CDAN1

Summary: Codanin-1 binds and sequesters ASF1B.

Reason: The original study demonstrates direct binding to both ASF1 paralogs using recombinant pull-downs and cellular coimmunoprecipitation. Binding-site mutations and cellular relocalization establish a regulatory interaction, while subsequent structures and mutagenesis show occupation of histone and downstream-chaperone interfaces. Protein sequestering activity describes the demonstrated mechanism more precisely than generic binding. ASF1A and ASF1B differ in their dependence on individual Codanin-1 interaction elements; binding does not make Codanin-1 a histone chaperone.

Proposed replacements: protein sequestering activity

Summary: Codanin-1 binds and sequesters ASF1A.

Reason: The original study demonstrates direct binding to both ASF1 paralogs using recombinant pull-downs and cellular coimmunoprecipitation. Binding-site mutations and cellular relocalization establish a regulatory interaction, while subsequent structures and mutagenesis show occupation of histone and downstream-chaperone interfaces. Protein sequestering activity describes the demonstrated mechanism more precisely than generic binding. ASF1A and ASF1B differ in their dependence on individual Codanin-1 interaction elements; binding does not make Codanin-1 a histone chaperone.

Proposed replacements: protein sequestering activity

Summary: Nuclear localization does not resolve the stronger is_active_in assertion.

Reason: The IBA source qualifier asserts activity in the nucleus, not merely presence there. The 2012 paper reports a less abundant nuclear ASF1–Codanin-1 complex, but leaves its relationship to heterochromatin unresolved; inhibition of downstream chaperones after nuclear entry is proposed conditionally rather than demonstrated by a nuclear activity assay. The 2025 endogenous experiments establish a predominantly cytosolic complex in their cell system. Retain the original PAINT node and source fields, but leave nuclear molecular activity undecided. This does not reject independently observed nuclear localization, and target self-evidence in the IBA donor list is not circular.

Summary: Nuclear localization is reported but is not the principal established activity site.

Reason: Nuclear Codanin-1 was reported in primary erythroblasts, and the 2012 study describes a less abundant nuclear complex. More recent endogenous tagging, fractionation and live imaging establish predominantly cytosolic localization in Flp-In 293 T-REx cells. Retain the nuclear observation as contextual rather than treating cytosolic predominance as proof of universal nuclear exclusion.

Summary: Nuclear localization is reported but is not the principal established activity site.

Reason: Nuclear Codanin-1 was reported in primary erythroblasts, and the 2012 study describes a less abundant nuclear complex. More recent endogenous tagging, fractionation and live imaging establish predominantly cytosolic localization in Flp-In 293 T-REx cells. Retain the nuclear observation as contextual rather than treating cytosolic predominance as proof of universal nuclear exclusion. The 2012 full Results and Discussion were inspected; no independent nuclear-specific activity is established here.

Summary: Nuclear localization is reported but is not the principal established activity site.

Reason: Nuclear Codanin-1 was reported in primary erythroblasts, and the 2012 study describes a less abundant nuclear complex. More recent endogenous tagging, fractionation and live imaging establish predominantly cytosolic localization in Flp-In 293 T-REx cells. Retain the nuclear observation as contextual rather than treating cytosolic predominance as proof of universal nuclear exclusion.

Summary: Refine the predominant functional location to cytosol.

Reason: The original biochemical fractionation and complex purification locate Codanin-1 in the soluble cytosolic compartment. Endogenous tagging and fractionation independently support this location. Cytosol is the precise site of the established ASF1-sequestering activity; this refinement does not negate separate nuclear or membrane-associated observations.

Proposed replacements: cytosol

Summary: Refine the predominant functional location to cytosol.

Reason: The original biochemical fractionation and complex purification locate Codanin-1 in the soluble cytosolic compartment. Endogenous tagging and fractionation independently support this location. Cytosol is the precise site of the established ASF1-sequestering activity; this refinement does not negate separate nuclear or membrane-associated observations.

Proposed replacements: cytosol

Summary: Cytosol is the principal established site of Codanin-1 function.

Reason: The source immunofluorescence annotation agrees with the current Human Protein Atlas enhanced cytosol assignment. Independent biochemical fractionation and live imaging of endogenously tagged Codanin-1 support a cytosolic complex with ASF1 and CDIN1.

Summary: Retain the additional plasma-membrane localization from immunofluorescence.

