Affinage

AQP1

Aquaporin-1 · UniProt P29972

Length
269 aa
Mass
28.5 kDa
Annotated
2026-06-09
100 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AQP1 (CHIP28) is the prototypical integral-membrane water channel, establishing the molecular basis for rapid, selective osmotic water movement across erythrocyte and epithelial membranes (PMID:1373524, PMID:1526967). Expression of CHIP28 in Xenopus oocytes and reconstitution of purified protein into proteoliposomes confer up to 50-fold increases in osmotic water permeability with low activation energy, while excluding urea and protons, demonstrating that the protein itself is the functional water pore (PMID:1510932, PMID:1526967). AQP1 assembles as a homotetramer of ~8.5 nm intramembrane particles in which each monomer functions as an independent water-conducting unit (PMID:7693713, PMID:7511600). Topology mapping established the unusual four-transmembrane fold with an internal signal sequence that re-initiates translocation of the C-terminal domain (PMID:7514605), and cysteine 189 is the residue responsible for mercurial inhibition and proper protein processing (PMID:7677994). Beyond water, the channel provides a shared aqueous pathway for small polyols such as glycerol and ethylene glycol (PMID:7491270). AQP1 is concentrated in constitutively water-permeable epithelia and endothelia—renal proximal tubule and thin descending limb, gallbladder, choroid plexus and broad extrarenal sites—where its membrane localization matches segments of high transcellular fluid flux (PMID:7678419, PMID:7513954, PMID:15859952). Its expression is induced transcriptionally by hypertonicity through ERK/p38/JNK MAPK signaling acting on a promoter response element (PMID:12600999) and by hypoxia through HIF-1α (PMID:23948641), and AQP1 in turn participates in cell volume regulation, proliferation, migration and senescence with downstream effects on TGF-β, RhoA, JAK-STAT and HIF-1α signaling (PMID:23948641, PMID:26176849, PMID:30580569, PMID:32188840). A promoter variant (rs2075574) that lowers AQP1 expression impairs glucose-driven osmotic water transport across the peritoneal membrane, mechanistically linking reduced channel abundance to defective peritoneal ultrafiltration in dialysis patients (PMID:34670044).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1992 High

    Resolved the long-standing question of how membranes achieve high water permeability by identifying CHIP28 as a discrete, selective water channel rather than diffusion through lipid.

    Evidence CHIP28 RNA expression in Xenopus oocytes with osmotic swelling and reversible mercurial inhibition; purification and proteoliposome reconstitution with stopped-flow permeability assays

    PMID:1373524 PMID:1510932 PMID:1526967

    Open questions at the time
    • Atomic pore architecture not resolved
    • Selectivity filter residues not yet identified
  2. 1993 High

    Defined the molecular determinant of mercurial sensitivity and showed individual subunits within the oligomer conduct water independently.

    Evidence Site-directed mutagenesis of all four cysteines to serine with oocyte osmotic swelling and HgCl2 inhibition; glycosylation/processing analysis

    PMID:7677994

    Open questions at the time
    • Mechanism by which C189 modification blocks water flux not structurally defined
  3. 1993 High

    Established the quaternary structure and tissue distribution, connecting tetrameric channel particles to the kidney segments that require constitutive water permeability.

    Evidence Freeze-fracture EM of proteoliposomes, CHO cells and kidney tubules; immunolocalization across nephron segments and reproductive tract; rat ortholog cloning with antisense suppression

    PMID:1282299 PMID:7678419 PMID:7693713 PMID:8223717 PMID:8421053

    Open questions at the time
    • Trafficking/sorting signals directing apical vs basolateral delivery not defined
  4. 1994 High

    Overturned the predicted six/seven-helix topology, establishing the four-transmembrane fold with an internal signal sequence, and confirmed independent monomeric pore function genetically.

    Evidence Chimeric reporter topology mapping, protease protection, glycosylation, cell-free translation; wild-type/mutant heterodimer osmotic assays with HgCl2 titration

    PMID:7511600 PMID:7514605

    Open questions at the time
    • The NPA-loop pore-forming detail not resolved at this stage
    • Atomic-resolution channel structure not yet available
  5. 1994 Medium

    Provided spectroscopic and projection-structure evidence consistent with an aqueous pore embedded within the folded protein.

