ANKRD17

UniProt ID: O75179
Organism: Homo sapiens
Review Status: COMPLETE
πŸ“ Provide Detailed Feedback

Gene Description

ANKRD17 is a large ankyrin-repeat protein with a type-1 KH domain that occupies nuclear and cytoplasmic pools. Its chromatin-associated pool supports DNA-replication and G1/S cell-cycle regulation and interacts with cyclin E/CDK2 and replication factors. In innate immune signaling, ANKRD17 promotes association of the RNA sensors RIG-I and MDA5 with MAVS and supports NOD1/NOD2-dependent inflammatory responses. It is also implicated in YAP protein stability. Heterozygous loss of function causes a neurodevelopmental syndrome characterized by intellectual disability, speech delay and dysmorphic features.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000785 chromatin
IDA
PMID:19150984
Identification and functional analysis of a novel cyclin e/c...
ACCEPT
Summary: ANKRD17 has a regulated chromatin-associated nuclear pool.
Reason: Human U2OS and HeLa fractionation, salt extraction and cell-cycle loading experiments support the existing chromatin location. This does not identify sequence-specific DNA recognition or obligate replisome membership.
Supporting Evidence:
PMID:19150984
These results strongly indicate that the CSK-insoluble fraction of Ankrd17 binds to chromatin, not a nuclear matrix protein.
GO:0003676 nucleic acid binding
IEA
GO_REF:0000002
MODIFY
Summary: The KH-domain nucleic-acid annotation can be refined to RNA binding.
Reason: The original IPR004087 KH-domain mapping is retained. The same human sequence contains the type-1 KH signature represented by IPR004088/IPR036612 and PROSITE PS50084; the official PROSITE definition describes RNA-binding KH domains. RNA binding is the supported specific activity, while the exact target row of the independent HDA study remains unread. This is a domain-based specificity refinement, not a claim that the HDA supplemental evidence was inspected.
Propagation Review
Root cause: TERM SCOPING PROBLEM
Failure modes: GRANULARITY MISMATCH
Sources checked:
InterPro:IPR004087 UNRESOLVED
Original source identifier retained. Biological target support is assessed separately; exact historical rule or ancestral-node experiment was not reconstructed.
Proposed replacements: RNA binding
GO:0003682 chromatin binding
IDA
PMID:19150984
Identification and functional analysis of a novel cyclin e/c...
ACCEPT
Summary: Cell fractionation supports chromatin binding.
Reason: ANKRD17 is retained in the CSK-insoluble fraction, resists micrococcal nuclease and is salt released like chromatin-associated proteins rather than the nuclear matrix control. Retain the curator's chromatin-binding interpretation without adding sequence-specific DNA binding or a catalytic loading activity.
Supporting Evidence:
PMID:19150984
These results strongly indicate that the CSK-insoluble fraction of Ankrd17 binds to chromatin, not a nuclear matrix protein.
GO:0003723 RNA binding
HDA
PMID:22658674
Insights into RNA biology from an atlas of mammalian mRNA-bi...
UNDECIDED
Summary: The RNA-interactome study is relevant, but its ANKRD17-specific supplementary result was not recovered.
Reason: The complete abstract describes covalent UV-crosslinking and mRNA-interactome capture in human HeLa cells. The exact ANKRD17 identity/peptide record and controls are unavailable in the accessed source. Its type-1 KH domain independently makes RNA binding plausible, but cannot substitute for reading this experimental record; retain source-specific uncertainty without asserting that the curator was wrong.
Supporting Evidence:
GO:0003723 RNA binding
IEA
GO_REF:0000002
ACCEPT
Summary: Type-1 KH architecture supports the RNA-binding domain inference.
Reason: The preserved human UniProt record identifies a type-1 KH domain and the original InterPro domain and superfamily mappings. Official PROSITE KH-domain documentation supports RNA binding as the general activity. No RNA sequence preference, substrate class beyond RNA, or downstream RNA-processing mechanism is inferred. The separate HDA row remains source-specifically unresolved.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
InterPro:IPR004088 UNRESOLVED
Original source identifier retained. Biological target support is assessed separately; exact historical rule or ancestral-node experiment was not reconstructed.
InterPro:IPR036612 UNRESOLVED
Original source identifier retained. Biological target support is assessed separately; exact historical rule or ancestral-node experiment was not reconstructed.
GO:0005515 protein binding
IPI
PMID:19150984
Identification and functional analysis of a novel cyclin e/c...
REMOVE
