LCMT1 leucine carboxyl methyltransferase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: LCMT1provided by HGNC
Official Full Name: leucine carboxyl methyltransferase 1provided by HGNC
Primary source: HGNC:HGNC:17557
See related: Ensembl:ENSG00000205629 MIM:610286; AllianceGenome:HGNC:17557
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: LCMT; PPMT1; CGI-68
Summary: LCMT1 catalyzes the methylation of the carboxyl group of the C-terminal leucine residue (leu309) of the catalytic subunit of protein phosphatase-2A (PPP2CA; MIM 176915) (De Baere et al., 1999 [PubMed 10600115]).[supplied by OMIM, Mar 2008]
Expression: Ubiquitous expression in testis (RPKM 19.0), brain (RPKM 15.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 16p12.1

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (25111742..25178228)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (25391240..25457759)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (25123063..25189549)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Loss of LCMT1 and biased protein phosphatase 2A heterotrimerization drive prostate cancer progression and therapy resistance.
Title: Loss of LCMT1 and biased protein phosphatase 2A heterotrimerization drive prostate cancer progression and therapy resistance.
We demonstrate that NNMT outcompetes leucine carboxyl methyl transferase 1 (LCMT1) for methyl transfer from principal methyl donor SAM in biological systems. Inhibiting NNMT increased the availability of methyl groups for LCMT1 to methylate PP2A, resulting in the inhibition of oncogenic serine/threonine kinases (STK).
Title: NNMT Silencing Activates Tumor Suppressor PP2A, Inactivates Oncogenic STKs, and Inhibits Tumor Forming Ability.
LCMT1-PME-1 methylation equilibrium is critical for regulating mitotic spindle size and thereby proper cell division
Title: A LCMT1-PME-1 methylation equilibrium controls mitotic spindle size.
alterations in the membrane localization of PP2A and Tau following down-regulation of LCMT1 may lead to PP2A and Tau dysfunction in AD.
Title: Leucine carboxyl methyltransferase 1 (LCMT1)-dependent methylation regulates the association of protein phosphatase 2A and Tau protein with plasma membrane microdomains in neuroblastoma cells.
Data indicate that PP2A holoenzyme biogenesis and activity are controlled by five PP2A modulators, consisting of alpha4, PTPA, LCMT1, PME-1 and TIPRL1, which serve to prevent promiscuous phosphatase activity until the holoenzyme is completely assembled.
Title: The biogenesis of active protein phosphatase 2A holoenzymes: a tightly regulated process creating phosphatase specificity.
GSK-3beta can inhibit PP2A by increasing the inhibitory L309-demethylation involving upregulation of PME-1 and inhibition of PPMT1
Title: Glycogen synthase kinase-3β regulates leucine-309 demethylation of protein phosphatase-2A via PPMT1 and PME-1.
determined crystal structures of human LCMT-1 in isolation and in complex with PP2A stabilized by a cofactor mimic. The structures show that the LCMT-1 active-site pocket recognizes the carboxyl terminus of PP2A
Title: The structural basis for tight control of PP2A methylation and function by LCMT-1.
X-ray crystal structure of human LCMT1 protein in complex with the cofactor S-adenosylmethionine (AdoMet) has been solved to a resolution of 2 A.
Title: The structure of human leucine carboxyl methyltransferase 1 that regulates protein phosphatase PP2A.
LCMT-1 is important for normal progression through mitosis and cell survival and is essential for embryonic development
Title: Leucine carboxyl methyltransferase-1 is necessary for normal progression through mitosis in mammalian cells.

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Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH120317 (e-PCR)
- UniSTS:132457

RH70074 (e-PCR)
- UniSTS:19578

RH64916 (e-PCR)
- UniSTS:90533

RH68799 (e-PCR)
- UniSTS:7611

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables S-adenosylmethionine-dependent methyltransferase activity	TAS Traceable Author Statement more info	PubMed
enables protein C-terminal carboxyl O-methyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein C-terminal leucine carboxyl O-methyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein C-terminal leucine carboxyl O-methyltransferase activity	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within C-terminal protein methylation	IDA Inferred from Direct Assay more info	PubMed
involved_in G2/M transition of mitotic cell cycle	TAS Traceable Author Statement more info
acts_upstream_of_or_within negative regulation of protein-containing complex assembly	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within protein methylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein modification process	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of glucose metabolic process	IEA Inferred from Electronic Annotation more info
involved_in regulation of mitotic cell cycle spindle assembly checkpoint	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within regulation of mitotic cell cycle spindle assembly checkpoint	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleoplasm	TAS Traceable Author Statement more info

