AKIRIN1 encodes a conserved nuclear Akirin-family protein that functions as a transcriptional cofactor in inducible gene-expression programs. It also has a context-dependent promyogenic role supporting myoblast and satellite-cell proliferation and differentiation during muscle repair. The protein localizes to the nucleus and nucleoplasm and is not an enzyme; its main role is to help regulate transcription in chromatin-associated nuclear contexts rather than to catalyze a biochemical reaction.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0005634
nucleus
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Nuclear localization is the central, conserved cellular context for AKIRIN1.
Reason: The paper that established the human homologs reports strict nuclear localization for HsAkirin1, and the UniProt record also places the protein in the nucleus. This is consistent with the conserved Akirin role as a nuclear transcriptional cofactor.
Supporting Evidence:
PMID:18066067
strict nuclear localization
|
|
GO:0045944
positive regulation of transcription by RNA polymerase II
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: This captures the best-supported conserved biological process for AKIRIN1.
Reason: AKIRIN1 is best understood as a nuclear cofactor that supports inducible transcriptional output. The canonical Akirin paper places the protein downstream of NF-kappaB-dependent gene expression and describes Akirins as nuclear cofactors regulating transcriptional activities of main transactivators, which fits this GO term well.
Supporting Evidence:
PMID:18066067
regulating the transcriptional activities of main transactivators
|
|
GO:0000785
chromatin
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Chromatin association is plausible and consistent with the nuclear cofactor role.
Reason: The 2008 paper argues that Akirins likely act by associating with chromatin or the transcriptional engine, and the conserved nuclear localization supports a chromatin-associated transcriptional role. This is not over-specific for the available evidence.
Supporting Evidence:
PMID:18066067
interacting with components of the chromatin or the transcriptional engine
|
|
GO:0003712
transcription coregulator activity
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: This is the most direct molecular-function summary for AKIRIN1.
Reason: AKIRIN1 is not a DNA-binding enzyme or a catalytic factor; the direct human and mouse literature supports a nuclear transcriptional cofactor role downstream of NF-kappaB. This MF term is appropriately specific without overstating a direct DNA-binding or catalytic activity.
Supporting Evidence:
PMID:18066067
novel important nuclear cofactors regulating the transcriptional activities of main transactivators
|
|
GO:0010592
positive regulation of lamellipodium assembly
|
IBA
GO_REF:0000033 |
MARK AS OVER ANNOTATED |
Summary: This is a family/orthology-derived motility call that is not supported for human AKIRIN1.
Reason: The conserved human AKIRIN1 literature supports a nuclear transcriptional cofactor role, not direct actin-remodeling or lamellipodium biology. In the same paper, Akirin1 knockout mice were viable and showed no gross developmental abnormalities, which argues against promoting a specific cell-motility process for the human paralog on the basis of family-level transfer alone.
Supporting Evidence:
PMID:18066067
MmAkirin1-/- mice were born in a Mendelian ratio, grew healthily and did not show gross developmental abnormalities
PMID:18066067
the functional role of MmAkirin1, attested by its sequence conservation, is unknown thus far
|
|
GO:0010759
positive regulation of macrophage chemotaxis
|
IBA
GO_REF:0000033 |
MARK AS OVER ANNOTATED |
Summary: This macrophage-migration term is over-propagated relative to the human AKIRIN1 evidence.
Reason: Human AKIRIN1 is supported as a nuclear transcriptional cofactor, not as a direct regulator of macrophage migration. The family paper specifically notes that the role of Akirin1 is unknown and that the immune-response phenotype belongs to Akirin2, not Akirin1, so this process annotation is too strong for AKIRIN1.
Supporting Evidence:
PMID:18066067
the functional role of MmAkirin1, attested by its sequence conservation, is unknown thus far
PMID:18066067
MmAkirin2, but not MmAkirin1, was responsible for the production of IL-6
|
|
GO:0014839
myoblast migration involved in skeletal muscle regeneration
|
IBA
GO_REF:0000033 |
KEEP AS NON CORE |
Summary: This is a real but context-dependent muscle-regeneration annotation, not a core function.
Reason: The muscle literature supports AKIRIN1 as a promyogenic factor in satellite-cell activation and regeneration, including increased MyoD/myogenin and improved proliferation/differentiation after AKIRIN1 overexpression. That is sufficient to keep this as a non-core regenerative annotation, but the term is more specific than the evidence and should not be elevated to the main conserved function.
Supporting Evidence:
PMID:23516508
Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation
file:human/AKIRIN1/AKIRIN1-deep-research-falcon.md
supports myoblast/satellite cell proliferation and differentiation
|
|
GO:0045663
positive regulation of myoblast differentiation
|
IBA
GO_REF:0000033 |
KEEP AS NON CORE |
Summary: This is a supported but non-core promyogenic annotation for human AKIRIN1.
Reason: The Falcon deep research and Dong et al. 2013 support AKIRIN1 as a promyogenic nuclear factor. In that study, AKIRIN1 overexpression increased MyoD and myogenin and improved myoblast proliferation and differentiation, so this term is supported. It is still context-specific muscle biology rather than the main conserved function of the protein, so it should be retained as non-core.
Supporting Evidence:
PMID:23516508
Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation
PMID:23516508
a promyogenic gene
file:human/AKIRIN1/AKIRIN1-deep-research-falcon.md
promyogenic nuclear factor
|
|
GO:1902723
negative regulation of skeletal muscle satellite cell proliferation
|
IBA
GO_REF:0000033 |
MARK AS OVER ANNOTATED |
Summary: This direction is inconsistent with the AKIRIN1 muscle literature.
Reason: The direct AKIRIN1 muscle literature supports the opposite direction: AKIRIN1 expression promotes satellite-cell activity, myoblast proliferation, and myogenic differentiation. This negative-regulation term therefore overstates the biology for human AKIRIN1 even though the pathway is clearly linked to muscle repair.
Supporting Evidence:
PMID:23516508
When myostatin was inhibited in Dex-treated mice, Akirin1 expression increased as did satellite cell activity, muscle regeneration and muscle growth
PMID:23516508
Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation
|
|
GO:0005634
nucleus
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: This is a redundant but correct UniProt-derived nuclear localization call.
Reason: The subcellular-location mapping agrees with the direct human localization result in PMID:18066067 and does not conflict with the IBA nuclear annotation.
Supporting Evidence:
PMID:18066067
strict nuclear localization
|
|
GO:0005515
protein binding
|
IPI
PMID:25416956 A proteome-scale map of the human interactome network. |
MODIFY |
Summary: The interaction evidence is real, but the generic protein-binding parent is too vague.
Reason: A direct interaction is supported by the IntAct-derived record, but the annotation should not remain at the uninformative protein-binding parent term. The most conservative informative replacement is protein-containing complex binding. This should not be conflated with the PN projection to proteasome binding, which is not directly supported by the local human literature cache.
Proposed replacements:
protein-containing complex binding
Supporting Evidence:
file:human/AKIRIN1/AKIRIN1-uniprot.txt
Q9H9L7; Q9HD26: GOPC; NbExp=3; IntAct=EBI-10309796, EBI-349832
|
|
GO:0010592
positive regulation of lamellipodium assembly
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: This family-transfer call is not justified for human AKIRIN1.
Reason: The human paper supports nuclear transcriptional cofactor activity, not a direct lamellipodium-assembly role. This appears to be a propagated family phenotype rather than an AKIRIN1-specific process.
Supporting Evidence:
PMID:18066067
regulating the transcriptional activities of main transactivators
|
|
GO:0010759
positive regulation of macrophage chemotaxis
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: This is an over-specific immune-cell migration annotation for human AKIRIN1.