Summary: PCNA association is supported, but the generic protein-binding term is uninformative.
Reason: Tagged and endogenous ANKRD17 co-immunoprecipitation support PCNA association; the positive interaction is not disputed. Remove the uninformative generic binding annotation under the protein-binding policy. The paper leaves direct versus indirect PCNA-loading regulation unresolved, and no supported PCNA-binding GO refinement was found. DNA clamp-loader or replication-adaptor activity would add an unestablished mechanism.
Supporting Evidence:
PMID:19150984
endogenous Ankrd17 can interact with MCM7, Cdc6, and PCNA
GO:0005515 protein binding
IPI
PMID:19150984
Identification and functional analysis of a novel cyclin e/c...
MODIFY
Summary: The CDK2 interaction is more informative as protein kinase binding.
Reason: Endogenous co-immunoprecipitation, cyclin-docking-region perturbation and the phosphorylation assays support association with the cyclin E/CDK2 kinase. ANKRD17 is the substrate in these experiments. The replacement describes kinase binding, not kinase catalysis or activation; historical isoform-b residue numbering is not remapped to the current canonical sequence.
Proposed replacements: protein kinase binding
Supporting Evidence:
PMID:19150984
endogenous Ankrd17 binds to Cdk2
GO:0005515 protein binding
IPI
PMID:19150984
Identification and functional analysis of a novel cyclin e/c...
MODIFY
Summary: MCM3 association is more informative as ATPase binding.
Reason: Tagged human ANKRD17 co-immunoprecipitation supports association with MCM3, a subunit of the MCM2-7 AAA+ ATPase motor. The replacement classifies the named partner using the same IPI association standard as CDC6. MCM ATPase sites are formed between neighboring subunits; this does not assert autonomous catalysis by an isolated subunit. Shared-complex recovery remains possible, so no purified binary interface, active-site contact, ATPase stimulation, intrinsic ANKRD17 ATPase activity or replication-loader mechanism is inferred. MCM chromatin loading was unchanged after ANKRD17 depletion.
Proposed replacements: ATPase binding
Supporting Evidence:
PMID:19150984
Ankrd17 can interact with MCM3, MCM5, MCM7, Cdc6, and PCNA
GO:0005515 protein binding
IPI
PMID:19150984
Identification and functional analysis of a novel cyclin e/c...
MODIFY
Summary: MCM5 association is more informative as ATPase binding.
Reason: Tagged human ANKRD17 co-immunoprecipitation supports association with MCM5, a subunit of the MCM2-7 AAA+ ATPase motor. The replacement classifies the named partner using the same IPI association standard as CDC6. MCM ATPase sites are formed between neighboring subunits; this does not assert autonomous catalysis by an isolated subunit. Shared-complex recovery remains possible, so no purified binary interface, active-site contact, ATPase stimulation, intrinsic ANKRD17 ATPase activity or replication-loader mechanism is inferred. MCM chromatin loading was unchanged after ANKRD17 depletion.
Proposed replacements: ATPase binding
Supporting Evidence:
PMID:19150984
Ankrd17 can interact with MCM3, MCM5, MCM7, Cdc6, and PCNA
GO:0005515 protein binding
IPI
PMID:19150984
Identification and functional analysis of a novel cyclin e/c...
MODIFY
Summary: MCM7 association is more informative as ATPase binding.
Reason: Tagged human ANKRD17 co-immunoprecipitation supports association with MCM7, a subunit of the MCM2-7 AAA+ ATPase motor. Endogenous co-immunoprecipitation additionally confirms MCM7 association. The replacement classifies the named partner using the same IPI association standard as CDC6. MCM ATPase sites are formed between neighboring subunits; this does not assert autonomous catalysis by an isolated subunit. Shared-complex recovery remains possible, so no purified binary interface, active-site contact, ATPase stimulation, intrinsic ANKRD17 ATPase activity or replication-loader mechanism is inferred. MCM chromatin loading was unchanged after ANKRD17 depletion.
Proposed replacements: ATPase binding
Supporting Evidence:
PMID:19150984
Ankrd17 can interact with MCM3, MCM5, MCM7, Cdc6, and PCNA
GO:0005515 protein binding
IPI
PMID:19150984
Identification and functional analysis of a novel cyclin e/c...
MODIFY
Summary: CDC6 association can be represented as ATPase binding.
Reason: Tagged and endogenous co-immunoprecipitation support association with the replication ATPase CDC6. As for the MCM3/5/7 associations, the replacement describes the named partner class at the source IPI evidence level. Shared-complex recovery is possible; no purified binary interface, active-site contact, ATPase stimulation or intrinsic ANKRD17 ATPase activity is established. CDC6 total abundance also decreases after ANKRD17 depletion, so decreased chromatin-associated CDC6 does not establish an ANKRD17 loading mechanism.
Proposed replacements: ATPase binding
Supporting Evidence:
PMID:19150984
endogenous Ankrd17 can interact with MCM7, Cdc6, and PCNA
GO:0005515 protein binding
IPI
PMID:22328336
Ankrd17 positively regulates RIG-I-like receptor (RLR)-media...
MODIFY
Summary: The RIG-I/DDX58 interaction contributes to RLR signaling-adaptor activity.
Reason: The complete source abstract explicitly reports ANKRD17 interaction with RIG-I, MDA5 and VISA, enhancement of receptor–VISA association, and perturbation effects on signaling. These combined results support the noncatalytic coordination captured by signaling adaptor activity, beyond an isolated generic interaction with RIG-I/DDX58. This is not an assertion that ANKRD17 itself senses viral RNA. Full Methods and construct/host details were not accessed, and the NOD-study HeLa/Sendai negative result is retained as a context limit rather than a universal contradiction.
Proposed replacements: signaling adaptor activity
Supporting Evidence:
PMID:22328336
ankrd17 enhances the interaction of RIG-I and MDA5 with VISA
GO:0005515 protein binding
IPI
PMID:22328336
Ankrd17 positively regulates RIG-I-like receptor (RLR)-media...
MODIFY
Summary: The VISA/MAVS interaction contributes to RLR signaling-adaptor activity.
Reason: The complete source abstract explicitly reports ANKRD17 interaction with RIG-I, MDA5 and VISA, enhancement of receptor–VISA association, and perturbation effects on signaling. These combined results support the noncatalytic coordination captured by signaling adaptor activity, beyond an isolated generic interaction with VISA/MAVS. This is not an assertion that ANKRD17 itself senses viral RNA. Full Methods and construct/host details were not accessed, and the NOD-study HeLa/Sendai negative result is retained as a context limit rather than a universal contradiction.
Proposed replacements: signaling adaptor activity
Supporting Evidence:
PMID:22328336
ankrd17 enhances the interaction of RIG-I and MDA5 with VISA
GO:0005515 protein binding
IPI
PMID:22328336
Ankrd17 positively regulates RIG-I-like receptor (RLR)-media...
MODIFY
Summary: The MDA5/IFIH1 interaction contributes to RLR signaling-adaptor activity.
Reason: The complete source abstract explicitly reports ANKRD17 interaction with RIG-I, MDA5 and VISA, enhancement of receptor–VISA association, and perturbation effects on signaling. These combined results support the noncatalytic coordination captured by signaling adaptor activity, beyond an isolated generic interaction with MDA5/IFIH1. This is not an assertion that ANKRD17 itself senses viral RNA. Full Methods and construct/host details were not accessed, and the NOD-study HeLa/Sendai negative result is retained as a context limit rather than a universal contradiction.
Proposed replacements: signaling adaptor activity
Supporting Evidence:
PMID:22328336
ankrd17 enhances the interaction of RIG-I and MDA5 with VISA
GO:0005515 protein binding
IPI
PMID:23711367
A role for the Ankyrin repeat containing protein Ankrd17 in ...
MODIFY
Summary: The NOD2 interaction supports signaling receptor binding.
Reason: The source abstract explicitly identifies ANKRD17 as a NOD2-binding partner and maps this interaction to its N-terminal domain, with functional perturbation evidence in human myeloid and epithelial cells. NOD2 is an intracellular pattern-recognition receptor, fitting signaling receptor binding. This does not make ANKRD17 a receptor agonist or transfer the RIG-I/MDA5-to-MAVS bridging mechanism to NOD2. The full paper was not accessed.
Proposed replacements: signaling receptor binding
Supporting Evidence:
PMID:23711367
its N-terminal domain mediates Nod2 binding.
GO:0005634 nucleus
EXP
PMID:17276651
The VP1 structural protein of enterovirus 71 interacts with ...
ACCEPT
Summary: The broad nuclear location is independently established.
Reason: The original EV71/GTAR abstract identifies human GTAR experiments in Vero cells but does not expose the exact localization panels. Retain the curator's nuclear assertion because independent human U2OS/HeLa fractionation and HPA nucleoplasmic staining establish this broad location. The independent support is cited separately; no claim is made that the original full microscopy experiment was read.
Supporting Evidence:
PMID:19150984
Ankrd17 was localized in the nucleus in both cell lines
GO:0005634 nucleus
IDA
PMID:19150984
Identification and functional analysis of a novel cyclin e/c...
ACCEPT
Summary: ANKRD17 is detected in the nucleus of human U2OS and HeLa cells.
Reason: The full Results show nuclear/cytosolic fractionation with controls and a chromatin-associated nuclear pool. Retain this directly supported location, without interpreting the nucleus as ANKRD17's only cellular compartment.
Supporting Evidence:
PMID:19150984
Ankrd17 was localized in the nucleus in both cell lines
GO:0005634 nucleus
IDA
PMID:22328336
Ankrd17 positively regulates RIG-I-like receptor (RLR)-media...
ACCEPT
Summary: The broad nuclear location is corroborated by independent human experiments.
Reason: The RLR source abstract does not show its nuclear-localization panel. Human U2OS/HeLa fractionation in PMID:19150984 and the official HPA nucleoplasmic staining independently support the broad annotation. Retain the source assertion with the original-paper access limit, rather than claiming a contradicted location from its immune-signaling subject matter.
Supporting Evidence:
PMID:19150984
Ankrd17 was localized in the nucleus in both cell lines
GO:0005634 nucleus
IEA
GO_REF:0000120
ACCEPT
Summary: The automated nuclear-location mappings agree with direct human evidence.
Reason: The original ARBA and UniProt subcellular-location identifiers are preserved. Human-cell fractionation and HPA staining independently support a nuclear pool. The historical rule implementation was not reconstructed and is not counted as additional independent experimental evidence.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
ARBA:ARBA00026330 UNRESOLVED
Original source identifier retained. Biological target support is assessed separately; exact historical rule or ancestral-node experiment was not reconstructed.
UniProtKB-SubCell:SL-0191 UNRESOLVED
Original source identifier retained. Biological target support is assessed separately; exact historical rule or ancestral-node experiment was not reconstructed.
Supporting Evidence:
PMID:19150984
Ankrd17 was localized in the nucleus in both cell lines
GO:0005654 nucleoplasm
IDA
GO_REF:0000052
ACCEPT
Summary: Official HPA imaging supports nucleoplasmic localization.
Reason: The official ENSG00000132466-ANKRD17 HPA subcellular page reports supported nucleoplasm as the main location, with human CACO-2, Rh30 and U2OS imaging and HPA063731. Its additional nuclear-membrane observation does not require a redundant new nuclear-location assertion.
Supporting Evidence:
file:human/ANKRD17/ANKRD17-notes.md
Mainly localized to the nucleoplasm. In addition localized to the nuclear membrane.
GO:0005737 cytoplasm
EXP
PMID:17276651
The VP1 structural protein of enterovirus 71 interacts with ...
ACCEPT
Summary: ANKRD17 has an independently observed cytoplasmic pool.
Reason: The original EV71 source used human GTAR with Vero-cell microscopy, but the exact localization panels were not accessed. Independent PMID:31661072 Mask2 immunostaining in human Caco-2 cells supports nuclear and cytoplasmic pools. This broad location is retained with source-specific access limits; it is not inferred solely from a signaling pathway name. The recovered primary body and Methods identify endogenous Mask2 staining in human Caco2 cells (Figure 8A); this target-specific observation is distinct from the paper's Mask1-only knockdown and fly assays.
Supporting Evidence:
PMID:31661072
Endogenous Mask1/2 and YAP co-localise in intracellular granules in both the nucleus and cytoplasm
GO:0005737 cytoplasm
IDA
PMID:22328336
Ankrd17 positively regulates RIG-I-like receptor (RLR)-media...
ACCEPT
Summary: ANKRD17 has an independently observed cytoplasmic pool.
Reason: The RLR abstract does not display the original cytoplasmic-localization experiment. Independent PMID:31661072 Mask2 immunostaining in human Caco-2 cells supports nuclear and cytoplasmic pools. This broad location is retained with source-specific access limits; it is not inferred solely from a signaling pathway name. The recovered primary body and Methods identify endogenous Mask2 staining in human Caco2 cells (Figure 8A); this target-specific observation is distinct from the paper's Mask1-only knockdown and fly assays.
Supporting Evidence:
PMID:31661072
Endogenous Mask1/2 and YAP co-localise in intracellular granules in both the nucleus and cytoplasm
GO:0005737 cytoplasm
IEA
GO_REF:0000044
ACCEPT
Summary: ANKRD17 has an independently observed cytoplasmic pool.
Reason: The original UniProt subcellular-location mapping is preserved; its historical implementation is not treated as independent experimental evidence. Independent PMID:31661072 Mask2 immunostaining in human Caco-2 cells supports nuclear and cytoplasmic pools. This broad location is retained with source-specific access limits; it is not inferred solely from a signaling pathway name. The recovered primary body and Methods identify endogenous Mask2 staining in human Caco2 cells (Figure 8A); this target-specific observation is distinct from the paper's Mask1-only knockdown and fly assays.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
