CTC1 is the large DNA-binding subunit of the CTC1–STN1–TEN1 (CST) complex. Its oligonucleotide-binding domains contact single-stranded DNA and organize the template with polymerase alpha–primase, supporting initiation of telomeric C-strand synthesis and replication recovery. CST also limits telomerase initiation by sequestering DNA substrate. CTC1 acts in the nucleus, including chromosome ends, and defects in its replication-support functions cause telomere instability. Biallelic pathogenic variants cause cerebroretinal microangiopathy with calcifications and cysts 1 (CRMCC1, Coats plus syndrome). The characterized full-length product contains 1,217 residues; a shorter alternatively spliced product lacks part of the C-terminal DNA-binding and assembly region, and its functional activity has not been established.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000723 telomere maintenance | IMP PMID:19854131 Conserved telomere maintenance component 1 interacts with ST... | ACCEPT | Summary: telomere maintenance is supported. Reason: Human CTC1 siRNA experiments in PMID:19854131 show increased G-overhang signal and signal-free chromosome ends, supporting telomere maintenance. Severe Arabidopsis deprotection is a distinct experimental context; the human results do not resolve the relative contributions of end protection and replication. Supporting Evidence: PMID:19854131 CTC1 depletion caused a modest but consistent increase in ss G-strand DNA |
| GO:0000781 chromosome, telomeric region | IDA PMID:19854130 RPA-like mammalian Ctc1-Stn1-Ten1 complex binds to single-st... | ACCEPT | Summary: chromosome, telomeric region is supported. Reason: The complete PMID:19854130 abstract reports mammalian CST at a fraction of telomeres. Its original Methods and Results remain unavailable, so the curated experimental localization is retained with that access limit. Independent human CTC1 ChIP in PMID:22763445 corroborates the location without substituting for the original assay. Supporting Evidence: PMID:19854130 CST associates with a fraction of telomeres |
| GO:0000781 chromosome, telomeric region | IEA GO_REF:0000120 | ACCEPT | Summary: chromosome, telomeric region is supported. Reason: The literal composite source combines mouse Ctc1 Q5SUQ9, its Ensembl protein and the telomeric-compartment mapping SL-0276. Current mouse Ctc1 has the experimental telomeric-location assertion citing PMID:19854130, and human CTC1 ChIP in PMID:22763445 independently supports this location. Preserve the broad electronic assertion without claiming all products localize identically. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q5SUQ9 SUPPORTS TRANSFER Official mouse Ctc1 identity and the exact experimental donor term are verified in the complete current annotation response; primary access limits are recorded separately. ensembl:ENSMUSP00000112063 SUPPORTS TRANSFER The exact Ensembl protein cross-reference occurs on the current official mouse Ctc1 record; this preserves the stated ortholog-transfer source. UniProtKB-SubCell:SL-0276 SUPPORTS TRANSFER The literal UniProt compartment mapping matches the stated location and independently supported human CTC1 localization. Supporting Evidence: |
| GO:0003697 single-stranded DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: single-stranded DNA binding is supported. Reason: The current PAINT IBD at PTN001804660 explicitly carries this term with mouse Ctc1 and human CTC1 descendant evidence. Human CTC1 DNA-contact mutations in PMID:32499435 impair binding while retaining CST assembly. The current family entries contain both proteins, but tree/MSA data were unavailable, so the target-to-node path was not independently reconstructed. This access gap does not establish a misplaced node, loss of activity, or circularity of target evidence. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN001804660 UNRESOLVED The current IBD contains this exact term and experimental descendant sources; the target and mouse Ctc1 are present in current family entries. Tree/MSA access failed, so the precise ancestral path was not independently reconstructed. The biological annotation is supported independently, with no inferred node misplacement or loss. Supporting Evidence: |
