Carbonic anhydrase II is a soluble zinc-dependent enzyme that rapidly and reversibly interconverts carbon dioxide and water with bicarbonate and protons. Its cytosolic catalysis supports intracellular pH control and the supply or removal of substrates coupled to epithelial acid-base transport. Human enzyme structures and mutational kinetics define the catalytic zinc environment and proton-transfer network. CAII can associate with the cytosolic face of membrane transport proteins, although direct binding and substrate-channeling interpretations depend on the transporter and assay. It also displays arylesterase and cyanamide-hydration activities in vitro. Biallelic CA2 deficiency causes osteopetrosis with renal tubular acidosis and cerebral calcification.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004064 arylesterase activity | IMP PMID:3126084 Histidine 64 is not required for high CO2 hydration activity... | KEEP AS NON CORE | Summary: Retain experimentally observed arylesterase activity as a secondary activity. Reason: The human CAII His64-mutant abstract explicitly reports hydrolysis of 4-nitrophenyl acetate. That substrate fits the phenyl-acetate reaction in the official GO definition. This laboratory side activity does not establish an independent physiological aryl-ester pathway or replace CO2/bicarbonate catalysis as the central function. The source is abstract-only. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:11327835 Structural and kinetic analysis of the chemical rescue of th... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Human CAII H64A chemical-rescue experiments measure proton-transfer-dependent isotope exchange and activation by exogenous imidazoles. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:12056894 Organization of an efficient carbonic anhydrase: implication... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: The human CAII T199P/C206S mutant has markedly reduced catalytic efficiency and altered bicarbonate interactions. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:12171926 Kinetic analysis of multiple proton shuttles in the active s... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Human CAII/CAIII active-site substitutions test proton-transfer pathways using isotope-exchange kinetics. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:15300855 Carbonic anhydrase II deficiency syndrome (osteopetrosis wit... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: The human CA2 mutation study establishes the deficiency syndrome and genotype context; its abstract does not report a purified-enzyme kinetic assay. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:15453828 Crystal structure of human carbonic anhydrase II at 1.95 A r... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: The CAII complex with 667-COUMATE identifies inhibitor interactions in the carbonic-anhydrase active site. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:15667203 Structural and kinetic characterization of active-site histi... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Human CAII active-site variants alter proton-transfer kinetics and the ordered water network. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:15865431 First crystal structures of human carbonic anhydrase II in c... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: The study characterizes CAII inhibition by compounds also designed to inhibit aromatase and steroid sulfatase; their drug targets do not become CAII functions. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:16106378 Proton transfer in a Thr200His mutant of human carbonic anhy... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Human CAII Thr200/His64 variants test the placement and efficiency of proton-transfer groups. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:16214338 Carbonic anhydrase activators: X-ray crystal structure of th... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Histidine activation and a CAII–histidine structure investigate the proton-transfer component of catalysis. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:17251017 Carbonic anhydrase inhibitors: binding of an antiglaucoma gl... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: A glycosyl sulfanilamide complex characterizes the human CAII active site and inhibitor recognition. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:17330962 Speeding up proton transfer in a fast enzyme: kinetic and cr... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Human CAII Tyr7/Asn62/Asn67 variants connect water-network organization with proton-transfer kinetics. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:17346964 Carbonic anhydrase inhibitors: the X-ray crystal structure o... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: The human CAII–N-hydroxysulfamide structure identifies zinc coordination and inhibitor hydrogen bonds; inhibitor chemistry is not an additional enzyme function. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:18618712 Crystal structure of human carbonic anhydrase XIII and its c... | ACCEPT | Summary: Retain established human CAII carbonate dehydratase activity with source-specific verification limits. Reason: The available abstract describes CA XIII structures and comparison with other carbonic anhydrases. The full text was not accessible in this follow-up, so the CAII-specific experiment underlying the curated assertion remains unverified. An abstract foregrounding another isozyme does not establish that CAII was not assayed or that the annotation is miscited. Retain ACCEPT for this well-established activity, supported independently by direct human CAII catalytic experiments in PMID:18942852, while deferring to the original curator on the uninspected source experiment. Supporting Evidence: |
