Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q16740 (CLPP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | 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:
Putative ATP-dependent Clp protease proteolytic subunit, mitochondrial

EC=3.4.21.92
Alternative name(s):
Endopeptidase Clp
Gene names
Name:CLPP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length277 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Clp cleaves peptides in various proteins in a process that requires ATP hydrolysis. Clp may be responsible for a fairly general and central housekeeping function rather than for the degradation of specific substrates. HAMAP-Rule MF_00444

Catalytic activity

Hydrolysis of proteins to small peptides in the presence of ATP and magnesium. Alpha-casein is the usual test substrate. In the absence of ATP, only oligopeptides shorter than five residues are hydrolyzed (such as succinyl-Leu-Tyr-|-NHMec; and Leu-Tyr-Leu-|-Tyr-Trp, in which cleavage of the -Tyr-|-Leu- and -Tyr-|-Trp bonds also occurs). HAMAP-Rule MF_00444

Subunit structure

Tetradecamer that assembles into a two heptameric rings with a central cavity. Ref.5

Subcellular location

Mitochondrion matrix Ref.5.

Tissue specificity

Predominantly expressed in skeletal muscle. Intermediate levels in heart, liver and pancreas. Low in brain, placenta, lung and kidney. Ref.1

Involvement in disease

Perrault syndrome 3 (PRLTS3) [MIM:614129]: A sex-influenced disorder characterized by sensorineural deafness in both males and females, and ovarian dysgenesis in females. Affected females have primary amenorrhea, streak gonads, and infertility, whereas affected males show normal pubertal development and are fertile. A spectrum of additional clinical features, including cerebellar ataxia, learning disability, and peripheral neuropathy, have been described in some PRLTS3 affected individuals.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Sequence similarities

Belongs to the peptidase S14 family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 5656Mitochondrion Ref.4
Chain57 – 277221Putative ATP-dependent Clp protease proteolytic subunit, mitochondrial HAMAP-Rule MF_00444
PRO_0000005516

Sites

Active site1531 Probable
Active site1781 Probable

Amino acid modifications

Modified residue2001N6-succinyllysine By similarity
Modified residue2111N6-acetyllysine Ref.7

Natural variations

Natural variant1451T → P in PRLTS3. Ref.10
VAR_070092
Natural variant1471C → S in PRLTS3. Ref.10
VAR_070093

Experimental info

Sequence conflict1111N → S in BAG34912. Ref.2

Secondary structure

............................... 277
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q16740 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: B03AAC5D50F7880E

FASTA27730,180
        10         20         30         40         50         60 
MWPGILVGGA RVASCRYPAL GPRLAAHFPA QRPPQRTLQN GLALQRCLHA TATRALPLIP 

        70         80         90        100        110        120 
IVVEQTGRGE RAYDIYSRLL RERIVCVMGP IDDSVASLVI AQLLFLQSES NKKPIHMYIN 

       130        140        150        160        170        180 
SPGGVVTAGL AIYDTMQYIL NPICTWCVGQ AASMGSLLLA AGTPGMRHSL PNSRIMIHQP 

       190        200        210        220        230        240 
SGGARGQATD IAIQAEEIMK LKKQLYNIYA KHTKQSLQVI ESAMERDRYM SPMEAQEFGI 

