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

Summary

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
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

Location:: 1q21.3

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
109.20211119	current	GRCh38.p13 (GCF_000001405.39)	1	NC_000001.11 (151870866..151909511, complement)
105.20201022	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (151843342..151881987, complement)

Chromosome 1 - NC_000001.11 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: 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Enolase-phosphatase 1 acts as an oncogenic driver in glioma.
Title: Enolase-phosphatase 1 acts as an oncogenic driver in glioma.
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.
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.
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.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
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.
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.
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.
CTMP induces translocation of Akt to the membrane and thereby increases the level of Akt phosphorylation. As a result, CTMP enhances various cellular activities that are principally mediated by the PI3-kinase/Akt pathway.
Title: Carboxy-terminal modulator protein induces Akt phosphorylation and activation, thereby enhancing antiapoptotic, glycogen synthetic, and glucose uptake pathways.

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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

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH48117 (e-PCR)
- UniSTS:47626

D11S2560 (e-PCR)
- UniSTS:37928

D8S2279 (e-PCR)
- UniSTS:473907

L18426 (e-PCR)
- UniSTS:34648

D15S1477 (e-PCR)
- UniSTS:474482

D1S1423 (e-PCR)
- UniSTS:149619

RH64680 (e-PCR)
- UniSTS:87936

WI-17569 (e-PCR)
- UniSTS:25740

RH94002 (e-PCR)
- UniSTS:88513

GDB:313783 (e-PCR)
- UniSTS:13512

Homology

Homologs of the THEM4 gene: The THEM4 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, zebrafish, and frog.
Orthologs from Annotation Pipeline: 173 organisms have orthologs with human gene THEM4
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables myristoyl-CoA hydrolase activity	IEA Inferred from Electronic Annotation more info
enables palmitoyl-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 protein kinase B signaling	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	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

EC 3.1.2.2

XP_011507444.1

EC 3.1.2.2

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_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

Q5T1C6

UniProtKB/TrEMBL

A8K0C9

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: Homo sapiens Updated Annotation Release 109.20211119

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p13 Primary Assembly

Range

151870866..151909511 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011509142.2 → XP_011507444.1 acyl-coenzyme A thioesterase THEM4 isoform X1

Conserved Domains (1) summary

cd03443
Location:55 → 167

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 ...

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_176853.2: Suppressed sequence

Description

NM_176853.2: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.