| GO:0003697 single-stranded DNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: single-stranded DNA binding is supported. Reason: The literal combined source includes mouse Ctc1 and InterPro IPR029156. The current InterPro entry maps the CTC1 N-terminal domain to this term, and mouse Ctc1 has an experimental annotation citing PMID:19119139. Human CTC1 DNA contacts and contact-patch mutants independently establish the broad activity within CST (PMID:32499435); the mapping is not proof that the N-terminal domain alone is sufficient for binding. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q5SUQ9 SUPPORTS TRANSFER Official mouse Ctc1 identity and the exact experimental donor term are verified in the complete current annotation response; primary access limits are recorded separately. ensembl:ENSMUSP00000112063 SUPPORTS TRANSFER The exact Ensembl protein cross-reference occurs on the current official mouse Ctc1 record; this preserves the stated ortholog-transfer source. InterPro:IPR029156 SUPPORTS TRANSFER The current InterPro CTC1 N-terminal domain entry explicitly maps to ssDNA binding. Target-level activity is independently established; the domain mapping is not an isolated-domain assay. Supporting Evidence: |
| GO:0003697 single-stranded DNA binding | ISS GO_REF:0000024 | ACCEPT | Summary: single-stranded DNA binding is supported. Reason: The literal donor Q5SUQ9 is mouse Ctc1 and carries ssDNA binding IDA to PMID:19119139. The available abstract describes AAF-44/AAF-132 DNA-binding/cofactor assays; full construct details were not recovered. Independent human CST structure and CTC1 contact-patch mutants support the transfer (PMID:32499435), without asserting equal activity of the shorter official product. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q5SUQ9 SUPPORTS TRANSFER Official mouse Ctc1 identity and the exact experimental donor term are verified in the complete current annotation response; primary access limits are recorded separately. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19854130 RPA-like mammalian Ctc1-Stn1-Ten1 complex binds to single-st... | KEEP AS NON CORE | Summary: Supported association retained at its source-specific assay resolution. Reason: The original IPI names TEN1. Although the full PMID:19854130 target assay could not be recovered, its abstract identifies mammalian CST and later human reconstitution/structure corroborates association. Retain the supported generic interaction as non-core under the project policy. TEN1 is bridged through STN1 within the heterotrimer in PMID:32499435; this does not establish an isolated binary CTC1–TEN1 affinity. |
| GO:0005515 protein binding | IPI PMID:19854130 RPA-like mammalian Ctc1-Stn1-Ten1 complex binds to single-st... | KEEP AS NON CORE | Summary: Supported association retained at its source-specific assay resolution. Reason: The original IPI names STN1. The complete abstract identifies mammalian CST, with later human purification and structural contacts independently supporting association. Current literal GOA contains two date variants of this same assertion, both preserved in the evidence projection. Retain the generic binding as non-core without inventing an additional molecular activity. |
| GO:0005515 protein binding | IPI PMID:22763445 The human CST complex is a terminator of telomerase activity... | KEEP AS NON CORE | Summary: Supported association retained at its source-specific assay resolution. Reason: The recovered original PMID:22763445 reports yeast two-hybrid and human-cell co-immunoprecipitation supporting CTC1 association with ACD/shelterin TPP1 (Q96AP0). Its purified TPP1 construct is residues 87–544 with mutations disrupting TIN2 association. This is positive interaction evidence, not a demonstration of an autonomous CTC1 signaling or catalytic activity. Retain generic binding as non-core; do not confuse Q96AP0 with the unrelated O14773 entry also named TPP1 in UniProt interaction metadata. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22763445 The human CST complex is a terminator of telomerase activity... | KEEP AS NON CORE | Summary: Supported association retained at its source-specific assay resolution. Reason: Human CST coexpression and sequential purification in PMID:22763445 support CTC1–STN1 association. The protein preparations include full-length CTC1 and minor truncated material; separate CTC1 fragments are not the official shorter product. Retain positive generic binding as non-core without assigning isolated-subunit affinity from whole-complex purification. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22763445 The human CST complex is a terminator of telomerase activity... | KEEP AS NON CORE | Summary: Supported association retained at its source-specific assay resolution. Reason: The original PMID:22763445 reports yeast two-hybrid and co-immunoprecipitation evidence for CTC1–POT1 association. Later structural work corroborates a CTC1 interface but uses engineered POT1/TPP1 constructs and does not establish every native human phosphorylation state (PMID:38838667). Retain the source-specific positive interaction as non-core, without treating POT1 activity as a CTC1 activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Supported association retained at its source-specific assay resolution. Reason: Three complete current IntAct records from PMID:25416956 match