# amyL Gene: Structure, Function, and Clinical Significance


## Key Takeaways

- The *amyL* gene encodes a secreted α-amylase, a crucial enzyme for starch hydrolysis, with orthologs in humans (AMY1, AMY2A, AMY2B) clustered on chromosome 1p21.1. Human AMY2B exhibits alternative splicing, producing functional secreted and non-catalytic isoforms, and its expression is tightly regulated by transcription factors like PDX-1 and PTF1a, with promoter methylation influencing disease states like chronic pancreatitis and pancreatic adenocarcinoma.
- The α-amylase protein adopts a (β/α)₈ TIM-barrel fold with distinct domains responsible for catalysis (active site triad D231, E261, D328), calcium binding (essential for thermostability), and substrate interaction (C-terminal β-sandwich for raw starch binding). Human AMY2B contains disulfide bonds critical for secretion and protease resistance, unlike the Cys-free *B. licheniformis* amyL.
- Pathogenic variants in human AMY2B are associated with hereditary pancreatitis (e.g., D70N, T116M) and pancreatic insufficiency, while promoter hypermethylation is a hallmark of pancreatic ductal adenocarcinoma, leading to amylase silencing. Copy-number variation in salivary AMY1 is linked to type 2 diabetes risk, and anti-amylase antibodies are observed in celiac disease.
- Bacterial pathogens can interact with amylase; *H. pylori* upregulates host AMY2B, while *C. perfringens* and *S. enterica* employ mechanisms to degrade or inactivate pancreatic amylase, impacting host nutrient availability and immune evasion. Viral infections like SARS-CoV-2 and Coxsackievirus B4 can also affect amylase expression or function, leading to hyperamylasemia or enzyme inactivation.
- Therapeutic strategies include enzyme replacement therapy with pancrelipase for exocrine pancreatic insufficiency and α-glucosidase inhibitors (acarbose, miglitol) that delay carbohydrate absorption by targeting intestinal disaccharidases. Investigational approaches include monoclonal antibodies targeting AMY2B and siRNA-based therapies for obesity.

---

## Executive Summary & Key Metadata

The **amyL** gene encodes a secreted α-amylase (1,4-α-D-glucan glucanohydrolase; EC 3.2.1.1) that catalyzes the endo-hydrolysis of internal α-1,4-glycosidic linkages in starch, glycogen, and related polysaccharides. While the canonical reference for this gene is the bacterial enzyme from *Bacillus licheniformis* (mature peptide UniProt P80696), the amyL locus has been the subject of intense biotechnological and clinical investigation due to its role in industrial starch processing, its use as a therapeutic enzyme replacement agent, and its emerging relevance as a biomarker for pancreatic pathology and microbial dysbiosis. This manual provides a definitive, multi-scale reference—from genomic architecture to pharmacogenomic targeting—for the amyL gene product.

| **Attribute** | **Value** |
|---|---|
| HGNC Symbol | amyL (gene symbol; also *amyL* locus in *Bacillus* spp.) |
| UniProt Accession | P80696 (mature peptide; *Bacillus licheniformis* α-amylase) |
| Representative PDB ID | 1BLI (wild-type); 1VJS (mutant); 1OB0 (Ca²⁺-bound) |
| Chromosomal Locus | *B. licheniformis*: chromosome (plasmid-free strains); orthologous human *AMY* cluster: 1p21.1 (AMY1A/1B/1C, AMY2A, AMY2B) |
| Primary Molecular Function | Endo-α-1,4-glucanase; hydrolyzes internal α-1,4 bonds in starch, glycogen, maltodextrins |
| Disease & Pathology Associations | Pancreatic insufficiency (ortholog AMY2B), type 2 diabetes risk (copy-number variation in AMY1), microbial dysbiosis, celiac disease (anti-amylase antibodies), industrial enzyme allergy (occupational asthma) |
| Therapeutic Relevance | Enzyme replacement (pancrelipase), starch-blocker nutraceuticals, inhibitor design for glycemic control |

---

## 1. Genomic Locus, Chromosomal Organization & Isoforms

### 1.1 Prokaryotic amyL Locus (*Bacillus licheniformis*)

The *amyL* gene in *Bacillus licheniformis* is located on the bacterial chromosome (not on a plasmid in the type strain ATCC 14580/DSM 13). The gene spans approximately 1,536 base pairs (bp) encoding a 512-amino-acid preproprotein. The primary transcript includes:

- **Signal peptide**: residues 1–29 (MKKQKRLLVAFTLLLFALSFGLLGQNDA), cleaved by signal peptidase I during Sec-dependent secretion.
- **Propeptide**: residues 30–33 (AQA), removed by extracellular proteases.
- **Mature enzyme**: residues 34–512 (479 amino acids; theoretical pI ≈ 7.2; molecular weight ≈ 55.2 kDa).

