ID FLII_HUMAN Reviewed; 1269 AA. AC Q13045; B4DIL0; F5H407; J3QLG3; DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 2. DT 27-MAR-2024, entry version 220. DE RecName: Full=Protein flightless-1 homolog; GN Name=FLII; Synonyms=FLIL; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9177775; DOI=10.1006/geno.1997.4709; RA Campbell H.D., Fountain S., Young I.G., Claudianos C., Hoheisel J.D., RA Chen K.-S., Lupski J.R.; RT "Genomic structure, evolution, and expression of human FLII, a gelsolin and RT leucine-rich-repeat family member: overlap with LLGL."; RL Genomics 42:46-54(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Hippocampus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Kidney; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP PROTEIN SEQUENCE OF 1-11, AND ACETYLATION AT MET-1. RC TISSUE=Platelet; RX PubMed=12665801; DOI=10.1038/nbt810; RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., RA Vandekerckhove J.; RT "Exploring proteomes and analyzing protein processing by mass spectrometric RT identification of sorted N-terminal peptides."; RL Nat. Biotechnol. 21:566-569(2003). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-1269 (ISOFORM 1). RC TISSUE=Hippocampus; RX PubMed=8248259; DOI=10.1073/pnas.90.23.11386; RA Campbell H.D., Schimansky T., Claudianos C., Ozsarac N., Kasprzak A.B., RA Cotsell J.N., Young I.G., de Couet H.G., Miklos G.L.G.; RT "The Drosophila melanogaster flightless-I gene involved in gastrulation and RT muscle degeneration encodes gelsolin-like and leucine-rich repeat domains RT and is conserved in Caenorhabditis elegans and humans."; RL Proc. Natl. Acad. Sci. U.S.A. 90:11386-11390(1993). RN [7] RP INTERACTION WITH ACTIN AND LRRFIP1, AND TISSUE SPECIFICITY. RX PubMed=9525888; DOI=10.1074/jbc.273.14.7920; RA Liu Y.-T., Yin H.L.; RT "Identification of the binding partners for flightless I, a novel protein RT bridging the leucine-rich repeat and the gelsolin superfamilies."; RL J. Biol. Chem. 273:7920-7927(1998). RN [8] RP INTERACTION WITH LRRFIP1. RX PubMed=9671805; DOI=10.1093/nar/26.15.3460; RA Wilson S.A., Brown E.C., Kingsman A.J., Kingsman S.M.; RT "TRIP: a novel double stranded RNA binding protein which interacts with the RT leucine rich repeat of flightless I."; RL Nucleic Acids Res. 26:3460-3467(1998). RN [9] RP INTERACTION WITH LRRFIP1 AND LRRFIP2. RC TISSUE=Skeletal muscle; RX PubMed=10366446; DOI=10.1006/geno.1999.5817; RA Fong K.S.K., de Couet H.G.; RT "Novel proteins interacting with the leucine-rich repeat domain of human RT flightless-I identified by the yeast two-hybrid system."; RL Genomics 58:146-157(1999). RN [10] RP FUNCTION, INTERACTION WITH CARM1; ESR1; THRB; NCOA2 AND ACTL6A, AND RP MUTAGENESIS OF GLU-586 AND GLY-603. RX PubMed=14966289; DOI=10.1128/mcb.24.5.2103-2117.2004; RA Lee Y.-H., Campbell H.D., Stallcup M.R.; RT "Developmentally essential protein flightless I is a nuclear receptor RT coactivator with actin binding activity."; RL Mol. Cell. Biol. 24:2103-2117(2004). