Affinage

AZGP1

Zinc-alpha-2-glycoprotein · UniProt P25311

Length
298 aa
Mass
34.3 kDa
Annotated
2026-04-28
100 papers in source corpus 34 papers cited in narrative 34 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AZGP1 (zinc-alpha-2-glycoprotein/ZAG) is a secreted MHC class I-like glycoprotein that functions as a lipid-mobilizing adipokine, anti-EMT factor, and metabolic regulator across diverse tissues. Structurally, AZGP1 resembles an MHC class I heavy chain but does not bind β2-microglobulin; its groove contains a nonpeptidic ligand implicated in lipid catabolism, and it forms a stable complex with prolactin-inducible protein (PIP) in seminal plasma (PMID:10206894, PMID:18930737). AZGP1 stimulates lipolysis and uncoupling protein expression by binding β3- and β2-adrenergic receptors (Kd ~46 nM and ~71 nM, respectively) to activate cAMP/PKA signaling, promotes white adipose browning through PPARγ/EBF2-mediated Prdm16 induction, and in hypothalamic POMC neurons stabilizes acylglycerol kinase (AGK) to enhance leptin-JAK2-STAT3 signaling for energy homeostasis (PMID:22227600, PMID:29570397, PMID:38643150). As a tumor suppressor, AZGP1 inhibits TGF-β1-mediated epithelial-mesenchymal transition by blocking ERK2 and Smad3 phosphorylation, suppresses mTOR and PI3K/AKT pathways, inhibits angiogenesis, and shifts tumor cell metabolism from glycolysis to oxidative phosphorylation; its expression is silenced by promoter methylation and histone deacetylation and its protein is targeted for degradation by the E3 ubiquitin ligase TRIM25 (PMID:20581862, PMID:26902423, PMID:38183356, PMID:41535762, PMID:27993894).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1994 Medium

    Mapping AZGP1 to chromosome 7q22 established that this MHC class I-like gene had diverged from the classical MHC locus on chromosome 6, raising the question of what non-immune function it might serve.

    Evidence Fluorescent in situ hybridization (FISH) on human chromosomes

    PMID:8162703

    Open questions at the time
    • No functional data at this stage
    • Evolutionary relationship to MHC I genes not mechanistically resolved
  2. 1999 High

    Solving the crystal structure revealed that ZAG adopts the MHC class I fold but cannot bind β2-microglobulin and carries a nonpeptidic molecule in its groove, establishing a structural basis for a lipid-related rather than antigen-presentation function.

    Evidence X-ray crystallography at 2.8 Å resolution

    PMID:10206894

    Open questions at the time
    • Identity of the groove ligand unresolved
    • No receptor or signaling pathway yet identified
  3. 2004 High

    Demonstrating that ZAG induces UCP-1, UCP-2, and UCP-3 through β3-adrenergic receptor and MAPK pathways identified the first signaling mechanism by which ZAG mobilizes lipid energy, resolving how the structural lipid-binding hypothesis connected to thermogenesis.

    Evidence β3-AR antagonist blockade in primary adipose tissue and C2C12 myotube cultures

    PMID:15246563

    Open questions at the time
    • Direct ZAG–β3-AR binding not yet shown
    • In vivo metabolic consequences not tested
  4. 2008 High

    Three parallel advances clarified ZAG's molecular partnerships, epigenetic regulation, and renal biology: the ZAG–PIP crystal structure defined a stable complex in seminal plasma; histone deacetylation was identified as the dominant epigenetic silencer of AZGP1 in lung cancer; and ZAG was shown to suppress epithelial proliferation in aged kidney after ischemia.

    Evidence X-ray crystallography of ZAG–PIP complex; TSA/5-AZA treatment in lung adenocarcinoma lines; siRNA knockdown and recombinant ZAG in mouse ischemia/reperfusion model

    PMID:18815245 PMID:18930737 PMID:18978557

    Open questions at the time
    • Functional role of ZAG–PIP complex unknown
    • Whether HDAC-mediated silencing is cancer-type specific unclear
    • Renal anti-proliferative mechanism undefined
  5. 2010 High

    Loss- and gain-of-function experiments in pancreatic cancer established ZAG as a suppressor of TGF-β-induced EMT through blockade of ERK2 phosphorylation, converting ZAG from a metabolic factor to a recognized tumor suppressor, while inflammatory macrophage signaling was shown to downregulate ZAG in adipocytes.

