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

    Gene ID: 51451, updated on 17-Jun-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_2023_10 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (25111742..25178228)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (25391240..25457759)
    105.20220307 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
    • 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. A LCMT1-PME-1 methylation equilibrium controls mitotic spindle size. Xia X, et al. Cell Cycle, 2015. PMID 25839665, Free PMC Article
    3. 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
    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. NNMT Silencing Activates Tumor Suppressor PP2A, Inactivates Oncogenic STKs, and Inhibits Tumor Forming Ability. Palanichamy K, et al. Clin Cancer Res, 2017 May 1. PMID 27810903, Free PMC Article

    See all (32) 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.
    Submit: New GeneRIF Correction

    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
    involved_in C-terminal protein methylation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    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
    		  
    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_2023_10

    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

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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