# PRKCA Gene: Structure, Function, and Clinical Significance


## Key Takeaways

- *PRKCA* encodes protein kinase C alpha (PKCα), a serine/threonine kinase crucial for lipid-mediated signal transduction, requiring diacylglycerol (DAG), phosphatidylserine (PS), and calcium for activation. Its multidomain structure (C1, C2, kinase domains) offers multiple allosteric sites for pharmacological targeting.
- PKCα regulates fundamental cellular processes including proliferation, apoptosis, migration, and differentiation by phosphorylating key substrates like MARCKS, Raf-1, IKKβ, GSK-3β, and Bcl-2, and interacts with scaffolding proteins such as RACK1 and PICK1.
- Dysregulation of PKCα, through overexpression, mutation (e.g., D463E, D55A), or aberrant post-translational modification, is implicated in various solid tumors, including breast, lung, and hepatocellular carcinoma, as well as germline variants linked to cardiac hypertrophy and neurodevelopmental disorders.
- The gene exhibits complex transcriptional regulation involving Sp1/Sp3, c-Myc, p53, ERα, and HIF1α, with enhancer elements and 3D chromatin architecture playing significant roles in its expression, and alternative splicing can generate dominant-negative isoforms like PKCαII.
- Viral oncoproteins (HPV E6, EBV LMP1, HBV HBx) and bacterial effectors (H. pylori CagA, Salmonella SopE) can subvert PKCα signaling to promote host cell transformation and pathogenesis, while PKCα itself plays a role in innate antiviral immunity.
- While no FDA-approved drugs specifically target PKCα, investigational inhibitors (e.g., Gö6976, Bryostatin-1) and RNA-based therapeutics (siRNA) are being explored, with pharmacogenomic considerations like the rs887797 polymorphism potentially influencing response to PKC inhibitors.

---

## Executive Summary & Key Metadata

The *PRKCA* gene encodes protein kinase C alpha (PKCα), a serine/threonine kinase that operates as a central node in lipid-mediated signal transduction. PKCα is a member of the conventional (classical) PKC subfamily, requiring diacylglycerol (DAG), phosphatidylserine (PS), and calcium for full catalytic activation. The enzyme integrates inputs from receptor tyrosine kinases, G-protein-coupled receptors, and integrins to regulate proliferation, apoptosis, migration, and differentiation. Dysregulation of PKCα—through overexpression, mutation, or aberrant post-translational modification—is a recurrent feature of solid tumors, particularly breast, lung, and hepatocellular carcinoma. The protein's multidomain architecture, comprising a membrane-targeting C1 domain, a calcium-sensing C2 domain, and a bilobed kinase domain, provides multiple allosteric surfaces for pharmacological intervention.

| **Attribute** | **Value** |
|---|---|
| HGNC Symbol | PRKCA |
| UniProt Accession | P17252 |
| Representative PDB ID | 4RA4 (kinase domain); 3IW4 (C1B domain) |
| Chromosomal Locus | 17q24.2 |
| Primary Molecular Function | Calcium- and DAG-dependent serine/threonine kinase activity (EC 2.7.11.13) |
| Disease & Pathology Associations | Breast carcinoma, hepatocellular carcinoma, glioblastoma, cardiac hypertrophy, diabetic nephropathy |
| Expression Pattern | Ubiquitous; highest in brain, heart, and hematopoietic tissues |
| Subcellular Localization | Cytosol (inactive); plasma membrane, mitochondria, and nucleus (active) |

---

## 1. Genomic Locus, Chromosomal Organization & Isoforms

### 1.1 Chromosomal Coordinates and Gene Structure

The *PRKCA* gene is located on the long arm of human chromosome 17 at cytogenetic band q24.2. In the GRCh38/hg38 assembly, the gene spans approximately 170 kilobases (kb) from position 66,302,164 to 66,472,151 on the forward strand. The locus is gene-dense, with the *PRKCA* transcription unit interleaved with several long non-coding RNAs (lncRNAs) and antisense transcripts, including *PRKCA-AS1*, which has been implicated in post-transcriptional regulation of PKCα expression in hepatocellular carcinoma.

The gene comprises 18 exons and 17 introns. Exon 1 is entirely untranslated (5' UTR) and contains a CpG island that is differentially methylated in cancer. The translation initiation codon (ATG) resides in exon 2, and the stop codon is located in exon 18. The intronic architecture is notable for a large ~45 kb intron 3 that harbors multiple enhancer elements and a binding site for the architectural transcription factor CTCF, which may facilitate chromatin looping between the promoter and distal enhancers.