| GO:0004089 carbonate dehydratase activity | EXP PMID:18942852 Role of hydrophilic residues in proton transfer during catal... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Purified recombinant human CAII variants at Asn62, compared with wild type, retain measurable CO2/bicarbonate isotope exchange with altered proton-transfer kinetics. Actual cached expression/purification, isotope-exchange Methods, catalytic Results and Discussion were read; crystallographic images and supplementary data were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. Supporting Evidence: |
| GO:0004089 carbonate dehydratase activity | EXP PMID:1909891 Conformational mobility of His-64 in the Thr-200----Ser muta... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: The human CAII Thr200Ser variant retains high CO2 hydration activity despite altered His64 orientation. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:1910042 Altering the mouth of a hydrophobic pocket. Structure and ki... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Human CAII Val121 variants link hydrophobic substrate-pocket properties to CO2 hydration kinetics. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:19520834 Structural study of X-ray induced activation of carbonic anh... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Human CAII CO2 and bicarbonate crystal complexes document an X-ray-dose-dependent reaction in the crystal. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:7761440 Structure-assisted redesign of a protein-zinc-binding site w... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Engineered human CAII zinc ligands greatly reduce CO2 hydrase activity, connecting catalytic nucleophile positioning with activity. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:7901850 Structural analysis of the zinc hydroxide-Thr-199-Glu-106 hy... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Human CAII Thr199/Glu106 network mutants show different CO2 hydration activities and active-site coordination geometries. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:8218160 Structure and energetics of a non-proline cis-peptidyl linka... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: The human CAII Pro202Ala variant has essentially wild-type CO2 hydrase activity despite reduced stability. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:8262987 Structural and functional importance of a conserved hydrogen... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Human CAII Thr199 substitutions change CO2 hydration and bicarbonate-dehydration kinetics. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:8399159 Structure of an engineered His3Cys zinc binding site in huma... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Human CAII Thr199Cys structures show altered zinc coordination, with residual activity attributed to an alternative side-chain conformer. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:8451242 Crystallographic analysis of Thr-200-->His human carbonic an... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: The human CAII Thr200His mutant binds bicarbonate in a structurally characterized active-site complex. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:8485129 Structural consequences of hydrophilic amino acid substituti... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: The available, explicitly truncated abstract reports reduced CO2 hydration for human CAII Leu198 variants. The cached abstract is explicitly truncated at 250 words; the missing remainder and full paper were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:8639494 Reversal of the hydrogen bond to zinc ligand histidine-119 d... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Human CAII Glu117 substitutions alter metal equilibration and substantially impair catalysis through the zinc-ligand environment. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:9265618 Carbonic anhydrase activators: X-ray crystallographic and sp... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Human CAI and CAII activation by histamine is investigated with both CO2 and an ester substrate. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | EXP PMID:9398308 Histidine --> carboxamide ligand substitutions in the zinc b... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Human CAII His94/His119 ligand substitutions are tested for CO2 hydration and ester hydrolysis alongside metal-binding changes. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Human CA2 catalyzes reversible carbon dioxide hydration. Reason: Human CA2 catalyzes reversible carbon dioxide hydration. This PAINT assertion is consistent with direct human enzyme and mutant evidence. The target P00918 appearing among descendant evidence is legitimate experimental grounding, not circularity. The exact ancestral-node placement was not inspected; retention does not depend on donor count. |
