field gel electrophoresis and distribution of the genes zag and fnz in isolates of Streptococcus equi. Research in veterinary science 24 10208886
2012 Adipocytokine zinc α2 glycoprotein (ZAG) as a novel urinary biomarker for normo-albuminuric diabetic nephropathy. Diabetic medicine : a journal of the British Diabetic Association 23 22211921
2014 The relationship between renal function and plasma concentration of the cachectic factor zinc-alpha2-glycoprotein (ZAG) in adult patients with chronic kidney disease. PloS one 21 25076420
2017 Albumin-binding domain from Streptococcus zooepidemicus protein Zag as a novel strategy to improve the half-life of therapeutic proteins. Journal of biotechnology 20 28549690
2023 LncRNA LINC01094 Promotes Cells Proliferation and Metastasis through the PTEN/AKT Pathway by Targeting AZGP1 in Gastric Cancer. Cancers 17 36831602
2018 Serum levels of the adipokine zinc-alpha2-glycoprotein (ZAG) predict mortality in hemodialysis patients. Kidney international 17 30348306
2012 Role of β-adrenergic receptors in the oral activity of zinc-α2-glycoprotein (ZAG). Endocrinology 17 22903615
2007 AZGP1 mRNA levels in normal human lung tissue correlate with lung cancer disease status. Oncogene 17 17724461
2018 ZAG alleviates HFD-induced insulin resistance accompanied with decreased lipid depot in skeletal muscle in mice. Journal of lipid research 16 30318474
2023 AZGP1 activation by lenvatinib suppresses intrahepatic cholangiocarcinoma epithelial-mesenchymal transition through the TGF-β1/Smad3 pathway. Cell death & disease 15 37669935
2014 AZGP-1 immunohistochemical marker in prostate cancer: potential predictive marker of biochemical recurrence in post radical prostatectomy specimens. Applied immunohistochemistry & molecular morphology : AIMM 15 24508823
2014 Biodistribution of a (67)Ga-labeled anti-TNF VHH single-domain antibody containing a bacterial albumin-binding domain (Zag). Nuclear medicine and biology 15 24530366
2014 Alpha-2-glycoprotein 1(AZGP1) regulates biological behaviors of LoVo cells by down-regulating mTOR signaling pathway and endogenous fatty acid synthesis. PloS one 15 24918753
2024 AZGP1 deficiency promotes angiogenesis in prostate cancer. Journal of translational medicine 14 38659028
2022 Adipose and serum zinc alpha-2-glycoprotein (ZAG) expressions predict longitudinal change of adiposity, wasting and predict survival in dialysis patients. Scientific reports 14 35641588
2017 A prospective multicentre phase III validation study of AZGP1 as a biomarker in localized prostate cancer. Annals of oncology : official journal of the European Society for Medical Oncology 14 28486686
2014 Regulation of C. elegans neuronal differentiation by the ZEB-family factor ZAG-1 and the NK-2 homeodomain factor CEH-28. PloS one 13 25474681
1994 Reversible conformational transition gives rise to 'zig-zag' temperature dependence of the rate constant of irreversible thermoinactivation of enzymes. European journal of biochemistry 12 8306989
2018 AZGP1 inhibits soft tissue sarcoma cells invasion and migration. BMC cancer 11 29357838
2016 Loss of AZGP1 as a Superior Predictor of Relapse in Margin-Positive Localized Prostate Cancer. The Prostate 11 27473574
2014 The complete mitochondrial genome of the Zig-zag eel Mastacembelus armatus (Teleostei, Mastacembelidae). Mitochondrial DNA. Part A, DNA mapping, sequencing, and analysis 11 24617467
2012 AZGP1 and SPDEF mRNA expression differentiates breast carcinoma from ovarian serous carcinoma. Virchows Archiv : an international journal of pathology 11 23242172
2020 Serum ZAG and Adiponectin Levels Were Closely Related to Obesity and the Metabolically Abnormal Phenotype in Chinese Population. Diabetes, metabolic syndrome and obesity : targets and therapy 10 32904655
2024 Blocking the MIR155HG/miR-155 axis reduces CTGF-induced inflammatory cytokine production and α-SMA expression via upregulating AZGP1 in hypertrophic scar fibroblasts. Cellular signalling 9 38729323
2023 AZGP1 as a potential biomarker of IgA vasculitis with nephritis in a children‑based urinary proteomics study by diaPASEF. Molecular medicine reports 9 37417365
2022 Adipokines as New Biomarkers of Immune Recovery: Apelin Receptor, RBP4 and ZAG Are Related to CD4+ T-Cell Reconstitution in PLHIV on Suppressive Antiretroviral Therapy. International journal of molecular sciences 9 35216318
2020 AZGP1 suppresses the process of colorectal cancer after upregulating FASN expression via mTOR signal pathway. General physiology and biophysics 9 32525817
2022 The Therapeutic Potential of Zinc-Alpha2-Glycoprotein (AZGP1) in Fibrotic Kidney Disease. International journal of molecular sciences 8 35054830
2013 Ultra-broadband performance enhancement of thin-film amorphous silicon solar cells with conformal zig-zag configuration. Optics letters 8 24281512
2025 Taurine and proline promote lung tumour growth by co-regulating Azgp1/mTOR signalling pathway. NPJ precision oncology 7 40155495
2024 Degradation of AZGP1 suppresses apoptosis and facilitates cholangiocarcinoma tumorigenesis via TRIM25. Journal of cellular and molecular medicine 7 38183356
2022 AZGP1 Up-Regulation is a Potential Target for Andrographolide Reversing Radioresistance of Colorectal Cancer. Pharmacogenomics and personalized medicine 7 36536885