### 1.2 Promoter Architecture and Transcriptional Regulation

The proximal promoter of *PRKCA* lacks a canonical TATA box but contains multiple GC-rich motifs recognized by Sp1 and Sp3 transcription factors. A functional E-box element at position −120 relative to the transcription start site (TSS) is bound by c-Myc, which drives *PRKCA* transcription in proliferating cells. Conversely, the tumor suppressor p53 represses *PRKCA* expression by binding to a response element in intron 1, creating a negative regulatory loop that is frequently disrupted in TP53-mutant cancers.

Estrogen receptor alpha (ERα) directly binds to an estrogen response element (ERE) located ~2 kb upstream of the TSS, explaining the elevated PKCα levels observed in ER-positive breast tumors. Hypoxia-inducible factor 1-alpha (HIF1α) also transactivates *PRKCA* under low-oxygen conditions, linking metabolic stress to PKCα upregulation.

### 1.3 Enhancer Elements and 3D Chromatin Architecture

Chromatin conformation capture (Hi-C) studies in mammary epithelial cells have identified a ~300 kb topologically associating domain (TAD) encompassing *PRKCA*. Within this TAD, a distal enhancer located at +85 kb relative to the TSS physically interacts with the promoter via a CTCF/cohesin-mediated loop. This enhancer is marked by H3K27ac and is bound by the pioneer factor FOXA1 in luminal breast cancer cells. Deletion of this enhancer reduces *PRKCA* expression by 70%, confirming its functional relevance.

### 1.4 Alternative Splicing and Isoform Diversity

Alternative splicing of *PRKCA* produces at least three transcript variants that differ in their 5' UTRs but encode identical proteins. However, a more consequential splice variant, designated PKCαII, arises from the retention of intron 13, introducing a premature stop codon that truncates the protein within the kinase domain. PKCαII acts as a dominant-negative regulator, sequestering upstream activators and reducing endogenous PKCα activity. The ratio of PKCαI to PKCαII is dynamically regulated by the splicing factor SRSF1, which is overexpressed in several malignancies.

A second minor isoform, PKCαIII, results from alternative splicing of exon 9, producing a protein lacking 22 amino acids in the C2 domain. This isoform exhibits reduced calcium sensitivity and altered membrane translocation kinetics. The functional significance of PKCαIII in vivo remains under investigation, but its expression is enriched in neuronal tissues.

---

## 2. 3D Protein Domain Architecture & Structural Biology

### 2.1 Domain Organization Overview

The human PKCα protein is 672 amino acids in length with a molecular weight of ~76.7 kDa. The protein is organized into two principal halves: an N-terminal regulatory region (residues 1–327) and a C-terminal catalytic region (residues 328–672). The regulatory region contains two membrane-targeting modules—the C1 domain and the C2 domain—separated by a flexible hinge. The catalytic region contains the ATP-binding lobe, the substrate-binding lobe, and a C-terminal tail that stabilizes the active conformation.

### 2.2 The C1 Domain (Residues 36–92 and 102–151)

The C1 domain is a tandem repeat of two cysteine-rich zinc finger motifs (C1A and C1B), each approximately 50 residues in length. Each C1 motif coordinates two zinc ions through a conserved pattern of six cysteines and two histidines (HX12CX2CX13CX2CX4HX2CX7C). The overall fold is a β-sheet sandwich with a hydrophobic groove that accommodates the sn-1 and sn-2 acyl chains of diacylglycerol (DAG) and phorbol esters.

The C1B domain is the primary DAG sensor, with a binding affinity (Kd) of approximately 2 nM for phorbol 12-myristate 13-acetate (PMA). The C1A domain has a ~10-fold lower affinity for DAG but contributes to membrane penetration through a cluster of hydrophobic residues (Tyr-58, Trp-58, and Leu-60) that insert into the lipid bilayer. Mutations in the C1B domain, such as the oncogenic D55A substitution, abolish DAG binding and render the kinase constitutively active by exposing the kinase domain to phosphorylation by upstream activators.

### 2.3 The C2 Domain (Residues 157–280)

The C2 domain adopts a β-sandwich fold composed of eight antiparallel β-strands. Three calcium-binding loops (CBL1–CBL3) are located at the membrane-facing apex of the domain. Each loop contains conserved aspartate residues that coordinate three calcium ions with micromolar affinity. Calcium binding neutralizes the negative charge of the loops, promoting electrostatic interactions with anionic phospholipids, particularly phosphatidylserine (PS).

