Protein: Nuclear cap-binding protein subunit 1 (80 kDa nuclear cap-binding protein) (CBP80) (NCBP 80 kDa subunit) (Q3UYV9)
Organism: Mus musculus (Mouse)
Function: 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 is required for miRNA-mediated RNA interference. The CBC complex also acts as a negative regulator of PARN, thereby acting as an inhibitor of mRNA deadenylation. In the CBC complex, NCBP1/CBP80 does not bind directly capped RNAs (m7GpppG-capped RNA) but is required to stabilize the movement of the N-terminal loop of NCBP2/CBP20 and lock the CBC into a high affinity cap-binding state with the cap structure. Associates with NCBP3 to form an alternative cap-binding complex (CBC) which plays a key role in mRNA export and is particularly important in cellular stress situations such as virus infections. The conventional CBC with NCBP2 binds both small nuclear RNA (snRNA) and messenger (mRNA) and is involved in their export from the nucleus whereas the alternative CBC with NCBP3 does not bind snRNA and associates only with mRNA thereby playing a role only in mRNA export. NCBP1/CBP80 is required for cell growth and viability (By similarity).
Subcellular location: Nucleus {ECO:0000269|PubMed:22767893}. Cytoplasm {ECO:0000250|UniProtKB:Q09161}. Note=Localized in cytoplasmic mRNP granules containing untranslated mRNAs. {ECO:0000250|UniProtKB:Q09161}.
Sequence: MSRRRHSYENDGGQPHKRRKTSDANETEDHLESLICKVGEKSACSLESNLEGLAGVLEADLPNYKSKILRLLCTVARLLPEKLTIYTTLVGLLNARNYNFGGEFVEAMIRQLKESLKANNYNEAVYLVRFLSDLVNCHVIAAPSMVAMFENFVSVTQEEDVPQVRRDWYVYAFLSSLPWVGKELYEKKDAEMDRIFSTTESYLKRRQKTHVPMLQVWTADKPHPQEEYLDCLWAQIQKLKKDRWQERHILRPYLAFDSILCEALQHNLPPFTPPPHTEDSVYPMPRVIFRMFDYTDDPEGPVMPGSHSVERFVIEENLHCIIKSYWKERKTCAAQLVSYPGKNKIPLNYHIVEVIFAELFQLPAPPHIDVMYTTLLIELCKLQPGSLPQVLAQATEMLYMRLDTMSTTCVDRFINWFSHHLSNFQFRWSWEDWSDCLTQDLESPKPKFVREVLEKCMRLSYHQHILDIVPPTFSALCPANPTCIYKYGDESSNSLPGHSVALCLSVAFKSKATNDEIFSILKDVPNPNQVDDDDEGFRFNPLKIEVFVQTLLHLAAKSFSHSFSALAKFHEVFKTLAESDKGKLHVLRVMFEVWRNHPQMIAVLVDKMIRTQIVDCAAVANWIFSSELSRDFTRLFVWEILHSTIRKMNKHVLKIQKELEEAKEKLARQHKRRSDDDDRSSDRKDGALEEQIERLQEKVEAAQSEQKNLFLVIFQRFIMILTEHLVRCETDGTSILTPWYKNCIERLQQIFLQHHQTIQQYMVTLENLLFTAELDPHILAVFQQFCALQA
InterPro domains: - IPR016024: Armadillo-type fold (homologous_superfamily) [28-790]
- IPR003890: MIF4G-like, type 3 (domain) [28-240]
- IPR015174: MIF4G-like, type 2 (domain) [485-759]
- IPR027159: Nuclear cap-binding protein subunit 1 (family) [3-790]
- IPR015172: MIF4G-like, type 1 (domain) [326-470]
Interaction partners: - Nuclear cap-binding protein subunit 2
- Serrate RNA effector molecule homolog
- Importin subunit alpha-1
- Eukaryotic translation initiation factor 4E
- Small nuclear ribonucleoprotein Sm D2
- Small nuclear ribonucleoprotein-associated protein N
- Pre-mRNA-processing factor 17
- Nuclear cap-binding protein subunit 3
- Small nuclear ribonucleoprotein F
- U4/U6.U5 tri-snRNP-associated protein 1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0097159 (organic cyclic compound binding), GO:1901363 (heterocyclic compound binding), GO:0005515 (protein binding), GO:0003676 (nucleic acid binding), GO:0003723 (RNA binding), GO:0000339 (RNA cap binding), GO:0000340 (RNA 7-methylguanosine cap binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0009628 (response to abiotic stimulus), GO:0009058 (biosynthetic process), GO:0019222 (regulation of metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0071704 (organic substance metabolic process), GO:0009056 (catabolic process), GO:0009892 (negative regulation of metabolic process), GO:0050793 (regulation of developmental process), GO:0044237 (cellular metabolic process), GO:0050794 (regulation of cellular process), GO:0009893 (positive regulation of metabolic process), GO:0051094 (positive regulation of developmental process), GO:0044238 (primary metabolic process), GO:0048522 (positive regulation of cellular process), GO:0045597 (positive regulation of cell differentiation), GO:1901576 (organic substance biosynthetic process), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0046483 (heterocycle metabolic process), GO:0009314 (response to radiation), GO:0044248 (cellular catabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0044249 (cellular biosynthetic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0043170 (macromolecule metabolic process), GO:0009891 (positive regulation of biosynthetic process), GO:1901360 (organic cyclic compound metabolic process), GO:0006139 (nucleobase-containing compound metabolic process), GO:0031325 (positive regulation of cellular metabolic process), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0045595 (regulation of cell differentiation), GO:0031323 (regulation of cellular metabolic process), GO:0080090 (regulation of primary metabolic process), GO:1901575 (organic substance catabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0034655 (nucleobase-containing compound catabolic process), GO:0009059 (macromolecule biosynthetic process), GO:0009416 (response to light stimulus), GO:0044270 (cellular nitrogen compound catabolic process), GO:1901362 (organic cyclic compound biosynthetic process), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0051246 (regulation of protein metabolic process), GO:0019438 (aromatic compound biosynthetic process), GO:0019439 (aromatic compound catabolic process), GO:0046700 (heterocycle catabolic process), GO:0010468 (regulation of gene expression), GO:0034654 (nucleobase-containing compound biosynthetic process), GO:0010557 (positive regulation of macromolecule biosynthetic process), GO:0009057 (macromolecule catabolic process), GO:0045935 (positive regulation of nucleobase-containing compound metabolic process), GO:0051254 (positive regulation of RNA metabolic process), GO:0034248 (regulation of amide metabolic process), GO:0090304 (nucleic acid metabolic process), GO:0044265 (cellular macromolecule catabolic process), GO:0018130 (heterocycle biosynthetic process), GO:1901361 (organic cyclic compound catabolic process), GO:0031326 (regulation of cellular biosynthetic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0044271 (cellular nitrogen compound biosynthetic process), GO:0051252 (regulation of RNA metabolic process), GO:0010467 (gene expression), GO:0010629 (negative regulation of gene expression), GO:0031328 (positive regulation of cellular biosynthetic process), GO:0016070 (RNA metabolic process), GO:0006402 (mRNA catabolic process), GO:0006401 (RNA catabolic process), GO:0006396 (RNA processing), GO:2000112 (regulation of cellular macromolecule biosynthetic process), GO:1902680 (positive regulation of RNA biosynthetic process), GO:0006417 (regulation of translation), GO:0032774 (RNA biosynthetic process), GO:0097659 (nucleic acid-templated transcription), GO:0045727 (positive regulation of translation), GO:0010608 (post-transcriptional regulation of gene expression), GO:0032784 (regulation of DNA-templated transcription elongation), GO:0045893 (positive regulation of DNA-templated transcription), GO:0000956 (nuclear-transcribed mRNA catabolic process), GO:0008380 (RNA splicing), GO:0006397 (mRNA processing), GO:0016071 (mRNA metabolic process), GO:1903508 (positive regulation of nucleic acid-templated transcription), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0006351 (DNA-templated transcription), GO:0000398 (mRNA splicing, via spliceosome), GO:0000184 (nuclear-transcribed mRNA catabolic process, nonsense-mediated decay), GO:0000375 (RNA splicing, via transesterification reactions), GO:0031124 (mRNA 3'-end processing), GO:0006366 (transcription by RNA polymerase II), GO:0042789 (mRNA transcription by RNA polymerase II), GO:0000377 (RNA splicing, via transesterification reactions with bulged adenosine as nucleophile)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0032991 (protein-containing complex), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0034518 (RNA cap binding complex), GO:0140535 (intracellular protein-containing complex), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus)