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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PAM
peptidylglycine alpha-amidating monooxygenase
Chromosome 5 · 5q21.1
NCBI Gene: 5066Ensembl: ENSG00000145730.21HGNC: HGNC:8596UniProt: A0A804HIQ0
66PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein maturationzinc ion bindingpeptidylglycine monooxygenase activitypeptide amidationtype 2 diabetes mellitusdiabetes mellitusAbnormality of the skeletal systemintelligence
✦AI Summary

PAM (peptidylglycine alpha-amidating monooxygenase) is a bifunctional enzyme that catalyzes the C-terminal amidation of proteins, a critical post-translational modification required for the biological activity of many endocrine hormones and neuropeptides 1. The enzyme operates through two sequential reactions catalyzed by distinct domains: the PHM (peptidyl alpha-hydroxylating monooxygenase) domain performs copper-, ascorbate-, and oxygen-dependent stereospecific hydroxylation of the alpha-carbon of the C-terminal glycine residue, while the PAL (peptidylglycine amidoglycolate lyase) domain catalyzes zinc-dependent cleavage of the N-C-alpha bond to produce the alpha-amidated peptide and glyoxylate 1. Beyond hormone processing, PAM also responds to oxidative stress by promoting C-terminal amidation of protein fragments generated during cellular damage, facilitating their subsequent degradation by the proteasome 2. The enzyme additionally catalyzes the conversion of N-fatty acylglycines to primary fatty acid amides. PAM's dual catalytic mechanism and essential role in hormone maturation make it crucial for proper endocrine function and cellular stress responses.

Sources cited
1
PAM is a bifunctional enzyme with PHM and PAL domains that catalyze sequential copper/zinc-dependent reactions for C-terminal protein amidation
PMID: 12699694
2
PAM promotes C-terminal amidation of oxidative stress-induced protein fragments, facilitating their proteasome-mediated degradation
PMID: 2207077
⚠Limited data available — This gene has 2 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
type 2 diabetes mellitusOpen Targets
0.58Moderate
diabetes mellitusOpen Targets
0.56Moderate
Abnormality of the skeletal systemOpen Targets
0.50Moderate
intelligenceOpen Targets
0.43Moderate
diabetic eye diseaseOpen Targets
0.42Moderate
diabetic retinopathyOpen Targets
0.41Moderate
diabetic neuropathyOpen Targets
0.41Moderate
mathematical abilityOpen Targets
0.40Weak
androgenetic alopeciaOpen Targets
0.39Weak
insomniaOpen Targets
0.39Weak
type 1 diabetes mellitusOpen Targets
0.39Weak
restless legs syndromeOpen Targets
0.33Weak
Chest painOpen Targets
0.33Weak
myocardial infarctionOpen Targets
0.33Weak
autism spectrum disorderOpen Targets
0.28Weak
neurodegenerative diseaseOpen Targets
0.27Weak
attention deficit hyperactivity disorderOpen Targets
0.26Weak
hypothyroidismOpen Targets
0.23Weak
type 2 diabetes nephropathyOpen Targets
0.22Weak
ovarian neoplasmOpen Targets
0.20Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
KALRNProtein interaction97%RASSF9Protein interaction88%CYB561Protein interaction87%TOR2AProtein interaction83%CPEProtein interaction72%CCSShared pathway33%
Tissue Expression6 tissues
Heart
100%
Brain
11%
Ovary
10%
Lung
9%
Bone Marrow
1%
Liver
1%
Gene Interaction Network
Click a node to explore
PAMKALRNRASSF9CYB561TOR2ACPECCS
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt O43832
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.86LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.58 [0.40–0.86]
RankingsWhere PAM stands among ~20K protein-coding genes
  • #7,097of 20,598
    Most Researched66
  • #7,569of 17,882
    Most Constrained (LOEUF)0.86
Genes detectedPAM
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
PI3K/AKT/mTOR-Targeted Therapy for Breast Cancer.
PMID: 36010585
Cells · 2022
1.00
2
Wnt and PI3K/Akt/mTOR Survival Pathways as Therapeutic Targets in Glioblastoma.
PMID: 35163279
Int J Mol Sci · 2022
0.90
3
Engineered CRISPR-Cas9 nucleases with altered PAM specificities.
PMID: 26098369
Nature · 2015
0.80
4
Directed evolution of adenine base editors with increased activity and therapeutic application.
PMID: 32284586
Nat Biotechnol · 2020
0.70
5
Naegleria fowleri: Sources of infection, pathophysiology, diagnosis, and management; a review.
PMID: 31612525
Clin Exp Pharmacol Physiol · 2020
0.60