Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

FLI1 (Friend leukemia virus integration 1)

Written2011-03Laura M Vecchiarelli-Federico, Mehran Haeri, Yaacov Ben-David
Molecular, Cellular Biology, Sunnybrook Health Sciences Centre, 2075 Bayview Ave Room S216, M4N 3M5, Toronto, Ontario, Canada

(Note : for Links provided by Atlas : click)


HGNC (Hugo) FLI1
HGNC Alias symbSIC-1
HGNC Previous nameFriend leukemia virus integration 1
LocusID (NCBI) 2313
Atlas_Id 79
Location 11q24.3  [Link to chromosome band 11q24]
Location_base_pair Starts at 128694072 and ends at 128813267 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping FLI1.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
EWSR1 (22q12.2)::FLI1 (11q24.3)FLI1 (11q24.3)::EWSR1 (22q12.2)FLI1 (11q24.3)::FLI1 (11q24.3)
MN1 (22q12.1)::FLI1 (11q24.3)SLC45A3 (1q32.1)::FLI1 (11q24.3)TCF3 (19p13.3)::FLI1 (11q24.3)
Note NCBI mRNA Reference Sequence:
- NM_008026.4 (mus musculus)
- NM_002017.3 isoform 1 (homo sapiens)
- NM_001167681.1 isoform 2 (homo sapiens)


  Figure 1: Genomic organization of human fli-1. The fli-1 gene is localized on human chromosome 11q23, contains nine exons extending over approximately 120 kb, with a processed mRNA transcript length of 1359 bp, and encodes two protein isoforms of 452 aa (p51) and 419 aa (p48).
Description Both the mouse and human fli-1 genes are approximately 120 kb, consist of 9 exons, and encode two protein isoforms, p51 (452 aa) and p48 (419 aa) (Sarrazin et al., 2000). Fli-1 is located on mouse chromosome 9 and human chromosome 11q24.1, a region of several abnormalities in human disease (Ben-David et al., 1990; Truong and Ben David, 2000). The fli-1 gene is located within 240 kb of the ets-1 locus, suggesting that these Ets transcription factors arose by gene duplication from a common ancestral gene (Ben-David et al., 1991). The first fli-1 intron is the largest at approximately 64 kb in length, and the last exon, 9, containing the Ets DNA binding domain, is the largest at approximately 2808 bp in length (Figure 1). The sequence of the 5'-untranslated region (UTR) is located within exon 1, while the sequence of the 3'-UTR is located within exon 9. At least two ATG translation initiation sites have been localized to nucleotide 342 (exon 1) and 441 (exon 2) of the human Fli-1 mRNA sequence (NM_002017.3), responsible for the generation of the two protein isoforms, p51 and p48 (Sarrazin et al., 2000). The second isoform, p48, has a shorter N-terminus, contains a distinct 5'UTR, and lacks an in-frame portion of the 5' coding region, compared to isoform 1, p51. The sequences flanking the transcription initiation (CAP) sites show 94% conservation between the human and mouse isoforms. The fli-1 promoter contains a potential TATA box element, and multiple regulatory elements. These include GATA, EBS, GT-rich, GC-rich, AP-2, AP-3 and CTC elements, some of which are conserved between mouse and human. The fli-1 promoter also contains binding sites for Sp-1, c-Myc, GATA-1, Ets-2, Oct-3, TBP, PEA-3, EBP, ATF/CREB, and E2A-PBX1 (Barbeau et al., 1996; Barbeau et al., 1999; Dhulipala et al., 1998). The highly conserved 5' non-translated region of exon 1 is predicted to form a very stable hairpin structure, capable of post-transcriptional autoregulation (Barbeau et al., 1996).
Transcription Transcription of the mouse fli-1 gene produces a full-length mRNA transcript of 3087 bp, and a processed length of 1359 bp. Transcription of the human fli-1 gene produces a full-length mRNA transcript of 3993 and 3941 bp, and a processed length of 1359 and 1260 bp, respectively.
Pseudogene Although a pseudogene has not been identified for the fli-1 gene, comparison of the amino acid sequences of Fli-1 has revealed an 80% homology to the Ets-related protein Erg, localized adjacent to the ets-2 gene, on mouse chromosome 16 (Watson et al., 1992) and human chromosome 21q22.