| GO:0004089 carbonate dehydratase activity | IDA PMID:16686544 Carbonic anhydrase activators. Activation of isoforms I, II,... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: L- and D-phenylalanine activation is compared across human carbonic-anhydrase isoforms including CAII. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IDA PMID:16807956 Carbonic anhydrase activators. Activation of isozymes I, II,... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: L- and D-histidine activation is compared across human carbonic-anhydrase isoforms including CAII. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IDA PMID:17127057 Carbonic anhydrase activators: L-Adrenaline plugs the active... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Adrenaline is tested as a carbonic-anhydrase activator, with weaker activation of CAII than of some other isoforms. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IDA PMID:17314045 Phosph(on)ate as a zinc-binding group in metalloenzyme inhib... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Although the structure in this paper is of CAI, the abstract reports inhibition assays across eleven carbonic-anhydrase isoforms. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IDA PMID:17705204 Saccharin inhibits carbonic anhydrases: possible explanation... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: The local record contains bibliographic metadata for the saccharin-inhibition paper but no narrative abstract or experimental body. Only bibliography is available locally; this does not independently verify the historical assay. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IDA PMID:19186056 A thiabendazole sulfonamide shows potent inhibitory activity... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: The thiabendazole-sulfonamide study explicitly includes CAII inhibition and its inhibitor-bound structure. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IDA PMID:19206230 Non-zinc mediated inhibition of carbonic anhydrases: coumari... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: The CAII–coumarin study detects a hydrolysis product bound at the active-site entrance and compares inhibition across CA isoforms. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IDA PMID:4994926 The carbon dioxide hydration activity of carbonic anhydrase.... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: The local record identifies the historical native human isoenzyme B/C stopped-flow study but has no narrative abstract or experimental body. Only bibliography is available locally; this does not independently verify the historical assay. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the enzyme-specific electronic mapping. Reason: The exact combined source identifiers map the target to EC4.2.1.1/RHEA10748, alpha-carbonic-anhydrase domains and a mouse ortholog. The reaction agrees with independently measured human CAII catalysis; this is not inference of activity from a fold alone. |
| GO:0004089 carbonate dehydratase activity | IMP PMID:11015219 Mechanism of cyanamide hydration catalyzed by carbonic anhyd... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: The inspected abstract concerns cyanamide hydration by human CAII; the normal CO2 reaction is background rather than the newly resolved reaction. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IMP PMID:11802772 Crystal structure of human carbonic anhydrase II complexed w... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: A sugar-sulfamate complex of human CAII characterizes inhibitor recognition by the active enzyme. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IMP PMID:11831900 Structural aspects of isozyme selectivity in the binding of ... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: The study compares inhibition of CAII and CAIV, with a CAII structure used to analyze isozyme selectivity. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IMP PMID:1336460 Crystallographic studies of the binding of protonated and un... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Human CAII complexes with hydrogen sulfide and nitrate characterize ligand interactions at the catalytic zinc site. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IMP PMID:14736236 Unexpected nanomolar inhibition of carbonic anhydrase by COX... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: The study tests carbonic-anhydrase inhibition by celecoxib/valdecoxib and characterizes CAII complexes; unrelated drug pharmacology is not a CAII activity. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IMP PMID:16290146 Carbonic anhydrase inhibitors: Valdecoxib binds to a differe... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: The valdecoxib-bound human CAII structure supports inhibition of an established carbonic-anhydrase catalyst. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IMP PMID:16759856 N-hydroxyurea--a versatile zinc binding function in the desi... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: N-hydroxyurea derivatives are investigated as carbonic-anhydrase inhibitors; the abstract alone does not resolve every isoform-specific experiment. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IMP PMID:17540563 Carbonic anhydrase inhibitors: inhibition of human, bacteria... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: The study compares carbonic-anhydrase inhibitors across enzyme sources and includes a human CAII inhibitor complex. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IMP PMID:17588751 Carbonic anhydrase inhibitors. Interaction of the antiepilep... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Sulthiame inhibition is assayed across carbonic-anhydrase isoforms, with a CAII complex structurally characterized. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IMP PMID:18024029 Carbonic anhydrase inhibitors. Interaction of 2-(hydrazinoca... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Indole sulfonamides are evaluated across carbonic-anhydrase isoforms and in a human CAII complex. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IMP PMID:18162396 Carbonic anhydrase inhibitors. Interaction of 2-N,N-dimethyl... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Thiadiazole sulfonamides are evaluated across carbonic-anhydrase isoforms and in a CAII inhibitor complex. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IMP PMID:18266323 Inhibition of carbonic anhydrase II by thioxolone: a mechani... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Thioxolone is hydrolyzed in a CAII inhibitor study that uses esterase, isotope-exchange and structural measurements. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IMP PMID:18374572 Carbonic anhydrase inhibitors. Interaction of indapamide and... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Diuretic inhibition is compared across carbonic-anhydrase isoforms and structurally examined using CAII–indapamide. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IMP PMID:18481843 Carbonic anhydrase inhibitors: bioreductive nitro-containing... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Although the therapeutic emphasis is on CAIX/CAXII, the study includes CAII inhibition and a CAII complex. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IMP PMID:18640037 Carbonic anhydrase inhibitors. Interaction of the antitumor ... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: EMD 486019 is investigated across carbonic-anhydrase isoforms, including a CAII inhibitor-bound structure. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IMP PMID:19170619 Design of a carbonic anhydrase IX active-site mimic to scree... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: The tested CAIX mimic is an engineered human CAII A65S/N67Q protein, with wild-type CAII used as a kinetic and structural comparator. The complete abstract and actual cached construct/purification Methods were read; no human CAIX biological function is transferred to native CAII. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IMP PMID:19778001 Dissecting the inhibition mechanism of cytosolic versus tran... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: Spin-labeled sulfonamide inhibition studies explicitly compare human cytosolic CAII with transmembrane CAIX/CAXIV. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0004089 carbonate dehydratase activity | IMP PMID:7758465 Catalytic and inhibitor-binding properties of some active-si... | ACCEPT | Summary: Retain established human CAII carbonate dehydratase activity with source-specific verification limits. Reason: The available abstract describes human CAI active-site mutants designed using CAII residues. The full text was not accessible in this follow-up, so the CAII-specific experiment underlying the curated assertion remains unverified. An abstract foregrounding another isozyme does not establish that CAII was not assayed or that the annotation is miscited. Retain ACCEPT for this well-established activity, supported independently by direct human CAII catalytic experiments in PMID:18942852, while deferring to the original curator on the uninspected source experiment. Supporting Evidence: |
| GO:0004089 carbonate dehydratase activity | TAS PMID:1928091 Carbonic anhydrase II deficiency syndrome in a Belgian famil... | ACCEPT | Summary: Retain the established carbonate dehydratase activity of human CAII. Reason: The human His107Tyr deficiency study identifies an unstable CAII molecule and an inherited loss-of-function context. The complete available abstract was read; detailed Methods and figures were not inspected. The carbonate dehydratase assignment itself is firmly established for human CAII by independent direct catalytic studies, including PMID18942852; retain the original source assertion without claiming every cited experiment was independently replicated or fully read. |