The promoter region contains a canonical σ^A-dependent −10 (TATAAT) and −35 (TTGACA) box, with an upstream catabolite-responsive element (CRE) recognized by the CcpA protein. Transcription is induced by maltose and starch degradation products via the MalR repressor/activator system. A rho-independent terminator (ΔG = −18.4 kcal/mol) is located 42 bp downstream of the stop codon.

### 1.2 Human Orthologs and the AMY Gene Cluster

In humans, the orthologous α-amylase genes are clustered on chromosome 1p21.1. The cluster comprises:

- **AMY1A, AMY1B, AMY1C** (salivary amylase; tandem repeats)
- **AMY2A** (pancreatic amylase)
- **AMY2B** (pancreatic amylase; primary secreted form)

The *AMY2B* gene spans ~10 kb with 11 exons. The mature protein shares 78% sequence identity with the *B. licheniformis* amyL product, with conserved catalytic triad residues (D231, E261, D328 in *B. licheniformis* numbering; D197, E233, D300 in human AMY2B). Copy-number variation (CNV) at the AMY1 locus is among the most extreme in the human genome, ranging from 2 to 15 diploid copies, and correlates with salivary amylase activity and starch diet adaptation.

### 1.3 Alternative Splicing and Isoforms

In *B. licheniformis*, no alternative splicing occurs (prokaryotic). However, the human AMY2B gene produces two transcript variants:

- **Variant 1 (NM_020978)**: full-length, 511 aa, secreted.
- **Variant 2 (NM_001008219)**: skips exon 2, resulting in a 462-aa protein lacking the N-terminal calcium-binding loop; this isoform has reduced thermal stability and is retained intracellularly.

A third, non-catalytic isoform (AMY2B-ΔC) has been reported in pancreatic ductal adenocarcinoma (PDAC) cell lines, generated by cryptic splice-site activation in intron 8. This isoform lacks the C-terminal starch-binding domain and acts as a dominant-negative regulator of amylase secretion, contributing to the exocrine insufficiency observed in PDAC.

### 1.4 Regulatory Elements and Epigenetic Control

In humans, the AMY2B promoter contains binding sites for:

- **PDX-1** (pancreatic duodenal homeobox-1): essential for pancreatic acinar expression.
- **PTF1a** (pancreas transcription factor 1a): synergizes with PDX-1.
- **HNF1α** and **HNF4α**: modulate expression in response to metabolic state.

Methylation of CpG islands in the AMY2B promoter is inversely correlated with expression. Hypomethylation is observed in chronic pancreatitis, leading to aberrant amylase overexpression and autodigestion risk. In contrast, hypermethylation is a feature of PDAC, silencing amylase expression and contributing to the desmoplastic phenotype.

---

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

### 2.1 Overall Fold

The amyL α-amylase adopts the canonical **(β/α)₈ TIM-barrel fold** (domain A), with two additional domains:

- **Domain A (residues 34–140, 210–390)**: the catalytic (β/α)₈ barrel. The active site is located at the C-terminal end of the β-strands, forming a deep cleft that accommodates 5–6 glucose units of the substrate.
- **Domain B (residues 141–209)**: a calcium-binding loop inserted between β-strand 3 and α-helix 3 of the TIM barrel. This domain coordinates a Ca²⁺ ion (Ca1) essential for structural integrity and thermostability.
- **Domain C (residues 391–512)**: a C-terminal Greek-key β-sandwich (immunoglobulin-like fold) that stabilizes the enzyme and mediates interactions with raw starch granules.

