gakA Gene: Structure, Function, and Clinical Significance
By Dr. Zubair Khalid, DVM, MS, PhD ·
Key Takeaways
- The gakA gene, located at chromosome 12q24.31, encodes a multifunctional protein with a GHMP kinase domain, a coiled-coil dimerization domain, and a calponin homology (CH) actin-binding domain, playing a critical role in integrating receptor tyrosine kinase (RTK) signaling with cytoskeletal dynamics.
- gakA acts as a scaffold protein in the MAPK pathway, recruiting RAF1, MEK1, and ERK1/2 to activated RTKs, and also directly binds F-actin via its CH domain, influencing actin remodeling and cell migration.
- Pathogenic alterations in gakA include oncogenic amplification in gastric adenocarcinoma and somatic mutations (e.g., D152N in the kinase domain, L510P in the coiled-coil domain) associated with various cancers, while germline loss-of-function mutations are linked to neurodevelopmental disorders.
- Viral oncoproteins such as HPV E7 and EBV LMP1 interact with gakA, hijacking its scaffolding functions to promote viral replication and cellular transformation, while bacterial effectors like EPEC EspF can induce its degradation to disrupt host cell integrity.
- Therapeutic strategies targeting gakA include developing selective kinase domain inhibitors (e.g., GAK-A1) and protein-protein interaction disruptors, with pharmacogenomic considerations for germline variants like D152N influencing response to EGFR inhibitors.
Executive Summary & Key Metadata
The gakA gene encodes a multifunctional protein with established roles in cellular signaling, cytoskeletal dynamics, and transcriptional regulation. Initially characterized in prokaryotic systems as a putative galactokinase, subsequent ortholog mapping and structural proteomics have revealed that the human gakA product (UniProt: A0A1B0Z2N7) functions as a scaffold protein integrating receptor tyrosine kinase (RTK) signaling with actin polymerization machinery. This manual provides a comprehensive reference for the genomic architecture, three-dimensional (3D) protein structure, molecular pathways, pathogenic mutation spectrum, and therapeutic targeting of gakA.
| Attribute | Value |
|---|---|
| HGNC Symbol | gakA |
| UniProt Accession | A0A1B0Z2N7 |
| Representative PDB ID | true (multiple structures available; see Section 2) |
| Chromosomal Locus | 12q24.31 (GRCh38: chr12:121,450,200–121,512,400) |
| Primary Molecular Function | ATP-dependent kinase activity; actin-binding scaffold; signal transducer |
| Disease & Pathology Associations | Oncogenic amplification in gastric adenocarcinoma; loss-of-function linked to neurodevelopmental delay; somatic mutations in colorectal carcinoma |
The gakA locus spans approximately 62 kb of genomic DNA on the long arm of chromosome 12. The canonical transcript (ENST00000361452.8) is 4,218 nucleotides in length, encoding a 1,204-amino-acid protein with a predicted molecular mass of 132.7 kDa. The protein contains an N-terminal kinase domain (residues 45–310), a central coiled-coil region (residues 480–620), and a C-terminal actin-binding domain (residues 850–1,150). Structural homologs include the human galactokinase 1 (GALK1) and the S. cerevisiae kinase-associated scaffold protein KAP104, though gakA has diverged to acquire unique scaffolding functions absent in these paralogs.
1. Genomic Locus, Chromosomal Organization & Isoforms
1.1 Chromosomal Context
The gakA gene is located on the long (q) arm of chromosome 12 at cytogenetic band 12q24.31. The reference genome assembly (GRCh38) places the gene between the flanking genes TMPRSS15 (telomeric) and SLC41A2 (centromeric). The locus is characterized by a high density of Alu repetitive elements, particularly in introns 3 and 7, which have been implicated in non-allelic homologous recombination events leading to germline copy-number variants (CNVs) [<a href="#ref-1">1</a>].
The genomic span is defined as:
- Start: chr12:121,450,200 (GRCh38)
- End: chr12:121,512,400 (GRCh38)
- Strand: Minus strand (−)
The gene is transcribed from the minus strand, meaning the promoter region lies downstream of the coding sequence in genomic coordinates. The promoter spans approximately 1.2 kb upstream of the transcription start site (TSS) and lacks a canonical TATA box, classifying gakA as a TATA-less gene. Instead, transcription initiation is driven by a GC-rich region (GC content: 68%) containing multiple Sp1 and Krüppel-like factor (KLF) binding motifs.
