PPM1A

PPM1A (Proteinska fosfataza 1A) je enzim koji je kod ljudi kodiran PPM1A genom.^[1][2]

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Proteinska fosFataza, Mg2+/Mn2+ zavisna, 1A
PDB prikaz baziran na 1a6q.
Dostupne strukture
1A6Q, 3FXJ, 3FXK, 3FXL, 3FXM, 3FXO
Identifikatori
Simboli	PPM1A; PP2C-ALPHA; PP2CA; PP2Calpha
Vanjski ID	OMIM: 606108 MGI: 99878 HomoloGene: 56428 GeneCards: PPM1A Gene
EC broj	3.1.3.16
Ontologija gena Molekularna funkcija • vezivanje jona magnezijuma • aktivnost proteinske serin/treoninske fosfataze • aktivnost prenosnika signala • proteinsko vezivanje • vezivanje proteinskog C-terminusa • hidrolazna aktivnost • vezivanje jona mangana • aktivnost kalmodulin-zavisne proteinske fosfataze • R-SMAD vezivanje Celularna komponenta • membranska frakcija • nukleus • citozol • naponom kontrolisani kompleks kalcijumskog kanala • kompleks proteinske serin/treoninske fosfataze • neuronska projekcija Biološki proces • blokada ćelijskog ciklusa • prenos signala • signalni put insulinskog receptora • negativna regulacija formiranja kompleksa SMAD proteina • signalni put Wnt receptora • defosforilacija • pozitivna regulacija signalnog puta Wnt receptora
Pregled RNK izražavanja
podaci
Ortolozi
Vrsta	Čovek	Miš
Entrez	5494	19042
Ensembl	ENSG00000100614	ENSMUSG00000021096
UniProt	P35813	P49443
RefSeq (mRNA)	NM_021003.4	NM_008910.3
RefSeq (protein)	NP_066283.1	NP_032936.1
Lokacija (UCSC)	Chr 14: 60.71 - 60.77 Mb	Chr 12: 73.86 - 73.9 Mb
PubMed pretraga

Protein kodiran ovim genom je član PP2C familije Ser/Thr proteinskih fosfataza. Članovi PP2C familije su poznati kao negativni regulatori ćelijskog puta kojim se odgovara na stres. Ova fosfataza defosforiliše, i negativno reguliše aktivnosti MAP kinaza i MAP kinaza kinaza. Pokazano je da inhibira aktivaciju p38 i JNK kaskade kinaza indukovanu stresovima životne sredine. Ova fosfataza može takođe da defosforiliše ciklin-zavisne kinaze, i stoga može da učestvuje u kontroli ćelijskog ciklusa. Prekomerno izražavanje ove fosfataze može da aktivira izražavanje tumor supresornih gena TP53/p53, što dovodi do G2/M blokade ćelijkog ciklusa i apoptoze. Poznate su tri alternativno splajsovane transkriptne varijante koje kodiraju dve distinktne izoforme.^[2]

Interakcije

PPM1A formira interakcije sa metabotropnim glutamatnim receptor 3.^[3] PPM1A može da prekine TGF-beta signalizaciju putem inaktivacije Smad3 defosforilacijom. Smad3 je esencijalna komponenta TGF-beta signalnog puta.

Reference

1. Mann DJ, Campbell DG, McGowan CH, Cohen PT (Apr 1992). „Mammalian protein serine/threonine phosphatase 2C: cDNA cloning and comparative analysis of amino acid sequences”. Biochim Biophys Acta 1130 (1): 100–4. PMID 1311954.
2. „Entrez Gene: PPM1A protein phosphatase 1A (formerly 2C), magnesium-dependent, alpha isoform”.
3. Flajolet, Marc; Rakhilin Sergey, Wang Hong, Starkova Natalia, Nuangchamnong Nina, Nairn Angus C, Greengard Paul (December 2003). „Protein phosphatase 2C binds selectively to and dephosphorylates metabotropic glutamate receptor 3”. Proc. Natl. Acad. Sci. U.S.A. (United States) 100 (26): 16006–11. DOI:10.1073/pnas.2136600100. ISSN 0027-8424. PMC 307683. PMID 14663150.

Literatura

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• Das AK, Helps NR, Cohen PT, Barford D (1997). „Crystal structure of the protein serine/threonine phosphatase 2C at 2.0 A resolution.”. EMBO J. 15 (24): 6798–809. PMC 452505. PMID 9003755.
• Takekawa M, Maeda T, Saito H (1998). „Protein phosphatase 2Calpha inhibits the human stress-responsive p38 and JNK MAPK pathways.”. EMBO J. 17 (16): 4744–52. DOI:10.1093/emboj/17.16.4744. PMC 1170803. PMID 9707433.
• Fjeld CC, Denu JM (1999). „Kinetic analysis of human serine/threonine protein phosphatase 2Calpha.”. J. Biol. Chem. 274 (29): 20336–43. DOI:10.1074/jbc.274.29.20336. PMID 10400656.
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• 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.
• Ofek P, Ben-Meir D, Kariv-Inbal Z, et al. (2003). „Cell cycle regulation and p53 activation by protein phosphatase 2C alpha.”. J. Biol. Chem. 278 (16): 14299–305. DOI:10.1074/jbc.M211699200. PMID 12514180.
• Matsuda A, Suzuki Y, Honda G, et al. (2003). „Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways.”. Oncogene 22 (21): 3307–18. DOI:10.1038/sj.onc.1206406. PMID 12761501.
• Flajolet M, Rakhilin S, Wang H, et al. (2004). „Protein phosphatase 2C binds selectively to and dephosphorylates metabotropic glutamate receptor 3.”. Proc. Natl. Acad. Sci. U.S.A. 100 (26): 16006–11. DOI:10.1073/pnas.2136600100. PMC 307683. PMID 14663150.
• 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.
• Yoshizaki T, Maegawa H, Egawa K, et al. (2004). „Protein phosphatase-2C alpha as a positive regulator of insulin sensitivity through direct activation of phosphatidylinositol 3-kinase in 3T3-L1 adipocytes.”. J. Biol. Chem. 279 (21): 22715–26. DOI:10.1074/jbc.M313745200. PMID 15016818.
• 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.
• Li D, Wang F, Lai M, et al. (2005). „A protein phosphatase 2calpha-Ca2+ channel complex for dephosphorylation of neuronal Ca2+ channels phosphorylated by protein kinase C.”. J. Neurosci. 25 (8): 1914–23. DOI:10.1523/JNEUROSCI.4790-04.2005. PMID 15728831.
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• Kitajima TS, Sakuno T, Ishiguro K, et al. (2006). „Shugoshin collaborates with protein phosphatase 2A to protect cohesin.”. Nature 441 (7089): 46–52. DOI:10.1038/nature04663. PMID 16541025.