ANKRD49

Summary: Protein binding (IPI, PMID:17003112) with HIF1AN (FIH), an asparaginyl hydroxylase that hydroxylates ankyrin repeats. This row comes from the FIH interaction screen of that study (only the abstract is cached); the pair recurs across five studies. Modified to enzyme binding.

Reason: [PMID:17003112 "After the identification of a series of ankyrin repeat domain (ARD)-containing proteins in a screen for proteins interacting with FIH"] [PMID:17003112 "peptides derived from a diverse range of ARD-containing proteins supported FIH enzyme activity."] [file:human/ANKRD49/ANKRD49-uniprot.txt "CC Q8WVL7; Q9NWT6: HIF1AN; NbExp=8; IntAct=EBI-9381820, EBI-745632;"] Whether FIH hydroxylates ANKRD49 itself is not shown; enzyme binding names the partner class.

Proposed replacements: enzyme binding

Summary: Protein binding (IPI) with RAN. The source study shows that ankyrin repeats with a defined code bind RanGDP and enter the nucleus independently of importins; GOA's curated IPI records ANKRD49 binding RAN in that study (only the abstract is cached). Modified to small GTPase binding (GO:0008536 Ran GTPase binding has been merged into GO:0031267).

Reason: [PMID:24855949 "AR-containing proteins (ARPs) with a hydrophobic residue at the 13th position of two consecutive ARs bind RanGDP efficiently, and consequently enter the nucleus."] [file:human/ANKRD49/ANKRD49-uniprot.txt "CC Q8WVL7; P62826: RAN; NbExp=2; IntAct=EBI-9381820, EBI-286642;"] This also offers a mechanism for ANKRD49's nuclear localization.

Proposed replacements: small GTPase binding

Summary: Protein binding (IPI, PMID:25036637) with FKBPL. The pair is reproducible across affinity purification and yeast two-hybrid studies, but its significance is unknown and no informative function term fits; GO:0005515 is uninformative.

Reason: The interaction is deposited as [file:human/ANKRD49/ANKRD49-uniprot.txt "CC Q8WVL7; Q9UIM3: FKBPL; NbExp=9; IntAct=EBI-9381820, EBI-719882;"]; it is raised as a question rather than annotated.

Summary: Protein binding (IPI, PMID:28514442) with HIF1AN (FIH), an asparaginyl hydroxylase that hydroxylates ankyrin repeats. This row comes from a proteome-scale affinity purification-mass spectrometry study; the pair recurs across five studies. Modified to enzyme binding.

Reason: [PMID:17003112 "After the identification of a series of ankyrin repeat domain (ARD)-containing proteins in a screen for proteins interacting with FIH"] [PMID:17003112 "peptides derived from a diverse range of ARD-containing proteins supported FIH enzyme activity."] [file:human/ANKRD49/ANKRD49-uniprot.txt "CC Q8WVL7; Q9NWT6: HIF1AN; NbExp=8; IntAct=EBI-9381820, EBI-745632;"] Whether FIH hydroxylates ANKRD49 itself is not shown; enzyme binding names the partner class.

Proposed replacements: enzyme binding

Summary: Protein binding (IPI, PMID:28514442) with FKBPL. The pair is reproducible across affinity purification and yeast two-hybrid studies, but its significance is unknown and no informative function term fits; GO:0005515 is uninformative.

Reason: The interaction is deposited as [file:human/ANKRD49/ANKRD49-uniprot.txt "CC Q8WVL7; Q9UIM3: FKBPL; NbExp=9; IntAct=EBI-9381820, EBI-719882;"]; it is raised as a question rather than annotated.

Summary: Protein binding (IPI, PMID:29426014) with HIF1AN (FIH), an asparaginyl hydroxylase that hydroxylates ankyrin repeats. This row comes from a proteome-scale affinity purification-mass spectrometry study; the pair recurs across five studies. Modified to enzyme binding.

Reason: [PMID:17003112 "After the identification of a series of ankyrin repeat domain (ARD)-containing proteins in a screen for proteins interacting with FIH"] [PMID:17003112 "peptides derived from a diverse range of ARD-containing proteins supported FIH enzyme activity."] [file:human/ANKRD49/ANKRD49-uniprot.txt "CC Q8WVL7; Q9NWT6: HIF1AN; NbExp=8; IntAct=EBI-9381820, EBI-745632;"] Whether FIH hydroxylates ANKRD49 itself is not shown; enzyme binding names the partner class.

Proposed replacements: enzyme binding

Summary: Protein binding (IPI) with SMARCD1 from the HuRI yeast two-hybrid map. There is no follow-up, and GO:0005515 is uninformative.

Reason: The interaction is deposited as [file:human/ANKRD49/ANKRD49-uniprot.txt "CC Q8WVL7; Q96GM5: SMARCD1; NbExp=4; IntAct=EBI-9381820, EBI-358489;"], from a single yeast two-hybrid map without functional follow-up; its possible relevance to transcription is raised as a question for SMARCD1.