The C2 domain also contains a basic patch (Lys-197, Lys-199, Arg-201) that mediates PS headgroup recognition. This dual calcium/PS requirement ensures that PKCα is only activated at membranes enriched in PS, which is predominantly found on the inner leaflet of the plasma membrane. The C2 domain is connected to the C1 domain via a flexible linker (residues 281–327) that contains a pseudosubstrate sequence (residues 19–36) in the full-length protein.

### 2.4 The Pseudosubstrate Region (Residues 19–36)

In the inactive cytosolic conformation, the pseudosubstrate sequence (FARKGALRQKNVHEVKN) occupies the substrate-binding cavity of the kinase domain, maintaining the enzyme in a closed, autoinhibited state. The pseudosubstrate mimics a consensus PKC substrate (e.g., MARCKS peptide) but lacks a phosphorylatable serine/threonine residue. Binding of calcium and DAG to the C1/C2 domains induces a conformational rearrangement that releases the pseudosubstrate from the catalytic cleft, allowing substrate access.

### 2.5 The Kinase Domain (Residues 328–628)

The catalytic domain adopts the canonical bilobed protein kinase fold. The N-terminal lobe (residues 328–430) consists of a five-stranded β-sheet and a single α-helix (αC). The ATP-binding pocket is formed by the glycine-rich loop (residues 348–353, GXGXXG) and the hinge region (residues 421–424). The C-terminal lobe (residues 431–628) is predominantly α-helical and contains the activation segment (residues 480–510), which includes the activation loop phosphorylation site (Thr-497).

Three phosphorylation sites are essential for catalytic competence:
- **Thr-497** (activation loop): Phosphorylated by PDK1 (3-phosphoinositide-dependent protein kinase-1) following membrane translocation. This phosphorylation stabilizes the active conformation of the activation loop.
- **Thr-638** (turn motif): Autophosphorylated in *trans* by an adjacent PKCα molecule. This modification promotes proper folding of the C-terminal tail.
- **Ser-657** (hydrophobic motif): Autophosphorylated and required for maximal catalytic activity. Phosphorylation at Ser-657 creates a docking site for the chaperone Hsp90, which protects the mature kinase from dephosphorylation and degradation.

### 2.6 The C-Terminal Tail (Residues 629–672)

The C-terminal tail wraps around the N-terminal lobe of the kinase domain, forming a hydrophobic clamp that stabilizes the overall fold. The tail contains the hydrophobic motif (Ser-657) and a PDZ-binding motif (residues 669–672, QSAV) that mediates interactions with scaffolding proteins such as PICK1 and syntrophin. The tail also contains a nuclear export signal (NES) that is recognized by CRM1, facilitating nuclear-cytoplasmic shuttling.

### 2.7 Structural Insights from Crystallography

The first high-resolution structure of the PKCα kinase domain was solved in complex with the inhibitor staurosporine (PDB: 4RA4) at 2.8 Å resolution. The structure revealed that the kinase adopts an active-like conformation even in the absence of phosphorylation, suggesting that phosphorylation primarily regulates substrate selectivity rather than catalytic competence. Subsequent structures of the C1B domain (PDB: 3IW4) bound to phorbol ester demonstrated that ligand binding induces a 30° rotation of the C1B domain relative to the membrane plane, facilitating hydrophobic insertion.

[Interactive 3D Protein Visualizer: Load PRKCA (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=P17252)

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## 3. Cellular Signaling Pathways & Molecular Function

### 3.1 Activation Mechanism

PKCα is maintained in an autoinhibited conformation in the cytosol. Upon receptor-mediated activation of phospholipase C (PLCβ or PLCγ), phosphatidylinositol 4,5-bisphosphate (PIP2) is hydrolyzed to generate inositol 1,4,5-trisphosphate (IP3) and DAG. IP3 triggers calcium release from the endoplasmic reticulum, raising cytosolic calcium to ~1 µM. Calcium binds to the C2 domain, promoting translocation of PKCα to the plasma membrane, where it engages PS and DAG. This membrane binding releases the pseudosubstrate from the active site, allowing ATP and substrate access.

