PABPC1

PABPC1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1CVJ, 1G9L, 1JGN, 1JH4, 2K8G, 2RQG, 2RQH, 2X04, 3KTP, 3KTR, 3KUI, 3KUJ, 3KUR, 3KUS, 3KUT, 3PKN, 3PTH, 4F02, 4F25, 4F26, 5DX1, 5DXA, 5DX8, 2D9P
Identifiers
Aliases	PABPC1 , PAB1, PABP, PABP1, PABPC2, PABPL1, poly(A) binding protein cytoplasmic 1
External IDs	OMIM: 604679; MGI: 1349722; HomoloGene: 37638; GeneCards: PABPC1; OMA:PABPC1 - orthologs
Gene location (Human) Chr. Chromosome 8 (human) [1] Band 8q22.3 Start 100,685,816 bp [1] End 100,722,809 bp [1]
Gene location (Mouse) Chr. Chromosome 15 (mouse) [2] Band 15|15 B3.1 Start 36,595,905 bp [2] End 36,609,912 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in parotid gland pylorus gonad amniotic fluid vulva tonsil nipple trabecular bone monocyte oral cavity Top expressed in tail of embryo genital tubercle ventricular zone yolk sac spermatocyte morula neural layer of retina spermatid embryo lip More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding nucleic acid binding protein C-terminus binding translation activator activity poly(U) RNA binding poly(A) binding mRNA 3'-UTR binding RNA binding mRNA binding Cellular component focal adhesion catalytic step 2 spliceosome cytoplasmic stress granule cytoplasm cytoplasmic ribonucleoprotein granule spliceosomal complex membrane extracellular exosome nucleus cytosol dendrite ribonucleoprotein granule synapse messenger ribonucleoprotein complex ribonucleoprotein complex Biological process nuclear-transcribed mRNA catabolic process, nonsense-mediated decay mRNA stabilization mRNA splicing, via spliceosome regulation of mRNA stability RNA splicing mRNA polyadenylation mRNA processing nuclear-transcribed mRNA poly(A) tail shortening positive regulation of viral genome replication translational initiation negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay positive regulation of translation gene silencing positive regulation of nuclear-transcribed mRNA poly(A) tail shortening positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 26986 18458 Ensembl ENSG00000070756 ENSMUSG00000022283 UniProt P11940 P29341 RefSeq (mRNA) NM_002568 NM_008774 RefSeq (protein) NP_002559 NP_032800 Location (UCSC) Chr 8: 100.69 – 100.72 Mb Chr 15: 36.6 – 36.61 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Polyadenylate-binding protein 1 is a protein that in humans is encoded by the PABPC1 gene. ^[5] The protein PABP1 binds mRNA and facilitates a variety of functions such as transport into and out of the nucleus, degradation, translation, and stability. There are two separate PABP1 proteins, one which is located in the nucleus (PABPN1) and the other which is found in the cytoplasm (PABPC1). The location of PABP1 affects the role of that protein and its function with RNA. ^[6]

Function

The poly(A)-binding protein (PAB or PABP), which is found complexed to the 3' poly(A) tail of eukaryotic mRNA, is required for poly(A) lengthening and the termination of translation. In humans, the PABPs comprise a small nuclear isoform and a conserved gene family of other poly(A)-binding proteins.[supplied by OMIM] ^[7]

PABPC1 is usually diffused within the cytoplasm and concentrated at sites of high mRNA concentration such as stress granules, processing bodies, and locations of high translational activity. PABPC1 is also associated with nonsense-mediated mRNA decay (NMD). PABPC1 binds to the poly(A) tail and interact with eIF4G, which stabilizes the circularization of mRNAs. This structure is required for the prevention of mRNA degradation via NMD. ^[8]

In the nucleus PABP1 binds to the poly(A) tails of pre-mRNAs to facilitate stability, export, transport, and degradation. PABP1 binding is also required for nuclear-mediated degradation. PABPC1 contains four RNA-recognition motifs (RRMs). The first two, RRM1 and RRM2, bind both α-importin and the poly(A) tail of processed mRNA. This feature prevents mRNA from going back into the nucleus. ^[6]

Interactions

PABPC1 has been shown to interact with:

• ANAPC5, ^[9]
• CNOT7, ^[10]
• EIF4G3, ^[11]
• EIF4G1, ^[11]
• GSPT2, ^[12]
• PAIP1, ^{[13] [14]} and
• PAIP2. ^[15]

