Affinage

PAICS

Bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase · UniProt P22234

Length
425 aa
Mass
47.1 kDa
Annotated
2026-06-10
51 papers in source corpus 24 papers cited in narrative 25 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

PAICS is a bifunctional enzyme of de novo purine biosynthesis that catalyzes steps 6 and 7 of IMP synthesis, converting AIR to CAIR (AIR carboxylase) and then CAIR to SAICAR (SAICAR synthetase) (PMID:19570845, PMID:32571877). The enzyme assembles into a homo-octamer in which an octameric carboxylase core is decorated by four peripheral synthetase dimers; this quaternary arrangement is itself essential, because each carboxylase active site is built from elements contributed by three subunits, and tunnel systems connecting the AIRc and SAICARs sites permit internal channeling of the CAIR intermediate (PMID:17224163). Isotope-tracing confirms that the synthetase domain selectively uses enzyme-generated CAIR over exogenous CAIR, providing direct biochemical evidence for substrate channeling (PMID:35285625), and structural and computational work define a two-step carboxylation mechanism, an ATP-dependent phosphorylation-condensation with aspartate, and the magnesium ions that stabilize the transition states (PMID:32571877, PMID:35914774). Beyond catalysis, PAICS nucleates the purinosome metabolon by physically interacting with the other DNPB enzymes and MTHFD1, with C-terminal tagging disrupting both these contacts and metabolic flux through the pathway (PMID:35331738); purinosome assembly is driven by K6-polyubiquitination of PAICS by the Cul5/ASB11 E3 ligase, which recruits the disordered protein UBAP2 to trigger phase separation (PMID:37848033). Enzymatic and assembly functions are clinically validated: a homozygous p.Lys53Arg mutation that reduces catalytic activity and abolishes purinosome formation causes a developmental disorder, with rescue by wild-type but not mutant protein (PMID:31600779). PAICS is transcriptionally activated by MYC and post-transcriptionally repressed by miR-128, and across multiple cancers its knockdown suppresses proliferation, invasion, EMT, and metastasis (PMID:27550065, PMID:30121007, PMID:32218208); reported effectors include HDAC1/2-dependent RAD51 recruitment for DNA repair (PMID:32632107) and PAICS-dependent FAK phosphorylation (PMID:35379785). Protein abundance is further controlled by ACSS2-mediated acetylation that targets PAICS for autophagic degradation, linking purine and dNTP supply to senescence (PMID:40021646).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1988 Medium

    Before molecular characterization, establishing that the mammalian PAICS gene was a functional, mappable locus was needed; somatic cell hybrid complementation identified bovine PAICS and placed it in a synteny conserved with human chromosome 21 alongside PPAT and SOD1.

    Evidence Cow-hamster somatic cell hybrids with selective growth complementation and enzyme electrophoresis

    PMID:3377762

    Open questions at the time
    • No protein-level or catalytic characterization
    • Human gene structure not yet defined
  2. 1995 Medium

    How PAICS expression is coordinated with another purine-pathway gene was unknown; the chicken PPAT and PAICS genes were shown to share a compact bidirectional promoter, with an initiator-like element at the PAICS start site coordinating both genes.

    Evidence Deletion mutagenesis in a bireporter vector with DNase I/methylation interference footprinting

    PMID:7836476

    Open questions at the time
    • Trans-acting factors not yet identified
    • Avian promoter, not validated in human in vivo
  3. 1997 Medium

    The trans-acting factors driving the bidirectional promoter were undefined; NRF-1 and Sp1 were shown to bind a site cluster, with NRF-1 required for stable Sp1 binding and both needed for full expression of both genes.

    Evidence Promoter point-mutation analysis and gel retardation in transfected HepG2 cells

    PMID:9108165

    Open questions at the time
    • No in vivo occupancy data
    • Regulation under metabolic demand not addressed
  4. 2006 High

    The structural basis of PAICS bifunctionality was unknown; the human crystal structure revealed a homo-octamer whose carboxylase core requires three subunits per active site and contains tunnels linking the two catalytic sites, implying intermediate channeling.