Reason: The direct evidence does not support macrophage chemotaxis as an AKIRIN1 function. The family-level literature instead separates the immune-response phenotype onto Akirin2.
Supporting Evidence:
PMID:18066067
MmAkirin2, but not MmAkirin1, was responsible for the production of IL-6
|
|
GO:0014839
myoblast migration involved in skeletal muscle regeneration
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: This is a real but context-dependent muscle-regeneration annotation, not a core function.
Reason: The deeper muscle literature supports AKIRIN1 in myoblast/satellite-cell proliferation and differentiation during regeneration. That is sufficient to keep the lineage-specific regeneration call as non-core, but not as a primary conserved function for AKIRIN1.
Supporting Evidence:
PMID:23516508
Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation
file:human/AKIRIN1/AKIRIN1-deep-research-falcon.md
supports myoblast/satellite cell proliferation and differentiation
|
|
GO:0045663
positive regulation of myoblast differentiation
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: This is a supported but non-core promyogenic annotation for human AKIRIN1.
Reason: Dong et al. 2013 directly links AKIRIN1 to promyogenic behavior: in myoblasts, AKIRIN1 overexpression increased MyoD and myogenin and improved proliferation and differentiation. This supports the annotation, but it remains a context-dependent muscle-repair function rather than the principal conserved role of the protein.
Supporting Evidence:
PMID:23516508
Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation
PMID:23516508
a promyogenic gene
file:human/AKIRIN1/AKIRIN1-deep-research-falcon.md
promyogenic nuclear factor
|
|
GO:0045944
positive regulation of transcription by RNA polymerase II
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: This is the same core transcriptional role seen in the experimentally supported set.
Reason: The IEA ortholog transfer is consistent with the direct human evidence that Akirins regulate transcriptional output downstream of NF-kappaB.
Supporting Evidence:
PMID:18066067
regulating the transcriptional activities of main transactivators
|
|
GO:1902723
negative regulation of skeletal muscle satellite cell proliferation
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: This direction is inconsistent with the AKIRIN1 muscle literature.
Reason: The available muscle literature supports AKIRIN1 as a positive regulator of satellite-cell activity and regeneration, not as a negative regulator. This term therefore conflicts with the promyogenic evidence and should not be kept.
Supporting Evidence:
PMID:23516508
When myostatin was inhibited in Dex-treated mice, Akirin1 expression increased as did satellite cell activity, muscle regeneration and muscle growth
PMID:23516508
Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation
|
|
GO:1902725
negative regulation of satellite cell differentiation
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: This direction is inconsistent with the AKIRIN1 muscle literature.
Reason: The muscle paper shows the opposite direction: AKIRIN1 increases myogenic regulators and improves differentiation. That makes this negative-regulation term a poor fit for AKIRIN1 even though the pathway is relevant to muscle repair.
Supporting Evidence:
PMID:23516508
Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation
PMID:23516508
a promyogenic gene
|
|
GO:0005654
nucleoplasm
|
IDA
GO_REF:0000052 |
ACCEPT |
Summary: Direct experimental localization to the nucleoplasm is compatible with the nuclear role.
Reason: This narrower nuclear compartment annotation is compatible with the direct nuclear localization evidence and does not conflict with the IBA nucleus term. It is reasonable to retain as a finer-grained CC call.
Supporting Evidence:
PMID:18066067
strict nuclear localization
|
|
GO:0045663
positive regulation of myoblast differentiation
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: The ISS transfer duplicates an over-specific muscle process call.
Reason: The same logic applied to the IBA/IEA versions applies here: the direct AKIRIN1 evidence is nuclear transcriptional cofactor activity, but the muscle paper still supports a context-dependent promyogenic role. Keep this as non-core rather than over-annotation.
Supporting Evidence:
PMID:23516508
Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation
|
|
GO:0045944
positive regulation of transcription by RNA polymerase II
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: This ISS transfer is consistent with the conserved transcriptional core function.
Reason: The orthology-based transfer is reasonable because the direct literature supports the same transcriptional role in human AKIRIN1.
Supporting Evidence:
PMID:18066067
regulating the transcriptional activities of main transactivators
|
|
GO:0010592
positive regulation of lamellipodium assembly
|
ISS
GO_REF:0000024 |
MARK AS OVER ANNOTATED |
Summary: This ISS lamellipodium call is an over-annotation.
Reason: The direct AKIRIN1 literature does not support lamellipodium assembly as a core function of the human protein; retain the nuclear transcriptional role instead.
Supporting Evidence:
PMID:18066067
strict nuclear localization
|
|
GO:0010759
positive regulation of macrophage chemotaxis
|
ISS
GO_REF:0000024 |
MARK AS OVER ANNOTATED |
Summary: This ISS macrophage-chemotaxis call is over-specific for human AKIRIN1.
Reason: The direct literature does not support this immune-cell migration process for AKIRIN1; the immune-response phenotype in the family is better attributed to Akirin2.
Supporting Evidence:
PMID:18066067
MmAkirin2, but not MmAkirin1, was responsible for the production of IL-6
|
|
GO:0014839
myoblast migration involved in skeletal muscle regeneration
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: This ISS muscle-regeneration call is an over-annotation for the human paralog.
Reason: AKIRIN1 is supported as a nuclear transcriptional cofactor, but the muscle literature still supports a context-dependent promyogenic role. Keep this as non-core rather than removing it entirely.
Supporting Evidence:
PMID:23516508
Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation
|
|
GO:1902723
negative regulation of skeletal muscle satellite cell proliferation
|
ISS
GO_REF:0000024 |
MARK AS OVER ANNOTATED |
Summary: This ISS satellite-cell proliferation term is too specific for AKIRIN1.
Reason: No direct AKIRIN1 evidence supports this phenotype-like process term.
Supporting Evidence:
PMID:18066067
the functional role of MmAkirin1, attested by its sequence conservation, is unknown thus far
|
|
GO:1902725
negative regulation of satellite cell differentiation
|
ISS
GO_REF:0000024 |
MARK AS OVER ANNOTATED |
Summary: This ISS satellite-cell differentiation call is also over-annotated.
Reason: The available evidence supports a transcriptional cofactor role rather than a satellite-cell differentiation function.
Supporting Evidence:
PMID:18066067
novel important nuclear cofactors regulating the transcriptional activities of main transactivators
|
|
GO:0005634
nucleus
|
IDA
PMID:18066067 Akirins are highly conserved nuclear proteins required for N... |
ACCEPT |
Summary: Direct experimental localization to the nucleus is well supported.
Reason: This is the key experimental localization result for human Akirin1 and is perfectly consistent with the conserved nuclear cofactor model.
Supporting Evidence:
PMID:18066067
strict nuclear localization
|
Q: Is there any direct human evidence that AKIRIN1 binds the proteasome or a proteasome-adaptor complex, given that PMID:34711951 supports AKIRIN2 proteasome import and UniProt explicitly contrasts AKIRIN1 with that activity?
Q: Do the muscle and motility annotations belong to AKIRIN1 specifically, or are they better treated as family/paralog transfer that should remain out of the human review?
Experiment: Test AKIRIN1 proximity to proteasome subunits and adaptor/shuttle proteins in human cells by co-IP or proximity labeling under basal and stimulated conditions.
Experiment: Deplete or edit AKIRIN1 in a human cell model and measure NF-kappaB-dependent transcription plus chromatin association at inducible target loci.
