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Protein

ATP-dependent Clp protease ATP-binding subunit clpX-like, mitochondrial

Gene

CLPX

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

ATP-dependent specificity component of the Clp protease complex. Hydrolyzes ATP (PubMed:28874591). Targets specific substrates for degradation by the Clp complex (PubMed:11923310, PubMed:22710082). Can perform chaperone functions in the absence of CLPP. Enhances the DNA-binding activity of TFAM and is required for maintaining a normal mitochondrial nucleoid structure (PubMed:22841477). ATP-dependent unfoldase that stimulates the incorporation of the pyridoxal phosphate cofactor into 5-aminolevulinate synthase, thereby activating 5-aminolevulinate (ALA) synthesis, the first step in heme biosynthesis (PubMed:28874591). Important for efficient erythropoiesis through upregulation of heme biosynthesis (PubMed:25957689, PubMed:28874591).5 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri105 – 130C4-typeAdd BLAST26
Nucleotide bindingi294 – 301ATPBy similarity8

GO - Molecular functioni

  • ATPase activity Source: UniProtKB
  • ATP binding Source: UniProtKB
  • ATP-dependent peptidase activity Source: GO_Central
  • metal ion binding Source: UniProtKB-KW
  • peptidase activator activity Source: UniProtKB
  • unfolded protein binding Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionChaperone
LigandATP-binding, Metal-binding, Nucleotide-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
ATP-dependent Clp protease ATP-binding subunit clpX-like, mitochondrial
Gene namesi
Name:CLPX
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000166855.9
HGNCiHGNC:2088 CLPX
MIMi615611 gene
neXtProtiNX_O76031

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion, Mitochondrion nucleoid

Pathology & Biotechi

Involvement in diseasei

Protoporphyria, erythropoietic, 2 (EPP2)1 Publication
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant form of porphyria with onset in infancy. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. Erythropoietic protoporphyria is marked by excessive protoporphyrin in erythrocytes, plasma, liver and feces, and by widely varying photosensitive skin changes ranging from a burning or pruritic sensation to erythema, edema and wheals.
See also OMIM:618015
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_081001298G → D in EPP2; results in decreased ATP hydrolysis; cells with the mutant protein show increased ALA levels and accumulation of the heme biosynthesis intermediate protoporphyrin IX. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi359E → A: Abolishes ATP hydrolysis. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi618015 phenotype
OpenTargetsiENSG00000166855
PharmGKBiPA26614

Chemistry databases

ChEMBLiCHEMBL3797014

Polymorphism and mutation databases

BioMutaiCLPX

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 56MitochondrionSequence analysisAdd BLAST56
ChainiPRO_000000551857 – 633ATP-dependent Clp protease ATP-binding subunit clpX-like, mitochondrialAdd BLAST577

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei437N6-acetyllysineCombined sources1
Modified residuei617PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO76031
MaxQBiO76031
PaxDbiO76031
PeptideAtlasiO76031
PRIDEiO76031
ProteomicsDBi50351

PTM databases

iPTMnetiO76031
PhosphoSitePlusiO76031

Expressioni

Tissue specificityi

Higher expression in skeletal muscle and heart and to a lesser extent in liver, brain, placenta, lung, kidney and pancreas.1 Publication

Gene expression databases

BgeeiENSG00000166855 Expressed in 223 organ(s), highest expression level in sperm
CleanExiHS_CLPX
ExpressionAtlasiO76031 baseline and differential
GenevisibleiO76031 HS

Organism-specific databases

HPAiHPA040262
HPA048199

Interactioni

Subunit structurei

Homohexamer that forms a ring structure; this hexamerization requires ATP binding. Component of the Clp complex formed by the assembly of two CLPP heptameric rings with two CLPX hexameric rings, giving rise to a symmetrical structure with two central CLPP rings flanked by a CLPX ring at either end of the complex. Interacts with TFAM.5 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116056, 59 interactors
CORUMiO76031
DIPiDIP-50293N
IntActiO76031, 44 interactors
MINTiO76031
STRINGi9606.ENSP00000300107