References

1. GRCh38: Ensembl release 89: ENSG00000070756 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000022283 – Ensembl, May 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.
5. Grange T, de Sa CM, Oddos J, Pictet R (June 1987). "Human mRNA polyadenylate binding protein: evolutionary conservation of a nucleic acid binding motif". Nucleic Acids Research. 15 (12): 4771–87. doi:10.1093/nar/15.12.4771. PMC   305917 . PMID   2885805.
6. Gray NK, Hrabálková L, Scanlon JP, Smith RW (December 2015). "Poly(A)-binding proteins and mRNA localization: who rules the roost?". Biochemical Society Transactions. 43 (6): 1277–84. doi: 10.1042/BST20150171 . PMID   26614673.
7. "Entrez Gene: PABPC1 poly(A) binding protein, cytoplasmic 1".
8. Fatscher T, Boehm V, Weiche B, Gehring NH (October 2014). "The interaction of cytoplasmic poly(A)-binding protein with eukaryotic initiation factor 4G suppresses nonsense-mediated mRNA decay". RNA. 20 (10): 1579–92. doi:10.1261/rna.044933.114. PMC   4174440 . PMID   25147240.
9. Koloteva-Levine N, Pinchasi D, Pereman I, Zur A, Brandeis M, Elroy-Stein O (May 2004). "The Apc5 subunit of the anaphase-promoting complex/cyclosome interacts with poly(A) binding protein and represses internal ribosome entry site-mediated translation". Molecular and Cellular Biology. 24 (9): 3577–87. doi:10.1128/mcb.24.9.3577-3587.2004. PMC   387753 . PMID   15082755.
10. Funakoshi Y, Doi Y, Hosoda N, Uchida N, Osawa M, Shimada I, Tsujimoto M, Suzuki T, Katada T, Hoshino S (December 2007). "Mechanism of mRNA deadenylation: evidence for a molecular interplay between translation termination factor eRF3 and mRNA deadenylases". Genes & Development. 21 (23): 3135–48. doi:10.1101/gad.1597707. PMC   2081979 . PMID   18056425.
11. Imataka H, Gradi A, Sonenberg N (December 1998). "A newly identified N-terminal amino acid sequence of human eIF4G binds poly(A)-binding protein and functions in poly(A)-dependent translation". The EMBO Journal. 17 (24): 7480–9. doi:10.1093/emboj/17.24.7480. PMC   1171091 . PMID   9857202.
12. Hoshino S, Imai M, Kobayashi T, Uchida N, Katada T (June 1999). "The eukaryotic polypeptide chain releasing factor (eRF3/GSPT) carrying the translation termination signal to the 3'-Poly(A) tail of mRNA. Direct association of erf3/GSPT with polyadenylate-binding protein". The Journal of Biological Chemistry. 274 (24): 16677–80. doi: 10.1074/jbc.274.24.16677 . PMID   10358005.
13. Roy G, De Crescenzo G, Khaleghpour K, Kahvejian A, O'Connor-McCourt M, Sonenberg N (June 2002). "Paip1 interacts with poly(A) binding protein through two independent binding motifs". Molecular and Cellular Biology. 22 (11): 3769–82. doi:10.1128/mcb.22.11.3769-3782.2002. PMC   133836 . PMID   11997512.
14. Craig AW, Haghighat A, Yu AT, Sonenberg N (April 1998). "Interaction of polyadenylate-binding protein with the eIF4G homologue PAIP enhances translation". Nature. 392 (6675): 520–3. Bibcode:1998Natur.392..520C. doi:10.1038/33198. PMID   9548260. S2CID   10891925.
15. Khaleghpour K, Kahvejian A, De Crescenzo G, Roy G, Svitkin YV, Imataka H, O'Connor-McCourt M, Sonenberg N (August 2001). "Dual interactions of the translational repressor Paip2 with poly(A) binding protein". Molecular and Cellular Biology. 21 (15): 5200–13. doi:10.1128/MCB.21.15.5200-5213.2001. PMC   87244 . PMID   11438674.

