CPLM-008487

Genbank Nucleotide ID

Nuclear cap-binding protein subunit 2

Protein Synonyms/Alias

20 kDa nuclear cap-binding protein; Cell proliferation-inducing gene 55 protein; NCBP 20 kDa subunit; CBP20; NCBP-interacting protein 1; NIP1

Homo sapiens (Human)

Position	Peptide	Type	References
7	*MSGGLLKALRSDSY	ubiquitination	[1, 2]
120	TDWDAGFKEGRQYGR	ubiquitination	[1, 2, 3, 4, 5]
151	AGRGGYGKLAQNQ**	acetylation	[6]
151	AGRGGYGKLAQNQ**	ubiquitination	[1, 2, 7]

[1] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
[2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[3] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[4] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[5] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
[6] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
[7] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]

Functional Description

Component of the cap-binding complex (CBC), which binds co-transcriptionally 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, thereby being 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, NCBP2/CBP20 recognizes and binds capped RNAs (m7GpppG-capped RNA) but requires NCBP1/CBP80 to stabilize the movement of its N-terminal loop and lock the CBC into a high affinity cap-binding state with the cap structure.

DOMAIN 40 118 RRM.
REGION 112 116 mRNA cap-binding.
REGION 123 127 mRNA cap-binding.
REGION 133 134 mRNA cap-binding.
BINDING 20 20 mRNA cap.
BINDING 43 43 mRNA cap.
MOD_RES 13 13 Phosphoserine (By similarity).
MOD_RES 18 18 Phosphoserine.

3D-structure; Alternative splicing; Complete proteome; Cytoplasm; Direct protein sequencing; mRNA capping; mRNA processing; mRNA splicing; mRNA transport; Nonsense-mediated mRNA decay; Nucleus; Phosphoprotein; Reference proteome; RNA-binding; RNA-mediated gene silencing; Translation regulation; Transport.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005829; C:cytosol; TAS:Reactome.
GO:0005845; C:mRNA cap binding complex; IDA:UniProtKB.
GO:0005846; C:nuclear cap binding complex; IEA:InterPro.
GO:0005654; C:nucleoplasm; IDA:UniProtKB.
GO:0000166; F:nucleotide binding; IEA:InterPro.
GO:0000340; F:RNA 7-methylguanosine cap binding; IDA:UniProtKB.
GO:0006370; P:7-methylguanosine mRNA capping; IDA:UniProtKB.
GO:0031047; P:gene silencing by RNA; IEA:UniProtKB-KW.
GO:0008334; P:histone mRNA metabolic process; TAS:Reactome.
GO:0031124; P:mRNA 3'-end processing; TAS:Reactome.
GO:0045292; P:mRNA cis splicing, via spliceosome; IDA:UniProtKB.
GO:0006406; P:mRNA export from nucleus; TAS:Reactome.
GO:0034660; P:ncRNA metabolic process; TAS:Reactome.
GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IDA:UniProtKB.
GO:0046833; P:positive regulation of RNA export from nucleus; ISS:UniProtKB.
GO:0050434; P:positive regulation of viral transcription; TAS:Reactome.
GO:0006446; P:regulation of translational initiation; IDA:UniProtKB.
GO:0006408; P:snRNA export from nucleus; ISS:UniProtKB.
GO:0000387; P:spliceosomal snRNP assembly; TAS:Reactome.
GO:0006369; P:termination of RNA polymerase II transcription; TAS:Reactome.
GO:0006368; P:transcription elongation from RNA polymerase II promoter; TAS:Reactome.
GO:0022415; P:viral reproductive process; TAS:Reactome.

IPR027157; NCBP2.
IPR012677; Nucleotide-bd_a/b_plait.
IPR000504; RRM_dom.