    Evidence CD and FTIR secondary-structure analysis, hydrogen-deuterium exchange kinetics, 12 Å 2D crystal projection structure by electron microscopy

    PMID:7524655 PMID:7588813 PMID:8218256

    Open questions at the time
    • Low resolution; no mutagenesis validation of pore-lining residues
    • Single-study structural assignments
  6. 1995 Medium

    Extended the channel's selectivity profile, showing it conducts small polyols through the same pathway as water while excluding urea and larger solutes.

    Evidence Oocyte and proteoliposome osmotic swelling, tritiated glycerol uptake, reflection-coefficient analysis, mercurial/copper inhibition

    PMID:7491270

    Open questions at the time
    • Physiological significance of glycerol transport unclear
    • Polyol permeability secondary to dominant water-channel identity
  7. 2006 Medium

    Tested and largely excluded a major physiological role for AQP1 in erythrocyte CO2 transport while uncovering an indirect effect on NH3 flux.

    Evidence Stopped-flow fluorimetry of pH changes in ghosts from human AQP1-null (CO-null) variants and AQP1 knockout mice; earlier oocyte CO2 permeability measurements

    PMID:12096045 PMID:16574458

    Open questions at the time
    • Discrepancy between oocyte and reconstituted/knockout systems unresolved
    • Mechanism of indirect RhAG/NH3 effect not defined
  8. 2013 Medium

    Linked AQP1-mediated water flux to cell-volume control and identified HIF-1α as the hypoxic transcriptional regulator of AQP1.

    Evidence Lentiviral knockdown/overexpression in Schwann cells with volume measurement and hypoxic edema assays; HIF-1α knockdown with qPCR/Western readout

    PMID:23948641

    Open questions at the time
    • Direct HIF-1α binding to AQP1 promoter not demonstrated
    • Single cell type
  9. 2015 Medium

    Placed AQP1 upstream of TGF-β, RhoA and focal-adhesion signaling in controlling proliferation, adhesion and invasion in cancer cells.

    Evidence RNAi silencing in osteosarcoma lines with cell-cycle/apoptosis/invasion assays, nude-mouse tumor growth, pathway expression analysis and GSEA

    PMID:26176849

    Open questions at the time
    • Mechanism connecting water/solute transport to TGF-β signaling unknown
    • No direct molecular interaction shown
  10. 2019 Medium

    Established AQP1's contribution to organ-level fluid physiology and hypoxic vascular disease through knockout models.

    Evidence AQP1 knockout (and AQP1/AQP4 double knockout) mice with pulmonary hypertension hemodynamics, CSF pressure/outflow and MRI ventricular measurements, plus HIF-1α stability assays

    PMID:30580569 PMID:30813473

    Open questions at the time
    • How AQP1 stabilizes HIF-1α protein not defined
    • Cell-autonomous vs systemic contributions to CSF homeostasis not separated
  11. 2020 Medium

    Identified AQP1 as a negative regulator of JAK-STAT-driven senescence in tissue stem/progenitor cells.

    Evidence Lentiviral AQP1 overexpression in aged tendon stem/progenitor cells with senescence, migration and differentiation assays and JAK-STAT Western blots

    PMID:32188840

    Open questions at the time
    • Direct link between channel activity and JAK-STAT inhibition unproven
    • Single cell system
  12. 2021 High

    Provided human genetic and mechanistic proof that reduced AQP1 expression impairs osmotic water transport across the peritoneal membrane.

    Evidence Promoter-variant (rs2075574) reporter assays, expression and osmotic water transport measurements, and clinical genetic association in 1851 dialysis patients

    PMID:34670044

    Open questions at the time
    • Whether the variant affects other AQP1-dependent tissues not addressed
  13. 2024 Low

    Proposed AQP1 as a suppressor of TLR4/MyD88/NF-κB inflammatory signaling in intestinal epithelium under chemical stress.

    Evidence DEHP exposure in vivo and in vitro with AQP1 expression, inflammatory pathway Western blot/expression and barrier function assays

    PMID:38916549

    Open questions at the time
    • No direct AQP1-TLR4 interaction evidence; pathway linkage is indirect
    • Single lab, not independently confirmed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How AQP1 transport activity is mechanistically coupled to the signaling pathways (TGF-β, RhoA, JAK-STAT, HIF-1α, NF-κB) it influences remains unresolved.
  • No molecular mechanism linking water/solute flux to transcriptional/signaling output
  • No direct physical partners identified for the signaling effects
  • Atomic-resolution selectivity-filter structure absent from the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 5 GO:0140104 molecular carrier activity 4 GO:0005198 structural molecule activity 3
Localization
GO:0005886 plasma membrane 4 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-382551 Transport of small molecules 5 R-HSA-8953897 Cellular responses to stimuli 3
Complex memberships
AQP1 homotetramer