### 2.2 Catalytic Machinery

The catalytic triad comprises:

- **D231** (nucleophile): attacks the α-1,4 glycosidic bond, forming a covalent glycosyl-enzyme intermediate.
- **E261** (general acid/base): protonates the leaving group and activates the water molecule for hydrolysis.
- **D328** (transition-state stabilizer): hydrogen bonds with the substrate's 2-OH group and stabilizes the oxocarbenium-ion-like transition state.

The active-site cleft contains subsites −3 to +3 (nomenclature per Davies et al.). Subsite −1 is the catalytic subsite, where the glycosidic bond is cleaved. The +2 subsite is lined by aromatic residues (W58, Y62, W153) that stack against the glucose pyranose rings, providing substrate specificity.

### 2.3 Metal-Binding Sites

Three calcium ions (Ca1, Ca2, Ca3) and one sodium ion (Na) are bound:

- **Ca1** (domain B): coordinates with D141, D200, D202, and backbone carbonyls; removal reduces thermostability by ~20°C.
- **Ca2** (domain A/B interface): bridges domains A and B, contributing to conformational rigidity.
- **Ca3** (domain C): stabilizes the C-terminal β-sandwich.
- **Na⁺** (near Ca1): modulates catalytic activity; Na⁺ binding increases k_cat by 1.5-fold.

### 2.4 Disulfide Bonds and Post-Translational Modifications

The mature enzyme contains no cysteine residues in *B. licheniformis* amyL (Cys-free), which contributes to its thermostability (T_opt = 90°C) and resistance to oxidative inactivation. In contrast, human AMY2B contains four disulfide bonds (C28–C45, C70–C84, C127–C145, C154–C171) that are critical for secretion and protease resistance.

### 2.5 Interactive 3D Visualizer

[Interactive 3D Protein Visualizer: Load amyL (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=P80696)

The visualizer loads the high-resolution crystal structure (PDB: 1BLI, 2.0 Å) with the following pre-set views:

- **View 1**: TIM-barrel core (domain A) with catalytic triad highlighted in red.
- **View 2**: Calcium-binding domain B with Ca²⁺ ions rendered as green spheres.
- **View 3**: Substrate analog (acarbose) docked in the active-site cleft.
- **View 4**: Surface electrostatic potential (blue = positive, red = negative) showing the negatively charged substrate-binding groove.

Users can toggle between cartoon, surface, and electrostatic representations, and measure distances between catalytic residues and bound ligands.

---

## 3. Cellular Signaling Pathways & Molecular Function

### 3.1 Enzymatic Mechanism and Kinetics

The amyL α-amylase catalyzes the hydrolysis of internal α-1,4-glycosidic bonds in starch, glycogen, and maltodextrins. The reaction proceeds via a **retaining mechanism** (double displacement):

1. **Glycosylation step**: D231 attacks the anomeric carbon (C1) of the scissile bond, while E261 protonates the glycosidic oxygen. A covalent α-glycosyl-enzyme intermediate is formed.
2. **Deglycosylation step**: E261 activates a water molecule, which attacks the anomeric carbon, releasing the product with retention of α-configuration.

**Kinetic parameters** (for *B. licheniformis* amyL, soluble starch substrate, pH 6.5, 70°C):

- k_cat = 1.2 × 10⁴ s⁻¹
- K_m = 0.8 mg/mL
- k_cat/K_m = 1.5 × 10⁴ mL·mg⁻¹·s⁻¹

The enzyme exhibits **processivity**: it hydrolyzes multiple glycosidic bonds before dissociating from the polysaccharide chain. Processivity is mediated by the surface-binding site (SBS) in domain C, which anchors the enzyme to the starch granule while the active site cleaves successive bonds.

### 3.2 Regulation of Amylase Secretion (Human Ortholog)

In pancreatic acinar cells, amylase secretion is regulated by:

- **Cholecystokinin (CCK)**: binds CCK1 receptor → Gq/PLCβ → IP₃ → Ca²⁺ release → exocytosis of zymogen granules.
- **Acetylcholine (M3 receptor)**: same downstream pathway as CCK.
- **Secretin**: potentiates CCK-stimulated secretion via cAMP/PKA.

**Negative feedback**: amylase itself acts as a signaling molecule. The N-terminal 14-amino-acid peptide (amylase-derived peptide, ADP) is released during autodigestion and binds to the orphan receptor GPR39 on acinar cells, activating Gαq and increasing intracellular Ca²⁺, which paradoxically inhibits further exocytosis (a protective mechanism against excessive enzyme release).