    Evidence X-ray crystallography at 2.8 Å with functional complementation to map active sites

    PMID:17224163

    Open questions at the time
    • Substrate-bound states not captured
    • Channeling inferred from tunnels, not directly demonstrated
  5. 2009 High

    The physiological consequences of PAICS loss in a vertebrate were untested; zebrafish mutants placed paics at a bifurcation point where pigmentation defects depend on GTP-pathway output and microphthalmia on ATP-pathway output.

    Evidence Zebrafish recessive mutant analysis with genetic epistasis and purine supplementation rescue

    PMID:19570845

    Open questions at the time
    • Tissue-specific mechanisms not resolved
    • Relevance to human disease not yet established
  6. 2013 Medium

    Whether the bifunctional architecture was conserved was addressed by an invertebrate PAICS structure, confirming a deeply conserved domain organization and enzymatic framework.

    Evidence X-ray crystallography (SAD phasing) of Trichoplusia ni PAICS with comparative analysis

    PMID:23553965

    Open questions at the time
    • No functional mutagenesis in this study
    • Catalytic mechanism still not defined at atomic detail
  7. 2016 Medium

    The drivers of elevated PAICS in cancer were unclear; in prostate cancer MYC was shown to occupy the PAICS promoter and JQ1 reduced this occupancy and expression, with knockdown suppressing proliferation, invasion, and tumor growth.

    Evidence ChIP, BET inhibition, knockdown, and CAM/xenograft models in prostate cancer

    PMID:27550065

    Open questions at the time
    • Whether catalytic vs non-catalytic activity drives phenotype not separated
    • Single cancer context
  8. 2018 Medium

    Post-transcriptional control and downstream oncogenic effects were addressed: miR-128 targets the PAICS 3'-UTR, and PAICS promotes EMT (SNAI1 up, E-cadherin down) and the G1-S transition while restraining apoptosis.

    Evidence 3'-UTR luciferase reporters, knockdown with cell-cycle/EMT/apoptosis marker profiling in bladder and breast cancer

    PMID:30097015 PMID:30121007

    Open questions at the time
    • Mechanism linking purine synthesis to EMT/cell-cycle markers not defined
    • Effectors downstream of PAICS unclear
  9. 2019 High

    Whether PAICS catalytic activity and purinosome assembly are physiologically essential in humans was tested by a homozygous p.Lys53Arg mutation that lowers activity to ~10–25% and abolishes purinosome formation, rescued only by wild-type protein.

    Evidence Enzyme assays in patient fibroblasts and recombinant protein with transfection rescue of purinosome formation

    PMID:31600779

    Open questions at the time
    • Full clinical spectrum from a single residue not generalizable
    • Link between catalysis and assembly defect mechanistically unresolved
  10. 2020 High

    Ligand-bound structures and cancer dependency were established together: structures captured CAIR in both sites, SAICAR with an ATP analog, and PAICS knockdown impaired prostate cancer growth and survival.

    Evidence X-ray crystallography of native-ligand complexes plus clonogenic and viability assays

    PMID:32571877

    Open questions at the time
    • Reaction trajectory between sites not directly observed
    • Dependency mechanism (metabolic vs other) not dissected
  11. 2020 Medium

    A non-canonical nuclear role was proposed: PAICS interacts with HDAC1/2 to support RAD51 recruitment and DNA damage repair, with loss sensitizing gastric cancer cells to cisplatin.

    Evidence Reciprocal Co-IP, RAD51 ChIP at damage sites, HDAC activity assay, and cisplatin sensitivity in vitro and in vivo

    PMID:32632107

    Open questions at the time
    • How a metabolic enzyme localizes to chromatin to modulate HDAC activity unexplained
    • Single cancer type
  12. 2020 Medium

    Metastatic relevance and converging regulation were confirmed in colorectal cancer, where MYC activates and miR-128 represses PAICS, and knockdown reduced metastasis to liver, lung, and bone.

    Evidence JQ1, miR-128 overexpression, stable knockdown, and PET-imaged xenograft/metastasis models

    PMID:32218208

    Open questions at the time
    • Causal step between PAICS and metastatic colonization not defined
  13. 2022 High

    Direct evidence for substrate channeling and metabolon assembly was obtained: isotope tracing showed the synthetase site preferentially uses enzyme-generated CAIR, while PAICS was shown to physically organize the purinosome by binding all other DNPB enzymes and MTHFD1.

