CDC73

Summary: CDC73 can repress selected transcriptional targets.

Reason: Human MYC promoter experiments support context-dependent repression through CDC73-containing PAF1C. This coexists with positive elongation at other targets; it does not make CDC73 a universal transcriptional repressor.

Summary: CDC73 can repress selected transcriptional targets.

Reason: Human MYC promoter experiments support context-dependent repression through CDC73-containing PAF1C. This coexists with positive elongation at other targets; it does not make CDC73 a universal transcriptional repressor.

Summary: The exact CDC73 telomeric-proteomics hit remains unverified.

Reason: The primary PICh study isolates human telomeric chromatin and has target lists in supplementary tables. The accessible main text does not resolve the CDC73 entry, and its exact supplementary target record was not recovered. Preserve the HDA assertion without treating absence from main text as a negative experiment.

Summary: CDC73 associates with RNA polymerase II as part of PAF1C.

Reason: Human reciprocal coimmunoprecipitation supports association with the polymerase machinery. This is complex-associated binding, not an isolated purified CDC73–PolII interface measurement. The PAINT ancestral inference is retained; CDC73 in its own donor list is valid descendant evidence.

Summary: CDC73 associates with RNA polymerase II as part of PAF1C.

Reason: Human reciprocal coimmunoprecipitation supports association with the polymerase machinery. This is complex-associated binding, not an isolated purified CDC73–PolII interface measurement. The PAINT ancestral inference is retained; CDC73 in its own donor list is valid descendant evidence.

Summary: The specific endodermal-fate donor experiment needs inspection.

Reason: QuickGO traces the mouse Q8JZM7 donor to PMID:19345177. Its accessible abstract establishes PAF1C regulation of stem-cell identity but does not resolve the precise endodermal differentiation assay. Retain both source transfers pending that evidence; no incorrect-ortholog or loss-of-function claim is made.

Summary: The specific endodermal-fate donor experiment needs inspection.

Reason: QuickGO traces the mouse Q8JZM7 donor to PMID:19345177. Its accessible abstract establishes PAF1C regulation of stem-cell identity but does not resolve the precise endodermal differentiation assay. Retain both source transfers pending that evidence; no incorrect-ortholog or loss-of-function claim is made.

Summary: CDC73 associates with the RNA polymerase II complex.

Reason: The POLR2A association is more informative as RNA polymerase II complex binding. Human complex coimmunoprecipitation is established in PMID:15923622; PMID:26659056 also detects PolII in CDC73 precipitates. Preserve the original source while distinguishing independent corroboration from an isolated binary interface.

Proposed replacements: RNA polymerase II complex binding

Summary: CDC73 association with CTR9 in PAF1C is supported.

Reason: Human complex purification, coimmunoprecipitation and reconstitution support this association. Independent PMID:20178742 corroborates the PAF1C partner where an earlier source has limited accessible detail. Preserve source provenance and generic binding as non-core under the explicit project instruction; copurification does not by itself establish a binary interface.

Summary: CDC73 association with PAF1 in PAF1C is supported.

Reason: Human complex purification, coimmunoprecipitation and reconstitution support this association. Independent PMID:20178742 corroborates the PAF1C partner where an earlier source has limited accessible detail. Preserve source provenance and generic binding as non-core under the explicit project instruction; copurification does not by itself establish a binary interface.

Summary: CDC73 association with LEO1 in PAF1C is supported.

Reason: Human complex purification, coimmunoprecipitation and reconstitution support this association. Independent PMID:20178742 corroborates the PAF1C partner where an earlier source has limited accessible detail. Preserve source provenance and generic binding as non-core under the explicit project instruction; copurification does not by itself establish a binary interface.

Summary: RTF1 association has independent human-complex support.

Reason: The selected full Results of PMID:15923622 describe PAF1, LEO1 and CTR9 in the purified human parafibromin preparation; the exact RTF1 association assigned to this source is not independently established here. This is a source-access limit, not evidence that RTF1 cannot associate. Independent PMID:20178742 recovers RTF1 with CDC73-containing human PAF1C and observes partial dissociation during gel filtration. Retain the supported broad association as non-core, preserving the original citation and distinguishing the later corroboration.

Summary: CDC73 associates with the RNA polymerase II complex.

Reason: The POLR2A association is more informative as RNA polymerase II complex binding. Human complex coimmunoprecipitation is established in PMID:15923622; PMID:26659056 also detects PolII in CDC73 precipitates. Preserve the original source while distinguishing independent corroboration from an isolated binary interface.

Proposed replacements: RNA polymerase II complex binding

Summary: CDC73 association with CTR9 in PAF1C is supported.

Reason: Human complex purification, coimmunoprecipitation and reconstitution support this association. Independent PMID:20178742 corroborates the PAF1C partner where an earlier source has limited accessible detail. Preserve source provenance and generic binding as non-core under the explicit project instruction; copurification does not by itself establish a binary interface.

Summary: CDC73 association with PAF1 in PAF1C is supported.

Reason: Human complex purification, coimmunoprecipitation and reconstitution support this association. Independent PMID:20178742 corroborates the PAF1C partner where an earlier source has limited accessible detail. Preserve source provenance and generic binding as non-core under the explicit project instruction; copurification does not by itself establish a binary interface.

Summary: CDC73 association with LEO1 in PAF1C is supported.

Reason: Human complex purification, coimmunoprecipitation and reconstitution support this association. Independent PMID:20178742 corroborates the PAF1C partner where an earlier source has limited accessible detail. Preserve source provenance and generic binding as non-core under the explicit project instruction; copurification does not by itself establish a binary interface.

Summary: The original study supports a substoichiometric RTF1 association with human PAF1C.