UniProtKB-SubCell:SL-0086 UNRESOLVED
Original source identifier retained. Biological target support is assessed separately; exact historical rule or ancestral-node experiment was not reconstructed.
Supporting Evidence:
PMID:31661072
Endogenous Mask1/2 and YAP co-localise in intracellular granules in both the nucleus and cytoplasm
GO:0006275 regulation of DNA replication
IMP
PMID:19150984
Identification and functional analysis of a novel cyclin e/c...
ACCEPT
Summary: ANKRD17 regulates DNA synthesis in human cells.
Reason: Knockdown reduces BrdU incorporation and S-phase entry, with chromatin association and replication-factor interactions providing mechanistic context. The existing regulatory process is supported. Direct versus indirect PCNA-loading control remains unresolved, and neither a new DNA-replication participation term nor clamp-loader catalysis is inferred.
Supporting Evidence:
PMID:19150984
These results further indicated that depletion of Ankrd17 blocked the DNA replication and the S phase entry.
GO:0016020 membrane
HDA
PMID:19946888
Defining the membrane proteome of NK cells.
UNDECIDED
Summary: The ANKRD17-specific membrane-proteome record remains unread.
Reason: The cached abstract describes a YTS membrane survey containing both predicted membrane proteins and potentially transiently associated proteins. The exact ANKRD17 peptide identification and fraction controls were not recovered. Nuclear and cytoplasmic pools do not disprove membrane association, so retain this source-specific uncertainty rather than remove the assertion.
Supporting Evidence:
GO:0042742 defense response to bacterium
IDA
PMID:23711367
A role for the Ankyrin repeat containing protein Ankrd17 in ...
ACCEPT
Summary: ANKRD17 contributes to antibacterial innate responses.
Reason: The complete source abstract reports NOD1/NOD2-dependent responses in human myeloid and epithelial cells and Shigella-induced pro-inflammatory responses in HeLa cells. This supports the existing broad antibacterial response as part of the immune-regulatory role; no direct bacterial killing or pathogen binding by ANKRD17 is implied.
Supporting Evidence:
PMID:23711367
Ankrd17 contributed to pro-inflammatory responses induced by Shigella flexneri
GO:0043123 positive regulation of canonical NF-kappaB signal transduction
IDA
PMID:22328336
Ankrd17 positively regulates RIG-I-like receptor (RLR)-media...
ACCEPT
Summary: ANKRD17 positively regulates RLR-associated NF-kappa-B signaling.
Reason: The source abstract reports enhanced NF-kappa-B output with ANKRD17 overexpression and impaired RLR signaling with depletion, together with receptor–VISA association. Retain the curator's positive regulatory process. This is not direct NF-kappa-B DNA-binding or transcription-factor activity, and the exact canonical-pathway panels were not independently accessed.
Supporting Evidence:
PMID:22328336
Overexpression of ankrd17 enhances RLR-mediated activation of IRF-3 and NF-ΞΊB
GO:0045087 innate immune response
IBA
GO_REF:0000033
ACCEPT
Summary: Human ANKRD17 experiments support the inherited innate-immunity function.
Reason: The PAINT IBA represents an ancestral-node judgment, not a donor-count vote. ANKRD17's self-inclusion is legitimate descendant experimental grounding. Human NOD/RLR findings independently support the functional assertion. The exact node/tree could not be recovered after one failed normal PAINT attempt; this provenance limit does not negate the target evidence or demonstrate a propagation failure.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN001506277 UNRESOLVED
Original source identifier retained. Biological target support is assessed separately; exact historical rule or ancestral-node experiment was not reconstructed.
UniProtKB:O75179 UNRESOLVED
Target self-inclusion is legitimate experimental descendant evidence, not circular; exact IBD/node provenance remains unread.
Supporting Evidence:
PMID:23711367
Ankrd17 is functionally involved in Nod2- and Nod1-mediated responses in human myeloid and epithelial cells.
GO:0045087 innate immune response
IDA
PMID:23711367
A role for the Ankyrin repeat containing protein Ankrd17 in ...
ACCEPT
Summary: ANKRD17 regulates innate immune receptor responses.
Reason: NOD2 association and perturbation effects on NOD1/NOD2 responses in human myeloid and epithelial cells support this existing innate-immune process. The source's lack of a Sendai-induced interferon effect in HeLa is retained as a cell-context limit rather than concealed or generalized.