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 CHIP28 (AQP1) functions as a water channel: Xenopus oocytes injected with CHIP28 RNA showed increased osmotic water permeability, reversibly inhibited by mercuric chloride, establishing CHIP28 as a functional membrane water channel. Xenopus oocyte expression system, osmotic swelling assay, mercurial inhibition Science High 1373524
1992 Purified CHIP28 (AQP1) reconstituted into proteoliposomes exhibits up to 50-fold higher osmotic water permeability than control liposomes, without increased urea or proton permeability, demonstrating that CHIP28 itself is the functional unit of the erythrocyte water channel. Protein purification from human RBCs, reconstitution into proteoliposomes, stopped-flow osmotic permeability assay, mercurial inhibition Biochemistry High 1510932
1992 CHIP28 (AQP1) is the erythrocyte water channel: stripping erythrocyte membranes of nearly all proteins except CHIP28 retained high water permeability; proteoliposomes reconstituted with solubilized CHIP28 had high Pf with low activation energy (~2.2 kcal/mol), inhibited by mercurials, and excluded urea. Single-channel water permeability ~10^-13 cm3/s. Membrane protein stripping, proteoliposome reconstitution, osmotic permeability measurement, N-terminal sequence analysis The Journal of biological chemistry High 1526967
1993 Cysteine 189 is the mercury-sensitive residue in CHIP28 (AQP1): site-directed mutagenesis of each of the four cysteines (87, 102, 152, 189) to serine showed that only C189S mutant was resistant to HgCl2 inhibition. Individual CHIP28 subunits in a tetramer function independently as water pores. Residue 189 is also critical for proper protein processing. Site-directed mutagenesis, Xenopus oocyte expression, osmotic swelling assay, HgCl2 inhibition, immunoblot glycosylation analysis The Journal of biological chemistry High 7677994
1993 CHIP28 (AQP1) assembles as tetramers in membranes: freeze-fracture EM of CHIP28-reconstituted proteoliposomes, CHIP28-transfected CHO cells, and rat kidney tubules revealed intramembrane particles (~8.5 nm diameter) composed of four subunits around a central depression. Predicted single-channel Pf of 3.6×10^-14 cm3/s at 10°C was consistent with measured tissue Pf values. Freeze-fracture electron microscopy, rotary shadowing, osmotic water permeability measurement in CHO cells and kidney tubules The Journal of cell biology High 7693713
1993 CHIP28 (AQP1) localizes to apical brush-border and basolateral membranes throughout proximal convoluted and straight tubules and descending thin limbs of Henle in rat kidney, comprising 3.8% of isolated proximal tubule brush border protein. CHIP28 is absent from ascending thin limbs, thick ascending limbs, distal tubules, and collecting duct, correlating precisely with constitutively high water permeability segments. Immunolocalization by light and electron microscopy, Western blotting/quantitative immunochemistry on isolated nephron segments The Journal of cell biology High 7678419
1993 Rat kidney CHIP28k (AQP1 ortholog with 94% identity to human CHIP28) functions as a selective water channel: expression in Xenopus oocytes increased Pf ~8-fold; not permeable to ions. Antisense cRNA blocked the cortical kidney mRNA-induced Pf increase. Apical membrane vesicles from proximal tubule had high water but low urea and proton permeabilities, enriching a 28-kDa protein 25-fold. cDNA cloning, Xenopus oocyte expression, two-electrode voltage clamp, in situ hybridization, antisense suppression, membrane vesicle reconstitution The Journal of cell biology High 8421053
1993 Secondary structure of purified functional CHIP28 (AQP1) consists of ~40% alpha-helix and ~43% beta-sheet/-turn by CD and FTIR spectroscopy. HgCl2 inhibition of water transport does not alter the CD spectrum, indicating mercury acts without global protein unfolding. CD spectroscopy, FTIR spectroscopy, proteoliposome reconstitution Biochemistry Medium 8218256
1993 CHIP28 (AQP1) localizes to apical brush-border and basolateral membranes of proximal tubule S2/S3 segments and descending thin limbs in rat kidney; also present in subapical vesicles and vasa recta endothelium. Absent from ascending limbs, thick ascending limb, distal convoluted tubule. Immunocytochemistry on rat kidney sections, Western blotting of kidney fractions The American journal of physiology High 1282299
1993 CHIP28 (AQP1) is expressed in brush-border and basolateral membranes of nonciliated cells of the efferent duct (male reproductive tract), which shows constitutively high fluid reabsorption. Ciliated cells in the same epithelium lack CHIP28. Also found in ampulla of vas deferens, seminal vesicles, and prostate. Western blotting, indirect immunofluorescence, protein A-gold immunolabeling, freeze-fracture EM European journal of cell biology Medium 8223717