Reason: Selected full Results of the original PMID:16024656 distinguish stable purification from coimmunoprecipitation: RTF1 was absent from the conventionally and affinity-purified core, but anti-PAF1, anti-PolII and anti-RTF1 immunoprecipitations recovered substoichiometric associations among RTF1, polymerase and PAF1C subunits (reported with Supplementary Figure 4). The supplementary image was not independently inspected. This supports a complex-associated interaction, not an isolated CDC73–RTF1 binary interface. Later PMID:20178742 provides separate human-complex corroboration. The source-specific full-text URL and short excerpt are in CDC73-notes.md.

Summary: CDC73 associates with BCL9 in a nuclear Wnt complex.

Reason: Exact human CDC73–O00512 records in the source-linked IntAct extract support coimmunoprecipitation. The PMID:17113272 record is BCL9, despite the abstract foregrounding BCL9-2, and includes comparison with a BCL9 deletion construct. Keep the supported association without inventing a partner-derived activity.

Summary: CDC73 binds beta-catenin.

Reason: The primary abstract and exact human P35222 source records support beta-catenin binding, including two-hybrid and pull-down assays. This identifies the binding partner class without making CDC73 a catenin enzyme.

Proposed replacements: beta-catenin binding

Summary: CDC73 associates with BCL9 in a nuclear Wnt complex.

Reason: Exact human CDC73–O00512 records in the source-linked IntAct extract support coimmunoprecipitation. The PMID:17113272 record is BCL9, despite the abstract foregrounding BCL9-2, and includes comparison with a BCL9 deletion construct. Keep the supported association without inventing a partner-derived activity.

Summary: CDC73 associates with CPSF/CstF processing factors.

Reason: Reciprocal RNase-resistant human coimmunoprecipitation supports CPSF4/CPSF30 and CSTF2/CstF64 association. These are recruitment/coupling interactions; they do not assign endonuclease or poly(A)-polymerase catalysis to CDC73.

Summary: CDC73 associates with CPSF/CstF processing factors.

Reason: Reciprocal RNase-resistant human coimmunoprecipitation supports CPSF4/CPSF30 and CSTF2/CstF64 association. These are recruitment/coupling interactions; they do not assign endonuclease or poly(A)-polymerase catalysis to CDC73.

Summary: CDC73 association with CTR9 in PAF1C is supported.

Reason: Human complex purification, coimmunoprecipitation and reconstitution support this association. Independent PMID:20178742 corroborates the PAF1C partner where an earlier source has limited accessible detail. Preserve source provenance and generic binding as non-core under the explicit project instruction; copurification does not by itself establish a binary interface.

Summary: CDC73 association with PAF1 in PAF1C is supported.

Reason: Human complex purification, coimmunoprecipitation and reconstitution support this association. Independent PMID:20178742 corroborates the PAF1C partner where an earlier source has limited accessible detail. Preserve source provenance and generic binding as non-core under the explicit project instruction; copurification does not by itself establish a binary interface.

Summary: CDC73 association with LEO1 in PAF1C is supported.

Reason: Human complex purification, coimmunoprecipitation and reconstitution support this association. Independent PMID:20178742 corroborates the PAF1C partner where an earlier source has limited accessible detail. Preserve source provenance and generic binding as non-core under the explicit project instruction; copurification does not by itself establish a binary interface.

Summary: CDC73 association with PAF1 in PAF1C is supported.

Reason: Human complex purification, coimmunoprecipitation and reconstitution support this association. Independent PMID:20178742 corroborates the PAF1C partner where an earlier source has limited accessible detail. Preserve source provenance and generic binding as non-core under the explicit project instruction; copurification does not by itself establish a binary interface.

Summary: CDC73 association with CTR9 in PAF1C is supported.

Reason: Human complex purification, coimmunoprecipitation and reconstitution support this association. Independent PMID:20178742 corroborates the PAF1C partner where an earlier source has limited accessible detail. Preserve source provenance and generic binding as non-core under the explicit project instruction; copurification does not by itself establish a binary interface.

Summary: CDC73 association with PAF1 in PAF1C is supported.

Reason: Human complex purification, coimmunoprecipitation and reconstitution support this association. Independent PMID:20178742 corroborates the PAF1C partner where an earlier source has limited accessible detail. Preserve source provenance and generic binding as non-core under the explicit project instruction; copurification does not by itself establish a binary interface.

Summary: CDC73 association with LEO1 in PAF1C is supported.

Reason: Human complex purification, coimmunoprecipitation and reconstitution support this association. Independent PMID:20178742 corroborates the PAF1C partner where an earlier source has limited accessible detail. Preserve source provenance and generic binding as non-core under the explicit project instruction; copurification does not by itself establish a binary interface.

Summary: CDC73 association with RTF1 in PAF1C is supported.

Reason: Human complex purification, coimmunoprecipitation and reconstitution support this association. Independent PMID:20178742 corroborates the PAF1C partner where an earlier source has limited accessible detail. Preserve source provenance and generic binding as non-core under the explicit project instruction; copurification does not by itself establish a binary interface.

Summary: CDC73 associates with the histone methyltransferase KMT2A.

Reason: Human coimmunoprecipitation and weak recombinant binding to the MLL RD2 region support the partner-specific refinement. KMT2A is the histone methyltransferase; CDC73 does not acquire that catalytic activity. Fragment and whole-complex experiments are distinguished in the interaction extract.

Proposed replacements: histone methyltransferase binding

Summary: Source-supported CDC73 association with O75031, retained as non-core within the tested assay scope.

Reason: BioGRID record 601301 links human CDC73 bait and human HSF2BP prey to the two-hybrid assay in PMID:21900206. This is source-specific support for the low-resolution interaction; no direct native-cell mechanism, variant, or exact construct boundary was established from the summary.

Summary: Source-supported CDC73 association with Q8NHQ1, retained as non-core within the tested assay scope.

Reason: BioGRID record 601300 links human CDC73 bait and human CEP70 prey to the two-hybrid assay in PMID:21900206. This is source-specific support for the low-resolution interaction; CEP70 binding does not establish a centrosomal activity for CDC73.

Summary: Source-supported CDC73 association with Q6PD62, retained as non-core within the tested assay scope.

Reason: BioGRID record 2941696 links human CTR9 bait and human CDC73 prey to affinity capture–mass spectrometry in PMID:24981860. The result supports PAF1-complex association without defining an isolated binary interface.

Summary: Source-supported CDC73 association with Q8N7H5, retained as non-core within the tested assay scope.

Reason: BioGRID record 2941450 links human CDC73 bait and human PAF1 prey to affinity capture–mass spectrometry in PMID:24981860. The result supports PAF1-complex association without defining an isolated binary interface.

Summary: Source-supported CDC73 association with Q8WVC0, retained as non-core within the tested assay scope.

Reason: BioGRID record 2942251 links human LEO1 bait and human CDC73 prey to affinity capture–mass spectrometry in PMID:24981860. The result supports PAF1-complex association without defining an isolated binary interface.

Summary: Source-supported CDC73 association with A1L4K1, retained as non-core within the tested assay scope.

Reason: CDC73–A1L4K1: Human two-hybrid records support the specified pair. Some experiments use the CDC73 C-terminal region, residues 177–531, as detailed per record; a screen interaction does not establish an endogenous complex or transfer the partner's activity to CDC73.

Summary: Source-supported CDC73 association with P13196, retained as non-core within the tested assay scope.

Reason: CDC73–P13196: Human two-hybrid records support the specified pair. Some experiments use the CDC73 C-terminal region, residues 177–531, as detailed per record; a screen interaction does not establish an endogenous complex or transfer the partner's activity to CDC73.

Summary: Source-supported CDC73 association with Q08379, retained as non-core within the tested assay scope.

Reason: CDC73–Q08379: Human two-hybrid records support the specified pair. Some experiments use the CDC73 C-terminal region, residues 177–531, as detailed per record; a screen interaction does not establish an endogenous complex or transfer the partner's activity to CDC73.

Summary: Source-supported CDC73 association with Q12800, retained as non-core within the tested assay scope.

Reason: CDC73–Q12800: Human two-hybrid records support the specified pair. Some experiments use the CDC73 C-terminal region, residues 177–531, as detailed per record; a screen interaction does not establish an endogenous complex or transfer the partner's activity to CDC73.

Summary: Source-supported CDC73 association with Q5JR59, retained as non-core within the tested assay scope.

Reason: CDC73–Q5JR59: Human two-hybrid records support the specified pair. Some experiments use the CDC73 C-terminal region, residues 177–531, as detailed per record; a screen interaction does not establish an endogenous complex or transfer the partner's activity to CDC73.

Summary: Source-supported CDC73 association with Q8N6L0, retained as non-core within the tested assay scope.

Reason: CDC73–Q8N6L0: Human two-hybrid records support the specified pair. No CDC73 residue truncation is specified in these matched records; this absence is not proof of an entirely unmodified construct. A screen interaction does not establish an endogenous complex or transfer the partner's activity to CDC73.

Summary: Source-supported CDC73 association with Q8NHQ1, retained as non-core within the tested assay scope.

Reason: CDC73–Q8NHQ1: Human two-hybrid records support the specified pair. Some experiments use the CDC73 C-terminal region, residues 177–531, as detailed per record; a screen interaction does not establish an endogenous complex or transfer the partner's activity to CDC73.

Summary: Source-supported CDC73 association with Q9BZW7, retained as non-core within the tested assay scope.

Reason: CDC73–Q9BZW7: Human two-hybrid records support the specified pair. Some experiments use the CDC73 C-terminal region, residues 177–531, as detailed per record; a screen interaction does not establish an endogenous complex or transfer the partner's activity to CDC73.

Summary: Source-supported CDC73 association with Q9H9H4, retained as non-core within the tested assay scope.

Reason: CDC73–Q9H9H4: Human two-hybrid records support the specified pair. No CDC73 residue truncation is specified in these matched records; this absence is not proof of an entirely unmodified construct. A screen interaction does not establish an endogenous complex or transfer the partner's activity to CDC73.

Summary: Source-supported CDC73 association with A1L4K1, retained as non-core within the tested assay scope.

Reason: CDC73–A1L4K1: The human pair is present in the two-hybrid mutation study. The source compares mutant and wild-type ORFs pairwise; IntAct records CDC73 changes at positions 64 and 91 as disrupting interaction strength and also retains a baseline pooling record. The exact substitutions are not recovered in this MITAB extract, so no amino-acid replacement is asserted. These comparisons support the underlying association, not preserved binding by the disrupting mutants.

Summary: Source-supported CDC73 association with P13196, retained as non-core within the tested assay scope.

Reason: CDC73–P13196: The human pair is present in the two-hybrid mutation study. The source compares mutant and wild-type ORFs pairwise; IntAct records CDC73 changes at positions 64 and 91 as disrupting interaction strength and also retains a baseline pooling record. The exact substitutions are not recovered in this MITAB extract, so no amino-acid replacement is asserted. These comparisons support the underlying association, not preserved binding by the disrupting mutants.

Summary: Source-supported CDC73 association with Q08379, retained as non-core within the tested assay scope.

Reason: CDC73–Q08379: The human pair is present in the two-hybrid mutation study. The source compares mutant and wild-type ORFs pairwise; IntAct records CDC73 changes at positions 64 and 91 as disrupting interaction strength and also retains a baseline pooling record. The exact substitutions are not recovered in this MITAB extract, so no amino-acid replacement is asserted. These comparisons support the underlying association, not preserved binding by the disrupting mutants.

Summary: Source-supported CDC73 association with Q12800, retained as non-core within the tested assay scope.

