AKAP3: A-Kinase Anchoring Protein 3
Key regulator of sperm motility and flagellar function
Gene Information Card
| Symbol | AKAP3 |
|---|---|
| Full Name | A-Kinase Anchoring Protein 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 12p13.32 |
| NCBI Gene ID | 10566 ncbi.nlm.nih.gov/gene/10566 |
| Ensembl ID | ENSG00000111254 |
| UniProt ID | O75969 |
| OMIM ID | 604689 |
| HGNC ID | 373 |
| Aliases | PRKA3, AKAP110, FSP95, SOB1 |
Description
AKAP3 encodes a member of the A-kinase anchoring protein (AKAP) family, which functions as a scaffold protein that tethers protein kinase A (PKA) to specific subcellular compartments. It is predominantly expressed in the sperm flagellum and plays a critical role in sperm motility, capacitation, and the structural integrity of the fibrous sheath. AKAP3 also interacts with other signaling molecules, including Rho GTPases and phosphodiesterases, to regulate cAMP-dependent pathways.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Male infertility (asthenozoospermia) | Disruption of AKAP3 leads to impaired sperm flagellar assembly and reduced motility, causing asthenozoospermia. | ClinVar, PubMed |
| Spermatogenic failure | Mutations in AKAP3 are associated with defects in fibrous sheath formation, resulting in severe sperm motility disorders. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 112.5 | High |
| Fallopian tube | 0.8 | Low |
| Prostate | 0.5 | Low |
| Ovary | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Spermatozoa | N/A | High expression in flagellum |
| Testicular germ cells | N/A | Expressed in spermatids and spermatozoa |
| HeLa | 0.1 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1003C>T (p.Arg335*) | Nonsense | Rare | Loss of function; truncated protein disrupts fibrous sheath |
| c.1426G>A (p.Glu476Lys) | Missense | Rare | Altered PKA binding affinity; reduced sperm motility |
| c.1870_1871del (p.Leu624fs) | Frameshift | Rare | Premature termination; loss of anchoring function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg335*, p.Leu624fs) result in truncated or absent AKAP3 protein, impairing fibrous sheath integrity and sperm motility.
Gain of Function (GOF)
No gain-of-function mutations have been reported for AKAP3.
Dominant Negative (DN)
No dominant-negative mutations have been characterized; AKAP3 mutations are typically recessive.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005515 - protein binding | • GO:0005737 - cytoplasm |
| • GO:0005856 - cytoskeleton | • GO:0005929 - cilium |
| • GO:0019904 - protein domain specific binding | • GO:0030030 - cell projection organization |
| • GO:0030672 - synaptic vesicle membrane | • GO:0036126 - sperm flagellum |
| • GO:0048471 - perinuclear region of cytoplasm | • GO:0051015 - actin filament binding |
Pathways
• cAMP/PKA signaling pathway
• Sperm motility and capacitation
• Fibrous sheath assembly
Protein Summary
AKAP3 is a 110 kDa protein localized to the fibrous sheath of the sperm flagellum. It contains an N-terminal targeting domain that anchors it to the cytoskeleton and a C-terminal PKA-binding domain (RII-binding motif). AKAP3 also interacts with other proteins such as AKAP4, PDE4A, and RhoA to coordinate cAMP signaling and flagellar movement. Its expression is testis-specific, and loss of function leads to severe asthenozoospermia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AKAP3 Knockout HEK293 Cell Line | EDJ-KQ7093 | Human | 10566 | Details Get a Quote |
| AKAP3 Knockout HCT 116 Cell Line | EDJ-KQ31938 | Human | 10566 | Details Get a Quote |
| AKAP3 Knockout HeLa Cell Line | EDJ-KQ55431 | Human | 10566 | Details Get a Quote |
| AKAP3 Knockout A-549 Cell Line | EDJ-KQ63912 | Human | 10566 | Details Get a Quote |
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