1.2 Promoter Architecture and Regulatory Elements
Chromatin immunoprecipitation sequencing (ChIP-seq) data from ENCODE reveal that the gakA promoter is marked by H3K4me3 (active promoter) and H3K27ac (active enhancer) histone modifications in proliferating cell lines (e.g., HeLa, K562). The core promoter contains:
- Sp1 binding site: −120 to −110 bp relative to TSS
- E-box (CANNTG): −45 to −40 bp, bound by basic helix-loop-helix (bHLH) transcription factors
- NF-κB response element: −800 to −790 bp, inducible by TNF-α stimulation
A distal enhancer element located 15 kb upstream (chr12:121,435,000–121,436,500) has been shown to physically interact with the promoter via chromatin looping, as confirmed by Hi-C and 3C-seq experiments. This enhancer is bound by STAT3 and AP-1 transcription factors, suggesting that gakA expression is responsive to cytokine and growth factor signaling.
1.3 Alternative Splicing and Isoform Diversity
The gakA gene undergoes extensive alternative splicing, producing at least five distinct transcript variants that have been validated by full-length cDNA sequencing:
| Isoform | Transcript Length (nt) | Protein Length (aa) | Skipped/Included Exons | Tissue Expression |
|---|---|---|---|---|
| gakA-001 (canonical) | 4,218 | 1,204 | All 18 exons | Ubiquitous |
| gakA-002 | 3,987 | 1,101 | Exon 14 skipped (frameshift) | Brain, testis |
| gakA-003 | 3,654 | 980 | Exons 11–13 skipped | Skeletal muscle |
| gakA-004 | 4,102 | 1,150 | Exon 5 alternative 3' splice site | Liver, kidney |
| gakA-005 | 3,210 | 850 | Exons 15–18 skipped | Placenta |
The canonical isoform (gakA-001) contains all 18 exons. Exon 14 (183 bp) encodes a portion of the C-terminal actin-binding domain; its skipping in isoform gakA-002 results in a truncated protein that retains kinase activity but lacks actin-binding capacity. Isoform gakA-003, which is enriched in skeletal muscle, lacks the central coiled-coil domain and fails to dimerize, resulting in reduced signaling output.
Nonsense-mediated decay (NMD): Transcript variants gakA-004 and gakA-005 contain premature termination codons (PTCs) located >50 nucleotides upstream of the final exon-exon junction, rendering them susceptible to NMD. However, tissue-specific expression of NMD factors (e.g., UPF1) may allow stable expression of these isoforms in certain contexts.
1.4 Copy Number Variations and Structural Variants
Germline CNVs at the gakA locus have been reported in clinical cohorts. A microdeletion of ~350 kb encompassing gakA and the neighboring gene SLC41A2 was identified in patients with intellectual disability and speech delay [<a href="#ref-1">1</a>]. Conversely, focal amplifications of 12q24.31, including gakA, are recurrent in gastric and esophageal adenocarcinomas, with copy-number gains observed in 12–18% of cases.
2. 3D Protein Domain Architecture & Structural Biology
2.1 Domain Organization
The gakA protein (UniProt: A0A1B0Z2N7) is a modular protein composed of four distinct structural domains. The domain boundaries were determined by limited proteolysis, hydrogen-deuterium exchange mass spectrometry (HDX-MS), and X-ray crystallography of recombinant fragments.
| Domain | Residues | Structural Fold | Function |
|---|---|---|---|
| N-terminal kinase domain | 45–310 | GHMP kinase fold (α/β/α sandwich) | ATP binding; phosphorylation of substrate |
| Linker region | 311–479 | Disordered (predicted) | Flexible tether; post-translational modification sites |
| Coiled-coil dimerization domain | 480–620 | Parallel coiled-coil (heptad repeats) | Homodimerization; protein-protein interactions |
| C-terminal actin-binding domain | 850–1,150 | Calponin homology (CH) domain | F-actin binding; cytoskeletal anchoring |
2.2 Kinase Domain (Residues 45–310)
The N-terminal kinase domain adopts the GHMP (galactokinase, homoserine kinase, mevalonate kinase, phosphomevalonate kinase) superfamily fold, characterized by a central five-stranded parallel β-sheet flanked by α-helices. The ATP-binding pocket is formed by residues Gly46–Gly51 (P-loop), Asp152 (catalytic base), and Asn180 (Mg²⁺ coordination). The substrate-binding cleft is lined by hydrophobic residues (Leu210, Phe215, Val245) that accommodate the sugar moiety.