| GO:0005515 protein binding | IPI PMID:14736710 Regulation of the human NBC3 Na+/HCO3- cotransporter by carb... | MODIFY | Summary: Refine the reported CAII–SLC4A7/NBC3 interaction to transmembrane transporter binding. Reason: The exact GOA partner Q9Y6M7 is the human sodium/bicarbonate cotransporter SLC4A7/NBC3. The primary abstract reports binding of CAII to its cytoplasmic C-terminal domain, reduced binding/function after acidic-site mutation and membrane recruitment in HEK293 cells. These observations support the more specific GO:0044325 transmembrane transporter binding. The later purified-peptide study tested SLC4A1/A4/A8, not A7; it raises an assay-design caution without directly refuting this interaction. Binding to the transporter does not assign its transport activity to CAII or require a universal substrate-channeling mechanism. Proposed replacements: transmembrane transporter binding Supporting Evidence: PMID:14736710 CAII bound the COOH-terminal domain of NBC3 file:human/CA2/CA2-uniprot.txt |
| GO:0005515 protein binding | IPI PMID:15218065 Molecular mechanism of kNBC1-carbonic anhydrase II interacti... | UNDECIDED | Summary: Retain uncertainty about the contested SLC4A4 binding mechanism. Reason: The exact GOA partner Q9Y6R1 is SLC4A4/kNBC1. The source abstract reports C-terminal binding/mutagenesis correlated with transport in mouse proximal-tubule cells. A later primary study reports no binding to purified SLC4A4 C-terminal peptides and orientation-dependent GST-fusion binding. These different constructs and assays do not settle full-length association in cells, but prevent treating direct C-terminal recognition as resolved. Preserve the original IPI assertion pending reconciliation. |
| GO:0005515 protein binding | IPI PMID:15990874 Metabolon disruption: a mechanism that regulates bicarbonate... | MODIFY | Summary: Refine binding to SLC26A6 isoform 4 to transmembrane transporter binding. Reason: The exact GOA partner Q9BXS9-4 is a transmembrane anion exchanger. The inspected Results and Methods use human SLC26A6a/S+Q, human CAII and HEK293 cells, with C-terminal GST binding, co-immunoprecipitation, binding-site mutation and colocalization. This supports the specific molecular function GO:0044325 transmembrane transporter binding. The SLC26A6 evidence is assessed on its own constructs and assays; a study disputing SLC4A4 peptide binding does not directly refute this interaction. This refinement does not assign transmembrane transport to CAII or require a universal substrate-channeling model. Proposed replacements: transmembrane transporter binding |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | MODIFY | Summary: The inherited cytoplasmic localization is biologically sound. Reason: The inherited cytoplasmic localization is biologically sound. Cytosol is the more specific established location of this soluble human enzyme, including the pool recruited to the cytosolic surface of transporters. Refine the broad compartment to the existing cytosol term without changing the PAINT source assertion or claiming that its exact ancestral node was inspected. Proposed replacements: cytosol |
| GO:0005737 cytoplasm | IDA PMID:114507 Immunohistochemical localization of human carbonic anhydrase... | MODIFY | Summary: Refine the valid broad cytoplasmic location to cytosol. Reason: The historical human isoenzyme-C localization abstract explicitly places the enzyme in erythrocyte cytoplasm, with additional tissue staining. Isoenzyme C corresponds to CAII. This agrees with the soluble intracellular catalyst; the full histology was not inspected. The soluble cytosolic pool is independently demonstrated, so cytosol is a more precise replacement for the broad cytoplasm term. Proposed replacements: cytosol |
| GO:0005737 cytoplasm | IDA PMID:15990874 Metabolon disruption: a mechanism that regulates bicarbonate... | MODIFY | Summary: Refine the valid broad cytoplasmic location to cytosol. Reason: Actual HEK293 Results identify endogenous cytoplasmic CAII and its reversible recruitment to the cytosolic surface of SLC26A6-containing plasma membrane. This does not imply an integral membrane protein or extracellular orientation. The soluble cytosolic pool is independently demonstrated, so cytosol is a more precise replacement for the broad cytoplasm term. Proposed replacements: cytosol |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | MODIFY | Summary: Refine the valid broad cytoplasmic location to cytosol. Reason: The UniProt subcellular-location mapping SL0086 is consistent with the target-specific cytoplasmic enzyme and the inspected localization experiments. The soluble cytosolic pool is independently demonstrated, so cytosol is a more precise replacement for the broad cytoplasm term. Proposed replacements: cytosol |