2022 Characterization and expression analysis of the interferon regulatory factor (IRF) gene family in zig-zag eel (Mastacembelus armatus) against Aeromonas veronii infection. Developmental and comparative immunology 7 36543267
2020 Long non-coding RNA00844 inhibits MAPK signaling to suppress the progression of hepatocellular carcinoma by targeting AZGP1. Annals of translational medicine 7 33313110
2019 Zinc-α2-Glycoprotein (ZAG): A New Deficiency in Vitiligo Patients. Skinmed 7 31627786
2024 RNA-binding protein AZGP1 inhibits epithelial cell proliferation by regulating the genes of alternative splicing in COPD. Gene 6 38950687
2023 Degradation of AZGP1 suppresses the progression of breast cancer cells via TRIM25. Environmental toxicology 5 37927217
2019 Predictive value of AZGP1 following radical prostatectomy for prostate cancer: a cohort study and meta-analysis. Journal of clinical pathology 5 31331953
2013 Crosstalk in human brain between globoid cell leucodystrophy and zinc-α-2-glycoprotein (ZAG), a biomarker of lipid catabolism. Folia neuropathologica 5 24374959
2024 Multiple Tissues Transcriptome of Zig-Zag Eel (Mastacembelus armatus) with Different Growth Rates. Animals : an open access journal from MDPI 4 38254417
2022 Adipokine ZAG Alters Depression-Like Behavior by Regulating Oxidative Stress in Hippocampus. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 4 35255519
2021 Development of a prediction model for mortality and cardiovascular outcomes in older adults taking into account AZGP1. Scientific reports 4 34083628
2020 Unveiling the Dynamical Assembly of Magnetic Nanocrystal Zig-Zag Chains via In Situ TEM Imaging in Liquid. Small (Weinheim an der Bergstrasse, Germany) 4 32459051
1985 A back-to-back zig-zag model for higher order chromatin structure. Cytobios 4 4075844
2025 Adipocyte ZAG improves obesity-triggered insulin resistance by reshaping macrophages populations in adipose tissue. International immunopharmacology 3 40068519
2024 Multi-Omics Reveals the Effects of Spirulina platensis Powder Replacement of Fish Meal on Intestinal Metabolism and Stress in Zig-Zag Eel (Mastacembelus armatus). Antioxidants (Basel, Switzerland) 3 39061919
2024 Zig, Zag, and 'Zyme: leveraging structural biology to engineer disease resistance. aBIOTECH 3 39279864
2023 Effects of electroacupuncture on the glucose-lipid metabolism and the expression of ZAG and GLUT4 in the femoral quadriceps and adipose tissue in the rats with type 2 diabetes mellitus. Zhongguo zhen jiu = Chinese acupuncture & moxibustion 3 38092542
2020 New insights into the zinc-α2-glycoprotein (ZAG) scaffold and its metal ions binding abilities using spectroscopic techniques. Life sciences 3 32097664
2014 Zig-zag wall lattice in a nematic liquid crystal with an in-plane switching configuration. Physical review. E, Statistical, nonlinear, and soft matter physics 3 25215746
2024 Heavy metal exposure and its effects on APOC3, CFAI, and ZA2G. Journal of hazardous materials 2 39579699
2021 Changes in AZGP1 Serum Levels and Correlation With Pulse Wave Velocity After Kidney Transplantation. Frontiers in cardiovascular medicine 2 34291094
2013 Zig Zag versus Top Hat configuration in IntraLase-enabled penetrating keratoplasty. The British journal of ophthalmology 2 24081500
2008 [Polymorphisms of ZAG gene with growth traits in Jiaxian red cattle]. Yi chuan = Hereditas 2 19073549
2024 Zinc Alpha-2-Glycoprotein (ZAG/AZGP1) secreted by triple-negative breast cancer promotes tumor microenvironment fibrosis. bioRxiv : the preprint server for biology 1 38496643
2023 Down Regulation of EGF and AZGP1 Were Associated with Clinical Characteristics in Chronic Rhinosinusitis with Nasal Polyps: An Observation Study. Journal of inflammation research 1 37920240
2022 A study on serum pro-neurotensin (PNT), furin, and zinc alpha-2-glycoprotein (ZAG) levels in patients with acromegaly. Journal of endocrinological investigation 1 35670958
2022 [The plant immune system – zig-zag model]. Postepy biochemii 1 35792644
2021 Assessment of Zinc- alpha2 glycoprotein (ZAG) and Lipase Maturation Factor 1 (LMF1) concentration in children with chronic kidney disease. Physiological research 1 34062067
2012 Genotype and haplotype analysis of the AZGP1 gene in cattle. Molecular biology reports 1 23073769
1990 Chromatin higher-order structure: two-start double superhelix formed by zig-zag shaped nucleosome chain with folded linker DNA. Journal of biomolecular structure & dynamics 1 2275789
2026 Methylation-induced silencing of AZGP1 enhances prostate cancer metastasis by stimulating tumoral glycolysis. Cellular & molecular biology letters 0 41535762
2025 Evolutionary insights and expression patterns of sex-related gene families in the zig-zag eel Mastacembelus armatus. Comparative biochemistry and physiology. Part A, Molecular & integrative physiology 0 39756790
2025 AZGP1 Attenuates Subretinal Fibrosis and Inhibits Epithelial-Mesenchymal Transition by Blocking the PI3K/AKT Signaling Pathway. Investigative ophthalmology & visual science 0 40305469
2025 ET-1, MMPs, ZAG, and APN Link Reduced Ocular Perfusion to Glaucoma. Biomolecules 0 41154592
2024 ZAG promotes colorectal cancer cell proliferation and epithelial-mesenchymal transition by promoting lipid synthesis. Open life sciences 0 39711976

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