Supporting Evidence:
PMID:23711367
Ankrd17 is functionally involved in Nod2- and Nod1-mediated responses in human myeloid and epithelial cells.
GO:0045787 positive regulation of cell cycle
IMP
PMID:19150984
Identification and functional analysis of a novel cyclin e/c...
ACCEPT
Summary: ANKRD17 positively regulates cell-cycle progression.
Reason: Independent knockdown and overexpression experiments in human U2OS cells support a positive regulatory role centered on G1/S progression. This broad existing parent term describes the same core regulatory biology as the more specific G1/S row, not an extra independent function. Effects on p53/p21 abundance do not identify a direct transcriptional mechanism.
Supporting Evidence:
PMID:19150984
These results further indicated that depletion of Ankrd17 blocked the DNA replication and the S phase entry.
GO:0090575 RNA polymerase II transcription regulator complex
IBA
GO_REF:0000033
UNDECIDED
Summary: The inherited Pol-II transcription-regulator-complex assignment remains unresolved.
Reason: GO:0090575 denotes a complex acting at a regulatory DNA region. PMID:31661072 reports that fly Mask lacks intrinsic activation in a GAL4-UAS assay in Drosophila S2 cells, while separate fly experiments support Yki nuclear import. Human Mask2 overexpression stabilizes YAP. These observations distinguish trafficking/stability from a demonstrated regulatory-DNA complex, but a negative intrinsic-activation assay does not exclude membership in such a complex. The exact PTN001506277 IBD placement and donor complex evidence remain untraced; the original fly and ancestral-node identifiers are preserved. Neither fly provenance nor donor count demonstrates an incorrect transfer or lineage-specific loss.
Propagation Review
Root cause: UNRESOLVED
Sources checked:
FB:FBgn0043884 UNRESOLVED
Original fly Mask identifier retained. The actual 2019 S2 GAL4 reporter result lacks intrinsic activation and the fly rescue experiments support Yki import, but the exact experimental assertion used by PAINT for complex membership has not been traced.
PANTHER:PTN001506277 UNRESOLVED
Original source identifier retained. Biological target support is assessed separately; exact historical rule or ancestral-node experiment was not reconstructed.
Supporting Evidence:
PMID:31661072
Mask has no intrinsic transcriptional co-activator activity in a GAL4-UAS reporter assay.
GO:1900087 positive regulation of G1/S transition of mitotic cell cycle
IMP
PMID:19150984
Identification and functional analysis of a novel cyclin e/c...
ACCEPT
Summary: ANKRD17 positively regulates G1/S transition.
Reason: Human U2OS knockdown reduces S-phase entry after serum release, and overexpression increases the S-phase fraction without causing an S-phase block in the nocodazole control. This directly supports the existing regulatory process. The paper does not establish that ANKRD17 itself catalyzes DNA synthesis or the phosphorylation controlling the transition.
Supporting Evidence:
PMID:19150984
These results further indicated that depletion of Ankrd17 blocked the DNA replication and the S phase entry.
GO:1900245 positive regulation of MDA-5 signaling pathway
IDA
PMID:22328336
Ankrd17 positively regulates RIG-I-like receptor (RLR)-media...
ACCEPT
Summary: ANKRD17 positively regulates MDA5 signaling.
Reason: The source abstract explicitly reports receptor interactions, enhanced receptor–VISA association and positive RLR signaling effects, supporting the existing MDA5-specific regulatory assertion. Preserve the original evidence code and receptor scope. Full experimental panels were not accessed; the separate NOD-study negative Sendai response in HeLa limits generalization across cell contexts rather than refuting all RLR regulation.
Supporting Evidence:
PMID:22328336
ankrd17 enhances the interaction of RIG-I and MDA5 with VISA
GO:1900246 positive regulation of RIG-I signaling pathway
IDA
PMID:22328336
Ankrd17 positively regulates RIG-I-like receptor (RLR)-media...
ACCEPT
Summary: ANKRD17 positively regulates RIG-I signaling.
Reason: The source abstract explicitly reports receptor interactions, enhanced receptor–VISA association and positive RLR signaling effects, supporting the existing RIG-I-specific regulatory assertion. Preserve the original evidence code and receptor scope. Full experimental panels were not accessed; the separate NOD-study negative Sendai response in HeLa limits generalization across cell contexts rather than refuting all RLR regulation.
Supporting Evidence:
PMID:22328336
ankrd17 enhances the interaction of RIG-I and MDA5 with VISA