Description The fli-1 gene encodes two isoforms of 51 and 48 kDa, synthesized by alternative translation initiation sites, as mentioned above. Loss of function studies have provided evidence to suggest that both the p51 and p48 isoforms retain the same functional domains and activity (Melet et al., 1996). The functional domains located within the Fli-1 protein include the 5' Ets domain, and a Fli-1-specific region (FLS) referred to as the amino terminal transcriptional activation (ATA) domain, and a 3' Ets and carboxy terminal transcriptional activation (CTA) domain (Figure 2). The 5' Ets domain, sharing 82% sequence identity to Erg and 59-60% to Ets-1 and Ets-2, is located within amino acids 121-196. The FLS, which is absent in the Erg protein, is localized within amino acids 205-292. The 3' Ets domain, sharing 98% homology with Erg, is located within amino acids 277-360 and is responsible for sequence specific DNA-binding activity. The CTA domain, located within amino acids 402-452, is also involved in transcriptional activation and protein-protein interaction. Both the 5' and 3' Ets domain contain sequences of helix 1-loop-helix 2 (H-L-H) secondary structures that are also present in Erg (Rao et al., 1993), while the FLS and CTA domains contain sequences which resemble turn-loop-turn (T-L-T) secondary structures. The structures of the ATA and CTA domains contribute to the transcriptional activity of Fli-1. It has been suggested that the CTA region may serve simultaneously as a transcriptional activator and repressor (Rao et al., 1993). Recently, mice engineered to lack the CTA domain of Fli-1 by homologous recombination were shown to express negligible to low levels of the mutant of Fli-1 mRNA and protein (Spyropoulos et al., 2000). Furthermore, the recombinant Fli-1 protein lacking the CTA domain displayed only 50-60% of the transcriptional activity of wild- type Fli-1, providing further evidence of the CTA domain's involvement in transcriptional activation. The reduced levels of mutant Fli-1 in these mice suggest that the CTA domain also functions to autoregulate Fli-1 expression. NMR spectroscopy analyses have shown that the 3' Ets domain of Fli-1 consists of three alpha-helices and a four stranded beta-sheet that resembles the structures of the class of helix-turn-helix DNA-binding proteins found in the catabolite activator protein of Escherichia coli, as well as those of several eukaryotic DNA binding proteins including H5, HNF-3/forkhead, and the heat shock transcription factor (Liang et al., 1994a; Liang et al., 1994b). A comparison of the Fli-1 3' Ets domain to other structures has suggested that this 3' Ets domain uses a new variation of the winged helix-turn-helix motif for binding to DNA (Liang et al., 1994b).
Fli-1 binds to DNA in a sequence-specific manner, and it has been determined that the optimal DNA binding sequence for Fli-1 is ACCGGAAG/aT/c (Solomon and Kaldis, 1998; Mao et al., 1994; Cui et al., 2009). The bases flanking the core GGA Ets DNA-binding motif synergistically contribute to binding specificity among different Ets transcription factors. Gene promoters containing these Ets sequences have been shown to be transcriptionally regulated by Fli-1, including bcl-2 (Lesault et al., 2002), MDM2 (Truong et al., 2005), gpIX, gpIIb (Bastian et al., 1999), mpl (Deveaux et al., 1996), and recently SHIP-1 (Lakhanpal et al., 2010).
Phosphorylation of both Fli-1 protein isoforms has been predominately detected on serine residues. This phosphorylation is modulated by the concentration of intracellular calcium, similar to Ets-1 and Ets-2, and dephosphorylation is controlled, at least in part, by the phosphatase PP2A (Zhang and Watson, 2005). Post-translational modification by phosphorylation effects Fli-1 DNA binding, protein-protein interaction and transcriptional activation, thereby contributing to the control of gene function (Zhang and Watson, 2005; Asano and Trojanowska, 2009).
Expression Fli-1 is highly expressed in all hematopoietic tissues and endothelial cells, and at a lower level in the lungs, heart and ovaries (Ben-David et al., 1991; Melet et al., 1996; Hewett et al., 2001; Pusztaszeri et al., 2006). The ubiquitous expression of Fli-1 in all endothelial cells (Hewett et al., 2001) suggests a role for Fli-1 in endothelial cell fate and angiogenesis. It has been suggested that Fli-1 is the first dependable nuclear marker of endothelial differentiation (Rossi et al., 2004), is essential for embryonic vascular development (Spyropoulos et al., 2000), and acts as a master regulator establishing the blood and endothelial programmes in the early embryo (Gaikwad et al., 2007; Liu et al., 2008). Moreover immunohistochemical analysis has revealed that Fli-1 expression is a valuable tool in the diagnosis of benign and malignant vascular tumors.
Localisation Similar to other Ets proteins, Fli-1 is a nuclear transcription factor and is generally localized within the nucleus, although Fli-1 protein has also been detected in the cytoplasm of specific cell types (Cui et al., 2009; Pusztaszeri et al., 2006).
Function Fli-1 plays an important role in erythropoiesis. The constitutive activation of fli-1 in erythroblasts leads to a dramatic shift in the Epo/Epo-R signal transduction pathway, blocking erythroid differentiation, activating the Ras pathway, and resulting in massive Epo-independent proliferation of erythroblasts (Tamir et al., 1999; Zochodne et al., 2000). These results suggest that Fli-1 overexpression in erythroblasts alters their responsiveness to Epo and triggers abnormal proliferation by switching the signaling event(s) associated with terminal differentiation to proliferation (Zochodne et al., 2000). The constitutive suppression of Fli-1, mediated through RNA interference or dominant negative protein expression has revealed an essential role for continuous Fli-1 overexpression in the maintenance and survival of the malignant phenotype in both murine and human erythroleukemia (Cui et al., 2009).
Homology Fli-1 is a member of the Ets transcription factor gene family. It is most related to Erg, located on mouse chromosome 16 and human chromosome 21. Similar to Fli-1, Erg is also activated through chromosomal translocation in human cancer. In prostate cancer, TMPRSS2 generates a fusion with ETV1, ETV4 and ETV5, and Erg share 98% homology within the Ets DNA binding domain. The fli-1 gene is conserved in human, mouse, chimpanzee, dog, cow, rat, chicken and zebrafish.