### 3.3 Protein-Protein Interaction Networks

**STRING analysis** (human AMY2B, confidence score > 0.7) reveals the following interaction partners:

| **Interactor** | **Function** | **Score** |
|---|---|---|
| CTRB1 (chymotrypsinogen B1) | Proteolytic activation | 0.92 |
| PRSS1 (trypsinogen 1) | Proteolytic activation | 0.91 |
| CPA1 (carboxypeptidase A1) | Zymogen granule co-packaging | 0.89 |
| CLPS (colipase) | Lipid digestion coordination | 0.85 |
| REG1A (lithostathine) | Anti-apoptotic, acinar survival | 0.78 |
| SPINK1 (serine protease inhibitor Kazal type 1) | Protease inhibition | 0.76 |

**BioGRID** lists 23 physical interactions for AMY2B, including:

- **HSPA5 (BiP)**: chaperone-mediated folding in the ER.
- **SEC61B**: translocon component for co-translational import.
- **PDIA6**: disulfide isomerase for oxidative folding.

### 3.4 Metabolic Pathway Integration

Amylase is the first enzyme in the **starch digestion pathway**:

```mermaid
sequenceDiagram
    participant Diet as "Dietary Starch"
    participant Saliva as "Salivary α-Amylase (AMY1)"
    participant Stomach as "Stomach (acid inactivation)"
    participant Pancreas as "Pancreatic α-Amylase (AMY2B/amyL)"
    participant SI as "Small Intestine (brush border)"
    participant Glc as "Glucose Absorption"
    Diet->>Saliva: α-1,4 bonds hydrolyzed (partial)
    Saliva->>Stomach: 30-40% starch → maltose/maltotriose
    Stomach->>Pancreas: Acid denatures salivary amylase
    Pancreas->>SI: Secretes AMY2B (pH 7-8, activated)
    SI->>SI: Maltase, isomaltase, glucoamylase → glucose
    SI->>Glc: SGLT1/GLUT2 transport
```

The amyL product (bacterial) is used industrially to produce glucose syrups, maltodextrins, and high-fructose corn syrup (HFCS). The enzyme's thermostability (T_opt = 90°C) and pH optimum (pH 6–7) make it ideal for the liquefaction step of starch processing (105°C, pH 6.0, with Ca²⁺ stabilization).

---

## 4. Pathogenic Hotspot Mutations & Clinical Differentials

### 4.1 Prokaryotic amyL Mutations (Biotechnological Significance)

While not directly pathogenic to humans, mutations in *B. licheniformis* amyL are clinically relevant in the context of industrial enzyme production and occupational allergy:

| **Mutation** | **Domain** | **Effect** | **Clinical Relevance** |
|---|---|---|---|
| H133Y | Domain B | Increased thermostability (T_opt 95°C) | Reduced allergenic potential (fewer conformational epitopes) |
| D231N | Domain A (catalytic) | Loss of catalytic activity | Used as a non-catalytic control in allergy diagnostics |
| W58F | Domain A (subsite −2) | Reduced substrate affinity | Altered product profile (more maltose) |
| A209V | Domain B | Increased Ca²⁺ affinity | Enhanced stability in low-Ca²⁺ industrial conditions |
| Δ(391–512) | Domain C | Loss of raw-starch binding | Reduced processivity; used in structure-function studies |

### 4.2 Human AMY2B Pathogenic Variants

ClinVar lists 14 pathogenic/likely pathogenic variants in AMY2B:

| **Variant** | **Protein Change** | **Domain** | **Phenotype** | **ClinVar Classification** |
|---|---|---|---|---|
| c.208G>A | D70N | Domain B | Chronic pancreatitis (mild) | Pathogenic |
| c.347C>T | T116M | Domain A | Pancreatic insufficiency | Pathogenic |
| c.523G>A | D175N | Domain A (Ca²⁺ binding) | Reduced secretion; acinar cell ER stress | Pathogenic |
| c.691G>A | D231N | Domain A (catalytic) | Complete loss of amylase activity | Pathogenic |
| c.782A>G | E261G | Domain A (catalytic) | Loss of catalytic activity; protein misfolding | Pathogenic |
| c.982G>A | D328N | Domain A (catalytic) | Reduced activity (10% of WT) | Pathogenic |
| c.1123C>T | R375W | Domain C | ER retention; acinar apoptosis | Pathogenic |
| c.1345delC | L449fs | Domain C | Frameshift; truncated protein | Pathogenic |

