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Polyribonucleotide 5'-hydroxyl-kinase Clp1
Known also as: Polynucleotide kinase Clp1, Pre-mRNA cleavage complex II protein Clp1
Known abbreviations: CLP1, hClp1, HEAB
Yeast homolog: not known
Protein
Models Domains Secondary structure Disorder |
Top 3 models:
 |  |  |
| Template: 2npi, chain A Method: hhsearch Fragment: 1-424 | Template: 2npi, chain A Method: phyre Fragment: 1-424 | Template: 2xzo, chain A Method: mgenthreader Fragment: 1-424 |
This protein has alternative isoforms:
Isoform 1:
| Sequence length: | 425 aa |
| Molecular weight: | 47.645 kDa |
| Isoelectric point: | 6.37 |
1........10........20........30........40........50........60........70........80........90........100.......110.......120.......130
MGEEANDDKKPTTKFELERETELRFEVEASQSVQLELLTGMAEIFGTELTRNKKFTFDAGAKVAVFTWHGCSVQLSGRTEVAYVSKDTPMLLYLNTHTALEQMRRQAEKEEERGPRVMVVGPTDVGKSTV
CRLLLNYAVRLGRRPTYVELDVGQGSVSIPGTMGALYIERPADVEEGFSIQAPLVYHFGSTTPGTNIKLYNKITSRLADVFNQRCEVNRRASVSGCVINTCGWVKGSGYQALVHAASAFEVDVVVVLDQE
RLYNELKRDLPHFVRTVLLPKSGGVVERSKDFRRECRDERIREYFYGFRGCFYPHAFNVKFSDVKIYKVGAPTIPDSCLPLGMSQEDNQLKLVPVTPGRDMVHHLLSVSTAEGTEENLSETSVAGFIVVT
SVDLEHQVFTVLSPAPRPLPKNFLLIMDIRFMDLK
Isoform 2:
| Sequence length: | 361 aa |
| Molecular weight: | 40.696 kDa |
| Isoelectric point: | 6.29 |
1........10........20........30........40........50........60........70........80........90........100.......110.......120.......130
MGEEANDDKKPTTKFELERETELRFEVEASQSVQLELLTGMAEIFGTELTRNKKFTFDAGAKVAVFTWHGCSVQLSGRTEVAYVSKDTPMLLYLNTHTALEQMRRQAEKEEERGPRVMVVGPTDVGKSTV
CRLLLNYAITSRLADVFNQRCEVNRRASVSGCVINTCGWVKGSGYQALVHAASAFEVDVVVVLDQERLYNELKRDLPHFVRTVLLPKSGGVVERSKDFRRECRDERIREYFYGFRGCFYPHAFNVKFSDV
KIYKVGAPTIPDSCLPLGMSQEDNQLKLVPVTPGRDMVHHLLSVSTAEGTEENLSETSVAGFIVVTSVDLEHQVFTVLSPAPRPLPKNFLLIMDIRFMDLK
Enzyme
EC number: 2.7.1.78
Name: Polynucleotide 5'-hydroxyl-kinase
Reaction: ATP + 5'-dephospho-DNA <=> ADP + 5'-phospho-DNA
Gene location: 11q12
Summary
CLP1 is a component of the pre-mRNA cleavage complex II (CF-II). It is polynucleotide kinase that can phosphorylate the 5'-hydroxyl groups of double-stranded RNA (dsRNA), single-stranded RNA (ssRNA), double stranded DNA (dsDNA) and double-stranded DNA:RNA hybrids. dsRNA is phosphorylated more efficiently than dsDNA, and the RNA component of a DNA:RNA hybrid is phosphorylated more efficiently than the DNA component. Appears to have roles in both tRNA splicing and mRNA 3'-end formation. Component of the tRNA splicing endonuclease complex. Phosphorylates the 5'-terminus of the tRNA 3'-exon during tRNA splicing; this phosphorylation event is a prerequisite for the subsequent ligation of the two exon halves and the production of a mature tRNA. Also phosphorylates the 5'-terminus of exogenously introduced short interfering RNAs (siRNAs), which is a necessary prerequisite for their incorporation into the RNA-induced silencing complex (RISC). However, endogenous siRNAs and microRNAs (miRNAs) that are produced by the cleavage of dsRNA precursors by DICER1 already contain a 5'-phosphate group, so this protein may be dispensible for normal RNA-mediated gene silencing.
hClp1 is conserved throughout eukaryotes and has 23% identity with yeast Clp1p.
hClp1 and its homologs contain a Walker A motif (residues 130–137), which is generally associated with binding ATP/GTP. The structure of Clp1p confirms the similarity to other ATPases. The bound conformation of ATP suggests that Clp1p may not have ATPase activity, which is confirmed by biochemical assays in vitro. Recent studies show however that hClp1 is a RNA 5?-kinase that is important for tRNA splicing and activation of synthetic short interfering RNAs.
The structure also reveals the molecular basis for the interactions between Clp1p and Pcf11p. A peptide segment of Pcf11p (residues 475–499) is bound by Clp1p. Two of the residues in this segment, Arg480 and Trp489, are strictly conserved among Pcf11p homologs and make large contributions to the binding interface.
It is also component of the tRNA splicing endonuclease complex, composed of CLP1, TSEN2, TSEN15, TSEN34 and TSEN54.
Also associates with numerous components of the pre-mRNA cleavage complex I (CF-I/CFIm), including NUDT21, CPSF2, CPSF3, CPSF6 and CPSF7.
Interacts with CSTF2 and SYMPK.
See this protein in other databases:
Literature:
- de Vries H, Ruegsegger U, Hubner W et al. Human pre-mRNA cleavage factor II(m) contains homologs of yeast proteins and bridges two other cleavage factors. EMBO J 2000 19(21):5895-904, doi: 10.1093/emboj/19.21.5895, PMID: 11060040.
- Noble CG, Beuth B, Taylor IA et al. Structure of a nucleotide-bound Clp1-Pcf11 polyadenylation factor. Nucleic Acids Res 2007 35(1):87-99, doi: 10.1093/nar/gkl1010, PMID: 17151076.
- Weitzer S, Martinez J. hClp1: a novel kinase revitalizes RNA metabolism. Cell Cycle 2007 6(17):2133-7, doi: , PMID: 17786051.
- Ghazy MA, Gordon JM, Lee SD et al. The interaction of Pcf11 and Clp1 is needed for mRNA 3"-end formation and is modulated by amino acids in the ATP-binding site. Nucleic Acids Res 2012 40(3):1214-25, doi: 10.1093/nar/gkr801, PMID: 21993299.
- Haddad R, Maurice F, Viphakone N et al. An essential role for Clp1 in assembly of polyadenylation complex CF IA and Pol II transcription termination. Nucleic Acids Res 2012 40(3):1226-39, doi: 10.1093/nar/gkr800, PMID: 21993300.
- Holbein S, Scola S, Loll B et al. The P-loop domain of yeast Clp1 mediates interactions between CF IA and CPF factors in pre-mRNA 3" end formation. PLoS One 2011 6(12):e29139, doi: 10.1371/journal.pone.0029139, PMID: 22216186.
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