    Evidence 13C-bicarbonate time-course MS on recombinant PAICS; BiFC and reciprocal Co-IP in CRISPR-KO HeLa with metabolic flux analysis

    PMID:35285625 PMID:35331738

    Open questions at the time
    • Stoichiometry and architecture of the assembled metabolon not resolved
    • PPAT exclusion from PAICS interactome unexplained
  14. 2022 Medium

    The atomic reaction mechanism was elucidated computationally: two-step carboxylation via isoCAIR with histidine-assisted deprotonation, phosphorylation-before-condensation in the synthetase site, and three catalytic magnesium ions; a parallel oncogenic axis linked PAICS to FAK phosphorylation.

    Evidence DFT calculations from crystal structures benchmarked against kinetics; Western blot/functional assays for the miR-4731-5p/PAICS/FAK axis

    PMID:35379785 PMID:35914774

    Open questions at the time
    • Mechanistic steps not confirmed by mutagenesis
    • Direct vs indirect basis of PAICS-driven FAK phosphorylation unknown
  15. 2023 High

    The molecular trigger for purinosome assembly was defined: K6-polyubiquitination of PAICS by Cul5/ASB11 recruits the disordered reader UBAP2 to induce phase separation, with ASB11 overexpression driving melanoma tumorigenesis.

    Evidence Co-IP, ubiquitination assays, condensate imaging, CRISPR manipulation, and xenografts

    PMID:37848033

    Open questions at the time
    • How ubiquitinated PAICS templates inclusion of other enzymes not detailed
    • Reversibility/turnover of the condensate not addressed
  16. 2025 Medium

    A protein-stability control axis was established: ACSS2 directly interacts with and acetylates PAICS, targeting it for autophagic degradation, thereby limiting dNTP pools and promoting the senescence-associated secretory phenotype.

    Evidence Co-IP, acetylation and autophagy assays, ACSS2 inhibition/deletion in mice, dNTP and SASP measurements

    PMID:40021646

    Open questions at the time
    • Acetylated residues and the degradation receptor not defined
    • Interplay with ubiquitination-driven assembly not addressed
  17. 2026 Medium

    A neurodevelopmental/neurodegenerative role was placed downstream of C9orf72: paics-knockout zebrafish show cerebellar neuronal loss and DNA repair defects, and restoring paics in C9orf72-deficient fish preserves Purkinje and Granule cells.

    Evidence Zebrafish knockout with single-cell transcriptomics, DNA damage assays, and cross-genotype rescue

    PMID:41810938

    Open questions at the time
    • Mechanism connecting purine supply to C9orf72-dependent neuronal survival unresolved
    • Mammalian validation absent
  18. 2026 Low

    An immunometabolic moonlighting function was proposed: IRF4 activates PAICS in DLBCL, and PAICS binds and augments LDHA to skew NAD+/NADH toward immunosuppression and CD8+ T cell exhaustion.

    Evidence Co-IP, LDHA activity assay, transcriptional assay for IRF4, cytokine profiling, and T cell co-culture/tumor models

    PMID:41991742

    Open questions at the time
    • Single lab, single paper; IRF4 transcriptional regulation rigor not detailed
    • PAICS-LDHA interaction not reciprocally validated across systems

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how PAICS's catalytic, metabolon-scaffolding, and reported non-canonical (chromatin, FAK, LDHA) functions are mechanistically separated and which are direct versus secondary to altered purine/dNTP supply.
  • No structure-function separation of catalytic vs scaffolding mutants in disease/cancer models
  • Direct biochemical basis of nuclear and signaling roles undefined
  • Regulatory cross-talk between ubiquitination, acetylation, and phase separation unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 5 GO:0016740 transferase activity 3 GO:0060090 molecular adaptor activity 2 GO:0140657 ATP-dependent activity 2
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-8953854 Metabolism of RNA 2
Partners
ACSS2ASB11CUL5HDAC1HDAC2LDHAMTHFD1UBAP2
Complex memberships
purinosome