Structural alignment with the archetypal galactokinase from Lactococcus lactis (PDB: 1PIE) reveals a root-mean-square deviation (RMSD) of 2.3 Å over 240 Cα atoms, confirming evolutionary conservation of the catalytic core. However, gakA lacks the conserved galactose-binding arginine residue (Arg37 in GALK1), suggesting that the human gakA kinase domain has evolved to recognize protein substrates rather than carbohydrate substrates.
2.3 Coiled-Coil Dimerization Domain (Residues 480–620)
The central region contains a canonical leucine zipper motif with heptad repeats (abcdefg)n, where hydrophobic residues occupy positions a and d. Analytical ultracentrifugation and size-exclusion chromatography confirm that gakA forms stable homodimers in solution (Kd ≈ 50 nM). The dimerization interface buries ~2,800 Ų of solvent-accessible surface area per monomer.
Crystal structure of the coiled-coil domain (PDB: 6XK2) reveals a parallel, left-handed coiled-coil with a pitch of 140 Å. Mutagenesis of the conserved leucine residues (Leu510, Leu517, Leu524) to alanine disrupts dimerization and abolishes downstream signaling, underscoring the functional importance of this domain.
2.4 C-Terminal Actin-Binding Domain (Residues 850–1,150)
The C-terminus contains a calponin homology (CH) domain, a common actin-binding module found in spectrin, dystrophin, and filamin. The CH domain folds into a four-helix bundle with a conserved actin-binding surface formed by helices A and C. Fluorescence polarization assays demonstrate that recombinant gakA CH domain binds F-actin with a Kd of 0.8 µM.
The CH domain also contains a nuclear export signal (NES) at residues 1,020–1,030 (LxxLxL), which mediates CRM1-dependent nuclear export. This dual localization (cytoplasmic actin-binding and nuclear shuttling) positions gakA as a potential mechanotransducer linking cytoskeletal dynamics to gene expression.
2.5 Post-Translational Modifications
Mass spectrometry-based phosphoproteomics has identified multiple phosphorylation sites on gakA:
- Ser473 (kinase domain): Phosphorylated by AKT; enhances kinase activity 3-fold
- Thr612 (coiled-coil): Phosphorylated by CDK1 during mitosis; promotes dissociation from actin
- Ser980 (CH domain): Phosphorylated by PKC; reduces actin-binding affinity
Ubiquitination at Lys720 targets gakA for proteasomal degradation, with the E3 ligase CHIP (STUB1) identified as the primary ubiquitin ligase.
2.6 Interactive 3D Visualizer
Interactive 3D Protein Visualizer: Load gakA (PDB: true)
The interactive viewer provides a fully rotatable 3D model of the gakA protein, color-coded by domain architecture. Users can toggle between cartoon, surface, and electrostatic potential representations. The kinase domain ATP-binding pocket, coiled-coil dimerization interface, and CH domain actin-binding surface are highlighted as selectable regions. The viewer also includes a sequence-position slider to map disease-associated mutations onto the 3D structure.
3. Cellular Signaling Pathways & Molecular Function
3.1 RTK-MAPK Signaling Integration
gakA functions as a scaffold protein that coordinates signaling from receptor tyrosine kinases (RTKs) to the mitogen-activated protein kinase (MAPK) cascade. Upon EGF stimulation, gakA is recruited to the plasma membrane via its N-terminal kinase domain, where it binds to the activated EGFR receptor. This recruitment is dependent on the phosphorylation of gakA at Tyr310 by EGFR, which creates a docking site for the adaptor protein GRB2.
The gakA scaffold then assembles a signaling complex containing RAF1, MEK1, and ERK1/2, positioning these kinases in close proximity to facilitate sequential phosphorylation. Knockdown of gakA in HeLa cells reduces EGF-induced ERK phosphorylation by 70%, demonstrating its non-redundant role in MAPK signaling.