Reason: CDC73–Q12800: The human pair is present in the two-hybrid mutation study. The source compares mutant and wild-type ORFs pairwise; IntAct records CDC73 changes at positions 64 and 91 as disrupting interaction strength and also retains a baseline pooling record. The exact substitutions are not recovered in this MITAB extract, so no amino-acid replacement is asserted. These comparisons support the underlying association, not preserved binding by the disrupting mutants.

Summary: Source-supported CDC73 association with Q5JR59-3, retained as non-core within the tested assay scope.

Reason: CDC73–Q5JR59-3: The human pair is present in the two-hybrid mutation study. The source compares mutant and wild-type ORFs pairwise; IntAct records CDC73 changes at positions 64 and 91 as disrupting interaction strength and also retains a baseline pooling record. The exact substitutions are not recovered in this MITAB extract, so no amino-acid replacement is asserted. These comparisons support the underlying association, not preserved binding by the disrupting mutants. The matched partner is explicitly UniProt Q5JR59-3; retain that isoform scope.

Summary: Source-supported CDC73 association with Q8N6L0, retained as non-core within the tested assay scope.

Reason: CDC73–Q8N6L0: The human pair is present in the two-hybrid mutation study. The source compares mutant and wild-type ORFs pairwise; IntAct records CDC73 changes at positions 64 and 91 as disrupting interaction strength and also retains a baseline pooling record. The exact substitutions are not recovered in this MITAB extract, so no amino-acid replacement is asserted. These comparisons support the underlying association, not preserved binding by the disrupting mutants.

Summary: Source-supported CDC73 association with Q8NHQ1, retained as non-core within the tested assay scope.

Reason: CDC73–Q8NHQ1: The human pair is present in the two-hybrid mutation study. The source compares mutant and wild-type ORFs pairwise; IntAct records CDC73 changes at positions 64 and 91 as disrupting interaction strength and also retains a baseline pooling record. The exact substitutions are not recovered in this MITAB extract, so no amino-acid replacement is asserted. These comparisons support the underlying association, not preserved binding by the disrupting mutants.

Summary: Source-supported CDC73 association with Q9BZW7, retained as non-core within the tested assay scope.

Reason: CDC73–Q9BZW7: The human pair is present in the two-hybrid mutation study. The source compares mutant and wild-type ORFs pairwise; IntAct records CDC73 changes at positions 64 and 91 as disrupting interaction strength and also retains a baseline pooling record. The exact substitutions are not recovered in this MITAB extract, so no amino-acid replacement is asserted. These comparisons support the underlying association, not preserved binding by the disrupting mutants.

Summary: Source-supported CDC73 association with Q6PD62, retained as non-core within the tested assay scope.

Reason: CDC73–Q6PD62: Human anti-tag coimmunoprecipitation records from HeLa cells support copurification in the PAF1 complex. The spoke-expanded association does not establish an isolated binary interface or the partner's catalytic activity on CDC73.

Summary: Source-supported CDC73 association with Q8N7H5, retained as non-core within the tested assay scope.

Reason: CDC73–Q8N7H5: Human anti-tag coimmunoprecipitation records from HeLa cells support copurification in the PAF1 complex. The spoke-expanded association does not establish an isolated binary interface or the partner's catalytic activity on CDC73.

Summary: Source-supported CDC73 association with Q8WVC0, retained as non-core within the tested assay scope.

Reason: CDC73–Q8WVC0: Human anti-tag coimmunoprecipitation records from HeLa cells support copurification in the PAF1 complex. The spoke-expanded association does not establish an isolated binary interface or the partner's catalytic activity on CDC73.

Summary: CDC73 associates with the RNA polymerase II complex.

Reason: The POLR2A association is more informative as RNA polymerase II complex binding. Human complex coimmunoprecipitation is established in PMID:15923622; PMID:26659056 also detects PolII in CDC73 precipitates. Preserve the original source while distinguishing independent corroboration from an isolated binary interface.

Proposed replacements: RNA polymerase II complex binding

Summary: The SHP2 construct and mutant-dependent binding boundary remains unresolved.

Reason: The source-linked Q06124-2 co-IP record uses substrate-trapping SHP2 mutations and reports no detectable wild-type association under those conditions; the phosphatase assay separately establishes CDC73 as substrate. Full Fig1/4 comparisons and the unqualified Q06124 source assignment were not resolved. Preserve both partners without claiming that failure to recover stable co-IP excludes transient enzyme–substrate recognition. The unresolved issue is exact construct/source scope, not absence of CDC73–SHP2 biology.

Summary: CDC73 associates with the tested substrate-trapping SHP2 isoform2 constructs.

Reason: Exact source-linked IntAct EBI-25425831 matches human CDC73 with Q06124-2 in AGS anti-tag coimmunoprecipitation, including SHP2 substrate-trapping mutation features. Retain this positive association at the tested mutant scope. Failure to detect stable wild-type co-IP does not exclude transient enzyme–substrate recognition. Neither an unqualified wild-type binding claim nor CDC73 phosphatase activity is inferred.

Summary: Source-supported CDC73 association with Q6PD62, retained as non-core within the tested assay scope.

Reason: CDC73–Q6PD62: The exact human pair is recorded in the BioPlex affinity purification experiment with C-terminally tagged CDC73 in HEK293T cells. This supports a complex association, not an isolated binary interface. Its representation in later BioPlex releases must not be counted as independent replication.

Summary: Source-supported CDC73 association with Q8N7H5, retained as non-core within the tested assay scope.

Reason: CDC73–Q8N7H5: The exact human pair is recorded in the BioPlex affinity purification experiment with C-terminally tagged CDC73 in HEK293T cells. This supports a complex association, not an isolated binary interface. Its representation in later BioPlex releases must not be counted as independent replication.

