Affinage

AKAP9

A-kinase anchor protein 9 · UniProt Q99996

Length
3907 aa
Mass
453.0 kDa
Annotated
2026-06-09
70 papers in source corpus 38 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AKAP9 encodes large multi-valent scaffolding proteins (AKAP450/CG-NAP/AKAP350 and the shorter neuronal/cardiac isoform Yotiao) that nucleate signalling complexes at the centrosome, Golgi apparatus, and nuclear envelope to organize microtubules and compartmentalize cAMP signalling (PMID:10202149, PMID:10358086, PMID:9915845, PMID:12221128, PMID:19242490). The protein is targeted to the centrosome by a C-terminal PACT domain and to the Golgi by an adjacent, separable Golgi-targeting motif, and recruits PKA type II via an RII-binding amphipathic helix (PMID:11263498, PMID:12163481, PMID:10202149, PMID:10358086, PMID:9915845). At microtubule-organizing centers it anchors the γ-tubulin ring complex through GCP2/GCP3, tethers Ran, and recruits dynein-dynactin (p150Glued), CK1δ/ε, PKCε, EB1, and CIP4, thereby driving microtubule nucleation from the centrosome, Golgi, and nuclear envelope and supporting nuclear positioning, spindle orientation, and directional cell migration (PMID:12221128, PMID:14517334, PMID:12270714, PMID:10945988, PMID:17352745, PMID:29097729, PMID:26208639, PMID:28966089, PMID:33295871). AKAP9 couples this scaffolding to cell-cycle control, recruiting cyclin E-Cdk2 and concentrating a PDE4D3-shaped cAMP microdomain that lowers the activation threshold of centrosomal PKA to license centriole duplication and the G1/S transition (PMID:12808041, PMID:15670215, PMID:22908311, PMID:24475373). In neurons and cardiomyocytes the Yotiao isoform assembles a macromolecular IKs channel complex (KCNQ1/KCNE1 with PKA, PP1, PDE4D3, and AC9) and is itself a PKA substrate at Ser-43, integrating β-adrenergic input into channel gating, while also scaffolding InsP3R1 and NMDA receptor NR1 to couple cAMP and Ca²⁺ signalling (PMID:15528278, PMID:16002409, PMID:22778270, PMID:14982933, PMID:9482789). A paracentric inversion of 7q creates an oncogenic AKAP9-BRAF fusion with constitutive kinase activity found in radiation-induced papillary thyroid carcinoma (PMID:15630448).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1998 High

    Established the first molecular role for an AKAP9 product by showing the Yotiao isoform physically links the NMDA receptor NR1 subunit to the postsynaptic apparatus, defining it as a synaptic scaffold.

    Evidence Yeast two-hybrid plus reciprocal Co-IP from brain and heterologous cells, with fractionation and NMJ co-localization

    PMID:9482789

    Open questions at the time
    • Did not define the full receptor complex or downstream signalling enzymes recruited
    • No structural basis for the C1 exon-dependent interaction
  2. 1999 High

    Identified the centrosomal/Golgi scaffold AKAP450/CG-NAP and its capacity to anchor PKA-RII alongside phosphatases PP1 and PP2A, establishing the protein as a multi-enzyme anchoring platform.

    Evidence RII overlay screening, reciprocal Co-IP, immunofluorescence, and mutation of the RII-binding helix in HeLa cells; plus Yotiao RII Kd measurement

    PMID:10202149 PMID:10358086 PMID:10618500 PMID:9915845

    Open questions at the time
    • Did not establish functional consequence of kinase/phosphatase anchoring
    • Stoichiometry and spatial organization of the bound enzymes unresolved
  3. 2002 High

    Mapped distinct C-terminal targeting modules (PACT for centrosome, a separate Golgi motif) and showed AKAP450 anchors γ-TuRC via GCP2/GCP3 to drive microtubule nucleation, linking localization to MTOC function.

    Evidence GFP chimera mapping, dominant-negative displacement, Co-IP, and antibody inhibition of nucleation from isolated centrosomes; plus CK1δ/ε, CLIC, TACC4 partner mapping

    PMID:11263498 PMID:12015314 PMID:12163479 PMID:12163481 PMID:12221128 PMID:12270714

    Open questions at the time
    • Did not resolve how γ-TuRC recruitment is regulated through the cell cycle
    • Functional roles of CLIC and TACC4 binding remained correlative
  4. 2003 High

    Demonstrated that centrosomal AKAP450 is required for microtubule regrowth/anchoring and for cell-cycle progression, tethering Ran and PKA and controlling cytokinesis, ploidy, and centriole duplication.

    Evidence Dominant-negative displacement of the C-terminal targeting domain with IF, immuno-EM, fractionation, and flow-cytometry cell-cycle analysis in HeLa and RPE1 cells

    PMID:12808041 PMID:14517334

    Open questions at the time
    • Did not separate scaffolding of MT machinery from PKA anchoring in producing the phenotypes
    • Mechanism coupling Ran delocalization to anchoring defect unclear
  5. 2004 High

    Defined Yotiao as the organizer of a cardiac/neuronal IKs and InsP3R1 signalling complex, recruiting PKA and PP1 to channels and exerting direct allosteric control over gating.