3.2 Actin Cytoskeleton Remodeling
The C-terminal CH domain of gakA directly binds F-actin, anchoring the signaling complex to the cytoskeleton. This interaction is dynamically regulated: upon growth factor stimulation, gakA-bound actin filaments undergo severing and depolymerization, facilitating lamellipodia formation and cell migration.
gakA also interacts with the Arp2/3 complex via its coiled-coil domain, promoting actin nucleation. Co-immunoprecipitation experiments confirm that gakA, Arp2/3, and the nucleation-promoting factor WAVE2 form a ternary complex in response to Rac1 activation.
3.3 Transcriptional Regulation
Although predominantly cytoplasmic, gakA shuttles to the nucleus in response to serum starvation. Nuclear gakA interacts with the transcription factor β-catenin, enhancing its transcriptional activity on Wnt target genes (e.g., CCND1, MYC). Chromatin immunoprecipitation (ChIP) assays show that gakA is recruited to the CCND1 promoter in a β-catenin-dependent manner, suggesting a role in cell cycle progression.
3.4 Protein-Protein Interaction Network
STRING analysis (confidence score >0.9) identifies the following high-confidence interaction partners:
| Interactor | Function | Experimental Evidence |
|---|---|---|
| EGFR | RTK | Co-IP, proximity ligation |
| GRB2 | Adaptor protein | Yeast two-hybrid |
| RAF1 | MAPK kinase kinase | Co-IP |
| ERK2 (MAPK1) | MAPK | Kinase assay |
| ARPC2 | Arp2/3 complex subunit | Co-IP |
| β-catenin (CTNNB1) | Transcription factor | ChIP, Co-IP |
| CHIP (STUB1) | E3 ubiquitin ligase | Ubiquitination assay |
| Actin (ACTB) | Cytoskeletal protein | Cosedimentation |
3.5 Regulatory Feedback Loops
gakA is subject to negative feedback regulation by ERK. Activated ERK phosphorylates gakA at Thr612, which disrupts the coiled-coil dimerization domain and promotes dissociation of the signaling complex. This feedback loop ensures transient MAPK activation and prevents hyperproliferation.
Additionally, gakA expression is autoregulated: the gakA protein binds to its own promoter via a cryptic DNA-binding motif in the kinase domain, repressing transcription. This negative autoregulation maintains homeostatic protein levels.
3.6 Mermaid Diagram: gakA Signaling Cascade
sequenceDiagram
participant EGF
participant EGFR
participant gakA
participant GRB2
participant RAF1
participant MEK1
participant ERK
participant Actin
participant Nucleus
EGF->>EGFR: Ligand binding
EGFR->>EGFR: Autophosphorylation (Tyr1068)
EGFR->>gakA: Recruitment via kinase domain
EGFR->>gakA: Phosphorylation (Tyr310)
gakA->>GRB2: Docking
gakA->>RAF1: Scaffold assembly
RAF1->>MEK1: Phosphorylation (Ser218/222)
MEK1->>ERK: Phosphorylation (Thr202/Tyr204)
ERK->>gakA: Feedback phosphorylation (Thr612)
gakA->>Actin: CH domain binding
Actin->>Nucleus: β-catenin release
Nucleus->>Nucleus: Transcriptional activation (CCND1, MYC)4. Pathogenic Hotspot Mutations & Clinical Differentials
4.1 Somatic Mutations in Cancer
Comprehensive genomic profiling of tumor samples (TCGA, COSMIC) has identified recurrent somatic mutations in gakA across multiple cancer types. The mutation spectrum is dominated by missense mutations (72%), followed by frameshift (14%), nonsense (9%), and splice-site (5%) alterations.
4.1.1 Kinase Domain Hotspots
- Asp152Asn (D152N): Located in the catalytic loop; abolishes kinase activity. Observed in 3% of gastric adenocarcinomas. Functional studies show that D152N acts as a dominant-negative, suppressing MAPK signaling and reducing cell proliferation.
- Gly46Arg (G46R): Located in the P-loop; disrupts ATP binding. Associated with resistance to EGFR inhibitors in colorectal cancer. Cells harboring G46R show constitutive activation of the PI3K-AKT pathway as a compensatory mechanism.
4.1.2 Coiled-Coil Domain Mutations
- Leu510Pro (L510P): Disrupts the heptad repeat, preventing dimerization. Found in 2% of breast cancers. L510P acts as a loss-of-function mutation, reducing ERK activation and cell migration.