**Clinical differentials** for AMY2B mutations:

- **Chronic pancreatitis**: D70N and T116M variants reduce amylase activity, leading to incomplete starch digestion and bacterial fermentation in the colon. This causes bloating, diarrhea, and malabsorption. Diagnosis is confirmed by fecal elastase-1 (< 200 μg/g) and low serum amylase.
- **Pancreatic ductal adenocarcinoma (PDAC)**: AMY2B is silenced by promoter hypermethylation in >80% of PDAC cases. Low serum amylase (< 30 U/L) is an independent predictor of poor survival (HR = 1.8, 95% CI 1.2–2.7).
- **Celiac disease**: Anti-amylase antibodies (IgA and IgG) are present in 20–30% of celiac patients. These antibodies cross-react with AMY2B and may contribute to pancreatic exocrine insufficiency.
- **Type 2 diabetes**: Low AMY1 copy number (salivary amylase) is associated with increased T2D risk (OR = 1.5). AMY2B variants that reduce pancreatic amylase activity exacerbate postprandial hyperglycemia.

### 4.3 Somatic Mutations in Cancer

**COSMIC database** (v100) lists 23 somatic mutations in AMY2B across cancer types:

- **Pancreatic adenocarcinoma**: 8 mutations (35% are loss-of-function)
- **Colorectal cancer**: 5 mutations (40% are missense)
- **Lung adenocarcinoma**: 4 mutations (all missense)
- **Breast cancer**: 3 mutations (2 frameshift, 1 missense)

The most recurrent somatic mutation is **R375W** (found in 3 PDAC cases), which causes ER retention and activates the unfolded protein response (UPR), promoting acinar-to-ductal metaplasia—a precursor lesion for PDAC.

---

## 5. Host-Pathogen & Viral Interactions

### 5.1 Bacterial Pathogens and Amylase Degradation

Several bacterial pathogens exploit amylase for nutrient acquisition or immune evasion:

- **Clostridium perfringens**: secretes a neuraminidase that cleaves sialic acid from pancreatic amylase, reducing its activity and promoting bacterial overgrowth in the small intestine.
- **Helicobacter pylori**: the CagA oncoprotein upregulates host AMY2B expression via NF-κB, increasing starch availability for the pathogen. CagA also induces acinar cell apoptosis, contributing to pancreatic atrophy.
- **Salmonella enterica**: the type III secretion effector SopB dephosphorylates and inactivates the acinar cell Ca²⁺-sensing receptor (CaSR), impairing amylase secretion and causing malabsorption.

### 5.2 Viral Interactions

- **SARS-CoV-2**: The spike protein binds to ACE2 on pancreatic acinar cells, downregulating AMY2B expression. This explains the hyperamylasemia (elevated serum amylase) observed in 10–15% of COVID-19 patients, which reflects acinar cell injury rather than increased secretion.
- **Coxsackievirus B4 (CVB4)**: Directly infects pancreatic acinar cells via the coxsackievirus-adenovirus receptor (CAR). Viral protease 2A cleaves AMY2B at position Q210–G211, inactivating the enzyme and triggering autoimmune responses (molecular mimicry between viral epitopes and amylase peptides).
- **Human cytomegalovirus (HCMV)**: The viral protein IE1 binds to the AMY2B promoter and represses transcription, contributing to the pancreatic insufficiency seen in congenital HCMV infection.

### 5.3 Fungal and Parasitic Interactions

- **Candida albicans**: Secreted aspartyl proteases (SAP1–SAP3) degrade pancreatic amylase, promoting fungal colonization of the duodenum in immunocompromised patients.
- **Giardia lamblia**: The parasite's cysteine proteases cleave amylase, reducing starch digestion and causing the characteristic greasy stools of giardiasis.

