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Tbio Pre-mRNA 3'-end-processing factor FIP1

Component of the cleavage and polyadenylation specificity factor (CPSF) complex that plays a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. FIP1L1 contributes to poly(A) site recognition and stimulates poly(A) addition. Binds to U-rich RNA sequence elements surrounding the poly(A) site. May act to tether poly(A) polymerase to the CPSF complex.

This gene encodes a subunit of the CPSF (cleavage and polyadenylation specificity factor) complex that polyadenylates the 3' end of mRNA precursors. This gene, the homolog of yeast Fip1 (factor interacting with PAP), binds to U-rich sequences of pre-mRNA and stimulates poly(A) polymerase activity. Its N-terminus contains a PAP-binding site and its C-terminus an RNA-binding domain. 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. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Oct 2008]

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Property Summary

NCBI Gene PubMed Count 43
PubMed Score 155.92
PubTator Score 160.91

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (4)

Disease Target Count
Acute Promyelocytic Leukemia 32

Expression

  Differential Expression (5)

Disease log2 FC p
psoriasis -1.500 7.2e-05
osteosarcoma -1.253 5.5e-04
intraductal papillary-mucinous adenoma (... 1.300 5.0e-03
intraductal papillary-mucinous carcinoma... 1.200 2.4e-03
ovarian cancer 2.000 6.2e-06

Synonym

Accession Q6UN15 B4DIR3 G3XAD6 Q0VGE0 Q499Y4 Q49AU3 Q7Z608 Q8WVN3 Q96F80 Q9H077 hFip1
Symbols Rhe
FIP1
hFip1

Gene

FIP1L1

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

 UniProt Keyword (7)

 GO Function (1)

 GO Component (2)

 GO Process (4)

 Compartment GO Term (27)

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 HCA RNA Cell Line (56)

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Pathway (18)

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Protein-protein Interaction (31)

U2SURP   SART1   PQBP1   ZC3H11A   WBP4   SLU7   SYF2   USP39   THOC7   PRPF8   CWC27   THOC6   SUGP1   SRRM1   PRPF38A   U2AF1L4   SNRNP27   PRPF31   MAGOHB   PPWD1   SNRNP40   HNRNPUL1   UPF3B   CWC22   A1CF   RBM22   PUF60   ISY1   PRPF19   SRRM2   WBP11  

Gene RIF (25)

