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    THEM4 thioesterase superfamily member 4 [ Homo sapiens (human) ]

    Gene ID: 117145, updated on 10-Dec-2024

    Summary

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    Official Symbol
    THEM4provided by HGNC
    Official Full Name
    thioesterase superfamily member 4provided by HGNC
    Primary source
    HGNC:HGNC:17947
    See related
    Ensembl:ENSG00000159445 MIM:606388; AllianceGenome:HGNC:17947
    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
    CTMP
    Summary
    Protein kinase B (PKB) is a major downstream target of receptor tyrosine kinases that signal via phosphatidylinositol 3-kinase. Upon cell stimulation, PKB is translocated to the plasma membrane, where it is phosphorylated in the C-terminal regulatory domain. The protein encoded by this gene negatively regulates PKB activity by inhibiting phosphorylation. Transcription of this gene is commonly downregulated in glioblastomas. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in kidney (RPKM 4.4), testis (RPKM 3.1) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See THEM4 in Genome Data Viewer
    Location:
    1q21.3
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (151870866..151909511, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (150994382..151033015, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (151843342..151881987, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1327 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1328 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1329 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1725 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1726 Neighboring gene C2CD4D and THEM5 antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:151820400-151821167 Neighboring gene C2 calcium dependent domain containing 4D Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:151832751-151833558 Neighboring gene thioesterase superfamily member 5 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr1:151870195-151871394 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:151878733-151879272 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1330 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1727 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr1:151882372-151882959 Neighboring gene Sharpr-MPRA regulatory region 4547 Neighboring gene uncharacterized LOC124904421 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1331 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr1:151909054-151909699 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr1:151918150-151918685 Neighboring gene keratin 8 pseudogene 28 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:151941289-151941789 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr1:151964375-151965574 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1332 Neighboring gene S100 calcium binding protein A10

    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. Carboxyl-terminal modulator protein facilitates tumor metastasis in triple-negative breast cancer. Lin CH, et al. Cancer Gene Ther, 2023 Mar. PMID 36400965, Free PMC Article
    2. Hypermethylation and transcriptional downregulation of the carboxyl-terminal modulator protein gene in glioblastomas. Knobbe CB, et al. J Natl Cancer Inst, 2004 Mar 17. PMID 15026474
    3. Carboxyl-terminal modulator protein induces apoptosis by regulating mitochondrial function in lung cancer cells. Hwang SK, et al. Int J Oncol, 2012 May. PMID 22200884
    4. Carboxyl-Terminal Modulator Protein Positively Acts as an Oncogenic Driver in Head and Neck Squamous Cell Carcinoma via Regulating Akt phosphorylation. Chang JW, et al. Sci Rep, 2016 Jun 22. PMID 27328758, Free PMC Article
    5. CTMP, a predictive biomarker for trastuzumab resistance in HER2-enriched breast cancer patient. Chen YC, et al. Oncotarget, 2017 May 2. PMID 27447863, Free PMC Article

    See all (42) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Overview of carboxyl-terminal modulator protein 1 and its importance in various metabolic regulations (Review).
      Title: Overview of carboxyl‑terminal modulator protein 1 and its importance in various metabolic regulations (Review).
    2. Carboxyl-terminal modulator protein facilitates tumor metastasis in triple-negative breast cancer.
      Title: Carboxyl-terminal modulator protein facilitates tumor metastasis in triple-negative breast cancer.
    3. Enolase-phosphatase 1 acts as an oncogenic driver in glioma.
      Title: Enolase-phosphatase 1 acts as an oncogenic driver in glioma.
    4. Results find that head and neck squamous cell carcinoma (HNSCC) tumor tissues and cell lines had high levels of CTMP expression. These data suggest that CTMP functions as a positive regulator of Akt and facilitates HNSCC invasion such as LN metastasis by regulating EMT in a Snail-dependent manner indicating the oncogenic activity of CTMP in HNSCC, and its expression is an independent predictor of clinical prognosis.
      Title: Carboxyl-Terminal Modulator Protein Positively Acts as an Oncogenic Driver in Head and Neck Squamous Cell Carcinoma via Regulating Akt phosphorylation.
    5. CTMP expression may be considered as a prognostic biomarker in HER2-enriched breast cancer and high expression may indicate a utility for AKT-inhibition in these patients.
      Title: CTMP, a predictive biomarker for trastuzumab resistance in HER2-enriched breast cancer patient.
    6. Suggest that CTMP may therefore play a critical role in mitochondrial-mediated apoptosis in lung cancer cells.
      Title: Carboxyl-terminal modulator protein induces apoptosis by regulating mitochondrial function in lung cancer cells.
    7. Observational study of gene-disease association. (HuGE Navigator)
      Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
    8. Data show low or moderate methylation was found in seven selected genes BAD, BBC3, CAV1, CDK2AP1, NPM1, PRKCDBP and THEM4.
      Title: The DNA methylome of pediatric acute lymphoblastic leukemia.
    9. Phosphorylation on Ser37/Ser38 of CTMP is important for the prevention of mitochondrial localization of CTMP, eventually leading to cell death by binding to heat shock protein 70.
      Title: Heat shock protein 70-mediated sensitization of cells to apoptosis by Carboxyl-Terminal Modulator Protein.
    10. Proper maturation of CTMP is essential for its pro-apoptotic function. CTMP delays PKB phosphorylation following cell death induction, suggesting that CTMP regulates apoptosis via inhibition of PKB.
      Title: Carboxy-Terminal Modulator Protein (CTMP) is a mitochondrial protein that sensitizes cells to apoptosis.
    Submit: New GeneRIF Correction See all GeneRIFs (11)

    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

    EBI GWAS Catalog

    Description
    An atlas of genetic influences on human blood metabolites.
    EBI GWAS Catalog
    Genetic determinants influencing human serum metabolome among African Americans.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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

    • FLJ27206, MGC29636

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables long-chain fatty acyl-CoA hydrolase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in fatty acid metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of mitochondrial membrane permeability involved in apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrial inner membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in mitochondrial intermembrane space IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HTP PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in ruffle membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    acyl-coenzyme A thioesterase THEM4
    Names
    C-terminal modulator protein
    acyl-CoA thioesterase THEM4
    carboxyl-terminal modulator protein
    NP_444283.2
    XP_054190154.1

    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_053055.5 → NP_444283.2  acyl-coenzyme A thioesterase THEM4

      See identical proteins and their annotated locations for NP_444283.2

      Status: REVIEWED

      Source sequence(s)
      AF075119, AJ313515, AL450992, DC353229
      Consensus CDS
      CCDS1006.1
      UniProtKB/Swiss-Prot
      B2RBX2, Q5T1C6, Q96KR2
      Related
      ENSP00000357804.3, ENST00000368814.8
      Conserved Domains (1) summary
      cd03443
      Location:119 → 231
      PaaI_thioesterase; PaaI_thioesterase is a tetrameric acyl-CoA thioesterase with a hot dog fold and one of several proteins responsible for phenylacetic acid (PA) degradation in bacteria. Although orthologs of PaaI exist in archaea and eukaryotes, their function has not ...

    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_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      151870866..151909511 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      150994382..151033015 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054334179.1 → XP_054190154.1  acyl-coenzyme A thioesterase THEM4 isoform X1

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_176853.2: Suppressed sequence

      Description
      NM_176853.2: 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
    Q5T1C6.1 GenPept UniProtKB/Swiss-Prot:Q5T1C6

    Gene LinkOut

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

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