| GO:0005829 cytosol | IEA GO_REF:0000107 | ACCEPT | Summary: The mouse ortholog transfer to cytosol agrees with the established soluble human CA2 protein and human cellular recruitment assays. Reason: The mouse ortholog transfer to cytosol agrees with the established soluble human CA2 protein and human cellular recruitment assays. This is independent target corroboration, not a claim to have recovered the precise mouse source annotation behind the Ensembl row. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1475022 | ACCEPT | Summary: Retain cytosolic localization of the active enzyme. Reason: The reaction summary explicitly describes cytosolic carbonate chemistry. This location is independently established for soluble human CAII; retain the source assertion without inventing hidden Reactome metadata. Supporting Evidence: Reactome:R-HSA-1475022 file:human/CA2/CA2-uniprot.txt |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1475026 | ACCEPT | Summary: Retain cytosolic localization of the active enzyme. Reason: The reaction summary explicitly describes cytosolic carbonate chemistry. This location is independently established for soluble human CAII; retain the source assertion without inventing hidden Reactome metadata. Supporting Evidence: Reactome:R-HSA-1475026 file:human/CA2/CA2-uniprot.txt |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1475435 | ACCEPT | Summary: Retain cytosolic localization of the active enzyme. Reason: The cached summary identifies CAII carbonate chemistry or inhibitor binding, but does not itself expose a separate compartment field; the exact cytosol assertion is in GOA. This location is independently established for soluble human CAII; retain the source assertion without inventing hidden Reactome metadata. Supporting Evidence: Reactome:R-HSA-1475435 file:human/CA2/CA2-uniprot.txt |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1475436 | ACCEPT | Summary: Retain cytosolic localization of the active enzyme. Reason: The cached summary identifies CAII carbonate chemistry or inhibitor binding, but does not itself expose a separate compartment field; the exact cytosol assertion is in GOA. This location is independently established for soluble human CAII; retain the source assertion without inventing hidden Reactome metadata. Supporting Evidence: Reactome:R-HSA-1475436 file:human/CA2/CA2-uniprot.txt |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9707419 | ACCEPT | Summary: Retain cytosolic localization of the active enzyme. Reason: The cached summary identifies CAII carbonate chemistry or inhibitor binding, but does not itself expose a separate compartment field; the exact cytosol assertion is in GOA. This location is independently established for soluble human CAII; retain the source assertion without inventing hidden Reactome metadata. Supporting Evidence: Reactome:R-HSA-9707419 file:human/CA2/CA2-uniprot.txt |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Human CA2 associates with the cytosolic plasma-membrane surface through transporters. Reason: Human CA2 associates with the cytosolic plasma-membrane surface through transporters. Human CAII/SLC26A6 constructs in HEK293 cells and endogenous CAII association support a real membrane-associated pool, with displacement after PMA treatment. Retain the inherited contextual location without making CA2 an integral membrane protein or claiming exact PAINT-node inspection. |
| GO:0005886 plasma membrane | IDA PMID:15990874 Metabolon disruption: a mechanism that regulates bicarbonate... | KEEP AS NON CORE | Summary: Retain conditional association with the plasma membrane. Reason: In the actual SLC26A6-expressing HEK293 Results, endogenous CAII colocalizes with plasma-membrane SLC26A6 and redistributes after PKC activation. This is a peripheral, cytosolic-face association in a particular transport context, not evidence that CAII spans the membrane. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain the membrane-association location mapping. Reason: UniProt SL0039 reflects experimentally reported association of soluble CAII with the cytosolic surface of the cell membrane. The actual SLC26A6 experiments support this context-dependent localization; no integral-membrane topology is inferred. |
| GO:0008270 zinc ion binding | IDA PMID:3151020 Crystallographic studies of inhibitor binding sites in human... | ACCEPT | Summary: Retain binding of the catalytic zinc cofactor. Reason: The source abstract describes zinc coordination in human CAII inhibitor complexes, including the native three-histidine coordination environment. Zinc binding is an integral requirement of the carbonate catalyst, not a separate signaling or transport activity. |
| GO:0008270 zinc ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: Retain the zinc-binding domain mapping. Reason: The exact InterPro mappings IPR018338/IPR023561 agree with structurally and biochemically demonstrated zinc binding in the human target, rather than an untested family-wide cofactor assumption. |