Summary: Protein binding (IPI) with ENKD1 from the HuRI yeast two-hybrid map. There is no follow-up, and GO:0005515 is uninformative.

Reason: The interaction is deposited as [file:human/ANKRD49/ANKRD49-uniprot.txt "CC Q8WVL7; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-9381820, EBI-744099;"], from a single yeast two-hybrid map without functional follow-up; its possible relevance to transcription is raised as a question for SMARCD1.

Summary: Protein binding (IPI, PMID:32296183) with FKBPL. The pair is reproducible across affinity purification and yeast two-hybrid studies, but its significance is unknown and no informative function term fits; GO:0005515 is uninformative.

Reason: The interaction is deposited as [file:human/ANKRD49/ANKRD49-uniprot.txt "CC Q8WVL7; Q9UIM3: FKBPL; NbExp=9; IntAct=EBI-9381820, EBI-719882;"]; it is raised as a question rather than annotated.

Summary: Protein binding (IPI, PMID:33961781) with HIF1AN (FIH), an asparaginyl hydroxylase that hydroxylates ankyrin repeats. This row comes from a proteome-scale affinity purification-mass spectrometry study; the pair recurs across five studies. Modified to enzyme binding.

Reason: [PMID:17003112 "After the identification of a series of ankyrin repeat domain (ARD)-containing proteins in a screen for proteins interacting with FIH"] [PMID:17003112 "peptides derived from a diverse range of ARD-containing proteins supported FIH enzyme activity."] [file:human/ANKRD49/ANKRD49-uniprot.txt "CC Q8WVL7; Q9NWT6: HIF1AN; NbExp=8; IntAct=EBI-9381820, EBI-745632;"] Whether FIH hydroxylates ANKRD49 itself is not shown; enzyme binding names the partner class.

Proposed replacements: enzyme binding

Summary: Protein binding (IPI, PMID:33961781) with FKBPL. The pair is reproducible across affinity purification and yeast two-hybrid studies, but its significance is unknown and no informative function term fits; GO:0005515 is uninformative.

Reason: The interaction is deposited as [file:human/ANKRD49/ANKRD49-uniprot.txt "CC Q8WVL7; Q9UIM3: FKBPL; NbExp=9; IntAct=EBI-9381820, EBI-719882;"]; it is raised as a question rather than annotated.

Summary: Protein binding (IPI, PMID:40205054) with HIF1AN (FIH), an asparaginyl hydroxylase that hydroxylates ankyrin repeats. This row comes from a proteome-scale affinity purification-mass spectrometry study; the pair recurs across five studies. Modified to enzyme binding.

Reason: [PMID:17003112 "After the identification of a series of ankyrin repeat domain (ARD)-containing proteins in a screen for proteins interacting with FIH"] [PMID:17003112 "peptides derived from a diverse range of ARD-containing proteins supported FIH enzyme activity."] [file:human/ANKRD49/ANKRD49-uniprot.txt "CC Q8WVL7; Q9NWT6: HIF1AN; NbExp=8; IntAct=EBI-9381820, EBI-745632;"] Whether FIH hydroxylates ANKRD49 itself is not shown; enzyme binding names the partner class.

Proposed replacements: enzyme binding

Summary: Protein binding (IPI, PMID:40205054) with FKBPL. The pair is reproducible across affinity purification and yeast two-hybrid studies, but its significance is unknown and no informative function term fits; GO:0005515 is uninformative.

Reason: The interaction is deposited as [file:human/ANKRD49/ANKRD49-uniprot.txt "CC Q8WVL7; Q9UIM3: FKBPL; NbExp=9; IntAct=EBI-9381820, EBI-719882;"]; it is raised as a question rather than annotated.

Summary: Nucleus (IC). ANKRD49 is predominantly nuclear in mouse germ cells, consistent with its transactivation activity; accepted.

Reason: [PMID:26043108 "we found that ANKRD49 resides primarily in nucleus of spermatogonia, spermatocytes and round spermatids."] [PMID:11162141 "Transactivation assays in the yeast hybrid system and transient transfection assays in COS cells showed that a potent trans-activating domain resides in the N-terminus of this protein."]

Summary: Nucleus (IEA). ANKRD49 is predominantly nuclear in mouse germ cells, consistent with its transactivation activity; accepted.

Reason: [PMID:26043108 "we found that ANKRD49 resides primarily in nucleus of spermatogonia, spermatocytes and round spermatids."] [PMID:11162141 "Transactivation assays in the yeast hybrid system and transient transfection assays in COS cells showed that a potent trans-activating domain resides in the N-terminus of this protein."]

Summary: Nucleus (ISS). ANKRD49 is predominantly nuclear in mouse germ cells, consistent with its transactivation activity; accepted.