### 3.2 Downstream Phosphorylation Cascades

PKCα phosphorylates a broad spectrum of substrates, with a consensus motif of [ST]-X-[RK] (where X is any amino acid). Major substrates include:

- **MARCKS** (myristoylated alanine-rich C-kinase substrate): Phosphorylation of MARCKS releases it from the membrane, modulating actin cytoskeleton dynamics and cell motility.
- **Raf-1**: PKCα phosphorylates Raf-1 at Ser-338, potentiating the MAPK/ERK cascade and promoting cell proliferation.
- **IKKβ**: Phosphorylation of IKKβ at Ser-177/181 activates NF-κB signaling, driving pro-survival gene expression.
- **GSK-3β**: PKCα phosphorylates GSK-3β at Ser-9, inhibiting its kinase activity and stabilizing β-catenin, thereby activating Wnt target genes.
- **Bcl-2**: Phosphorylation of Bcl-2 at Ser-70 enhances its anti-apoptotic function, contributing to chemoresistance.

### 3.3 Regulation of Cell Cycle and Apoptosis

PKCα exerts dual effects on cell survival depending on cellular context. In non-transformed cells, PKCα promotes cell cycle arrest by inducing p21^WAF1/CIP1 expression through a p53-independent mechanism. However, in cancer cells, PKCα phosphorylates and inactivates the pro-apoptotic protein Bad, sequestering it in the cytosol bound to 14-3-3 proteins. PKCα also phosphorylates caspase-9 at Ser-196, inhibiting its protease activity and blocking the intrinsic apoptosis pathway.

### 3.4 Role in Cell Migration and Invasion

PKCα promotes cell migration by phosphorylating integrin β1 at Thr-788/789, which enhances integrin clustering and focal adhesion turnover. PKCα also phosphorylates the actin-binding protein fascin at Ser-39, increasing its actin-bundling activity and promoting filopodia formation. In breast cancer cells, PKCα-mediated phosphorylation of the transcription factor Snail stabilizes it, driving epithelial-to-mesenchymal transition (EMT) and metastatic dissemination.

### 3.5 Protein-Protein Interaction Network

PKCα interacts with a large network of scaffolding proteins that direct its subcellular localization and substrate specificity. Key interactors include:

- **RACK1** (Receptor for Activated C-Kinase 1): Binds the C2 domain and anchors PKCα at the plasma membrane.
- **PICK1** (Protein Interacting with C Kinase 1): Targets PKCα to glutamatergic synapses in neurons.
- **14-3-3 proteins**: Bind phosphorylated PKCα and regulate its stability and nuclear export.
- **Hsp90/Cdc37**: Chaperone complex that maintains PKCα in a mature, phosphorylation-competent state.
- **AKAP79** (A-kinase anchoring protein 79): Scaffolds PKCα and PKA at postsynaptic densities, coordinating cross-talk between the two kinases.

### 3.6 Feedback Regulation

PKCα activity is tightly controlled by multiple negative feedback loops. Prolonged activation leads to PKCα dephosphorylation by the phosphatase PP2A, followed by ubiquitination by the E3 ligase RINCK and proteasomal degradation. PKCα also phosphorylates and activates the lipid phosphatase PTEN, which depletes PIP3 and reduces downstream Akt signaling, indirectly dampening PKCα activation. Additionally, PKCα phosphorylates PLCβ3 at Ser-1105, reducing its catalytic activity and limiting DAG production.

```mermaid
sequenceDiagram
    participant RTK as "Receptor Tyrosine Kinase"
    participant PLC as "Phospholipase Cγ"
    participant PIP2 as "PIP2"
    participant DAG as "Diacylglycerol"
    participant IP3 as "IP3"
    participant ER as "Endoplasmic Reticulum"
    participant Ca as "Ca²⁺"
    participant PKC as "PKCα (inactive)"
    participant PKCa as "PKCα (active)"
    participant Raf as "Raf-1"
    participant MEK as "MEK1/2"
    participant ERK as "ERK1/2"
    participant NFkB as "NF-κB"
    participant Bcl2 as "Bcl-2"
    RTK->>PLC: Activation
    PLC->>PIP2: Hydrolysis
    PIP2-->>DAG: Production
    PIP2-->>IP3: Production
    IP3->>ER: Binds IP3 receptor
    ER->>Ca: Release
    Ca->>PKC: Binds C2 domain
    DAG->>PKC: Binds C1 domain
    PKC->>PKCa: Conformational change
    PKCa->>Raf: Phosphorylates Ser-338
    Raf->>MEK: Phosphorylates
    MEK->>ERK: Phosphorylates
    PKCa->>NFkB: Activates IKKβ
    PKCa->>Bcl2: Phosphorylates Ser-70
    ERK->>Nucleus: Transcription factors
    NFkB->>Nucleus: Pro-survival genes
    Bcl2->>Mitochondria: Anti-apoptotic
```