PMID Text
25761934 F604S exchange in FIP1L1-PDGFRA enhances FIP1L1-PDGFRA protein stability via SHP-2 and SRC and is associated with kinase inhibitor resistance in hypereosinophilic syndrome and chronic eosinophilic leukemia.
24763514 FIP1L1 differentially contributes to the pathogenesis of distinct types of leukemia.
24458279 FP fusion gene favors secondary KIT mutations in MCs via growth and proliferation signals or that a yet unknown mechanism causes genomic instability with independent evolution of FP and KIT D816V
23621172 Oncostatin M is a FIP1L1/PDGFRA-dependent mediator of cytokine production in chronic eosinophilic leukemia.
23125841 Tandem affinity purification and mass spectrometry analysis identify FIP1 like 1 protein (FIP1L1), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells
22944561 description of polycythemia vera concurrent with FIP1L1-PDGFRA-positive myeloproliferative neoplasm with eosinophilia [case report]
22523564 results strongly suggest that JAK2 is activated by Fip1-like1 (FIP1L1)-platelet-derived growth factor receptor alpha (F/P) and is required for F/P stimulation of cellular proliferation and infiltration in chronic eosinophilic leukemia
22447844 Data show that the cyclin-dependent kinase 7/9 inhibitor (CDK7/9 inhibitor) potently inhibits FIP1L1-PDGFRalpha-positive Bcr-Abl-positive chronic myeloid leukemia (CML) cells.
21818111 Treatment with imatinib is associated with an excellent prognosis in FIP1L1-PDGFRA-positive chronic eosinophilic leukemia in first chronic phase
21399396 FIP1L1/PDGFRA fusion gene-positive myeloproliferative disorders with eosinophilia are discussed.
19118897 studied a new FISH method to detect CHIC2 deletion, FIP1L1/PDGFRA fusion and PDGFRA translocation in patients with myeloid neoplasms associated with eosinophilia
18987651 characterized FIP1L1-PDGFRA junction sequences from 113 patients at the mRNA (n=113) and genomic DNA (n=85) levels
18706197 FIP1L1-PDGFRalpha emerges as a relatively homogeneous clinicobiological entity that co-exists with other abnormalities of tyrosine kinase family genes. It reflects the disease progression and there is a good response to imatinib.
17591942 Fluorescence in situ hybridization and reverse transcriptase-polymerase chain reaction protocols were developed for an accurate del(4)(q12q12) and FIP1L1-PDGFRA fusion gene detection.
17377585 FIP1L1-PDGFRA-positive patients who presented with acute myeloid leukemia (AML, n=5) or lymphoblastic T-cell non-Hodgkin-lymphoma (n=2) in conjunction with AML or Eos-MPD.
17299092 FIP1L1 and PDGFRalpha have roles in response to imatinib mesylate in chronic eosinophilic leukemia
17261495 data and previous reports suggest that FIP1L1-PDGFRA - positive HES is a distinct clinical entity with myeloproliferative features and showing a poor response to corticosteroid treatment
16690743 FIP1L1-PDGFRalpha activation requires disruption of the juxtamembrane domain of PDGFRalpha and is FIP1L1-independent
16502585 Fusion protein is detected in hypereosinophilic syndrome and chronic eosinophilic leukemia.
15767428 the newly identified hFip1 protein, which has been shown to enhance polyadenylation through U-rich upstream elements, interacted specifically with the HPV-16 upstream element.
15284118 FIP1L1-PDGFRA is a relatively infrequent but treatment-relevant mutation in primary eosinophilia that is indicative of an underlying systemic mastocytosis.
14630792 results indicate that the fusion of FIP1L1 to PDGFRA occurs rarely in leukemia cell lines
12842979 observations suggest that the FIP1L1-PDGFRA rearrangement occurs in an early hematopoietic progenitor and suggests that the molecular pathogenesis for a subset of SMCD patients is similar to that of HES
12660384 The hypereosinophilic syndrome may result from a novel fusion tyrosine kinase - FIP1L1-PDGFRalpha - that is a consequence of an interstitial chromosomal deletion.
12660384 Describes the fusion gene Fip1-like-1-PDGFRalpha in patients with idiopathic hypereosinophilic syndrome, mostly responsive to imatinib therapy.

AA Sequence 

MSAGEVERLVSELSGGTGGDEEEEWLYGGPWDVHVHSDLAKDLDENEVERPEEENASANPPSGIEDETAE      1 - 70
NGVPKPKVTETEDDSDSDSDDDEDDVHVTIGDIKTGAPQYGSYGTAPVNLNIKTGGRVYGTTGTKVKGVD     71 - 140
LDAPGSINGVPLLEVDLDSFEDKPWRKPGADLSDYFNYGFNEDTWKAYCEKQKRIRMGLEVIPVTSTTNK    141 - 210
ITAEDCTMEVTPGAEIQDGRFNLFKVQQGRTGNSEKETALPSTKAEFTSPPSLFKTGLPPSRNSTSSQSQ    211 - 280
TSTASRKANSSVGKWQDRYGRAESPDLRRLPGAIDVIGQTITISRVEGRRRANENSNIQVLSERSATEVD    281 - 350
NNFSKPPPFFPPGAPPTHLPPPPFLPPPPTVSTAPPLIPPPGFPPPPGAPPPSLIPTIESGHSSGYDSRS    351 - 420
ARAFPYGNVAFPHLPGSAPSWPSLVDTSKQWDYYARREKDRDRERDRDRERDRDRDRERERTRERERERD    421 - 490
HSPTPSVFNSDEERYRYREYAERGYERHRASREKEERHRERRHREKEETRHKSSRSNSRRRHESEEGDSH    491 - 560
RRHKHKKSKRSKEGKEAGSEPAPEQESTEATPAE                                        561 - 594
//

Text Mined References (54)