Reason: [PMID:26043108 "we found that ANKRD49 resides primarily in nucleus of spermatogonia, spermatocytes and round spermatids."] [PMID:11162141 "Transactivation assays in the yeast hybrid system and transient transfection assays in COS cells showed that a potent trans-activating domain resides in the N-terminus of this protein."]

Summary: Positive regulation of DNA-templated transcription (IBA). ANKRD49 (FGIF) carries a potent N-terminal transactivation domain and raises gamma-globin expression; accepted.

Reason: [PMID:11162141 "Transactivation assays in the yeast hybrid system and transient transfection assays in COS cells showed that a potent trans-activating domain resides in the N-terminus of this protein."] [PMID:11162141 "Stable transfection assays provided evidence that the product of this gene may increase the level of gamma mRNA in HFE x MEL cell hybrids"] [PMID:16131492 "was reactivated by an artificial zinc finger-gamma-globin transcription factor and the previously identified fetal globin transactivators fetal Krüppel-like factor (FKLF) and fetal globin-increasing factor (FGIF)."]

Summary: Positive regulation of DNA-templated transcription (IDA). ANKRD49 (FGIF) carries a potent N-terminal transactivation domain and raises gamma-globin expression; accepted.

Reason: [PMID:11162141 "Transactivation assays in the yeast hybrid system and transient transfection assays in COS cells showed that a potent trans-activating domain resides in the N-terminus of this protein."] [PMID:11162141 "Stable transfection assays provided evidence that the product of this gene may increase the level of gamma mRNA in HFE x MEL cell hybrids"] [PMID:16131492 "was reactivated by an artificial zinc finger-gamma-globin transcription factor and the previously identified fetal globin transactivators fetal Krüppel-like factor (FKLF) and fetal globin-increasing factor (FGIF)."]

Summary: Positive regulation of DNA-templated transcription (IDA). ANKRD49 (FGIF) carries a potent N-terminal transactivation domain and raises gamma-globin expression; accepted.

Reason: [PMID:11162141 "Transactivation assays in the yeast hybrid system and transient transfection assays in COS cells showed that a potent trans-activating domain resides in the N-terminus of this protein."] [PMID:11162141 "Stable transfection assays provided evidence that the product of this gene may increase the level of gamma mRNA in HFE x MEL cell hybrids"] [PMID:16131492 "was reactivated by an artificial zinc finger-gamma-globin transcription factor and the previously identified fetal globin transactivators fetal Krüppel-like factor (FKLF) and fetal globin-increasing factor (FGIF)."]

Summary: Transcription coactivator activity (NEW, IDA). ANKRD49 has a potent N-terminal acidic transactivation domain, and it physically binds the DNA-binding transcription factor PKNOX1, raising expression of the PKNOX1 target TGF-B1.

Reason: [PMID:11162141 "The second pair coded for a protein containing an acidic domain in the N-terminus and three consecutive CDC10/SW16/ankyrin repeats in the C-terminus."] [PMID:11162141 "Transactivation assays in the yeast hybrid system and transient transfection assays in COS cells showed that a potent trans-activating domain resides in the N-terminus of this protein."] [PMID:41821002 "Mechanistically, ANKRD49 physically interacts with PKNOX1, and PKNOX1 binds to the TGF-β1 promoter, elevating TGF-β1 expression and subsequently activating SMAD signaling."] In ANKRD49-overexpressing cells, [PMID:41821002 "ChIP-qPCR analysis showed specific enrichment of the − 1455 to − 1441 region in Flag-PKNOX1 pulldowns from ANKRD49-OE cells compared with controls"], [PMID:41821002 "confirming that PKNOX1 directly binds this site and that ANKRD49 strengthens the interaction"] An acidic activation domain, binding to a DNA-binding factor, and increased occupancy of that factor at its target fit the coactivator signature, and ANKRD49 has no DNA-binding domain. Most directly, in the reporter assay with PKNOX1 supplied from a plasmid, [PMID:41821002 "Notably, PKNOX1 overexpression alone significantly enhanced TGF-β1 promoter activity, and co-expression of ANKRD49 further amplified this effect, suggesting that ANKRD49 potentiates PKNOX1 binding to the TGF-β1 promoter and enhances its transcriptional output"] Limits: in overexpressing cells [PMID:41821002 "both mRNA and protein levels of PKNOX1 were significantly elevated in ANKRD49-OE A549 or H1299 cells"], and [PMID:41821002 "Subcellular fractionation assays further demonstrated increased nuclear accumulation of PKNOX1 in ANKRD49-OE cells"], so part of the effect could be more nuclear PKNOX1 rather than coactivation; the plasmid-driven reporter result argues against transcriptional upregulation alone, but not against nuclear accumulation. ANKRD49 occupancy at the promoter was not measured.