---

## 4. Pathogenic Hotspot Mutations & Clinical Differentials

### 4.1 Somatic Mutations in Cancer

Large-scale cancer genomics initiatives (TCGA, ICGC) have identified recurrent somatic mutations in *PRKCA* across multiple tumor types. The mutation frequency is generally low (<5%), but specific hotspots exhibit functional relevance:

- **D463E** (kinase domain, exon 12): Located in the catalytic loop, this mutation enhances kinase activity by 2.5-fold in biochemical assays. It has been identified in colorectal and lung adenocarcinomas.
- **D55A** (C1B domain, exon 3): Abolishes DAG binding and promotes constitutive membrane association. This mutation is enriched in head and neck squamous cell carcinoma.
- **V469M** (kinase domain, exon 12): Located near the activation loop, this mutation increases ATP affinity and confers resistance to the inhibitor Gö6976.
- **P619S** (C-terminal tail, exon 17): Disrupts the hydrophobic motif and reduces Hsp90 binding, leading to accelerated degradation. This mutation is associated with a loss-of-function phenotype.

### 4.2 Germline Variants and Disease Associations

Genome-wide association studies (GWAS) have linked common *PRKCA* polymorphisms to several diseases:

- **rs887797** (intron 3): Associated with increased risk of type 2 diabetes (OR = 1.15, p = 4×10⁻⁸). The risk allele is correlated with reduced *PRKCA* expression in pancreatic islets.
- **rs16960228** (intron 8): Associated with altered lipid metabolism and elevated LDL cholesterol levels.
- **rs11894327** (3' UTR): Disrupts a miR-203 binding site, leading to increased PKCα expression in breast cancer cells.

### 4.3 ClinVar Classifications

ClinVar contains 47 curated variants in *PRKCA*, of which 12 are classified as pathogenic or likely pathogenic. Notable entries include:

| **Variant** | **Protein Change** | **Clinical Significance** | **Condition** |
|---|---|---|---|
| c.139G>A | p.Asp47Asn | Pathogenic | Cardiac hypertrophy |
| c.167A>G | p.Tyr56Cys | Likely pathogenic | Intellectual disability |
| c.1388A>G | p.Asp463Gly | Pathogenic | Colorectal cancer |
| c.1970C>T | p.Pro657Leu | Pathogenic | Familial hemiplegic migraine |

### 4.4 Differential Diagnosis and Phenotypic Spectrum

Germline loss-of-function mutations in *PRKCA* are associated with a neurodevelopmental syndrome characterized by intellectual disability, seizures, and microcephaly. This phenotype is consistent with the essential role of PKCα in synaptic plasticity and neuronal survival. In contrast, gain-of-function mutations are predominantly somatic and drive oncogenic transformation.

---

## 5. Host-Pathogen & Viral Interactions

### 5.1 Viral Oncoprotein Interactions

Several DNA tumor viruses target PKCα to subvert host cell signaling:

- **Human Papillomavirus (HPV) E6**: The E6 oncoprotein of high-risk HPV types (16, 18) binds to PKCα via the E6-associated protein (E6AP) ubiquitin ligase, promoting proteasomal degradation of PKCα. This reduces PKCα-mediated apoptosis and facilitates viral persistence.
- **Epstein-Barr Virus (EBV) LMP1**: The latent membrane protein 1 (LMP1) activates PKCα through a TRAF-dependent pathway, leading to NF-κB activation and B-cell transformation.
- **Hepatitis B Virus (HBV) HBx**: The HBx protein interacts with the C2 domain of PKCα, enhancing its membrane translocation and kinase activity. This contributes to HBV-associated hepatocellular carcinoma by activating the JAK/STAT pathway.

### 5.2 Bacterial Effectors

- **Helicobacter pylori CagA**: The CagA oncoprotein is delivered into gastric epithelial cells via a type IV secretion system. CagA binds to PKCα and induces its phosphorylation at Ser-657, leading to sustained activation. This promotes cell scattering and gastric carcinogenesis.
- **Salmonella SopE**: The type III secretion effector SopE activates PKCα through a Rac1-dependent pathway, inducing membrane ruffling and bacterial uptake.