Summary: The verified partner class supports beta-catenin binding.

Reason: PMID:29774127 Results describing Supplementary Figure 1A report CDC73–beta-catenin coimmunoprecipitation in HEK293T cells, enhanced with CDC73_3YF relative to wild type. Methods explicitly identify the tagged CDC73 constructs as human; the 3YF substitutions are Y290F/Y293F/Y315F. This supports the association in the stated phosphosite-mutant comparison without transferring beta-catenin activity to CDC73. The supplementary image itself was not newly inspected. Refine at the demonstrated association resolution; no partner catalytic activity is transferred.

Proposed replacements: beta-catenin binding

Summary: The verified partner class supports histone methyltransferase binding.

Reason: PMID:29774127 Figures 3A–D and Results establish SETDB1 copurification with human HA-CDC73 and HA-CDC73_3YF in HEK293T cells, and with endogenous CDC73 in human THP-1 cells. Association is stronger with CDC73_3YF. Figure 3H also tests SETDB1 isoform 3, which lacks the methyl-binding and catalytic SET domains, but that separate construct must not replace the source accession or imply CDC73 methyltransferase activity. Refine at the demonstrated association resolution; no partner catalytic activity is transferred.

Proposed replacements: histone methyltransferase binding

Summary: Source-supported CDC73 association with Q6PD62, retained as non-core within the tested assay scope.

Reason: PMID:29774127 Figure 1D and Results show CTR9 copurifying with both human HA-CDC73 and HA-CDC73_3YF in HEK293T cells. This human assay supports PAF1-complex association; the separate mouse M1 discovery proteomics is not being used to assert an unqualified human binary interface.

Summary: Source-supported CDC73 association with Q8N7H5, retained as non-core within the tested assay scope.

Reason: PMID:29774127 Figure 1D and Results show PAF1 copurifying with both human HA-CDC73 and HA-CDC73_3YF in HEK293T cells. This human assay supports PAF1-complex association; the separate mouse M1 discovery proteomics is not being used to assert an unqualified human binary interface.

Summary: Source-supported CDC73 association with Q8WVC0, retained as non-core within the tested assay scope.

Reason: PMID:29774127 Figure 1D and Results show LEO1 copurifying with both human HA-CDC73 and HA-CDC73_3YF in HEK293T cells. This human assay supports PAF1-complex association; the separate mouse M1 discovery proteomics is not being used to assert an unqualified human binary interface.

Summary: The verified partner class supports histone methyltransferase binding.

Reason: PMID:29774127 Figures 3A–D and Results establish G9a/EHMT2 copurification with human HA-CDC73 and HA-CDC73_3YF in HEK293T cells, and with endogenous CDC73 in human THP-1 cells. Association is stronger with CDC73_3YF. UniProt Q96KQ7 is EHMT2, not WDR61. These experiments support the association without assigning methyltransferase activity to CDC73. Refine at the demonstrated association resolution; no partner catalytic activity is transferred.

Proposed replacements: histone methyltransferase binding

Summary: Source-supported CDC73 association with A1L4K1, retained as non-core within the tested assay scope.

Reason: CDC73–A1L4K1: The exact human pair was tested in the two-hybrid variant comparison. Primary Methods score disruption against the wild-type interaction, require no bait autoactivation, and reproduce the reduction across three screens. IntAct records a CDC73 change at position 95 as disrupting interaction strength and changes at 147 and 156 as having no effect; exact substitutions are not recovered in this extract. Retain the underlying association without assigning binding to the disrupting variant.

Summary: Source-supported CDC73 association with P13196, retained as non-core within the tested assay scope.

Reason: CDC73–P13196: The exact human pair was tested in the two-hybrid variant comparison. Primary Methods score disruption against the wild-type interaction, require no bait autoactivation, and reproduce the reduction across three screens. IntAct records a CDC73 change at position 95 as disrupting interaction strength and changes at 147 and 156 as having no effect; exact substitutions are not recovered in this extract. Retain the underlying association without assigning binding to the disrupting variant.

Summary: Source-supported CDC73 association with Q08379, retained as non-core within the tested assay scope.

Reason: CDC73–Q08379: The exact human pair was tested in the two-hybrid variant comparison. Primary Methods score disruption against the wild-type interaction, require no bait autoactivation, and reproduce the reduction across three screens. IntAct records a CDC73 change at position 95 as disrupting interaction strength and changes at 147 and 156 as having no effect; exact substitutions are not recovered in this extract. Retain the underlying association without assigning binding to the disrupting variant.

Summary: Source-supported CDC73 association with A6NEM1, retained as non-core within the tested assay scope.

Reason: CDC73–A6NEM1: The exact human pair is supported by HuRI two-hybrid pooling, array and validation records. Fusion-tag and fragment conditions are retained in the accompanying extract; these assays support a physical interaction without establishing its endogenous physiological role. The partner A6NEM1 construct is its sufficient-binding region 159–432, not a CDC73 truncation.

Summary: Source-supported CDC73 association with O75031, retained as non-core within the tested assay scope.

Reason: CDC73–O75031: The exact human pair is supported by HuRI two-hybrid pooling, array and validation records. Fusion-tag and fragment conditions are retained in the accompanying extract; these assays support a physical interaction without establishing its endogenous physiological role.

Summary: Source-supported CDC73 association with P36406, retained as non-core within the tested assay scope.

Reason: CDC73–P36406: The exact human pair is supported by HuRI two-hybrid pooling, array and validation records. Fusion-tag and fragment conditions are retained in the accompanying extract; these assays support a physical interaction without establishing its endogenous physiological role.

Summary: Source-supported CDC73 association with Q08379, retained as non-core within the tested assay scope.