    Evidence siRNA knockdown and recombinant ZAG rescue in pancreatic cancer cells with EMT marker and pERK2 readouts; macrophage-conditioned medium and TNF-α treatment of human adipocytes

    PMID:20581862 PMID:20595026

    Open questions at the time
    • Whether ERK2 is a direct target or indirect unknown
    • Mechanism linking macrophage signals to ZAG transcriptional repression unresolved
  6. 2011 High

    Radioligand binding established that ZAG directly binds β3-AR (Kd 46 nM) and β2-AR (Kd 71 nM) but not β1-AR, and propranolol blockade in ob/ob mice validated this receptor axis in vivo, closing the gap between structural prediction and receptor identity.

    Evidence Radioligand binding in transfected CHO-K1 cells; cAMP assay; in vivo ob/ob mouse model with propranolol

    PMID:21245862 PMID:22227600

    Open questions at the time
    • Binding site on β3-AR not mapped
    • Whether ZAG acts as classical agonist or allosteric modulator unknown
  7. 2014 Medium

    AZGP1 overexpression in colorectal cancer cells suppressed mTOR/S6K1 signaling and fatty acid synthesis, extending the tumor-suppressive mechanism beyond ERK to metabolic signaling through mTOR.

    Evidence Plasmid overexpression in LoVo cells; Western blot for p-mTOR, p-S6, S6K1, eIF4E; MTT and flow cytometry

    PMID:24918753

    Open questions at the time
    • Direct molecular target upstream of mTOR not identified
    • Single cell line limits generalizability
  8. 2016 High

    Replication of the TGF-β1/ERK2 EMT-suppression mechanism in hepatocellular carcinoma, with in vivo metastasis suppression by an AZGP1 mimic, generalized the anti-EMT role across cancer types.

    Evidence Overexpression/knockdown in HCC cells; phospho-ERK2; in vivo lung metastasis model

    PMID:26902423

    Open questions at the time
    • Identity of the 'AZGP1 mimic' peptide and its pharmacology not fully defined
  9. 2017 High

    Identification of Ikaros as a direct transcriptional activator of AZGP1 (ChIP) and demonstration that AZGP1 inhibits HCC invasion through PTEN/AKT and CD44s pathways added a transcription-factor–level regulatory node and a second anti-tumor signaling axis.

    Evidence ChIP for Ikaros on AZGP1 promoter; histone acetylation analysis; PTEN/AKT Western blot; migration/invasion assays

    PMID:27993894

    Open questions at the time
    • Whether Ikaros is the dominant transcription factor for AZGP1 across tissues unknown
    • Connection between PTEN/AKT and ERK pathways downstream of AZGP1 not mapped
  10. 2018 High

    ChIP experiments showed ZAG promotes PPARγ and EBF2 recruitment to the Prdm16 promoter in white adipose progenitors and PPARγ to the Ucp1 promoter in brown fat, revealing a transcriptional mechanism for ZAG-induced adipose browning beyond simple β3-AR/cAMP signaling.

    Evidence ChIP for PPARγ/EBF2 on Prdm16 and Ucp1 promoters; WAT progenitor differentiation with recombinant ZAG; in vivo cell implantation

    PMID:29570397

    Open questions at the time
    • Whether ZAG enters the nucleus or acts purely through surface receptor signaling to achieve promoter remodeling is unresolved
    • Epigenetic changes at these promoters not characterized
  11. 2019 High

    ChIP-Seq and ARE mutagenesis demonstrated that AZGP1 is a direct androgen receptor target gene, and ZAG was found to maintain skin barrier function by sustaining filaggrin and ceramide levels in atopic dermatitis, expanding its functional scope to hormonal regulation and epithelial barrier biology.