Further reading

• Görlach M, Burd CG, Dreyfuss G (April 1994). "The mRNA poly(A)-binding protein: localization, abundance, and RNA-binding specificity". Experimental Cell Research. 211 (2): 400–7. doi: 10.1006/excr.1994.1104 . PMID   7908267.
• Campbell LH, Borg KT, Haines JK, Moon RT, Schoenberg DR, Arrigo SJ (September 1994). "Human immunodeficiency virus type 1 Rev is required in vivo for binding of poly(A)-binding protein to Rev-dependent RNAs". Journal of Virology. 68 (9): 5433–8. doi:10.1128/jvi.68.9.5433-5438.1994. PMC   236943 . PMID   8057425.
• Huang Y, Carmichael GG (April 1996). "Role of polyadenylation in nucleocytoplasmic transport of mRNA". Molecular and Cellular Biology. 16 (4): 1534–42. doi:10.1128/mcb.16.4.1534. PMC   231138 . PMID   8657127.
• Craig AW, Haghighat A, Yu AT, Sonenberg N (April 1998). "Interaction of polyadenylate-binding protein with the eIF4G homologue PAIP enhances translation". Nature. 392 (6675): 520–3. Bibcode:1998Natur.392..520C. doi:10.1038/33198. PMID   9548260. S2CID   10891925.
• Afonina E, Stauber R, Pavlakis GN (May 1998). "The human poly(A)-binding protein 1 shuttles between the nucleus and the cytoplasm". The Journal of Biological Chemistry. 273 (21): 13015–21. doi: 10.1074/jbc.273.21.13015 . PMID   9582337.
• Imataka H, Gradi A, Sonenberg N (December 1998). "A newly identified N-terminal amino acid sequence of human eIF4G binds poly(A)-binding protein and functions in poly(A)-dependent translation". The EMBO Journal. 17 (24): 7480–9. doi:10.1093/emboj/17.24.7480. PMC   1171091 . PMID   9857202.
• Hornstein E, Git A, Braunstein I, Avni D, Meyuhas O (January 1999). "The expression of poly(A)-binding protein gene is translationally regulated in a growth-dependent fashion through a 5'-terminal oligopyrimidine tract motif". The Journal of Biological Chemistry. 274 (3): 1708–14. doi: 10.1074/jbc.274.3.1708 . PMID   9880551.
• Laroia G, Cuesta R, Brewer G, Schneider RJ (April 1999). "Control of mRNA decay by heat shock-ubiquitin-proteasome pathway". Science. 284 (5413): 499–502. Bibcode:1999Sci...284..499L. doi:10.1126/science.284.5413.499. PMID   10205060.
• Hoshino S, Imai M, Kobayashi T, Uchida N, Katada T (June 1999). "The eukaryotic polypeptide chain releasing factor (eRF3/GSPT) carrying the translation termination signal to the 3'-Poly(A) tail of mRNA. Direct association of erf3/GSPT with polyadenylate-binding protein". The Journal of Biological Chemistry. 274 (24): 16677–80. doi: 10.1074/jbc.274.24.16677 . PMID   10358005.
• Deo RC, Bonanno JB, Sonenberg N, Burley SK (September 1999). "Recognition of polyadenylate RNA by the poly(A)-binding protein". Cell. 98 (6): 835–45. doi: 10.1016/S0092-8674(00)81517-2 . PMID   10499800. S2CID   16247357.
• Féral C, Mattéi MG, Pawlak A, Guellaën G (October 1999). "Chromosomal localization of three human poly(A)-binding protein genes and four related pseudogenes". Human Genetics. 105 (4): 347–53. doi:10.1007/s004399900148. PMC   1865476 . PMID   10543404.
• Grosset C, Chen CY, Xu N, Sonenberg N, Jacquemin-Sablon H, Shyu AB (September 2000). "A mechanism for translationally coupled mRNA turnover: interaction between the poly(A) tail and a c-fos RNA coding determinant via a protein complex". Cell. 103 (1): 29–40. doi: 10.1016/S0092-8674(00)00102-1 . PMID   11051545. S2CID   18135412.
• Khaleghpour K, Svitkin YV, Craig AW, DeMaria CT, Deo RC, Burley SK, Sonenberg N (January 2001). "Translational repression by a novel partner of human poly(A) binding protein, Paip2". Molecular Cell. 7 (1): 205–16. doi: 10.1016/S1097-2765(01)00168-X . PMID   11172725.
• Bushell M, Wood W, Carpenter G, Pain VM, Morley SJ, Clemens MJ (June 2001). "Disruption of the interaction of mammalian protein synthesis eukaryotic initiation factor 4B with the poly(A)-binding protein by caspase- and viral protease-mediated cleavages". The Journal of Biological Chemistry. 276 (26): 23922–8. doi: 10.1074/jbc.M100384200 . PMID   11274152.
• Féral C, Guellaën G, Pawlak A (May 2001). "Human testis expresses a specific poly(A)-binding protein". Nucleic Acids Research. 29 (9): 1872–83. doi:10.1093/nar/29.9.1872. PMC   37253 . PMID   11328870.
• Khaleghpour K, Kahvejian A, De Crescenzo G, Roy G, Svitkin YV, Imataka H, O'Connor-McCourt M, Sonenberg N (August 2001). "Dual interactions of the translational repressor Paip2 with poly(A) binding protein". Molecular and Cellular Biology. 21 (15): 5200–13. doi:10.1128/MCB.21.15.5200-5213.2001. PMC   87244 . PMID   11438674.
• Woods AJ, Roberts MS, Choudhary J, Barry ST, Mazaki Y, Sabe H, Morley SJ, Critchley DR, Norman JC (February 2002). "Paxillin associates with poly(A)-binding protein 1 at the dense endoplasmic reticulum and the leading edge of migrating cells". The Journal of Biological Chemistry. 277 (8): 6428–37. doi: 10.1074/jbc.M109446200 . PMID   11704675.
• Lee J, Bedford MT (March 2002). "PABP1 identified as an arginine methyltransferase substrate using high-density protein arrays". EMBO Reports. 3 (3): 268–73. doi:10.1093/embo-reports/kvf052. PMC   1084016 . PMID   11850402.
• Jurica MS, Licklider LJ, Gygi SR, Grigorieff N, Moore MJ (April 2002). "Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis". RNA. 8 (4): 426–39. doi:10.1017/S1355838202021088. PMC   1370266 . PMID   11991638.