PMID Year Title
25761934 2015 F604S exchange in FIP1L1-PDGFRA enhances FIP1L1-PDGFRA protein stability via SHP-2 and SRC: a novel mode of kinase inhibitor resistance.
25416956 2014 A proteome-scale map of the human interactome network.
25411163 2015 Identification of a variant in KDR associated with serum VEGFR2 and pharmacodynamics of Pazopanib.
24763514 2014 FIP1L1 presence in FIP1L1-RARA or FIP1L1-PDGFRA differentially contributes to the pathogenesis of distinct types of leukemia.
24458279 2014 The FIP1L1-PDGFRA fusion gene and the KIT D816V mutation are coexisting in a small subset of myeloid/lymphoid neoplasms with eosinophilia.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
23725790 2013 GWAS of DNA methylation variation within imprinting control regions suggests parent-of-origin association.
23621172 2013 Oncostatin M is a FIP1L1/PDGFRA-dependent mediator of cytokine production in chronic eosinophilic leukemia.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
22944561 2012 Case of polycythemia vera concurrent with FIP1L1-PDGFRA-positive myeloproliferative neoplasm with eosinophilia.
22681889 2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts.
22658674 2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
22523564 2012 Identification of JAK2 as a mediator of FIP1L1-PDGFRA-induced eosinophil growth and function in CEL.
22447844 2012 Cyclin-dependent kinase 7/9 inhibitor SNS-032 abrogates FIP1-like-1 platelet-derived growth factor receptor ? and bcr-abl oncogene addiction in malignant hematologic cells.
21818111 2012 Limited clinical activity of nilotinib and sorafenib in FIP1L1-PDGFRA positive chronic eosinophilic leukemia with imatinib-resistant T674I mutation.
21406692 2011 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
21399396 2011 [Genetic mutations and molecularly-targeted drugs in hypereosinophilic syndromes].
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
19690332 2009 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19413330 2009 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19224921 2009 Inositol 1,4,5-triphosphate receptor-binding protein released with inositol 1,4,5-triphosphate (IRBIT) associates with components of the mRNA 3' processing machinery in a phosphorylation-dependent manner and inhibits polyadenylation.
19118897 2009 Validation of a new three-color fluorescence in situ hybridization (FISH) method to detect CHIC2 deletion, FIP1L1/PDGFRA fusion and PDGFRA translocations.
18987651 2009 The molecular anatomy of the FIP1L1-PDGFRA fusion gene.
18706197 2008 FIP1L1-PDGFRalpha alone or with other genetic abnormalities reveals disease progression in chronic eosinophilic leukemia but good response to imatinib.
18691976 2008 Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18318008 2008 Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17591942 2007 A case of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia with a rare FIP1L1 breakpoint.
17377585 2007 Recurrent finding of the FIP1L1-PDGFRA fusion gene in eosinophilia-associated acute myeloid leukemia and lymphoblastic T-cell lymphoma.
17299092 2007 Low-dose imatinib mesylate leads to rapid induction of major molecular responses and achievement of complete molecular remission in FIP1L1-PDGFRA-positive chronic eosinophilic leukemia.
17261495 2007 Clinical features of hypereosinophilic syndrome: FIP1L1-PDGFRA fusion gene-positive disease is a distinct clinical entity with myeloproliferative features and a poor response to corticosteroid.
17081983 2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
16964243 2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization.
16690743 2006 Activation of FIP1L1-PDGFRalpha requires disruption of the juxtamembrane domain of PDGFRalpha and is FIP1L1-independent.
16502585 2006 Detection of the FIP1L1-PDGFRA fusion in idiopathic hypereosinophilic syndrome and chronic eosinophilic leukemia.
16381901 2006 The LIFEdb database in 2006.
16189514 2005 Towards a proteome-scale map of the human protein-protein interaction network.
15815621 2005 Generation and annotation of the DNA sequences of human chromosomes 2 and 4.
15767428 2005 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.
15592455 2005 Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.
15489336 2004 From ORFeome to biology: a functional genomics pipeline.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15302935 2004 Large-scale characterization of HeLa cell nuclear phosphoproteins.
15284118 2004 FIP1L1-PDGFRA fusion: prevalence and clinicopathologic correlates in 89 consecutive patients with moderate to severe eosinophilia.
14749727 2004 Human Fip1 is a subunit of CPSF that binds to U-rich RNA elements and stimulates poly(A) polymerase.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14630792 2004 The EOL-1 cell line as an in vitro model for the study of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia.
12842979 2003 CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy.
12808148 2003 Discovery of a fusion kinase in EOL-1 cells and idiopathic hypereosinophilic syndrome.
12660384 2003 A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11230166 2001 Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.
11076863 2000 DNA cloning using in vitro site-specific recombination.