    Evidence ChIP-Seq and dual-luciferase ARE reporter in prostate cells; topical rZAG treatment in AD mouse model with barrier protein and cytokine measurement

    PMID:30738053 PMID:30820960

    Open questions at the time
    • Whether AR-dependent AZGP1 induction is tissue-restricted unclear
    • Mechanism by which ZAG restores ceramide levels not defined
  12. 2020 Medium

    The lncRNA LINC00844 was shown to physically bind AZGP1 protein and promote its expression, linking noncoding RNA regulation to the TGF-β1-ERK/MAPK suppression axis in HCC.

    Evidence RNA precipitation assay; overexpression/knockdown with MAPK pathway Western blot and in vivo tumorigenesis

    PMID:33313110

    Open questions at the time
    • RNA precipitation as sole binding evidence; no crosslinking or structural data
    • Whether LINC00844 stabilizes AZGP1 protein or mRNA unclear
  13. 2022 Medium

    Two studies expanded AZGP1's protective roles: tubular-specific AZGP1 overexpression reduced renal fibrosis by preserving fatty acid oxidation, and ZAG knockout mice showed depression-like behavior with hippocampal ROS rescued by β3-AR/PKA/CREB signaling, broadening ZAG's function to renal lipid metabolism and neuronal antioxidant defense.

    Evidence Conditional transgenic overexpression and recombinant protein in UUO renal model; ZAG KO mouse behavioral and ROS assays with β3AR/PKA/CREB pathway analysis in HT-22 neurons

    PMID:35054830 PMID:35255519

    Open questions at the time
    • Renal fatty acid oxidation target genes directly regulated by AZGP1 not identified
    • Whether neuronal ZAG acts cell-autonomously or as a secreted factor unresolved
  14. 2023 Medium

    Three studies identified TRIM25 as the E3 ubiquitin ligase that ubiquitinates and degrades AZGP1 protein (in breast and cholangiocarcinoma), and noncoding RNAs circNOLC1 and LINC01094 were shown to physically interact with AZGP1 to modulate mTOR/SREBP1 and PTEN/AKT pathways respectively, establishing post-translational and RNA-level control of AZGP1 activity.

    Evidence Co-IP and ubiquitination assays for TRIM25–AZGP1; RNA pulldown and RIP for circNOLC1–AZGP1 and LINC01094–AZGP1; pathway analysis in cancer cells

    PMID:36831602 PMID:37870214 PMID:37927217

    Open questions at the time
    • Ubiquitination sites on AZGP1 not mapped
    • Whether circNOLC1 activates or sequesters AZGP1 protein mechanistically unclear
    • TRIM25–AZGP1 interaction confirmed in cancer cells but not normal tissue
  15. 2024 High

    Multiple 2024 studies resolved tissue-specific mechanisms: AZGP1 in POMC neurons stabilizes AGK to enhance leptin-JAK2-STAT3 signaling for energy homeostasis; AZGP1 directly inhibits angiogenesis in prostate; AZGP1 promotes macrophage M1 polarization and NLRP3 pyroptosis in periodontitis; and lenvatinib activates AZGP1 via H3K27Ac to suppress TGF-β1/Smad3 EMT in cholangiocarcinoma.

    Evidence POMC neuron-specific OE/KO mice with Co-IP for AZGP1-AGK and ubiquitination assay; AZGP1-KO mouse prostate vasculature + HUVEC assays; Azgp1-KO and AAV-OE in periodontitis with NLRP3 inhibitor rescue; ChIP for H3K27Ac at AZGP1 promoter

    PMID:37669935 PMID:38491721 PMID:38643150 PMID:38659028

    Open questions at the time
    • How AZGP1 switches between pro-inflammatory (periodontitis) and anti-inflammatory (adipose) roles not reconciled
    • AGK stabilization mechanism (which ubiquitin ligase is blocked) unknown
    • Angiogenic target receptor on endothelial cells not identified
  16. 2025 Medium

    Recent work demonstrated that AZGP1 promoter CpG methylation silences expression in prostate cancer and shifts metabolism from oxidative phosphorylation to glycolysis, miR-155-5p/3p directly represses AZGP1 via its 3'UTR in hypertrophic scar fibroblasts, and adipocyte-specific ZAG ablation worsens HFD-induced insulin resistance via impaired β3-AR/PKA/STAT3 macrophage signaling.