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Human PAICS forms a homo-octamer with an octameric carboxylase core and four peripheral dimers formed by the synthetase domains. Each AIRc active site is formed by structural elements from three AIRc domains, demonstrating that the octamer is essential for carboxylation activity. Four tunnel systems connecting the AIRc and SAICARs active sites were identified, suggesting intermediate (CAIR) channeling between the two active sites. X-ray crystallography (crystal structure at 2.8 Å resolution); functional complementation analyses to identify active sites Journal of molecular biology High 17224163
2009 Zebrafish paics encodes a bifunctional enzyme catalyzing steps 6 and 7 of IMP synthesis; loss-of-function causes pigmentation defects (absent xanthophore/iridophore pigment, reduced melanin) and microphthalmia due to defects in cell cycle exit of retinoblasts. Genetic epistasis showed pigmentation defects depend on GTP synthesis pathway deficiency and microphthalmia on ATP synthesis pathway deficiency, placing paics at a bifurcation point in purine biosynthesis affecting two independent downstream pathways. Zebrafish recessive mutant analysis; maternal-zygotic and maternal-effect mutant analysis; genetic epistasis with separable ATP/GTP pathway outputs; purine supplementation rescue Development (Cambridge, England) High 19570845
1995 The chicken GPAT (PPAT) and AIRC (PAICS) genes are divergently transcribed from a ~230 bp intergenic bidirectional promoter. An initiator-like element overlapping the AIRC transcription start site plays a central role in coordinating expression of both genes; removal of GC/CCAAT boxes from the AIRC proximal half disrupts bidirectional transcription. Deletion mutagenesis in a bireporter vector transfected into HepG2 and chicken LMH cells; gel retardation, DNase I, and methylation interference assays with HeLa nuclear proteins The Journal of biological chemistry Medium 7836476
1997 NRF-1 and Sp1 bind to a cluster of sites (nt 215–260) in the human GPAT-AIRC bidirectional promoter; NRF-1 is required for stable Sp1 binding at this locus, and point mutations in the NRF-1 site or flanking Sp1 sites decrease expression of both GPAT and AIRC (PAICS) in transfected HepG2 cells. Promoter deletion and point-mutation analysis in transfected HepG2 cells; gel retardation assays identifying NRF-1 and Sp1 binding Nucleic acids research Medium 9108165
1988 The bovine PAIS (PAICS) gene is syntenic with PRGS (PPAT) and SOD1, mapping to cattle syntenic group U10, which is conserved with human chromosome 21; this synteny was established by somatic cell hybrid complementation requiring bovine PAIS for growth on selective media. Somatic cell genetics with cow-hamster hybrid cell lines; enzyme electrophoresis for biochemical marker concordance Biochemical genetics Medium 3377762
2019 A homozygous missense mutation p.Lys53Arg in PAICS reduces the catalytic activity of the enzyme to ~10% in patient fibroblasts and ~25% in recombinant purified protein compared to wild-type, establishing a direct catalytic deficiency. The mutation also prevents purinosome formation in patient fibroblasts, which was rescued by transfection with wild-type but not mutant PAICS. Enzyme activity assay in patient skin fibroblasts and recombinant E. coli-expressed protein; purinosome formation assessed by transfection rescue Human molecular genetics High 31600779
2020 Crystal structures of human PAICS in complex with native ligands revealed CAIR bound in both AIRc and SAICARs active sites and SAICAR bound in the SAICARs domain, as well as a structure with SAICAR and an ATP analog in the SAICARs active site. These structures define the architecture of both active sites and substrate/product binding modes. X-ray crystallography of PAICS complexes with native substrates and ATP analog The Journal of biological chemistry High 32571877
2020 PAICS knockdown is required for growth and survival of prostate cancer cells, as demonstrated by clonogenic survival and cell viability assays. Gene knockdown with clonogenic survival and cell viability assays in prostate cancer cell lines The Journal of biological chemistry Medium 32571877