Reason: The current Human Protein Atlas target page lists supported plasma-membrane localization alongside enhanced cytosol localization. Its antibody/cell-line table includes plasma-membrane and cytosolic staining in A-431, U-251MG, U2OS or HeLa cells depending on antibody. The displayed annotation is supported, but a specific membrane function is not established. This term does not imply integral or multipass membrane topology.

Summary: Specify regulation of chromatin organization.

Reason: The conserved connection to chromatin organization is consistent with the PAINT assertion and human disease evidence. Direct mechanistic studies place Codanin-1 upstream of histone deposition through ASF1 sequestration, rather than identifying it as a nucleosome assembly enzyme. Regulation of chromatin organization captures this role; no inference of evolutionary loss or weak donor support is made.

Proposed replacements: regulation of chromatin organization

Summary: Retain the chromatin-organization phenotype in patient erythroblasts.

Reason: The source examines abnormal chromatin and altered HP1alpha distribution in human CDA-I erythroblasts. The preserved acts_upstream_of_or_within qualifier accommodates an upstream contribution. These findings support the biological consequence, while the direct mechanistic activity is ASF1 sequestration; they do not establish intrinsic chromatin-remodeling catalysis.

Summary: Describe chromatin regulation through control of ASF1 availability.

Reason: The full 2012 study reports increased chromatin-bound ASF1 and DNA synthesis after Codanin-1 depletion, with the opposite response to ectopic expression. This is a regulatory effect on histone supply. The original acts_upstream_of_positive_effect qualifier is preserved as source provenance, but the experiments do not demonstrate direct promotion of nucleosome assembly by Codanin-1. Use the direction-neutral regulation term to avoid conflating proper chromatin organization with the rate of histone deposition.

Proposed replacements: regulation of chromatin organization

Summary: Codanin-1 defects alter intracellular HP1alpha distribution in erythroblasts.

Reason: The original source reports HP1alpha accumulation at the Golgi in patient intermediate erythroblasts and interaction with Codanin-1. Its preserved upstream-or-within qualifier is appropriate for the observed localization phenotype. Retain this contextual effect without substituting the distinct ASF1 mechanism for the source-specific HP1alpha observation or assigning a general vesicle-transport activity.

Summary: Retain the reported endomembrane-associated localization.

Reason: Selected primary Results available through the publisher search extract describe ER/Golgi-marker costaining and a vesicle-like cytoplasmic pattern in erythroblasts. This supports the existing broad endomembrane assertion, without refining it to an individual organelle or claiming a COPII-complex role. Complete original supplemental images were not inspected; the normal publication cache remains abstract-only.

Summary: Retain broad membrane association as a contextual localization.

Reason: The source maps the UniProt membrane location to GO:0016020. Independent Human Protein Atlas data support additional plasma-membrane localization, and the erythroblast study reports endomembrane-associated staining. These observations can support membrane association without establishing the multipass topology suggested in the UniProt prose. The core mechanism is cytosolic sequestration.

Summary: Codanin-1 inhibits ASF1 nuclear access through sequestration.

Reason: The full study shows that ectopic Codanin-1 shifts ASF1 toward the cytoplasm and that additional ASF1 restores its nuclear pool and S-phase progression. Binding-site mutations diminish this effect. This supports negative regulation of protein import into nucleus, not an autonomous nuclear-import carrier activity of Codanin-1. The definition concerns reduced movement of proteins from cytoplasm into nucleus.

Proposed replacements: negative regulation of protein import into nucleus

Summary: Codanin-1 directly stimulates CDIN1 RNA exonuclease activity in purified assays.

Reason: The CDAN1 C-terminal fragment (residues 866–1227) binds CDIN1 and enhances RNA cleavage relative to CDIN1 alone, broadening substrate use and product formation. Codanin-1 alone is inactive, and catalytic CDIN1 substitutions abolish cleavage. The experimentally demonstrated role is exoribonuclease activation, not intrinsic nuclease catalysis. The purified in vitro assay used bacterially expressed proteins, including a stabilized CDIN1 W237R/C223S/V18M background; activity of an unmodified full-length endogenous complex and its physiological RNA substrates remain to be established. This distinct directly assayed MF is absent from the seed and is not an ancestor or descendant of the proposed sequestering activity. No new RNA-processing BP is inferred.