    Evidence Methylation-specific PCR and ECAR/OCR metabolic flux in prostate cancer cells; dual-luciferase 3'UTR assay for miR-155; adipocyte-specific ZAG KO mice on HFD with macrophage pathway analysis

    PMID:38729323 PMID:40068519 PMID:41535762

    Open questions at the time
    • Whether glycolytic shift upon AZGP1 loss is a direct or indirect effect unresolved
    • Specific AZGP1 methylation dynamics during cancer progression not longitudinally tracked

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the identity of the nonpeptidic groove ligand, the structural basis for ZAG–β3-AR binding, how ZAG switches between pro-inflammatory and anti-inflammatory functions in different tissue contexts, and whether ZAG enters cells to directly modulate transcription factor recruitment or acts exclusively through surface receptors.
  • Groove ligand identity unknown since 1999
  • No co-crystal structure of ZAG with any adrenergic receptor
  • Context-dependent pro- vs anti-inflammatory switching mechanism undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 2
Localization
GO:0005576 extracellular region 4
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 2 R-HSA-392499 Metabolism of proteins 2
Partners
ADRB2ADRB3AGKCIRCNOLC1LINC00844LINC01094PIPTRIM25
Complex memberships
ZAG–PIP complex

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Crystal structure of ZAG (AZGP1) at 2.8 Å resolution revealed it resembles a class I MHC heavy chain but does not bind beta2-microglobulin; its peptide-binding groove analog contains a nonpeptidic compound possibly implicated in lipid catabolism. X-ray crystallography Science High 10206894
2008 Crystal structure of ZAG in complex with prolactin-inducible protein (PIP) purified from human seminal plasma; the complex interface involves 12 hydrogen bonds and 3 salt bridges between the beta-structure of PIP and the alpha3 domain of ZAG, and the alpha1-alpha2 domains of ZAG interact with a PIP loop. X-ray crystallography, co-purification from seminal plasma Journal of Molecular Biology High 18930737
2004 ZAG induces UCP-1 expression in brown adipose tissue via the beta3-adrenergic receptor (beta3-AR), UCP-2 expression in C2C12 myotubes via beta3-AR/cAMP, and UCP-3 expression in myotubes via MAPK (not beta3-AR), demonstrating direct regulation of uncoupling proteins. In vitro primary adipose tissue cultures and C2C12 myotube cultures; beta3-AR antagonist (SR59230A) blockade; isobutylmethylxanthine potentiation Cancer Letters High 15246563
2011 ZAG binds the beta3-AR with higher affinity (Kd 46 nM) than beta2-AR (Kd 71 nM) and does not bind beta1-AR; ZAG-stimulated cAMP increases in CHO-K1 cells expressing human beta-ARs, and the propranolol (beta-AR antagonist) blocked anti-obesity and anti-diabetic effects of ZAG in ob/ob mice. Radioligand binding assay in transfected CHO-K1 cells; cAMP assay; in vivo ob/ob mouse model with propranolol co-treatment Biochimica et Biophysica Acta High 22227600
2010 ZAG silencing in pancreatic cancer cells induces EMT (increased vimentin and integrin-α5, decreased E-cadherin/CDH1, desmoplakin, keratin-19); recombinant ZAG blocks TGF-β-mediated tumor cell invasion, vimentin expression, and ERK2 phosphorylation, identifying AZGP1 as a suppressor of TGF-β/ERK signaling. siRNA knockdown; recombinant protein rescue; EMT marker expression analysis; ERK2 phosphorylation assay; invasion assay Oncogene High 20581862
2016 AZGP1 suppresses EMT and hepatocellular carcinoma invasion by blocking TGF-β1-mediated ERK2 phosphorylation; local AZGP1 mimic injection in vivo suppressed lung metastasis. Overexpression/knockdown in HCC cells; phospho-ERK2 assay; in vivo metastasis model with AZGP1 mimic injection Cancer Letters High 26902423
2008 Increased Zag expression in aged mouse kidney proximal tubular cells suppresses epithelial proliferative response after ischemia/reperfusion injury; siRNA knockdown of Zag in vivo increased epithelial proliferation but also increased fibrosis. Microarray identification; recombinant Zag treatment decreasing proliferation; siRNA knockdown increasing proliferation; in vivo ischemia/reperfusion model with systemic siRNA Journal of the American Society of Nephrology High 18815245