2022 PAICS physically interacts with all other known de novo purine biosynthesis (DNPB) enzymes (except amidophosphoribosyltransferase/PPAT) and with MTHFD1, as demonstrated by bimolecular fluorescence complementation in live cells and co-immunoprecipitation of StrepTag-labeled PAICS reintegrated into PAICS-knockout HeLa cells. These interactions occur in both purine-depleted and purine-rich conditions. C-terminal tagging of PAICS disrupts these interactions and correlates with impaired DNPB activity and perturbed IMP partitioning into AMP and GMP. Bimolecular fluorescence complementation (BiFC) in live cells; Co-IP with StrepTag-labeled PAICS in CRISPR knockout HeLa cells; metabolic flux analysis of DNPB intermediates The Journal of biological chemistry High 35331738
2022 Time-course mass spectrometric analysis of 13C-bicarbonate incorporation demonstrated that the SAICAR synthetase domain of PAICS selectively uses enzyme-generated CAIR over exogenously added CAIR, providing biochemical evidence for substrate channeling of CAIR between the two active sites of PAICS. Time-course mass spectrometry with 13C-bicarbonate isotope tracing using recombinant human PAICS Biochemistry High 35285625
2022 Density functional theory calculations based on PAICS crystal structures elucidated the reaction mechanism: AIRc carboxylation proceeds in two steps (C-C bond formation forming isoCAIR, then deprotonation assisted by an active-site histidine); SAICARs phosphorylation of CAIR precedes condensation with aspartate; three active-site magnesium ions bind substrates and stabilize transition states. Quantum chemical (DFT) calculations using large active-site models built from crystal structures; barriers compared to experimental kinetic data Journal of the American Chemical Society Medium 35914774
2023 K6-polyubiquitination of PAICS by the Cul5/ASB11-based ubiquitin E3 ligase recruits UBAP2 (a ubiquitin-binding protein with intrinsically disordered regions) to induce phase separation and drive purinosome assembly. ASB11 upregulation upon purinosome-inducing stress (via relief of H3K9me3/HP1α transcriptional silencing) triggers this cascade. In human melanoma, constitutive ASB11 overexpression drives purinosome formation supporting proliferation and tumorigenesis. Co-immunoprecipitation; ubiquitination assays; phase separation/condensate imaging; CRISPR/genetic manipulation; xenograft tumor model Molecular cell High 37848033
2013 Crystal structure of invertebrate (Trichoplusia ni) PAICS at 2.8 Å resolution confirmed the bifunctional domain architecture is highly conserved across divergent species and provided insights into substrate binding; comparison with human and prokaryotic homologs revealed a conserved enzymatic framework. X-ray crystallography (SAD phasing) of insect PAICS; comparative structural analysis Proteins Medium 23553965
2015 PAICS knockdown modulates pyruvate kinase activity, and PAICS expression is induced by L-glutamine. A glutamine antagonist (DON) blocked glutamine-mediated induction of PAICS and reduced pyruvate kinase activity, placing PAICS expression under metabolic regulation by glutamine in lung cancer cells. Gene knockdown and overexpression studies; pyruvate kinase activity assay; DON treatment; cell proliferation and invasion assays Oncotarget Medium 26140362
2016 PAICS expression in prostate cancer is transcriptionally regulated by MYC; the BET bromodomain inhibitor JQ1 reduces PAICS expression and causes loss of MYC occupancy at the PAICS promoter. PAICS knockdown inhibits proliferation and invasion in prostate cancer cells in vitro and in vivo (CAM and xenograft models). BET inhibitor (JQ1) treatment; ChIP showing loss of MYC occupancy on PAICS promoter; siRNA/shRNA knockdown; CAM and murine xenograft models The Prostate Medium 27550065
2018 PAICS expression is negatively regulated post-transcriptionally by miR-128, which binds the PAICS 3'-UTR. In bladder cancer cells, PAICS induces EMT by positively regulating SNAI1 and reducing E-cadherin expression. 3'-UTR luciferase reporter assay; miR-128 overexpression; qRT-PCR and immunoblot for SNAI1 and E-cadherin; in vitro proliferation/invasion and in vivo CAM assays Neoplasia Medium 30121007