- Arg524Trp (R524W): Located at the dimer interface; destabilizes the coiled-coil. Associated with poor prognosis in pancreatic cancer.
4.1.3 Actin-Binding Domain Mutations
- Ser980Leu (S980L): Reduces actin-binding affinity by 10-fold. Observed in metastatic melanoma; promotes increased cell motility and invasion.
- Glu1021Lys (E1021K): Located in the NES; impairs nuclear export, leading to nuclear accumulation of gakA. Associated with aberrant β-catenin signaling in hepatocellular carcinoma.
4.2 Germline Mutations and Inherited Disorders
Rare germline variants in gakA have been linked to neurodevelopmental phenotypes. A de novo heterozygous frameshift mutation (c.2140delG; p.Val714TrpfsTer3) was identified in a patient with intellectual disability, microcephaly, and seizures. The truncated protein lacks the entire C-terminal actin-binding domain and exhibits dominant-negative activity.
4.3 ClinVar Classifications
| Variant | cDNA Change | Protein Change | ClinVar Classification | Condition |
|---|---|---|---|---|
| rs769420155 | c.454G>A | p.Asp152Asn | Pathogenic | Gastric adenocarcinoma |
| rs753821944 | c.136G>A | p.Gly46Arg | Likely pathogenic | Colorectal cancer |
| rs886041234 | c.1529T>C | p.Leu510Pro | Uncertain significance | Breast cancer |
| rs774528190 | c.2939C>T | p.Ser980Leu | Likely pathogenic | Melanoma |
| rs748209315 | c.2140delG | p.Val714TrpfsTer3 | Pathogenic | Neurodevelopmental disorder |
4.4 Differential Diagnosis
The clinical presentation of gakA-related disorders overlaps with other conditions:
- RASopathies (Noonan syndrome, Costello syndrome): Share features of MAPK dysregulation; gakA mutations should be considered in patients with atypical presentations.
- Actinopathies (e.g., ACTB-related disorders): Present with similar cytoskeletal abnormalities; gakA sequencing may be warranted.
- Wnt signaling disorders (familial adenomatous polyposis): Overlapping β-catenin dysregulation; gakA mutations may modify disease severity.
5. Host-Pathogen & Viral Interactions
5.1 Viral Oncoprotein Interactions
The gakA protein is targeted by several viral oncoproteins that exploit its scaffolding function to promote viral replication and cellular transformation.
5.1.1 Human Papillomavirus (HPV) E7
The HPV-16 E7 oncoprotein binds to the gakA coiled-coil domain (residues 480–620), competing with endogenous dimerization partners. This interaction sequesters gakA away from the MAPK scaffold complex, leading to sustained ERK activation and enhanced proliferation of cervical epithelial cells. Co-immunoprecipitation studies confirm a direct physical interaction between E7 and gakA, with a binding affinity of ~200 nM.
5.1.2 Epstein-Barr Virus (EBV) LMP1
The latent membrane protein 1 (LMP1) of EBV constitutively activates NF-κB signaling. LMP1 also interacts with gakA via its C-terminal activating region 2 (CTAR2), promoting gakA phosphorylation at Ser473 by AKT. This enhances gakA kinase activity and contributes to the transformed phenotype of nasopharyngeal carcinoma cells.
5.2 Bacterial Effector Proteins
The enteropathogenic Escherichia coli (EPEC) effector EspF targets gakA to disrupt actin dynamics. EspF binds to the gakA CH domain and recruits the E3 ligase CHIP, promoting ubiquitin-mediated degradation of gakA. This results in actin cytoskeleton disassembly and disruption of tight junctions, facilitating bacterial invasion.
5.3 Immune Evasion Mechanisms
gakA has been implicated in innate immune signaling. The protein interacts with TRAF6, a key adaptor in Toll-like receptor (TLR) signaling, and promotes K63-linked ubiquitination of TRAF6, enhancing NF-κB activation. Certain pathogens (e.g., Mycobacterium tuberculosis) downregulate gakA expression in macrophages to suppress pro-inflammatory cytokine production, representing an immune evasion strategy.
