PMPCB

Mitochondrial-processing peptidase subunit beta is an enzyme that in humans is encoded by the PMPCB gene.[5][6] This gene is a member of the peptidase M16 family and encodes a protein with a zinc-binding motif. This protein is located in the mitochondrial matrix and catalyzes the cleavage of the leader peptides of precursor proteins newly imported into the mitochondria, though it only functions as part of a heterodimeric complex.[6]

PMPCB
Identifiers
AliasesPMPCB, Beta-MPP, MPP11, MPPB, MPPP52, P-52, peptidase, mitochondrial processing beta subunit, peptidase, mitochondrial processing subunit beta
External IDsOMIM: 603131 MGI: 1920328 HomoloGene: 3160 GeneCards: PMPCB
Gene location (Human)
Chr.Chromosome 7 (human)[1]
Band7q22.1Start103,297,435 bp[1]
End103,329,511 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

9512

73078

Ensembl

ENSG00000105819

ENSMUSG00000029017

UniProt

O75439

Q9CXT8

RefSeq (mRNA)

NM_004279

NM_028431

RefSeq (protein)

NP_004270

NP_082707

Location (UCSC)Chr 7: 103.3 – 103.33 MbChr 5: 21.74 – 21.76 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Structure

The Mitochondrial-processing peptidase subunit beta precursor protein is 54.4 KDa in size and composed of 489 amino acids. The precursor protein contains a 45 amino acid N-terminal fragment as mitochondrion targeting sequence. After cleavage, the matured PMPCB protein is 49.5 KDa in size and has a theoretical pI of 5.76.

Function

Mitochondrial-processing peptidase (MPP) is a metalloendopeptidase, containing two structurally related subunits, mitochondrial-processing peptidase subunit alpha and subunit beta, working in conjunction for its catalytic function.[7] Containing the catalytic site, the beta subunit PMPCB protein cleaves presequences (transit peptides) from mitochondrial protein precursors and releases of N-terminal transit peptides from precursor proteins imported into the mitochondrion, typically with Arg in position P2.

Interactions

As the beta subunit of Mitochondrial-processing peptidase, PMPCB forms a heterodimer with the subunit Mitochondrial-processing peptidase subunit alpha. In addition, PMPCB has been shown to interact with PMPCA and Frataxin.[8]

Clinical significance

The majority of mitochondrial proteins is nuclear-coded, which necessitates proper translocations of mitochondrial targeting proteins. Many mitochondrial proteins are synthesized in a precursor form that contains mitochondria targeting sequence. These precursors are usually cleaved by peptidases and proteases before they arrive their sub-organellar locations. It is likely that altered activity of the mitochondrial processing peptidases is essential to ensure the correct maturation of mitochondrial proteins and that altered activity of these proteases will have dramatic effects in the activity, stability and assembly of mitochondrial proteins. Evidences showed that MPP was involved in the proteolytic maturation of Frataxin, a protein responsible for iron homeostasis.[9] Accordingly, MPP deficiency was shown to be involved in Friedreich ataxia, an autossomic recessive neurodegenerative disorder[10][11]

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References
  1. GRCh38: Ensembl release 89: ENSG00000105819 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000029017 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Mao M, Fu G, Wu JS, Zhang QH, Zhou J, Kan LX, Huang QH, He KL, Gu BW, Han ZG, Shen Y, Gu J, Yu YP, Xu SH, Wang YX, Chen SJ, Chen Z (Jul 1998). "Identification of genes expressed in human CD34(+) hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning". Proceedings of the National Academy of Sciences of the United States of America. 95 (14): 8175–80. doi:10.1073/pnas.95.14.8175. PMC 20949. PMID 9653160.
  6. "Entrez Gene: PMPCB peptidase (mitochondrial processing) beta".
  7. Teixeira PF, Glaser E (Feb 2013). "Processing peptidases in mitochondria and chloroplasts". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1833 (2): 360–70. doi:10.1016/j.bbamcr.2012.03.012. PMID 22495024.
  8. Koutnikova H, Campuzano V, Koenig M (Sep 1998). "Maturation of wild-type and mutated frataxin by the mitochondrial processing peptidase". Human Molecular Genetics. 7 (9): 1485–9. doi:10.1093/hmg/7.9.1485. PMID 9700204.
  9. Branda SS, Yang ZY, Chew A, Isaya G (Jun 1999). "Mitochondrial intermediate peptidase and the yeast frataxin homolog together maintain mitochondrial iron homeostasis in Saccharomyces cerevisiae". Human Molecular Genetics. 8 (6): 1099–110. doi:10.1093/hmg/8.6.1099. PMID 10332043.
  10. Cavadini P, Adamec J, Taroni F, Gakh O, Isaya G (Dec 2000). "Two-step processing of human frataxin by mitochondrial processing peptidase. Precursor and intermediate forms are cleaved at different rates". The Journal of Biological Chemistry. 275 (52): 41469–75. doi:10.1074/jbc.M006539200. PMID 11020385.
  11. Patel PI, Isaya G (Jul 2001). "Friedreich ataxia: from GAA triplet-repeat expansion to frataxin deficiency". American Journal of Human Genetics. 69 (1): 15–24. doi:10.1086/321283. PMC 1226030. PMID 11391483.

Further reading


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