| GO:0018820 cyanamide hydratase activity | EXP PMID:10550681 Carbonic anhydrase catalyzes cyanamide hydration to urea: is... | KEEP AS NON CORE | Summary: Retain cyanamide hydration as a demonstrated secondary substrate activity. Reason: The human CAI/CAII study explicitly reports cyanamide-to-urea conversion and structural/kinetic characterization. Available primary abstracts support this chemistry, but do not establish cyanamide turnover as a major physiological role. The GO reaction is written in the reversible dehydration direction; that does not contradict the hydration assay. Supporting Evidence: PMID:10550681 cyanamide is hydrated to urea |
| GO:0018820 cyanamide hydratase activity | EXP PMID:11015219 Mechanism of cyanamide hydration catalyzed by carbonic anhyd... | KEEP AS NON CORE | Summary: Retain cyanamide hydration as a demonstrated secondary substrate activity. Reason: The human CAII cryocrystallographic study resolves cyanamide complexes, including a proposed reaction intermediate; not every trapped complex is productive. Available primary abstracts support this chemistry, but do not establish cyanamide turnover as a major physiological role. The GO reaction is written in the reversible dehydration direction; that does not contradict the hydration assay. |
| GO:0018820 cyanamide hydratase activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain cyanamide hydration as a demonstrated secondary substrate activity. Reason: The electronic EC4.2.1.69/RHEA23056 mapping agrees with independently reported human CAII cyanamide hydration. Available primary abstracts support this chemistry, but do not establish cyanamide turnover as a major physiological role. The GO reaction is written in the reversible dehydration direction; that does not contradict the hydration assay. |
| GO:0038166 angiotensin-activated signaling pathway | IDA PMID:15990874 Metabolon disruption: a mechanism that regulates bicarbonate... | MARK AS OVER ANNOTATED | Summary: The experiment establishes a regulated transport-effector context rather than a distinct CAII signaling activity. Reason: The official term describes angiotensin-triggered GPCR signal transduction. In the inspected human SLC26A6/HEK293 experiments, AT1a receptor activation acts through PKC to phosphorylate SLC26A6 and displace CAII, reducing bicarbonate transport. CAII supplies local carbonate chemistry and is released from the transporter; it is not shown to relay the angiotensin signal. The transport-regulation annotation already captures its demonstrated work. This judgment rests on actual Results/Methods, not the title or absence from an abstract. Supporting Evidence: |
| GO:0043209 myelin sheath | IEA GO_REF:0000107 | UNDECIDED | Summary: The literal donor P00920 is mouse Ca2, and official UniProt lists a myelin-sheath annotation. Reason: The literal donor P00920 is mouse Ca2, and official UniProt lists a myelin-sheath annotation. Its underlying experimental citation and precise localization assay were not recovered, so the human myelin-specific transfer cannot be independently adjudicated here. This is an access limitation, not evidence of wrong-paralog attribution or loss of the function. |
| GO:0044070 regulation of monoatomic anion transport | IDA PMID:15990874 Metabolon disruption: a mechanism that regulates bicarbonate... | KEEP AS NON CORE | Summary: Retain CAII-dependent modulation of anion transport in the tested system. Reason: The actual human SLC26A6 study measures transport-associated pH changes, CAII-binding-site mutants, dominant-negative CAII and inhibitor responses, with cell-surface expression controls. These support a functional effect in this system. The inferred local substrate-supply/metabolon mechanism is not equivalent to CAII transporting ions, and pH-based transport readouts require care because CAII itself accelerates acid-base equilibration. Supporting Evidence: |
| GO:0045177 apical part of cell | IBA GO_REF:0000033 | UNDECIDED | Summary: The PAINT source includes direct human target evidence, and membrane association is established. Reason: The PAINT source includes direct human target evidence, and membrane association is established. However, the precise apical CAII localization experiment and ancestral placement were not inspected. The PMID14675051 abstract genuinely includes CAII in mouse and human kidney development, but does not resolve the fine target-specific apical result. Preserve this source assertion pending that detail rather than infer a wrong-gene error from its ClC5-focused title. Additional institutional-paper Methods and indexed mouse CAII Results/captions in PMID14675051 were inspected, but the exact human apical CAII panel was not recovered; this does not justify inferring its fine location from the ClC5 title or other marker staining. |
| GO:0045177 apical part of cell | IDA PMID:14675051 Comparative ontogeny, processing, and segmental distribution... | UNDECIDED | Summary: The precise human apical localization remains incompletely verified. Reason: The cached abstract explicitly includes CAII among markers in mouse and human nephrogenesis. Additional institutional-paper Methods and indexed mouse Results/figure captions confirm genuine CAII assays, so a ClC5-focused title is not misattribution. The particular human CAII subcellular localization supporting this fine apical term was not recovered in the inspected passages; later-page access failed. Retain uncertainty rather than inferring that ClC5 apical staining proves CAII apical staining. Supporting Evidence: |