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-856, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-406 AND SER-856, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-856, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-856, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [16] RP PHOSPHORYLATION AT SER-436 AND THR-818, AND INTERACTION WITH SGK3. RX PubMed=19293151; DOI=10.1074/jbc.m807770200; RA Xu J., Liao L., Qin J., Xu J., Liu D., Songyang Z.; RT "Identification of Flightless-I as a substrate of the cytokine-independent RT survival kinase CISK."; RL J. Biol. Chem. 284:14377-14385(2009). RN [17] RP INTERACTION WITH LRRFIP1; LRRFIP2 AND MYD88. RX PubMed=19265123; DOI=10.4049/jimmunol.0802260; RA Dai P., Jeong S.Y., Yu Y., Leng T., Wu W., Xie L., Chen X.; RT "Modulation of TLR signaling by multiple MyD88-interacting partners RT including leucine-rich repeat Fli-I-interacting proteins."; RL J. Immunol. 182:3450-3460(2009). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-856, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [19] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-21, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-406; SER-436 AND SER-856, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [21] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-436 AND SER-856, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [23] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [24] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-406; SER-856 AND SER-860, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-436 AND SER-856, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). CC -!- FUNCTION: May play a role as coactivator in transcriptional activation CC by hormone-activated nuclear receptors (NR) and acts in cooperation CC with NCOA2 and CARM1. Involved in estrogen hormone signaling. Involved CC in early embryonic development (By similarity). May play a role in CC regulation of cytoskeletal rearrangements involved in cytokinesis and CC cell migration, by inhibiting Rac1-dependent paxillin phosphorylation. CC {ECO:0000250, ECO:0000269|PubMed:14966289}. CC -!- SUBUNIT: Interacts with actin, ACTL6A, NCOA2, CARM1 and MYD88. CC Interacts with LRRFIP1 and LRRFIP2. Upon LPS stimulation, LRRFIP2 CC competes for MYD88-binding. LRRFIP1 constitutively blocks the CC interaction with MyD88, even in the absence of LPS. Interacts with the CC nuclear receptors ESR1 and THRB. Interacts with SGK3. CC {ECO:0000269|PubMed:10366446, ECO:0000269|PubMed:14966289, CC ECO:0000269|PubMed:19265123, ECO:0000269|PubMed:19293151, CC ECO:0000269|PubMed:9525888, ECO:0000269|PubMed:9671805}. CC -!- INTERACTION: CC Q13045; Q32MZ4: LRRFIP1; NbExp=2; IntAct=EBI-351549, EBI-1369100; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm, cytoskeleton CC {ECO:0000250}. Cytoplasm, cytoskeleton, microtubule organizing center, CC centrosome {ECO:0000250}. Cell junction, focal adhesion {ECO:0000250}. CC Note=Colocalizes to actin-rich structures in blastocysts and, together CC with HRAS, RHOA and CDC42, in migrating fibroblasts. Localizes to CC centrosomes (By similarity). {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q13045-1; Sequence=Displayed; CC Name=2; CC IsoId=Q13045-2; Sequence=VSP_044686, VSP_044687; CC Name=3; CC IsoId=Q13045-3; Sequence=VSP_046887; CC -!