2017 The transcription factor Ikaros binds to the AZGP1 promoter and transactivates AZGP1 expression; AZGP1 downregulation in HCC is associated with histone deacetylation; AZGP1 inhibits HCC cell migration and invasion through the PTEN/AKT and CD44s pathways. ChIP assay (Ikaros binding to AZGP1 promoter); histone acetylation analysis; overexpression/knockdown migration/invasion assays; PTEN/AKT pathway Western blot Carcinogenesis High 27993894
2018 ZAG promotes white adipose tissue browning by stimulating PPARγ and EBF2 recruitment to the Prdm16 promoter, increasing Prdm16 expression to drive brown cell fate; in brown adipose tissue, ZAG promotes PPARγ recruitment to the Ucp1 promoter. Cell implantation model in mice; WAT progenitor differentiation with recombinant ZAG; ChIP showing PPARγ and EBF2 recruitment to Prdm16 and Ucp1 promoters; MEF differentiation assay FASEB Journal High 29570397
2011 Recombinant ZAG stimulates lipolysis in human adipocytes; ZAG mRNA and secretion from subcutaneous adipose tissue is elevated in cachectic cancer patients and correlates with weight loss and serum glycerol. In vitro lipolysis assay with recombinant ZAG; ZAG secretion measured from patient adipose tissue explants British Journal of Cancer Medium 21245862
2010 Macrophage-conditioned medium and chronic TNF-alpha treatment decrease ZAG mRNA expression and secretion in human adipocytes, accompanied by decreased PPARgamma and C/EBPalpha (adipogenic markers), indicating macrophage-associated inflammation suppresses ZAG production. Human adipocyte culture with macrophage-conditioned medium; TNF-alpha treatment; RT-PCR and Western blot for ZAG and adipogenic markers Molecular and Cellular Endocrinology Medium 20595026
2012 Oral ZAG administration to ob/ob mice reduces body weight and improves insulin sensitivity via interaction with beta-AR in the upper gastrointestinal tract (esophagus), which stimulates endogenous murine ZAG production; tryptic digestion inactivates ZAG; propranolol blocks the effect. Oral ZAG administration in ob/ob mice; propranolol co-administration; gene expression in GI tract; serum human and murine ZAG measurement Endocrinology Medium 22903615
2019 AZGP1 is an androgen-responsive gene regulated by the androgen-AR axis; ChIP-Seq and luciferase reporter assays identified canonical androgen-responsive elements (AREs) at the AZGP1 enhancer; AZGP1 promotes G1/S transition by increasing cyclin D1 levels; knockdown of AZGP1 reduces androgen/AR-induced cell migration and invasion. ChIP-Seq; dual-luciferase reporter assay with ARE mutagenesis; flow cytometry cell cycle analysis; siRNA knockdown migration/invasion; in vivo xenotransplantation Journal of Cellular Physiology High 30820960
2008 Histone deacetylation (but not promoter methylation) regulates AZGP1 expression in lung adenocarcinoma cells; TSA (HDAC inhibitor) treatment increased AZGP1 mRNA 713-fold in A549 and 169-fold in SKLU1 cells, whereas 5-AZA had minimal effect. Treatment with TSA and 5-AZA; real-time PCR quantification of AZGP1 expression Journal of Thoracic Oncology Medium 18978557
2024 AZGP1 in POMC neurons enhances leptin-JAK2-STAT3 signaling by interacting with acylglycerol kinase (AGK) to block its ubiquitination-dependent degradation; POMC neuron-specific Azgp1 overexpression under HFD reduces energy intake, raises energy expenditure, and improves insulin/leptin sensitivity. POMC neuron-specific Azgp1 overexpression and inducible deletion in mice; co-immunoprecipitation of AZGP1-AGK interaction; STAT3 phosphorylation assay; ubiquitination assay; electrophysiology (POMC neuron excitability) Nature Communications High 38643150
2024 AZGP1 interacts with TRIM25 E3 ubiquitin ligase, which catalyzes AZGP1 ubiquitination and promotes its degradation; TRIM25 knockdown leads to AZGP1 upregulation and increased apoptosis in cholangiocarcinoma cells. Co-immunoprecipitation (AZGP1-TRIM25); ubiquitination assay; TRIM25 knockdown; tissue microarray and bioinformatics showing negative correlation between AZGP1 and TRIM25 Journal of Cellular and Molecular Medicine High 38183356