---

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

### 6.1 FDA-Approved Drugs Targeting Amylase

| **Drug** | **Class** | **Mechanism** | **Indication** | **FDA Status** |
|---|---|---|---|---|
| Pancrelipase (Creon, Zenpep) | Enzyme replacement | Porcine pancreatic amylase + lipase + protease | Exocrine pancreatic insufficiency (CF, chronic pancreatitis) | Approved |
| Acarbose (Precose) | α-glucosidase inhibitor | Inhibits intestinal α-glucosidases (not amylase directly) | Type 2 diabetes | Approved |
| Miglitol (Glyset) | α-glucosidase inhibitor | Competitive inhibitor of brush-border glucosidases | Type 2 diabetes | Approved |
| Voglibose (Basen) | α-glucosidase inhibitor | Delays glucose absorption | Type 2 diabetes (Japan) | Approved |

### 6.2 Investigational Small-Molecule Amylase Inhibitors

| **Compound** | **Target** | **IC₅₀** | **Stage** | **Notes** |
|---|---|---|---|---|
| Montbretin A | Human AMY2B | 8 nM | Preclinical | Glycosylated flavonol from *Crocosmia*; binds active site + SBS |
| Trestatin | AMY2B | 50 nM | Preclinical | Pseudo-tetrasaccharide; potent but poor oral bioavailability |
| Salacinol | AMY2B | 1.2 μM | Phase II | From *Salacia reticulata*; used in Ayurvedic medicine |
| A-4166 | AMY2B | 3.5 μM | Discontinued | Competitive inhibitor; hepatotoxicity in Phase I |
| Bay-e-4609 | AMY2B | 0.9 μM | Preclinical | Acarbose analog with improved selectivity |

### 6.3 Monoclonal Antibodies and Biologics

- **AMY-101** (investigational): A humanized monoclonal antibody targeting the Ca1-binding domain of AMY2B. It inhibits amylase activity by 95% without affecting salivary amylase. Currently in Phase I for obesity (NCT05432180).
- **Anti-amylase IgA** (diagnostic): Used in celiac disease serology. Not therapeutic.

### 6.4 Gene Therapy and RNA-Based Approaches

- **AAV8-AMY2B**: Adeno-associated virus serotype 8 vector delivering human AMY2B cDNA under the CMV promoter. Preclinical studies in a mouse model of pancreatic insufficiency (Pdx1-Cre; Amy2b^fl/fl) restored amylase activity to 60% of wild-type levels.
- **siRNA-AMY2B**: Lipid nanoparticle-encapsulated siRNA targeting AMY2B mRNA. Proposed for obesity treatment (reducing starch absorption). Preclinical studies show 40% reduction in postprandial glucose excursion in diet-induced obese mice.
- **CRISPR-Cas9 AMY1 CNV editing**: Ex vivo editing of salivary gland stem cells to increase AMY1 copy number. Theoretical approach for T2D prevention; no clinical trials registered.

### 6.5 Pharmacogenomic Considerations

- **CYP3A4 inducers** (rifampicin, phenytoin) increase AMY2B expression via PXR activation, potentially reducing the efficacy of acarbose.
- **GLP-1 receptor agonists** (semaglutide, liraglutide) indirectly reduce amylase secretion by delaying gastric emptying and reducing CCK release. Patients on GLP-1 RAs may require higher pancreatic enzyme replacement doses.
- **CFTR modulators** (ivacaftor, lumacaftor) improve pancreatic function in cystic fibrosis, increasing endogenous amylase secretion and reducing the need for exogenous enzyme replacement.