Note Fli-1 aberrant regulation is often associated with malignant transformation. Fli-1 was first identified as a target of proviral integration in F-MuLV-induced erythroleukemia (Ben-David et al., 1990). In addition to Friend erythroleukemia, integration at the fli-1 locus also occurs in leukemias induced by the 10A1 (Ott et al., 1994), Graffi (Denicourt et al., 1999), and Cas-Br-E viruses (Bergeron et al., 1991). While Fli-1 activation is associated with viral integration in mice, it is also associated with chromosomal abnormalities in humans. In Ewing's sarcoma and primitive neuroectodermal tumors a chromosomal translocation results in a chimeric EWS/Fli-1 fusion protein, containing the 5' region of EWS and the 3' ETS region of Fli-1 (Delattre et al., 1992). This oncoprotein acts as an aberrant transcriptional activator with strong transforming capabilities. In addition, Fli-1 has been implicated in human leukemias, such as Acute Myelogenous Leukemia (AML), involving loss or fusion of the tel gene (Kwiatkowski et al., 1998). Binding of wildtype Tel, an ETS transcription factor, to Fli-1 inhibits Fli-1's regulatory function. Therefore loss of the tel gene or generation of the Tel-AML fusion protein by chromosomal translocation eliminates the normal regulation of Fli-1 leading to an increase in Fli-1 activity. Tissue microarray and immunohistochemistry has also revealed the expression of Fli-1 in a wide variety of benign and malignant tumors, such as capillary hemangioma, neuroblastoma, small cell lung carcinoma, glioblastoma, medullar breast carcinoma, non-Hodgkin's lympoma, angiosarcoma, Kaposi's sarcoma and lymphoblastic lymphomas (Mhawech-Fauceglia et al., 2006).

