Cleavage and polyadenylation specificity factor subunit 5

Known also as: Cleavage and polyadenylation specificity factor 25 kDa subunit, Nucleoside diphosphate-linked moiety X motif 21, Nudix motif 21, Pre-mRNA cleavage factor Im 25 kDa subunit
Known abbreviations: CPSF5, CFIm25, CPSF25, NUDT21

Yeast homolog: not known

Protein

227

NUDIX_2

Structures

Models
Domains

Secondary structure

Disorder

Top 3 models:


Template: 3bap, chain A Method: ffas Fragment: 1-227	Template: 2cl3, chain A Method: phyre Fragment: 7-227	Template: 3fcm, chain A Method: hhblits Fragment: 75-222

Sequence length:	227 aa
Molecular weight:	26.227 kDa
Isoelectric point:	9.05

Sequence:
1........10........20........30........40........50........60........70........80........90........100.......110.......120.......130
MSVVPPNRSQTGWPRGVTQFGNKYIQQTKPLTLERTINLYPLTNYTFGTKEPLYEKDSSVAARFQRMREEFDKIGMRRTVEGVLIVHEHRLPHVLLLQLGTTFFKLPGGELNPGEDEVEGLKRLMTEILG
RQDGVLQDWVIDDCIGNWWRPNFEPPQYPYIPAHITKPKEHKKLFLVQLQEKALFAVPKNYKLVAAPLFELYDNAPGYGPIISSLPQLLSRFNFIYN

Gene location: 16q12.2

Summary
NUDT21/CPSF5 binds to cleavage and polyadenylation RNA substrates. The homodimer mediates simultaneous sequence-specific recognition of two 5'-UGUA-3' elements within the pre-mRNA. Binds to, but does not hydrolyze mono- and di-adenosine nucleotides. May have a role in mRNA export. Component of the cleavage factor Im (CFIm) complex, composed of, at least, NUDT21/CPSF5 and CPSF6 or CPSF7. Within the cleavage factor Im complex, the NUDT21/CPSF5 homodimer is at the core of a heterotetramer, and is clasped by two additional subunits (CPSF6 or CPSF7).

Residues 81–160 of CFIm25 mediate interactions with the C-terminus of PAP (residues 472–739) and PABP. The primary function of CF Im may be to provide additional recognition of the pre-mRNA substrate and aid the definition of the proper polyadenylation site. SELEX analysis revealed that CF Im prefers to bind to the RNA sequences containing UGUAA, which is generally found just upstream of the PAS.

Interacts with CPSF6, CPSF7, PABPN1 and SNRNP70.
Interacts with PAPOLA (the interaction is diminished by acetylation).

Acetylated mainly by p300/CBP, recruited to the complex by CPSF6. Acetylation decreases interaction with PAPAO. Deacetylated by the class I/II HDACs, HDAC1, HDAC3 and HDAC10, and by the class III HDACs, SIRT1 AND SIRT2.

Althught it contains NUDIX hydrolase domain, it lacks the conserved metal-binding residues in the NUDIX motif and does not have hydrolase activity.

See this protein in other databases:

Literature:

Brown KM, Gilmartin GM. A mechanism for the regulation of pre-mRNA 3" processing by human cleavage factor Im. Mol Cell 2003 12(6):1467-76, doi: , PMID: 14690600.
Kubo T, Wada T, Yamaguchi Y et al. Knock-down of 25 kDa subunit of cleavage factor Im in Hela cells alters alternative polyadenylation within 3"-UTRs. Nucleic Acids Res 2006 34(21):6264-71, doi: 10.1093/nar/gkl794, PMID: 17098938.
Sartini BL, Wang H, Wang W et al. Pre-messenger RNA cleavage factor I (CFIm): potential role in alternative polyadenylation during spermatogenesis. Biol Reprod 2008 78(3):472-82, doi: 10.1095/biolreprod.107.064774, PMID: 18032416.
Kim S, Yamamoto J, Chen Y et al. Evidence that cleavage factor Im is a heterotetrameric protein complex controlling alternative polyadenylation. Genes Cells 2010 15(9):1003-13, doi: 10.1111/j.1365-2443.2010.01436.x, PMID: 20695905.
Yang Q, Coseno M, Gilmartin GM et al. Crystal structure of a human cleavage factor CFI(m)25/CFI(m)68/RNA complex provides an insight into poly(A) site recognition and RNA looping. Structure 2011 19(3):368-77, doi: 10.1016/j.str.2010.12.021, PMID: 21295486.
Fukumitsu H, Soumiya H, Furukawa S et al. Knockdown of pre-mRNA cleavage factor Im 25 kDa promotes neurite outgrowth. Biochem Biophys Res Commun 2012 425(4):848-53, doi: 10.1016/j.bbrc.2012.07.164, PMID: 22898046.
Ruegsegger U, Beyer K, Keller W et al. Purification and characterization of human cleavage factor Im involved in the 3" end processing of messenger RNA precursors. J Biol Chem 1996 271(11):6107-13, doi: , PMID: 8626397.

Additional computationally mapped references ...

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