ANKRD44

UniProt ID: Q8N8A2
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

ANKRD44 (ankyrin repeat domain-containing 44; PP6-ARS-B) is one of three alternative ankyrin-repeat subunits of protein phosphatase 6 (PP6), together with ANKRD28 and ANKRD52, which diverged early in vertebrates and are thought to have distinct functions. It associates with a SAPS-domain subunit such as PPP6R1, which in turn binds the PPP6C catalytic subunit, forming a heterotrimer that helps set PP6 substrate specificity. Like ANKRD28, but unlike ANKRD52, it is needed for PP6 function in mitosis. In a HER2-positive breast cancer line, its silencing activates NF-kB and confers partial trastuzumab resistance.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005515 protein binding
IPI
PMID:16555005
The Tre2 oncoprotein, implicated in Ewing's sarcoma, interac...
MODIFY
Summary: Protein binding (IPI) with USP6 (Tre2), confirmed in the source study by pulldown, co-immunoprecipitation and colocalization with the Tre2 GAP region; modified to enzyme binding.
Reason: [PMID:16555005 "Two components of the cytoskeleton were thus identified, whose interaction with the GAP region was confirmed by GST-pulldown, co-immunoprecipitation, and colocalisation experiments."] [file:human/ANKRD44/ANKRD44-uniprot.txt "CC Q8N8A2; P35125-3: USP6; NbExp=4; IntAct=EBI-1245329, EBI-954590;"] The functional consequence for ANKRD44 is untested; enzyme binding names the partner class without overstating.
Proposed replacements: enzyme binding
Supporting Evidence:
PMID:16555005
Two components of the cytoskeleton were thus identified, whose interaction with the GAP region was confirmed by GST-pulldown, co-immunoprecipitation, and colocalisation experiments.
file:human/ANKRD44/ANKRD44-uniprot.txt
CC Q8N8A2; P35125-3: USP6; NbExp=4; IntAct=EBI-1245329, EBI-954590;
GO:0005515 protein binding
IPI
PMID:18186651
Protein phosphatase 6 regulatory subunits composed of ankyri...
REMOVE
Summary: Protein binding (IPI, PMID:18186651) with PPP6R1, the SAPS-domain subunit of the PP6 holoenzyme. Real and reproducible, but it is co-membership of one complex, captured here by the NEW phosphatase-complex and regulator rows; GO:0005515 adds nothing.
Reason: [PMID:18186651 "Mass spectrometry identified coprecipitating proteins as PP6 catalytic subunit and three ankyrin repeat proteins (Ankrd28, Ankrd44, and Ankrd52)."] [file:human/ANKRD44/ANKRD44-uniprot.txt "CC Q8N8A2; Q9UPN7: PPP6R1; NbExp=8; IntAct=EBI-1245329, EBI-359745;"]
Supporting Evidence:
PMID:18186651
Mass spectrometry identified coprecipitating proteins as PP6 catalytic subunit and three ankyrin repeat proteins (Ankrd28, Ankrd44, and Ankrd52).
file:human/ANKRD44/ANKRD44-uniprot.txt
CC Q8N8A2; Q9UPN7: PPP6R1; NbExp=8; IntAct=EBI-1245329, EBI-359745;
GO:0005515 protein binding
IPI
PMID:24255178
Protein interaction network of the mammalian Hippo pathway r...
REMOVE
Summary: Protein binding (IPI, PMID:24255178) with PPP6R1, the SAPS-domain subunit of the PP6 holoenzyme. Real and reproducible, but it is co-membership of one complex, captured here by the NEW phosphatase-complex and regulator rows; GO:0005515 adds nothing.
Reason: [PMID:18186651 "Mass spectrometry identified coprecipitating proteins as PP6 catalytic subunit and three ankyrin repeat proteins (Ankrd28, Ankrd44, and Ankrd52)."] [file:human/ANKRD44/ANKRD44-uniprot.txt "CC Q8N8A2; Q9UPN7: PPP6R1; NbExp=8; IntAct=EBI-1245329, EBI-359745;"]
Supporting Evidence:
PMID:18186651
Mass spectrometry identified coprecipitating proteins as PP6 catalytic subunit and three ankyrin repeat proteins (Ankrd28, Ankrd44, and Ankrd52).
file:human/ANKRD44/ANKRD44-uniprot.txt
CC Q8N8A2; Q9UPN7: PPP6R1; NbExp=8; IntAct=EBI-1245329, EBI-359745;
GO:0005515 protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network.
REMOVE
Summary: Protein binding (IPI, PMID:25416956) with WWP2 from a proteome-scale yeast two-hybrid screen. There is no functional follow-up, and GO:0005515 is uninformative.
Reason: The pair is recorded as [file:human/ANKRD44/ANKRD44-uniprot.txt "CC Q8N8A2; O00308: WWP2; NbExp=5; IntAct=EBI-1245329, EBI-743923;"]