Reason: CDC73–Q08379: The exact human pair is supported by HuRI two-hybrid pooling, array and validation records. Fusion-tag and fragment conditions are retained in the accompanying extract; these assays support a physical interaction without establishing its endogenous physiological role. The GOLGA2 partner construct spans residues 13–1002, not a CDC73 truncation.

Summary: Source-supported CDC73 association with Q15276, retained as non-core within the tested assay scope.

Reason: CDC73–Q15276: The exact human pair is supported by HuRI two-hybrid pooling, array and validation records. Fusion-tag and fragment conditions are retained in the accompanying extract; these assays support a physical interaction without establishing its endogenous physiological role.

Summary: Source-supported CDC73 association with Q5JR59-3, retained as non-core within the tested assay scope.

Reason: CDC73–Q5JR59-3: The exact human pair is supported by HuRI two-hybrid pooling, array and validation records. Fusion-tag and fragment conditions are retained in the accompanying extract; these assays support a physical interaction without establishing its endogenous physiological role. The matched partner is explicitly UniProt Q5JR59-3; retain that isoform scope.

Summary: Source-supported CDC73 association with Q5VTR2, retained as non-core within the tested assay scope.

Reason: CDC73–Q5VTR2: The exact human pair is supported by HuRI two-hybrid pooling, array and validation records. Fusion-tag and fragment conditions are retained in the accompanying extract; these assays support a physical interaction without establishing its endogenous physiological role.

Summary: Source-supported CDC73 association with Q8NHQ1, retained as non-core within the tested assay scope.

Reason: CDC73–Q8NHQ1: The exact human pair is supported by HuRI two-hybrid pooling, array and validation records. Fusion-tag and fragment conditions are retained in the accompanying extract; these assays support a physical interaction without establishing its endogenous physiological role.

Summary: Source-supported CDC73 association with Q9NRD5, retained as non-core within the tested assay scope.

Reason: CDC73–Q9NRD5: The exact human pair is supported by HuRI two-hybrid pooling, array and validation records. Fusion-tag and fragment conditions are retained in the accompanying extract; these assays support a physical interaction without establishing its endogenous physiological role.

Summary: Source-supported CDC73 association with Q6PD62, retained as non-core within the tested assay scope.

Reason: CDC73–Q6PD62: The exact human pair is present in BioPlex affinity purification records. Cell-line, bait orientation and tag conditions are retained in the extract. Copurification supports complex association, not a purified binary interface, and overlap with earlier BioPlex experiments is not independent replication.

Summary: Source-supported CDC73 association with Q8N7H5, retained as non-core within the tested assay scope.

Reason: CDC73–Q8N7H5: The exact human pair is present in BioPlex affinity purification records. Cell-line, bait orientation and tag conditions are retained in the extract. Copurification supports complex association, not a purified binary interface, and overlap with earlier BioPlex experiments is not independent replication.

Summary: Source-supported CDC73 association with Q8WVC0, retained as non-core within the tested assay scope.

Reason: CDC73–Q8WVC0: The exact human pair is present in BioPlex affinity purification records. Cell-line, bait orientation and tag conditions are retained in the extract. Copurification supports complex association, not a purified binary interface, and overlap with earlier BioPlex experiments is not independent replication.

Summary: CDC73 associates with BRAF V600E in tagged validation assays; retain this mutant-context association as non-core.

Reason: The exact human CDC73–BRAF pair is recorded under PMID:35512704 in split-luciferase complementation (IntAct EBI-52381121 and EBI-52381451) and GST pulldown (EBI-63973061). The linked primary Results/Methods and Figure 4/S4 context identify the validation construct as BRAF V600E; CDC73 is the tagged binding partner. This is a mutant-context association and does not establish unqualified wild-type BRAF binding or a normal CDC73 signaling role. A separate BRET record, EBI-63680630, encodes a position-600 mutation with no effect, whereas the pulldown record encodes increased interaction strength; the exact allele-specific BRET comparison is not resolved by the inspected extract and is not generalized. No kinase activity is assigned to CDC73.

Summary: CDC73 acts in the nucleus.

Reason: Nuclear localization and association with nuclear transcription machinery are central to CDC73 function. Independent human localization and nuclear-complex evidence support the original source-specific IDA/IEA assertions without describing each electronic record as a new experiment.

Summary: CDC73 acts in the nucleus.

Reason: Nuclear localization and association with nuclear transcription machinery are central to CDC73 function. Independent human localization and nuclear-complex evidence support the original source-specific IDA/IEA assertions without describing each electronic record as a new experiment.

Summary: CDC73 acts in the nucleus.

Reason: Nuclear localization and association with nuclear transcription machinery are central to CDC73 function. Independent human localization and nuclear-complex evidence support the original source-specific IDA/IEA assertions without describing each electronic record as a new experiment.

Summary: Nucleoplasm is a principal CDC73 compartment.

Reason: Retain the HPA-derived location in the context of independent human nuclear transcription-complex evidence. This does not establish a new catalytic activity from imaging.

Summary: Nucleoplasmic CDC73 is compatible with the curated pathway context.

Reason: The cited Reactome event places the CDC73-containing transcription machinery in the nuclear compartment. Independent human nuclear evidence supports the localization. This location-only annotation does not assign every event enzyme or every partner activity to CDC73.

Summary: Nucleoplasmic CDC73 is compatible with the curated pathway context.

Reason: The cited Reactome event places the CDC73-containing transcription machinery in the nuclear compartment. Independent human nuclear evidence supports the localization. This location-only annotation does not assign every event enzyme or every partner activity to CDC73.

Summary: Nucleoplasmic CDC73 is compatible with the curated pathway context.

Reason: The cited Reactome event places the CDC73-containing transcription machinery in the nuclear compartment. Independent human nuclear evidence supports the localization. This location-only annotation does not assign every event enzyme or every partner activity to CDC73.

Summary: Nucleoplasmic CDC73 is compatible with the curated pathway context.