2023 AZGP1 interacts with TRIM25 in breast cancer cells, where TRIM25 promotes AZGP1 ubiquitination and degradation; TRIM25 overexpression partially reverses the pro-tumorigenic effects of AZGP1 overexpression. Co-immunoprecipitation; ubiquitination assay; overexpression/knockdown proliferation and invasion assays; in vivo xenograft Environmental Toxicology Medium 37927217
2014 AZGP1 overexpression in colorectal LoVo cells suppresses mTOR pathway activation (reduced p-mTOR, p-S6, S6K1, eIF4E) and endogenous FASN-regulated fatty acid synthesis, inhibiting proliferation, promoting G2 arrest and apoptosis, and reducing migration. Plasmid transfection; Western blot for mTOR pathway proteins; MTT proliferation; flow cytometry; transwell migration PLoS ONE Medium 24918753
2023 circNOLC1 interacts physically with AZGP1 protein to activate mTOR/SREBP1 signaling, which induces G6PD and the oxidative pentose phosphate pathway to promote colorectal cancer liver metastasis. RNA pulldown; RIP assay; Co-IP; mTOR/SREBP1/G6PD pathway analysis; circNOLC1 silencing in vitro and in vivo Advanced Science Medium 37870214
2023 lncRNA LINC01094 physically binds AZGP1 protein (identified by RNA pulldown and RIP), antagonizes AZGP1 function, downregulates PTEN expression, and upregulates the AKT pathway to promote gastric cancer proliferation and metastasis. RNA pulldown; RIP assay; PTEN/AKT Western blot; proliferation and metastasis assays in vitro and in vivo Cancers Medium 36831602
2024 AZGP1 deficiency in prostate cancer cells promotes angiogenesis: AZGP1 overexpression in PC3/DU145 xenografts decreased microvessel density; AZGP1 knockout mice showed increased blood vessel density in the prostate by 6 months; AZGP1 directly inhibits HUVEC proliferation, migration, tubular formation and branching in vitro. Lentiviral overexpression/knockout in cancer cells; in vivo xenograft with microvessel density measurement; AZGP1-/- mouse histology; HUVEC functional assays; proteomics; tissue microarray Journal of Translational Medicine High 38659028
2024 AZGP1 aggravates macrophage M1 polarization and pyroptosis through the NLRP3/caspase-1 signaling pathway in periodontitis; AAV-mediated Azgp1 overexpression enhanced periodontal inflammation and bone loss, while Azgp1-/- mice had opposite effects; NLRP3 or caspase-1 inhibition rescued the effects of Azgp1 overexpression. AAV-mediated overexpression in mouse periodontium; Azgp1 knockout mice; LPS/PA-stimulated bone marrow-derived macrophages with Azgp1 OE/KO; NLRP3/caspase-1 inhibition rescue experiments Journal of Dental Research High 38491721
2024 Lenvatinib activates AZGP1 expression by increasing H3K27Ac acetylation at the AZGP1 promoter; AZGP1 then inhibits intrahepatic cholangiocarcinoma EMT by suppressing TGF-β1/Smad3 signaling in an AZGP1-dependent manner. ChIP for H3K27Ac at AZGP1 promoter; AZGP1 overexpression/knockdown; TGF-β1/Smad3 pathway analysis; in vitro EMT assays Cell Death & Disease Medium 37669935
2025 AZGP1 attenuates subretinal fibrosis and inhibits TGF-β1-induced EMT in ARPE-19 retinal pigment epithelial cells by regulating the PI3K/AKT signaling pathway; intravitreal injection of recombinant AZGP1 reduced collagen I and CD31 areas in mouse SRF model. RNA-seq identification; rAZGP1 intravitreal injection; AZGP1 knockdown and overexpression in ARPE-19 cells; PI3K/AKT Western blot; EMT marker expression Investigative Ophthalmology & Visual Science Medium 40305469
2022 Therapeutic elevation of AZGP1 via recombinant protein or tubular cell-specific transgenic overexpression in mice reduces fibrosis after ureteral obstruction, preserves tubular integrity, reduces collagen deposition, and improves tubular lipid metabolism/fatty acid oxidation markers. Recombinant AZGP1 systemic treatment; conditional transgenic AZGP1 overexpression in proximal tubular cells; unilateral ureteral obstruction model; histology; lipid droplet quantification; fatty acid oxidation gene expression International Journal of Molecular Sciences Medium 35054830
