Nuclear cap-binding protein subunit 1 (NCBP1)

The protein contains 790 amino acids for an estimated molecular weight of 91839 Da.

 

Component of the cap-binding complex (CBC), which binds cotranscriptionally to the 5'-cap of pre-mRNAs and is involved in various processes such as pre-mRNA splicing, translation regulation, nonsense-mediated mRNA decay, RNA-mediated gene silencing (RNAi) by microRNAs (miRNAs) and mRNA export. The CBC complex is involved in mRNA export from the nucleus via its interaction with ALYREF/THOC4/ALY, leading to the recruitment of the mRNA export machinery to the 5'-end of mRNA and to mRNA export in a 5' to 3' direction through the nuclear pore. The CBC complex is also involved in mediating U snRNA and intronless mRNAs export from the nucleus. The CBC complex is essential for a pioneer round of mRNA translation, before steady state translation when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. The pioneer round of mRNA translation mediated by the CBC complex plays a central role in nonsense-mediated mRNA decay (NMD), NMD only taking place in mRNAs bound to the CBC complex, but not on eIF4E-bound mRNAs. The CBC complex enhances NMD in mRNAs containing at least one exon-junction complex (EJC) via its interaction with UPF1, promoting the interaction between UPF1 and UPF2. The CBC complex is also involved in 'failsafe' NMD, which is independent of the EJC complex, while it does not participate in Staufen-mediated mRNA decay (SMD). During cell proliferation, the CBC complex is also involved in microRNAs (miRNAs) biogenesis via its interaction with SRRT/ARS2 and i (updated: April 1, 2015)

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. 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.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  4. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

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.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 100%
Model score: 100
No model available.

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The reference OMIM entry for this protein is 600469

Nuclear cap-binding protein 1; ncbp1
Nuclear cap-binding protein, 80-kd
Ncbp
Cbp80

CLONING

Monomethylated cap structures are found on many eukaryotic mRNAs. The cap can stimulate cytoplasmic translation by facilitating ribosome binding to mRNA. There is also evidence that the cap can play a role in nuclear events such as splicing, where in vitro assays indicate that it is required for the formation of the spliceosome. Further, it has been suggested that the cap facilitates export of RNAs transcribed by RNA polymerase II from the nucleus to the cytoplasm. Proteins that bind to the cap structure are likely to be involved in these processes. Kataoka et al. (1994) described the cloning of a gene that encodes an 80-kD nuclear cap-binding protein (NCBP) found in HeLa cell nuclear extracts that may be involved in mRNA splicing and RNA export. Partially purified protein was sequenced, from which PCR primers were designed and used to isolate a cDNA from a HeLa cell library (Kataoka et al., 1994). The cDNA encodes a predicted 790-amino acid protein. Recombinant epitope-tagged NCBP was exclusively localized to the nucleus and the nuclear localization activity was demonstrated to be restricted to the N-terminal 70 amino acids (Kataoka et al., 1994). The same cDNA was also cloned by Izaurralde et al. (1994), who noted sequence similarity to the yeast GRC3/STO1 protein.

GENE FUNCTION

Nonsense-mediated decay (NMD) eliminates mRNAs that prematurely terminate translation. Ishigaki et al. (2001) used antibody to CBP80 or its cytoplasmic counterpart eIF4E (133440) to immunopurify ribonucleoprotein (RNP) containing nonsense-free or nonsense-containing transcripts. Data indicated that NMD takes place in association with CBP80. The authors defined other components of NMD-susceptible mRNP as CBP20 (605133), PABP2 (602279), eIF4G (600495), and the NMD factors UPF2 (605529) and UPF3 (see 605530). Consistent with the dependence of NMD on translation, the NMD of CBP80-bound mRNA was blocked by cycloheximide or suppressor tRNA. These findings provided evidence that translation can take place in association with CBP80. They also indicated that CBP80-bound mRNA undergoes a 'pioneer' round of translation, before CBP80-CBP20 are replaced by eIF4E and the UPF2 and UPF3 proteins dissociate from upstream of exon-exon junctions.

BIOCHEMICAL FEATURES

Mazza et al. (2001) determined the 2-angstrom crystal structure of the human nuclear cap-binding complex. The structure showed that the large subunit, CBP80, has 3 domains, each containing consecutive helical hairpins and resembling the so-called MIF4G domain found in several other proteins involved in RNA metabolism. The small subunit, CBP20, has an RNP fold and associates with the second and third domains of CBP80. Site-directed mutagenesis revealed 4 residues of CBP20 that are critical for cap binding.

MAPPING

By hybridizing to genomic DNA from a somatic cell hybrid panel, Chadwick et al. (1996) mapped the NCBP1 gene to 9q34.1. There was no evidence for a second locus in the human genome. Furthermore, NCBP1 hybridized to the same cosmid as the XPA gene (611153), indicating close physical proximity of the 2 loci. The close proximity of the 2 loci was conserved also in the mouse, where the genes are located on chromosome 4. ... More on the omim web site

Subscribe to this protein entry history

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 600469 was added.