Structurei

3D structure databases

ProteinModelPortaliO76031
SMRiO76031
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the ClpX chaperone family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri105 – 130C4-typeAdd BLAST26

Keywords - Domaini

Transit peptide, Zinc-finger

Phylogenomic databases

eggNOGiKOG0745 Eukaryota
COG1219 LUCA
GeneTreeiENSGT00390000017625
HOGENOMiHOG000010093
HOVERGENiHBG004940
InParanoidiO76031
KOiK03544
OMAiNDNDKNF
OrthoDBiEOG091G07XR
PhylomeDBiO76031
TreeFamiTF312884

Family and domain databases

InterProiView protein in InterPro
IPR003593 AAA+_ATPase
IPR003959 ATPase_AAA_core
IPR019489 Clp_ATPase_C
IPR004487 Clp_protease_ATP-bd_su_ClpX
IPR027417 P-loop_NTPase
PANTHERiPTHR11262 PTHR11262, 1 hit
PfamiView protein in Pfam
PF07724 AAA_2, 1 hit
PF10431 ClpB_D2-small, 1 hit
SMARTiView protein in SMART
SM00382 AAA, 1 hit
SM01086 ClpB_D2-small, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
TIGRFAMsiTIGR00382 clpX, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

O76031-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MPSCGACTCG AAAVRLITSS LASAQRGISG GRIHMSVLGR LGTFETQILQ
60 70 80 90 100
RAPLRSFTET PAYFASKDGI SKDGSGDGNK KSASEGSSKK SGSGNSGKGG
110 120 130 140 150
NQLRCPKCGD LCTHVETFVS STRFVKCEKC HHFFVVLSEA DSKKSIIKEP
160 170 180 190 200
ESAAEAVKLA FQQKPPPPPK KIYNYLDKYV VGQSFAKKVL SVAVYNHYKR
210 220 230 240 250
IYNNIPANLR QQAEVEKQTS LTPRELEIRR REDEYRFTKL LQIAGISPHG
260 270 280 290 300
NALGASMQQQ VNQQIPQEKR GGEVLDSSHD DIKLEKSNIL LLGPTGSGKT
310 320 330 340 350
LLAQTLAKCL DVPFAICDCT TLTQAGYVGE DIESVIAKLL QDANYNVEKA
360 370 380 390 400
QQGIVFLDEV DKIGSVPGIH QLRDVGGEGV QQGLLKLLEG TIVNVPEKNS
410 420 430 440 450
RKLRGETVQV DTTNILFVAS GAFNGLDRII SRRKNEKYLG FGTPSNLGKG
460 470 480 490 500
RRAAAAADLA NRSGESNTHQ DIEEKDRLLR HVEARDLIEF GMIPEFVGRL
510 520 530 540 550
PVVVPLHSLD EKTLVQILTE PRNAVIPQYQ ALFSMDKCEL NVTEDALKAI
560 570 580 590 600
ARLALERKTG ARGLRSIMEK LLLEPMFEVP NSDIVCVEVD KEVVEGKKEP
610 620 630
GYIRAPTKES SEEEYDSGVE EEGWPRQADA ANS
Length:633
Mass (Da):69,224
Last modified:July 11, 2001 - v2
Checksum:iCF46A6DC0DDBF022
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YK07H0YK07_HUMAN
ATP-dependent Clp protease ATP-bind...
CLPX
130Annotation score:
H0YM48H0YM48_HUMAN
ATP-dependent Clp protease ATP-bind...
CLPX
268Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti21L → P in BAF85005 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_081001298G → D in EPP2; results in decreased ATP hydrolysis; cells with the mutant protein show increased ALA levels and accumulation of the heme biosynthesis intermediate protoporphyrin IX. 1 Publication1
Natural variantiVAR_048826488I → T. Corresponds to variant dbSNP:rs35754835Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ006267 mRNA Translation: CAA06933.2
AJ276980
, AJ276981, AJ276966, AJ276967, AJ276968, AJ276969, AJ276970, AJ276971, AJ276972, AJ276973, AJ276974, AJ276975, AJ276976, AJ276977 Genomic DNA Translation: CAC01291.1
AK292316 mRNA Translation: BAF85005.1
CH471082 Genomic DNA Translation: EAW77715.1
BC130373 mRNA Translation: AAI30374.1
BC136487 mRNA Translation: AAI36488.1
CCDSiCCDS10202.1
RefSeqiNP_006651.2, NM_006660.4
UniGeneiHs.113823

Genome annotation databases

EnsembliENST00000300107; ENSP00000300107; ENSG00000166855
GeneIDi10845
KEGGihsa:10845
UCSCiuc002aom.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ006267 mRNA Translation: CAA06933.2
AJ276980
, AJ276981, AJ276966, AJ276967, AJ276968, AJ276969, AJ276970, AJ276971, AJ276972, AJ276973, AJ276974, AJ276975, AJ276976, AJ276977 Genomic DNA Translation: CAC01291.1
AK292316 mRNA Translation: BAF85005.1
CH471082 Genomic DNA Translation: EAW77715.1
BC130373 mRNA Translation: AAI30374.1
BC136487 mRNA Translation: AAI36488.1
CCDSiCCDS10202.1
RefSeqiNP_006651.2, NM_006660.4
UniGeneiHs.113823

3D structure databases

ProteinModelPortaliO76031
SMRiO76031
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116056, 59 interactors
CORUMiO76031
DIPiDIP-50293N
IntActiO76031, 44 interactors
MINTiO76031
STRINGi9606.ENSP00000300107

Chemistry databases

ChEMBLiCHEMBL3797014

PTM databases

iPTMnetiO76031
PhosphoSitePlusiO76031

Polymorphism and mutation databases

BioMutaiCLPX

Proteomic databases

EPDiO76031
MaxQBiO76031
PaxDbiO76031
PeptideAtlasiO76031
PRIDEiO76031
ProteomicsDBi50351

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000300107; ENSP00000300107; ENSG00000166855
GeneIDi10845
KEGGihsa:10845
UCSCiuc002aom.4 human

Organism-specific databases

CTDi10845
EuPathDBiHostDB:ENSG00000166855.9
GeneCardsiCLPX
HGNCiHGNC:2088 CLPX
HPAiHPA040262
HPA048199
MIMi615611 gene
618015 phenotype
neXtProtiNX_O76031
OpenTargetsiENSG00000166855
PharmGKBiPA26614
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0745 Eukaryota
COG1219 LUCA
GeneTreeiENSGT00390000017625
HOGENOMiHOG000010093
HOVERGENiHBG004940
InParanoidiO76031
KOiK03544
OMAiNDNDKNF
OrthoDBiEOG091G07XR
PhylomeDBiO76031
TreeFamiTF312884

Miscellaneous databases

ChiTaRSiCLPX human
GenomeRNAii10845
PROiPR:O76031
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000166855 Expressed in 223 organ(s), highest expression level in sperm
CleanExiHS_CLPX
ExpressionAtlasiO76031 baseline and differential
GenevisibleiO76031 HS

Family and domain databases

InterProiView protein in InterPro
IPR003593 AAA+_ATPase
IPR003959 ATPase_AAA_core
IPR019489 Clp_ATPase_C
IPR004487 Clp_protease_ATP-bd_su_ClpX
IPR027417 P-loop_NTPase
PANTHERiPTHR11262 PTHR11262, 1 hit
PfamiView protein in Pfam
PF07724 AAA_2, 1 hit
PF10431 ClpB_D2-small, 1 hit
SMARTiView protein in SMART
SM00382 AAA, 1 hit
SM01086 ClpB_D2-small, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
TIGRFAMsiTIGR00382 clpX, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCLPX_HUMAN
AccessioniPrimary (citable) accession number: O76031
Secondary accession number(s): A1L428
, A8K8F1, B9EGI8, Q9H4D9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 11, 2001
Last modified: November 7, 2018
This is version 164 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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