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Pre-mRNA 3'-end-processing factor FIP1
Known also as: Factor interacting with PAP, FIP1-like 1 protein
Known abbreviations: FIP1L1, FIP1, hFip1, RHE
Yeast homolog: FIP1p
Protein
Domains Secondary structure Disorder |
This protein is highly disordered (90 % of residues are predicted to be disordered)
Top 3 models:
 |  |  |
| Template: 1s58, chain A Method: mgenthreader Fragment: 1-498 | Template: 3dxj, chain N Method: compass Fragment: 171-534 | Template: 3bg5, chain A Method: compass Fragment: 16-161 |
This protein has alternative isoforms:
Isoform 1:
| Sequence length: | 594 aa |
| Molecular weight: | 66.526 kDa |
| Isoelectric point: | 5.35 |
1........10........20........30........40........50........60........70........80........90........100.......110.......120.......130
MSAGEVERLVSELSGGTGGDEEEEWLYGGPWDVHVHSDLAKDLDENEVERPEEENASANPPSGIEDETAENGVPKPKVTETEDDSDSDSDDDEDDVHVTIGDIKTGAPQYGSYGTAPVNLNIKTGGRVYG
TTGTKVKGVDLDAPGSINGVPLLEVDLDSFEDKPWRKPGADLSDYFNYGFNEDTWKAYCEKQKRIRMGLEVIPVTSTTNKITAEDCTMEVTPGAEIQDGRFNLFKVQQGRTGNSEKETALPSTKAEFTSP
PSLFKTGLPPSRNSTSSQSQTSTASRKANSSVGKWQDRYGRAESPDLRRLPGAIDVIGQTITISRVEGRRRANENSNIQVLSERSATEVDNNFSKPPPFFPPGAPPTHLPPPPFLPPPPTVSTAPPLIPP
PGFPPPPGAPPPSLIPTIESGHSSGYDSRSARAFPYGNVAFPHLPGSAPSWPSLVDTSKQWDYYARREKDRDRERDRDRERDRDRDRERERTRERERERDHSPTPSVFNSDEERYRYREYAERGYERHRA
SREKEERHRERRHREKEETRHKSSRSNSRRRHESEEGDSHRRHKHKKSKRSKEGKEAGSEPAPEQESTEATPAE
Isoform 3:
| Sequence length: | 520 aa |
| Molecular weight: | 58.376 kDa |
| Isoelectric point: | 5.34 |
1........10........20........30........40........50........60........70........80........90........100.......110.......120.......130
MSAGEVERLVSELSGGTGGDEEEEWLYGDENEVERPEEENASANPPSGIEDETAENGVPKPKVTETEDDSDSDSDDDEDDVHVTIGDIKTGAPQYGSYGTAPVNLNIKTGGRVYGTTGTKVKGVDLDAPG
SINGVPLLEVDLDSFEDKPWRKPGADLSDYFNYGFNEDTWKAYCEKQKRIRMGLEVIPVTSTTNKITVQQGRTGNSEKETALPSTKAEFTSPPSLFKTGLPPSRRLPGAIDVIGQTITISRVEGRRRANE
NSNIQVLSERSATEVDNNFSKPPPFFPPGAPPTHLPPPPFLPPPPTVSTAPPLIPPPGFPPPPGAPPPSLIPTIESGHSSGYDSRSARAFPYGNVAFPHLPGSAPSWPSLVDTSKQWDYYARREKDRDRE
RDRDRERDRDRDRERERTRERERERDHSPTPSVFNSDEERYRYREYAERGYERHRASREKEERHRERRHREKEETRHKSSRSNSRRRHESEEGDSHRRHKHKKSKRSKEGKEAGSEPAPEQESTEATPAE
Isoform 4:
| Sequence length: | 378 aa |
| Molecular weight: | 40.835 kDa |
| Isoelectric point: | 4.43 |
1........10........20........30........40........50........60........70........80........90........100.......110.......120.......130
MSAGEVERLVSELSGGTGGDEEEEWLYGDENEVERPEEENASANPPSGIEDETAENGVPKPKVTETEDDSDSDSDDDEDDVHVTIGDIKTGAPQYGSYGTAPVNLNIKTGGRVYGTTGTKVKGVDLDAPG
SINGVPLLEVDLDSFEDKPWRKPGADLSDYFNYGFNEDTWKAYCEKQKRIRMGLEVIPVTSTTNKITAEDCTMEVTPGAEIQDGRFNLFKVQQGRTGNSEKETALPSTKAEFTSPPSLFKTGLPPSRNST
SSQSQTSTASRKANSSVGKWQDRYGRAESPDLRRLPGAIDVIGQTITISRVEGRRRANENSNIQVLSERSATEVDNNFSKPPPFFPPGAPPTHLPPPPFLPPPPTVSTAPPLIPPPGK
Gene location: 4q12
Summary
FIP1L1 is a subunit of the CPSF (cleavage and polyadenylation specificity factor) complex that polyadenylates the 3' end of mRNA precursors. The homolog of yeast Fip1 (factor interacting with PAP), binds to U-rich RNA sequence elements surrounding the poly(A) site and stimulates poly(A) polymerase activity. Its N-terminus contains a PAP-binding site and its C-terminus an RNA-binding domain.
