PDPR

PDPR
Identifikatori
Aliasi	PDPR
Vanjski ID-jevi	OMIM: 617835 MGI: 2442188 HomoloGene: 9948 GeneCards: PDPR
Lokacija gena (čovjek)
Hrom.	Hromosom 16 (čovjek)
Kraj	70,162,537 bp
Lokacija gena (miš)
Hrom.	Hromosom 8 (miš)
Kraj	111,863,706 bp
Ontologija gena
Molekularna funkcija	• [pyruvate dehydrogenase (lipoamide) phosphatase activity]; • oxidoreductase activity;
Ćelijska komponenta	• mitohondrija; • mitochondrial matrix; • citoplazma;
Biološki proces	• regulation of acetyl-CoA biosynthetic process from pyruvate; • GO:0016576 protein dephosphorylation;
	Izvori:Amigo / QuickGO
Ortolozi
	55066
	319518
	ENSG00000090857
	ENSMUSG00000033624
	Q8NCN5
	Q7TSQ8
	NM_017990; NM_001322117; NM_001322118; NM_001322119
	NM_198308
	NP_001309046; NP_001309047; NP_001309048; NP_060460
	NP_938050
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Regulacijska podjedinica piruvat-dehidrogenazne fosfataze je protein koji je kod ljudi kodiran genom PDPR.^[5]

Struktura

Kompletna cDNK PDPR, koja sadrži 2885 baznih parova, ima otvoreni okvir čitanja od 2634 nukleotida, koji kodiraju navodnu predsekvencu od 31 aminokiselinska ostatka i zreli protein od 847. Karakteristike nativnog PDPR uključuju sposobnost smanjenja osetljivosti katalitske podjedinice na Mg2 + i poništavanje ovog inhibitornog efekta poliaminom sperminom. Pretragom baza podataka o proteinima BLAST otkriveno je da je PDPr u daljnjoj vezi sa mitohondrijskim flavoproteinom dimetilglicin-dehidrogenaza, koji funkcionira u razgradnji holina.^[6]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 879 aminokiselina, a molekulska težina 99.364 Da.^[7].

10	20	30	40	50
MMFYRLLSIV	GRQRASPGWQ	NWSSARNSTS	AAEARSMALP	TQAQVVICGG
GITGTSVAYH	LSKMGWKDIV	LLEQGRLAAG	STRFCAGILS	TARHLTIEQK
MADYSNKLYY	QLEQETGIQT	GYTRTGSIFL	AQTQDRLISL	KRINAGLNVI
GIPSEIISPK	KVAELHHLLN	VHDLVGAMHV	PEDAVVSSAD	VALALASAAS
QNGVQIYDRT	SVLHVMVKKG	QVTGVETDKG	QIECQYFVNC	AGQWAYELGL
SNEEPVSIPL	HACEHFYLLT	RPLETPLQSS	TPTIVDADGR	IYIRNWQGGI
LSGGFEKNPK	PIFTEGKNQL	EIQNLQEDWD	HFEPLLSSLL	RRMPELETLE
IMKLVNCPET	FTPDMRCIMG	ESPAVQGYFV	LAGMNSAGLS	FGGGAGKYLA
EWMVHGYPSE	NVWELDLKRF	GALQSSRTFL	RHRVMEVMPL	MYDLKVPRWD
FQTGRQLRTS	PLYDRLDAQG	ARWMEKHGFE	RPKYFVPPDK	DLLALEQSKT
FYKPDWFDIV	ESEVKCCKEA	VCVIDMSSFT	KFEITSTGDQ	ALEVLQYLFS
NDLDVPVGHI	VHTGMLNEGG	GYENDCSIAR	LNKRSFFMIS	PTDQQVHCWA
WLKKHMPKDS	NLLLEDVTWK	YTALNLIGPR	AVDVLSELSY	APMTPDHFPS
LFCKEMSVGY	ANGIRVMSMT	HTGEPGFMLY	IPIEYALHVY	NEVMSVGQKY
GIRNAGYYAL	RSLRIEKFFA	FWGQDINNLT	TPLECGRESR	VKLEKGMDFI
GRDALLQQKQ	NGVYKRLTMF	ILDDHDSDLD	LWPWWGEPIY	RNGQYVGKTT
SSAYSYSLER	HVCLGFVHNF	SEDTGEEQVV	TADFINRGEY	EIDIAGYRFQ
AKAKLYPVAS	LFTQKRRKDD	MELSDLHGK