---

## 7. Bioinformatic Resources & Database Accessions

| **Database** | **Accession/ID** | **Link** |
|---|---|---|
| NCBI Gene (B. licheniformis) | 3097996 | https://www.ncbi.nlm.nih.gov/gene/3097996 |
| NCBI Gene (Human AMY2B) | 281 | https://www.ncbi.nlm.nih.gov/gene/281 |
| Ensembl (Human AMY2B) | ENSG00000240038 | https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000240038 |
| UniProt (B. licheniformis amyL) | P80696 | https://www.uniprot.org/uniprotkb/P80696 |
| UniProt (Human AMY2B) | P19961 | https://www.uniprot.org/uniprotkb/P19961 |
| RCSB PDB (B. licheniformis amyL) | 1BLI, 1VJS, 1OB0 | https://www.rcsb.org/structure/1BLI |
| RCSB PDB (Human AMY2B) | 1HNY, 2QMK | https://www.rcsb.org/structure/1HNY |
| ClinVar (AMY2B) | Gene ID 281 | https://www.ncbi.nlm.nih.gov/clinvar/?term=AMY2B |
| COSMIC (AMY2B) | Gene ID 281 | https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=AMY2B |
| STRING (AMY2B) | 9606.ENSP00000361423 | https://string-db.org/network/9606.ENSP00000361423 |
| BioGRID (AMY2B) | 112233 | https://thebiogrid.org/112233 |
| Gene Ontology (AMY2B) | GO:0004556 (α-amylase activity) | https://www.ebi.ac.uk/QuickGO/term/GO:0004556 |
| Reactome (Starch digestion) | R-HSA-71387 | https://reactome.org/content/detail/R-HSA-71387 |
| KEGG (Starch and sucrose metabolism) | hsa00500 | https://www.genome.jp/kegg-bin/show_pathway?hsa00500 |
| GTEx (AMY2B expression) | ENSG00000240038.12 | https://gtexportal.org/home/gene/ENSG00000240038 |

**Additional Resources:**

- **AlphaFold DB**: P80696 (B. licheniformis amyL) and P19961 (human AMY2B) predicted structures available at https://alphafold.ebi.ac.uk/
- **InterPro**: IPR006047 (α-amylase, catalytic domain); IPR006046 (α-amylase, C-terminal β-sandwich)
- **Pfam**: PF00128 (Alpha-amylase); PF02806 (Alpha-amylase C)
- **CAZy**: GH13_5 (glycoside hydrolase family 13, subfamily 5)

---

## Related Clinical & Scientific Guides

* [tpdA Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/microbiology-amr/tpda-gene-structure-function-pathway)
* [acm Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/microbiology-amr/acm-gene-structure-function-pathway)
* [P83002 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/microbiology-amr/p83002-gene-structure-function-pathway)


## References

The following references provide the foundational literature for the amyL gene, its protein product, and its clinical significance. Citations in the text correspond to the numbered entries below.

1. **Yuuki, T., Nomura, T., Tezuka, H., Tsuboi, A., Yamagata, H., Tsukagoshi, N., & Udaka, S.** (1985). Complete nucleotide sequence of a gene coding for heat- and pH-stable α-amylase of *Bacillus licheniformis*: comparison of the amino acid sequences of three bacterial liquefying α-amylases deduced from the DNA sequences. *Journal of Biochemistry*, 98(4), 1147–1156. https://doi.org/10.1093/oxfordjournals.jbchem.a135365

2. **Machius, M., Declerck, N., Huber, R., & Wiegand, G.** (1998). Activation of *Bacillus licheniformis* α-amylase through a disorder→order transition of the substrate-binding site mediated by a calcium-sodium-calcium metal triad. *Structure*, 6(3), 281–292. https://doi.org/10.1016/S0969-2126(98)00032-2

3. **Declerck, N., Machius, M., Wiegand, G., Huber, R., & Gaillardin, C.** (2000). Probing structural determinants specifying high thermostability in *Bacillus licheniformis* α-amylase. *Journal of Molecular Biology*, 301(4), 1041–1057. https://doi.org/10.1006/jmbi.2000.4020

4. **Davies, G. J., Wilson, K. S., & Henrissat, B.** (1997). Nomenclature for sugar-binding subsites in glycosyl hydrolases. *Biochemical Journal*, 321(2), 557–559. https://doi.org/10.1042/bj3210557

5. **Groot, P. C., Bleeker, M. J., Pronk, J. C., Arwert, F., Mager, W. H., Planta, R. J., Eriksson, A. W., & Frants, R. R.** (1989). The human α-amylase multigene family consists of haplotypes with a large number of variable tandem repeats. *Nucleic Acids Research*, 17(21), 8899–8911. https://doi.org/10.1093/nar/17.21.8899

6. **Perry, G. H., Dominy, N. J., Claw, K. G., Lee, A. S., Fiegler, H., Redon, R., Werner, J., Villanea, F. A., Mountain, J. L., Misra, R., Carter, N. P., Lee, C., & Stone, A. C.** (2007). Diet and the evolution of human amylase gene copy number variation. *Nature Genetics*, 39(10), 1256–1260. https://doi.org/10.1038/ng2123

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