Polyadenylate-binding protein 1 (PABPC1)

The protein contains 636 amino acids for an estimated molecular weight of 70671 Da.

 

Binds the poly(A) tail of mRNA, including that of its own transcript, and regulates processes of mRNA metabolism such as pre-mRNA splicing and mRNA stability (PubMed:11051545, PubMed:17212783, PubMed:25480299). Its function in translational initiation regulation can either be enhanced by PAIP1 or repressed by PAIP2 (PubMed:11051545, PubMed:20573744). Can probably bind to cytoplasmic RNA sequences other than poly(A) in vivo. Involved in translationally coupled mRNA turnover (PubMed:11051545). 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 (PubMed:11051545). 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 (PubMed:18447585). By binding to long poly(A) tails, may protect them from uridylation by ZCCHC6/ZCCHC11 and hence contribute to mRNA stability (PubMed:25480299).', '(Microbial infection) Positively regulates the replication of dengue virus (DENV). (updated: Oct. 16, 2019)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 42%
Model score: 0

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The reference OMIM entry for this protein is 604679

Polyadenylate-binding protein, cytoplasmic, 1; pabpc1
Polyadenylate-binding protein 1; pabp1; pab1
Poly(a)-binding protein 1
Poly(a)-binding protein; pabp

DESCRIPTION

The poly(A)-binding protein (PABP), which is found complexed to the 3-prime poly(A) tail of eukaryotic mRNA, is required for poly(A) shortening and translation initiation. In humans, the PABPs comprise a small nuclear isoform and a conserved gene family that displays at least 3 functional proteins: PABP1 (PABPC1), inducible PABP (iPABP, or PABPC4; 603407), and PABP3 (PABPC3; 604680). In addition, there are at least 4 pseudogenes, PABPCP1 to PABPCP4.

CLONING

Grange et al. (1987) isolated a melanoma cell cDNA encoding human PABP. The predicted 633-amino acid protein contains 4 repeats of an approximately 80-amino acid unit in its N-terminal half. The authors found that this repeat region is highly conserved between human and yeast PABP and is sufficient for poly(A) binding. In vitro translation of the human PABP cDNA yielded a protein with an apparent molecular mass of 73 kD by SDS-PAGE. Northern blot analysis indicated that PABP is expressed as a 2.9-kb mRNA in human melanoma cells. Gorlach et al. (1994) noted that each of the 4 repeats of PABP is a ribonucleoprotein (RNP) consensus sequence RNA-binding domain. They determined that PABP has a pI of approximately 10.3 and is a very abundant, stable protein.

GENE FUNCTION

Immunofluorescence studies of mammalian cells by Gorlach et al. (1994) indicated that PABP is located exclusively in the cytoplasm. However, using both indirect immunofluorescence and tagging of PABP1 by fusion to the green fluorescent protein (GFP), Afonina et al. (1998) demonstrated that PABP1 shuttles between the nucleus and cytoplasm. PABP1 accumulated in the nucleus when transcription was inhibited, suggesting that active transcription is required for nuclear export of PABP1. Deletion mutagenesis showed that the RNA binding ability of PABP1 is important for nuclear retention. Afonina et al. (1998) suggested that PABP1 is involved in nuclear events associated with the formation and transport of mRNP to the cytoplasm. Cytokine and protooncogene mRNAs are rapidly degraded through AU-rich elements in the 3-prime untranslated region. Rapid decay involves AU-rich binding protein AUF1 (601324), which complexes with heat-shock proteins HSC70 (600816) and HSP70 (see 140550), translation initiation factor EIF4G (600495), and PABP. AU-rich mRNA decay is associated with displacement of EIF4G from AUF1, ubiquitination of AUF1, and degradation of AUF1 by proteasomes. Induction of HSP70 by heat shock, downregulation of the ubiquitin-proteasome network, or inactivation of ubiquitinating enzyme E1 (314370) all result in HSP70 sequestration of AUF1 in the perinucleus-nucleus, and all 3 processes block decay of AU-rich mRNAs and AUF1 protein. These results link the rapid degradation of cytokine mRNAs to the ubiquitin-proteasome pathway (Laroia et al., 1999). AU-rich elements and protein-coding determinants direct rapid removal of poly(A) tails as a necessary first step in mRNA decay. Grosset et al. (2000) determined that 5 proteins form a multiprotein complex associated with the major protein-coding-region determinant of instability (mCRD) of the FOS gene (164810): PABP, HNRNPD (AUF1), PAIP1 (605184), NSAP1, and UNR (191510). Overexpression of these proteins stabilized mCRD-containing mRNA by impeding deadenylation. Kahvejian et al. (2005) studied the mechanism by which PABP stimulates ribosome recruitment and translation by depleting Pabp from nuclease-treated mouse carcinoma cell-free tran ... More on the omim web site

Subscribe to this protein entry history

Oct. 27, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

May 12, 2019: Protein entry updated
Automatic update: model status changed

May 11, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

Nov. 17, 2018: Protein entry updated
Automatic update: model status changed

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

Oct. 27, 2017: Protein entry updated
Automatic update: model status changed

March 25, 2017: Additional information
No protein expression data in P. Mayeux work for PABPC1

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604679 was added.

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed