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AKAP17A

A-kinase anchor protein 17A · UniProt Q02040

Length
695 aa
Mass
80.7 kDa
Annotated
2026-06-09
19 papers in source corpus 8 papers cited in narrative 7 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AKAP17A (originally XE7) is a ubiquitously expressed, X-inactivation-escaping pseudoautosomal nuclear protein that functions at the RNA level, where its arginine/serine (RS)-rich region drives interactions with the splicing machinery (PMID:1302606, PMID:1496421, PMID:16982639). Through this RS domain it binds the SR protein ASF/SF2 and SR-related protein ZNF265, colocalizes with them in nuclear speckles, and modulates alternative splice site selection (PMID:16982639). Beyond canonical splicing, AKAP17A is the essential mRNA-binding subunit of 'SOS splicing,' a spliceosome-independent RNA defense system that excises DNA transposons from host transcripts: it directly recognizes TE-containing mRNAs bearing dsRNA hairpins formed by inverted terminal repeats, while CAAP1 bridges AKAP17A to the RNA ligase RTCB, which religates the cleaved mRNA fragments — a function conserved from C. elegans to human cells (PMID:41372403). The AKAP17A–CAAP1 axis also modulates cisplatin sensitivity in platinum-resistant ovarian cancer cells (PMID:36870674). AKAP17A additionally supports HIF1α protein synthesis and hypoxic adaptation through a PKA-independent mechanism, and its loss impairs hypoxia tolerance and suppresses tumor growth (PMID:41391802).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 1992 High

    Establishing the gene's identity and architecture: XE7/AKAP17A was defined as a pseudoautosomal, X-inactivation-escaping gene producing two isoforms via alternative splicing, providing the structural foundation for later functional work.

    Evidence Northern blot, cDNA/genomic clone sequencing, and somatic cell hybrid cDNA library screening

    PMID:1302606 PMID:1496421

    Open questions at the time
    • No molecular function assigned at this stage
    • Functional difference between the 385- and 695-aa isoforms not resolved
  2. 2006 High

    Assigning a molecular function: the RS-rich region was shown to mediate binding to splicing factors and influence splice site selection, identifying AKAP17A as an alternative splicing regulator localized to nuclear speckles.

    Evidence Yeast two-hybrid, co-immunoprecipitation, immunofluorescence colocalization, and minigene splicing assays for ASF/SF2 and ZNF265

    PMID:16982639

    Open questions at the time
    • Endogenous splicing targets beyond minigene reporters not defined
    • Whether splicing regulation requires catalytic partners unclear
  3. 2007 Medium

    Extending the spliceosomal interactome: AKAP17A was linked to ZRANB2 alongside core splicing factors U1-70K and U2AF35, embedding it in early spliceosome assembly contacts.

    Evidence Protein interaction assay reported within a review of ZRANB2 function

    PMID:17905639

    Open questions at the time
    • Limited methodological detail in the abstract/review format
    • Direct vs. indirect ZRANB2 contact not established
  4. 2023 Medium

    Connecting AKAP17A to drug response: its interaction with CAAP1 was implicated in modulating cisplatin sensitivity of resistant ovarian cancer cells through mRNA splicing.

    Evidence IP-mass spectrometry, lentiviral overexpression, and cell viability assays

    PMID:36870674

    Open questions at the time
    • AKAP17A's direct mechanistic contribution to the phenotype not isolated
    • Single lab; splicing events responsible for cisplatin sensitivity not mapped
  5. 2025 High

    Defining a novel pathway: AKAP17A was identified as the mRNA-binding core of spliceosome-independent SOS splicing, recognizing transposon-derived dsRNA hairpins and recruiting RTCB via CAAP1 to religate cleaved mRNA — a conserved RNA-level transposon defense system.