General protein information

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Preferred Names: leucine carboxyl methyltransferase 1

Names: [Phosphatase 2A protein]-leucine-carboxy methyltransferase 1; protein phosphatase methyltransferase 1; protein-leucine O-methyltransferase

NP_001027563.1

EC 2.1.1.233

NP_057393.2

EC 2.1.1.233

XP_005255411.1

EC 2.1.1.233

XP_011544164.1

EC 2.1.1.233

XP_011544166.1

EC 2.1.1.233

XP_047290153.1

EC 2.1.1.233

XP_054236414.1

EC 2.1.1.233

XP_054236415.1

EC 2.1.1.233

XP_054236416.1

EC 2.1.1.233

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001032391.2 → NP_001027563.1 leucine carboxyl methyltransferase 1 isoform b

See identical proteins and their annotated locations for NP_001027563.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks two alternate internal exons that encode an in-frame segment, compared to variant 1. The resulting isoform (b) is shorter than isoform a.

Source sequence(s)

AL560574, BC001214, BI459868

Consensus CDS

CCDS45446.1

UniProtKB/Swiss-Prot

Q9UIC8

Related

ENSP00000370353.4, ENST00000380966.8

Conserved Domains (1) summary

pfam04072
Location:26 → 162

LCM; Leucine carboxyl methyltransferase
NM_016309.3 → NP_057393.2 leucine carboxyl methyltransferase 1 isoform a

See identical proteins and their annotated locations for NP_057393.2

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).

Source sequence(s)

BC001214, BI459868

Consensus CDS

CCDS45445.1

UniProtKB/Swiss-Prot

A6NL89, A8K770, Q53FC5, Q96CI5, Q9H6I9, Q9NTG4, Q9UIC8, Q9Y378

Related

ENSP00000382021.3, ENST00000399069.8

Conserved Domains (1) summary

pfam04072
Location:26 → 217

LCM; Leucine carboxyl methyltransferase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000016.10 Reference GRCh38.p14 Primary Assembly

Range

25111742..25178228

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011545864.2 → XP_011544166.1 leucine carboxyl methyltransferase 1 isoform X1

See identical proteins and their annotated locations for XP_011544166.1

UniProtKB/Swiss-Prot

Q9UIC8

Conserved Domains (1) summary

pfam04072
Location:67 → 240

LCM; Leucine carboxyl methyltransferase
XM_011545862.3 → XP_011544164.1 leucine carboxyl methyltransferase 1 isoform X3

Conserved Domains (1) summary

pfam04072
Location:67 → 185

LCM; Leucine carboxyl methyltransferase
XM_047434197.1 → XP_047290153.1 leucine carboxyl methyltransferase 1 isoform X2
XM_005255354.5 → XP_005255411.1 leucine carboxyl methyltransferase 1 isoform X4

Conserved Domains (1) summary

cl17173
Location:1 → 117

AdoMet_MTases; S-adenosylmethionine-dependent methyltransferases (SAM or AdoMet-MTase), class I; AdoMet-MTases are enzymes that use S-adenosyl-L-methionine (SAM or AdoMet) as a substrate for methyltransfer, creating the product S-adenosyl-L-homocysteine (AdoHcy). ...

Alternate T2T-CHM13v2.0

Genomic

NC_060940.1 Alternate T2T-CHM13v2.0

Range

25391240..25457759

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054380441.1 → XP_054236416.1 leucine carboxyl methyltransferase 1 isoform X4
XM_054380439.1 → XP_054236414.1 leucine carboxyl methyltransferase 1 isoform X1
XM_054380440.1 → XP_054236415.1 leucine carboxyl methyltransferase 1 isoform X3

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_016015.3: Suppressed sequence

Description

NM_016015.3: This RefSeq record was removed by NCBI staff. Contact [email protected] for further information.