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
The target in this report is human AKIRIN1 (UniProt accession Q9H9L7), encoding Akirin-1 (historically termed “Mighty” in the muscle field), a member of the conserved akirin family of small nuclear proteins. Authoritative reviews describe mammalian Akirin proteins as ~200 aa (~22 kDa) nuclear factors with a conserved N-terminal nuclear localization signal (NLS), lacking obvious catalytic domains—supporting classification as a non-enzymatic transcriptional cofactor/adaptor rather than an enzyme or transporter. (https://doi.org/10.1007/s00018-020-03531-w; published 2020-05) (bosch2020akirinproteinsin pages 1-3, bosch2020akirinproteinsin pages 3-4). AKIRIN1 is distinct from AKIRIN2, which is more often essential in development; Akirin1-null mice are reported as viable/outwardly normal in review summaries, indicating paralog divergence. (bosch2020akirinproteinsin pages 1-3)
Akirin proteins are best understood as context-dependent transcriptional cofactors that help couple sequence-specific transcriptional regulators to chromatin remodeling and promoter selection. Reviews emphasize that akirins are highly conserved and largely intrinsically disordered, with minimal recognizable domains, consistent with a role as a “bridge” or scaffold for protein–protein interactions rather than a catalytic function. (https://doi.org/10.1007/s00018-020-03531-w; 2020-05) (bosch2020akirinproteinsin pages 1-3, bosch2020akirinproteinsin pages 15-15). A complementary review (developmental context) similarly frames Akirin as a secondary cofactor linking transcription factors to SWI/SNF-class chromatin remodeling complexes while noting that direct DNA-binding has not been clearly established. (https://doi.org/10.4161/bioa.22907; 2012-11) (nowak2012akirin pages 1-2)
Across species and in vertebrates, Akirin proteins show predominantly nuclear localization, consistent with roles at promoters/enhancers. Bosch et al. highlight strong nuclear localization across species while also noting that some non-nuclear protein can be observed and that clear cytoplasmic functions are not yet established. (bosch2020akirinproteinsin pages 4-6)
Although some of the most detailed mechanistic dissection is for Akirin2 or in Drosophila, the core mechanistic concept is conserved: akirins provide transcriptional selectivity by enabling recruitment or stabilization of SWI/SNF (BAF/Brahma) remodeling complexes at only a subset of inducible genes.
In Drosophila innate immunity, Akirin acts as an NF-κB (Relish) cofactor required for expression of a subset of Relish-dependent genes; genome-wide expression analysis reported Relish required for 170 induced genes after immune challenge, of which 17 were also Akirin-dependent, and Akirin alone was required for 31 genes independent of Relish—supporting a selector/cofactor model. (https://doi.org/10.15252/embj.201488456; 2014-09) (bonnay2014akirinspecifiesnfκb pages 1-2). Proteomics and co-IP data further linked Akirin to SWI/SNF-like Brahma complex components (e.g., BAP60) and stimulus-enhanced association with Relish. (bonnay2014akirinspecifiesnfκb pages 3-5)
In vertebrates/mammals, reviews synthesize evidence that Akirin2 forms complexes with IκBζ and BAF60 isoforms to promote inflammatory gene transcription (e.g., IL-6) through recruitment of SWI/SNF core machinery (Brg1). (bosch2020akirinproteinsin pages 3-4, bosch2020akirinproteinsin pages 7-8)
The strongest AKIRIN1-specific mechanistic evidence in the retrieved corpus concerns skeletal muscle biology, where AKIRIN1/Mighty functions as a promyogenic nuclear factor that supports myoblast/satellite cell proliferation and differentiation.
A key primary study in mouse and myogenic cell models (Dong et al., PLoS ONE; 2013-03-13) provides multiple lines of evidence:
- Glucocorticoids (dexamethasone, Dex) suppress satellite cell proliferation/differentiation, accompanied by myostatin induction and Akirin1 suppression. (https://doi.org/10.1371/journal.pone.0058554; 2013-03) (dong2013myostatinsuppressionof pages 1-2, dong2013myostatinsuppressionof pages 3-4)
- Dex or recombinant myostatin decreases Akirin1 mRNA/protein in satellite cells; myostatin knockdown/inhibition prevents Dex-mediated Akirin1 suppression and improves proliferation/differentiation even with Dex present. (dong2013myostatinsuppressionof pages 8-11, dong2013myostatinsuppressionof pages 3-4)
- Akirin1 overexpression in myoblasts increases myogenic regulators MyoD and myogenin and improves proliferation/differentiation; these improvements are reported to persist despite Dex treatment. (dong2013myostatinsuppressionof pages 4-8, dong2013myostatinsuppressionof pages 1-2)
Interpretation: these data support AKIRIN1 as a downstream positive effector of myogenic gene programs whose expression is negatively regulated by myostatin in settings of glucocorticoid stress, positioning AKIRIN1 as part of a regulatory axis relevant to muscle wasting and impaired regeneration. (dong2013myostatinsuppressionof pages 8-11)
The Dong et al. data explicitly argue for the pathway: glucocorticoid → myostatin upregulation → AKIRIN1 downregulation → satellite cell dysfunction, with experimental rescue by myostatin inhibition and by AKIRIN1 overexpression. (dong2013myostatinsuppressionof pages 8-11, dong2013myostatinsuppressionof pages 3-4)
In the retrieved material, the most direct mechanistic NF-κB/SWI-SNF bridging evidence is from Drosophila Akirin and mammalian Akirin2-centered work; reviews emphasize akirins as conserved nuclear proteins required for NF-κB-dependent gene expression, but AKIRIN1-specific immune phenotyping is less developed in the excerpts here. (bosch2020akirinproteinsin pages 15-15, bonnay2014akirinspecifiesnfκb pages 1-2)
Accordingly, current understanding supported by these sources is:
- Akirin family: transcriptional selectivity in NF-κB programs via chromatin remodeler recruitment. (bonnay2014akirinspecifiesnfκb pages 1-2, bonnay2014akirinspecifiesnfκb pages 3-5)
- AKIRIN1: well-supported promyogenic regulator; immune-specific roles are plausible by family conservation but less directly established by AKIRIN1-only experiments in the retrieved excerpts. (bosch2020akirinproteinsin pages 3-4)
A 2024 Scientific Reports study analyzed spermatozoal “RNA elements” (REs) from 47 normozoospermic males undergoing fertility treatment with donor oocytes and examined associations between sperm RNA elements and blastocyst rate. (https://doi.org/10.1038/s41598-024-60586-6; 2024-05) (hamilton2024acomprehensiveanalysis pages 5-7)
Within this analysis:
- AKIRIN1 (multiple transcript isoforms) is shown in Figure 3 with its abundance plotted against miR-224-5p; values were normalized as a proportion of the mean abundance per blastocyst-rate group relative to the overall mean across samples to allow comparison between gene and miRNA patterns. (hamilton2024acomprehensiveanalysis pages 5-7)
- AKIRIN1 is described as following a “down-same” pattern relative to blastocyst-rate groups (a pattern class defined by the authors for RE abundance trends). (hamilton2024acomprehensiveanalysis pages 4-5)
- In the excerpted pages, AKIRIN1 is also listed among RE-RNAs overlapping with enriched miRNA targets in their TargetScan/miRTarBase overlap analyses (Table 4 context), but the excerpt does not provide a gene-specific correlation coefficient or effect size for AKIRIN1. (hamilton2024acomprehensiveanalysis pages 5-7, hamilton2024acomprehensiveanalysis pages 4-5)
Interpretation: this is association-level human evidence placing AKIRIN1 within a sperm RNA signature related to embryo development outcomes and linked to miR-224-5p patterns. It does not, by itself, establish mechanism, but it provides a concrete 2024 human context and motivates follow-up functional studies. (hamilton2024acomprehensiveanalysis pages 5-7, hamilton2024acomprehensiveanalysis pages 4-5)
Open Targets lists AKIRIN1 (ENSG00000174574) associations with traits/diseases including aging and atrial fibrillation, supported by multiple evidence items and literature links (PubMed IDs listed in the Open Targets evidence payload). (OpenTargets Search: -AKIRIN1)
Interpretation: these associations indicate that AKIRIN1 appears in human genetic/biomedical evidence streams for complex traits, but they should be treated as hypothesis-generating rather than definitive function proof without mechanism-resolving experiments. (OpenTargets Search: -AKIRIN1)
The glucocorticoid–myostatin–AKIRIN1 pathway has practical relevance because glucocorticoid excess and myostatin signaling are clinically relevant in sarcopenia/cachexia contexts. Dong et al. conclude that inhibiting myostatin or increasing AKIRIN1 expression could be therapeutic strategies to improve satellite-cell activation and muscle growth in diseases with increased glucocorticoid production. (dong2013myostatinsuppressionof pages 1-2)
