Details for: AKAP14

Gene ID: 158798

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: AKAP14

Ensembl ID: ENSG00000186471

Description: A-kinase anchoring protein 14

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • ciliated epithelial cell CL0000067
    CSI 9.91
    rCSI 8.71%
    PRS 98.17
  • ciliated cell CL0000064
    CSI 5.55
    rCSI 8.99%
    PRS 98.05
  • choroid plexus epithelial cell CL0000706
    CSI 5.46
    rCSI 8.94%
    PRS 98.47
  • multi-ciliated epithelial cell CL0005012
    CSI 3.56
    rCSI 3.55%
    PRS 98.65
  • lung ciliated cell CL1000271
    CSI 3.14
    rCSI 3.63%
    PRS 98.68
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 2.48
    rCSI 5.66%
    PRS 98.04
  • deuterosomal cell CL4033044
    CSI 1.26
    rCSI 4.27%
    PRS 97.91

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [AKAP14](/details-gene/158798) (A-Kinase Anchoring Protein 14) is a protein-coding gene located on the X chromosome that encodes a member of the A-kinase anchoring protein (AKAP) family. These proteins are structural scaffolds that bind to the regulatory subunit of protein kinase A (PKA), thereby confining the kinase to specific subcellular locations. Consistent with this function, [AKAP14](/details-gene/158798) is annotated with '[protein kinase a regulatory subunit binding](/details-cell/GO:0034237)' and is a component of the '[axoneme](/details-cell/GO:0005930)', the microtubule-based core of cilia and flagella. Its expression pattern is highly specific to ciliated cell types, suggesting a crucial role in regulating ciliary function through localized PKA signaling. Clinical associations point towards a role in spermatogenesis ([Link](https://omim.org/entry/300462)). ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [AKAP14](/details-gene/158798) demonstrates a highly specialized role in ciliated cells. It is most significantly expressed in '[ciliated epithelial cell](/details-cell/CL0000067)' (CSI: 9.91), '[ciliated cell](/details-cell/CL0000064)' (CSI: 5.55), and '[choroid plexus epithelial cell](/details-cell/CL0000706)' (CSI: 5.46), which are known for their motile cilia. This pattern is reinforced by its high significance in more specific ciliated populations, including '[multi-ciliated epithelial cell](/details-cell/CL0005012)', '[lung ciliated cell](/details-cell/CL1000271)', and '[ciliated columnar cell of tracheobronchial tree](/details-cell/CL0002145)'. Furthermore, its expression in '[deuterosomal cell](/details-cell/CL4033044)' (CSI: 1.26), which are progenitor cells that generate basal bodies for multiciliated cells, suggests that [AKAP14](/details-gene/158798) may be involved early in the process of ciliogenesis. The collective data strongly indicate that [AKAP14](/details-gene/158798) is a key structural and regulatory component of the ciliary machinery across various tissues. ## Pathways and Molecular Function The molecular function of [AKAP14](/details-gene/158798) is centered on its role as a scaffold protein. GO annotations confirm its capacity for '[protein binding](/details-cell/GO:0005515)', specifically '[protein kinase a regulatory subunit binding](/details-cell/GO:0034237)'. By tethering the '[cAMP-dependent protein kinase complex](/details-cell/GO:0005952)' to the '[axoneme](/details-cell/GO:0005930)', [AKAP14](/details-gene/158798) ensures that cAMP-mediated signaling through PKA occurs in close proximity to its ciliary substrates. This localized signaling is critical for the regulation of ciliary and flagellar motility. Research has confirmed the presence of an A-kinase anchoring protein, consistent with [AKAP14](/details-gene/158798), within human ciliary axonemes, supporting its direct role in ciliary function ([Link](https://doi.org/10.1091/mbc.e02-07-0391)). ## Research Directions The highly specific expression and function of [AKAP14](/details-gene/158798) in cilia and flagella provide a clear basis for further investigation, particularly concerning its role in human health and disease. **Proposed Hypotheses:** 1. Loss-of-function mutations in [AKAP14](/details-gene/158798) disrupt PKA localization within the axoneme, leading to impaired phosphorylation of key motor proteins like dynein and resulting in defective ciliary beat frequency or waveform, contributing to respiratory diseases or infertility. 2. [AKAP14](/details-gene/158798) is essential for the structural integrity of the axoneme during ciliogenesis, and its absence in '[deuterosomal cell](/details-cell/CL4033044)' leads to defects in the assembly or elongation of cilia. **Experimental Approach:** To test the first hypothesis regarding ciliary motility, a CRISPR-Cas9 knockout of [AKAP14](/details-gene/158798) could be performed in primary human bronchial epithelial cells cultured at an air-liquid interface to induce differentiation into a ciliated epithelium. Subsequent analysis would involve: * **Immunofluorescence microscopy** to confirm the absence of [AKAP14](/details-gene/158798) protein and assess the mislocalization of PKA subunits within the cilia of knockout cells compared to wild-type controls. * **High-speed video microscopy** to quantify ciliary beat frequency and analyze the waveform of the cilia. * **Phosphoproteomics** to identify downstream PKA substrates in the axoneme whose phosphorylation status is dependent on [AKAP14](/details-gene/158798) anchoring. **Therapeutic Potential:** Given its association with X-linked spermatogenic failure ([OMIM: 300462](https://omim.org/entry/300462)), [AKAP14](/details-gene/158798) is a gene of significant clinical interest for male infertility. As a structural scaffold protein, it is not a conventional target for small-molecule inhibition or activation. However, its high specificity to cilia and flagella makes it a potential candidate for gene-replacement therapies aimed at correcting genetic defects that cause ciliopathies or certain forms of infertility. Furthermore, it could serve as a valuable diagnostic biomarker for assessing ciliary function and integrity in patients with unexplained infertility or chronic respiratory conditions.

Genular Protein ID: 3554219627

Symbol: AKA28_HUMAN

Name: A-kinase anchor protein 14

UniProtKB Accession Codes:

Q86UN6 A6NNZ0 Q86UN4 Q86UN5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 EMBL 5 Ensembl 4 GO 3 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 RNAct 1 RefSeq 3 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 12475942

Title: Characterization of an A-kinase anchoring protein in human ciliary axonemes.

PubMed ID: 12475942

DOI: 10.1091/mbc.e02-07-0391

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

Sequence Information:

  • Length: 197
  • Mass: 22815
  • Checksum: 3A76B9C3036EAEB9
  • Sequence:
    • MSETQNSTSQ KAMDEDNKAA SQTMPNTQDK NYEDELTQVA LALVEDVINY AVKIVEEERN 
PLKNIKWMTH GEFTVEKGLK QIDEYFSKCV SKKCWAHGVE FVERKDLIHS FLYIYYVHWS 
ISTADLPVAR ISAGTYFTMK VSKTKPPDAP IVVSYVGDHQ ALVHRPGMVR FRENWQKNLT 
DAKYSFMESF PFLFNRV