PAPOLA

PAPOLA
Identifikatori
Aliasi	PAPOLA
Vanjski ID-jevi	OMIM: 605553 MGI: 109301 HomoloGene: 23389 GeneCards: PAPOLA
Lokacija gena (čovjek)
Hrom.	Hromosom 14 (čovjek)
Kraj	96,567,116 bp
Lokacija gena (miš)
Hrom.	Hromosom 12 (miš)
Kraj	105,805,203 bp
Obrazac RNK ekspresije
	; ; ; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• aktivnost sa transferazom; • nucleotide binding; • nucleotidyltransferase activity; • manganese ion binding; • vezivanje iona metala; • GO:0001948, GO:0016582 vezivanje za proteine; • vezivanje sa RNK; • ATP binding; • magnesium ion binding; • polynucleotide adenylyltransferase activity;
Ćelijska komponenta	• citoplazma; • nukleoplazma; • jedro;
Biološki proces	• mRNA splicing, via spliceosome; • termination of RNA polymerase II transcription; • RNA 3'-end processing; • mRNA processing; • mRNA polyadenylation; • mRNA 3'-end processing; • regulation of mRNA 3'-end processing; • RNA polyadenylation;
	Izvori:Amigo / QuickGO
Ortolozi
	10914
	18789
	ENSG00000090060
	ENSMUSG00000021111
	P51003
	Q61183
NM_001252006; NM_001252007; NM_001293627; NM_001293628; NM_001293632;
	NM_032632; NM_001363662; NM_001363664; NM_001363665; NM_001363666
	NM_011112; NM_001347440
NP_001238935; NP_001238936; NP_001280556; NP_001280557; NP_001280561;
	NP_116021; NP_001350591; NP_001350593; NP_001350594; NP_001350595
	NP_001334369; NP_035242
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Poli(A) polimeraza alfa je enzim koji je kod ljudi kodiran genom PAPOLA.^[5]^[6]^[7]

Primjenom fluorescentne in situ hibridizacije i radijacijskom hibridnom analizom, Yamauchi et al. (1999) locirali su gen PAP na poziciji 14q32.1-q32.2.^[8]

PAPOLA se veže za FIP1L1 (Faktor koji djeluje u interakciji s PAPOLA i CPSF1), podjedinicu faktora specifičnosti cijepanja i poliadenilacije (CPSF1). Ovaj složeni poliadenilirajući 3' kraj je prekursor iRNK (pre-iRNK) (vidi CPSF). CPSF1 je proteinska RNK koja se prerađuje i veže se za sekvence bogate uracilom u pre-iRNK. Veže se i stimulira aktivnost polinukleotid adenililtransferaza i time dodaje adenililne ostatke pre-mRNK. Ovo djelovanje poli-adenilila povećava sazrijevanje i pomicanje pre iRNK iz jedra u citoplazmu, dok dramatično povećava stabilnost iRNK nastale iz pre-iRNK: FIP1L1 je faktor 3'-završne prerade pre-iRNK. Fuzije gena FIP1L1 između njega i PDGFRA (PGDFRA) ili receptora retinojske kiseline (RARA) su uzročni geni određenih ljudskih bolesti povezanih s patološki povećanim nivoom eozinofila u krvi i/ili leukemija.^[9]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 745 aminokiselina, a molekulska težina 82.843 Da ^[10].