This represents a preclinical “actionable node” concept: AKIRIN1 itself is not an enzyme target, but it is a downstream transcriptional effector that could potentially be modulated indirectly (e.g., through upstream myostatin pathway interventions). (dong2013myostatinsuppressionof pages 8-11)
The 2024 sperm RNA element study explicitly positions REs (including AKIRIN1) as a knowledge base that can be leveraged to improve clinical screening in male infertility. AKIRIN1 is present as a gene in their RE–miRNA and blastocyst rate pattern results. (hamilton2024acomprehensiveanalysis pages 5-7, hamilton2024acomprehensiveanalysis pages 4-5)
Although outside the user’s 2023–2024 priority window, a 2025 Scientific Reports paper provides mechanistic and translationally oriented evidence that AKIRIN1 is a direct target of miR-224 in lung fibroblasts, and that AKIRIN1 depletion promotes cancer-associated fibroblast activation and increases lung cancer cell migration/invasion in co-culture and in vivo models; it also reports a survival association with low AKIRIN1 in LUAD. (https://doi.org/10.1038/s41598-024-82189-x; 2025-01) (oh2025mir224activatescancerassociated pages 6-7)
This supports a plausible real-world application domain for AKIRIN1: tumor microenvironment biology and prognostic stratification (pending further validation). (oh2025mir224activatescancerassociated pages 6-7)
A domain-leading review (Bosch et al., 2020) frames Akirin proteins as evolutionarily conserved regulators of gene-expression programs affecting development (brain/limb/muscle), immune responses, and tumorigenesis, emphasizing that despite strong phenotypic evidence, key molecular unknowns remain (e.g., direct DNA binding; structural basis of “bridge” function; post-translational regulation). (https://doi.org/10.1007/s00018-020-03531-w; 2020-05) (bosch2020akirinproteinsin pages 15-15)
In developmental and immunity contexts, primary Drosophila work argues that Akirin-mediated selection of NF-κB target genes via chromatin remodeling could enable more selective anti-inflammatory interventions compared with global NF-κB inhibition, because only subsets of NF-κB targets would be affected. (bonnay2014akirinspecifiesnfκb pages 1-2)
Collectively, the evidence supports the following functional annotation for human AKIRIN1 (Q9H9L7):
- Primary molecular role: a nuclear transcriptional cofactor/adaptor, lacking catalytic domains, that promotes context-specific gene expression programs—most directly supported in myogenic contexts as a promyogenic regulator. (bosch2020akirinproteinsin pages 1-3, dong2013myostatinsuppressionof pages 1-2)
- Primary biological process emphasis (best-supported): skeletal muscle myogenesis and regeneration; AKIRIN1 supports myoblast/satellite cell proliferation and differentiation and is negatively regulated by myostatin under glucocorticoid stress. (dong2013myostatinsuppressionof pages 8-11, dong2013myostatinsuppressionof pages 3-4)
- Subcellular site of action: nucleus (promoter/enhancer-linked gene regulation), with some reports of non-nuclear protein but unclear cytoplasmic function. (bosch2020akirinproteinsin pages 4-6)
- Pathway links: myostatin/glucocorticoid axis (strong AKIRIN1-specific evidence); NF-κB/chromatin remodeling selectivity (strong akirin-family evidence; more direct for Akirin2 and Drosophila orthologs than for AKIRIN1 alone in the retrieved excerpts). (dong2013myostatinsuppressionof pages 8-11, bonnay2014akirinspecifiesnfκb pages 1-2, bosch2020akirinproteinsin pages 3-4)
| Aspect | Key points | Best supporting citations |
|---|---|---|
| Definition / localization | • Human AKIRIN1 corresponds to Akirin-1 (UniProt Q9H9L7), also called Mighty in earlier literature. • Small akirin-family protein (~200 aa; ~20–25 kDa) with conserved N-terminal nuclear localization signal and predominantly nuclear localization. • Lacks recognizable catalytic domains, supporting a non-enzymatic cofactor/adaptor role rather than enzyme or transporter function. | (bosch2020akirinproteinsin pages 1-3, bosch2020akirinproteinsin pages 3-4, bosch2020akirinproteinsin pages 4-6) |
| Molecular mechanism | • Best-supported model is that Akirin proteins act as transcriptional cofactors that bridge sequence-specific regulators to chromatin-remodeling machinery. • Family-level mechanistic work shows recruitment/stabilization of SWI/SNF/BAF complexes at selected promoters and effects on activating histone marks/chromatin accessibility. • For AKIRIN1 specifically, available mammalian evidence supports promyogenic transcriptional regulation, but direct structural mechanism remains less defined than for AKIRIN2. | (bosch2020akirinproteinsin pages 15-15, bosch2020akirinproteinsin pages 7-8, peek2021cellularandmolecular pages 44-49) |
| Key partners / complexes | • Family evidence supports interactions with SWI/SNF/BAF components such as BAF60 isoforms and Brg1-associated remodeling machinery. • In inflammatory transcription, Akirin-family proteins cooperate with NF-κB pathway components including IκBζ and p50-linked transcriptional complexes. • AKIRIN1-specific recent disease-oriented evidence also implicates functional linkage to FOXO3/MuRF1 regulation and direct targeting by miR-224 in fibroblasts. | (bosch2020akirinproteinsin pages 3-4, bosch2020akirinproteinsin pages 7-8, peek2021cellularandmolecular pages 44-49, oh2025mir224activatescancerassociated pages 6-7) |
| Pathways | • Muscle biology: glucocorticoid → myostatin induction → AKIRIN1 suppression is supported in mouse satellite cells/myoblasts. • Family-level immunity/chromatin work links akirins to NF-κB-selective transcription via SWI/SNF remodeling. • Reviews also place AKIRIN1/Akirin family within broader developmental and signaling contexts including myogenesis, inflammatory signaling, and chromatin-dependent gene regulation. | (dong2013myostatinsuppressionof pages 8-11, dong2013myostatinsuppressionof pages 1-2, bonnay2014akirinspecifiesnfκb pages 1-2, bosch2020akirinproteinsin pages 3-4) |
| Phenotypes / biology | • AKIRIN1 is a promyogenic factor: overexpression increases MyoD and myogenin and improves proliferation/differentiation of myoblasts even under dexamethasone stress. • Dex or myostatin lowers AKIRIN1 mRNA/protein, whereas myostatin inhibition restores AKIRIN1 and improves satellite-cell activity, regeneration, and muscle growth. • Akirin1-null mice are reported as viable/outwardly normal, suggesting paralog-specific divergence from the more essential AKIRIN2. | (dong2013myostatinsuppressionof pages 8-11, dong2013myostatinsuppressionof pages 4-8, dong2013myostatinsuppressionof pages 3-4, bosch2020akirinproteinsin pages 1-3) |
| Recent human association evidence (2024) | • In a 2024 human sperm RNA study of 47 idiopathic infertile males, AKIRIN1 RNA elements were among transcripts associated with blastocyst-rate patterns and were plotted against miR-224-5p. • AKIRIN1 was categorized within a “down-same” abundance pattern relative to blastocyst-rate groups and appeared in RE–miRNA overlap analyses, though no AKIRIN1-specific effect size was provided in the excerpt. • Open Targets currently shows modest literature-backed associations for AKIRIN1 with traits/diseases such as aging and atrial fibrillation, but these are association-level rather than mechanism-proving evidence. | (hamilton2024acomprehensiveanalysis pages 5-7, hamilton2024acomprehensiveanalysis pages 4-5, OpenTargets Search: -AKIRIN1) |
| Translational / application notes | • Preclinical muscle studies position AKIRIN1 as a candidate downstream node in glucocorticoid-myostatin muscle wasting and regeneration pathways. • In 2025 human lung-cancer microenvironment work, miR-224 directly targeted AKIRIN1 in fibroblasts, and AKIRIN1 loss promoted pro-metastatic CAF behavior, suggesting biomarker/therapeutic relevance. • Expert reviews emphasize that akirins may offer selective control points for chromatin-coupled transcriptional programs, but direct AKIRIN1-targeted therapies are not yet established. | (dong2013myostatinsuppressionof pages 8-11, oh2025mir224activatescancerassociated pages 6-7, bosch2020akirinproteinsin pages 1-3, bosch2020akirinproteinsin pages 15-15) |
Table: This table summarizes the main functional annotation points for human/mammalian AKIRIN1, emphasizing its nuclear cofactor role, muscle-related biology, conserved chromatin-remodeling links, and recent human association evidence. It is useful as a compact evidence map connecting core mechanism, biology, and translational relevance.
