PMPCA

PMPCA
Identifikatori
Aliasi	PMPCA
Vanjski ID-jevi	OMIM: 613036 MGI: 1918568 HomoloGene: 6078 GeneCards: PMPCA
Lokacija gena (čovjek)
Hrom.	Hromosom 9 (čovjek)
Kraj	136,423,761 bp
Lokacija gena (miš)
Hrom.	Hromosom 2 (miš)
Kraj	26,287,134 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• GO:0070122 peptidase activity; • hydrolase activity; • metallopeptidase activity; • metalloendopeptidase activity; • vezivanje iona cinka; • vezivanje iona metala; • catalytic activity; • endopeptidase activity;
Ćelijska komponenta	• mitochondrial matrix; • mitohondrija; • membrana; • mitochondrial inner membrane; • Vanćelijsko; • mitochondrial processing peptidase complex;
Biološki proces	• Proteoliza; • protein processing involved in protein targeting to mitochondrion; • mitochondrial calcium ion transmembrane transport;
	Izvori:Amigo / QuickGO
Ortolozi
	23203
	66865
	ENSG00000165688
	ENSMUSG00000026926
	Q10713; Q5SXN9
	Q9DC61
	NM_001282944; NM_001282946; NM_015160
	NM_173180
	NP_001269873; NP_001269875; NP_055975
	NP_775272
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Podjedinica alfa mitohondrijsko-preradne peptidaze je enzim koji je kod ljudi kodiran genom PMPCA.^[5]^[6]^[7] Gen PMPCA kodira protein koji je član porodice peptidaza M16. Ovaj protein se nalazi u mitohondrijskom matriksu i katalizira cijepanje vodećih peptida prekursorskih proteina koji su tek uneseni u mitohondrije, iako funkcionira samo kao dio heterodimernog kompleksa.

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 525 aminokiselina, а molekulska težina 58.253 Da.^[8]

10	20	30	40	50
MAAVVLAATR	LLRGSGSWGC	SRLRFGPPAY	RRFSSGGAYP	NIPLSSPLPG
VPKPVFATVD	GQEKFETKVT	TLDNGLRVAS	QNKFGQFCTV	GILINSGSRY
EAKYLSGIAH	FLEKLAFSST	ARFDSKDEIL	LTLEKHGGIC	DCQTSRDTTM
YAVSADSKGL	DTVVALLADV	VLQPRLTDEE	VEMTRMAVQF	ELEDLNLRPD
PEPLLTEMIH	EAAYRENTVG	LHRFCPTENV	AKINREVLHS	YLRNYYTPDR
MVLAGVGVEH	EHLVDCARKY	LLGVQPAWGS	AEAVDIDRSV	AQYTGGIAKL
ERDMSNVSLG	PTPIPELTHI	MVGLESCSFL	EEDFIPFAVL	NMMMGGGGSF
SAGGPGKGMF	SRLYLNVLNR	HHWMYNATSY	HHSYEDTGLL	CIHASADPRQ
VREMVEIITK	EFILMGGTVD	TVELERAKTQ	LTSMLMMNLE	SRPVIFEDVG
RQVLATRSRK	LPHELCTLIR	NVKPEDVKRV	ASKMLRGKPA	VAALGDLTDL
PTYEHIQTAL	SSKDGRLPRT	YRLFR

C: Cistein
D: Aspartat
E: Glutamat
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin

W: Triptofan

Y: Tirozin

Struktura

Podjedinica alfa prekursorskog peptidaznog proteina je podjedinica za mitohondrijsku preradu veličine 58,2 KDa i sastavljena je od 525 aminokiselina. Proteinski prekursor sadrži 33-aminokiselinski N-terminalni fragment kao sekvencu za ciljanje mitohondrija. Nakon cijepanja, zreli protein PMPCA je veličine 54,6 KDa i ima teorijsku pI od 5,88.

Funkcija

Peptidaza za preradu mitohondrija (MPP) je metaloendopeptidaza koja sadrži dvije strukturno povezane podjedinice, podjedinicu alfa i peptidaznu podjedinicu beta za preradu mitohondrija, koje u predviđenoj katalitskoj funkciji djeluju zajedno.^[9] Sadrži katalitsko mjesto, PMPCB protein podjedinice beta koji cijepa predsekvence (tranzitne peptide) iz prekursora mitohondrijskih proteina i oslobađa tranzitne peptide N-terminala iz proteinskog prekursora unesenih u mitohondrije, obično s argom u položaju P2.

Interakcije

Kao podjedinica alfa peptidaze za preradu mitohondrija, PMPCA tvori heterodimer sa podjedinicom PMPCB.