CTC1–APPBP2 (Q92624) in the human ORFeome yeast two-hybrid screen; participant backbone checks are exact. The selected cache contains introduction rather than detailed target Methods, so the literal assay records provide the target-specific evidence. The positive contact does not establish a distinct CTC1 function; retain generic binding as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: Supported association retained at its source-specific assay resolution. Reason: The exact current IntAct record for PMID:28514442 matches CTC1–TEN1 in HEK293T affinity-purification mass spectrometry. The original Methods describe tagged ORFeome expression and interaction-network construction. Association in this screen is positive but is not an isolated binary binding assay or isoform-specific native proof; retain generic binding as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: Supported association retained at its source-specific assay resolution. Reason: The exact current PMID:28514442 IntAct record matches CTC1–STN1 in HEK293T affinity-purification mass spectrometry with spoke expansion. Independent structural work supports the interaction, but the screen itself measures association in a tagged cellular complex. Retain the supported generic term as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32499435 The structure of human CST reveals a decameric assembly boun... | KEEP AS NON CORE | Summary: Supported association retained at its source-specific assay resolution. Reason: The original human CST structure in PMID:32499435 supports TEN1 association. Within one heterotrimer TEN1 is bridged by STN1, whereas neighboring CTC1–TEN1 contacts are observed in the DNA-induced decamer. Preserve those distinct contexts rather than calling every pair a purified binary interaction or obligate native decamer. Generic binding is positive but non-core. Supporting Evidence: PMID:32499435 TEN1 binding to CTC1 is bridged by STN1n |
| GO:0005515 protein binding | IPI PMID:32499435 The structure of human CST reveals a decameric assembly boun... | KEEP AS NON CORE | Summary: Supported association retained at its source-specific assay resolution. Reason: PMID:32499435 directly resolves STN1 contacts with CTC1 and reports interaction-patch perturbations. The structural association is positive; it does not itself justify a separate enzyme or regulatory activity annotation for this pair. Retain generic binding as non-core alongside the more informative CST and DNA-binding annotations. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Supported association retained at its source-specific assay resolution. Reason: Two complete current IntAct records from PMID:33961781 match CTC1–TEN1 in HEK293T and HCT116 affinity-purification mass spectrometry, both spoke-expanded associations. The selected cache omits detailed Methods, but target records are independently available and support the pair. Retain the generic interaction as non-core without native stoichiometry or direct-contact claims. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Supported association retained at its source-specific assay resolution. Reason: Two complete current IntAct records from PMID:33961781 match CTC1–STN1 in HEK293T and HCT116 affinity-purification mass spectrometry with spoke expansion. Positive association is corroborated by the CST structure; preserve the assay-specific record rather than infer an isolated binding constant. The generic term remains non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: Supported association retained at its source-specific assay resolution. Reason: The literal curated IPI in PMID:40205054 names TEN1. The original selected Methods describe tagged U2OS affinity-purification mass spectrometry, but the target-specific supplementary row was not recovered and no same-paper current IntAct record was found. CST reconstitution and structure independently establish the biological association, so retain the positive generic assertion as non-core with curator deference and this explicit source-access limit. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: Supported association retained at its source-specific assay resolution. Reason: The literal curated IPI in PMID:40205054 names STN1. The U2OS interaction-screen Methods were read, but its target-specific supplementary record remains unavailable after a bounded retrieval failure; absence from current IntAct is not a contradiction. Independent human CST structure strongly corroborates the pair. Retain generic binding as non-core without claiming that the original target row was independently verified. |