Recent (2023–2024) mechanistic AKIRIN1-focused primary literature was limited in the retrieved set; the strongest mechanistic AKIRIN1 evidence available here remains anchored in earlier muscle biology studies, while 2024 work is more association/expression-context oriented (fertility outcomes; target–disease associations). Therefore, immune/NF-κB mechanistic conclusions are presented primarily as akirin-family mechanisms rather than AKIRIN1-exclusive mechanisms unless explicitly supported. (bosch2020akirinproteinsin pages 3-4, bonnay2014akirinspecifiesnfκb pages 1-2)
References
(bosch2020akirinproteinsin pages 1-3): Peter J. Bosch, Stacey L. Peek, Sarit Smolikove, and Joshua A. Weiner. Akirin proteins in development and disease: critical roles and mechanisms of action. Cellular and Molecular Life Sciences, 77:4237-4254, May 2020. URL: https://doi.org/10.1007/s00018-020-03531-w, doi:10.1007/s00018-020-03531-w. This article has 26 citations and is from a domain leading peer-reviewed journal.
(bosch2020akirinproteinsin pages 3-4): Peter J. Bosch, Stacey L. Peek, Sarit Smolikove, and Joshua A. Weiner. Akirin proteins in development and disease: critical roles and mechanisms of action. Cellular and Molecular Life Sciences, 77:4237-4254, May 2020. URL: https://doi.org/10.1007/s00018-020-03531-w, doi:10.1007/s00018-020-03531-w. This article has 26 citations and is from a domain leading peer-reviewed journal.
(bosch2020akirinproteinsin pages 15-15): Peter J. Bosch, Stacey L. Peek, Sarit Smolikove, and Joshua A. Weiner. Akirin proteins in development and disease: critical roles and mechanisms of action. Cellular and Molecular Life Sciences, 77:4237-4254, May 2020. URL: https://doi.org/10.1007/s00018-020-03531-w, doi:10.1007/s00018-020-03531-w. This article has 26 citations and is from a domain leading peer-reviewed journal.
(nowak2012akirin pages 1-2): Scott J. Nowak and Mary K. Baylies. Akirin. Bioarchitecture, 2:209-213, Nov 2012. URL: https://doi.org/10.4161/bioa.22907, doi:10.4161/bioa.22907. This article has 26 citations.
(bosch2020akirinproteinsin pages 4-6): Peter J. Bosch, Stacey L. Peek, Sarit Smolikove, and Joshua A. Weiner. Akirin proteins in development and disease: critical roles and mechanisms of action. Cellular and Molecular Life Sciences, 77:4237-4254, May 2020. URL: https://doi.org/10.1007/s00018-020-03531-w, doi:10.1007/s00018-020-03531-w. This article has 26 citations and is from a domain leading peer-reviewed journal.
(bonnay2014akirinspecifiesnfκb pages 1-2): François Bonnay, Xuan‐Hung Nguyen, Eva Cohen‐Berros, Laurent Troxler, Eric Batsche, Jacques Camonis, Osamu Takeuchi, Jean‐Marc Reichhart, and Nicolas Matt. Akirin specifies nf-κb selectivity of drosophila innate immune response via chromatin remodeling. The EMBO Journal, 33:2349-2362, Sep 2014. URL: https://doi.org/10.15252/embj.201488456, doi:10.15252/embj.201488456. This article has 124 citations.
(bonnay2014akirinspecifiesnfκb pages 3-5): François Bonnay, Xuan‐Hung Nguyen, Eva Cohen‐Berros, Laurent Troxler, Eric Batsche, Jacques Camonis, Osamu Takeuchi, Jean‐Marc Reichhart, and Nicolas Matt. Akirin specifies nf-κb selectivity of drosophila innate immune response via chromatin remodeling. The EMBO Journal, 33:2349-2362, Sep 2014. URL: https://doi.org/10.15252/embj.201488456, doi:10.15252/embj.201488456. This article has 124 citations.
(bosch2020akirinproteinsin pages 7-8): Peter J. Bosch, Stacey L. Peek, Sarit Smolikove, and Joshua A. Weiner. Akirin proteins in development and disease: critical roles and mechanisms of action. Cellular and Molecular Life Sciences, 77:4237-4254, May 2020. URL: https://doi.org/10.1007/s00018-020-03531-w, doi:10.1007/s00018-020-03531-w. This article has 26 citations and is from a domain leading peer-reviewed journal.
(dong2013myostatinsuppressionof pages 1-2): Yanjun Dong, Jenny S. Pan, and Liping Zhang. Myostatin suppression of akirin1 mediates glucocorticoid-induced satellite cell dysfunction. PLoS ONE, 8:e58554, Mar 2013. URL: https://doi.org/10.1371/journal.pone.0058554, doi:10.1371/journal.pone.0058554. This article has 67 citations and is from a peer-reviewed journal.
(dong2013myostatinsuppressionof pages 3-4): Yanjun Dong, Jenny S. Pan, and Liping Zhang. Myostatin suppression of akirin1 mediates glucocorticoid-induced satellite cell dysfunction. PLoS ONE, 8:e58554, Mar 2013. URL: https://doi.org/10.1371/journal.pone.0058554, doi:10.1371/journal.pone.0058554. This article has 67 citations and is from a peer-reviewed journal.
(dong2013myostatinsuppressionof pages 8-11): Yanjun Dong, Jenny S. Pan, and Liping Zhang. Myostatin suppression of akirin1 mediates glucocorticoid-induced satellite cell dysfunction. PLoS ONE, 8:e58554, Mar 2013. URL: https://doi.org/10.1371/journal.pone.0058554, doi:10.1371/journal.pone.0058554. This article has 67 citations and is from a peer-reviewed journal.
(dong2013myostatinsuppressionof pages 4-8): Yanjun Dong, Jenny S. Pan, and Liping Zhang. Myostatin suppression of akirin1 mediates glucocorticoid-induced satellite cell dysfunction. PLoS ONE, 8:e58554, Mar 2013. URL: https://doi.org/10.1371/journal.pone.0058554, doi:10.1371/journal.pone.0058554. This article has 67 citations and is from a peer-reviewed journal.