Klinički značaj

Većina mitohondrijskih proteina je jedarno kodirana, što zahtijeva pravilnu translokaciju proteina koji ciljaju na mitohondrije. Mnogi mitohondrijski proteini sintetizirani su u obliku prekursora koji sadrži sekvence usmjerene na mitohondrije. Ove prekursore obično cijepaju peptidaze i proteaze, prije nego što stignu na svoja podorganelna mjesta.

Vjerojatno je da je promijenjena aktivnost mitohondrijskih preradmih peptidaza bitna za osiguravanje pravilnog sazrijevanja mitohondrijskih proteina i da promijenjena aktivnosti ovih proteaza ima dramatične učinke na aktivnost, stabilnost i sastavljanje mitohondrijskih proteina. Dokazi su pokazali da je MPP uključen u proteolitsko sazrijevanje frataksina, proteina odgovornog za homeostazu gvožđa.^[10] U skladu s tim, pokazalo se da je nedostatak MPP uključen u Friedreichovu ataksiju, autosomni recesivni neurodegenerativni poremećaj.^[11]^[12]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000165688 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000026926 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Nagase T, Seki N, Tanaka A, Ishikawa K, Nomura N (Mar 1996). "Prediction of the coding sequences of unidentified human genes. IV. The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1". DNA Res. 2 (4): 167–74, 199–210. doi:10.1093/dnares/2.4.167. PMID 8590280.
^ Nagase T, Miyajima N, Tanaka A, Sazuka T, Seki N, Sato S, Tabata S, Ishikawa K, Kawarabayasi Y, Kotani H, et al. (Jul 1995). "Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1". DNA Res. 2 (1): 37–43. doi:10.1093/dnares/2.1.37. PMID 7788527.
^ "Entrez Gene: PMPCA peptidase (mitochondrial processing) alpha".
^ "UniProt, Q10713". Pristupljeno 11. 9. 2021.
^ 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.
^ 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.
^ 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.
^ 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.

Dopunska literatura

Srinivasan M, Kalousek F, Curthoys NP (1995). "In vitro characterization of the mitochondrial processing and the potential function of the 68-kDa subunit of renal glutaminase". J. Biol. Chem. 270 (3): 1185–90. doi:10.1074/jbc.270.3.1185. PMID 7836378.
Luciano P, Geoffroy S, Brandt A, et al. (1997). "Functional cooperation of the mitochondrial processing peptidase subunits". J. Mol. Biol. 272 (2): 213–25. doi:10.1006/jmbi.1997.1231. PMID 9299349.
Nagao Y, Kitada S, Kojima K, et al. (2000). "Glycine-rich region of mitochondrial processing peptidase alpha-subunit is essential for binding and cleavage of the precursor proteins". J. Biol. Chem. 275 (44): 34552–6. doi:10.1074/jbc.M003110200. PMID 10942759.
Harris RA, Yang A, Stein RC, et al. (2002). "Cluster analysis of an extensive human breast cancer cell line protein expression map database". Proteomics. 2 (2): 212–23. doi:10.1002/1615-9861(200202)2:2<212::AID-PROT212>3.0.CO;2-H. PMID 11840567.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Hassel S, Eichner A, Yakymovych M, et al. (2004). "Proteins associated with type II bone morphogenetic protein receptor (BMPR-II) and identified by two-dimensional gel electrophoresis and mass spectrometry". Proteomics. 4 (5): 1346–58. doi:10.1002/pmic.200300770. PMID 15188402. S2CID 6773754.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.

Vanjski linkovi

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000165688 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000026926 - Ensembl, maj 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.

[pmid8590280-5] Nagase T, Seki N, Tanaka A, Ishikawa K, Nomura N (Mar 1996). "Prediction of the coding sequences of unidentified human genes. IV. The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1". DNA Res. 2 (4): 167–74, 199–210. doi:10.1093/dnares/2.4.167. PMID 8590280.

[pmid7788527-6] Nagase T, Miyajima N, Tanaka A, Sazuka T, Seki N, Sato S, Tabata S, Ishikawa K, Kawarabayasi Y, Kotani H, et al. (Jul 1995). "Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1". DNA Res. 2 (1): 37–43. doi:10.1093/dnares/2.1.37. PMID 7788527.

[entrez-7] "Entrez Gene: PMPCA peptidase (mitochondrial processing) alpha".

[UniProt-8] "UniProt, Q10713". Pristupljeno 11. 9. 2021.

[9] 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.

[10] 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.

[11] 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.

[12] 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.

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