Q16740 (CLPP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Putative ATP-dependent Clp protease proteolytic subunit, mitochondrial
EC=3.4.21.92

Alternative name(s):
Endopeptidase Clp

Gene names

Name:

CLPP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	277 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
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).
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
Sequence similarities	Belongs to the peptidase S14 family.

Ontologies

Keywords
Cellular component	Mitochondrion
Domain	Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Hydrolase Protease Serine protease
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrial matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: UniProtKB serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 56

56

Mitochondrion Ref.4

Chain

57 – 277

221

Putative ATP-dependent Clp protease proteolytic subunit, mitochondrial

PRO_0000005516

Sites

Active site

153

1

Probable

Active site

178

1

Probable

Amino acid modifications

Modified residue

211

1

N6-acetyllysine Ref.7

Modified residue

277

1

Phosphothreonine Ref.6

Experimental info

Sequence conflict

111

1

N → S in BAG34912. Ref.2

Secondary structure

1

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277

Helix Strand Turn

Details...

Helix

75 – 80

6

Turn

81 – 83

3

Beta strand

84 – 91

8

Helix

93 – 109

17

Beta strand

111 – 113

3

Beta strand

115 – 121

7

Helix

126 – 138

13

Beta strand

143 – 152

10

Helix

154 – 160

7

Beta strand

167 – 169

3

Beta strand

174 – 177

4

Helix

188 – 213

26

Helix

217 – 224

8

Beta strand

228 – 230

3

Helix

232 – 238

7

Beta strand

242 – 244

3

Sequences

	Sequence		Length	Mass (Da)
	Q16740 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: B03AAC5D50F7880E	FASTA	277	30,180
	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

References

	« Hide 'large scale' referencesShow '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: 8543061] [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. , 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: 14702039] [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: 15489334] [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: 19892738] [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: 10525407] [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: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-277, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[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., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-211, MASS SPECTROMETRY.
[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: 21269460] [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: 15522782] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
+	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.

IPI

IPI00003870.

PIR

S68421.

RefSeq

NP_006003.1. NM_006012.2.

UniGene

Hs.515092.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TG6	X-ray	2.10	A/B/C/D/E/F/G	1-277	[»]

ProteinModelPortal

Q16740.

SMR

Q16740. Positions 57-261.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-50384N.

STRING

Q16740.

Protein family/group databases

MEROPS

S14.003.

PTM databases

PhosphoSite

Q16740.

Polymorphism databases

DMDM

3023512.

Proteomic databases

PeptideAtlas

Q16740.

PRIDE

Q16740.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000245816; ENSP00000245816; ENSG00000125656.

GeneID

8192.

KEGG

hsa:8192.

NMPDR

fig|9606.3.peg.15498.

UCSC

uc002mem.1. human.

Organism-specific databases

CTD

8192.

GeneCards

GC19P006315.

HGNC

HGNC:2084. CLPP.

HPA

HPA010649.

MIM

601119. gene.

neXtProt

NX_Q16740.

PharmGKB

PA26610.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG16416.

GeneTree

ENSGT00390000005830.

HOGENOM

HBG558421.

HOVERGEN

HBG001689.

InParanoid

Q16740.

OMA

MEAQDFG.

OrthoDB

EOG46T32D.

PhylomeDB

Q16740.

Enzyme and pathway databases

BRENDA

3.4.21.92. 2681.

Gene expression databases

ArrayExpress

Q16740.

Bgee

Q16740.

CleanEx

HS_CLPP.

Genevestigator

Q16740.

GermOnline

ENSG00000125656. Homo sapiens.

Family and domain databases

InterPro

IPR023562. Pept_S14/S49.
IPR001907. Pept_S14_ClpP.
IPR018215. Pept_S14_ClpP_AS.
[Graphical view]

KO

K01358.

PANTHER

PTHR10381. Pept_S14_ClpP. 1 hit.

Pfam

PF00574. CLP_protease. 1 hit.
[Graphical view]

PRINTS

PR00127. CLPPROTEASEP.

PROSITE

PS00382. CLP_PROTEASE_HIS. 1 hit.
PS00381. CLP_PROTEASE_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

30886.

SOURCE

Search...

Entry information

Entry name

CLPP_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 106 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.