Polypyrimidine tract-binding protein 1 (PTBP1)

The protein contains 531 amino acids for an estimated molecular weight of 57221 Da.

 

Plays a role in pre-mRNA splicing and in the regulation of alternative splicing events. Activates exon skipping of its own pre-mRNA during muscle cell differentiation. Binds to the polypyrimidine tract of introns. May promote RNA looping when bound to two separate polypyrimidine tracts in the same pre-mRNA. May promote the binding of U2 snRNP to pre-mRNA. Cooperates with RAVER1 to modulate switching between mutually exclusive exons during maturation of the TPM1 pre-mRNA. Represses the splicing of MAPT/Tau exon 10 (PubMed:15009664). In case of infection by picornaviruses, binds to the viral internal ribosome entry site (IRES) and stimulates the IRES-mediated translation (PubMed:21518806). (updated: Jan. 31, 2018)

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: 45%
Model score: 30

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The reference OMIM entry for this protein is 600693

Polypyrimidine tract-binding protein 1; ptbp1
Ptb
Heterogeneous nuclear ribonucleoprotein polypeptide i
Hnrnpi

DESCRIPTION

Polypyrimidine tract-binding protein (PTB), also known as heterogeneous nuclear ribonucleoprotein type I (hnRNP I), is a 59.6-kD nuclear protein that binds pre-mRNAs in specific regions of the hnRNA-protein complexes sensitive to micrococcal nuclease. The hnRNP I protein shows an unusual pattern of nuclear localization (Ghetti et al., 1992). It has been implicated in pre-mRNA splicing.

GENE FUNCTION

Inclusion of cardiac troponin T (TNNT2; 191045) exon 5 in embryonic muscle requires conserved flanking intronic elements (MSEs). Charlet-B. et al. (2002) found that ETR3 (CUGBP2; 602538), a member of the CELF family, binds U/G motifs in 2 MSEs and directly activates exon inclusion in vitro. They showed that binding and activation by ETR3 are directly antagonized by PTB. The use of dominant-negative mutants demonstrated that endogenous CELF and PTB activities are required for MSE-dependent activation and repression in muscle and nonmuscle cells, respectively. Combined use of CELF and PTB dominant-negative mutants provided an in vivo demonstration that antagonistic splicing activities exist within the same cells. Makeyev et al. (2007) showed that the expression of miR124 (see 609327) in mouse neuronal cells induced a switch from general to neuron-specific alternative splicing by directly targeting the mRNA of Ptbp1. They showed that miR124 increased the abundance of neuron-specific Ptbp2 (608449) and Gabbr1 (603540) mRNAs by preventing Ptbp1-dependent exon skipping that leads to nonsense-mediated decay of these mRNAs. Makeyev et al. (2007) further showed that retinoic acid-induced neuronal differentiation in a mouse embryonal carcinoma cell line resulted in the accumulation of miR124, which correlated with decreased Ptbp1 protein levels, increased Ptbp2 levels, and a switch to neuron-specific alternative splicing. David et al. (2010) showed that 3 heterogeneous nuclear ribonucleoprotein (hnRNP) proteins, PTB, hnRNPA1 (164017), and hnRNPA2 (600124), bind repressively to sequences flanking exon 9 of the PKM2 gene (179050), resulting in exon 10 inclusion and the expression of the PKM2 (embryonic) isoform. David et al. (2010) also demonstrated that the oncogenic transcription factor c-MYC (190080) upregulates transcription of PTB, hnRNPA1, and hnRNPA2, ensuring a high PKM2/PKM1 ratio. Establishing a relevance to cancer, David et al. (2010) showed that human gliomas (137800) overexpress c-Myc, PTB, hnRNPA1, and hnRNPA2 in a manner that correlates with PKM2 expression. David et al. (2010) concluded that their results defined a pathway that regulates an alternative splicing event required for tumor cell proliferation. Luco et al. (2010) demonstrated a direct role for histone modifications, specifically, trimethylation of H3 at lys36 (H3-K36me3; see 602810), in alternative splicing. The authors found that MRG15 (607303) distribution along the PTB-dependent alternatively spliced genes FGFR2 (176943), TPM2 (190990), TPM1 (191010), and PKM2, but not along the control gene CD44 (107269), mimicked H3-K36me3 distribution. Overexpression of MRG15 was sufficient to force exclusion of the PTB-dependent exons but did not significantly alter the inclusion levels of CD44 exon v6. Additional experiments led Luco et al. (2010) to conclude that the chromatin-binding protein MRG15 is a modulator of PTB-dependent alternative splice site selection. The results of Luco et al. (2010) led them to propose the existence of an adaptor system ... More on the omim web site

Subscribe to this protein entry history

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

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600693 was added.

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