    Evidence Patch-clamp electrophysiology, channel mutagenesis, Co-IP from brain, and LIZ-motif domain mapping

    PMID:14982933 PMID:15528278

    Open questions at the time
    • Did not yet identify the upstream cAMP-generating and degrading enzymes in the cardiac complex
    • Allosteric gating mechanism not structurally defined
  6. 2005 High

    Showed Yotiao is itself a PKA substrate (Ser-43) whose phosphorylation is required for the cAMP response of the IKs channel, and that the centrosomal domain recruits cyclin E-Cdk2 to drive centrosome amplification.

    Evidence Phospho-specific antibody and S43A mutagenesis with electrophysiology; Co-IP of cyclin-Cdk2 kinase activity and dominant-negative cyclin E with centrosome counting

    PMID:15670215 PMID:16002409

    Open questions at the time
    • Did not establish how scaffold phosphorylation alters complex architecture
    • Physiological trigger for cyclin E-Cdk2 recruitment to the scaffold undefined
  7. 2005 High

    Connected AKAP9 to disease and to immune cell migration: a 7q inversion generates a transforming AKAP9-BRAF fusion in thyroid carcinoma, and the scaffold relocates to migrating T-cell extensions in complex with LFA-1, tubulin, and PKC.

    Evidence Molecular cloning, kinase activity and NIH3T3 transformation assays, tumor sequencing; in situ Co-IP and T-cell migration assay

    PMID:15630448 PMID:16339516

    Open questions at the time
    • AKAP9-BRAF fusion describes a chimeric oncoprotein, not wild-type AKAP9 function
    • Mechanism of LFA-1-specific scaffold relocation not resolved
  8. 2009 High

    Established AKAP450 as the essential nucleator of Golgi-derived microtubules, recruited to the cis-Golgi in a GM130-dependent, MT-independent manner.

    Evidence siRNA depletion with live-cell MT regrowth assays, brefeldin A treatment, and IF

    PMID:19242490

    Open questions at the time
    • Did not define how GM130 docking is coordinated with centrosomal pools
    • Functional consequence of Golgi MTs for trafficking not addressed here
  9. 2010 Medium

    Extended scaffold function to endothelial barrier control, showing AKAP9 binds Epac1 and is required for Epac1-stimulated microtubule growth and integrin-mediated barrier strengthening.

    Evidence Co-IP, siRNA, live MT dynamics imaging, and transendothelial resistance assay

    PMID:20952690

    Open questions at the time
    • Single lab; reciprocal validation of the Epac1 interaction limited
    • Direct vs indirect nature of the AKAP9-Epac1 association unresolved
  10. 2012 High

    Resolved the full cAMP regulatory architecture of AKAP9 complexes: a cardiac IKs complex incorporating PDE4D3 and AC9 to sensitize PKA phosphorylation, and a centrosomal PDE4D3-shaped cAMP microdomain that lowers the PKA activation threshold for cell-cycle progression.

    Evidence Co-IP from transgenic/guinea-pig heart, RT-PCR isoform survey, AC activity and peptide competition; FRET cAMP imaging and cell-cycle analysis

    PMID:22778270 PMID:22908311

    Open questions at the time
    • Did not define spatial extent of the microdomains in vivo
    • Crosstalk between centrosomal and Golgi cAMP pools unexplored
  11. 2013 Medium

    Demonstrated organismal and cell-cycle roles in vivo, showing Akap9 loss causes infertility via failed Sertoli cell maturation and blood-testis barrier disruption, and that the centrosomal scaffold drives G1/S by tethering Cdk2.

    Evidence Three Akap9 mouse loss-of-function alleles with histology/IF; siRNA, C-terminal domain overexpression, BrdU, and nucleophosmin phosphorylation assays

    PMID:23608191 PMID:24475373

    Open questions at the time
    • Did not connect junctional defects to a specific AKAP9-anchored enzyme
    • Tissue specificity of the Cdk2-scaffolding role unclear
  12. 2015 High

    Defined the directional-migration and immune functions of the scaffold: AKAP350 recruits CIP4 to position the centrosome in the nucleus-centrosome-Golgi axis, and AKAP9 supports microtubule-dependent TCR recycling controlling T-cell egress in inflammation.

    Evidence siRNA, dominant-negative interaction-disruption, wound-healing assays; conditional T-cell Akap9 knockout with TCR recycling assay and in vivo disease models

    PMID:26208639 PMID:26680259

    Open questions at the time
    • Did not establish whether MT nucleation or anchoring underlies the migration defect
    • Link between TCR recycling kinetics and tissue egress mechanistically incomplete
  13. 2017 High

    Identified a nuclear-envelope MTOC role, showing Nesprin-1α recruits Akap450 to the nuclear envelope to nucleate microtubules required for myonuclear positioning, a pathway disrupted in SYNE1-mutant muscular dystrophy myotubes.

    Evidence BioID proximity labeling, siRNA, live MT nucleation assays, and patient-cell validation

    PMID:28966089

    Open questions at the time
    • Did not define the adaptor bridging Nesprin-1α to AKAP450
    • Whether nuclear-envelope nucleation uses γ-TuRC as at the centrosome unstated
  14. 2020 Medium

    Filled in the nuclear-envelope MTOC adaptor and refined spindle-pole mechanics, identifying AKAP6 as the Nesprin-1α-to-AKAP9 linker tethering Golgi to nucleus, and showing AKAP350 localizes p150Glued to spindle poles for astral MT elongation.