| GO:0005634 nucleus | IDA PMID:19854130 RPA-like mammalian Ctc1-Stn1-Ten1 complex binds to single-st... | ACCEPT | Summary: nucleus is supported. Reason: Nuclear localization is coherent with telomeric association and human CTC1 ChIP. Retain the curated 19854130 IDA with its original identity and explicit inaccessible full-text boundary; do not describe an independently read original human localization panel. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: nucleus is supported. Reason: The composite source combines mouse Ctc1, its Ensembl protein and nuclear compartment SL-0191. Current donor records include nuclear IDA annotations to PMID:19119139 and PMID:19854130. Human nuclear/telomeric experiments independently corroborate the location. The broad electronic location is valid and does not imply exclusive nuclear residence. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q5SUQ9 SUPPORTS TRANSFER Official mouse Ctc1 identity and the exact experimental donor term are verified in the complete current annotation response; primary access limits are recorded separately. ensembl:ENSMUSP00000112063 SUPPORTS TRANSFER The exact Ensembl protein cross-reference occurs on the current official mouse Ctc1 record; this preserves the stated ortholog-transfer source. UniProtKB-SubCell:SL-0191 SUPPORTS TRANSFER The literal UniProt compartment mapping matches the stated location and independently supported human CTC1 localization. Supporting Evidence: |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: nucleus is supported. Reason: Mouse Ctc1 Q5SUQ9 has literal nuclear IDA annotations to PMID:19119139 and PMID:19854130. The former abstract reports nuclear staining of both AAF components in HeLa cells, but its complete construct details were not recovered. Human CTC1 ChIP and HPA nucleoplasmic localization independently support the same broad location. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q5SUQ9 SUPPORTS TRANSFER Official mouse Ctc1 identity and the exact experimental donor term are verified in the complete current annotation response; primary access limits are recorded separately. Supporting Evidence: |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence supports nucleoplasmic localization. Reason: The actual HPA XML reports supported ICC/IF with antibody HPA052436 in A-549, HEK293 and U2OS cells, each with nucleoplasm and cytosol locations. This annotation correctly captures the nucleoplasmic signal at its stated resolution; it does not claim exclusive residence, resolve either official product, or establish a separate cytosolic function. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-174425 | ACCEPT | Summary: The curated RNA-primer synthesis event places CTC1-containing CST in the nucleoplasm. Reason: The complete current Reactome object graph for Reactome:R-HSA-174425 reaches Q2NKJ3 through CTC1-containing CST in its event participants. The nucleoplasmic compartment is explicit and biologically consistent with telomeric replication. This RNA-primer synthesis context does not assign the catalytic chemistry of PRIM1 or POLA1 to CTC1. Supporting Evidence: Reactome:R-HSA-174425 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-174427 | ACCEPT | Summary: The curated DNA-primer extension event places CTC1-containing CST in the nucleoplasm. Reason: The complete current Reactome object graph for Reactome:R-HSA-174427 reaches Q2NKJ3 through CTC1-containing CST in its event participants. The nucleoplasmic compartment is explicit and biologically consistent with telomeric replication. This DNA-primer extension context does not assign the catalytic chemistry of PRIM1 or POLA1 to CTC1. Supporting Evidence: Reactome:R-HSA-174427 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-174452 | ACCEPT | Summary: The curated polymerase displacement event places CTC1-containing CST in the nucleoplasm. Reason: The complete current Reactome object graph for Reactome:R-HSA-174452 reaches Q2NKJ3 through CTC1-containing CST in its event participants. The nucleoplasmic compartment is explicit and biologically consistent with telomeric replication. This polymerase displacement context does not assign the catalytic chemistry of PRIM1 or POLA1 to CTC1. Supporting Evidence: Reactome:R-HSA-174452 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9668597 | ACCEPT | Summary: The curated polymerase-primase association with telomeric DNA event places CTC1-containing CST in the nucleoplasm. Reason: The complete current Reactome object graph for Reactome:R-HSA-9668597 reaches Q2NKJ3 through CTC1-containing CST in its event participants. The nucleoplasmic compartment is explicit and biologically consistent with telomeric replication. This polymerase-primase association with telomeric DNA context does not assign the catalytic chemistry of PRIM1 or POLA1 to CTC1. Supporting Evidence: Reactome:R-HSA-9668597 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9668831 | ACCEPT | Summary: The curated CST assembly event places CTC1-containing CST in the nucleoplasm. Reason: The complete current Reactome object graph for Reactome:R-HSA-9668831 reaches Q2NKJ3 through CTC1-containing CST in its event participants. The nucleoplasmic compartment is explicit and biologically consistent with telomeric replication. This CST assembly context does not assign the catalytic chemistry of PRIM1 or POLA1 to CTC1. Supporting Evidence: Reactome:R-HSA-9668831 |
| GO:0010833 telomere maintenance via telomere lengthening | IBA GO_REF:0000033 | ACCEPT | Summary: telomere maintenance via telomere lengthening is supported. Reason: The current IBD at PTN001804660 contains this exact term with MGI:1916214, the mouse Ctc1 donor whose current IMP cites PMID:22531781. That abstract reports telomere replication failure and C-strand loss after CTC1 deletion; modern human DNA-anchor mutants and C-strand synthesis assays establish performed cofactor work (PMID:35831508). Negative regulation of telomerase does not contradict C-strand lengthening. The tree/MSA requests failed, so the precise path remains unverified rather than disproven. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN001804660 UNRESOLVED The current IBD contains this exact term and experimental descendant sources; the target and mouse Ctc1 are present in current family entries. Tree/MSA access failed, so the precise ancestral path was not independently reconstructed. The biological annotation is supported independently, with no inferred node misplacement or loss. |
| GO:0016233 telomere capping | TAS PMID:22763445 The human CST complex is a terminator of telomerase activity... | UNDECIDED | Summary: telomere capping is not resolved at the available source scope. Reason: PMID:22763445 cites prior telomere protection but directly tests DNA binding, telomerase inhibition and length regulation. The PMID:19854130 abstract reports increased single-stranded G-strand telomeric DNA after Stn1 knockdown, which supports a CST-complex protective context but does not resolve CTC1-specific capping; its unavailable full text may contain additional CTC1 experiments. Human CTC1 knockdown in PMID:19854131 perturbs telomere integrity, while its Discussion leaves replication versus end-protection contributions unresolved. Retain UNDECIDED for this source-specific assignment. GO:0016233 does not require a passive mechanism, and neither mammalian protection nor unseen experimental support is excluded. |
| GO:0032211 negative regulation of telomere maintenance via telomerase | IDA PMID:22763445 The human CST complex is a terminator of telomerase activity... | ACCEPT | Summary: negative regulation of telomere maintenance via telomerase is supported. Reason: Purified human CST inhibits telomerase activity and competes with the DNA/processivity-factor system; cellular CST perturbation changes telomere length in 22763445. This is performed negative regulation. Retain the process without asserting that CST always evicts an already elongating telomerase or limits every telomere to exactly one event. The later pulse-chase experiments in PMID:34718732 separate inhibition of initiation from eviction of elongating telomerase. Supporting Evidence: PMID:22763445 inhibits telomerase activity through primer sequestration |
| GO:0042162 telomeric repeat DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: telomeric repeat DNA binding is supported. Reason: Current PTN001804660 IBD explicitly uses human CTC1 experimental evidence for this term. Human CST binds telomeric DNA and CTC1 supplies mapped DNA contacts (PMID:22763445; PMID:32499435). The target appearing among descendants is legitimate experimental grounding. Family membership is recovered, but the current tree/MSA path could not be checked after bounded access failures. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN001804660 UNRESOLVED The current IBD contains this exact term and experimental descendant sources; the target and mouse Ctc1 are present in current family entries. Tree/MSA access failed, so the precise ancestral path was not independently reconstructed. The biological annotation is supported independently, with no inferred node misplacement or loss. Supporting Evidence: |
| GO:0042162 telomeric repeat DNA binding | IDA PMID:19854130 RPA-like mammalian Ctc1-Stn1-Ten1 complex binds to single-st... | ACCEPT | Summary: telomeric repeat DNA binding is supported. Reason: The complete PMID:19854130 abstract reports sequence-independent ssDNA binding by mammalian CST and its telomeric association, but the original binding assays remain unavailable. Retain the curated telomeric-repeat binding annotation with this source limit; reconstituted human CST binding in PMID:22763445 and CTC1 DNA-contact evidence in PMID:32499435 independently corroborate the biology without being relabeled as the original experiment. Supporting Evidence: PMID:19854130 binds to single-stranded DNA with high affinity |