Reason: The cited Reactome event places the CDC73-containing transcription machinery in the nuclear compartment. Independent human nuclear evidence supports the localization. This location-only annotation does not assign every event enzyme or every partner activity to CDC73.

Summary: Nucleoplasmic CDC73 is compatible with the curated pathway context.

Reason: The cited Reactome event places the CDC73-containing transcription machinery in the nuclear compartment. Independent human nuclear evidence supports the localization. This location-only annotation does not assign every event enzyme or every partner activity to CDC73.

Summary: Nucleoplasmic CDC73 is compatible with the curated pathway context.

Reason: The cited Reactome event places the CDC73-containing transcription machinery in the nuclear compartment. Independent human nuclear evidence supports the localization. This location-only annotation does not assign every event enzyme or every partner activity to CDC73.

Summary: Nucleoplasmic CDC73 is compatible with the curated pathway context.

Reason: The cited Reactome event places the CDC73-containing transcription machinery in the nuclear compartment. Independent human nuclear evidence supports the localization. This location-only annotation does not assign every event enzyme or every partner activity to CDC73.

Summary: Nucleoplasmic CDC73 is compatible with the curated pathway context.

Reason: The cited Reactome event places the CDC73-containing transcription machinery in the nuclear compartment. Independent human nuclear evidence supports the localization. This location-only annotation does not assign every event enzyme or every partner activity to CDC73.

Summary: Nucleoplasmic CDC73 is compatible with the curated pathway context.

Reason: The cited Reactome event places the CDC73-containing transcription machinery in the nuclear compartment. Independent human nuclear evidence supports the localization. This location-only annotation does not assign every event enzyme or every partner activity to CDC73.

Summary: Nucleoplasmic CDC73 is compatible with the curated pathway context.

Reason: The cited Reactome event places the CDC73-containing transcription machinery in the nuclear compartment. Independent human nuclear evidence supports the localization. This location-only annotation does not assign every event enzyme or every partner activity to CDC73.

Summary: Nucleoplasmic CDC73 is compatible with the curated pathway context.

Reason: The cited Reactome event places the CDC73-containing transcription machinery in the nuclear compartment. Independent human nuclear evidence supports the localization. This location-only annotation does not assign every event enzyme or every partner activity to CDC73.

Summary: Nucleoplasmic CDC73 is compatible with the curated pathway context.

Reason: The cited Reactome event places the CDC73-containing transcription machinery in the nuclear compartment. Independent human nuclear evidence supports the localization. This location-only annotation does not assign every event enzyme or every partner activity to CDC73.

Summary: Nucleoplasmic CDC73 is compatible with the curated pathway context.

Reason: The cited Reactome event places the CDC73-containing transcription machinery in the nuclear compartment. Independent human nuclear evidence supports the localization. This location-only annotation does not assign every event enzyme or every partner activity to CDC73.

Summary: Nucleoplasmic CDC73 is compatible with the curated pathway context.

Reason: The cited Reactome event places the CDC73-containing transcription machinery in the nuclear compartment. Independent human nuclear evidence supports the localization. This location-only annotation does not assign every event enzyme or every partner activity to CDC73.

Summary: Nucleoplasmic CDC73 is compatible with the curated pathway context.

Reason: The cited Reactome event places the CDC73-containing transcription machinery in the nuclear compartment. Independent human nuclear evidence supports the localization. This location-only annotation does not assign every event enzyme or every partner activity to CDC73.

Summary: Nucleoplasmic CDC73 is compatible with the curated pathway context.

Reason: The cited Reactome event places the CDC73-containing transcription machinery in the nuclear compartment. Independent human nuclear evidence supports the localization. This location-only annotation does not assign every event enzyme or every partner activity to CDC73.

Summary: CDC73 contributes to transcription elongation through PAF1C.

Reason: Human PAF1C purification and reconstituted chromatin-transcription assays establish a positive elongation role for the complex. CDC73 is a participating subunit, not the RNA polymerase catalyst. Preserve the experimental and InterPro source distinctions.

Summary: CDC73 contributes to transcription elongation through PAF1C.

Reason: Human PAF1C purification and reconstituted chromatin-transcription assays establish a positive elongation role for the complex. CDC73 is a participating subunit, not the RNA polymerase catalyst. Preserve the experimental and InterPro source distinctions.

Summary: CDC73 suppresses proliferation in the tested overexpression setting.

Reason: The source abstract reports reduced colony growth/proliferation and G1 accumulation after parafibromin overexpression, with mutant comparisons. Retain this context-dependent phenotype as non-core rather than a universal growth-suppression activity.

Summary: CDC73 is a component of the Cdc73/Paf1 complex.

Reason: Human endogenous purification and complex reconstitution substantiate PAF1C membership. Retain the original PAINT, InterPro and experimental sources; target-containing PAINT evidence is legitimate ancestral inference, and no isolated subunit catalytic activity follows from membership.

Summary: CDC73 is a component of the Cdc73/Paf1 complex.

Reason: Human endogenous purification and complex reconstitution substantiate PAF1C membership. Retain the original PAINT, InterPro and experimental sources; target-containing PAINT evidence is legitimate ancestral inference, and no isolated subunit catalytic activity follows from membership.

Summary: CDC73 is a component of the Cdc73/Paf1 complex.

Reason: Human endogenous purification and complex reconstitution substantiate PAF1C membership. Retain the original PAINT, InterPro and experimental sources; target-containing PAINT evidence is legitimate ancestral inference, and no isolated subunit catalytic activity follows from membership.

Summary: CDC73 is a component of the Cdc73/Paf1 complex.

Reason: Human endogenous purification and complex reconstitution substantiate PAF1C membership. Retain the original PAINT, InterPro and experimental sources; target-containing PAINT evidence is legitimate ancestral inference, and no isolated subunit catalytic activity follows from membership.

