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

Gene ID: 51451, updated on 2-Nov-2024

Summary

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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
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Genomic context

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See LCMT1 in Genome Data Viewer
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_000016.10Genomic Context describing neighboring genes Neighboring gene thyroid hormone receptor interactor 11 pseudogene Neighboring gene LCMT1 antisense RNA 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:25117841-25118342 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:25118343-25118842 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:25122486-25123013 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10605 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:25137470-25137712 Neighboring gene LCMT1 antisense RNA 2 Neighboring gene RNA, 7SL, cytoplasmic 557, pseudogene Neighboring gene aquaporin 8

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. The structure of human leucine carboxyl methyltransferase 1 that regulates protein phosphatase PP2A. Tsai ML, et al. Acta Crystallogr D Biol Crystallogr, 2011 Jan. PMID 21206058
  2. Leucine carboxyl methyltransferase 1 (LCMT1)-dependent methylation regulates the association of protein phosphatase 2A and Tau protein with plasma membrane microdomains in neuroblastoma cells. Sontag JM, et al. J Biol Chem, 2013 Sep 20. PMID 23943618, Free PMC Article
  3. A LCMT1-PME-1 methylation equilibrium controls mitotic spindle size. Xia X, et al. Cell Cycle, 2015. PMID 25839665, Free PMC Article
  4. The structural basis for tight control of PP2A methylation and function by LCMT-1. Stanevich V, et al. Mol Cell, 2011 Feb 4. PMID 21292165, Free PMC Article
  5. Loss of LCMT1 and biased protein phosphatase 2A heterotrimerization drive prostate cancer progression and therapy resistance. Rasool RU, et al. Nat Commun, 2023 Aug 29. PMID 37644036, Free PMC Article

See all (37) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

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
NP_057393.2
XP_005255411.1
XP_011544164.1
XP_011544166.1
XP_047290153.1
XP_054236414.1
XP_054236415.1
XP_054236416.1

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)

  1. 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

  2. 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

  1. NC_000016.10 Reference GRCh38.p14 Primary Assembly

    Range
    25111742..25178228
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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

  2. XM_011545862.3 → XP_011544164.1  leucine carboxyl methyltransferase 1 isoform X3

    Conserved Domains (1) summary
    pfam04072
    Location:67 → 185
    LCM; Leucine carboxyl methyltransferase

  3. XM_047434197.1 → XP_047290153.1  leucine carboxyl methyltransferase 1 isoform X2

  4. 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

  1. NC_060940.1 Alternate T2T-CHM13v2.0

    Range
    25391240..25457759
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054380441.1 → XP_054236416.1  leucine carboxyl methyltransferase 1 isoform X4

  2. XM_054380439.1 → XP_054236414.1  leucine carboxyl methyltransferase 1 isoform X1

  3. XM_054380440.1 → XP_054236415.1  leucine carboxyl methyltransferase 1 isoform X3

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_016015.3: Suppressed sequence

    Description
    NM_016015.3: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9UIC8.2 GenPept UniProtKB/Swiss-Prot:Q9UIC8

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