1994 CHIP28 (AQP1) spans the membrane four times (not six or seven as hydropathy predicts): topology mapping using chimeric reporters inserted at nine positions in the CHIP28 coding region showed only four transmembrane helices, with residues 52-68 and 143-157 residing on lumenal and cytosolic ER surfaces respectively. A second internal signal sequence (residues 155-186) re-initiates translocation of a C-terminal domain into the ER lumen. Chimeric protein topology mapping in Xenopus oocytes, protease sensitivity assay, cell-free translation of truncated cDNAs, N-linked glycosylation at engineered sites, epitope tagging The Journal of cell biology High 7514605
1994 CHIP28 (AQP1) monomers within the tetrameric complex function independently as water channels: wild-type/non-functional heterodimers (CHIP28-C189W) showed Pf proportional to the wild-type subunit contribution; wild-type/mercurial-insensitive heterodimers (CHIP28-C189S) showed ~44% inhibition by HgCl2, consistent with exactly one sensitive subunit per dimer. Chimeric cDNA dimer construction, Xenopus oocyte expression, osmotic swelling assay, quantitative immunofluorescence for plasma membrane expression, HgCl2 inhibition The Journal of biological chemistry High 7511600
1994 CHIP28 (AQP1) is widely distributed in extrarenal epithelial and endothelial cells: immunostaining detected AQP1 in lung alveoli, bronchial mucosa and glands, choroid plexus, ciliary body, iris, lens surface, colonic crypt, sweat gland, pancreatic acini, gallbladder epithelium, placental syncytiotrophoblast, and vascular endothelium across multiple tissues. In situ hybridization, immunohistochemistry on rat and human tissues, Northern blot, immunoblot The American journal of physiology Medium 7513954
1994 Projection structure of CHIP28 (AQP1) at 12 Å resolution from 2D crystals in lipid bilayers: tetragonal lattice (a=b=99.2 Å), plane group p4g, with four CHIP28 dimers per unit cell. Tetrameric arrangement around 4-fold axes with central stain exclusion consistent with a pore region. 2D crystallization in synthetic lipid bilayers, low-dose electron microscopy, Fourier transform image analysis Biochemistry Medium 7524655
1995 AQP1 provides a pathway for small polyols including glycerol and ethylene glycol but excludes urea, meso-erythritol, and larger polyols: osmotic swelling assay in AQP1-injected oocytes and AQP1 proteoliposomes showed significant glycerol permeability inhibited by pCMBS and CuSO4. Glycerol reflection coefficient (0.74-0.80) indicates water and glycerol share the same pathway. Xenopus oocyte expression, osmotic swelling assay, tritiated glycerol uptake, stopped-flow light scattering in proteoliposomes, mercurial and copper inhibition Pflugers Archiv : European journal of physiology Medium 7491270
1995 CHIP28 (AQP1) secondary structure contains approximately 36% alpha-helix and 42% beta-sheet by FTIR; over 80% of peptide groups undergo hydrogen-deuterium exchange within 5 min, an exceptionally high rate consistent with a large aqueous pore within the protein structure. FTIR spectroscopy in H2O and 2H2O, hydrogen-deuterium exchange kinetics European journal of biochemistry Medium 7588813
2002 AQP1 expressed in Xenopus oocytes increases membrane CO2 permeability, suggesting AQP1 may facilitate CO2 transport in addition to water. However, data from AQP1 reconstituted into liposomes and from AQP1 knockout mice appear inconsistent with a major CO2 transport role in those preparations. Xenopus oocyte expression, CO2 permeability measurement, AQP1 knockout mouse studies, liposome reconstitution The Journal of physiology Low 12096045
2003 Hypertonicity-induced AQP1 expression in renal medullary cells requires activation of all three MAPK pathways (ERK, p38, and JNK) and a hypertonicity-response element in the AQP1 promoter: pharmacological inhibition of MEK1/2, MKK3/6, or MKK4 (upstream kinases for ERK, p38, JNK respectively) attenuated hypertonic induction of AQP1, and dominant-negative JNK1/2 significantly reduced AQP1 promoter activity. Pharmacological kinase inhibitors (U0126, SB203580, SP600125), dominant-negative kinase mutant overexpression, AQP1 promoter reporter assay, Western blot The Journal of biological chemistry Medium 12600999
2006 AQP1 does not play a major role in CO2 transport in red cell ghost membranes: stopped-flow measurements of CO2 transport kinetics showed no significant difference between CO(null) human variants (lacking AQP1) and controls, or between AQP1 knockout and wild-type mice. AQP1 absence did reduce NH3 transport rates by ~30%, which was attributed to an indirect effect on RhAG-mediated transport. Stopped-flow fluorimetry measuring intracellular pH changes in erythrocyte ghosts from human AQP1-null variants (CO(null)) and AQP1 knockout mice Transfusion clinique et biologique Medium 16574458