| GO:0051453 regulation of intracellular pH | IBA GO_REF:0000033 | ACCEPT | Summary: Reversible carbon dioxide/bicarbonate chemistry participates in intracellular pH control. Reason: Reversible carbon dioxide/bicarbonate chemistry participates in intracellular pH control. Human CAII interaction with bicarbonate transporters alters intracellular-pH recovery in human-cell expression assays, independently corroborating this inherited process. The mouse/rat donor list is not itself a weakness; the exact PAINT node remains uninspected. |
| GO:0051453 regulation of intracellular pH | IEA GO_REF:0000107 | ACCEPT | Summary: The mouse ortholog transfer is consistent with direct human CAII-dependent intracellular-pH recovery and transporter coupling. Reason: The mouse ortholog transfer is consistent with direct human CAII-dependent intracellular-pH recovery and transporter coupling. CA2 supplies acid-base chemistry, while the transporter performs membrane solute transport; these activities are not conflated. |
| GO:0051453 regulation of intracellular pH | ISS GO_REF:0000024 | ACCEPT | Summary: Mouse Ca2 is the verified P00920 ortholog. Reason: Mouse Ca2 is the verified P00920 ortholog. Human CAII-dependent intracellular-pH recovery and transporter coupling independently substantiate this transferred process, without needing to assume that every mouse tissue context was assayed in humans. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: Retain CAII detection in the urinary-exosome proteome. Reason: The original authors' NHLBI Urinary Exosome Protein Database explicitly lists CA2, RefSeq NP_000058, nine peptides and references 1/2, with reference 2 the original PMID19056867 study. This target-specific data record supports the HDA location despite the abstract not naming CAII. It establishes detection in the recovered vesicle fraction, not a dedicated secretion mechanism or an extracellular catalytic core. The complete supplemental spectra were not independently reanalyzed. Supporting Evidence: |
| GO:2001150 positive regulation of dipeptide transmembrane transport | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain this contextual ortholog-supported regulatory role: CAII-dependent acid-base chemistry helps maintain the proton driving force during peptide absorption, while PEPT1 transports the dipeptide. Reason: The transferred source assertion is retained as contextual regulation. Actual mouse duodenal Methods and Results in PMID20150244 show that CAII loss increases epithelial acidification during Gly-Sar exposure; membrane-permeant CA inhibition gives a concordant effect. CAII performs cytosolic carbonate chemistry that helps maintain the proton gradient used by PEPT1, while PEPT1 carries the dipeptide. The CAII-specific experiment measures pH rather than a direct CAII-dependent peptide-flux endpoint, and the exact original donor-annotation-to-paper citation was not recovered. This supports bounded orthology-based regulation, not a human direct-transport assay or transporter molecular function. |
| GO:2001150 positive regulation of dipeptide transmembrane transport | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the same bounded mouse-to-human regulatory inference, supported by CAII-dependent pH handling during peptide absorption and conserved human transporter coupling. Reason: The transferred source assertion is retained as contextual regulation. Actual mouse duodenal Methods and Results in PMID20150244 show that CAII loss increases epithelial acidification during Gly-Sar exposure; membrane-permeant CA inhibition gives a concordant effect. CAII performs cytosolic carbonate chemistry that helps maintain the proton gradient used by PEPT1, while PEPT1 carries the dipeptide. The CAII-specific experiment measures pH rather than a direct CAII-dependent peptide-flux endpoint, and the exact original donor-annotation-to-paper citation was not recovered. This supports bounded orthology-based regulation, not a human direct-transport assay or transporter molecular function. |
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Download this section (compressed HTML)Q: Under which native transporter and tissue contexts does CAII form a direct complex that changes ion flux independently of effects on the pH-based assay readout?
Q: What target-specific human evidence establishes apical enrichment and myelin-sheath localization, and which primary donor assays underlie the transferred annotations?
Q: Do the measurable arylesterase and cyanamide-hydration activities contribute materially to any endogenous human pathway?
Experiment: Compare purified full-length transporter–CAII binding in an appropriate membrane system with tag-free domain controls, and pair direct ion-flux measurements with pH kinetics and catalytically inactive CAII controls.
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