Simboli

C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
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

Funkcija

Mitohondrijski kompleks piruvat-dehidrogenaze (PDC) katalizira oksidativnu dekarboksilaciju piruvata, povezujući glikolizu sa ciklusom trikarbonske kiseline i sintezom masnih kiselina (FA). Poznavanje mehanizama koji regulišu aktivnost PDC-a je važno, jer je inaktivacija PDC-a presudna za očuvanje glukoze kada je ima malo, dok je potrebna dovoljna aktivnost PDC-a, kako bi se omogućila proizvodnja ATP[]-a i FA iz glukoze. Mehanizmi koji kontroliraju PDC aktivnost sisara uključuju njegovu fosforilaciju (inaktivaciju) enzimima porodicve piruvat-dehidrogenazne kinaze (PDKs 1-4) i njenu defosforilaciju (aktivaciju, reaktivaciju) fosfatazom piruvat dehidrogenaza(PDP 1 i 2).^[8]

Klinički značaj

Kako je PDPR uključen u regulaciju centralnog metaboličkog puta, njegovo je učešće u patofiziološkim osnovama bolesti vjerovatno, ali o tome do sada nije objavljeno istraživanje.^[5]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000090857 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000033624 - 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.
^ ^a ^b "Entrez Gene: Pyruvate dehydrogenase phosphatase regulatory subunit".
^ Lawson JE, Park SH, Mattison AR, Yan J, Reed LJ (decembar 1997). "Cloning, expression, and properties of the regulatory subunit of bovine pyruvate dehydrogenase phosphatase". The Journal of Biological Chemistry. 272 (50): 31625–9. doi:10.1074/jbc.272.50.31625. PMID 9395502.
^ "UniProt, Q8NCN5". Pristupljeno 8. 7. 2021.
^ Sugden MC, Holness MJ (maj 2003). "Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs". American Journal of Physiology. Endocrinology and Metabolism. 284 (5): E855-62. doi:10.1152/ajpendo.00526.2002. PMID 12676647.

Dopunska literatura

Sugden MC, Holness MJ (maj 2003). "Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs". American Journal of Physiology. Endocrinology and Metabolism. 284 (5): E855-62. doi:10.1152/ajpendo.00526.2002. PMID 12676647.
Chen X, Li X, Wang P, Liu Y, Zhang Z, Zhao G, Xu H, Zhu J, Qin X, Chen S, Hu L, Kong X (august 2010). "Novel association strategy with copy number variation for identifying new risk Loci of human diseases". PLOS ONE. 5 (8): e12185. Bibcode:2010PLoSO...512185C. doi:10.1371/journal.pone.0012185. PMC 2924882. PMID 20808825.
Ohara O, Nagase T, Mitsui G, Kohga H, Kikuno R, Hiraoka S, Takahashi Y, Kitajima S, Saga Y, Koseki H (april 2002). "Characterization of size-fractionated cDNA libraries generated by the in vitro recombination-assisted method". DNA Research. 9 (2): 47–57. doi:10.1093/dnares/9.2.47. PMID 12056414.
Lawson JE, Park SH, Mattison AR, Yan J, Reed LJ (decembar 1997). "Cloning, expression, and properties of the regulatory subunit of bovine pyruvate dehydrogenase phosphatase". The Journal of Biological Chemistry. 272 (50): 31625–9. doi:10.1074/jbc.272.50.31625. PMID 9395502.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000090857 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000033624 - 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.

[entrez-5] "Entrez Gene: Pyruvate dehydrogenase phosphatase regulatory subunit".

[6] Lawson JE, Park SH, Mattison AR, Yan J, Reed LJ (decembar 1997). "Cloning, expression, and properties of the regulatory subunit of bovine pyruvate dehydrogenase phosphatase". The Journal of Biological Chemistry. 272 (50): 31625–9. doi:10.1074/jbc.272.50.31625. PMID 9395502.

[UniProt-7] "UniProt, Q8NCN5". Pristupljeno 8. 7. 2021.

[8] Sugden MC, Holness MJ (maj 2003). "Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs". American Journal of Physiology. Endocrinology and Metabolism. 284 (5): E855-62. doi:10.1152/ajpendo.00526.2002. PMID 12676647.

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