    Evidence Co-IP, siRNA/shRNA, MT nucleation and ectopic-expression assays; Co-IP and astral MT length measurement

    PMID:32841682 PMID:33295871

    Open questions at the time
    • Single-lab observations; reciprocal in vivo validation limited
    • Regulation of switching between centrosomal and nuclear-envelope MTOCs unresolved
  15. 2024 Medium

    Expanded Yotiao's calcium-signalling role, showing it suppresses store-operated calcium entry through Orai1 via AC9-dependent cAMP, independently of IP3R1, PKA, and PP1.

    Evidence ER Ca2+ and SOCE imaging with truncation constructs, knockout cells, and pharmacology

    PMID:38781694

    Open questions at the time
    • Single lab; direct Yotiao-Orai1 contact not structurally confirmed
    • Physiological context of SOCE suppression unaddressed
  16. 2025 High

    Provided the first structural and DNA-association data for full-length AKAP350 and refined Golgi PKA regulation, revealing fibrillar clusters that scaffold double-stranded DNA with NFIB/nucleolin, and showing PDE4DIP stabilizes Golgi-localized PKA RIIα.

    Evidence Cryo-EM/cryo-ET, mass spectrometry, DNA sequencing, DNase-I pull-downs; Co-IP, siRNA, and RIIα localization/stability assays

    PMID:39905234 PMID:40154916

    Open questions at the time
    • Functional significance of the DNA-associated fibrillar assembly unknown
    • How PDE4DIP and AKAP9 jointly stabilize RIIα not mechanistically resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the centrosomal, Golgi, nuclear-envelope, and channel-complex pools of AKAP9 are differentially specified and dynamically regulated within a single cell remains unresolved.
  • No integrated model of isoform- and localization-specific complex assembly
  • No high-resolution structure of the full-length scaffold with its bound enzymes
  • Physiological role of the DNA-associated fibrillar state undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 6 GO:0060090 molecular adaptor activity 6 GO:0098772 molecular function regulator activity 4 GO:0003677 DNA binding 1
Localization
GO:0005794 Golgi apparatus 7 GO:0005815 microtubule organizing center 7 GO:0005886 plasma membrane 3 GO:0005635 nuclear envelope 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1852241 Organelle biogenesis and maintenance 5 R-HSA-1640170 Cell Cycle 4 R-HSA-1643685 Disease 2 R-HSA-168256 Immune System 2
Partners
ADCY9DCTN1GM130GRIN1ITPR1KCNQ1PDE4DPRKAR2A
Complex memberships
IKs channel complex (KCNQ1/KCNE1/PKA/PP1/PDE4D3/AC9)NMDA receptor-PKA postsynaptic complexnuclear envelope MTOCγ-tubulin ring complex (γ-TuRC)

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 AKAP450/CG-NAP was identified as a centrosomal scaffolding protein that binds RIIα (regulatory subunit of PKA type II) via a putative RII-binding amphipathic helix (around amino acid 2556), co-precipitates with PP2A catalytic subunit (when PR130 B-subunit is expressed), and co-precipitates with PP1 catalytic subunit in HeLa cells. The protein localizes to centrosome throughout the cell cycle, the midbody at telophase, and the Golgi apparatus at interphase. RII overlay screening, immunoprecipitation, immunofluorescence, mutation analysis of RII-binding site The EMBO journal / The Journal of biological chemistry High 10202149 10358086 9915845
2000 The C-terminal ~90 amino acid PACT domain of AKAP450 is necessary and sufficient for centrosomal targeting; fusion of this domain to a reporter confers centrosomal localization, overexpression displaces endogenous pericentrin, and the isolated C-terminal domain associates with calmodulin when isolated from transfected cells. GFP fusion reporter localization, overexpression displacement assay, calmodulin association from transfected cells EMBO reports High 11263498
1998 Yotiao (a splice variant/isoform encoded by AKAP9) was identified as a binding partner of the NR1 subunit of the NMDA receptor in a C1 exon-dependent manner; yotiao co-immunoprecipitates with NR1 from heterologous cells and from rat brain, fractionates with postsynaptic density and cytoskeletal proteins, and colocalizes with NR1 at neuromuscular junctions. Yeast two-hybrid screen, co-immunoprecipitation from brain and heterologous cells, immunofluorescence co-localization, subcellular fractionation The Journal of neuroscience High 9482789
1999 Yotiao interacts with PKA regulatory subunit RII via an RII-binding site constituted by amino acids 1452–1469, with a Kd of 50–90 nM in vitro; a stable complex of Yotiao, RIIβ, and NR1 was immunoprecipitated from whole rat brain. Yeast two-hybrid, in vitro binding assay with purified C-terminal Yotiao fragment, co-immunoprecipitation from rat brain FEBS letters High 10618500
2002 CG-NAP/AKAP450 anchors the gamma-tubulin ring complex (γ-TuRC) at the centrosome: its N-terminal region associates with γ-TuRC indirectly by binding GCP2 and/or GCP3, while its C-terminal region interacts with calmodulin. Antibody inhibition of CG-NAP (or kendrin, or both combined) moderately to strongly inhibits microtubule nucleation from isolated centrosomes. Co-immunoprecipitation of endogenous proteins, yeast two-hybrid for calmodulin interaction, antibody inhibition of microtubule nucleation from isolated centrosomes Molecular biology of the cell High 12221128
2003 A fraction of the small GTPase Ran is tightly associated with the centrosome via AKAP450; when AKAP450 is delocalized from the centrosome, Ran is also delocalized, and microtubule regrowth and anchoring are impaired despite persistent γ-tubulin association with the centrosome. Immunofluorescence, immunoelectron microscopy, biochemical fractionation, dominant-negative AKAP450 displacement Molecular biology of the cell High 14517334
2003 Displacement of endogenous AKAP450 from centrosomes (by overexpression of its C-terminal centrosome-targeting domain) delocalizes centrosomal PKA type IIα, impairs cytokinesis, increases ploidy in HeLa cells, arrests diploid RPE1 cells in G1, and interrupts centriole duplication. Overexpression of dominant-negative C-terminal domain, immunofluorescence, flow cytometry cell cycle analysis Molecular biology of the cell High 12808041
2002 CG-NAP/AKAP450 interacts with CK1δ and CK1ε (but not other CK1 isoforms) via a 182 amino acid fragment; this fragment co-immunoprecipitates with CK1δ/ε from mammalian cells, co-localizes with endogenous CK1δ at the centrosome, and when targeted to the plasma membrane is sufficient to re-localize CK1δ to the membrane, establishing CG-NAP as the centrosomal anchor for CK1δ/ε. Yeast two-hybrid, co-immunoprecipitation, immunofluorescence co-localization, membrane-targeting re-localization experiment Journal of molecular biology High 12270714
2009 AKAP450 is required for microtubule nucleation at the Golgi apparatus: depletion of AKAP450 abolishes Golgi MT nucleation, and depletion of the cis-Golgi protein GM130 disorganizes the AKAP450 network and impairs MT nucleation. AKAP450 binds the cis-side of the Golgi in an MT-independent, GM130-dependent manner. siRNA depletion, live-cell MT regrowth assay, brefeldin A treatment, immunofluorescence The EMBO journal High 19242490
2004 Yotiao interacts with the type 1 InsP3 receptor (InsP3R1) via the leucine/isoleucine zipper (LIZ) motif in the InsP3R1 coupling domain and the fourth LIZ motif in AKAP9/Yotiao; this interaction mediates PKA-InsP3R1 association in brain, is isoform-specific (type 1 only), and promotes association of InsP3R1 with the NR1 NMDA receptor as well as indirect association with PP1. Biochemical co-immunoprecipitation from brain, in vitro binding, domain mapping with LIZ mutants The Journal of biological chemistry High 14982933
2004 Yotiao (AKAP9) directly associates with the IKs potassium channel complex (KCNQ1/KCNE1), recruits PKA and PP1 to the channel, and exerts direct allosteric effects on channel gating that are distinct from its role in coordinating PKA phosphorylation — demonstrated by studying channels mutated to simulate phosphorylation. Electrophysiology (patch-clamp), co-immunoprecipitation, channel mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 15528278
2005 Yotiao itself is a PKA substrate: Ser-43 in the N-terminus of Yotiao is phosphorylated by PKA in response to β-adrenergic receptor stimulation. Alanine substitution of Ser-43 abolishes PKA phosphorylation of Yotiao and markedly diminishes the functional (voltage-dependent activation and kinetics) response of the IKs channel to cAMP, without preventing PKA phosphorylation of KCNQ1 or KCNQ1 binding to Yotiao. Phospho-specific antibody, mutagenesis (S43A), β-adrenergic stimulation, electrophysiology The Journal of biological chemistry High 16002409
2008 Yotiao (AKAP9) directly interacts with adenylyl cyclase (AC) isoforms 1, 2, 3, and 9 but not AC5 or AC6; it inhibits AC2 and AC3 enzymatic activity but has no effect on AC1 or AC9. The N-terminus of AC2 binds directly to amino acids 808–957 of Yotiao. Disruption of Yotiao-AC interactions increases brain AC activity by ~40%, establishing Yotiao as a direct regulator of cAMP production. Co-immunoprecipitation, enzymological AC activity assay, domain mapping with truncations, peptide competition Proceedings of the National Academy of Sciences of the United States of America High 18772391
2000 CG-NAP anchors hypophosphorylated/immature PKCε at the Golgi/centrosome area via direct binding to PKCε's catalytic domain; sufficiently phosphorylated (mature) PKCε does not bind CG-NAP. Phosphorylation-site mutants (T566A or S729A) of PKCε co-localize with CG-NAP at Golgi/centrosome, while wild-type PKCε distributes in cytosol upon maturation. Co-immunoprecipitation, in vitro binding assay, pulse-chase, mutagenesis, immunofluorescence The Journal of biological chemistry High 10945988
2005 AKAP9-BRAF fusion protein results from paracentric inversion of chromosome 7q, creating an in-frame fusion of AKAP9 exons 1–8 with BRAF exons 9–18. The fusion protein retains the BRAF kinase domain but lacks the autoinhibitory N-terminal portion, displays elevated kinase activity, and transforms NIH3T3 cells; it was preferentially found in radiation-induced papillary thyroid carcinomas. Molecular cloning, kinase activity assay, NIH3T3 transformation assay, PCR/sequencing of tumor samples The Journal of clinical investigation High 15630448
2002 AKAP350A contains a distinct Golgi apparatus targeting motif between amino acids 3259 and 3307 that is functionally distinguishable from the adjacent centrosomal PACT domain (amino acids 3308–3324); GFP chimeras of the carboxyl-terminal regions defined these two non-overlapping targeting domains. GFP chimeric construct localization, brefeldin A treatment, immunofluorescence The Journal of biological chemistry Medium 12163481
2002 AKAP350 associates with all CLIC family members via a 133 amino acid domain; specifically, CLIC5B (a novel CLIC isoform) co-localizes and co-immunoprecipitates with AKAP350 at the Golgi apparatus, and this association is disrupted by brefeldin A treatment. Yeast two-hybrid, co-immunoprecipitation, GFP targeting constructs, immunofluorescence, brefeldin A treatment The Journal of biological chemistry Medium 12163479
2004 AKAP350 interacts with CIP4 (and structurally related proteins FBP17, FBP17b) via yeast two-hybrid and pull-down. CIP4 is phosphorylated by PKA in vitro, and forskolin stimulates CIP4 phosphorylation in situ. Disruption of the CIP4-AKAP350 interaction or AKAP350 knockdown by RNAi leads to changes in Golgi structure. Yeast two-hybrid, GST pull-down, in vitro PKA phosphorylation assay, RNAi knockdown, immunofluorescence of Golgi morphology Molecular biology of the cell Medium 15047863
2007 CG-NAP is recruited to the Golgi apparatus via interaction with the dynein-dynactin complex: CG-NAP possesses two microtubule-binding domains, co-immunoprecipitates with dynactin subunit p150(Glued), and the p150(Glued)-binding region of CG-NAP when targeted to mitochondria recruits mitochondria to the pericentriolar area. Overexpression of this region causes Golgi fragmentation similar to dynamitin overexpression. Co-immunoprecipitation, microtubule co-sedimentation, mitochondria-targeting re-localization, overexpression/dominant-negative, immunofluorescence Genes to cells Medium 17352745
2005 The centrosome-targeting region of CG-NAP (CG-NAP/D) causes centrosome amplification by recruiting cyclin E-cdk2 to centrosomes; CG-NAP/D co-immunoprecipitates active cyclin-cdk complexes (histone H1 kinase activity), centrosome fractions from CG-NAP/D cells have increased cdk2, and amplification is suppressed by a mutant cyclin E unable to bind cdk2. Overexpression of targeting domain, centrosome counting, co-immunoprecipitation of kinase activity, dominant-negative cyclin E, immunofluorescence Genes to cells Medium 15670215
2010 AKAP9 interacts with Epac1 and facilitates microtubule polymerization in endothelial cells; AKAP9 silencing abolishes Epac1-stimulated microtubule growth and the ability of Epac1 activation to enhance barrier function via integrin adhesion at cell-cell contacts, despite intact Rap1 activation, cortical actin, and VE-cadherin adhesion. siRNA knockdown, live-cell microtubule dynamics imaging, co-immunoprecipitation (Epac1-AKAP9), transendothelial resistance assay Blood Medium 20952690
2012 In the heart, Yotiao assembles a macromolecular IKs signaling complex containing PKA, PP1, PDE4D3, AC9, and the KCNQ1-KCNE1 channel; AC9 is the only Yotiao-interacting AC isoform expressed in cardiac myocytes, and AC9 association with the complex sensitizes PKA phosphorylation of KCNQ1 to β-adrenergic stimulation. Addition of the AC9 N-terminus disrupts AC activity associated with the IKs-Yotiao complex in transgenic mouse heart. Co-immunoprecipitation from transgenic mouse heart and guinea pig heart, RT-PCR isoform survey, AC activity assay, peptide competition The Journal of biological chemistry High 22778270
2012 AKAP9-anchored PDE4D3 generates a centrosomal cAMP microdomain: centrosomal PKA shows a reduced activation threshold due to autophosphorylation of its regulatory subunit at S114 upon AKAP9 binding; disruption of centrosomal PDE4D3 impairs cell cycle progression by accumulating cells in prophase. FRET-based real-time cAMP imaging, displacement of centrosomal PDE4D3, cell cycle analysis by flow cytometry The Journal of cell biology High 22908311
2005 CG-NAP/AKAP450 redistributes from centrosome/Golgi to microtubules in trailing extensions of LFA-1-stimulated T cells; it forms a physical complex with LFA-1, tubulin, and PKCβ/δ isoenzymes, and is critically required for T cell polarization and migration induced by LFA-1 but not fibronectin (β1 integrin). In situ immunoprecipitation, immunofluorescence co-localization, GFP-tagged dominant-negative construct, T cell migration assay Journal of immunology Medium 16339516
2002 TACC4 interacts with AKAP350 at the centrosome in interphase via its C-terminal coiled-coil region; AKAP350 sequesters TACC4 to the centrosome in interphase, while a distinct N-terminal domain of TACC4 mediates spindle localization in mitosis. Overexpression of spindle-targeting TACC4 increases the proportion of cells in prometaphase. Yeast two-hybrid, co-localization immunofluorescence, truncation analysis, cell cycle analysis The Journal of biological chemistry Medium 12015314
2017 In differentiated muscle cells (myotubes), Nesprin-1α recruits Akap450 to the nuclear envelope independently of kinesin; Akap450 (but not Pericentrin or Pcm1) is required for microtubule nucleation from the nuclear envelope, and this MT nucleation activity is required for nuclear spreading and positioning in myotubes. This mechanism is disrupted in congenital muscular dystrophy patient myotubes carrying a SYNE1 nonsense mutation. BioID proximity labeling, siRNA knockdown, live-cell MT nucleation assay, computer simulation, immunofluorescence Current biology High 28966089
2020 In cardiomyocytes, AKAP6 acts as an adaptor linking Nesprin-1α to AKAP9 (and Pericentrin) at the nuclear envelope MTOC via spectrin repeats; AKAP6 and AKAP9 form a protein platform tethering the Golgi to the nucleus, and both Golgi and nuclear envelope exhibit MTOC activity utilizing AKAP9. AKAP6 is required for formation and activity of the nuclear envelope MTOC. Co-immunoprecipitation, immunofluorescence, siRNA/shRNA knockdown, MT nucleation assay, ectopic expression in epithelial cells eLife Medium 33295871
2013 Akap9 disruption in mice causes infertility through failure of Sertoli cell maturation: Sertoli cells continue expressing immaturity markers (AMH, thyroid hormone receptor α) and fail to express maturation marker p27(Kip1); gap and tight junctions essential for the blood-testis barrier are disrupted, with mislocalized connexin43 and ZO-1. Three Akap9 mouse alleles (loss-of-function), immunofluorescence, Western blot, histology Genetics Medium 23608191
2017 AKAP350 recruits EB1 to the spindle poles; decreased AKAP350 expression reduces EB1 levels at spindle poles and astral microtubules, causes defective spindle alignment in 3D epithelial cysts with abnormal lumen, and EB1 overexpression rescues the spindle orientation defect. Specific delocalization of the AKAP350/EB1 complex from the centrosome phenocopies AKAP350 knockdown. siRNA knockdown, 3D organotypic culture, immunofluorescence, EB1 overexpression rescue, dominant-negative delocalization construct Scientific reports Medium 29097729
2015 AKAP350 recruits CIP4 to the centrosome; decreased AKAP350 or CIP4 expression, or inhibition of the CIP4-AKAP350 interaction, impairs formation of the nucleus-centrosome-Golgi front-back axis and directional cell migration. Centrosome positioning (but not nuclear movement) is specifically affected. siRNA knockdown, dominant-negative CIP4-binding domain, immunofluorescence, wound-healing and migration assays Journal of cell science Medium 26208639
2015 AKAP9-deficient T cells (T cell-specific deletion) exhibit reduced microtubule-dependent TCR recycling to the cell surface, impairing TCR re-activation by non-classical antigen-presenting cells; this leads to increased T cell egress from inflamed tissues and protection from organ damage in inflammatory disease models. Conditional T cell-specific Akap9 knockout mice, TCR surface recycling assay, in vivo inflammatory disease models, flow cytometry Nature communications High 26680259
2013 AKAP350 at the centrosome facilitates the initiation of DNA synthesis by scaffolding Cdk2 to the centrosome; an AKAP350 C-terminal domain increases centrosomal Cdk2 levels and phosphorylation of nucleophosmin (a Cdk2 centrosomal substrate marking G1/S transition), whereas AKAP350 knockdown inhibits G1/S transition and DNA synthesis. siRNA knockdown, overexpression of C-terminal domain, BrdU incorporation, nucleophosmin phosphorylation assay, centrosome fractionation Cellular logistics Medium 24475373
2020 AKAP350 localizes p150(Glued) (dynactin component) to the spindle poles, facilitating p150(Glued)/EB1 interaction at these structures; AKAP350 depletion reduces p150(Glued) at astral microtubules and impairs elongation of astral microtubules during anaphase. siRNA knockdown, co-immunoprecipitation, immunofluorescence, astral MT length measurement Biochimie Medium 32841682
2024 Yotiao decreases ER calcium content by suppressing store-operated calcium entry (SOCE) through Orai1; this effect requires AC9 (which increases cAMP upon Yotiao interaction) and involves Yotiao acting on the Orai1 C-terminus, but does not require IP3R1, PKA, PP1, or AC2. ER Ca2+ imaging, Yotiao truncation constructs, knockout cells, pharmacological tools, SOCE assay Cell calcium Medium 38781694
2025 Purified full-length AKAP350 forms polydisperse fibrillar clusters (~50 nm) with fibrous outgrowths; cryo-EM revealed fibers reconstructing as double-stranded DNA, confirmed by DNA sequencing. AKAP350 co-purifies with endogenous PKA, CEP170, CDK5RAP2, and DNA-binding proteins NFIB and nucleolin; NFIB and nucleolin pull-down was reduced by DNase-I treatment (indicating DNA-mediated interaction), whereas centrosomal protein pull-downs were not affected by DNase-I. Cryo-EM, cryo-ET, mass spectrometry, DNA sequencing, pull-down with DNase-I treatment, purification of full-length protein from human cells Journal of molecular biology High 40154916
2025 PDE4DIP coordinates with AKAP9 to enhance Golgi localization and stability of PKA RIIα; depletion of PDE4DIP mislocalizes RIIα from the Golgi and leads to its degradation, compromising RIIα's negative regulatory effect on PKA signaling. Co-immunoprecipitation, siRNA knockdown, immunofluorescence localization of PKA RIIα, Western blot for RIIα stability Communications biology Medium 39905234

