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Cleavage and polyadenylation specificity factor subunit 4
Known also as: Cleavage and polyadenylation specificity factor 30 kDa subunit, CPSF 30 kDa subunit, NS1 effector domain-binding protein 1
Known abbreviations: CPSF4, CPSF30, NAR, NEB1
Yeast homolog: YTH1
Protein
Structures Models Domains Secondary structure Disorder |
This protein is highly disordered (45 % of residues are predicted to be disordered)
Top 3 models:
 |  |  |
| Template: 2d9n, chain A Method: hhsearch Fragment: 52-130 | Template: 2d9n, chain A Method: phyre Fragment: 30-95 | Template: 2cqe, chain A Method: hhsearch Fragment: 52-86, 145-213 |
This protein has alternative isoforms:
Isoform 1:
| Sequence length: | 269 aa |
| Molecular weight: | 30.255 kDa |
| Isoelectric point: | 8.12 |
1........10........20........30........40........50........60........70........80........90........100.......110.......120.......130
MQEIIASVDHIKFDLEIAVEQQLGAQPLPFPGMDKSGAAVCEFFLKAACGKGGMCPFRHISGEKTVVCKHWLRGLCKKGDQCEFLHEYDMTKMPECYFYSKFGECSNKECPFLHIDPESKIKDCPWYDRG
FCKHGPLCRHRHTRRVICVNYLVGFCPEGPSCKFMHPRFELPMGTTEQPPLPQQTQPPAKQSNNPPLQRSSSLIQLTSQNSSPNQQRTPQVIGVMQSQNSSAGNRGPRPLEQVTCYKCGEKGHYANRCTK
GHLAFLSGQ
Isoform 2:
| Sequence length: | 244 aa |
| Molecular weight: | 27.547 kDa |
| Isoelectric point: | 8.03 |
1........10........20........30........40........50........60........70........80........90........100.......110.......120.......130
MQEIIASVDHIKFDLEIAVEQQLGAQPLPFPGMDKSGAAVCEFFLKAACGKGGMCPFRHISGEKTVVCKHWLRGLCKKGDQCEFLHEYDMTKMPECYFYSKFGECSNKECPFLHIDPESKIKDCPWYDRG
FCKHGPLCRHRHTRRVICVNYLVGFCPEGPSCKFMHPRFELPMGTTEQPPLPQQTQPPAKQRTPQVIGVMQSQNSSAGNRGPRPLEQVTCYKCGEKGHYANRCTKGHLAFLSGQ
Isoform 3:
| Sequence length: | 243 aa |
| Molecular weight: | 27.419 kDa |
| Isoelectric point: | 8.03 |
1........10........20........30........40........50........60........70........80........90........100.......110.......120.......130
MQEIIASVDHIKFDLEIAVEQQLGAQPLPFPGMDKSGAAVCEFFLKAACGKGGMCPFRHISGEKTVVCKHWLRGLCKKGDQCEFLHEYDMTKMPECYFYSKFGECSNKECPFLHIDPESKIKDCPWYDRG
FCKHGPLCRHRHTRRVICVNYLVGFCPEGPSCKFMHPRFELPMGTTEQPPLPQQTQPPAKRTPQVIGVMQSQNSSAGNRGPRPLEQVTCYKCGEKGHYANRCTKGHLAFLSGQ
Gene location: 7q22.1
Summary
CPSF4 is a component of the cleavage and polyadenylation specificity factor (CPSF) complex that play a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. CPSF4 binds RNA polymers with a preference for poly(U).
CPSF-30 is required for both cleavage and polyadenylation.
CPSF-30 has a second isoform in humans (locus XP_945726), sharing 54% sequence identity, but its function is not known.
CPSF-30 contains five CCCH zinc finger motifs (ZF1-ZF5) in all eukaryotes, and metazoan CPSF-30 has an additional CCHC zinc knuckle at the C-terminus. CCCH zinc fingers have the consensus sequence CX8CX5CX3H, while CCHC zinc knuckles have the consensus sequence CX2CX4HX4C. CCCH zinc finger motifs are involved in protein-protein interactions (e.g. ZF4 and ZF5 are required for interactions with Fip1p).
Association with influenza A virus NS1 blocks processing of pre-mRNAs, thereby preventing nuclear export of host cell mRNAs. The NS1 effector domain functionally interacts with the cellular 30 kDa subunit of cleavage and polyadenylation specific factor 4. In influenza virus-infected cells, the NS1 protein is physically associated with cleavage and polyadenylation specific factor 4, 30kD subunit. Binding of the NS1 protein to the 30 kDa protein in vitro prevents CPSF binding to the RNA substrate and inhibits 3' end cleavage and polyadenylation of host pre-mRNAs. Thus the NS1 protein selectively inhibits the nuclear export of cellular, and not viral, mRNAs. Multiple alternatively spliced transcript variants that encode different isoforms have been described for this gene.
See this protein in other databases:
Literature:
- Murthy KG, Manley JL. Characterization of the multisubunit cleavage-polyadenylation specificity factor from calf thymus. J Biol Chem 1992 267(21):14804-11, doi: , PMID: 1634525.
- Thomas PE, Wu X, Liu M et al. Genome-wide control of polyadenylation site choice by CPSF30 in Arabidopsis. Plant Cell 2012 24(11):4376-88, doi: 10.1105/tpc.112.096107, PMID: 23136375.
- Barabino SM, Hubner W, Jenny A et al. The 30-kD subunit of mammalian cleavage and polyadenylation specificity factor and its yeast homolog are RNA-binding zinc finger proteins. Genes Dev 1997 11(13):1703-16, doi: , PMID: 9224719.
- Nemeroff ME, Barabino SM, Li Y et al. Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3"end formation of cellular pre-mRNAs. Mol Cell 1998 1(7):991-1000, doi: , PMID: 9651582.
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