PPM1A

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

[1]

[2]

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

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

^ Mann DJ, Campbell DG, McGowan CH, Cohen PT (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.
^ ^а ^б „Entrez Gene: PPM1A protein phosphatase 1A (formerly 2C), magnesium-dependent, alpha isoform”.
^ Flajolet, Marc; Rakhilin Sergey; et al. (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. ISSN 0027-8424. PMC 307683 . PMID 14663150. doi:10.1073/pnas.2136600100.

Literatura

Redpath NT, Price NT, Severinov KV, Proud CG (1993). „Regulation of elongation factor-2 by multisite phosphorylation.”. Eur. J. Biochem. 213 (2): 689—99. PMID 8386634. doi:10.1111/j.1432-1033.1993.tb17809.x.
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. PMC 1170803 . PMID 9707433. doi:10.1093/emboj/17.16.4744.
Fjeld CC, Denu JM (1999). „Kinetic analysis of human serine/threonine protein phosphatase 2Calpha.”. J. Biol. Chem. 274 (29): 20336—43. PMID 10400656. doi:10.1074/jbc.274.29.20336.
Hishiya A, Ohnishi M, Tamura S, Nakamura F (1999). „Protein phosphatase 2C inactivates F-actin binding of human platelet moesin.”. J. Biol. Chem. 274 (38): 26705—12. PMID 10480873. doi:10.1074/jbc.274.38.26705.
Cheng A, Ross KE, Kaldis P, Solomon MJ (2000). „Dephosphorylation of cyclin-dependent kinases by type 2C protein phosphatases.”. Genes Dev. 13 (22): 2946—57. PMC 317162 . PMID 10580002. doi:10.1101/gad.13.22.2946.
Strovel ET, Wu D, Sussman DJ (2000). „Protein phosphatase 2Calpha dephosphorylates axin and activates LEF-1-dependent transcription.”. J. Biol. Chem. 275 (4): 2399—403. PMID 10644691. doi:10.1074/jbc.275.4.2399.
Lifschitz-Mercer B; Sheinin Y; Ben-Meir D; et al. (2001). „Protein phosphatase 2Calpha expression in normal human tissues: an immunohistochemical study.”. Histochem. Cell Biol. 116 (1): 31—9. PMID 11479720.
Srivastava J, Goris J, Dilworth SM, Parker PJ (2002). „Dephosphorylation of PKCdelta by protein phosphatase 2Ac and its inhibition by nucleotides.”. FEBS Lett. 516 (1-3): 265—9. PMID 11959144. doi:10.1016/S0014-5793(02)02500-0.
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. PMC 139241 . PMID 12477932. doi:10.1073/pnas.242603899.
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. PMID 12514180. doi:10.1074/jbc.M211699200.
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. PMID 12761501. doi:10.1038/sj.onc.1206406.
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. PMC 307683 . PMID 14663150. doi:10.1073/pnas.2136600100.
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. PMID 14702039. doi:10.1038/ng1285.
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. PMID 15016818. doi:10.1074/jbc.M313745200.
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. PMC 528928 . PMID 15489334. doi:10.1101/gr.2596504.
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. PMID 15728831. doi:10.1523/JNEUROSCI.4790-04.2005.
Rual JF; Venkatesan K; Hao T; et al. (2005). „Towards a proteome-scale map of the human protein-protein interaction network.”. Nature. 437 (7062): 1173—8. PMID 16189514. doi:10.1038/nature04209.
Kitajima TS; Sakuno T; Ishiguro K; et al. (2006). „Shugoshin collaborates with protein phosphatase 2A to protect cohesin.”. Nature. 441 (7089): 46—52. PMID 16541025. doi:10.1038/nature04663.