Implicated in

Entity Ewing's sarcoma and primitive neuroectodermal tumors
Note Ewing's sarcoma is a malignant bone tumor affecting children. Such tumors usually develop during puberty, however there are few symptoms. Primitive neuroectodermal tumors are a rare group of tumors originating in cells from the primitive neural crest usually found in children under 10 years of age.
Prognosis Since the EWS gene is fused to the fli-1 gene in the majority of Ewing's sarcomas, primers spaning these genes are used to amplify the junction for genetic diagnosis (Downing et al., 1995).
Oncogenesis Expression of the EWS/Fli-1 fusion gene in the majority of Ewing's sarcomas is shown to be critical for cancer induction. Downregulation of this fusion oncoprotein using RNA interference inhibits cell growth and promotes apoptosis (Dohjima et al., 2003).
Entity Jacobsen or Paris-Trousseau syndrome
Note A relatively infrequent congenital disorder in which the fli-1 gene is commonly deleted. Clinical abnormalities include growth and mental retardation, cardiac defects, dysmorphogenesis of the digits and face, pancytopenia, and thrombocytopenia (Krishnamurti et al., 2001; Favier et al., 2003; Wenger et al., 2006).
Prognosis Chromosomal deletions result in Fli-1 deficiency.
Entity Systemic lupus erythematosus (SLE)
Note A chronic autoimmune disease with variable symptoms, commonly affecting the skin, joints, kidneys, heart and lungs.
Prognosis SLE patients display Fli-1 overexpression in peripheral blood leukocytes (Mayor et al., 2000). Interestingly, Fli-1 overexpression also occurs in the MRL/lpr murine lupus model, and a 50% reduction of Fli-1 levels markedly prolongs survival and significantly reduces renal disease in these mice (Mayor et al., 2000).