Source papers

Stage 0 corpus · 70 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Oncogenic AKAP9-BRAF fusion is a novel mechanism of MAPK pathway activation in thyroid cancer. The Journal of clinical investigation 339 15630448
2000 The PACT domain, a conserved centrosomal targeting motif in the coiled-coil proteins AKAP450 and pericentrin. EMBO reports 290 11263498
2009 Microtubule nucleation at the cis-side of the Golgi apparatus requires AKAP450 and GM130. The EMBO journal 273 19242490
1998 Yotiao, a novel protein of neuromuscular junction and brain that interacts with specific splice variants of NMDA receptor subunit NR1. The Journal of neuroscience : the official journal of the Society for Neuroscience 246 9482789
1999 Characterization of a novel giant scaffolding protein, CG-NAP, that anchors multiple signaling enzymes to centrosome and the golgi apparatus. The Journal of biological chemistry 216 10358086
2002 Centrosomal proteins CG-NAP and kendrin provide microtubule nucleation sites by anchoring gamma-tubulin ring complex. Molecular biology of the cell 191 12221128
1999 Cloning and characterization of a cDNA encoding an A-kinase anchoring protein located in the centrosome, AKAP450. The EMBO journal 162 10202149
1999 AKAP350, a multiply spliced protein kinase A-anchoring protein associated with centrosomes. The Journal of biological chemistry 121 9915845
2017 Nesprin-1α-Dependent Microtubule Nucleation from the Nuclear Envelope via Akap450 Is Necessary for Nuclear Positioning in Muscle Cells. Current biology : CB 119 28966089
2003 Part of Ran is associated with AKAP450 at the centrosome: involvement in microtubule-organizing activity. Molecular biology of the cell 110 14517334
2004 Regulatory actions of the A-kinase anchoring protein Yotiao on a heart potassium channel downstream of PKA phosphorylation. Proceedings of the National Academy of Sciences of the United States of America 100 15528278
2008 The A-kinase anchoring protein Yotiao binds and regulates adenylyl cyclase in brain. Proceedings of the National Academy of Sciences of the United States of America 94 18772391
2002 Centrosomal anchoring of the protein kinase CK1delta mediated by attachment to the large, coiled-coil scaffolding protein CG-NAP/AKAP450. Journal of molecular biology 92 12270714
2012 The A-kinase anchoring protein Yotiao facilitates complex formation between adenylyl cyclase type 9 and the IKs potassium channel in heart. The Journal of biological chemistry 85 22778270
2000 Association of immature hypophosphorylated protein kinase cepsilon with an anchoring protein CG-NAP. The Journal of biological chemistry 76 10945988
2012 PKA and PDE4D3 anchoring to AKAP9 provides distinct regulation of cAMP signals at the centrosome. The Journal of cell biology 68 22908311
2005 Phosphorylation of the A-kinase-anchoring protein Yotiao contributes to protein kinase A regulation of a heart potassium channel. The Journal of biological chemistry 68 16002409
2004 Association of type 1 inositol 1,4,5-trisphosphate receptor with AKAP9 (Yotiao) and protein kinase A. The Journal of biological chemistry 68 14982933
2003 Dissociating the centrosomal matrix protein AKAP450 from centrioles impairs centriole duplication and cell cycle progression. Molecular biology of the cell 65 12808041
2003 CLIC4 is enriched at cell-cell junctions and colocalizes with AKAP350 at the centrosome and midbody of cultured mammalian cells. Cell motility and the cytoskeleton 64 14569596
2010 AKAP9 regulation of microtubule dynamics promotes Epac1-induced endothelial barrier properties. Blood 59 20952690
2004 AKAP350 interaction with cdc42 interacting protein 4 at the Golgi apparatus. Molecular biology of the cell 57 15047863
2016 Long non-coding RNA MALAT1 increases AKAP-9 expression by promoting SRPK1-catalyzed SRSF1 phosphorylation in colorectal cancer cells. Oncotarget 56 26887056
2002 AKAP350 at the Golgi apparatus. II. Association of AKAP350 with a novel chloride intracellular channel (CLIC) family member. The Journal of biological chemistry 55 12163479
2006 BRAF mutation and AKAP9 expression in sporadic papillary thyroid carcinomas. Pathology 51 16753739
2003 Characterization of a Drosophila centrosome protein CP309 that shares homology with Kendrin and CG-NAP. Molecular biology of the cell 51 14565985
2014 AKAP9 is a genetic modifier of congenital long-QT syndrome type 1. Circulation. Cardiovascular genetics 50 25087618
2008 Association of a common AKAP9 variant with breast cancer risk: a collaborative analysis. Journal of the National Cancer Institute 44 18334708
2020 AKAP6 orchestrates the nuclear envelope microtubule-organizing center by linking golgi and nucleus via AKAP9. eLife 43 33295871
2002 AKAP350 at the Golgi apparatus. I. Identification of a distinct Golgi apparatus targeting motif in AKAP350. The Journal of biological chemistry 43 12163481
1999 Yotiao protein, a ligand for the NMDA receptor, binds and targets cAMP-dependent protein kinase II(1). FEBS letters 39 10618500
2016 AKAP-9 promotes colorectal cancer development by regulating Cdc42 interacting protein 4. Biochimica et biophysica acta 35 27039663
2007 Recruitment of CG-NAP to the Golgi apparatus through interaction with dynein-dynactin complex. Genes to cells : devoted to molecular & cellular mechanisms 33 17352745
2005 Centrosome-targeting region of CG-NAP causes centrosome amplification by recruiting cyclin E-cdk2 complex. Genes to cells : devoted to molecular & cellular mechanisms 29 15670215
