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    ICMT isoprenylcysteine carboxyl methyltransferase [ Homo sapiens (human) ]

    Gene ID: 23463, updated on 11-Apr-2024

    Summary

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    Official Symbol
    ICMTprovided by HGNC
    Official Full Name
    isoprenylcysteine carboxyl methyltransferaseprovided by HGNC
    Primary source
    HGNC:HGNC:5350
    See related
    Ensembl:ENSG00000116237 MIM:605851; AllianceGenome:HGNC:5350
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    PCMT; PPMT; PCCMT; HSTE14; MST098; MSTP098
    Summary
    This gene encodes the third of three enzymes that posttranslationally modify isoprenylated C-terminal cysteine residues in certain proteins and target those proteins to the cell membrane. This enzyme localizes to the endoplasmic reticulum. Alternative splicing may result in other transcript variants, but the biological validity of those transcripts has not been determined. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in kidney (RPKM 21.7), placenta (RPKM 18.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ICMT in Genome Data Viewer
    Location:
    1p36.31
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (6221193..6235964, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (5746837..5761608, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (6281253..6296024, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene ribosomal protein L22 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 138 Neighboring gene Sharpr-MPRA regulatory region 5942 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:6265555-6266374 Neighboring gene RNF207 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 139 Neighboring gene Sharpr-MPRA regulatory region 13921 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 140 Neighboring gene ring finger protein 207 Neighboring gene MPRA-validated peak28 silencer Neighboring gene ReSE screen-validated silencer GRCh37_chr1:6279526-6279711 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 141 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 142 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:6296257-6297229 Neighboring gene OCT4-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:6299873-6300619 Neighboring gene ICMT divergent transcript Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:6304377-6304934 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:6305171-6305522 Neighboring gene hes family bHLH transcription factor 3

    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. ICMT contributes to hepatocellular carcinoma growth, survival, migration and chemoresistance via multiple oncogenic pathways. Xu J, et al. Biochem Biophys Res Commun, 2019 Oct 20. PMID 31451223
    2. Isoprenylcysteine carboxylmethyltransferase is associated with nasopharyngeal carcinoma chemoresistance and Ras activation. Zhu Y, et al. Biochem Biophys Res Commun, 2019 Aug 27. PMID 31253403
    3. Isoprenylcysteine carboxylmethyltransferase is critical for malignant transformation and tumor maintenance by all RAS isoforms. Lau HY, et al. Oncogene, 2017 Jul 6. PMID 28192404, Free PMC Article
    4. Isoprenylcysteine carboxylmethyltransferase regulates mitochondrial respiration and cancer cell metabolism. Teh JT, et al. Oncogene, 2015 Jun. PMID 25151967
    5. RHO methylation matters: a role for isoprenylcysteine carboxylmethyltransferase in cell migration and adhesion. Cushman I, et al. Cell Adh Migr, 2011 Jan-Feb. PMID 20798596, Free PMC Article