       250        260        270 
LDKVLVHPPQ DGEDEPTLVQ KEPVEAAPAA EPVPAST 

« Hide

References

« Hide 'large scale' references
[1]"Human ClpP protease: cDNA sequence, tissue-specific expression and chromosomal assignment of the gene."
Bross P., Andresen B.S., Knudsen I., Kruse T.A., Gregersen N.
FEBS Lett. 377:249-252(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Tissue: Placenta.
[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: Skeletal muscle.
[3]"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: Lymph.
[4]"Global profiling of protease cleavage sites by chemoselective labeling of protein N-termini."
Xu G., Shin S.B., Jaffrey S.R.
Proc. Natl. Acad. Sci. U.S.A. 106:19310-19315(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE [LARGE SCALE ANALYSIS] OF 57-69.
Tissue: Leukemic T-cell.
[5]"Mitochondrial localization and oligomeric structure of HClpP, the human homologue of E. coli ClpP."
de Sagarra M.R., Mayo I., Marco S., Rodriguez-Vilarino S., Oliva J., Carrascosa J.L., Castano J.G.
J. Mol. Biol. 292:819-825(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, SUBCELLULAR LOCATION.
[6]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"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-211, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"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].
[9]"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: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
[10]"Perrault syndrome is caused by recessive mutations in CLPP, encoding a mitochondrial ATP-dependent chambered protease."
University of Washington Center for Mendelian Genomics
Jenkinson E.M., Rehman A.U., Walsh T., Clayton-Smith J., Lee K., Morell R.J., Drummond M.C., Khan S.N., Naeem M.A., Rauf B., Billington N., Schultz J.M., Urquhart J.E., Lee M.K., Berry A., Hanley N.A., Mehta S., Cilliers D. expand/collapse author list , Clayton P.E., Kingston H., Smith M.J., Warner T.T., Black G.C., Trump D., Davis J.R., Ahmad W., Leal S.M., Riazuddin S., King M.C., Friedman T.B., Newman W.G.
Am. J. Hum. Genet. 92:605-613(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PRLTS3 PRO-145 AND SER-147.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z50853 mRNA. Translation: CAA90705.1.
AK311973 mRNA. Translation: BAG34912.1.
BC002956 mRNA. Translation: AAH02956.1.
PIRS68421.
RefSeqNP_006003.1. NM_006012.2.
UniGeneHs.515092.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1TG6X-ray2.10A/B/C/D/E/F/G1-277[»]
ProteinModelPortalQ16740.
SMRQ16740. Positions 57-261.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113835. 2 interactions.
DIPDIP-50384N.
IntActQ16740. 1 interaction.
STRING9606.ENSP00000245816.

Protein family/group databases

MEROPSS14.003.

PTM databases

PhosphoSiteQ16740.

Polymorphism databases

DMDM3023512.

Proteomic databases

PaxDbQ16740.
PeptideAtlasQ16740.
PRIDEQ16740.

Protocols and materials databases

DNASU8192.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000245816; ENSP00000245816; ENSG00000125656.
GeneID8192.
KEGGhsa:8192.
UCSCuc002mem.1. human.

Organism-specific databases

CTD8192.
GeneCardsGC19P006315.
HGNCHGNC:2084. CLPP.
HPAHPA010649.
MIM601119. gene.
614129. phenotype.
neXtProtNX_Q16740.
Orphanet2855. Perrault syndrome.
PharmGKBPA26610.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0740.
HOGENOMHOG000285833.
HOVERGENHBG001689.
InParanoidQ16740.
KOK01358.
OMAANLIIAQ.
OrthoDBEOG77WWD5.
PhylomeDBQ16740.
TreeFamTF105002.

Enzyme and pathway databases

BRENDA3.4.21.92. 2681.

Gene expression databases

ArrayExpressQ16740.
BgeeQ16740.
CleanExHS_CLPP.
GenevestigatorQ16740.

Family and domain databases

HAMAPMF_00444. ClpP.
InterProIPR001907. ClpP.
IPR023562. ClpP/TepA.
IPR018215. ClpP_AS.
[Graphical view]
PANTHERPTHR10381. PTHR10381. 1 hit.
PfamPF00574. CLP_protease. 1 hit.
[Graphical view]
PRINTSPR00127. CLPPROTEASEP.
PROSITEPS00382. CLP_PROTEASE_HIS. 1 hit.
PS00381. CLP_PROTEASE_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ16740.
GeneWikiCLPP.
GenomeRNAi8192.
NextBio30886.
PROQ16740.
SOURCESearch...

Entry information

Entry nameCLPP_HUMAN
AccessionPrimary (citable) accession number: Q16740
Secondary accession number(s): B2R4W5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: March 19, 2014
This is version 126 of the entry and version 1 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

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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 19

Human chromosome 19: entries, gene names and cross-references to MIM