PAM (Peptidylglycine Alpha-Amidating Monooxygenase)

A key enzyme in neuroendocrine peptide amidation, with roles in cancer and neurological disorders.

Gene Information Card

Symbol PAM
Full Name Peptidylglycine Alpha-Amidating Monooxygenase
Gene Type protein-coding
Chromosomal Location 5q21.1
NCBI Gene ID 5066 ncbi.nlm.nih.gov/gene/5066
Ensembl ID ENSG00000145730
UniProt ID P19021
OMIM ID 170270
HGNC ID 8596
Aliases PAL, PHM, PAM-1, PAM-2

Description

The PAM gene encodes peptidylglycine alpha-amidating monooxygenase, a bifunctional enzyme that catalyzes the C-terminal amidation of peptides. This modification is essential for the biological activity of many neuropeptides and hormones. The enzyme has two catalytic domains: peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL). Alternative splicing generates multiple isoforms with distinct tissue distributions and functions.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Breast Cancer Altered PAM expression may affect peptide hormone signaling, promoting tumor growth and metastasis. PMID: 25691885
Neuroendocrine Tumors PAM is overexpressed in neuroendocrine tumors, contributing to peptide amidation and tumor progression. PMID: 23542377
Alzheimer's Disease Reduced PAM activity may impair neuropeptide amidation, affecting synaptic function and amyloid processing. PMID: 20628006

Expression Profile

Tissue Expression
Tissue nTPM level
Brain 15.2 Medium
Pituitary 45.8 High
Adrenal Gland 22.1 High
Heart 3.4 Low
Liver 1.2 Not detected
Cell Line Expression
Cell Line nTPM Notes
SH-SY5Y 12.5 Neuroblastoma cell line
HeLa 8.3 Cervical cancer cell line
MCF-7 6.7 Breast cancer cell line
HEK293 4.1 Embryonic kidney cell line
Data source：Human Protein Atlas（proteinatlas.org）

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.1234C>T (p.Arg412Trp) Missense <0.01% Reduced enzyme activity; associated with neuroendocrine dysfunction
c.1567G>A (p.Gly523Arg) Missense <0.01% Impaired substrate binding; reported in ClinVar
c.789_790insA Frameshift <0.01% Loss of function; rare variant
Mutation functional classification

Loss of Function (LOF)

Missense and frameshift mutations that reduce or abolish catalytic activity of PHM or PAL domains.

Gain of Function (GOF)

Not well documented; no known gain-of-function mutations reported in major databases.

Dominant Negative (DN)

Not established; no dominant-negative variants described.
View complete mutation data：
ClinVar：https://www.clinvar.com/gene/5066
COSMIC：https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=PAM

Gene Ontology (GO)

• peptidylglycine monooxygenase activity (GO:0004503) • peptidylglycine alpha-amidating lyase activity (GO:0004504)
• copper ion binding (GO:0005507) • cellular copper ion homeostasis (GO:0006878)
• protein processing (GO:0016485) • axon (GO:0030424)

Pathways

• Peptide hormone metabolism (Reactome: R-HSA-422085)
• Amidation of neuropeptides (Reactome: R-HSA-209952)

Protein Summary

Peptidylglycine alpha-amidating monooxygenase (PAM) is a bifunctional enzyme that catalyzes the two-step conversion of peptidylglycine substrates to amidated peptides. The N-terminal PHM domain hydroxylates the glycine-extended peptide, and the C-terminal PAL domain converts the intermediate to the amidated product. PAM is essential for the maturation of numerous bioactive peptides, including neuropeptides and hormones. The protein is localized to secretory vesicles and is highly expressed in neuroendocrine tissues. Alternative splicing generates isoforms that differ in their C-terminal region, affecting subcellular localization and function.

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Related Products

Product name Cat.No. Species Gene ID
GPAM Knockout HEK293 Cell Line EDJ-KQ3039 Human 57678 Details Get a Quote
PAM Knockout HEK293 Cell Line EDJ-KQ3963 Human 5066 Details Get a Quote
PAMR1 Knockout HEK293 Cell Line EDJ-KQ8284 Human 25891 Details Get a Quote
CPAMD8 Knockout HEK293 Cell Line EDJ-KQ8698 Human 27151 Details Get a Quote
SPAM1 Knockout HEK293 Cell Line EDJ-KQ15429 Human 6677 Details Get a Quote
GPAM Knockout A-549 Cell Line EDJ-KQ24277 Human 57678 Details Get a Quote
GPAM Knockout HCT 116 Cell Line EDJ-KQ24278 Human 57678 Details Get a Quote
GPAM Knockout HeLa Cell Line EDJ-KQ24279 Human 57678 Details Get a Quote
PAM Knockout HeLa Cell Line EDJ-KQ24895 Human 5066 Details Get a Quote
PAM Knockout A-549 Cell Line EDJ-KQ26238 Human 5066 Details Get a Quote
PAM Knockout HCT 116 Cell Line EDJ-KQ26239 Human 5066 Details Get a Quote
PAM16 Knockout HEK293 Cell Line EDJ-KQ51272 Human 51025 Details Get a Quote
CORO7-PAM16 Knockout HEK293 Cell Line EDJ-KQ52493 Human 100529144 Details Get a Quote
SPAM1 Knockout HeLa Cell Line EDJ-KQ54543 Human 6677 Details Get a Quote
PAMR1 Knockout HeLa Cell Line EDJ-KQ55843 Human 25891 Details Get a Quote
Displaying Records 1 To 15 Of 28 Records

Reference Databases

NCBI Gene https://www.ncbi.nlm.nih.gov/gene/5066
OMIM https://www.omim.org/entry/170270
HGNC https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:8596
Ensembl https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000145730
UniProt https://www.uniprot.org/uniprot/P19021
ClinVar https://www.ncbi.nlm.nih.gov/clinvar/?term=PAM%5Bgene%5D
COSMIC https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=PAM
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