(hamilton2024acomprehensiveanalysis pages 5-7): Matthew Hamilton, Stewart Russell, Grace M. Swanson, Stephen A. Krawetz, Karen Menezes, Sergey I. Moskovtsev, and Clifford Librach. A comprehensive analysis of spermatozoal rna elements in idiopathic infertile males undergoing fertility treatment. Scientific Reports, May 2024. URL: https://doi.org/10.1038/s41598-024-60586-6, doi:10.1038/s41598-024-60586-6. This article has 9 citations and is from a peer-reviewed journal.
(hamilton2024acomprehensiveanalysis pages 4-5): Matthew Hamilton, Stewart Russell, Grace M. Swanson, Stephen A. Krawetz, Karen Menezes, Sergey I. Moskovtsev, and Clifford Librach. A comprehensive analysis of spermatozoal rna elements in idiopathic infertile males undergoing fertility treatment. Scientific Reports, May 2024. URL: https://doi.org/10.1038/s41598-024-60586-6, doi:10.1038/s41598-024-60586-6. This article has 9 citations and is from a peer-reviewed journal.
(OpenTargets Search: -AKIRIN1): Open Targets Query (-AKIRIN1, 5 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(oh2025mir224activatescancerassociated pages 6-7): Seonyeong Oh, Sieun Lee, Inyoung Cheon, and Young-Ho Ahn. Mir-224 activates cancer-associated fibroblasts to enhance lung cancer cell migration and invasion by targeting akirin1. Scientific Reports, Jan 2025. URL: https://doi.org/10.1038/s41598-024-82189-x, doi:10.1038/s41598-024-82189-x. This article has 5 citations and is from a peer-reviewed journal.
(peek2021cellularandmolecular pages 44-49): Cellular and molecular mechanisms of Akirin2 function in maturing neurons
Human AKIRIN1 encodes a small, conserved nuclear Akirin-family protein. The strongest direct evidence in the local cache is for nuclear localization and a role as a transcriptional cofactor in NF-kappaB-dependent gene expression [PMID:18066067, "strict nuclear localization"; PMID:18066067, "novel important nuclear cofactors regulating the transcriptional activities of main transactivators"].
The 2008 mouse paper also makes the paralog split explicit: Akirin2, not Akirin1, is the paralog required for the IL-1/TLR cytokine-response phenotype, while Akirin1 knockout mice were viable and showed no gross developmental abnormalities [PMID:18066067, "MmAkirin1-/- mice were born in a Mendelian ratio, grew healthily and did not show gross developmental abnormalities"; PMID:18066067, "the functional role of MmAkirin1, attested by its sequence conservation, is unknown thus far"].
The Proteostasis PN projection for AKIRIN1 points to GO:0070628 proteasome binding in the adaptor/shuttle bucket [file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_annotations.tsv]. In the local literature cache I do not see direct AKIRIN1-specific proteasome-binding evidence, so that projection should be treated conservatively rather than promoted automatically.
Ubiquitin Proteasome System|Proteasome and associated proteins|adaptors|Akirin ; PN-node mapping: Akirin type no_mapping; group (adaptors) mapped→GO:0070628 (proteasome binding, propagate); class context_only→GO:0000502. Projection: GO:0070628 new_to_goa.adaptors|Akirin type so GO:0070628 proteasome binding propagates to AKIRIN2 only; mark AKIRIN1 as no_mapping (nuclear transcription cofactor, no proteasome-binding evidence).This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.
id: Q9H9L7
gene_symbol: AKIRIN1
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:9606
label: Homo sapiens
description: >
AKIRIN1 encodes a conserved nuclear Akirin-family protein that functions as a
transcriptional cofactor in inducible gene-expression programs. It also has a
context-dependent promyogenic role supporting myoblast and satellite-cell
proliferation and differentiation during muscle repair. The protein localizes to
the nucleus and nucleoplasm and is not an enzyme; its main role is to help
regulate transcription in chromatin-associated nuclear contexts rather than to
catalyze a biochemical reaction.
alternative_products:
- name: '1'
id: Q9H9L7-1
- name: '2'
id: Q9H9L7-2
sequence_note: VSP_042769
existing_annotations:
- term:
id: GO:0005634
label: nucleus
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: Nuclear localization is the central, conserved cellular context for AKIRIN1.
action: ACCEPT
reason: The paper that established the human homologs reports strict nuclear
localization for HsAkirin1, and the UniProt record also places the protein in
the nucleus. This is consistent with the conserved Akirin role as a nuclear
transcriptional cofactor.
supported_by:
- reference_id: PMID:18066067
supporting_text: "strict nuclear localization"
- term:
id: GO:0045944
label: positive regulation of transcription by RNA polymerase II
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: This captures the best-supported conserved biological process for AKIRIN1.
action: ACCEPT
reason: AKIRIN1 is best understood as a nuclear cofactor that supports inducible
transcriptional output. The canonical Akirin paper places the protein downstream
of NF-kappaB-dependent gene expression and describes Akirins as nuclear cofactors
regulating transcriptional activities of main transactivators, which fits this
GO term well.
supported_by:
- reference_id: PMID:18066067
supporting_text: "regulating the transcriptional activities of main transactivators"
- term:
id: GO:0000785
label: chromatin
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: Chromatin association is plausible and consistent with the nuclear cofactor role.
action: ACCEPT
reason: The 2008 paper argues that Akirins likely act by associating with chromatin
or the transcriptional engine, and the conserved nuclear localization supports a
chromatin-associated transcriptional role. This is not over-specific for the
available evidence.
supported_by:
- reference_id: PMID:18066067
supporting_text: "interacting with components of the chromatin or the transcriptional engine"
- term:
id: GO:0003712
label: transcription coregulator activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: enables
review:
summary: This is the most direct molecular-function summary for AKIRIN1.
action: ACCEPT
reason: AKIRIN1 is not a DNA-binding enzyme or a catalytic factor; the direct human
and mouse literature supports a nuclear transcriptional cofactor role downstream
of NF-kappaB. This MF term is appropriately specific without overstating a direct
DNA-binding or catalytic activity.
supported_by:
- reference_id: PMID:18066067
supporting_text: "novel important nuclear cofactors regulating the transcriptional activities of main transactivators"
- term:
id: GO:0010592
label: positive regulation of lamellipodium assembly
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: This is a family/orthology-derived motility call that is not supported for human AKIRIN1.
action: MARK_AS_OVER_ANNOTATED
reason: The conserved human AKIRIN1 literature supports a nuclear transcriptional
cofactor role, not direct actin-remodeling or lamellipodium biology. In the same
paper, Akirin1 knockout mice were viable and showed no gross developmental
abnormalities, which argues against promoting a specific cell-motility process
for the human paralog on the basis of family-level transfer alone.
supported_by:
- reference_id: PMID:18066067
supporting_text: "MmAkirin1-/- mice were born in a Mendelian ratio, grew healthily and did not show gross developmental abnormalities"
- reference_id: PMID:18066067
supporting_text: "the functional role of MmAkirin1, attested by its sequence conservation, is unknown thus far"
- term:
id: GO:0010759
label: positive regulation of macrophage chemotaxis
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: This macrophage-migration term is over-propagated relative to the human AKIRIN1 evidence.
action: MARK_AS_OVER_ANNOTATED
reason: Human AKIRIN1 is supported as a nuclear transcriptional cofactor, not as a
direct regulator of macrophage migration. The family paper specifically notes that
the role of Akirin1 is unknown and that the immune-response phenotype belongs to
Akirin2, not Akirin1, so this process annotation is too strong for AKIRIN1.