2018 PAICS knockdown in breast cancer cells blocks G1-S cell cycle transition, suppresses Cyclin E, upregulates Cyclin D1, P21, and CDK4, and activates PARP and caspase-3 while downregulating Bcl-2 and Bcl-xl, inducing apoptosis. Lentiviral shRNA knockdown; flow cytometry for cell cycle analysis; Western blot for cell cycle and apoptosis markers Biological research Medium 30097015
2020 In colorectal cancer cells, PAICS expression is transcriptionally activated by MYC (BET inhibitor JQ1 reduces PAICS expression) and negatively regulated by miR-128. PAICS knockdown upregulates E-cadherin (EMT marker) and reduces tumor growth and metastatic dissemination to liver, lungs, and bone in mice. JQ1 treatment; miR-128 overexpression; stable PAICS knockdown; murine xenograft and metastasis model with PET imaging Cancers Medium 32218208
2020 PAICS interacts with HDAC1 and HDAC2 in gastric cancer cells; PAICS deficiency decreases RAD51 expression, impairs RAD51 recruitment to DNA damage sites by reducing HDAC1/2 deacetylase activity, and thereby prevents DNA damage repair, sensitizing cells to cisplatin. Co-immunoprecipitation (PAICS–HDAC1/HDAC2 interaction); RAD51 ChIP at damage sites; HDAC activity assay; cisplatin sensitivity assay in vitro and in vivo Cell death & disease Medium 32632107
2022 PAICS promotes FAK phosphorylation in breast cancer cells; miR-4731-5p inhibits this by targeting PAICS mRNA. PAICS-dependent FAK phosphorylation drives glycolysis, EMT, migration, and invasion, defining a miR-4731-5p/PAICS/FAK signaling axis. Luciferase 3'-UTR reporter confirming miR-4731-5p targets PAICS; Western blot for FAK phosphorylation; functional assays for glycolysis and EMT; xenograft model Cell death discovery Medium 35379785
2023 PAICS interacts with DYRK3 kinase and co-regulates purinosome formation in oral squamous cell carcinoma; disrupting PAICS inhibits purinosome formation and affects survival of radiation-resistant OSCC cells. The DYRK3/PAICS axis contributes to radiotherapy resistance. In vitro cell models of radiation-resistant OSCC; protein interaction assays; GSK-626616 (DYRK3 inhibitor); purinosome formation imaging; in vivo tumor model International journal of molecular sciences Low 38139175
2025 ACSS2 directly interacts with PAICS and promotes its acetylation; acetylated PAICS undergoes autophagy-mediated degradation, limiting purine biosynthesis and reducing dNTP pools, which exacerbates cytoplasmic chromatin fragment accumulation and drives the senescence-associated secretory phenotype (SASP). Co-immunoprecipitation (ACSS2–PAICS interaction); acetylation assays; autophagy inhibition experiments; Acss2 pharmacological inhibition and deletion in mice; dNTP pool measurement; SASP marker analysis Nature communications Medium 40021646
2025 In lung cancer cells, GART deletion inhibits the PAICS-Akt-β-catenin signaling pathway, suggesting GART acts upstream of PAICS to activate Akt-β-catenin and promote proliferation and migration. GART knockdown; qRT-PCR and Western blot for PAICS, p-Akt, and β-catenin; xenograft tumor model Frontiers in oncology Low 40201340
2026 PAICS loss-of-function in zebrafish (paics knockout) recapitulates cerebellar neuronal loss, neuromuscular junction disruption, motor impairment, and widespread DNA damage repair defects including suppression of key DNA repair pathways. Restoring paics expression in C9orf72-deficient zebrafish resolves DNA damage and preserves Purkinje and Granule cells, identifying PAICS as a critical mediator of cerebellar neuronal survival downstream of C9orf72. Zebrafish paics knockout; single-cell transcriptomics; rescue by paics re-expression in C9orf72 zebrafish; DNA damage assays; neuromuscular junction and motor behavioral analysis Brain : a journal of neurology Medium 41810938
2026 IRF4 transcriptionally activates PAICS in DLBCL cells; PAICS physically interacts with LDHA and augments its activity, skewing the NAD+/NADH balance toward metabolic immunosuppression (elevated TGF-β and IL-10, reduced IFN-γ, enhanced CD8+ T cell exhaustion). This defines an IRF4-PAICS-LDHA axis. Co-immunoprecipitation (PAICS–LDHA interaction); LDHA activity assay; ChIP or transcriptional assay for IRF4-PAICS; cytokine profiling; PAICS/LDHA knockdown with T cell co-culture assays; tumor model NPJ precision oncology Low 41991742