| GO:0045740 positive regulation of DNA replication | IBA GO_REF:0000033 | ACCEPT | Summary: positive regulation of DNA replication is supported. Reason: The PTN001804660 IBD and mouse Ctc1 donor retain the positive-replication annotation to PMID:19119139, whose abstract describes polymerase-primase stimulation. Independent human regulation is demonstrated in PMID:25483097: overexpression of all three CST subunits in HeLa cells increases new origin firing after two hours of hydroxyurea, without increasing individual stalled-fork restart; EdU/PCNA controls exclude altered S-phase entry as the explanation. CTC1 abundance was estimated at mRNA level. CTC1 DNA-anchor mutants in PMID:35831508 separately establish performed cofactor activity. The current tree/MSA path remains unverified, not biologically contradicted. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN001804660 UNRESOLVED The current IBD contains this exact term and experimental descendant sources; the target and mouse Ctc1 are present in current family entries. Tree/MSA access failed, so the precise ancestral path was not independently reconstructed. The biological annotation is supported independently, with no inferred node misplacement or loss. |
| GO:0045740 positive regulation of DNA replication | IEA GO_REF:0000107 | ACCEPT | Summary: positive regulation of DNA replication is supported. Reason: The literal Ensembl transfer identifies mouse Ctc1 Q5SUQ9/ENSMUSP00000112063 with the positive-replication IDA to PMID:19119139. Human CST overexpression increases post-hydroxyurea origin firing rather than individual fork restart (PMID:25483097); TEN1 alone or STN1/TEN1 does not reproduce the enhanced DNA-synthesis recovery. This demonstrates regulation by CTC1-containing CST, rather than inferring regulation from participation alone. CTC1 template anchoring and the POLA1 interface provide complementary cofactor/recruitment evidence (PMID:35831508; PMID:35578024), without assigning polymerase or primase catalysis to CTC1. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q5SUQ9 SUPPORTS TRANSFER Official mouse Ctc1 identity and the exact experimental donor term are verified in the complete current annotation response; primary access limits are recorded separately. ensembl:ENSMUSP00000112063 SUPPORTS TRANSFER The exact Ensembl protein cross-reference occurs on the current official mouse Ctc1 record; this preserves the stated ortholog-transfer source. |
| GO:0045740 positive regulation of DNA replication | ISS GO_REF:0000024 | ACCEPT | Summary: positive regulation of DNA replication is supported. Reason: The literal ISS donor is mouse Ctc1 Q5SUQ9 with the positive-replication IDA to PMID:19119139; the abstract supports cofactor activity but leaves original construct details unresolved. Independent human evidence in PMID:25483097 shows that three-subunit CST overexpression enhances DNA-synthesis recovery and new origin firing after hydroxyurea, with S-phase-entry controls and no increase in individual stalled-fork restart. CTC1 DNA-anchor mutants that retain polymerase association but impair synthesis add target-specific mechanistic support (PMID:35831508). Recruitment or activation at dormant origins remains a proposed explanation, not a directly localized event. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q5SUQ9 SUPPORTS TRANSFER Official mouse Ctc1 identity and the exact experimental donor term are verified in the complete current annotation response; primary access limits are recorded separately. |
| GO:0098505 G-rich strand telomeric DNA binding | IDA PMID:22763445 The human CST complex is a terminator of telomerase activity... | ACCEPT | Summary: G-rich strand telomeric DNA binding is supported. Reason: Reconstituted human CST binds G-rich telomeric oligonucleotides directly in 22763445. The specificity is appropriate for this source despite broader CST ssDNA binding elsewhere. The assay uses the assembled complex and does not establish equal activity for both official products. Supporting Evidence: |
| GO:1990879 CST complex | IBA GO_REF:0000033 | ACCEPT | Summary: CST complex is supported. Reason: Current PTN001804660 IBD contains CST membership with mouse Ctc1 and human CTC1 experimental descendants. Human CST reconstitution and structure directly establish membership (PMID:22763445; PMID:32499435). Current family entries contain both proteins; failed tree/MSA recovery leaves the exact path unverified, not contradicted. No donor-count or target-self-evidence objection is made. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN001804660 UNRESOLVED The current IBD contains this exact term and experimental descendant sources; the target and mouse Ctc1 are present in current family entries. Tree/MSA access failed, so the precise ancestral path was not independently reconstructed. The biological annotation is supported independently, with no inferred node misplacement or loss. Supporting Evidence: |