Core Functions

Associates with nuclear chromatin and replication factors to regulate DNA synthesis and G1/S cell-cycle progression. The direct molecular step controlling PCNA loading remains unresolved; ANKRD17 is a cyclin E/CDK2 substrate rather than a demonstrated kinase or clamp loader.

Supporting Evidence:
  • PMID:19150984
    These results strongly indicate that the CSK-insoluble fraction of Ankrd17 binds to chromatin, not a nuclear matrix protein.
  • PMID:19150984
    These results further indicated that depletion of Ankrd17 blocked the DNA replication and the S phase entry.

Coordinates RIG-I/MDA5 association with MAVS to promote antiviral signaling. ANKRD17 also binds NOD2 and supports bacterial innate responses, although the NOD mechanism and cell-context dependence are distinct from the demonstrated receptor–MAVS coordination.

Supporting Evidence:
  • PMID:22328336
    ankrd17 enhances the interaction of RIG-I and MDA5 with VISA
  • PMID:23711367
    Ankrd17 is functionally involved in Nod2- and Nod1-mediated responses in human myeloid and epithelial cells.
  • PMID:31661072
    Endogenous Mask1/2 and YAP co-localise in intracellular granules in both the nucleus and cytoplasm

References

Loading supporting content…

Download this section (compressed HTML)

Suggested Questions for Experts

Q: Does ANKRD17 directly organize or load replication factors, or are the CDC6 and PCNA changes secondary to altered cell-cycle state and protein abundance?

Q: Which RNA targets and physiological mechanism depend on the ANKRD17 KH domain, and what is the exact supplementary evidence underlying the HDA RNA-binding annotation?

Q: Which exact PAINT IBD and donor complex-membership experiment justify GO:0090575 for ANKRD17, given the distinction between fly Mask-dependent Yki import, lack of intrinsic S2 GAL4 reporter activation, and human Mask2-dependent YAP stabilization?

Q: Which cell types and receptor stimuli account for the different RLR/Sendai phenotypes in the two immune-signaling studies?

Suggested Experiments

Experiment: Separate chromatin recruitment from cell-cycle and CDC6-abundance effects using endogenous ANKRD17 perturbations and matched cell-cycle populations; test purified replication-factor interactions before assigning a loader or bridging mechanism.

Experiment: Map endogenous human ANKRD17 RNA contacts and test KH-domain dependence while controlling protein abundance and localization.

πŸ“š Additional Documentation

Notes

(ANKRD17-notes.md)

Loading supporting content…

Download this section (compressed HTML)

πŸ“„ View Raw YAML

Loading supporting content…

Download this section (compressed HTML)