ID:PABP1_HUMAN DESCRIPTION: RecName: Full=Polyadenylate-binding protein 1; Short=PABP-1; Short=Poly(A)-binding protein 1; FUNCTION: Binds the poly(A) tail of mRNA. May be involved in cytoplasmic regulatory processes of mRNA metabolism such as pre- mRNA splicing. Its function in translational initiation regulation can either be enhanced by PAIP1 or repressed by PAIP2. Can probably bind to cytoplasmic RNA sequences other than poly(A) in vivo. Involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain. Involved in regulation of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons; for the recognition of premature termination codons (PTC) and initiation of NMD a competitive interaction between UPF1 and PABPC1 with the ribosome-bound release factors is proposed. SUBUNIT: Component of a multi subunit autoregulatory ribonucleoprotein complex (ARC), at least composed of IGF2BP1, PABPC1 and CSDE1. Interacts with IGF2BP1. Part of a complex associated with the FOS mCRD domain and consisting of HNRPD, SYNCRIP, PAIP1 and CSDE1/UNR. Interacts with the PABPC1- interacting motif-1 (PAM1) and -2 (PAM2) of PAIP1 and PAIP2. Interacts with PAIP1 with a 1:1 stoichiometry and with PAIP2 with a 1:2 stoichiometry. The interaction with CSDE1 is direct and RNA- independent. Found in a mRNP complex with YBX2. Interacts with PAPD4/GLD2. Identified in the spliceosome C complex. Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1. Identified in a mRNP granule complex, at least composed of ACTB, ACTN4, DHX9, ERG, HNRNPA1, HNRNPA2B1, HNRNPAB, HNRNPD, HNRNPL, HNRNPR, HNRNPU, HSPA1, HSPA8, IGF2BP1, ILF2, ILF3, NCBP1, NCL, PABPC1, PABPC4, PABPN1, RPLP0, RPS3, RPS3A, RPS4X, RPS8, RPS9, SYNCRIP, TROVE2, YBX1 and untranslated mRNAs. Interacts with IGF2BP1 and NFX1. Interacts with PIWIL1 (By similarity). Interacts with EIF2C1, EIF2C2, GSPT1 and GSPT2. Interacts with human cytomegalovirus/HHV-5 protein UL69. INTERACTION: Q99700:ATXN2; NbExp=3; IntAct=EBI-81531, EBI-697691; O00571:DDX3X; NbExp=9; IntAct=EBI-81531, EBI-353779; Q8IYD1:GSPT2; NbExp=3; IntAct=EBI-81531, EBI-3869637; Q14103-4:HNRNPD; NbExp=2; IntAct=EBI-81531, EBI-432545; Q9H074:PAIP1; NbExp=6; IntAct=EBI-81531, EBI-81519; Q96Q15:SMG1; NbExp=2; IntAct=EBI-81531, EBI-1049832; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Localized in cytoplasmic mRNP granules containing untranslated mRNAs. Shuttles between the cytoplasm and the nucleus. TISSUE SPECIFICITY: Ubiquitous. DOMAIN: The RNA-binding domains RRM1 and RRM2 and the C-terminus (last 138 amino acids) regions interact with the PABPC1- interacting motif-1 (PAM1) and -2 (PAM2) of PAIP1, respectively. DOMAIN: The RNA-binding domains RRM2 and RRM3 and the C-terminus (last 138 amino acids) regions interact with the PABPC1- interacting motif-1 (PAM1) and -2 (PAM2) of PAIP2, respectively. PTM: Phosphorylated by MAPKAPK2. PTM: Methylated by CARM1. Arg-493 is dimethylated, probably to asymmetric dimethylarginine. MISCELLANEOUS: Many viruses shutoff host mRNA translational machinery by inhibiting cellular PABPC1 activity using different mechanisms. Picornaviruses, caliciviruses or lentiviruses encode proteases that cleave PABPC1 at several defined sites in the proline-rich linker region between RRMs and the C-terminal domain. Rotaviruses, gammherpesviruses and bunyamwera virus relocalize PABPC1 from the cytoplasm to the nucleus thus altering its function. Many of these viruses translate their mRNA in a PABPC1- independent manner and are unaffected by host PABPC1 inhibition. SIMILARITY: Belongs to the polyadenylate-binding protein type-1 family. SIMILARITY: Contains 1 PABC domain. SIMILARITY: Contains 4 RRM (RNA recognition motif) domains. CAUTION: Was termed (Ref.5) polyadenylate binding protein II.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P11940