- TISSUE SPECIFICITY: Strongest expression in skeletal muscle with high CC expression also in the heart and lung. {ECO:0000269|PubMed:9525888}. CC -!- SEQUENCE CAUTION: CC Sequence=BAG58522.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U80184; AAC02796.1; -; Genomic_DNA. DR EMBL; AK295655; BAG58522.1; ALT_INIT; mRNA. DR EMBL; AC127537; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC025300; AAH25300.1; -; mRNA. DR EMBL; U01184; AAC03568.1; -; mRNA. DR CCDS; CCDS11192.1; -. [Q13045-1] DR CCDS; CCDS58521.1; -. [Q13045-3] DR CCDS; CCDS58522.1; -. [Q13045-2] DR PIR; A49674; A49674. DR RefSeq; NP_001243193.1; NM_001256264.1. [Q13045-3] DR RefSeq; NP_001243194.1; NM_001256265.1. [Q13045-2] DR RefSeq; NP_002009.1; NM_002018.3. [Q13045-1] DR AlphaFoldDB; Q13045; -. DR SMR; Q13045; -. DR BioGRID; 108603; 293. DR IntAct; Q13045; 75. DR MINT; Q13045; -. DR STRING; 9606.ENSP00000324573; -. DR GlyGen; Q13045; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q13045; -. DR MetOSite; Q13045; -. DR PhosphoSitePlus; Q13045; -. DR SwissPalm; Q13045; -. DR BioMuta; FLII; -. DR DMDM; 18202493; -. DR EPD; Q13045; -. DR jPOST; Q13045; -. DR MassIVE; Q13045; -. DR MaxQB; Q13045; -. DR PaxDb; 9606-ENSP00000324573; -. DR PeptideAtlas; Q13045; -. DR ProteomicsDB; 26432; -. DR ProteomicsDB; 59121; -. [Q13045-1] DR Pumba; Q13045; -. DR Antibodypedia; 1881; 207 antibodies from 32 providers. DR DNASU; 2314; -. DR Ensembl; ENST00000327031.9; ENSP00000324573.4; ENSG00000177731.16. [Q13045-1] DR Ensembl; ENST00000545457.6; ENSP00000438536.2; ENSG00000177731.16. [Q13045-2] DR Ensembl; ENST00000579294.5; ENSP00000463534.1; ENSG00000177731.16. [Q13045-3] DR Ensembl; ENST00000638207.2; ENSP00000491480.1; ENSG00000284571.2. [Q13045-1] DR Ensembl; ENST00000638404.1; ENSP00000492392.1; ENSG00000284571.2. [Q13045-2] DR Ensembl; ENST00000638812.1; ENSP00000491660.1; ENSG00000284571.2. [Q13045-3] DR GeneID; 2314; -. DR KEGG; hsa:2314; -. DR MANE-Select; ENST00000327031.9; ENSP00000324573.4; NM_002018.4; NP_002009.1. DR UCSC; uc002gsr.3; human. [Q13045-1] DR AGR; HGNC:3750; -. DR CTD; 2314; -. DR DisGeNET; 2314; -. DR GeneCards; FLII; -. DR HGNC; HGNC:3750; FLII. DR HPA; ENSG00000177731; Tissue enhanced (skeletal). DR MalaCards; FLII; -. DR MIM; 600362; gene. DR neXtProt; NX_Q13045; -. DR OpenTargets; ENSG00000177731; -. DR Orphanet; 819; Smith-Magenis syndrome. DR PharmGKB; PA28171; -. DR VEuPathDB; HostDB:ENSG00000177731; -. DR eggNOG; KOG0444; Eukaryota. DR GeneTree; ENSGT00940000156643; -. DR HOGENOM; CLU_002568_1_0_1; -. DR InParanoid; Q13045; -. DR OMA; CFHGWSA; -. DR OrthoDB; 25995at2759; -. DR PhylomeDB; Q13045; -. DR TreeFam; TF313468; -. DR PathwayCommons; Q13045; -. DR SignaLink; Q13045; -. DR SIGNOR; Q13045; -. DR BioGRID-ORCS; 2314; 219 hits in 1158 CRISPR screens. DR ChiTaRS; FLII; human. DR GeneWiki; FLII; -. DR GenomeRNAi; 2314; -. DR Pharos; Q13045; Tbio. DR PRO; PR:Q13045; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q13045; Protein. DR Bgee; ENSG00000177731; Expressed in lower esophagus mucosa and 92 other cell types or tissues. DR ExpressionAtlas; Q13045; baseline and differential. DR GO; GO:0015629; C:actin cytoskeleton; IBA:GO_Central. DR GO; GO:0005903; C:brush border; IEA:Ensembl. DR GO; GO:0034451; C:centriolar satellite; IDA:HPA. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0003779; F:actin binding; IDA:HGNC. DR GO; GO:0051015; F:actin filament binding; IBA:GO_Central. DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IBA:GO_Central. DR GO; GO:0051014; P:actin filament severing; IBA:GO_Central. DR GO; GO:0008154; P:actin polymerization or depolymerization; IBA:GO_Central. DR GO; GO:0051016; P:barbed-end actin filament capping; IBA:GO_Central. DR GO; GO:0030239; P:myofibril assembly; IBA:GO_Central. DR CDD; cd11280; gelsolin_like; 2. DR CDD; cd11290; gelsolin_S1_like; 1. DR CDD; cd11292; gelsolin_S3_like; 1. DR CDD; cd11288; gelsolin_S5_like; 1. DR CDD; cd11291; gelsolin_S6_like; 1. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 3. DR Gene3D; 3.40.20.10; Severin; 6. DR InterPro; IPR029006; ADF-H/Gelsolin-like_dom_sf. DR InterPro; IPR007123; Gelsolin-like_dom. DR InterPro; IPR001611; Leu-rich_rpt. DR InterPro; IPR025875; Leu-rich_rpt_4. DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp. DR InterPro; IPR032675; LRR_dom_sf. DR InterPro; IPR007122; Villin/Gelsolin. DR PANTHER; PTHR11977:SF139; PROTEIN FLIGHTLESS-1 HOMOLOG; 1. DR PANTHER; PTHR11977; VILLIN; 1. DR Pfam; PF00626; Gelsolin; 5. DR Pfam; PF00560; LRR_1; 1. DR Pfam; PF12799; LRR_4; 1. DR Pfam; PF13855; LRR_8; 3. DR PRINTS; PR00597; GELSOLIN. DR PRINTS; PR00019; LEURICHRPT. DR SMART; SM00262; GEL; 6. DR SMART; SM00364; LRR_BAC; 7. DR SMART; SM00365; LRR_SD22; 4. DR SMART; SM00369; LRR_TYP; 9. DR SUPFAM; SSF55753; Actin depolymerizing proteins; 6. DR SUPFAM; SSF52058; L domain-like; 2. DR PROSITE; PS51450; LRR; 11. DR Genevisible; Q13045; HS. PE 1: Evidence at protein level; KW Acetylation; Actin-binding; Activator; Alternative splicing; Cell junction; KW Cytoplasm; Cytoskeleton; Developmental protein; Direct protein sequencing; KW Leucine-rich repeat; Nucleus; Phosphoprotein; Reference proteome; Repeat; KW Transcription; Transcription regulation. FT CHAIN 1..1269 FT /note="Protein flightless-1 homolog" FT /id="PRO_0000218750" FT REPEAT 7..32 FT /note="LRR 1" FT REPEAT 33..55 FT /note="LRR 2" FT REPEAT 56..78 FT /note="LRR 3" FT REPEAT 80..103 FT /note="LRR 4" FT REPEAT 104..126 FT /note="LRR 5" FT REPEAT 127..149 FT /note="LRR 6" FT REPEAT 150..173 FT /note="LRR 7" FT REPEAT 175..196 FT /note="LRR 8" FT REPEAT 197..222 FT /note="LRR 9" FT REPEAT 223..245 FT /note="LRR 10" FT REPEAT 247..268 FT /note="LRR 11" FT REPEAT 269..291 FT /note="LRR 12" FT REPEAT 293..316 FT /note="LRR 13" FT REPEAT 318..339 FT /note="LRR 14" FT REPEAT 340..363 FT /note="LRR 15" FT REPEAT 501..559 FT /note="Gelsolin-like 1" FT REPEAT 640..670 FT /note="Gelsolin-like 2" FT REPEAT 755..798 FT /note="Gelsolin-like 3" FT REPEAT 1068..1115 FT /note="Gelsolin-like 4" FT REPEAT 1176..1218 FT /note="Gelsolin-like 5" FT REGION 1..427 FT /note="Interaction with LRRFIP1 and LRRFIP2" FT REGION 452..473 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 495..827 FT /note="Interaction with ACTL6A" FT /evidence="ECO:0000269|PubMed:14966289" FT REGION 951..975 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000269|PubMed:12665801, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" FT MOD_RES 21 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 406 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 436 FT /note="Phosphoserine; by SGK3" FT /evidence="ECO:0000269|PubMed:19293151, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:24275569" FT MOD_RES 818 FT /note="Phosphothreonine; by SGK3" FT /evidence="ECO:0000269|PubMed:19293151" FT MOD_RES 856 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 860 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..21 FT /note="MEATGVLPFVRGVDLSGNDFK -> MDLRGLRPVP (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_046887" FT VAR_SEQ 138..191 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_044686" FT VAR_SEQ 416 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_044687" FT VARIANT 1243 FT /note="R -> H (in dbSNP:rs8821)" FT /id="VAR_029258" FT MUTAGEN 586 FT /note="E->K: No change in ESR1 binding but reduced binding FT to ACTL6A and reduced coactivator function." FT /evidence="ECO:0000269|PubMed:14966289" FT MUTAGEN 603 FT /note="G->S: No change in binding to ACTL6A or in FT coactivator function." FT /evidence="ECO:0000269|PubMed:14966289" FT CONFLICT 1 FT /note="M -> V (in Ref. 2; BAG58522)" FT /evidence="ECO:0000305" FT CONFLICT 298 FT /note="Y -> N (in Ref. 2; BAG58522)" FT /evidence="ECO:0000305" SQ SEQUENCE 1269 AA; 144751 MW; 29AC7C07738B7B47 CRC64; MEATGVLPFV RGVDLSGNDF KGGYFPENVK AMTSLRWLKL NRTGLCYLPE ELAALQKLEH LSVSHNNLTT LHGELSSLPS LRAIVARANS LKNSGVPDDI FKLDDLSVLD LSHNQLTECP RELENAKNML VLNLSHNSID TIPNQLFINL TDLLYLDLSE NRLESLPPQM RRLVHLQTLV LNGNPLLHAQ LRQLPAMTAL QTLHLRSTQR TQSNLPTSLE GLSNLADVDL SCNDLTRVPE CLYTLPSLRR LNLSSNQITE LSLCIDQWVH VETLNLSRNQ LTSLPSAICK LSKLKKLYLN SNKLDFDGLP SGIGKLTNLE EFMAANNNLE LVPESLCRCP KLRKLVLNKN HLVTLPEAIH FLTEIEVLDV RENPNLVMPP KPADRAAEWY NIDFSLQNQL RLAGASPATV AAAAAAGSGP KDPMARKMRL RRRKDSAQDD QAKQVLKGMS DVAQEKNKKQ EESADARAPS GKVRRWDQGL EKPRLDYSEF FTEDVGQLPG LTIWQIENFV PVLVEEAFHG KFYEADCYIV LKTFLDDSGS LNWEIYYWIG GEATLDKKAC SAIHAVNLRN YLGAECRTVR EEMGDESEEF LQVFDNDISY IEGGTASGFY TVEDTHYVTR MYRVYGKKNI KLEPVPLKGT SLDPRFVFLL DRGLDIYVWR GAQATLSSTT KARLFAEKIN KNERKGKAEI TLLVQGQELP EFWEALGGEP SEIKKHVPED FWPPQPKLYK VGLGLGYLEL PQINYKLSVE HKQRPKVELM PRMRLLQSLL DTRCVYILDC WSDVFIWLGR KSPRLVRAAA LKLGQELCGM LHRPRHATVS RSLEGTEAQV FKAKFKNWDD VLTVDYTRNA EAVLQSPGLS GKVKRDAEKK DQMKADLTAL FLPRQPPMSL AEAEQLMEEW NEDLDGMEGF VLEGKKFARL PEEEFGHFYT QDCYVFLCRY WVPVEYEEEE KKEDKEEKAE GKEGEEATAE AEEKQPEEDF QCIVYFWQGR EASNMGWLTF TFSLQKKFES LFPGKLEVVR MTQQQENPKF LSHFKRKFII HRGKRKAVQG AQQPSLYQIR TNGSALCTRC IQINTDSSLL NSEFCFILKV PFESEDNQGI VYAWVGRASD PDEAKLAEDI LNTMFDTSYS KQVINEGEEP ENFFWVGIGA QKPYDDDAEY MKHTRLFRCS NEKGYFAVTE KCSDFCQDDL ADDDIMLLDN GQEVYMWVGT QTSQVEIKLS LKACQVYIQH MRSKEHERPR RLRLVRKGNE QHAFTRCFHA WSAFCKALA //