| GO:1990879 CST complex | IDA PMID:19854130 RPA-like mammalian Ctc1-Stn1-Ten1 complex binds to single-st... | ACCEPT | Summary: CST complex is supported. Reason: The complete PMID:19854130 abstract explicitly identifies the mammalian CTC1–STN1–TEN1 complex. Retain the curated membership annotation while its original Methods and Results remain unavailable. Later human reconstitution and structure corroborate membership independently (PMID:22763445; PMID:32499435). |
| GO:1990879 CST complex | IDA PMID:22763445 The human CST complex is a terminator of telomerase activity... | ACCEPT | Summary: CST complex is supported. Reason: Sequential purification of coexpressed human CTC1/STN1/TEN1 and biochemical assays in 22763445 directly support CST complex membership. Do not infer one universal native oligomer size or the activity of the shorter official product. Supporting Evidence: |
| GO:1990879 CST complex | IEA GO_REF:0000107 | ACCEPT | Summary: CST complex is supported. Reason: The literal Ensembl transfer uses mouse Ctc1 Q5SUQ9 and ENSMUSP00000112063. The donor has the exact CST-complex IDA citing PMID:19854130; independent human reconstitution and structure establish CTC1 membership (PMID:22763445; PMID:32499435). This does not assign intrinsic catalytic activities of other complex constituents. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q5SUQ9 SUPPORTS TRANSFER Official mouse Ctc1 identity and the exact experimental donor term are verified in the complete current annotation response; primary access limits are recorded separately. ensembl:ENSMUSP00000112063 SUPPORTS TRANSFER The exact Ensembl protein cross-reference occurs on the current official mouse Ctc1 record; this preserves the stated ortholog-transfer source. |
| GO:1990879 CST complex | ISS GO_REF:0000024 | ACCEPT | Summary: CST complex is supported. Reason: The literal mouse Ctc1 Q5SUQ9 donor has CST membership IDA citing PMID:19854130. Human CTC1 is independently demonstrated in reconstituted CST and its structure (PMID:22763445; PMID:32499435), supporting the biological transfer with no equal-product-function inference. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q5SUQ9 SUPPORTS TRANSFER Official mouse Ctc1 identity and the exact experimental donor term are verified in the complete current annotation response; primary access limits are recorded separately. |
| GO:1990879 CST complex | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation of CST complex membership whose WITH/FROM accession is mouse STN1 rather than mouse Ctc1; CTC1 membership of the CST complex is independently established. Reason: CTC1 is the defining large subunit of the CST complex, and membership is accepted on the IBA, IDA, IEA and other ISS rows for this term, supported by human reconstitution and structure (PMID:22763445, PMID:32499435); the claim therefore stands on this row as well. The defect lies in this row's source record: its WITH/FROM accession is mouse STN1, a different CST subunit, rather than the mouse Ctc1 ortholog, so the similarity transfer is mis-pointed even though the conclusion is right. That is recorded as a source defect rather than expressed by removing a true annotation. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG Sources checked: UniProtKB:Q8K2X3 SUPPORTS SOURCE BUT NOT TARGET Mouse STN1 has a valid CST-complex IDA to PMID:19854130, but is a different CST subunit, not the Ctc1 ortholog. The source annotation is sound; the ISS donor selection is not. |
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Download this section (compressed HTML)Q: Can the erroneous Q8K2X3 mouse STN1 WITH/FROM mapping be removed from the CTC1 CST-complex ISS record while retaining the independent experimental and valid Ctc1-based membership assertions?
Q: Does human CTC1 perform a separable telomere-end protection step beyond preventing replication-associated damage, and which direct assays distinguish these roles?
Q: Is the predicted 1,031-residue product expressed despite the premature-stop/NMD caveat, and does its altered C-terminal region support CST assembly, DNA binding or polymerase recruitment?
Experiment: Measure expression and sequence identity of the shorter product, then compare matched full-length and short-product CST preparations for heterotrimer assembly, DNA affinity and polymerase-primase initiation.
Experiment: Separate replication failure from end-protection defects using acute CTC1 perturbation outside S phase, matched restoration of replication support, and direct telomere damage/fusion readouts.
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