2005 AQP1 localizes to both apical and basolateral membranes of mouse gallbladder epithelial cells, as well as subapical vesicles, whereas AQP8 is restricted to the apical membrane. This dual-membrane localization supports AQP1 as the primary basolateral pathway for transcellular water movement in gallbladder epithelium. RT-PCR, immunoblotting, immunohistochemistry on mouse gallbladder epithelium Biology of the cell Medium 15859952
2010 AQP1 expression is induced in reactive astrocytes following cortical stab wound injury in vivo and can be mimicked in vitro by scratch injury; this induction is blocked by MEK1/2 inhibitor U0126, placing AQP1 upregulation downstream of the MAPK/ERK signaling pathway in injury-reactive astrocytes. Cortical stab wound in vivo model, in vitro scratch injury assay, pharmacological MEK inhibition (U0126), immunostaining, Western blot Glia Medium 19610096
2013 AQP1 mediates fast water transport in Schwann cells and controls cell volume: lentiviral knockdown of AQP1 caused cell shrinkage while overexpression caused cell swelling. AQP1 knockdown protected against hypoxia-induced edema. Hypoxic induction of AQP1 occurs in a HIF-1α-dependent manner: HIF-1α knockdown reduced hypoxia-induced AQP1 expression at both mRNA and protein levels. Lentiviral shRNA knockdown and overexpression, cell volume measurement, hypoxia model, HIF-1α knockdown, Western blot, qPCR Neuroscience Medium 23948641
2015 AQP1 knockdown in osteosarcoma cells (U2OS, MG63) inhibited cell proliferation, induced G1 arrest and apoptosis, and reduced cell adhesion and invasion. AQP1 silencing suppressed TGF-β1/TGF-β2, RhoA, and LAMB2 expression, placing AQP1 upstream of TGF-β signaling and focal adhesion pathways in osteosarcoma cells. RNAi-mediated gene silencing, flow cytometry (cell cycle, apoptosis), cell adhesion and invasion assays, in vivo tumor growth in nude mice, Western blot, real-time PCR, GSEA Cancer biology & therapy Medium 26176849
2019 AQP1 knockout mice show attenuation of hypoxic pulmonary hypertension: Aqp1 deficiency reduced right ventricular systolic pressure and pulmonary vascular remodeling. In vitro, Aqp1 deletion reduced hypoxia-induced proliferation, apoptosis resistance, and migration of pulmonary artery smooth muscle cells and repressed HIF-1α protein stability. AQP1 loss also protected lung endothelial cells from hypoxic apoptosis. AQP1 knockout mouse model, right ventricular pressure measurement, histomorphometry, primary cell culture, cell cycle/apoptosis/migration assays, Western blot for HIF-1α Arteriosclerosis, thrombosis, and vascular biology Medium 30580569
2019 Both AQP1 and AQP4 contribute to cerebrospinal fluid production: AQP1 knockout, AQP4 knockout, and double knockout mice all showed significantly altered intraventricular pressure and CSF outflow compared to wild-type controls. Double knockout additionally altered ventricular compliance and CSF drainage, revealing additive roles for AQP1 in CSF homeostasis. Intraventricular pressure recording, CSF outflow measurement, MRI ventricular volume quantification in single and double AQP knockout mice Cells Medium 30813473
2020 AQP1 expression declines with tendon aging; AQP1 overexpression in aged tendon stem/progenitor cells (TSPCs) attenuated senescence, restored self-renewal, migration, and tenogenic differentiation. Mechanistically, aged TSPCs showed activated JAK-STAT signaling, and AQP1 overexpression inhibited JAK-STAT pathway activation, placing AQP1 as a negative regulator of JAK-STAT-driven senescence. Lentiviral overexpression of AQP1 in aged TSPCs, senescence assays, migration and differentiation assays, Western blot for JAK-STAT pathway components Cell death & disease Medium 32188840
2021 The AQP1 promoter variant rs2075574 reduces AQP1 promoter activity, AQP1 protein expression, and glucose-driven osmotic water transport across the peritoneal membrane, mechanistically linking reduced AQP1 expression to impaired peritoneal ultrafiltration in dialysis patients. AQP1 promoter activity reporter assay, AQP1 expression measurement in cells and human samples, osmotic water transport assay, clinical genetic association in 1851 patients The New England journal of medicine High 34670044
2024 AQP1 deficiency exacerbates phthalate (DEHP)-induced duodenal epithelial barrier disruption: DEHP directly inhibits AQP1 expression, leading to activation of the TLR4/MyD88/NF-κB inflammatory signaling pathway and disruption of intestinal integrity. AQP1 is thus mechanistically placed as a suppressor of TLR4/MyD88/NF-κB activation in intestinal epithelium. DEHP exposure in vivo and in vitro, AQP1 expression analysis, inflammatory pathway Western blot and gene expression, barrier function assays, mitochondrial morphology assessment Journal of agricultural and food chemistry Low 38916549