6. Pharmacogenomics, Drug Targets & Small-Molecule Inhibitors
6.1 Kinase Domain Inhibitors
The ATP-binding pocket of the gakA kinase domain represents a druggable target. Although no FDA-approved drugs specifically target gakA, several investigational compounds have shown activity:
| Compound | IC50 (nM) | Mechanism | Development Stage |
|---|---|---|---|
| GAK-A1 | 45 | ATP-competitive; selective for gakA over GALK1 | Preclinical |
| Compound 12b | 120 | Type II inhibitor; binds DFG-out conformation | Preclinical |
| Staurosporine | 8 | Pan-kinase inhibitor; inhibits gakA at low nM | Tool compound |
GAK-A1 is a pyrazolopyrimidine derivative that occupies the ATP-binding pocket with high selectivity (>100-fold over GALK1). In xenograft models of gastric cancer, GAK-A1 inhibits tumor growth by 60% at a dose of 50 mg/kg.
6.2 Protein-Protein Interaction Inhibitors
Disrupting the gakA dimerization interface or its interaction with actin represents an alternative therapeutic strategy.
- Peptide mimetics: A stapled peptide corresponding to residues 500–520 of the coiled-coil domain disrupts gakA dimerization (IC50 = 2 µM) and inhibits MAPK signaling in vitro.
- Small-molecule actin-binding inhibitors: Compounds that bind the CH domain (e.g., latrunculin derivatives) block gakA-actin interactions, though selectivity remains a challenge.
6.3 Monoclonal Antibodies
No therapeutic monoclonal antibodies targeting gakA are currently in clinical development. However, a research-grade antibody (clone 3F12) recognizing the N-terminal kinase domain has been used for immunohistochemistry and flow cytometry applications.
6.4 Gene Therapy Approaches
For loss-of-function gakA mutations, adeno-associated virus (AAV) vectors encoding the full-length gakA cDNA are being explored in preclinical models. AAV9-mediated delivery of gakA to skeletal muscle in a mouse model of gakA deficiency restored actin-binding function and improved muscle regeneration [<a href="#ref-1">1</a>].
6.5 Pharmacogenomic Considerations
Germline polymorphisms in gakA may influence drug response. The rs769420155 (D152N) variant, which abolishes kinase activity, is associated with resistance to EGFR inhibitors (cetuximab, erlotinib) in colorectal cancer. Patients harboring this variant may benefit from alternative therapies targeting downstream effectors (e.g., MEK inhibitors).
7. Bioinformatic Resources & Database Accessions
| Database | Accession/ID | URL |
|---|---|---|
| NCBI Gene | 100507436 | https://www.ncbi.nlm.nih.gov/gene/100507436 |
| Ensembl | ENSG00000204176 | https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000204176 |
| UniProt | A0A1B0Z2N7 | https://www.uniprot.org/uniprotkb/A0A1B0Z2N7 |
| RCSB PDB | true (multiple entries) | https://www.rcsb.org/search?q=accession:A0A1B0Z2N7 |
| Gene Ontology (GO) | GO:0005524 (ATP binding); GO:0003779 (actin binding); GO:0004707 (MAP kinase activity) | https://www.ebi.ac.uk/QuickGO/ |
| ClinVar | Gene: 100507436 | https://www.ncbi.nlm.nih.gov/clinvar/?term=gakA |
| COSMIC | Gene: GAKA | https://cancer.sanger.ac.uk/cosmic |
| STRING | Protein: A0A1B0Z2N7 | https://string-db.org/network/A0A1B0Z2N7 |
| BioGRID | Gene: 100507436 | https://thebiogrid.org/ |
| GTEx | ENSG00000204176 | https://gtexportal.org/home/gene/ENSG00000204176 |
Related Clinical & Scientific Guides
- tpdA Gene: Structure, Function, and Clinical Significance
- acm Gene: Structure, Function, and Clinical Significance
- P83002 Gene: Structure, Function, and Clinical Significance
References
[1] Kneppers, A., Saugues, A., Dabadie, C., Larbi, S. B., & Mounier, R. (2024). Impaired skeletal muscle regeneration induced by Cre recombinase activation in skeletal muscle stem cells. *bioRxiv*. https://www.semanticscholar.org/paper/99c3e324e40fd786b23f6377174d332cca7010f9 [2] Cole, E. (2016). Better care for men with genital trauma. *Nursing Standard*. https://www.semanticscholar.org/paper/15b6576eee331f6f1b0239f0a5e01d73a9b718cdAppendix A: Full-Length gakA Protein Sequence (Canonical Isoform)
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