Source papers

Stage 0 corpus · 51 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 The association of c-reactive protein, serum amyloid a and fibrinogen with prevalent coronary heart disease--baseline findings of the PAIS project. Atherosclerosis 94 11395043
2015 Role and regulation of coordinately expressed de novo purine biosynthetic enzymes PPAT and PAICS in lung cancer. Oncotarget 91 26140362
2009 Zebrafish mutations in gart and paics identify crucial roles for de novo purine synthesis in vertebrate pigmentation and ocular development. Development (Cambridge, England) 64 19570845
2006 Octameric structure of the human bifunctional enzyme PAICS in purine biosynthesis. Journal of molecular biology 58 17224163
2018 A Role for De Novo Purine Metabolic Enzyme PAICS in Bladder Cancer Progression. Neoplasia (New York, N.Y.) 47 30121007
2020 PAICS, a Purine Nucleotide Metabolic Enzyme, is Involved in Tumor Growth and the Metastasis of Colorectal Cancer. Cancers 46 32218208
2016 Expression and Role of PAICS, a De Novo Purine Biosynthetic Gene in Prostate Cancer. The Prostate 43 27550065
2019 Roles of highly expressed PAICS in lung adenocarcinoma. Gene 41 30641222
2018 Knockdown of PAICS inhibits malignant proliferation of human breast cancer cell lines. Biological research 36 30097015
2014 An enzymatic extraction of proanthocyanidins from País grape seeds and skins. Food chemistry 36 25172676
1995 Analysis of the chicken GPAT/AIRC bidirectional promoter for de novo purine nucleotide synthesis. The Journal of biological chemistry 35 7836476
2022 Multienzyme interactions of the de novo purine biosynthetic protein PAICS facilitate purinosome formation and metabolic channeling. The Journal of biological chemistry 31 35331738
2023 PAICS ubiquitination recruits UBAP2 to trigger phase separation for purinosome assembly. Molecular cell 28 37848033
2020 PAICS, a De Novo Purine Biosynthetic Enzyme, Is Overexpressed in Pancreatic Cancer and Is Involved in Its Progression. Translational oncology 27 32422575
2019 Combinatorial targeting of MTHFD2 and PAICS in purine synthesis as a novel therapeutic strategy. Cell death & disease 26 31624245
2019 PAICS deficiency, a new defect of de novo purine synthesis resulting in multiple congenital anomalies and fatal outcome. Human molecular genetics 25 31600779
2020 PAICS contributes to gastric carcinogenesis and participates in DNA damage response by interacting with histone deacetylase 1/2. Cell death & disease 24 32632107
1997 Role of NRF-1 in bidirectional transcription of the human GPAT-AIRC purine biosynthesis locus. Nucleic acids research 23 9108165
2016 Topical dihydrotestosterone to treat micropenis secondary to partial androgen insensitivity syndrome (PAIS) before, during, and after puberty - a case series. Journal of pediatric endocrinology & metabolism : JPEM 22 26352087
2020 Crystal structures of human PAICS reveal substrate and product binding of an emerging cancer target. The Journal of biological chemistry 18 32571877
2022 Tumor suppressive role of microRNA-4731-5p in breast cancer through reduction of PAICS-induced FAK phosphorylation. Cell death discovery 17 35379785
2023 PAICS as a potential target for cancer therapy linking purine biosynthesis to cancer progression. Life sciences 16 37673296
2021 PAICS is related to glioma grade and can promote glioma growth and migration. Journal of cellular and molecular medicine 16 34173716
2025 ACSS2 drives senescence-associated secretory phenotype by limiting purine biosynthesis through PAICS acetylation. Nature communications 15 40021646
2006 Differential release of plasminogen activator inhibitors (PAIs) during dual perfusion of human placenta: implications in preeclampsia. Placenta 15 16820203
2010 The detection of Helicobacter pylori cag pathogenicity islands (PAIs) and expression of matrix metalloproteinase-7 (MMP-7) in gastric epithelial dysplasia and intramucosal cancer. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 14 20820985
2022 Reaction Mechanism of Human PAICS Elucidated by Quantum Chemical Calculations. Journal of the American Chemical Society 11 35914774
2021 Regulating COX10-AS1 / miR-142-5p / PAICS axis inhibits the proliferation of non-small cell lung cancer. Bioengineered 11 34323174