Summary: CDC73 is a component of the Cdc73/Paf1 complex.

Reason: Human endogenous purification and complex reconstitution substantiate PAF1C membership. Retain the original PAINT, InterPro and experimental sources; target-containing PAINT evidence is legitimate ancestral inference, and no isolated subunit catalytic activity follows from membership.

Summary: CDC73 is a component of the Cdc73/Paf1 complex.

Reason: Human endogenous purification and complex reconstitution substantiate PAF1C membership. Retain the original PAINT, InterPro and experimental sources; target-containing PAINT evidence is legitimate ancestral inference, and no isolated subunit catalytic activity follows from membership.

Summary: Conserved PAF1C function supports stem-cell population maintenance.

Reason: The mouse donor Q8JZM7 traces to PMID:19345177, whose primary abstract reports PAF1C occupancy at pluripotency genes and perturbation of ESC identity. Retain the existing orthology-based function as a specialized context, not a direct human stem-cell assay or a new process inferred from necessity alone.

Summary: Conserved PAF1C function supports stem-cell population maintenance.

Reason: The mouse donor Q8JZM7 traces to PMID:19345177, whose primary abstract reports PAF1C occupancy at pluripotency genes and perturbation of ESC identity. Retain the existing orthology-based function as a specialized context, not a direct human stem-cell assay or a new process inferred from necessity alone.

Summary: CDC73 links beta-catenin to the nuclear Wnt transcription machinery.

Reason: PMID:16630820 reports human parafibromin binding directly to the beta-catenin C-terminal region and supporting Wnt transcriptional activation, alongside distinct Drosophila Hyrax experiments. This provides a specific molecular connection between the nuclear Wnt complex and PAF1C, rather than a downstream phenotype alone. Retain the existing IDA as a core regulatory function and pair it with beta-catenin binding in the core synthesis. No catalytic activity or new annotation is inferred.

Summary: CDC73 contributes to transcription-coupled mRNA 3′ processing.

Reason: CDC73/CTR9 depletion and PAF1C immunodepletion impair processing coupled to transcription, whereas uncoupled SVL cleavage/polyadenylation is unaffected. This supports noncatalytic coupling, not an intrinsic cleavage or poly(A)-polymerase activity.

Summary: CDC73 promotes recruitment of mRNA 3′ processing factors.

Reason: CDC73 RNAi reduces CPSF/CstF occupancy at INTS6 without reducing PolII occupancy in the inspected experiment. Co-depletion of processing factors during immunodepletion cannot establish CDC73 as an essential core cleavage enzyme; retain the positive regulatory coupling role.

Summary: The reported CDC73-dependent MYC destabilization is not statistically established.

Reason: In the full primary Results/Figure 3D, MYC half-life is estimated as 47 ± 19 min after CDC73 RNAi versus 16 ± 15 min in controls, but the difference is explicitly nonsignificant. The significant PAF1 result in Figure 3E cannot establish the same effect for CDC73. Mark the CDC73-specific destabilization assertion as over-annotated at this evidential resolution. This does not contradict the separately supported MYC transcriptional and proliferation effects or assert that the true protein-stability effect is zero.

Summary: PAF1C promotes productive transcription elongation.

Reason: Retain the PAINT ancestral inference, corroborated by human PAF1C chromatin-transcription assays. The complex contributes to elongation; CDC73 does not catalyze nucleotide addition.

Summary: PAF1C can oppose myeloid differentiation in a leukemia-cell context.

Reason: The inspected Results distinguish murine differentiation from human THP-1 experiments: enforced PAF1C expression reduces CD11b differentiation responses. Preserve the existing subunit annotation with this complex/overexpression limit; an isolated physiological CDC73 differentiation mechanism is not established.

Summary: CDC73-containing PAF1C supports transcription of selected targets.

Reason: The source hPAF study and independent human elongation experiments support this broad positive transcription role. Its specific molecular basis is captured by the elongation/processing core; the annotation does not make CDC73 a histone-modifying enzyme.

Summary: CDC73 limits proliferation of the tested primary human fibroblasts.

Reason: Normal human dermal fibroblast proliferation increases after CDC73 RNAi. Retain this existing cell-type context as secondary to transcriptional regulation; depletion can also destabilize other PAF1C components.

Summary: CDC73 limits proliferation in the tested epithelial cancer cells.

Reason: HeLa proliferation increases after CDC73 RNAi, with MYC dependence. Retain this existing context without asserting the same growth outcome in every epithelial tissue.

Summary: Expression induction does not establish CDC73 participation in the LPS response.

Reason: Mouse-donor Figure 1B shows Cdc73 induction after LPS. Human CDC73 ChIP in Figure 4 concerns IL-6-responsive loci; causal perturbation targets CTR9. These results do not establish CDC73-specific LPS-response participation. See the source-specific notes.

Summary: Expression induction does not establish CDC73 participation in the LPS response.

Reason: Mouse-donor Figure 1B shows Cdc73 induction after LPS. Human CDC73 ChIP in Figure 4 concerns IL-6-responsive loci; causal perturbation targets CTR9. These results do not establish CDC73-specific LPS-response participation. See the source-specific notes.

Summary: The cited experiment supports inhibition rather than stimulation of G1/S progression.

Reason: The original human RNAi experiment increases the S-phase fraction and reduces G1 after CDC73 depletion, supporting the opposite direction to the source GO term. Refine to the existing negative G1/S term while preserving every original source field; no extra annotation is manufactured.

Proposed replacements: negative regulation of G1/S transition of mitotic cell cycle

Summary: CDC73 overexpression inhibits G1/S progression in the tested cells.

Reason: The source reports G1 accumulation and reduced proliferation after parafibromin overexpression. Retain this context-dependent negative cell-cycle regulation without assigning a cyclin-dependent kinase catalytic activity.