Supporting Evidence:
file:human/ANKRD44/ANKRD44-uniprot.txt
CC Q8N8A2; O00308: WWP2; NbExp=5; IntAct=EBI-1245329, EBI-743923;
GO:0005515 protein binding
IPI
PMID:31515488
Extensive disruption of protein interactions by genetic vari...
REMOVE
Summary: Protein binding (IPI, PMID:31515488) with WWP2 from a proteome-scale yeast two-hybrid screen. There is no functional follow-up, and GO:0005515 is uninformative.
Reason: The pair is recorded as [file:human/ANKRD44/ANKRD44-uniprot.txt "CC Q8N8A2; O00308: WWP2; NbExp=5; IntAct=EBI-1245329, EBI-743923;"]
Supporting Evidence:
file:human/ANKRD44/ANKRD44-uniprot.txt
CC Q8N8A2; O00308: WWP2; NbExp=5; IntAct=EBI-1245329, EBI-743923;
GO:0005515 protein binding
IPI
Q8N8A2-2
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ...
REMOVE
Summary: Protein binding (IPI, PMID:32814053) with WFS1 from a proteome-scale yeast two-hybrid screen. There is no functional follow-up, and GO:0005515 is uninformative.
Reason: The pair is recorded as [file:human/ANKRD44/ANKRD44-uniprot.txt "CC Q8N8A2-2; O76024: WFS1; NbExp=3; IntAct=EBI-21636328, EBI-720609;"]
Supporting Evidence:
file:human/ANKRD44/ANKRD44-uniprot.txt
CC Q8N8A2-2; O76024: WFS1; NbExp=3; IntAct=EBI-21636328, EBI-720609;
GO:0005515 protein binding
IPI
Q8N8A2-2
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ...
REMOVE
Summary: Protein binding (IPI, PMID:32814053) with HSPB1 from a proteome-scale yeast two-hybrid screen. There is no functional follow-up, and GO:0005515 is uninformative.
Reason: The pair is recorded as [file:human/ANKRD44/ANKRD44-uniprot.txt "CC Q8N8A2-2; P04792: HSPB1; NbExp=3; IntAct=EBI-21636328, EBI-352682;"]
Supporting Evidence:
file:human/ANKRD44/ANKRD44-uniprot.txt
CC Q8N8A2-2; P04792: HSPB1; NbExp=3; IntAct=EBI-21636328, EBI-352682;
GO:0005515 protein binding
IPI
Q8N8A2-2
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ...
REMOVE
Summary: Protein binding (IPI, PMID:32814053) with RNF11 from a proteome-scale yeast two-hybrid screen. There is no functional follow-up, and GO:0005515 is uninformative.
Reason: The pair is recorded as [file:human/ANKRD44/ANKRD44-uniprot.txt "CC Q8N8A2-2; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-21636328, EBI-396669;"]
Supporting Evidence:
file:human/ANKRD44/ANKRD44-uniprot.txt
CC Q8N8A2-2; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-21636328, EBI-396669;
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling...
REMOVE
Summary: Protein binding (IPI, PMID:33961781) with PPP6R1, the SAPS-domain subunit of the PP6 holoenzyme. Real and reproducible, but it is co-membership of one complex, captured here by the NEW phosphatase-complex and regulator rows; GO:0005515 adds nothing.
Reason: [PMID:18186651 "Mass spectrometry identified coprecipitating proteins as PP6 catalytic subunit and three ankyrin repeat proteins (Ankrd28, Ankrd44, and Ankrd52)."] [file:human/ANKRD44/ANKRD44-uniprot.txt "CC Q8N8A2; Q9UPN7: PPP6R1; NbExp=8; IntAct=EBI-1245329, EBI-359745;"]
Supporting Evidence:
PMID:18186651
Mass spectrometry identified coprecipitating proteins as PP6 catalytic subunit and three ankyrin repeat proteins (Ankrd28, Ankrd44, and Ankrd52).
file:human/ANKRD44/ANKRD44-uniprot.txt
CC Q8N8A2; Q9UPN7: PPP6R1; NbExp=8; IntAct=EBI-1245329, EBI-359745;
GO:0005515 protein binding
IPI
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human ce...
REMOVE
Summary: Protein binding (IPI, PMID:35271311) with PPP6R1, the SAPS-domain subunit of the PP6 holoenzyme. Real and reproducible, but it is co-membership of one complex, captured here by the NEW phosphatase-complex and regulator rows; GO:0005515 adds nothing.
Reason: [PMID:18186651 "Mass spectrometry identified coprecipitating proteins as PP6 catalytic subunit and three ankyrin repeat proteins (Ankrd28, Ankrd44, and Ankrd52)."] [file:human/ANKRD44/ANKRD44-uniprot.txt "CC Q8N8A2; Q9UPN7: PPP6R1; NbExp=8; IntAct=EBI-1245329, EBI-359745;"]
Supporting Evidence:
PMID:18186651
Mass spectrometry identified coprecipitating proteins as PP6 catalytic subunit and three ankyrin repeat proteins (Ankrd28, Ankrd44, and Ankrd52).
file:human/ANKRD44/ANKRD44-uniprot.txt