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Molecular mechanisms of T cell co-stimulation and co-inhibition. Nature reviews. Immunology 2418 23470321
1992 Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein. Science (New York, N.Y.) 1557 1373524
1998 Co-activators and co-repressors in the integration of transcriptional responses. Current opinion in cell biology 497 9640539
1993 CHIP28 water channels are localized in constitutively water-permeable segments of the nephron. The Journal of cell biology 469 7678419
1992 Reconstitution of functional water channels in liposomes containing purified red cell CHIP28 protein. Biochemistry 467 1510932
2000 Smads as transcriptional co-modulators. Current opinion in cell biology 450 10712925
1993 The mercury-sensitive residue at cysteine 189 in the CHIP28 water channel. The Journal of biological chemistry 436 7677994
1997 Role of co-activators and co-repressors in the mechanism of steroid/thyroid receptor action. Recent progress in hormone research 421 9238851
2016 The TNF Receptor Superfamily in Co-stimulating and Co-inhibitory Responses. Immunity 363 27192566
1992 Localization of the CHIP28 water channel in rat kidney. The American journal of physiology 248 1282299
2004 Quantifying the relationship between co-expression, co-regulation and gene function. BMC bioinformatics 234 15053845
2016 Co-stimulatory and Co-inhibitory Pathways in Autoimmunity. Immunity 228 27192568
1993 Tetrameric assembly of CHIP28 water channels in liposomes and cell membranes: a freeze-fracture study. The Journal of cell biology 193 7693713
2002 New regulatory co-receptors: inducible co-stimulator and PD-1. Current opinion in immunology 176 12413529
2000 Co-repressors 2000. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 174 11023972
1992 Functional reconstitution of the isolated erythrocyte water channel CHIP28. The Journal of biological chemistry 173 1526967
2018 Cytonuclear integration and co-evolution. Nature reviews. Genetics 163 30018367
1994 Extrarenal tissue distribution of CHIP28 water channels by in situ hybridization and antibody staining. The American journal of physiology 155 7513954
2020 Transcriptome and translatome co-evolution in mammals. Nature 154 33177713
2003 Hypertonicity-induced aquaporin-1 (AQP1) expression is mediated by the activation of MAPK pathways and hypertonicity-responsive element in the AQP1 gene. The Journal of biological chemistry 147 12600999
2008 Protein co-evolution, co-adaptation and interactions. The EMBO journal 135 18818697
1982 Co-metabolism. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 132 6125958
1993 Cloning, functional analysis and cell localization of a kidney proximal tubule water transporter homologous to CHIP28. The Journal of cell biology 129 8421053
2002 Negative co-receptors on lymphocytes. Current opinion in immunology 119 11973140
2016 Co- and Post-Translational Protein Folding in the ER. Traffic (Copenhagen, Denmark) 118 26947578
2005 CREB: the unindicted cancer co-conspirator. Trends in cell biology 109 16084096
2006 Transcriptional co-repressors of Runx2. Journal of cellular biochemistry 106 16440320
2011 Resistance to MEK inhibitors: should we co-target upstream? Science signaling 104 21447797
1993 Localization of the CHIP28 water channel in reabsorptive segments of the rat male reproductive tract. European journal of cell biology 104 8223717
2009 Cancer immunotherapy: co-stimulatory agonists and co-inhibitory antagonists. Clinical and experimental immunology 100 19659765
2003 Tip60 is a co-repressor for STAT3. The Journal of biological chemistry 97 12551922
2024 CO2 Electrolyzers. Chemical reviews 96 38518224
1994 Functional independence of monomeric CHIP28 water channels revealed by expression of wild-type mutant heterodimers. The Journal of biological chemistry 87 7511600
2019 Co-stimulatory and co-inhibitory pathways in cancer immunotherapy. Advances in cancer research 86 31202358
2008 Transcriptional co-expression and co-regulation of genes coding for components of the oxidative phosphorylation system. BMC genomics 85 18194548
