LCMT1: Leucine Carboxyl Methyltransferase 1

A key regulator of protein phosphatase 2A (PP2A) methylation and cellular signaling

Gene Information Card

Symbol LCMT1
Full Name Leucine carboxyl methyltransferase 1
Gene Type Protein coding
Chromosomal Location 16p12.1
NCBI Gene ID 51451 ncbi.nlm.nih.gov/gene/51451
Ensembl ID ENSG00000140564
UniProt ID O14744
OMIM ID 609474
HGNC ID 28987
Aliases LCMT, CGI-68, PPMT1

Description

LCMT1 encodes leucine carboxyl methyltransferase 1, an enzyme that methylates the C-terminal leucine residue of the protein phosphatase 2A (PP2A) catalytic subunit. This methylation is essential for PP2A holoenzyme assembly and activity, thereby regulating diverse cellular processes including cell cycle, apoptosis, and signal transduction.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Cancer (various) Altered PP2A methylation affects tumor suppressor pathways PMID: 21900206
Alzheimer's disease Reduced PP2A methylation linked to tau hyperphosphorylation PMID: 17984093
Intellectual disability LCMT1 mutations impair PP2A function in neuronal development PMID: 28135719

Expression Profile

Tissue Expression
Tissue nTPM level
Brain 12.5 Medium
Heart 8.3 Low
Liver 6.1 Low
Kidney 9.7 Low
Testis 15.2 Medium
Cell Line Expression
Cell Line nTPM Notes
HEK293 14.0 High expression
HeLa 11.5 Moderate expression
SH-SY5Y 13.2 High expression
MCF7 9.8 Low expression
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.442C>T (p.Arg148Trp) Missense <0.01% Reduced methyltransferase activity
c.625G>A (p.Gly209Ser) Missense <0.01% Impaired PP2A binding
c.1A>G (p.Met1Val) Start loss <0.01% Loss of protein expression
Mutation functional classification

Loss of Function (LOF)

Missense mutations (e.g., p.Arg148Trp) reduce enzymatic activity and PP2A methylation.

Gain of Function (GOF)

No gain-of-function mutations reported.

Dominant Negative (DN)

No dominant-negative mutations described.

Pathways

• PP2A methylation pathway
• Regulation of protein phosphatase activity
• Wnt signaling pathway

Protein Summary

LCMT1 is a 334-amino acid methyltransferase localized to the cytoplasm and nucleus. It specifically methylates the C-terminal leucine residue of the PP2A catalytic subunit (PPP2CA and PPP2CB), enabling PP2A holoenzyme assembly. This modification is critical for PP2A's role in dephosphorylating key signaling proteins, including those in the Akt, MAPK, and Wnt pathways.

Related Products

Product name Cat.No. Species Gene ID
LCMT1 Knockout HEK293 Cell Line EDJ-KQ11100 Human 51451 Details Get a Quote
LCMT1 Knockout A-549 Cell Line EDJ-KQ39056 Human 51451 Details Get a Quote
LCMT1 Knockout HCT 116 Cell Line EDJ-KQ39057 Human 51451 Details Get a Quote
LCMT1 Knockout HeLa Cell Line EDJ-KQ37748 Human 51451 Details Get a Quote
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