supported_by:
- reference_id: PMID:18066067
supporting_text: "the functional role of MmAkirin1, attested by its sequence conservation, is unknown thus far"
- reference_id: PMID:18066067
supporting_text: "MmAkirin2, but not MmAkirin1, was responsible for the production of IL-6"
- term:
id: GO:0014839
label: myoblast migration involved in skeletal muscle regeneration
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: This is a real but context-dependent muscle-regeneration annotation, not a core function.
action: KEEP_AS_NON_CORE
reason: The muscle literature supports AKIRIN1 as a promyogenic factor in
satellite-cell activation and regeneration, including increased MyoD/myogenin
and improved proliferation/differentiation after AKIRIN1 overexpression. That
is sufficient to keep this as a non-core regenerative annotation, but the term
is more specific than the evidence and should not be elevated to the main
conserved function.
supported_by:
- reference_id: PMID:23516508
supporting_text: "Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation"
- reference_id: file:human/AKIRIN1/AKIRIN1-deep-research-falcon.md
supporting_text: "supports myoblast/satellite cell proliferation and differentiation"
- term:
id: GO:0045663
label: positive regulation of myoblast differentiation
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: This is a supported but non-core promyogenic annotation for human AKIRIN1.
action: KEEP_AS_NON_CORE
reason: The Falcon deep research and Dong et al. 2013 support AKIRIN1 as a
promyogenic nuclear factor. In that study, AKIRIN1 overexpression increased
MyoD and myogenin and improved myoblast proliferation and differentiation, so
this term is supported. It is still context-specific muscle biology rather than
the main conserved function of the protein, so it should be retained as
non-core.
supported_by:
- reference_id: PMID:23516508
supporting_text: "Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation"
- reference_id: PMID:23516508
supporting_text: "a promyogenic gene"
- reference_id: file:human/AKIRIN1/AKIRIN1-deep-research-falcon.md
supporting_text: "promyogenic nuclear factor"
- term:
id: GO:1902723
label: negative regulation of skeletal muscle satellite cell proliferation
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: This direction is inconsistent with the AKIRIN1 muscle literature.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The direct AKIRIN1 muscle literature supports the opposite direction:
AKIRIN1 expression promotes satellite-cell activity, myoblast proliferation,
and myogenic differentiation. This negative-regulation term therefore
overstates the biology for human AKIRIN1 even though the pathway is clearly
linked to muscle repair.
supported_by:
- reference_id: PMID:23516508
supporting_text: "When myostatin was inhibited in Dex-treated mice, Akirin1 expression increased as did satellite cell activity, muscle regeneration and muscle growth"
- reference_id: PMID:23516508
supporting_text: "Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation"
- term:
id: GO:0005634
label: nucleus
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: This is a redundant but correct UniProt-derived nuclear localization call.
action: ACCEPT
reason: The subcellular-location mapping agrees with the direct human localization
result in PMID:18066067 and does not conflict with the IBA nuclear annotation.
supported_by:
- reference_id: PMID:18066067
supporting_text: "strict nuclear localization"
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:25416956
qualifier: enables
review:
summary: The interaction evidence is real, but the generic protein-binding parent is too vague.
action: MODIFY
reason: A direct interaction is supported by the IntAct-derived record, but the
annotation should not remain at the uninformative protein-binding parent term.
The most conservative informative replacement is protein-containing complex
binding. This should not be conflated with the PN projection to proteasome
binding, which is not directly supported by the local human literature cache.
proposed_replacement_terms:
- id: GO:0044877
label: protein-containing complex binding
supported_by:
- reference_id: file:human/AKIRIN1/AKIRIN1-uniprot.txt
supporting_text: "Q9H9L7; Q9HD26: GOPC; NbExp=3; IntAct=EBI-10309796, EBI-349832"
- term:
id: GO:0010592
label: positive regulation of lamellipodium assembly
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This family-transfer call is not justified for human AKIRIN1.
action: MARK_AS_OVER_ANNOTATED
reason: The human paper supports nuclear transcriptional cofactor activity, not a
direct lamellipodium-assembly role. This appears to be a propagated family
phenotype rather than an AKIRIN1-specific process.
supported_by:
- reference_id: PMID:18066067
supporting_text: "regulating the transcriptional activities of main transactivators"
- term:
id: GO:0010759
label: positive regulation of macrophage chemotaxis
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This is an over-specific immune-cell migration annotation for human AKIRIN1.
action: MARK_AS_OVER_ANNOTATED
reason: The direct evidence does not support macrophage chemotaxis as an AKIRIN1
function. The family-level literature instead separates the immune-response
phenotype onto Akirin2.
supported_by:
- reference_id: PMID:18066067
supporting_text: "MmAkirin2, but not MmAkirin1, was responsible for the production of IL-6"
- term:
id: GO:0014839
label: myoblast migration involved in skeletal muscle regeneration
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This is a real but context-dependent muscle-regeneration annotation, not a core function.
action: KEEP_AS_NON_CORE
reason: >-
The deeper muscle literature supports AKIRIN1 in myoblast/satellite-cell
proliferation and differentiation during regeneration. That is sufficient to
keep the lineage-specific regeneration call as non-core, but not as a primary
conserved function for AKIRIN1.
supported_by:
- reference_id: PMID:23516508
supporting_text: "Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation"
- reference_id: file:human/AKIRIN1/AKIRIN1-deep-research-falcon.md
supporting_text: "supports myoblast/satellite cell proliferation and differentiation"
- term:
id: GO:0045663
label: positive regulation of myoblast differentiation
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This is a supported but non-core promyogenic annotation for human AKIRIN1.
action: KEEP_AS_NON_CORE
reason: >-
Dong et al. 2013 directly links AKIRIN1 to promyogenic behavior: in myoblasts,
AKIRIN1 overexpression increased MyoD and myogenin and improved proliferation
and differentiation. This supports the annotation, but it remains a
context-dependent muscle-repair function rather than the principal conserved
role of the protein.
supported_by:
- reference_id: PMID:23516508
supporting_text: "Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation"
- reference_id: PMID:23516508
supporting_text: "a promyogenic gene"
- reference_id: file:human/AKIRIN1/AKIRIN1-deep-research-falcon.md
supporting_text: "promyogenic nuclear factor"
- term:
id: GO:0045944
label: positive regulation of transcription by RNA polymerase II
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This is the same core transcriptional role seen in the experimentally supported set.
action: ACCEPT
reason: The IEA ortholog transfer is consistent with the direct human evidence that
Akirins regulate transcriptional output downstream of NF-kappaB.
supported_by:
- reference_id: PMID:18066067
supporting_text: "regulating the transcriptional activities of main transactivators"
- term:
id: GO:1902723
label: negative regulation of skeletal muscle satellite cell proliferation
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This direction is inconsistent with the AKIRIN1 muscle literature.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The available muscle literature supports AKIRIN1 as a positive regulator of
satellite-cell activity and regeneration, not as a negative regulator. This
term therefore conflicts with the promyogenic evidence and should not be kept.
supported_by:
- reference_id: PMID:23516508
supporting_text: "When myostatin was inhibited in Dex-treated mice, Akirin1 expression increased as did satellite cell activity, muscle regeneration and muscle growth"
- reference_id: PMID:23516508
supporting_text: "Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation"
- term:
id: GO:1902725
label: negative regulation of satellite cell differentiation
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: This direction is inconsistent with the AKIRIN1 muscle literature.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The muscle paper shows the opposite direction: AKIRIN1 increases myogenic
regulators and improves differentiation. That makes this negative-regulation
term a poor fit for AKIRIN1 even though the pathway is relevant to muscle
repair.
supported_by:
- reference_id: PMID:23516508
supporting_text: "Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation"
- reference_id: PMID:23516508
supporting_text: "a promyogenic gene"
- term:
id: GO:0005654
label: nucleoplasm
evidence_type: IDA
original_reference_id: GO_REF:0000052
qualifier: located_in
review:
summary: Direct experimental localization to the nucleoplasm is compatible with the nuclear role.
action: ACCEPT
reason: This narrower nuclear compartment annotation is compatible with the direct
nuclear localization evidence and does not conflict with the IBA nucleus term.
It is reasonable to retain as a finer-grained CC call.
supported_by:
- reference_id: PMID:18066067
supporting_text: "strict nuclear localization"
- term:
id: GO:0045663
label: positive regulation of myoblast differentiation
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: The ISS transfer duplicates an over-specific muscle process call.
action: KEEP_AS_NON_CORE
reason: >
The same logic applied to the IBA/IEA versions applies here: the direct AKIRIN1
evidence is nuclear transcriptional cofactor activity, but the muscle paper
still supports a context-dependent promyogenic role. Keep this as non-core
rather than over-annotation.
supported_by:
- reference_id: PMID:23516508
supporting_text: "Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation"
- term:
id: GO:0045944
label: positive regulation of transcription by RNA polymerase II
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This ISS transfer is consistent with the conserved transcriptional core function.
action: ACCEPT
reason: The orthology-based transfer is reasonable because the direct literature
supports the same transcriptional role in human AKIRIN1.
supported_by:
- reference_id: PMID:18066067
supporting_text: "regulating the transcriptional activities of main transactivators"
- term:
id: GO:0010592
label: positive regulation of lamellipodium assembly
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This ISS lamellipodium call is an over-annotation.
action: MARK_AS_OVER_ANNOTATED
reason: The direct AKIRIN1 literature does not support lamellipodium assembly as a
core function of the human protein; retain the nuclear transcriptional role
instead.
supported_by:
- reference_id: PMID:18066067
supporting_text: "strict nuclear localization"
- term:
id: GO:0010759
label: positive regulation of macrophage chemotaxis
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This ISS macrophage-chemotaxis call is over-specific for human AKIRIN1.
action: MARK_AS_OVER_ANNOTATED
reason: The direct literature does not support this immune-cell migration process
for AKIRIN1; the immune-response phenotype in the family is better attributed to
Akirin2.
supported_by:
- reference_id: PMID:18066067
supporting_text: "MmAkirin2, but not MmAkirin1, was responsible for the production of IL-6"
- term:
id: GO:0014839
label: myoblast migration involved in skeletal muscle regeneration
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This ISS muscle-regeneration call is an over-annotation for the human paralog.
action: KEEP_AS_NON_CORE
reason: AKIRIN1 is supported as a nuclear transcriptional cofactor, but the
muscle literature still supports a context-dependent promyogenic role. Keep
this as non-core rather than removing it entirely.
supported_by:
- reference_id: PMID:23516508
supporting_text: "Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation"
- term:
id: GO:1902723
label: negative regulation of skeletal muscle satellite cell proliferation
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This ISS satellite-cell proliferation term is too specific for AKIRIN1.
action: MARK_AS_OVER_ANNOTATED
reason: No direct AKIRIN1 evidence supports this phenotype-like process term.
supported_by:
- reference_id: PMID:18066067
supporting_text: "the functional role of MmAkirin1, attested by its sequence conservation, is unknown thus far"
- term:
id: GO:1902725
label: negative regulation of satellite cell differentiation
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: This ISS satellite-cell differentiation call is also over-annotated.
action: MARK_AS_OVER_ANNOTATED
reason: The available evidence supports a transcriptional cofactor role rather than
a satellite-cell differentiation function.
supported_by:
- reference_id: PMID:18066067
supporting_text: "novel important nuclear cofactors regulating the transcriptional activities of main transactivators"
- term:
id: GO:0005634
label: nucleus
evidence_type: IDA
original_reference_id: PMID:18066067
qualifier: located_in
review:
summary: Direct experimental localization to the nucleus is well supported.
action: ACCEPT
reason: This is the key experimental localization result for human Akirin1 and is
perfectly consistent with the conserved nuclear cofactor model.
supported_by:
- reference_id: PMID:18066067
supporting_text: "strict nuclear localization"
references:
- id: GO_REF:0000024
title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
findings: []
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
findings: []
- id: GO_REF:0000052
title: Gene Ontology annotation based on curation of immunofluorescence data
findings: []
- id: GO_REF:0000107
title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
findings: []
- id: PMID:18066067
title: Akirins are highly conserved nuclear proteins required for NF-kappaB-dependent gene expression in drosophila and mice.
findings:
- statement: Human AKIRIN1 localizes to the nucleus and Akirins function as conserved nuclear cofactors in NF-kappaB-dependent gene expression.
- id: PMID:23516508
title: Myostatin suppression of Akirin1 mediates glucocorticoid-induced satellite cell dysfunction.
findings:
- statement: AKIRIN1 has a context-dependent promyogenic role in myoblast and satellite-cell proliferation and differentiation during muscle repair.
- id: PMID:34711951
title: AKIRIN2 controls the nuclear import of proteasomes in vertebrates.
findings:
- statement: This paper supports AKIRIN2-centered proteasome import and does not provide positive evidence for AKIRIN1 as a proteasome importer; it is best treated as a negative contrast for the AKIRIN1 proteostasis projection.
- id: PMID:25416956
title: A proteome-scale map of the human interactome network.
findings:
- statement: This is a high-throughput human PPI map; it supports interaction evidence but not a proteasome-specific AKIRIN1 function.
core_functions:
- description: Conserved nuclear transcriptional cofactor that helps drive inducible gene-expression programs, especially NF-kappaB-dependent transcription.
molecular_function:
id: GO:0003712
label: transcription coregulator activity
directly_involved_in:
- id: GO:0045944
label: positive regulation of transcription by RNA polymerase II
supported_by:
- reference_id: PMID:18066067
supporting_text: "regulating the transcriptional activities of main transactivators"
- reference_id: PMID:18066067
supporting_text: "together with or downstream of NF-κB"
- reference_id: file:human/AKIRIN1/AKIRIN1-deep-research-falcon.md
supporting_text: "promyogenic nuclear factor"
- reference_id: file:human/AKIRIN1/AKIRIN1-deep-research-falcon.md
supporting_text: "supports myoblast/satellite cell proliferation and differentiation"
- description: Context-dependent promyogenic nuclear regulator that supports myoblast and satellite-cell proliferation and differentiation during muscle repair.
molecular_function:
id: GO:0003712
label: transcription coregulator activity
supported_by:
- reference_id: PMID:23516508
supporting_text: "a promyogenic gene"
- reference_id: PMID:23516508
supporting_text: "Akirin1 in myoblasts increased their expression of MyoD and myogenin and improved cellular proliferation and differentiation"
- reference_id: file:human/AKIRIN1/AKIRIN1-deep-research-falcon.md
supporting_text: "promyogenic nuclear factor"
- reference_id: file:human/AKIRIN1/AKIRIN1-deep-research-falcon.md
supporting_text: "supports myoblast/satellite cell proliferation and differentiation"
proposed_new_terms: []
suggested_questions:
- question: Is there any direct human evidence that AKIRIN1 binds the proteasome or a proteasome-adaptor complex, given that PMID:34711951 supports AKIRIN2 proteasome import and UniProt explicitly contrasts AKIRIN1 with that activity?
- question: Do the muscle and motility annotations belong to AKIRIN1 specifically, or are they better treated as family/paralog transfer that should remain out of the human review?
suggested_experiments:
- description: Test AKIRIN1 proximity to proteasome subunits and adaptor/shuttle proteins in human cells by co-IP or proximity labeling under basal and stimulated conditions.
- description: Deplete or edit AKIRIN1 in a human cell model and measure NF-kappaB-dependent transcription plus chromatin association at inducible target loci.