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O76031 (CLPX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
ATP-dependent Clp protease ATP-binding subunit clpX-like, mitochondrial
Gene names
Name:CLPX
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length633 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

ATP-dependent specificity component of the Clp protease complex. Hydrolyzes ATP. Targets specific substrates for degradation by the Clp complex. 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. Ref.5 Ref.12 Ref.13

Subunit structure

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. Ref.5 Ref.6 Ref.7 Ref.12 Ref.13

Subcellular location

Mitochondrion. Mitochondrion matrixmitochondrion nucleoid Ref.1 Ref.12.

Tissue specificity

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

Sequence similarities

Belongs to the ClpX chaperone family.

Ontologies

Keywords
   Cellular componentMitochondrion
Mitochondrion nucleoid
   Coding sequence diversityPolymorphism
   DomainTransit peptide
Zinc-finger
   LigandATP-binding
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionChaperone
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processATP catabolic process

Inferred from direct assay Ref.13. Source: UniProtKB

positive regulation of peptidase activity

Inferred from direct assay Ref.5Ref.7. Source: GOC

protein folding

Inferred from electronic annotation. Source: InterPro

proteolysis involved in cellular protein catabolic process

Inferred from direct assay Ref.7. Source: UniProtKB

   Cellular_componentendopeptidase Clp complex

Inferred from direct assay Ref.5Ref.13. Source: UniProtKB

mitochondrial endopeptidase Clp complex

Inferred from direct assay Ref.7. Source: UniProtKB

mitochondrial inner membrane

Inferred from sequence or structural similarity. Source: UniProtKB

mitochondrial matrix

Inferred from direct assay PubMed 10525407. Source: UniProtKB

mitochondrial nucleoid

Inferred from direct assay PubMed 18063578. Source: BHF-UCL

mitochondrion

Inferred from direct assay Ref.1. Source: UniProtKB

   Molecular_functionATP binding

Inferred from sequence or structural similarity. Source: UniProtKB

ATPase activity

Inferred from direct assay Ref.13. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

peptidase activator activity

Inferred from direct assay Ref.5Ref.7. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.5Ref.7. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 5656Mitochondrion Potential
Chain57 – 633577ATP-dependent Clp protease ATP-binding subunit clpX-like, mitochondrial
PRO_0000005518

Regions

Zinc finger105 – 13026C4-type
Nucleotide binding294 – 3018ATP By similarity

Amino acid modifications

Modified residue4371N6-acetyllysine Ref.10
Modified residue6171Phosphoserine Ref.9

Natural variations

Natural variant4881I → T.
Corresponds to variant rs35754835 [ dbSNP | Ensembl ].
VAR_048826

Experimental info

Mutagenesis3591E → A: Abolishes ATP hydrolysis. Ref.13
Sequence conflict211L → P in BAF85005. Ref.2

Sequences

Sequence LengthMass (Da)Tools
O76031 [UniParc].

Last modified July 11, 2001. Version 2.
Checksum: CF46A6DC0DDBF022

FASTA63369,224
        10         20         30         40         50         60 
MPSCGACTCG AAAVRLITSS LASAQRGISG GRIHMSVLGR LGTFETQILQ RAPLRSFTET 

        70         80         90        100        110        120 
PAYFASKDGI SKDGSGDGNK KSASEGSSKK SGSGNSGKGG NQLRCPKCGD LCTHVETFVS 

       130        140        150        160        170        180 
STRFVKCEKC HHFFVVLSEA DSKKSIIKEP ESAAEAVKLA FQQKPPPPPK KIYNYLDKYV 

       190        200        210        220        230        240 
VGQSFAKKVL SVAVYNHYKR IYNNIPANLR QQAEVEKQTS LTPRELEIRR REDEYRFTKL 

       250        260        270        280        290        300 
LQIAGISPHG NALGASMQQQ VNQQIPQEKR GGEVLDSSHD DIKLEKSNIL LLGPTGSGKT 

       310        320        330        340        350        360 
LLAQTLAKCL DVPFAICDCT TLTQAGYVGE DIESVIAKLL QDANYNVEKA QQGIVFLDEV 

       370        380        390        400        410        420 
DKIGSVPGIH QLRDVGGEGV QQGLLKLLEG TIVNVPEKNS RKLRGETVQV DTTNILFVAS 

       430        440        450        460        470        480 
GAFNGLDRII SRRKNEKYLG FGTPSNLGKG RRAAAAADLA NRSGESNTHQ DIEEKDRLLR 

       490        500        510        520        530        540 
HVEARDLIEF GMIPEFVGRL PVVVPLHSLD EKTLVQILTE PRNAVIPQYQ ALFSMDKCEL 