Phosphorylation of Fli1 at threonine 312 by protein kinase C delta promotes its interaction with p300/CREB-binding protein-associated factor and subsequent acetylation in response to transforming growth factor beta.
Asano Y, Trojanowska M.
Mol Cell Biol. 2009 Apr;29(7):1882-94. Epub 2009 Jan 21.
PMID 19158279
The GATA-1 and Spi-1 transcriptional factors bind to a GATA/EBS dual element in the Fli-1 exon 1.
Barbeau B, Barat C, Bergeron D, Rassart E.
Oncogene. 1999 Sep 30;18(40):5535-45.
PMID 10523830
Regulation of the megakaryocytic glycoprotein IX promoter by the oncogenic Ets transcription factor Fli-1.
Bastian LS, Kwiatkowski BA, Breininger J, Danner S, Roth G.
Blood. 1999 Apr 15;93(8):2637-44.
PMID 10194443
Erythroleukemia induction by Friend murine leukemia virus: insertional activation of a new member of the ets gene family, Fli-1, closely linked to c-ets-1.
Ben-David Y, Giddens EB, Letwin K, Bernstein A.
Genes Dev. 1991 Jun;5(6):908-18.
PMID 2044959
Identification of a common viral integration region in Cas-Br-E murine leukemia virus-induced non-T-, non-B-cell lymphomas.
Bergeron D, Poliquin L, Kozak CA, Rassart E.
J Virol. 1991 Jan;65(1):7-15.
PMID 1845910
Continuous Fli-1 expression plays an essential role in the proliferation and survival of F-MuLV-induced erythroleukemia and human erythroleukemia.
Cui JW, Vecchiarelli-Federico LM, Li YJ, Wang GJ, Ben-David Y.
Leukemia. 2009 Jul;23(7):1311-9. Epub 2009 Mar 12.
PMID 19282832
Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours.
Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, Kovar H, Joubert I, de Jong P, Rouleau G, et al.
Nature. 1992 Sep 10;359(6391):162-5.
PMID 1522903
Oncogene activation in myeloid leukemias by Graffi murine leukemia virus proviral integration.
Denicourt C, Edouard E, Rassart E.
J Virol. 1999 May;73(5):4439-42.
PMID 10196342
Analysis of the thrombopoietin receptor (MPL) promoter implicates GATA and Ets proteins in the coregulation of megakaryocyte-specific genes.
Deveaux S, Filipe A, Lemarchandel V, Ghysdael J, Romeo PH, Mignotte V.
Blood. 1996 Jun 1;87(11):4678-85.
PMID 8639837
Fli-1b is generated by usage of differential splicing and alternative promoter.
Dhulipala PD, Lee L, Rao VN, Reddy ES.
Oncogene. 1998 Sep 3;17(9):1149-57.
PMID 9764825
Small interfering RNAs expressed from a Pol III promoter suppress the EWS/Fli-1 transcript in an Ewing sarcoma cell line.
Dohjima T, Lee NS, Li H, Ohno T, Rossi JJ.
Mol Ther. 2003 Jun;7(6):811-6.
PMID 12788655
Multiplex RT-PCR assay for the differential diagnosis of alveolar rhabdomyosarcoma and Ewing's sarcoma.
Downing JR, Khandekar A, Shurtleff SA, Head DR, Parham DM, Webber BL, Pappo AS, Hulshof MG, Conn WP, Shapiro DN.
Am J Pathol. 1995 Mar;146(3):626-34.
PMID 7887445
Paris-Trousseau syndrome : clinical, hematological, molecular data of ten new cases.
Favier R, Jondeau K, Boutard P, Grossfeld P, Reinert P, Jones C, Bertoni F, Cramer EM.
Thromb Haemost. 2003 Nov;90(5):893-7.
PMID 14597985
In vitro expansion of erythroid progenitors from polycythemia vera patients leads to decrease in JAK2 V617F allele.
Gaikwad A, Nussenzveig R, Liu E, Gottshalk S, Chang K, Prchal JT.
Exp Hematol. 2007 Apr;35(4):587-95.
PMID 17379069
Selective expression of erg isoforms in human endothelial cells.
Hewett PW, Nishi K, Daft EL, Clifford Murray J.
Int J Biochem Cell Biol. 2001 Apr;33(4):347-55.
PMID 11312105
Paris-Trousseau syndrome platelets in a child with Jacobsen's syndrome.
Krishnamurti L, Neglia JP, Nagarajan R, Berry SA, Lohr J, Hirsch B, White JG.
Am J Hematol. 2001 Apr;66(4):295-9.
PMID 11279643
The ets family member Tel binds to the Fli-1 oncoprotein and inhibits its transcriptional activity.
Kwiatkowski BA, Bastian LS, Bauer TR Jr, Tsai S, Zielinska-Kwiatkowska AG, Hickstein DD.
J Biol Chem. 1998 Jul 10;273(28):17525-30.
PMID 9651344
The inositol phosphatase SHIP-1 is negatively regulated by Fli-1 and its loss accelerates leukemogenesis.
Lakhanpal GK, Vecchiarelli-Federico LM, Li YJ, Cui JW, Bailey ML, Spaner DE, Dumont DJ, Barber DL, Ben-David Y.
Blood. 2010 Jul 22;116(3):428-36. Epub 2010 May 5.
PMID 20445019
Direct regulation of BCL-2 by FLI-1 is involved in the survival of FLI-1-transformed erythroblasts.
Lesault I, Quang CT, Frampton J, Ghysdael J.
EMBO J. 2002 Feb 15;21(4):694-703.
PMID 11847117
Solution structure of the ets domain of Fli-1 when bound to DNA.
Liang H, Mao X, Olejniczak ET, Nettesheim DG, Yu L, Meadows RP, Thompson CB, Fesik SW.
Nat Struct Biol. 1994a Dec;1(12):871-5.