CC Q8N8A2; Q9UPN7: PPP6R1; NbExp=8; IntAct=EBI-1245329, EBI-359745;
GO:0005515 protein binding
IPI
PMID:40205054
Multimodal cell maps as a foundation for structural and func...
REMOVE
Summary: Protein binding (IPI, PMID:40205054) with PPP6R1, the SAPS-domain subunit of the PP6 holoenzyme. Real and reproducible, but it is co-membership of one complex, captured here by the NEW phosphatase-complex and regulator rows; GO:0005515 adds nothing.
Reason: [PMID:18186651 "Mass spectrometry identified coprecipitating proteins as PP6 catalytic subunit and three ankyrin repeat proteins (Ankrd28, Ankrd44, and Ankrd52)."] [file:human/ANKRD44/ANKRD44-uniprot.txt "CC Q8N8A2; Q9UPN7: PPP6R1; NbExp=8; IntAct=EBI-1245329, EBI-359745;"]
Supporting Evidence:
PMID:18186651
Mass spectrometry identified coprecipitating proteins as PP6 catalytic subunit and three ankyrin repeat proteins (Ankrd28, Ankrd44, and Ankrd52).
file:human/ANKRD44/ANKRD44-uniprot.txt
CC Q8N8A2; Q9UPN7: PPP6R1; NbExp=8; IntAct=EBI-1245329, EBI-359745;
GO:0008287 protein serine/threonine phosphatase complex
IDA
PMID:18186651
Protein phosphatase 6 regulatory subunits composed of ankyri...
NEW
Summary: Protein serine/threonine phosphatase complex (NEW, IDA). Endogenous ANKRD44 co-purifies with the PP6 catalytic subunit through PPP6R1 in human cells, as one of the three alternative ankyrin-repeat subunits of PP6.
Reason: [PMID:18186651 "This study used a human SAPS domain subunit FLAG-PP6R1 to identify endogenous interacting proteins."] [PMID:18186651 "Mass spectrometry identified coprecipitating proteins as PP6 catalytic subunit and three ankyrin repeat proteins (Ankrd28, Ankrd44, and Ankrd52)."] A reciprocal purification of FLAG-PPP6C from mitotic HeLa cells found the same subunits: [PMID:21187329 "This revealed that HeLa cells express all known PP6 subunits and that these are present in PPP6C complexes during mitosis"] [PMID:39014521 "PP6 functions as a heterotrimer with a catalytic subunit (PP6c), regulatory subunits (PP6R1, PP6R2, and PP6R3), and scaffold subunits (ANKRD28, ANKRD44, and ANKRD52)."] The paralog ANKRD28 carries this term by IDA (PMID:35512830); ANKRD44 is a structural subunit of the complex, so the term applies by participation.
Supporting Evidence:
PMID:18186651
This study used a human SAPS domain subunit FLAG-PP6R1 to identify endogenous interacting proteins.
PMID:18186651
Mass spectrometry identified coprecipitating proteins as PP6 catalytic subunit and three ankyrin repeat proteins (Ankrd28, Ankrd44, and Ankrd52).
PMID:21187329
This revealed that HeLa cells express all known PP6 subunits and that these are present in PPP6C complexes during mitosis
PMID:39014521
PP6 functions as a heterotrimer with a catalytic subunit (PP6c), regulatory subunits (PP6R1, PP6R2, and PP6R3), and scaffold subunits (ANKRD28, ANKRD44, and ANKRD52).
GO:0019888 protein phosphatase regulator activity
IMP
PMID:21187329
Protein phosphatase 6 regulates mitotic spindle formation by...
NEW
Summary: Protein phosphatase regulator activity (NEW, IMP). Depleting ANKRD44, like ANKRD28 but unlike ANKRD52, disrupts PP6 function in mitosis.
Reason: [PMID:21187329 "Depletion of the ANKRD52 subunit had no effect on nuclear morphology, whereas ANKRD28 and ANKRD44 ankyrin repeat subunit depletion altered nuclear morphology"] [PMID:21187329 "The results presented here suggest that the ANKRD28 and 44 subunits are required for PP6 function in mitosis, whereas ANKRD52 is not."] The paralog ANKRD28 carries this term by IMP (PMID:35512830). The evidence here is phenotype-level (nuclear morphology after depletion), not a direct phosphatase activity assay with and without ANKRD44. ANKRD44 is a holoenzyme subunit, so the regulation is its own participation, not a downstream consequence.
Supporting Evidence:
PMID:21187329
Depletion of the ANKRD52 subunit had no effect on nuclear morphology, whereas ANKRD28 and ANKRD44 ankyrin repeat subunit depletion altered nuclear morphology
PMID:21187329
The results presented here suggest that the ANKRD28 and 44 subunits are required for PP6 function in mitosis, whereas ANKRD52 is not.