    See all (65) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. PFKFB4 interacts with ICMT and activates RAS/AKT signaling-dependent cell migration in melanoma.
      Title: PFKFB4 interacts with ICMT and activates RAS/AKT signaling-dependent cell migration in melanoma.
    2. CircRNA hsa_circ_0018289 exerts an oncogenic role in cervical cancer progression through miR-1294/ICMT axis.
      Title: CircRNA hsa_circ_0018289 exerts an oncogenic role in cervical cancer progression through miR-1294/ICMT axis.
    3. NRAS is unique among RAS proteins in requiring ICMT for trafficking to the plasma membrane.
      Title: NRAS is unique among RAS proteins in requiring ICMT for trafficking to the plasma membrane.
    4. Isoprenylcysteine carboxylmethyltransferase is required for the impact of mutant KRAS on TAZ protein level and cancer cell self-renewal.
      Title: Isoprenylcysteine carboxylmethyltransferase is required for the impact of mutant KRAS on TAZ protein level and cancer cell self-renewal.
    5. Findings show that isoprenylcysteine carboxylmethyltransferase (Icmt)plays an important role in the development of nasopharyngeal carcinoma (NPC) chemoresistance.
      Title: Isoprenylcysteine carboxylmethyltransferase is associated with nasopharyngeal carcinoma chemoresistance and Ras activation.
    6. ICMT expression is higher in hepatocellular carcinoma (HCC) tissues and cells than normal counterparts. ICMT is critical for HCC growth, migration, survival and chemoresistance.
      Title: ICMT contributes to hepatocellular carcinoma growth, survival, migration and chemoresistance via multiple oncogenic pathways.
    7. ICMT expression is repressed by WT p53. This work unveils a link between postprenylation protein processing and the p53 pathway, indicating that the functional interplay between WT and mutant p53 alters ICMT levels, thereby affecting tumor aggressiveness.
      Title: Isoprenylcysteine carboxy methyltransferase (ICMT) is associated with tumor aggressiveness and its expression is controlled by the p53 tumor suppressor.
    8. Using cell culturing system, mouse model and patient samples, this work is the first to demonstrate the essential roles of Icmt in ovarian cancer via Ras signaling, particularly on its response to chemotherapy.
      Title: Isoprenylcysteine carboxylmethyltransferase regulates ovarian cancer cell response to chemotherapy and Ras activation.
    9. Apoptosis, but not autophagy, that is induced via p21-activated BNIP3 expression accounts for the efficacy of ICMT inhibition in sensitive pancreatic cancer cells in both in vitro and in vivo models. In contrast, cells resistant to ICMT inhibition demonstrated no mitochondria dysfunction or p21 signaling changes under ICMT suppression
      Title: Inhibition of Isoprenylcysteine Carboxylmethyltransferase Induces Cell-Cycle Arrest and Apoptosis through p21 and p21-Regulated BNIP3 Induction in Pancreatic Cancer.
    10. ICMT catalyzed carboxylmethylation is critical for RAB4A activation and interaction with effectors, its localization to endosomes and recycling vesicles, and hence important for RAB4A-dependent integrin beta3 recycling to plasma membrane.
      Title: Isoprenylcysteine carboxylmethyltransferase function is essential for RAB4A-mediated integrin β3 recycling, cell migration and cancer metastasis.
    Submit: New GeneRIF Correction See all GeneRIFs (24)

    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

    Clone Names

    • MGC39955

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein C-terminal S-isoprenylcysteine carboxyl O-methyltransferase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein C-terminal S-isoprenylcysteine carboxyl O-methyltransferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein C-terminal carboxyl O-methyltransferase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    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
    		  
    involved_in C-terminal protein methylation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in S-adenosylhomocysteine metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in S-adenosylmethioninamine metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein modification process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in protein targeting to membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in endoplasmic reticulum IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    protein-S-isoprenylcysteine O-methyltransferase
    Names
    prenylated protein carboxyl methyltransferase
    prenylcysteine carboxyl methyltransferase
    NP_036537.1
    XP_011539442.1
    XP_047272548.1
    XP_054191679.1
    XP_054191680.1

    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_012405.4 → NP_036537.1  protein-S-isoprenylcysteine O-methyltransferase

      See identical proteins and their annotated locations for NP_036537.1

      Status: REVIEWED

      Source sequence(s)
      AL031847, BC028168, CN343480
      Consensus CDS
      CCDS61.1
      UniProtKB/Swiss-Prot
      O60725, Q6FHT0
      Related
      ENSP00000343552.5, ENST00000343813.10
      Conserved Domains (1) summary
      pfam04140
      Location:164 → 257
      ICMT; Isoprenylcysteine carboxyl methyltransferase (ICMT) family

    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_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      6221193..6235964 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011541140.3 → XP_011539442.1  protein-S-isoprenylcysteine O-methyltransferase isoform X1

      See identical proteins and their annotated locations for XP_011539442.1

      UniProtKB/TrEMBL
      B3KS61
      Conserved Domains (1) summary
      pfam04140
      Location:68 → 161
      ICMT; Isoprenylcysteine carboxyl methyltransferase (ICMT) family

    2. XM_047416592.1 → XP_047272548.1  protein-S-isoprenylcysteine O-methyltransferase isoform X2

      UniProtKB/TrEMBL
      A6NKX2, Q7Z750
      Related
      ENSP00000466222.1, ENST00000489498.5

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      5746837..5761608 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054335704.1 → XP_054191679.1  protein-S-isoprenylcysteine O-methyltransferase isoform X1

      UniProtKB/TrEMBL
      B3KS61

    2. XM_054335705.1 → XP_054191680.1  protein-S-isoprenylcysteine O-methyltransferase isoform X2

      UniProtKB/TrEMBL
      A6NKX2, Q7Z750

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_170705.1: Suppressed sequence

      Description
      NM_170705.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O60725.1 GenPept UniProtKB/Swiss-Prot:O60725

    Gene LinkOut

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

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