Icmt isoprenylcysteine carboxyl methyltransferase [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Icmtprovided by MGI
Official Full Name: isoprenylcysteine carboxyl methyltransferaseprovided by MGI
Primary source: MGI:MGI:1888594
See related: Ensembl:ENSMUSG00000039662 AllianceGenome:MGI:1888594
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: PPMT; STE14; pcCMT; HSTE14; Gm13095; 1700008E11Rik
Summary: Enables cAMP response element binding protein binding activity and protein C-terminal S-isoprenylcysteine carboxyl O-methyltransferase activity. Involved in CAAX-box protein maturation. Acts upstream of or within several processes, including C-terminal protein methylation; TOR signaling; and determination of adult lifespan. Predicted to be active in endoplasmic reticulum membrane. Is expressed in several structures, including alimentary system; genitourinary system; integumental system; nervous system; and sensory organ. Orthologous to human ICMT (isoprenylcysteine carboxyl methyltransferase). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Ubiquitous expression in cerebellum adult (RPKM 44.7), adrenal adult (RPKM 31.6) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 4 E2; 4 83.02 cM

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	4	NC_000070.7 (152381671..152391583)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	4	NC_000070.6 (152297214..152307126)

Chromosome 4 - NC_000070.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Isoprenylcysteine carboxyl methyltransferase is critical for glioblastoma growth and survival by activating Ras/Raf/Mek/Erk.
Title: Isoprenylcysteine carboxyl methyltransferase is critical for glioblastoma growth and survival by activating Ras/Raf/Mek/Erk.
Isoprenylcysteine Carboxyl Methyltransferase and Its Substrate Ras Are Critical Players Regulating TLR-Mediated Inflammatory Responses.
Title: Isoprenylcysteine Carboxyl Methyltransferase and Its Substrate Ras Are Critical Players Regulating TLR-Mediated Inflammatory Responses.
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.
simultaneous inhibition of BCR-ABL1 and Icmt may represent a potential therapeutic strategy for CML.
Title: Inhibition of isoprenylcysteine carboxylmethyltransferase augments BCR-ABL1 tyrosine kinase inhibition-induced apoptosis in chronic myeloid leukemia.
ICMT deficiency precisely phenocopied Notch1 deficiency in the Pdx1-Cre;LSL-KrasG12D model by exacerbating pancreatic intraepithelial neoplasias, promoting facial papillomas, and derepressing Wnt signaling.
Title: Isoprenylcysteine carboxylmethyltransferase deficiency exacerbates KRAS-driven pancreatic neoplasia via Notch suppression.
inactivating Icmt reduced splenomegaly, the number of immature myeloid cells in peripheral blood, tissue infiltration by myeloid cells, reduced lung tumor development and myeloproliferation phenotypes in a mouse model of K-RAS-induced cancer.
Title: Inactivating Icmt ameliorates K-RAS-induced myeloproliferative disease.
findings suggest that inhibition of isoprenylcysteine-O-carboxyl methyltransferase (ICMT) causes endothelial cell apoptosis by attenuation of Ras GTPase methylation and activation and its downstream antiapoptotic signaling pathway.
Title: Isoprenylcysteine carboxyl methyltransferase activity modulates endothelial cell apoptosis.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (2)
Targeted (3) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:235107

NoName (e-PCR)
- UniSTS:235108

Icmt (e-PCR), detects polymorphism
- UniSTS:506986

RH126968 (e-PCR)
- UniSTS:207732

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables cAMP response element binding protein binding	IMP Inferred from Mutant Phenotype more info	PubMed
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	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein C-terminal S-isoprenylcysteine carboxyl O-methyltransferase activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within C-terminal protein methylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in CAAX-box protein maturation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in S-adenosylhomocysteine metabolic process	ISO Inferred from Sequence Orthology more info
involved_in S-adenosylmethioninamine metabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within TOR signaling	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within bone mineralization	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within determination of adult lifespan	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of fibroblast proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within in utero embryonic development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within liver development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in methylation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within multicellular organism growth	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within multicellular organism growth	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within neuromuscular process	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within positive regulation of fibroblast proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within protein localization	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within protein methylation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of Ras protein signal transduction	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within regulation of cellular senescence	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within regulation of protein localization	IMP Inferred from Mutant Phenotype 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	ISO Inferred from Sequence Orthology more info
is_active_in endoplasmic reticulum membrane	ISO Inferred from Sequence Orthology 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_598549.1

EC 2.1.1.100

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_133788.2 → NP_598549.1 protein-S-isoprenylcysteine O-methyltransferase

See identical proteins and their annotated locations for NP_598549.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes a functional protein.

Source sequence(s)

AF209926, AL611985, BG404528

Consensus CDS

CCDS18998.1

UniProtKB/Swiss-Prot

Q9EQK7

UniProtKB/TrEMBL

Q3U4N2

Related

ENSMUSP00000043390.8, ENSMUST00000048892.14

Conserved Domains (1) summary

pfam04140
Location:164 → 257

ICMT; Isoprenylcysteine carboxyl methyltransferase (ICMT) family

RNA

NR_037908.1 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (2) contains an alternate internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AL611985, BC057132, BG404528

Related

ENSMUST00000151372.8
NR_161302.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AL611985
NR_161303.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AL611985
NR_161304.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AL611985
NR_161306.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AL611985
NR_161307.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AL611985