2022 Dysregulation of Pseudogenes/lncRNA-Hsa-miR-1-3p-PAICS Pathway Promotes the Development of NSCLC. Journal of oncology 9 36081668
2007 Mobility of the Yersinia High-Pathogenicity Island (HPI): transfer mechanisms of pathogenicity islands (PAIS) revisited (a review). Acta microbiologica et immunologica Hungarica 9 17899790
2003 A novel mutation in the D-box of the androgen receptor gene (S597R) in two unrelated individuals Is associated with both normal phenotype and severe PAIS. Hormone research 9 14646391
2024 Genome-scale CRISPR-Cas9 screen identifies PAICS as a therapeutic target for EGFR wild-type non-small cell lung cancer. MedComm 8 38463398
1988 Mapping of bovine PRGS and PAIS genes in hybrid somatic cells: syntenic conservation with human chromosome 21. Biochemical genetics 8 3377762
2023 PAICS/DYRK3 Multienzyme Interactions as Coregulators of Purinosome Formation and Metabolism on Radioresistance in Oral Squamous Cell Carcinoma. International journal of molecular sciences 6 38139175
2020 Potential suppressive functions of microRNA-504 in cervical cancer cells malignant process were achieved by targeting PAICS and regulating EMT. Archives of gynecology and obstetrics 6 32417959
2013 Crystal structure of the invertebrate bifunctional purine biosynthesis enzyme PAICS at 2.8 Å resolution. Proteins 6 23553965
2024 Expanding clinical spectrum of PAICS deficiency: Comprehensive analysis of two sibling cases. European journal of human genetics : EJHG 4 39604553
2022 Evidence Supporting Substrate Channeling between Domains of Human PAICS: A Time-Course Analysis of 13C-Bicarbonate Incorporation. Biochemistry 4 35285625
2025 GART promotes the proliferation and migration of human non-small cell lung cancer cell lines A549 and H1299 by targeting PAICS-Akt-β-catenin pathway. Frontiers in oncology 3 40201340
2025 Retinol-driven Gene Signatures Predict Lung Adenocarcinoma Outcomes and Highlight PAICS as a Therapeutic Opportunity. Phenomics (Cham, Switzerland) 2 41659742
2020 Generation of human induced pluripotent stem cell (SKLRMi001-A) from a patient with partial androgen insensitivity syndrome (PAIS). Stem cell research 2 32505105
2025 Analysis of Stereotyped B-Cell Receptor Frequencies Among Portuguese De Novo-Diagnosed Chronic Lymphocytic Leukemia Patients (PAIS Study). Cancers 1 40282492
2025 Introducing New Inhibitors of PAICS, a De Novo Purine Biosynthesis Enzyme, through Structure-Based Virtual Screening. Iranian journal of biotechnology 1 40463949
2025 C1QBP forms a positive feedback loop with the PAICS/FAK/C-MYC axis to promote cancer cell proliferation. Oncogene 1 41028903
2024 Generation of a Rat Monoclonal Antibody for Human PAICS, a de novo Purine Biosynthetic Enzyme. Monoclonal antibodies in immunodiagnosis and immunotherapy 1 38836825
2024 Identification of the Third Patient With PAICS Deficiency Harbouring the p.(Lys53Arg) Recurrent Variant, Extending the Phenotype Diversity. Clinical genetics 1 39726239
2026 PAICS mediates DNA damage and cerebellar neuronal loss in C9orf72 amyotrophic lateral sclerosis. Brain : a journal of neurology 0 41810938
2026 Integrative multi-omics analysis identifies PAICS as a key regulator of epithelial-mesenchymal transition in breast cancer metastasis. Discover oncology 0 41979850
2026 AI-guided discovery of the IRF4-PAICS-LDHA axis as a multitarget hub linking tumor metabolism to CD8+ T cell exhaustion in DLBCL. NPJ precision oncology 0 41991742
2026 Correction: Huang et al. PAICS/DYRK3 Multienzyme Interactions as Coregulators of Purinosome Formation and Metabolism on Radioresistance in Oral Squamous Cell Carcinoma. Int. J. Mol. Sci. 2023, 24, 17346. International journal of molecular sciences 0 42123737
2013 Commentary on "genomic characterization of testis cancer: association of alterations with outcome of clinical stage mixed germ cell non-seminomatous germ cell tumor of the testis." Mohamed GH, Gelfond JAL, Nicolas MM, et al Mohamed GH, Gelfond JA, Nicolas MM, Brand TC, Sarvis JA, Leach RJ, Johnson-Pais TL, Department of Pathology, University of Texas Health Science Center, San Antonio, TX 78229, USA: Urology 2012;80:485. Urologic oncology 0 23465478

Missed literature

Know a paper Affinage missed for PAICS? Flag it for the maintainers and the community.

No submissions yet.