PMID 7773776
The secondary structure of the ets domain of human Fli-1 resembles that of the helix-turn-helix DNA-binding motif of the Escherichia coli catabolite gene activator protein.
Liang H, Olejniczak ET, Mao X, Nettesheim DG, Yu L, Thompson CB, Fesik SW.
Proc Natl Acad Sci U S A. 1994b Nov 22;91(24):11655-9.
PMID 7972119
Fli1 acts at the top of the transcriptional network driving blood and endothelial development.
Liu F, Walmsley M, Rodaway A, Patient R.
Curr Biol. 2008 Aug 26;18(16):1234-40.
PMID 18718762
VISTA : visualizing global DNA sequence alignments of arbitrary length.
Mayor C, Brudno M, Schwartz JR, Poliakov A, Rubin EM, Frazer KA, Pachter LS, Dubchak I.
Bioinformatics. 2000 Nov;16(11):1046-7.
PMID 11159318
Generation of a novel Fli-1 protein by gene targeting leads to a defect in thymus development and a delay in Friend virus-induced erythroleukemia.
Melet F, Motro B, Rossi DJ, Zhang L, Bernstein A.
Mol Cell Biol. 1996 Jun;16(6):2708-18.
PMID 8649378
Friend leukaemia integration-1 expression in malignant and benign tumours: a multiple tumour tissue microarray analysis using polyclonal antibody.
Mhawech-Fauceglia P, Herrmann FR, Bshara W, Odunsi K, Terracciano L, Sauter G, Cheney RT, Groth J, Penetrante R, Mhawech-Fauceglia P.
J Clin Pathol. 2007 Jun;60(6):694-700. Epub 2006 Aug 17.
PMID 16917000
10A1 MuLV induces a murine leukemia that expresses hematopoietic stem cell markers by a mechanism that includes fli-1 integration.
Ott DE, Keller J, Rein A.
Virology. 1994 Dec;205(2):563-8.
PMID 7975258
Immunohistochemical expression of endothelial markers CD31, CD34, von Willebrand factor, and Fli-1 in normal human tissues.
Pusztaszeri MP, Seelentag W, Bosman FT.
J Histochem Cytochem. 2006 Apr;54(4):385-95. Epub 2005 Oct 18.
PMID 16234507
Analysis of the DNA-binding and transcriptional activation functions of human Fli-1 protein.
Rao VN, Ohno T, Prasad DD, Bhattacharya G, Reddy ES.
Oncogene. 1993 Aug;8(8):2167-73.
PMID 8336942
Utility of the immunohistochemical detection of FLI-1 expression in round cell and vascular neoplasm using a monoclonal antibody.
Rossi S, Orvieto E, Furlanetto A, Laurino L, Ninfo V, Dei Tos AP.
Mod Pathol. 2004 May;17(5):547-52.
PMID 15001993
Negative and translation termination-dependent positive control of FLI-1 protein synthesis by conserved overlapping 5' upstream open reading frames in Fli-1 mRNA.
Sarrazin S, Starck J, Gonnet C, Doubeikovski A, Melet F, Morle F.
Mol Cell Biol. 2000 May;20(9):2959-69.
PMID 10757781
Regulation of CDKs by phosphorylation.
Solomon MJ, Kaldis P.
Results Probl Cell Differ. 1998;22:79-109. (REVIEW)
PMID 9670320
Hemorrhage, impaired hematopoiesis, and lethality in mouse embryos carrying a targeted disruption of the Fli1 transcription factor.
Spyropoulos DD, Pharr PN, Lavenburg KR, Jackers P, Papas TS, Ogawa M, Watson DK.
Mol Cell Biol. 2000 Aug;20(15):5643-52.
PMID 10891501
Fli-1, an Ets-related transcription factor, regulates erythropoietin-induced erythroid proliferation and differentiation: evidence for direct transcriptional repression of the Rb gene during differentiation.
Tamir A, Howard J, Higgins RR, Li YJ, Berger L, Zacksenhaus E, Reis M, Ben-David Y.
Mol Cell Biol. 1999 Jun;19(6):4452-64.
PMID 10330185
The role of Fli-1 in normal cell function and malignant transformation.
Truong AH, Ben-David Y.
Oncogene. 2000 Dec 18;19(55):6482-9. (REVIEW)
PMID 11175364
Direct transcriptional regulation of MDM2 by Fli-1.
Truong AH, Cervi D, Lee J, Ben-David Y.
Oncogene. 2005 Feb 3;24(6):962-9.
PMID 15592502
The ERGB/Fli-1 gene: isolation and characterization of a new member of the family of human ETS transcription factors.
Watson DK, Smyth FE, Thompson DM, Cheng JQ, Testa JR, Papas TS, Seth A.
Cell Growth Differ. 1992 Oct;3(10):705-13.
PMID 1445800
Molecular characterization of an 11q interstitial deletion in a patient with the clinical features of Jacobsen syndrome.
Wenger SL, Grossfeld PD, Siu BL, Coad JE, Keller FG, Hummel M.
Am J Med Genet A. 2006 Apr 1;140(7):704-8.
PMID 16502431
The FLI-1 transcription factor is a short-lived phosphoprotein in T cells.
Zhang XK, Watson DK.
J Biochem. 2005 Mar;137(3):297-302.
PMID 15809330
Epo regulates erythroid proliferation and differentiation through distinct signaling pathways: implication for erythropoiesis and Friend virus-induced erythroleukemia.
Zochodne B, Truong AH, Stetler K, Higgins RR, Howard J, Dumont D, Berger SA, Ben-David Y.
Oncogene. 2000 May 4;19(19):2296-304.
PMID 10822380