10	20	30	40	50
MPFPVTTQGS	QQTQPPQKHY	GITSPISLAA	PKETDCVLTQ	KLIETLKPFG
VFEEEEELQR	RILILGKLNN	LVKEWIREIS	ESKNLPQSVI	ENVGGKIFTF
GSYRLGVHTK	GADIDALCVA	PRHVDRSDFF	TSFYDKLKLQ	EEVKDLRAVE
EAFVPVIKLC	FDGIEIDILF	ARLALQTIPE	DLDLRDDSLL	KNLDIRCIRS
LNGCRVTDEI	LHLVPNIDNF	RLTLRAIKLW	AKRHNIYSNI	LGFLGGVSWA
MLVARTCQLY	PNAIASTLVH	KFFLVFSKWE	WPNPVLLKQP	EECNLNLPVW
DPRVNPSDRY	HLMPIITPAY	PQQNSTYNVS	VSTRMVMVEE	FKQGLAITDE
ILLSKAEWSK	LFEAPNFFQK	YKHYIVLLAS	APTEKQRLEW	VGLVESKIRI
LVGSLEKNEF	ITLAHVNPQS	FPAPKENPDK	EEFRTMWVIG	LVFKKTENSE
NLSVDLTYDI	QSFTDTVYRQ	AINSKMFEVD	MKIAAMHVKR	KQLHQLLPNH
VLQKKKKHST	EGVKLTALND	SSLDLSMDSD	NSMSVPSPTS	ATKTSPLNSS
GSSQGRNSPA	PAVTAASVTN	IQATEVSVPQ	VNSSESSGGT	SSESIPQTAT
QPAISPPPKP	TVSRVVSSTR	LVNPPPRSSG	NAATSGNAAT	KIPTPIVGVK
RTSSPHKEES	PKKTKTEEDE	TSEDANCLAL	SGHDKTEAKE	QLDTETSTTQ
SETIQTAASL	LASQKTSSTD	LSDIPALPAN	PIPVIKNSIK	LRLNR

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

Kloniranje i ekspresija

Poliadenilacija tri osnovna kraja eukariotskih iRNK je ključni događaj koji se odvija u jedru tokom sazrijevanja iRNK. Reakcija se odvija u dva različita koraka: endoribonukleolitsko cijepanje pre-RNK na poli(A) mjestu, nakon čega slijedi sinteza poli(A) repa na 3-osnovnom kraju gornjeg produkta cijepanja. Poli (A) polimeraza (PAP) potrebna je za reakciju dodavanja adenozina (sažetak Thuresson et al., 1994).

Koristeći RT-PCR za citoplazmatsku RNK iz primarnih ljudskih fibroblasta, Thuresson et al. (1994) dobili su cDNK koja kodira PAP. Izvedeni protein od 500 aminokiselina je 99% sličan goveđoj sekvenci. Western blot analiza ekstrakata HeLa ćelija otkrila je proteine otporne na toplotu od 100 i 106-kD u jedarnim i citoplazmatskim frakcijama, te 90-kD-ni protein osjetljiv na toplotu u jedarnim frakcijama. Protein od 106 kD je fosforiliran. Funkcionalna analiza mutiranih peptida pokazala je da je N-terminalni region PAP potreban za nespecifičnu aktivnost polimeraze, dok su i N– i C-krajevi potrebni za specifičnu aktivnost polimeraze.^[11]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000090060 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000021111 - 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.
^ Thuresson AC, Astrom J, Astrom A, Gronvik KO, Virtanen A (Mar 1994). "Multiple forms of poly(A) polymerases in human cells". Proc Natl Acad Sci U S A. 91 (3): 979–83. doi:10.1073/pnas.91.3.979. PMC 521437. PMID 8302877.
^ Yamauchi T, Sugimoto J, Hatakeyama T, Asakawa S, Shimizu N, Isobe M (Sep 1999). "Assignment of the human poly(A) polymerase (PAP) gene to chromosome 14q32.1-q32.2 and isolation of a polymorphic CA repeat sequence". J Hum Genet. 44 (4): 253–5. doi:10.1007/s100380050154. PMID 10429366.
^ "Entrez Gene: PAPOLA poly(A) polymerase alpha".
^ Yamauchi, T., Sugimoto, J., Hatakeyama, T., Asakawa, S., Shimizu, N., Isobe, M. Assignment of the human poly(A) polymerase (PAP) gene to chromosome 14q32.1-q32.2 and isolation of a polymorphic CA repeat sequence. J. Hum. Genet. 44: 253-255, 1999. PubMed: 10429366
^ https://www.ncbi.nlm.nih.gov/gene/81608
^ "UniProt, P51003". Pristupljeno 28. 7. 2021.
^ Thuresson, A.-C., Astrom, J., Astrom, A., Gronvik, K.-O., Virtanen, A. Multiple forms of poly(A) polymerases in human cells. Proc. Nat. Acad. Sci. 91: 979-983, 1994. PubMed: 8302877

Dopunska literatura

Weichs an der Glon C, Ashe M, Eggermont J, Proudfoot NJ (1993). "Tat-dependent occlusion of the HIV poly(A) site". EMBO J. 12 (5): 2119–28. doi:10.1002/j.1460-2075.1993.tb05860.x. PMC 413433. PMID 8491200.
Pendurthi UR, Alok D, Rao LV (1997). "Binding of factor VIIa to tissue factor induces alterations in gene expression in human fibroblast cells: up-regulation of poly(A) polymerase". Proc. Natl. Acad. Sci. U.S.A. 94 (23): 12598–603. doi:10.1073/pnas.94.23.12598. PMC 25051. PMID 9356495.
Varani L, Gunderson SI, Mattaj IW, et al. (2000). "The NMR structure of the 38 kDa U1A protein - PIE RNA complex reveals the basis of cooperativity in regulation of polyadenylation by human U1A protein". Nat. Struct. Biol. 7 (4): 329–35. doi:10.1038/74101. PMID 10742179.
Mouland AJ, Coady M, Yao XJ, Cohen EA (2002). "Hypophosphorylation of poly(A) polymerase and increased polyadenylation activity are associated with human immunodeficiency virus type 1 Vpr expression". Virology. 292 (2): 321–30. doi:10.1006/viro.2001.1261. PMID 11878934.
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.
Kim H, Lee JH, Lee Y (2003). "Regulation of poly(A) polymerase by 14-3-3epsilon". EMBO J. 22 (19): 5208–19. doi:10.1093/emboj/cdg486. PMC 204469. PMID 14517258.
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.
Bouwmeester T, Bauch A, Ruffner H, et al. (2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216.
Kaufmann I, Martin G, Friedlein A, et al. (2005). "Human Fip1 is a subunit of CPSF that binds to U-rich RNA elements and stimulates poly(A) polymerase". EMBO J. 23 (3): 616–26. doi:10.1038/sj.emboj.7600070. PMC 1271804. PMID 14749727.
Dettwiler S, Aringhieri C, Cardinale S, et al. (2005). "Distinct sequence motifs within the 68-kDa subunit of cleavage factor Im mediate RNA binding, protein-protein interactions, and subcellular localization" (PDF). J. Biol. Chem. 279 (34): 35788–97. doi:10.1074/jbc.M403927200. PMID 15169763.
Colland F, Jacq X, Trouplin V, et al. (2004). "Functional proteomics mapping of a human signaling pathway". Genome Res. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748.
Beausoleil SA, Jedrychowski M, Schwartz D, et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
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.
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. doi:10.1038/nature04209. PMID 16189514.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000090060 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000021111 - 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.

[pmid8302877-5] Thuresson AC, Astrom J, Astrom A, Gronvik KO, Virtanen A (Mar 1994). "Multiple forms of poly(A) polymerases in human cells". Proc Natl Acad Sci U S A. 91 (3): 979–83. doi:10.1073/pnas.91.3.979. PMC 521437. PMID 8302877.

[pmid10429366-6] Yamauchi T, Sugimoto J, Hatakeyama T, Asakawa S, Shimizu N, Isobe M (Sep 1999). "Assignment of the human poly(A) polymerase (PAP) gene to chromosome 14q32.1-q32.2 and isolation of a polymorphic CA repeat sequence". J Hum Genet. 44 (4): 253–5. doi:10.1007/s100380050154. PMID 10429366.

[entrez-7] "Entrez Gene: PAPOLA poly(A) polymerase alpha".

[8] Yamauchi, T., Sugimoto, J., Hatakeyama, T., Asakawa, S., Shimizu, N., Isobe, M. Assignment of the human poly(A) polymerase (PAP) gene to chromosome 14q32.1-q32.2 and isolation of a polymorphic CA repeat sequence. J. Hum. Genet. 44: 253-255, 1999. PubMed: 10429366

[nih.gov-9] ttps://www.ncbi.nlm.nih.gov/gene/81608

[UniProt-10] "UniProt, P51003". Pristupljeno 28. 7. 2021.

[11] Thuresson, A.-C., Astrom, J., Astrom, A., Gronvik, K.-O., Virtanen, A. Multiple forms of poly(A) polymerases in human cells. Proc. Nat. Acad. Sci. 91: 979-983, 1994. PubMed: 8302877

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