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Cleavage and polyadenylation specificity factor subunit 3
Known also as: Cleavage and polyadenylation specificity factor 73 kDa subunit, mRNA 3'-end-processing endonuclease CPSF-73
Known abbreviations: CPSF3, CPSF-73, CPSF73
Yeast homolog: YSH1
Protein
Structures Models Domains Secondary structure Disorder |
Top 3 models:
 |  |  |
| Template: 2i7v, chain A Method: blastp Fragment: 1-459 | Template: 3zq4, chain A Method: hhsearch Fragment: 4-584 | Template: 3bk2, chain A Method: hhsearch Fragment: 1-600 |
| Sequence length: | 684 aa |
| Molecular weight: | 77.486 kDa |
| Isoelectric point: | 5.36 |
Sequence:
1........10........20........30........40........50........60........70........80........90........100.......110.......120.......130
MSAIPAEESDQLLIRPLGAGQEVGRSCIILEFKGRKIMLDCGIHPGLEGMDALPYIDLIDPAEIDLLLISHFHLDHCGALPWFLQKTSFKGRTFMTHATKAIYRWLLSDYVKVSNISADDMLYTETDLEE
SMDKIETINFHEVKEVAGIKFWCYHAGHVLGAAMFMIEIAGVKLLYTGDFSRQEDRHLMAAEIPNIKPDILIIESTYGTHIHEKREEREARFCNTVHDIVNRGGRGLIPVFALGRAQELLLILDEYWQNH
PELHDIPIYYASSLAKKCMAVYQTYVNAMNDKIRKQININNPFVFKHISNLKSMDHFDDIGPSVVMASPGMMQSGLSRELFESWCTDKRNGVIIAGYCVEGTLAKHIMSEPEEITTMSGQKLPLKMSVDY
ISFSAHTDYQQTSEFIRALKPPHVILVHGEQNEMARLKAALIREYEDNDEVHIEVHNPRNTEAVTLNFRGEKLAKVMGFLADKKPEQGQRVSGILVKRNFNYHILSPCDLSNYTDLAMSTVKQTQAIPYT
GPFNLLCYQLQKLTGDVEELEIQEKPALKVFKNITVIQEPGMVVLEWLANPSNDMYADTVTTVILEVQSNPKIRKGAVQKVSKKLEMHVYSKRLEIMLQDIFGEDCVSVKDDSILSVTVDGKTANLNLET
RTVECEEGSEDDESLREMVELAAQRLYEALTPVH
Enzyme
EC number: 3.1.27.-
Name: Endoribonucleases producing other than 5'-phosphomonoesters
Reaction:
Gene location: 2p25.1
Summary
CPSF3 is a 73kDa subunit of the cleavage and polyadenylation specificity factor and functions as an endonuclease that recognizes the pre-mRNA 3'-cleavage site AAUAAA prior to polyadenylation. It also cleaves after the pre-mRNA sequence ACCCA during histone 3'-end pre-mRNA processing. It is a member of the metallo-beta-lactamase family.
Interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition.Also involved in the histone 3'-end pre-mRNA processing. U7 snRNP-dependent protein that induces both the 3'-endoribonucleolytic cleavage of histone pre-mRNAs and acts as a 5' to 3' exonuclease for degrading the subsequent downstream cleavage product (DCP) of mature histone mRNAs. Cleavage occurs after the 5'-ACCCA-3' sequence in the histone pre-mRNA leaving a 3'hydroxyl group on the upstream fragment containing the stem loop (SL) and 5' phosphate on the downstream cleavage product (DCP) starting with CU nucleotides. The U7-dependent 5' to 3' exonuclease activity is processive and degrades the DCP RNA substrate even after complete removal of the U7-binding site. Binds to the downstream cleavage product (DCP) of histone pre-mRNAs and the cleaved DCP RNA substrate in a U7 snRNP dependent manner.
Interacts with CPSF2, CSTF2, WDR33 and SYMPK.
Interacts with TUT1; the interaction is direct and mediates the recruitment of the CPSF complex on the 3'UTR of pre-mRNAs.
While the N-terminal region active and highly conserved metallo-beta-lactamase domain, the C-terminal region of CPSF-73 is not as conserved, but removal of the C-terminus of Brr5p/Ysh1p (yeast homolog), by as little as the last 30 residues, results in cell death. Sequence analysis suggests that a leucine zipper, which is usually involved in protein-protein interactions, may be present in the final 30 residues of Brr5p/Ysh1p. The C-terminus of CPSF-73 does interact with other proteins in the 3?-end processing complex, including CPSF-100 and Pta1p. This association may bridge CPSF with CF IIm in mammals .
CPSF-73 has a second isoform in humans, known as RC-68 or Int9. It may be involved in 3?-end processing of small nuclear RNAs and it interacts with the second isoform of CPSF-100, RC-74 or Int11.
See this protein in other databases:
Literature:
- Ryan K, Calvo O, Manley JL et al. Evidence that polyadenylation factor CPSF-73 is the mRNA 3" processing endonuclease. RNA 2004 10(4):565-73, doi: , PMID: 15037765.
- Dominski Z, Yang XC, Marzluff WF et al. The polyadenylation factor CPSF-73 is involved in histone-pre-mRNA processing. Cell 2005 123(1):37-48, doi: 10.1016/j.cell.2005.08.002, PMID: 16213211.
- 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.
- Mandel CR, Kaneko S, Zhang H et al. Polyadenylation factor CPSF-73 is the pre-mRNA 3"-end-processing endonuclease. Nature 2006 444(7121):953-6, doi: 10.1038/nature05363, PMID: 17128255.
- Sullivan KD, Steiniger M, Marzluff WF et al. A core complex of CPSF73, CPSF100, and Symplekin may form two different cleavage factors for processing of poly(A) and histone mRNAs. Mol Cell 2009 34(3):322-32, doi: 10.1016/j.molcel.2009.04.024, PMID: 19450530.
- Phung DK, Rinaldi D, Langendijk-Genevaux PS et al. Archaeal beta-CASP ribonucleases of the aCPSF1 family are orthologs of the eukaryal CPSF-73 factor. Nucleic Acids Res 2013 41(2):1091-103, doi: 10.1093/nar/gks1237, PMID: 23222134.
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