       550        560        570        580        590        600 
NVTEDALKAI ARLALERKTG ARGLRSIMEK LLLEPMFEVP NSDIVCVEVD KEVVEGKKEP 

       610        620        630 
GYIRAPTKES SEEEYDSGVE EEGWPRQADA ANS 

« Hide

References

« Hide 'large scale' references
[1]"Human and mouse mitochondrial orthologs of bacterial ClpX."
Corydon T.J., Wilsbech M., Jespersgaard C., Andresen B.S., Borglum A.D., Pedersen S., Bolund L., Gregersen N., Bross P.
Mamm. Genome 11:899-905(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Skeletal muscle.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain and Testis.
[5]"Functional proteolytic complexes of the human mitochondrial ATP-dependent protease, hClpXP."
Kang S.G., Ortega J., Singh S.K., Wang N., Huang N.N., Steven A.C., Maurizi M.R.
J. Biol. Chem. 277:21095-21102(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT.
[6]"Crystallography and mutagenesis point to an essential role for the N-terminus of human mitochondrial ClpP."
Kang S.G., Maurizi M.R., Thompson M., Mueser T., Ahvazi B.
J. Struct. Biol. 148:338-352(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, INTERACTION WITH CLPP.
[7]"Human mitochondrial ClpP is a stable heptamer that assembles into a tetradecamer in the presence of ClpX."
Kang S.G., Dimitrova M.N., Ortega J., Ginsburg A., Maurizi M.R.
J. Biol. Chem. 280:35424-35432(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, IDENTIFICATION IN A COMPLEX WITH CLPP.
[8]"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-617, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[10]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-437, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Maintenance of mitochondrial genome distribution by mitochondrial AAA+ protein ClpX."
Kasashima K., Sumitani M., Endo H.
Exp. Cell Res. 318:2335-2343(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TFAM.
[13]"Substrate recognition and processing by a Walker B mutant of the human mitochondrial AAA+ protein CLPX."
Lowth B.R., Kirstein-Miles J., Saiyed T., Broetz-Oesterhelt H., Morimoto R.I., Truscott K.N., Dougan D.A.
J. Struct. Biol. 179:193-201(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF GLU-359, SUBUNIT, INTERACTION WITH CLPP.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ006267 mRNA. Translation: CAA06933.2.
AJ276980 expand/collapse EMBL AC list , 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.
CCDSCCDS10202.1.
RefSeqNP_006651.2. NM_006660.3.
UniGeneHs.113823.

3D structure databases

ProteinModelPortalO76031.
SMRO76031. Positions 167-600.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116056. 16 interactions.
IntActO76031. 12 interactions.
MINTMINT-3002168.
STRING9606.ENSP00000300107.

PTM databases

PhosphoSiteO76031.

Proteomic databases

MaxQBO76031.
PaxDbO76031.
PeptideAtlasO76031.
PRIDEO76031.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000300107; ENSP00000300107; ENSG00000166855.
GeneID10845.
KEGGhsa:10845.
UCSCuc002aom.3. human.

Organism-specific databases

CTD10845.
GeneCardsGC15M065440.
HGNCHGNC:2088. CLPX.
HPAHPA040262.
neXtProtNX_O76031.
PharmGKBPA26614.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1219.
HOGENOMHOG000010093.
HOVERGENHBG004940.
InParanoidO76031.
KOK03544.
OMAFSETPAY.
OrthoDBEOG7J17ZF.
PhylomeDBO76031.
TreeFamTF312884.

Gene expression databases

ArrayExpressO76031.
BgeeO76031.
CleanExHS_CLPX.
GenevestigatorO76031.

Family and domain databases

Gene3D3.40.50.300. 3 hits.
InterProIPR003593. AAA+_ATPase.
IPR003959. ATPase_AAA_core.
IPR019489. Clp_ATPase_C.
IPR004487. Clp_protease_ATP-bd_su_ClpX.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERPTHR11262:SF4. PTHR11262:SF4. 1 hit.
PfamPF07724. AAA_2. 1 hit.
PF10431. ClpB_D2-small. 1 hit.
[Graphical view]
SMARTSM00382. AAA. 1 hit.
SM01086. ClpB_D2-small. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 2 hits.
TIGRFAMsTIGR00382. clpX. 1 hit.
ProtoNetSearch...

Other

GenomeRNAi10845.
NextBio41174.
PROO76031.

Entry information

Entry nameCLPX_HUMAN
AccessionPrimary (citable) accession number: O76031
Secondary accession number(s): A1L428 expand/collapse secondary AC list , A8K8F1, B9EGI8, Q9H4D9
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 11, 2001
Last modified: July 9, 2014
This is version 123 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM