CLPX caseinolytic mitochondrial matrix peptidase chaperone subunit X [Homo sapiens (human)] - Gene

Summary

Official Symbol: CLPXprovided by HGNC
Official Full Name: caseinolytic mitochondrial matrix peptidase chaperone subunit Xprovided by HGNC
Primary source: HGNC:HGNC:2088
See related: Ensembl:ENSG00000166855 MIM:615611; AllianceGenome:HGNC:2088
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: EPP2
Summary: The protein encoded by this gene is part of a protease found in mitochondria. This protease is ATP-dependent and targets specific proteins for degradation. The protease consists of two heptameric rings of the CLPP catalytic subunit sandwiched between two hexameric rings of the chaperone subunit encoded by this gene. Targeted proteins are unwound by this protein and then passed on to the CLPP subunit for degradation. Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Nov 2015]
Expression: Ubiquitous expression in liver (RPKM 13.6), testis (RPKM 11.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 15q22.31

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (65148219..65185342, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (62957572..62994692, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (65440557..65477680, complement)

Chromosome 15 - NC_000015.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Inactivity of Peptidase ClpP Causes Primary Accumulation of Mitochondrial Disaggregase ClpX with Its Interacting Nucleoid Proteins, and of mtDNA.
Title: Inactivity of Peptidase ClpP Causes Primary Accumulation of Mitochondrial Disaggregase ClpX with Its Interacting Nucleoid Proteins, and of mtDNA.
Heme-dependent recognition of 5-aminolevulinate synthase by the human mitochondrial molecular chaperone ClpX.
Title: Heme-dependent recognition of 5-aminolevulinate synthase by the human mitochondrial molecular chaperone ClpX.
Experiencing community and domestic violence is associated with epigenetic changes in DNA methylation of BDNF and CLPX in adolescents.
Title: Experiencing community and domestic violence is associated with epigenetic changes in DNA methylation of BDNF and CLPX in adolescents.
The mutation in CLPX inactivates its ATPase activity, resulting in coassembly of mutant and WT protomers to form an enzyme with reduced activity. The presence of low-activity CLPX increases the posttranslational stability of ALAS, causing increased ALAS protein and ALA levels, leading to abnormal accumulation of PPIX.
Title: Mutation in human CLPX elevates levels of δ-aminolevulinate synthase and protoporphyrin IX to promote erythropoietic protoporphyria.
Data suggest that tumors exploit ClpXP-directed proteostasis to maintain mitochondrial bioenergetics, buffer oxidative stress, and enable metastatic competence.
Title: The Mitochondrial Unfoldase-Peptidase Complex ClpXP Controls Bioenergetics Stress and Metastasis.
results illustrate that ClpX overexpression is a good and simple model to study the underlying mechanisms of the UPRmt in mammalian cells.
Title: ClpX stimulates the mitochondrial unfolded protein response (UPRmt) in mammalian cells.
Optical trapping to assay single-molecule ClpXP unfolding and translocation of substrates consisting of domains with varying stabilities and sequences; find that ClpXP unfolds most domains by a single pathway, with kinetics that depend on the native fold and structural stability.
Title: Stochastic but highly coordinated protein unfolding and translocation by the ClpXP proteolytic machine.
Walker B mutation in human CLPX exhibits improved interaction with the model unfolded substrate casein and several putative physiological substrates in vitro.
Title: Substrate recognition and processing by a Walker B mutant of the human mitochondrial AAA+ protein CLPX.
human ClpX, a novel mtDNA regulator, maintains mtDNA nucleoid distribution through TFAM function as a chaperone rather than as a protease and its involvement in mtDNA segregation.
Title: Maintenance of mitochondrial genome distribution by mitochondrial AAA+ protein ClpX.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.

Submit: New GeneRIF Correction See all GeneRIFs (12)

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

Associated conditions

Description	Tests
Protoporphyria, erythropoietic, 2 MedGen: C4693947 OMIM: 618015 GeneReviews: Not available	Compare labs

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

A004Z39 (e-PCR)
- UniSTS:22098

G32749 (e-PCR)
- UniSTS:117330

RH77817 (e-PCR)
- UniSTS:47719

A009P37 (e-PCR)
- UniSTS:28800

STS-H79322 (e-PCR)
- UniSTS:31399

RH78776 (e-PCR)
- UniSTS:31694

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IBA Inferred from Biological aspect of Ancestor more info
enables ATP binding	ISS Inferred from Sequence or Structural Similarity more info
enables ATP hydrolysis activity	IBA Inferred from Biological aspect of Ancestor more info
enables ATP hydrolysis activity	IDA Inferred from Direct Assay more info	PubMed
contributes_to ATP-dependent peptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables ATP-dependent protein folding chaperone	IEA Inferred from Electronic Annotation more info
enables peptidase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein dimerization activity	IEA Inferred from Electronic Annotation more info
enables unfolded protein binding	IEA Inferred from Electronic Annotation more info
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in ATP metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in protein folding	IEA Inferred from Electronic Annotation more info
involved_in proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis involved in protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteolysis involved in protein catabolic process	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in cytosol	IDA Inferred from Direct Assay more info
part_of endopeptidase Clp complex	IDA Inferred from Direct Assay more info	PubMed
part_of endopeptidase Clp complex	IPI Inferred from Physical Interaction more info	PubMed
part_of mitochondrial endopeptidase Clp complex	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial inner membrane	ISS Inferred from Sequence or Structural Similarity more info
is_active_in mitochondrial matrix	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrial matrix	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial matrix	NAS Non-traceable Author Statement more info	PubMed
located_in mitochondrial matrix	TAS Traceable Author Statement more info
located_in mitochondrial nucleoid	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	HTP more info	PubMed
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: ATP-dependent Clp protease ATP-binding subunit clpX-like, mitochondrial

Names: ClpX caseinolytic peptidase X homolog; ClpX caseinolytic protease X homolog; energy-dependent regulator of proteolysis

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_006660.5 → NP_006651.2 ATP-dependent Clp protease ATP-binding subunit clpX-like, mitochondrial precursor

See identical proteins and their annotated locations for NP_006651.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer, protein-coding transcript.

Source sequence(s)

AC013553, AJ006267, BG717994, CA945006

Consensus CDS

CCDS10202.1

UniProtKB/Swiss-Prot

A1L428, A8K8F1, B9EGI8, O76031, Q9H4D9

UniProtKB/TrEMBL

Q9H072

Related

ENSP00000300107.3, ENST00000300107.7

Conserved Domains (4) summary

smart01086
Location:509 → 603

ClpB_D2-small; C-terminal, D2-small domain, of ClpB protein

TIGR00382
Location:102 → 600

clpX; endopeptidase Clp ATP-binding regulatory subunit (clpX)

pfam07724
Location:286 → 502

AAA_2; AAA domain (Cdc48 subfamily)

cl02609
Location:104 → 132

Zn-ribbon; C-terminal zinc ribbon domain of RNA polymerase intrinsic transcript cleavage subunit

RNA

NR_133680.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses two alternate splice junctions compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC013553, BC144166, BG717994, CA945006

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

NC_000015.10 Reference GRCh38.p14 Primary Assembly

Range

65148219..65185342 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011521164.4 → XP_011519466.1 ATP-dependent Clp protease ATP-binding subunit clpX-like, mitochondrial isoform X1

UniProtKB/TrEMBL

Q9H072

Conserved Domains (4) summary

smart01086
Location:495 → 589

ClpB_D2-small; C-terminal, D2-small domain, of ClpB protein

TIGR00382
Location:102 → 586

clpX; endopeptidase Clp ATP-binding regulatory subunit (clpX)

pfam07724
Location:272 → 488

AAA_2; AAA domain (Cdc48 subfamily)

cl02609
Location:104 → 132

Zn-ribbon; C-terminal zinc ribbon domain of RNA polymerase intrinsic transcript cleavage subunit