    Evidence Genetic loss-of-function (CRISPR/RNAi), RNA binding and protein interaction assays, and functional splicing assays in C. elegans and human cells

    PMID:40027818 PMID:41372403

    Open questions at the time
    • Structural basis of TE-mRNA recognition by AKAP17A not resolved
    • Relationship between SOS splicing and canonical SR-mediated splicing function unclear
  6. 2025 Medium

    Linking AKAP17A to hypoxic adaptation: it was shown to be required for HIF1α protein synthesis through a PKA-independent mechanism, supporting hypoxia tolerance, erythropoiesis, and tumor growth.

    Evidence siRNA/CRISPR depletion, zebrafish knockout, HIF1α protein and target-gene assays, and xenograft tumor models

    PMID:41391802

    Open questions at the time
    • Molecular link between AKAP17A and HIF1α translation not defined
    • Whether this role depends on its RNA-binding/splicing activity unknown
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How AKAP17A's distinct activities — SR-mediated alternative splicing, spliceosome-independent SOS splicing, and HIF1α protein synthesis — are mechanistically connected, and what PKA-related role (if any) underlies its AKAP designation, remains unresolved.
  • No unifying molecular model linking the splicing and HIF1α functions
  • No structural data for any AKAP17A complex
  • PKA-anchoring role implied by name not characterized in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3
Localization
GO:0005634 nucleus 2 GO:0005654 nucleoplasm 1
Pathway
R-HSA-8953854 Metabolism of RNA 2
Partners
CAAP1RTCBSRSF1ZNF265ZRANB2

Evidence

Reading pass · 7 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 XE7 (AKAP17A) is a pseudoautosomal gene located at terminal Xp/Yp that escapes X inactivation and is ubiquitously expressed; alternative RNA splicing produces two protein isoforms of 385 and 695 amino acids, where the smaller is a truncated version of the larger resulting from inclusion of a cassette exon introducing an in-frame stop codon. Northern blot, cDNA/genomic clone sequencing, somatic cell hybrid cDNA library screening Human molecular genetics High 1302606 1496421
2006 XE7 (AKAP17A) is an alternative splicing regulator that physically interacts with the SR protein ASF/SF2 and SR-related protein ZNF265 via its arginine/serine (RS)-rich region; it localizes to nuclear speckles where it colocalizes with these splicing factors, and influences alternative splice site selection of CD44, Tra2-beta1, and SRp20 pre-mRNA minigenes. Yeast two-hybrid screen, co-immunoprecipitation, immunofluorescence colocalization, minigene splicing assays Nucleic acids research High 16982639
2007 AKAP17A (SFRS17A/XE7) interacts with the splicing factor ZRANB2 as a novel splicing component; ZRANB2 binds AKAP17A along with essential splicing factors U1-70K and U2AF35. Protein interaction assay (pulldown/co-immunoprecipitation as described in review of ZRANB2 function) The international journal of biochemistry & cell biology Medium 17905639
2023 AKAP17A interacts with CAAP1 (a splicing-related protein), and this interaction is involved in the mRNA splicing pathway; overexpression of CAAP1 increased cisplatin sensitivity of platinum-resistant ovarian cancer cells via mRNA splicing through its interaction with AKAP17A. Immunoprecipitation-mass spectrometry, lentivirus-mediated overexpression, cell viability assay Journal of proteomics Medium 36870674
2025 AKAP17A is an essential component of 'SOS splicing,' a spliceosome-independent RNA-level defense system that excises DNA transposons from host mRNAs. AKAP17A directly binds TE-containing mRNAs (triggered by base-pairing of inverted terminal repeat elements forming dsRNA hairpins); CAAP1 bridges AKAP17A to the RNA ligase RTCB, allowing RTCB to religate the mRNA fragments generated after TE excision. This function is conserved between C. elegans and human cells. Genetic loss-of-function (CRISPR/RNAi), RNA binding assays, protein interaction assays, functional mRNA splicing assays in C. elegans and human cells Nature High 41372403
2025 AKAP17A is required for HIF1α protein synthesis and HIF1α signaling through a PKA-independent mechanism; depletion of AKAP17A in mammalian cells reduced HIF1α abundance and attenuated transcription of HIF target genes; akap17a-null zebrafish showed impaired hypoxia tolerance and diminished hypoxia-induced erythropoiesis; AKAP17A knockout suppressed cancer cell proliferation in vitro and tumor growth in vivo. siRNA/CRISPR depletion, zebrafish knockout model, HIF1α protein level measurement, HIF target gene transcriptional assays, in vitro proliferation assays, xenograft tumor models International journal of biological macromolecules Medium 41391802
2025 AKAP17A is required for SOS splicing in both C. elegans and human cells: AKAP17A binds TE-containing mRNAs, CAAP1 bridges RTCB and AKAP17A, and RTCB ligates mRNA fragments post-TE excision. This system operates independently of the spliceosome and is triggered by dsRNA hairpin structures formed by inverted terminal repeats of DNA transposons. (Preprint version of the Nature paper.) Genetic loss-of-function, RNA binding assays, protein interaction assays, functional mRNA splicing assays bioRxivpreprint High 40027818