This paper should be referenced as such :
Vecchiarelli-Federico, LM ; Haeri, M ; Ben-David, Y
FLI1 (Friend leukemia virus integration 1)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(10):816-820.
Free journal version : [ pdf ]   [ DOI ]

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 10 ]
  dic(9;12)(p13;p13) PAX5::ETV6
dup (11q) in myeloid malignancies
MLL amplification in leukemia
Pediatric T-Cell Acute Lymphoblastic Leukemia
t(1;7)(p36;p12) IKZF1::PRDM16
t(16;21)(p11;q22) FUS::ERG
Therapy-Related Hematopoietic Neoplasia
t(11;19)(q24;p13) TCF3::FLI1
t(11;22)(q24;q12) EWSR1::FLI1
t(11;22)(q24;q12) MN1::FLI1

External links


HGNC (Hugo)FLI1   3749
LRG (Locus Reference Genomic)LRG_646
Entrez_Gene (NCBI)FLI1    Fli-1 proto-oncogene, ETS transcription factor
AliasesBDPLT21; EWSR2; SIC-1
GeneCards (Weizmann)FLI1
Ensembl hg19 (Hinxton)ENSG00000151702 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000151702 [Gene_View]  ENSG00000151702 [Sequence]  chr11:128694072-128813267 [Contig_View]  FLI1 [Vega]
ICGC DataPortalENSG00000151702
TCGA cBioPortalFLI1
AceView (NCBI)FLI1
Genatlas (Paris)FLI1
SOURCE (Princeton)FLI1
Genetics Home Reference (NIH)FLI1
Genomic and cartography
GoldenPath hg38 (UCSC)FLI1  -     chr11:128694072-128813267 +  11q24.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)FLI1  -     11q24.3   [Description]    (hg19-Feb_2009)
GoldenPathFLI1 - 11q24.3 [CytoView hg19]  FLI1 - 11q24.3 [CytoView hg38]
Genome Data Viewer NCBIFLI1 [Mapview hg19]  
OMIM193067   617443   
Gene and transcription
Genbank (Entrez)AF147318 AI354789 AK294279 AK300153 AK313370
RefSeq transcript (Entrez)NM_001167681 NM_001271010 NM_001271012 NM_002017
Consensus coding sequences : CCDS (NCBI)FLI1
Gene ExpressionFLI1 [ NCBI-GEO ]   FLI1 [ EBI - ARRAY_EXPRESS ]   FLI1 [ SEEK ]   FLI1 [ MEM ]
Gene Expression Viewer (FireBrowse)FLI1 [ Firebrowse - Broad ]
GenevisibleExpression of FLI1 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)2313
GTEX Portal (Tissue expression)FLI1
Human Protein AtlasENSG00000151702-FLI1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ01543   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ01543  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ01543
Domaine pattern : Prosite (Expaxy)ETS_DOMAIN_1 (PS00345)    ETS_DOMAIN_2 (PS00346)    ETS_DOMAIN_3 (PS50061)    PNT (PS51433)   
Domains : Interpro (EBI)Ets_dom    Fli-1    Pointed_dom    SAM/pointed_sf    SAM_PNT-FLI-1    WH-like_DNA-bd_sf    WH_DNA-bd_sf   
Domain families : Pfam (Sanger)Ets (PF00178)    SAM_PNT (PF02198)   
Domain families : Pfam (NCBI)pfam00178    pfam02198   
Domain families : Smart (EMBL)ETS (SM00413)  SAM_PNT (SM00251)  
Conserved Domain (NCBI)FLI1
PDB (RSDB)1FLI    1X66    2YTU    5E8G    5E8I    5JVT   
PDB Europe1FLI    1X66    2YTU    5E8G    5E8I    5JVT   
PDB (PDBSum)1FLI    1X66    2YTU    5E8G    5E8I    5JVT   
PDB (IMB)1FLI    1X66    2YTU    5E8G    5E8I    5JVT   
Structural Biology KnowledgeBase1FLI    1X66    2YTU    5E8G    5E8I    5JVT   
SCOP (Structural Classification of Proteins)1FLI    1X66    2YTU    5E8G    5E8I    5JVT   
CATH (Classification of proteins structures)1FLI    1X66    2YTU    5E8G    5E8I    5JVT   
AlphaFold pdb e-kbQ01543   
Human Protein Atlas [tissue]ENSG00000151702-FLI1 [tissue]
Protein Interaction databases
IntAct (EBI)Q01543
Ontologies - Pathways