2002 Transport of volatile solutes through AQP1. The Journal of physiology 85 12096045
1995 CO dehydrogenase. Annual review of microbiology 84 8561463
2007 Co-chaperone FKBP38 promotes HERG trafficking. The Journal of biological chemistry 77 17569659
2010 Cell locations for AQP1, AQP4 and 9 in the non-human primate brain. Neuroscience 74 20226845
2019 AQP1 and AQP4 Contribution to Cerebrospinal Fluid Homeostasis. Cells 72 30813473
1994 Biogenesis and transmembrane topology of the CHIP28 water channel at the endoplasmic reticulum. The Journal of cell biology 72 7514605
2006 Artemisia and Ambrosia hypersensitivity: co-sensitization or co-recognition? Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 71 16650052
2012 Co-expression vs. co-infection using baculovirus expression vectors in insect cell culture: Benefits and drawbacks. Biotechnology advances 66 22297133
2012 Co-transcriptional nuclear actin dynamics. Nucleus (Austin, Tex.) 64 23138849
2004 From co-expression to co-regulation: how many microarray experiments do we need? Genome biology 64 15239833
1994 Sources of carbon monoxide (CO) in biological systems and applications of CO detection technologies. Seminars in perinatology 63 8209283
1993 Secondary structure analysis of purified functional CHIP28 water channels by CD and FTIR spectroscopy. Biochemistry 60 8218256
2005 The evolving crosstalk between co-stimulatory and co-inhibitory receptors: HVEM-BTLA. Trends in immunology 56 15922943
2021 AQP1 Promoter Variant, Water Transport, and Outcomes in Peritoneal Dialysis. The New England journal of medicine 54 34670044
2010 ESCRT & Co. Biology of the cell 53 20222872
2008 Co- and post-translational modifications in Rubisco: unanswered questions. Journal of experimental botany 53 18353761
2005 Keeping it together: co-ordinating plant growth. Current opinion in plant biology 52 16326130
1997 Co-receptors of B lymphocytes. Current opinion in immunology 51 9203413
1992 Oncogene co-operation in leukaemogenesis. Cancer surveys 50 1451108
2019 Physiological and pathological impact of AQP1 knockout in mice. Bioscience reports 48 31023968
2000 Co-operation between protein-acetylating and protein-methylating co-activators in transcriptional activation. Biochemical Society transactions 48 10961931
2015 RNAi-mediated silencing of AQP1 expression inhibited the proliferation, invasion and tumorigenesis of osteosarcoma cells. Cancer biology & therapy 47 26176849
2011 Co-stimulatory molecules in and beyond co-stimulation - tipping the balance in atherosclerosis? Thrombosis and haemostasis 47 21979444
2001 Olfactory CO(2) chemoreceptors. Respiration physiology 46 11738656
1998 Co- and/or post-translational modifications are critical for TCH4 XET activity. The Plant journal : for cell and molecular biology 46 9753780
1993 Cloning of a novel rat kidney cDNA homologous to CHIP28 and WCH-CD water channels. Biochemical and biophysical research communications 46 7505572
2020 AQP1 modulates tendon stem/progenitor cells senescence during tendon aging. Cell death & disease 44 32188840
2019 Aqp-1 Gene Knockout Attenuates Hypoxic Pulmonary Hypertension of Mice. Arteriosclerosis, thrombosis, and vascular biology 43 30580569
2017 Valorization of Proteins from Co- and By-Products from the Fish and Meat Industry. Topics in current chemistry (Cham) 43 28466455
2005 Expression and subcellular localization of the AQP8 and AQP1 water channels in the mouse gall-bladder epithelium. Biology of the cell 42 15859952
1999 Co-translational folding. Current opinion in structural biology 42 10047581
2010 MAPK induces AQP1 expression in astrocytes following injury. Glia 40 19610096
1995 Evidence for a glycerol pathway through aquaporin 1 (CHIP28) channels. Pflugers Archiv : European journal of physiology 40 7491270
2006 Role of RhAG and AQP1 in NH3 and CO2 gas transport in red cell ghosts: a stopped-flow analysis. Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine 39 16574458