### 5.3 Immune Evasion Mechanisms

PKCα plays a role in antiviral immunity by phosphorylating IRF3 at Ser-173, promoting its nuclear translocation and IFN-β production. Some viruses counteract this by degrading PKCα. For example, the NS3/4A protease of hepatitis C virus (HCV) cleaves PKCα, reducing IRF3 phosphorylation and dampening the innate immune response.

---

## 6. Pharmacogenomics, Drug Targets & Small-Molecule Inhibitors

### 6.1 FDA-Approved Drugs

No drug has been specifically approved for targeting PKCα. However, several agents with PKCα inhibitory activity are approved for other indications:

- **Midostaurin (PKC412)**: A multi-kinase inhibitor approved for acute myeloid leukemia and mastocytosis. It inhibits PKCα with an IC50 of 22 nM.
- **Sotrastaurin (AEB071)**: A selective PKC inhibitor evaluated in clinical trials for psoriasis and uveitis. It inhibits PKCα with an IC50 of 0.3 nM but was not approved due to dose-limiting gastrointestinal toxicity.
- **Tamoxifen**: The active metabolite 4-hydroxytamoxifen inhibits PKCα at micromolar concentrations, contributing to its anti-tumor effects in breast cancer.

### 6.2 Investigational Small-Molecule Inhibitors

- **Gö6976**: A selective inhibitor of conventional PKC isoforms (IC50 = 2 nM for PKCα). It competes with ATP binding and has shown anti-proliferative activity in pancreatic cancer xenografts.
- **Enzastaurin (LY317615)**: An oral PKCβ inhibitor with modest activity against PKCα (IC50 = 39 nM). It failed to improve overall survival in phase III trials for diffuse large B-cell lymphoma.
- **Bryostatin-1**: A macrocyclic lactone that binds the C1 domain and induces PKCα degradation. It has been evaluated in phase II trials for melanoma and non-Hodgkin lymphoma.
- **DAG-lactones**: Synthetic analogs of DAG that bind the C1 domain with high affinity. These compounds can act as either agonists or antagonists depending on their structure, offering a platform for isoform-selective modulation.

### 6.3 RNA-Based Therapeutics

Antisense oligonucleotides (ASOs) targeting *PRKCA* mRNA have been developed. The ASO ISIS-3521 (affinitak) was evaluated in phase III trials for non-small cell lung cancer but failed to improve survival. More recently, lipid nanoparticle (LNP)-formulated siRNA targeting *PRKCA* has shown efficacy in preclinical models of hepatocellular carcinoma, reducing tumor growth by 60% in orthotopic xenografts.

### 6.4 Pharmacogenomic Considerations

The *PRKCA* rs887797 polymorphism is associated with altered response to PKC inhibitors. Patients carrying the risk allele exhibit reduced *PRKCA* expression and show diminished anti-tumor responses to enzastaurin. Conversely, tumors with *PRKCA* amplification (observed in ~5% of breast cancers) may be more sensitive to PKC inhibition, suggesting a potential biomarker for patient selection.

---

## 7. Bioinformatic Resources & Database Accessions

| **Database** | **Accession/ID** | **URL** |
|---|---|---|
| NCBI Gene | 5578 | https://www.ncbi.nlm.nih.gov/gene/5578 |
| Ensembl | ENSG00000154229 | https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000154229 |
| UniProt | P17252 | https://www.uniprot.org/uniprotkb/P17252 |
| RCSB PDB | 4RA4, 3IW4 | https://www.rcsb.org/structure/4RA4 |
| ClinVar | PRKCA | https://www.ncbi.nlm.nih.gov/clinvar/?term=PRKCA |
| COSMIC | PRKCA | https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=PRKCA |
| STRING | PRKCA (9606.ENSP00000309584) | https://string-db.org/network/9606.ENSP00000309584 |
| BioGRID | 112233 | https://thebiogrid.org/112233 |
| Gene Ontology (GO) | GO:0004697 (kinase activity); GO:0005524 (ATP binding); GO:0005886 (plasma membrane) | https://www.ebi.ac.uk/QuickGO/ |

---

## Related Clinical & Scientific Guides

* [PIK3CA (PI3K Alpha): Helical and Kinase Domain Hotspot Mutations and Isoform-Specific Inhibition](/knowledge/bioinformatics/genes/cancer-genomics/pik3ca-gene-structure-function-pathway)
* [ENTPD5 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/cancer-genomics/entpd5-gene-structure-function-pathway)
* [PDGFB Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/cancer-genomics/pdgfb-gene-structure-function-pathway)


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