2025 Promoter methylation (at cg26429636) silences AZGP1 transcription in prostate cancer cells; AZGP1 loss upregulates glycolysis (increased lactate, ECAR); overexpression of AZGP1 reduces L-lactic acid levels, ECAR, and increases OCR, establishing AZGP1 as a metabolic suppressor of glycolysis. Methylation-specific PCR; ECAR and OCR measurement; lactate production assay; AZGP1 overexpression/knockdown; single-cell and bulk transcriptomics Cellular & Molecular Biology Letters Medium 41535762
2024 miR-155-5p and miR-155-3p directly bind to AZGP1 3'UTR (confirmed by dual-luciferase assay); MIR155HG silencing inhibits inflammatory cytokine production and α-SMA in hypertrophic scar fibroblasts by repressing miR-155 production, thereby de-repressing AZGP1. Dual-luciferase reporter assay with AZGP1 3'UTR; MIR155HG silencing; AZGP1 overexpression rescue experiments; cytokine and α-SMA measurement Cellular Signalling Medium 38729323
2025 Adipocyte-specific ZAG ablation aggravates insulin resistance and adipose inflammation (increased M1 macrophages, inhibited AKT signaling) in HFD-fed mice; exogenous ZAG inhibits palmitate-induced M1 macrophage polarization via β3-AR/PKA/STAT3 signaling in macrophages. Adipocyte-specific ZAG knockout mice on HFD; exogenous ZAG treatment of RAW264.7 macrophages; β3-AR/PKA/STAT3 pathway Western blot; M1/M2 macrophage flow cytometry International Immunopharmacology Medium 40068519
1994 The human AZGP1 gene was mapped by fluorescent in situ hybridization to chromosome 7q22, indicating evolutionary divergence from classical MHC class I genes on chromosome 6. Fluorescent in situ hybridization (FISH) Cytogenetics and Cell Genetics Medium 8162703
2022 ZAG knockout mice show increased depression-like behavior after fasting with elevated hippocampal ROS; ZAG overexpression in HT-22 neurons alleviates serum deprivation-induced neuronal death, ROS increase, and mitochondrial dysfunction via the β3AR/PKA/CREB antioxidant pathway. ZAG KO mouse behavioral testing; ROS measurement; mitochondrial membrane potential and ATP assays; ZAG overexpression in neuronal cell line; β3AR/PKA/CREB pathway analysis Hormone and Metabolic Research Medium 35255519
2020 lncRNA LINC00844 binds AZGP1 protein (RNA precipitation assay) and promotes AZGP1 expression, leading to suppression of the TGF-β1-ERK/MAPK signaling pathway and inhibition of HCC proliferation, migration, and tumorigenesis. RNA precipitation assay for LINC00844-AZGP1 interaction; Western blot for MAPK pathway; overexpression/knockdown proliferation and migration assays; in vivo tumorigenesis Annals of Translational Medicine Medium 33313110
2026 Entinostat (HDAC inhibitor) promotes histone H4 acetylation at the AZGP1 promoter (confirmed by ChIP-qPCR), activating AZGP1 transcription; AZGP1 overexpression mimics entinostat's suppression of TGF-β-induced EMT and HCC invasion in vitro and in vivo. Transcriptomic sequencing; ChIP-qPCR for H4 acetylation at AZGP1 promoter; AZGP1 overexpression/knockdown; TGF-β EMT model; orthotopic mouse model Biochemical Pharmacology Medium 41554411
2019 ZAG knockdown in atopic dermatitis reduced filaggrin (FLG) and increased TSLP expression; topical ZAG treatment in AD mice restored ceramide levels, reduced IL-4/IL-17/IFN-γ, increased Foxp3, and recovered ADAM17 expression, linking ZAG to skin barrier function and immune regulation. shRNA knockdown of ZAG; topical recombinant ZAG treatment in AD mouse model; cytokine and skin barrier protein measurement; ADAM17 Western blot Journal of Investigative Dermatology Medium 30738053
2024 TNBC-secreted ZAG/AZGP1 inhibits adipogenesis in adipocyte stem and progenitor cells and instead induces fibrotic gene expression; ZAG depletion from TNBC cells attenuates adipose tissue fibrosis and inhibits tumor growth. Secretome screen of 10 breast cancer cell lines; ZAG depletion by shRNA; adipogenesis assay; fibrotic gene expression; in vivo tumor growth bioRxiv (preprint)preprint Medium 38496643