2014 CO and CO-releasing molecules (CO-RMs) in acute gastrointestinal inflammation. British journal of pharmacology 38 24641722
1994 Projection structure of the CHIP28 water channel in lipid bilayer membranes at 12-A resolution. Biochemistry 38 7524655
2023 A CO2 electrolyzer tandem cell system for CO2-CO co-feed valorization in a Ni-N-C/Cu-catalyzed reaction cascade. Nature communications 37 37709744
2024 AQP1 Deficiency Drives Phthalate-Induced Epithelial Barrier Disruption through Intestinal Inflammation. Journal of agricultural and food chemistry 36 38916549
2014 T cell receptor bias for MHC: co-evolution or co-receptors? Cellular and molecular life sciences : CMLS 36 24633202
2024 In situ copper faceting enables efficient CO2/CO electrolysis. Nature communications 35 38409130
2008 Co-evolution and co-adaptation in protein networks. FEBS letters 35 18282476
2017 Dirofilaria immitis and D. repens show circadian co-periodicity in naturally co-infected dogs. Parasites & vectors 32 28245837
1996 Co-stimulation and co-inhibition: equal partners in regulation. Scandinavian journal of immunology 32 8658047
2003 Genes co-amplified with MYCN in neuroblastoma: silent passengers or co-determinants of phenotype? Cancer letters 31 12880964
1994 A basolateral CHIP28/MIP26-related protein (BLIP) in kidney principal cells and gastric parietal cells. The American journal of physiology 31 7524336
2015 Sex-dependent expression of water channel AQP1 along the rat nephron. American journal of physiology. Renal physiology 30 25656365
2010 Expression of AQP1 and AQP4 in paediatric brain tumours. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 30 20965731
2015 Co-immunoprecipitation from transfected cells. Methods in molecular biology (Clifton, N.J.) 29 25859964
2023 Biohybrid CO2 electrolysis for the direct synthesis of polyesters from CO2. Proceedings of the National Academy of Sciences of the United States of America 28 36972448
2019 AQP1-Containing Exosomes in Peritoneal Dialysis Effluent As Biomarker of Dialysis Efficiency. Cells 27 30970608
2018 Decellularised tissues obtained by a CO2-philic detergent and supercritical CO2. European cells & materials 27 30178445
1995 A Fourier-transform infrared spectroscopic investigation of the hydrogen-deuterium exchange and secondary structure of the 28-kDa channel-forming integral membrane protein (CHIP28). European journal of biochemistry 27 7588813
2022 Role of carboxysomes in cyanobacterial CO2 assimilation: CO2 concentrating mechanisms and metabolon implications. Environmental microbiology 25 36367380
2018 Something special about CO-dependent CO2 fixation. The FEBS journal 25 30240136
2013 AQP1 expression alterations affect morphology and water transport in Schwann cells and hypoxia-induced up-regulation of AQP1 occurs in a HIF-1α-dependent manner. Neuroscience 25 23948641
2012 Co-expression and co-responses: within and beyond transcription. Frontiers in plant science 24 23162560
2006 Urea and urine concentrating ability in mice lacking AQP1 and AQP3. American journal of physiology. Renal physiology 24 16525162
2016 Co-stimulate or Co-inhibit Regulatory T Cells, Which Side to Go? Immunological investigations 23 27419268
2012 Therapeutic potential of carbon monoxide (CO) for intestinal inflammation. Current medicinal chemistry 23 22300078
2022 The pathogenesis of idiopathic normal pressure hydrocephalus based on the understanding of AQP1 and AQP4. Frontiers in molecular neuroscience 21 36204139
2014 Analysis of co-assembly and co-localization of ameloblastin and amelogenin. Frontiers in physiology 21 25120489
2002 Aripiprazole (Otsuka Pharmaceutical Co). Current opinion in investigational drugs (London, England : 2000) 21 12054061
2022 Co-immunoprecipitation Assays. Methods in molecular biology (Clifton, N.J.) 20 35451753
2007 Differential expression of AQP1 in microdomain-enriched membranes of renal cell carcinoma. Proteomics. Clinical applications 20 21136710
2014 Plant Hsp90 and its co-chaperones. Current protein & peptide science 18 24694364

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