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Pre-mRNA 3'-end-processing factor FIP1Known also as: Factor interacting with PAP, FIP1-like 1 protein Known abbreviations: FIP1L1, FIP1, hFip1, RHE Yeast homolog: FIP1p Protein
This protein is highly disordered (90 % of residues are predicted to be disordered)
Top 3 models:
This protein has alternative isoforms: Isoform 1:
1........10........20........30........40........50........60........70........80........90........100.......110.......120.......130 MSAGEVERLVSELSGGTGGDEEEEWLYGGPWDVHVHSDLAKDLDENEVERPEEENASANPPSGIEDETAENGVPKPKVTETEDDSDSDSDDDEDDVHVTIGDIKTGAPQYGSYGTAPVNLNIKTGGRVYG TTGTKVKGVDLDAPGSINGVPLLEVDLDSFEDKPWRKPGADLSDYFNYGFNEDTWKAYCEKQKRIRMGLEVIPVTSTTNKITAEDCTMEVTPGAEIQDGRFNLFKVQQGRTGNSEKETALPSTKAEFTSP PSLFKTGLPPSRNSTSSQSQTSTASRKANSSVGKWQDRYGRAESPDLRRLPGAIDVIGQTITISRVEGRRRANENSNIQVLSERSATEVDNNFSKPPPFFPPGAPPTHLPPPPFLPPPPTVSTAPPLIPP PGFPPPPGAPPPSLIPTIESGHSSGYDSRSARAFPYGNVAFPHLPGSAPSWPSLVDTSKQWDYYARREKDRDRERDRDRERDRDRDRERERTRERERERDHSPTPSVFNSDEERYRYREYAERGYERHRA SREKEERHRERRHREKEETRHKSSRSNSRRRHESEEGDSHRRHKHKKSKRSKEGKEAGSEPAPEQESTEATPAE Isoform 3:
1........10........20........30........40........50........60........70........80........90........100.......110.......120.......130 MSAGEVERLVSELSGGTGGDEEEEWLYGDENEVERPEEENASANPPSGIEDETAENGVPKPKVTETEDDSDSDSDDDEDDVHVTIGDIKTGAPQYGSYGTAPVNLNIKTGGRVYGTTGTKVKGVDLDAPG SINGVPLLEVDLDSFEDKPWRKPGADLSDYFNYGFNEDTWKAYCEKQKRIRMGLEVIPVTSTTNKITVQQGRTGNSEKETALPSTKAEFTSPPSLFKTGLPPSRRLPGAIDVIGQTITISRVEGRRRANE NSNIQVLSERSATEVDNNFSKPPPFFPPGAPPTHLPPPPFLPPPPTVSTAPPLIPPPGFPPPPGAPPPSLIPTIESGHSSGYDSRSARAFPYGNVAFPHLPGSAPSWPSLVDTSKQWDYYARREKDRDRE RDRDRERDRDRDRERERTRERERERDHSPTPSVFNSDEERYRYREYAERGYERHRASREKEERHRERRHREKEETRHKSSRSNSRRRHESEEGDSHRRHKHKKSKRSKEGKEAGSEPAPEQESTEATPAE Isoform 4:
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:
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