Source papers

Stage 0 corpus · 19 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 The Human Pseudoautosomal Region (PAR): Origin, Function and Future. Current genomics 174 18660847
2000 Expression analysis of thirty one Y chromosome genes in human prostate cancer. Molecular carcinogenesis 81 10747295
2018 Transcriptome profiling of fetal Klinefelter testis tissue reveals a possible involvement of long non-coding RNAs in gonocyte maturation. Human molecular genetics 40 29186436
1992 Directed isolation of human genes that escape X inactivation. Somatic cell and molecular genetics 38 1496421
1998 Gene duplications as a recurrent theme in the evolution of the human pseudoautosomal region 1: isolation of the gene ASMTL. Human molecular genetics 35 9736779
2023 X chromosome dosage and the genetic impact across human tissues. Genome medicine 30 36978128
2006 XE7: a novel splicing factor that interacts with ASF/SF2 and ZNF265. Nucleic acids research 19 16982639
2020 Host Genetic and Gut Microbial Signatures in Familial Inflammatory Bowel Disease. Clinical and translational gastroenterology 18 32764209
1992 Structure and expression of the human pseudoautosomal gene XE7. Human molecular genetics 18 1302606
2012 Formulation and characterization of liquid crystal systems containing azelaic acid for topical delivery. Drug development and industrial pharmacy 12 22480294
2023 Proteomic analysis reveals CAAP1 negatively correlates with platinum resistance in ovarian cancer. Journal of proteomics 11 36870674
2007 ZRANB2: structural and functional insights into a novel splicing protein. The international journal of biochemistry & cell biology 11 17905639
2018 Design Graph Theoretical Analysis and In Silico Modeling of Dunaliella Bardawil Biomass Encapsulated N-Succinyl Chitosan Nanoparticles for Enhanced Anticancer Activity. Anti-cancer agents in medicinal chemistry 10 29956638
1992 Cloning and sequencing of a trophoblast-endothelial-activated lymphocyte surface protein: cDNA sequence and genomic structure. Proceedings of the National Academy of Sciences of the United States of America 8 1438229
2025 An RNA splicing system that excises DNA transposons from animal mRNAs. Nature 4 41372403
2025 An RNA Splicing System that Excises Transposons from Animal mRNAs. bioRxiv : the preprint server for biology 3 40027818
2026 ADAR-mediated tolerance and SOS splicing-mediated excision of transposable elements. Transcription 1 41744490
2025 Localization and Molecular Cloning of the ASMT Gene for Melatonin Synthesis in Pigs. International journal of molecular sciences 0 39859321
2025 A-kinase anchoring protein 17 A promotes hypoxic adaptation and tumor growth by augmenting HIF1α protein synthesis. International journal of biological macromolecules 0 41391802

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