hFip1 contains an acidic segment near the N-terminus, followed by a highly conserved segment of about 70 residues (48% identity and 72% similarity between hFip1 and Fip1p). The C-terminal region contains a Pro- rich segment, a segment with alternating Arg and Asp residues (RD segment), and an Arg-rich segment. Yeast Fip1p protein, at 35 kD, is much smaller than human Fip1 (66 kD), because it does not contain the RD and Arg-rich segments. The acidic segment (residues 1–111) of hFip1 mediates interactions with PAP, and the highly conserved segment (residues 137–243) interacts with CPSF-30. Both of these segments (residues 1–355) are required for binding CPSF-160 and CstF-77, and CPSF-160 may also interact with the C-terminal region of Fip1 (residues 443–594).
The primary function of hFip1 (Fip1p) may be to bring PAP close to the polyadenylation site. Removal of the C-terminal region beyond the Pro-rich segment of Fip1p produces temperature- sensitive growth in yeast. These cells are deficient in polyadenylation, but can be rescued by the addition of wild-type Fip1p. Interestingly, yeast Pap1p is inhibited in vitro by the addition of Fip1p, likely mediated by residues 105–206 of Fip1p. In contrast, the addition of recombinant hFip1 stimulates the activity of PAP in vitro, which is dependent on the U-rich auxiliary upstream element. The stimulation is abolished by the deletion of this element in the pre-mRNA, or by the deletion of the RD segment or the CPSF-160 binding segment in hFip1.
Interacts with CPSF1, CPSF4, CSTF2, CSTF3 and PAPOLA.
An interstitial chromosomal deletion on 4q12 creates an in-frame fusion of human genes FIP1L1 and PDGFRA (platelet-derived growth factor receptor, alpha). The FIP1L1-PDGFRA fusion gene encodes a constitutively activated tyrosine kinase that joins the first 233 amino acids of FIP1L1 to the last 523 amino acids of PDGFRA. This gene fusion and chromosomal deletion is the cause of some forms of idiopathic hypereosinophilic syndrome (HES). This syndrome, recently reclassified as chronic eosinophilic leukemia (CEL), is responsive to treatment with tyrosine kinase inhibitors.
See this protein in other databases:
Literature:
- Griffin JH, Leung J, Bruner RJ et al. Discovery of a fusion kinase in EOL-1 cells and idiopathic hypereosinophilic syndrome. Proc Natl Acad Sci U S A 2003 100(13):7830-5, doi: 10.1073/pnas.0932698100, PMID: 12808148.
- Kaufmann I, Martin G, Friedlein A et al. Human Fip1 is a subunit of CPSF that binds to U-rich RNA elements and stimulates poly(A) polymerase. EMBO J 2004 23(3):616-26, doi: 10.1038/sj.emboj.7600070, PMID: 14749727.
- Zhao X, Oberg D, Rush M et al. A 57-nucleotide upstream early polyadenylation element in human papillomavirus type 16 interacts with hFip1, CstF-64, hnRNP C1/C2, and polypyrimidine tract binding protein. J Virol 2005 79(7):4270-88, doi: 10.1128/JVI.79.7.4270-4288.2005, PMID: 15767428.
- Ezeokonkwo C, Zhelkovsky A, Lee R et al. A flexible linker region in Fip1 is needed for efficient mRNA polyadenylation. RNA 2011 17(4):652-64, doi: 10.1261/rna.2273111, PMID: 21282348.
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