PKIA: cAMP-Dependent Protein Kinase Inhibitor Alpha
A key regulator of PKA signaling with implications in cancer and neurological disorders
Gene Information Card
| Symbol | PKIA |
|---|---|
| Full Name | cAMP-dependent protein kinase inhibitor alpha |
| Gene Type | protein-coding |
| Chromosomal Location | 8q21.11 |
| NCBI Gene ID | 5569 ncbi.nlm.nih.gov/gene/5569 |
| Ensembl ID | ENSG00000171033 |
| UniProt ID | P61925 |
| OMIM ID | 176890 |
| HGNC ID | 9017 |
| Aliases | PKI-alpha, PRKACN1, PKI |
Description
The PKIA gene encodes the alpha isoform of the cAMP-dependent protein kinase inhibitor (PKI), a small heat-stable protein that specifically inhibits the catalytic subunit of PKA (protein kinase A). PKIA binds to the free catalytic subunit of PKA, preventing its nuclear translocation and thereby terminating cAMP-mediated signaling. This gene is involved in the regulation of various cellular processes including metabolism, gene expression, and cell cycle. Dysregulation of PKIA has been implicated in several cancers and neurological conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Altered PKIA expression disrupts PKA signaling, affecting cell proliferation and survival | COSMIC; PMID: 23481258 |
| Neurofibromatosis type 1 | Reduced PKIA expression may contribute to increased PKA activity in NF1-associated tumors | PMID: 19029989 |
| Major depressive disorder | PKIA polymorphisms associated with altered cAMP signaling in the brain | ClinVar; PMID: 21737568 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 9.7 | Low |
| Testis | 15.2 | Medium |
| Skeletal muscle | 4.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.1 | Moderate expression |
| HeLa | 7.8 | Low expression |
| K562 | 5.3 | Low expression |
| MCF7 | 14.6 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | <0.01% | Loss of start codon, likely loss of function |
| c.148C>T (p.Arg50Trp) | missense | <0.01% | Unknown effect, reported in ClinVar |
| c.205G>A (p.Glu69Lys) | missense | <0.01% | Unknown effect, reported in ClinVar |
Mutation functional classification
Loss of Function (LOF)
Mutations leading to premature stop codons or start codon loss are predicted to cause loss of function, reducing PKA inhibition.
Gain of Function (GOF)
No gain-of-function mutations have been reported for PKIA.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for PKIA.
View complete mutation data：
Gene Ontology (GO)
| • cAMP-dependent protein kinase inhibitor activity (GO:0004862) | • protein binding (GO:0005515) |
| • cytoplasm (GO:0005737) | • nucleus (GO:0005634) |
| • signal transduction (GO:0007165) | • regulation of protein kinase A signaling (GO:0010738) |
Pathways
• cAMP/PKA signaling pathway (Reactome: R-HSA-163615)
• PKA-mediated phosphorylation (Reactome: R-HSA-163615)
Protein Summary
PKIA is a 76-amino acid protein that acts as a potent and specific inhibitor of the catalytic subunit of cAMP-dependent protein kinase (PKA). It contains a pseudosubstrate sequence that binds to the active site of PKA, blocking substrate access. PKIA also contains a nuclear export signal that facilitates the export of PKA catalytic subunit from the nucleus, terminating nuclear PKA signaling. The protein is widely expressed, with highest levels in brain and testis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PKIA Knockout HEK293 Cell Line | EDJ-KQ50541 | Human | 5569 | Details Get a Quote |
| PKIA Knockout HeLa Cell Line | EDJ-KQ54209 | Human | 5569 | Details Get a Quote |
| PKIA Knockout A-549 Cell Line | EDJ-KQ62704 | Human | 5569 | Details Get a Quote |
| PKIA Knockout HCT 116 Cell Line | EDJ-KQ71175 | Human | 5569 | Details Get a Quote |