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BC015958 - Homo sapiens poly(A) binding protein, cytoplasmic 1, mRNA (cDNA clone MGC:15290 IMAGE:3940309), complete cds. Y00345 - Human mRNA for polyA binding protein. BC041863 - Homo sapiens poly(A) binding protein, cytoplasmic 1, mRNA (cDNA clone IMAGE:5271298). DL491276 - Novel nucleic acids. KC832802 - Homo sapiens hsa-miR-7705 miRNA, complete sequence. JD063382 - Sequence 44406 from Patent EP1572962. DL489916 - Novel nucleic acids. AK303120 - Homo sapiens cDNA FLJ57246 complete cds, highly similar to Poly(A)-binding protein 1. AK130523 - Homo sapiens cDNA FLJ27013 fis, clone SLV05396, highly similar to Polyadenylate-binding protein 1. AK298990 - Homo sapiens cDNA FLJ59219 complete cds, highly similar to Poly(A)-binding protein 1. JD487974 - Sequence 468998 from Patent EP1572962. JD127755 - Sequence 108779 from Patent EP1572962. JD557571 - Sequence 538595 from Patent EP1572962. BC023520 - Homo sapiens poly(A) binding protein, cytoplasmic 1, mRNA (cDNA clone MGC:12727 IMAGE:4123269), complete cds. BC023217 - Homo sapiens cDNA clone IMAGE:4522410. AK095194 - Homo sapiens cDNA FLJ37875 fis, clone BRSSN2018771, highly similar to Poly(A)-binding protein 1. Z48501 - H.sapiens mRNA for polyadenylate binding protein II. HZ454937 - JP 2015221026-A/6: Method for promoting the translation of artificial mRNA. DQ893508 - Synthetic construct clone IMAGE:100006138; FLH194899.01X; RZPDo839G0380D poly(A) binding protein, cytoplasmic 1 (PABPC1) gene, encodes complete protein. DQ896500 - Synthetic construct Homo sapiens clone IMAGE:100010960; FLH194895.01L; RZPDo839G0370D poly(A) binding protein, cytoplasmic 1 (PABPC1) gene, encodes complete protein. AB385157 - Synthetic construct DNA, clone: pF1KB5695, Homo sapiens PABPC1 gene for polyadenylate-binding protein 1, complete cds, without stop codon, in Flexi system. DQ584635 - Homo sapiens piRNA piR-51747, complete sequence. JD022332 - Sequence 3356 from Patent EP1572962. JD034265 - Sequence 15289 from Patent EP1572962. CU677537 - Synthetic construct Homo sapiens gateway clone IMAGE:100023362 5' read PABPC1 mRNA. JD127041 - Sequence 108065 from Patent EP1572962. JD489803 - Sequence 470827 from Patent EP1572962. JD270922 - Sequence 251946 from Patent EP1572962. JD300425 - Sequence 281449 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_eif4Pathway - Regulation of eIF4e and p70 S6 Kinase
Reactome (by CSHL, EBI, and GO)
Protein P11940 (Reactome details) participates in the following event(s):
R-HSA-156808 Formation of translation initiation complexes yielding circularized Ceruloplasmin mRNA in a 'closed-loop' conformation R-HSA-450551 AUF1 binds translation and heat shock proteins R-HSA-429955 CCR4-NOT complex deadenylates mRNA R-HSA-429992 PARN deadenylates mRNA R-HSA-156823 Association of phospho-L13a with GAIT element of Ceruloplasmin mRNA R-HSA-430021 PAN2-PAN3 complex partially deadenylates mRNA R-HSA-8941312 ZCCHC6, ZCCHC11 are mRNA uridyltransferases R-HSA-927832 UPF1 binds an mRNP with a termination codon preceding an Exon Junction Complex R-HSA-927789 Formation of UPF1:eRF3 complex on mRNA with a premature termination codon and no Exon Junction Complex R-HSA-927889 SMG1 phosphorylates UPF1 (enhanced by Exon Junction Complex) R-HSA-72649 Translation initiation complex formation R-HSA-450408 AUF1 (hnRNP D0) binds and destabilizes mRNA R-HSA-9010553 Regulation of expression of SLITs and ROBOs R-HSA-429947 Deadenylation of mRNA R-HSA-975957 Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) R-HSA-156827 L13a-mediated translation R-HSA-72662 Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S R-HSA-450531 Regulation of mRNA stability by proteins that bind AU-rich elements R-HSA-376176 Signaling by ROBO receptors R-HSA-429914 Deadenylation-dependent mRNA decay R-HSA-927802 Nonsense-Mediated Decay (NMD) R-HSA-72613 Eukaryotic Translation Initiation R-HSA-975956 Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) R-HSA-72737 Cap-dependent Translation Initiation R-HSA-8953854 Metabolism of RNA R-HSA-422475 Axon guidance R-HSA-72766 Translation R-HSA-1266738 Developmental Biology R-HSA-392499 Metabolism of proteins