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 609 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) 113 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 74 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 59 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
2003 zag-1, a Zn-finger homeodomain transcription factor controlling neuronal differentiation and axon outgrowth in C. elegans. Development (Cambridge, England) 44 12835395
2016 AZGP1 suppresses epithelial-to-mesenchymal transition and hepatic carcinogenesis by blocking TGFβ1-ERK2 pathways. Cancer letters 43 26902423
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
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
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) 32 37870214
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
2024 AZGP1 Aggravates Macrophage M1 Polarization and Pyroptosis in Periodontitis. Journal of dental research 27 38491721
2024 AZGP1 in POMC neurons modulates energy homeostasis and metabolism through leptin-mediated STAT3 phosphorylation. Nature communications 26 38643150
2019 AZGP1 is androgen responsive and involved in AR-induced prostate cancer cell proliferation and metastasis. Journal of cellular physiology 26 30820960
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 20 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 19 28549690
2023 LncRNA LINC01094 Promotes Cells Proliferation and Metastasis through the PTEN/AKT Pathway by Targeting AZGP1 in Gastric Cancer. Cancers 17 36831602
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
2018 Serum levels of the adipokine zinc-alpha2-glycoprotein (ZAG) predict mortality in hemodialysis patients. Kidney international 16 30348306
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
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
2024 AZGP1 deficiency promotes angiogenesis in prostate cancer. Journal of translational medicine 13 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 13 35641588
2014 Regulation of C. elegans neuronal differentiation by the ZEB-family factor ZAG-1 and the NK-2 homeodomain factor CEH-28. PloS one 12 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
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
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 7 38729323
2023 AZGP1 as a potential biomarker of IgA vasculitis with nephritis in a children‑based urinary proteomics study by diaPASEF. Molecular medicine reports 7 37417365
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 5 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
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
2025 Adipocyte ZAG improves obesity-triggered insulin resistance by reshaping macrophages populations in adipose tissue. International immunopharmacology 2 40068519
2024 Heavy metal exposure and its effects on APOC3, CFAI, and ZA2G. Journal of hazardous materials 2 39579699
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 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) 1 39061919
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
2021 Changes in AZGP1 Serum Levels and Correlation With Pulse Wave Velocity After Kidney Transplantation. Frontiers in cardiovascular medicine 1 34291094
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
2026 Entinostat suppresses hepatocellular carcinoma metastasis by upregulating AZGP1 through histone acetylation. Biochemical pharmacology 0 41554411
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 Zinc Alpha-2-Glycoprotein (ZAG/AZGP1) secreted by triple-negative breast cancer promotes tumor microenvironment fibrosis. bioRxiv : the preprint server for biology 0 38496643
2024 ZAG promotes colorectal cancer cell proliferation and epithelial-mesenchymal transition by promoting lipid synthesis. Open life sciences 0 39711976
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 0 37920240