Core Functions

Ankyrin-repeat scaffolding subunit of protein phosphatase 6 that, with a SAPS-domain subunit, helps select PP6 substrates and is needed for PP6 function in mitosis.

Supporting Evidence:
  • PMID:18186651
    Mass spectrometry identified coprecipitating proteins as PP6 catalytic subunit and three ankyrin repeat proteins (Ankrd28, Ankrd44, and Ankrd52).
  • PMID:21187329
    Depletion of the ANKRD52 subunit had no effect on nuclear morphology, whereas ANKRD28 and ANKRD44 ankyrin repeat subunit depletion altered nuclear morphology
  • PMID:21187329
    The results presented here suggest that the ANKRD28 and 44 subunits are required for PP6 function in mitosis, whereas ANKRD52 is not.
  • PMID:39014521
    PP6 functions as a heterotrimer with a catalytic subunit (PP6c), regulatory subunits (PP6R1, PP6R2, and PP6R3), and scaffold subunits (ANKRD28, ANKRD44, and ANKRD52).

References

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Suggested Questions for Experts

Q: Which PP6 substrates depend on ANKRD44 rather than ANKRD28 or ANKRD52?

Suggested Experiments

Experiment: Use paralog-specific knockouts of ANKRD28, ANKRD44 and ANKRD52 with phosphoproteomics to map the substrates each ankyrin subunit directs PP6 to.

Deep Research

Affinage

(ANKRD44-deep-research-affinage.md)

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πŸ“š Additional Documentation

Notes

(ANKRD44-notes.md)

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