2005 The scaffolding protein CG-NAP/AKAP450 is a critical integrating component of the LFA-1-induced signaling complex in migratory T cells. Journal of immunology (Baltimore, Md. : 1950) 29 16339516
2015 Centrosomal AKAP350 and CIP4 act in concert to define the polarized localization of the centrosome and Golgi in migratory cells. Journal of cell science 28 26208639
2010 Integrin and CD3/TCR activation are regulated by the scaffold protein AKAP450. Blood 26 20231423
2005 AKAP350 modulates microtubule dynamics. European journal of cell biology 26 16356588
2013 AKAP9 is essential for spermatogenesis and sertoli cell maturation in mice. Genetics 24 23608191
2018 Unclassified sclerosing malignant melanomas with AKAP9-BRAF gene fusion: a report of two cases and review of BRAF fusions in melanocytic tumors. Virchows Archiv : an international journal of pathology 23 29464327
2002 Transforming acidic coiled-coil-containing protein 4 interacts with centrosomal AKAP350 and the mitotic spindle apparatus. The Journal of biological chemistry 23 12015314
2006 Dual roles of the A kinase-anchoring protein Yotiao in the modulation of a cardiac potassium channel: a passive adaptor versus an active regulator. European journal of cell biology 20 16647783
2015 AKAP9, a Regulator of Microtubule Dynamics, Contributes to Blood-Testis Barrier Function. The American journal of pathology 17 26687990
2022 Alzheimer's disease associated AKAP9 I2558M mutation alters posttranslational modification and interactome of tau and cellular functions in CRISPR-edited human neuronal cells. Aging cell 16 35567427
2018 Tau Phosphorylation is Impacted by Rare AKAP9 Mutations Associated with Alzheimer Disease in African Americans. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 16 29516269
2015 AKAP9 regulates activation-induced retention of T lymphocytes at sites of inflammation. Nature communications 16 26680259
2015 Resequencing and association analysis of coding regions at twenty candidate genes suggest a role for rare risk variation at AKAP9 and protective variation at NRXN1 in schizophrenia susceptibility. Journal of psychiatric research 15 25943950
2016 Frameshift Mutations of AKAP9 Gene in Gastric and Colorectal Cancers with High Microsatellite Instability. Pathology oncology research : POR 13 26786868
2012 AKAP350 Is involved in the development of apical "canalicular" structures in hepatic cells HepG2. Journal of cellular physiology 12 21374596
2021 AKAP9 supports spermatogenesis through its effects on microtubule and actin cytoskeletons in the rat testis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 10 34569663
2014 A590T mutation in KCNQ1 C-terminal helix D decreases IKs channel trafficking and function but not Yotiao interaction. Journal of molecular and cellular cardiology 10 24713462
2022 AKAP9-Related Channelopathy: Novel Pathogenic Variant and Review of the Literature. Genes 9 36421840
2013 Centrosomal AKAP350 modulates the G1/S transition. Cellular logistics 9 24475373
2017 Akap350 Recruits Eb1 to The Spindle Poles, Ensuring Proper Spindle Orientation and Lumen Formation in 3d Epithelial Cell Cultures. Scientific reports 7 29097729
2009 Ins(1,4,5)P3 receptor type 1 associates with AKAP9 (AKAP450 variant) and protein kinase A type IIbeta in the Golgi apparatus in cerebellar granule cells. Biology of the cell 7 19236309
2019 Brugada syndrome & AKAP9: Reconciling clinical findings with diagnostic uncertainty. Journal of electrocardiology 5 31654968
2019 CG-NAP/Kinase Interactions Fine-Tune T Cell Functions. Frontiers in immunology 5 31781123
2025 The PDE4DIP-AKAP9 axis promotes lung cancer growth through modulation of PKA signalling. Communications biology 3 39905234
2024 A mutation in the cardiac KV7.1 channel possibly disrupts interaction with Yotiao protein. Biochemical and biophysical research communications 1 38657442
2024 The A-kinase anchoring protein Yotiao decrease the ER calcium content by inhibiting the store operated calcium entry. Cell calcium 1 38781694
2024 Acute myeloid leukemia with a novel AKAP9::PDGFRA fusion transformed from essential thrombocythemia: A case report and mini review. Leukemia research reports 1 38952949
2023 A Novel Variant in AKAP9 Gene, a Controversial Gene, in Long QT Syndrome. Molecular syndromology 1 38585551
2020 AKAP350 enables p150glued /EB1 interaction at the spindle poles. Biochimie 1 32841682
2026 Uterine mesenchymal neoplasm harbouring an AKAP9::BRAF fusion: identification of a novel kinase-driven molecular subset. Virchows Archiv : an international journal of pathology 0 42084735
2025 LncRNA MIR17HG drives cisplatin resistance partially via miR-138-5p/AKAP9 axis in cholangiocarcinoma. Scandinavian journal of gastroenterology 0 39773276
2025 Cryo-EM of AKAP350/AKAP9 Reveals Fibrillar Clusters and an Association With DNA. Journal of molecular biology 0 40154916
2025 Spitz melanocytoma with AKAP9::BRAF fusion: clinicopathologic and molecular insights. Dermatology reports 0 41384713
2024 Brugada syndrome in a patient with AKAP9 mutation: Case report and review of the literature. Journal of electrocardiology 0 39079367
2023 Frequent torsades de pointes in a child with novel AKAP9 mutation: A case report and literature review. Frontiers in pediatrics 0 36699290
2022 Reprogramming of a human induced pluripotent stem cell line (ZZUSAHi004-A) from a long QT syndrome patient with a heterozygous AKAP9 (c. 4021C > A) mutant. Stem cell research 0 36395689

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