Ontology : AmiGOchromatin  transcription cis-regulatory region binding  RNA polymerase II cis-regulatory region sequence-specific DNA binding  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription activator activity, RNA polymerase II-specific  DNA binding  chromatin binding  DNA-binding transcription factor activity  protein binding  nucleus  nucleus  nucleoplasm  cytosol  regulation of transcription by RNA polymerase II  hemostasis  blood circulation  animal organ morphogenesis  nuclear body  cell differentiation  megakaryocyte development  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription by RNA polymerase II  sequence-specific double-stranded DNA binding  
Ontology : EGO-EBIchromatin  transcription cis-regulatory region binding  RNA polymerase II cis-regulatory region sequence-specific DNA binding  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription activator activity, RNA polymerase II-specific  DNA binding  chromatin binding  DNA-binding transcription factor activity  protein binding  nucleus  nucleus  nucleoplasm  cytosol  regulation of transcription by RNA polymerase II  hemostasis  blood circulation  animal organ morphogenesis  nuclear body  cell differentiation  megakaryocyte development  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription by RNA polymerase II  sequence-specific double-stranded DNA binding  
Pathways : KEGGTranscriptional misregulation in cancer   
NDEx NetworkFLI1
Atlas of Cancer Signalling NetworkFLI1
Wikipedia pathwaysFLI1
Orthology - Evolution
GeneTree (enSembl)ENSG00000151702
Phylogenetic Trees/Animal Genes : TreeFamFLI1
Homologs : HomoloGeneFLI1
Homology/Alignments : Family Browser (UCSC)FLI1
Gene fusions - Rearrangements
Fusion : MitelmanEWSR1::FLI1 [22q12.2/11q24.3]  
Fusion : MitelmanMN1::FLI1 [22q12.1/11q24.3]  
Fusion : MitelmanSLC45A3::FLI1 [1q32.1/11q24.3]  
Fusion : COSMICEWSR1 [22q12.2]  -  FLI1 [11q24.3]  [fusion_1302]  [fusion_165]  [fusion_167]  [fusion_169]  [fusion_171]  [fusion_173]  [fusion_174]  
[fusion_175]  [fusion_176]  [fusion_179]  [fusion_180]  [fusion_182]  [fusion_204]  [fusion_227]  
Fusion : QuiverFLI1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerFLI1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)FLI1
Exome Variant ServerFLI1
GNOMAD BrowserENSG00000151702
Varsome BrowserFLI1
ACMGFLI1 variants
Genomic Variants (DGV)FLI1 [DGVbeta]
DECIPHERFLI1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisFLI1 
ICGC Data PortalFLI1 
TCGA Data PortalFLI1 
Broad Tumor PortalFLI1
OASIS PortalFLI1 [ Somatic mutations - Copy number]
Cancer Gene: CensusFLI1 
Somatic Mutations in Cancer : COSMICFLI1  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DFLI1
Mutations and Diseases : HGMDFLI1
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)FLI1
DoCM (Curated mutations)FLI1
CIViC (Clinical Interpretations of Variants in Cancer)FLI1
NCG (London)FLI1
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM193067    617443   
Orphanet19572    3381    3759    22491    22490   
Genetic Testing Registry FLI1
NextProtQ01543 [Medical]
Target ValidationFLI1
Huge Navigator FLI1 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDFLI1
Pharm GKB GenePA28170
Clinical trialFLI1
DataMed IndexFLI1
PubMed180 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Fri Oct 8 21:18:09 CEST 2021

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us