FLII_MOUSE
ID FLII_MOUSE Reviewed; 1271 AA.
AC Q9JJ28; Q8K095; Q8VI44;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Protein flightless-1 homolog;
GN Name=Flii; Synonyms=Fli1, Fliih;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=10902907; DOI=10.3109/10425170009033967;
RA Campbell H.D., Fountain S., Young I.G., Weitz S., Lichter P.,
RA Hoheisel J.D.;
RT "Fliih, the murine homologue of the Drosophila melanogaster flightless I
RT gene: nucleotide sequence, chromosomal mapping and overlap with Llglh.";
RL DNA Seq. 11:29-40(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney, and Liver;
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 [4]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10947868; DOI=10.1046/j.1440-1711.2000.00926.x;
RA Davy D.A., Ball E.E., Matthaei K.I., Campbell H.D., Crouch M.F.;
RT "The flightless I protein localizes to actin-based structures during
RT embryonic development.";
RL Immunol. Cell Biol. 78:423-429(2000).
RN [5]
RP FUNCTION.
RX PubMed=11971982; DOI=10.1128/mcb.22.10.3518-3526.2002;
RA Campbell H.D., Fountain S., McLennan I.S., Berven L.A., Crouch M.F.,
RA Davy D.A., Hooper J.A., Waterford K., Chen K.-S., Lupski J.R.,
RA Ledermann B., Young I.G., Matthaei K.I.;
RT "Fliih, a gelsolin-related cytoskeletal regulator essential for early
RT mammalian embryonic development.";
RL Mol. Cell. Biol. 22:3518-3526(2002).
RN [6]
RP INTERACTION WITH CARM1.
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 [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11171324; DOI=10.1242/jcs.114.3.549;
RA Davy D.A., Campbell H.D., Fountain S., de Jong D., Crouch M.F.;
RT "The flightless I protein colocalizes with actin- and microtubule-based
RT structures in motile Swiss 3T3 fibroblasts: evidence for the involvement of
RT PI 3-kinase and Ras-related small GTPases.";
RL J. Cell Sci. 114:549-562(2001).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, Liver, Lung, Pancreas, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION BY WOUND, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=21430700; DOI=10.1038/jid.2011.69;
RA Kopecki Z., O'Neill G.M., Arkell R.M., Cowin A.J.;
RT "Regulation of focal adhesions by flightless i involves inhibition of
RT paxillin phosphorylation via a Rac1-dependent pathway.";
RL J. Invest. Dermatol. 131:1450-1459(2011).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22581781; DOI=10.1096/fj.11-202051;
RA Mohammad I., Arora P.D., Naghibzadeh Y., Wang Y., Li J., Mascarenhas W.,
RA Janmey P.A., Dawson J.F., McCulloch C.A.;
RT "Flightless I is a focal adhesion-associated actin-capping protein that
RT regulates cell migration.";
RL FASEB J. 26:3260-3272(2012).
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 (By
CC similarity). Essential for early embryonic development. May play a role
CC in regulation of cytoskeletal rearrangements involved in cytokinesis
CC and cell migration, by inhibiting Rac1-dependent paxillin
CC phosphorylation. {ECO:0000250, ECO:0000269|PubMed:11171324,
CC ECO:0000269|PubMed:11971982, ECO:0000269|PubMed:21430700,
CC ECO:0000269|PubMed:22581781}.
CC -!- SUBUNIT: Interacts with actin, ACTL6A, NCOA2 and MYD88 (By similarity).
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 (By similarity).
CC Interacts with the nuclear receptors ESR1 and THRB (By similarity).
CC Interacts with CARM1. Interacts with SGK3. {ECO:0000250,
CC ECO:0000269|PubMed:14966289}.
CC -!- INTERACTION:
CC Q9JJ28; Q6PHZ2: Camk2d; NbExp=5; IntAct=EBI-7996161, EBI-2308458;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm, cytoskeleton. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome. Cell junction,
CC focal adhesion. Note=Colocalizes to actin-rich structures in
CC blastocysts and, together with HRAS, RHOA and CDC42, in migrating
CC fibroblasts. Localizes to centrosomes.
CC -!- TISSUE SPECIFICITY: Expressed in blastocyst.
CC {ECO:0000269|PubMed:10947868}.
CC -!- INDUCTION: Up-regulated in response to wounding.
CC {ECO:0000269|PubMed:21430700}.
CC -!- DISRUPTION PHENOTYPE: Increases the percentage of focal complex
CC positive cells. {ECO:0000269|PubMed:21430700}.
CC -!- MISCELLANEOUS: Flii deficiency causes lethality during early
CC embryogenesis at a stage preceding gastrulation.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH32282.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};
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DR EMBL; AF142329; AAF78453.1; -; Genomic_DNA.
DR EMBL; AF287264; AAL36557.1; -; mRNA.
DR EMBL; AL596215; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC027744; AAH27744.1; -; mRNA.
DR EMBL; BC032282; AAH32282.1; ALT_INIT; mRNA.
DR CCDS; CCDS24795.1; -.
DR RefSeq; NP_071292.1; NM_022009.2.
DR AlphaFoldDB; Q9JJ28; -.
DR SMR; Q9JJ28; -.
DR BioGRID; 199703; 13.
DR DIP; DIP-47641N; -.
DR IntAct; Q9JJ28; 8.
DR MINT; Q9JJ28; -.
DR STRING; 10090.ENSMUSP00000002889; -.
DR iPTMnet; Q9JJ28; -.
DR PhosphoSitePlus; Q9JJ28; -.
DR SwissPalm; Q9JJ28; -.
DR EPD; Q9JJ28; -.
DR MaxQB; Q9JJ28; -.
DR PaxDb; Q9JJ28; -.
DR PeptideAtlas; Q9JJ28; -.
DR PRIDE; Q9JJ28; -.
DR ProteomicsDB; 267482; -.
DR Antibodypedia; 1881; 178 antibodies from 32 providers.
DR DNASU; 14248; -.
DR Ensembl; ENSMUST00000002889; ENSMUSP00000002889; ENSMUSG00000002812.
DR GeneID; 14248; -.
DR KEGG; mmu:14248; -.
DR UCSC; uc007jgh.2; mouse.
DR CTD; 2314; -.
DR MGI; MGI:1342286; Flii.
DR VEuPathDB; HostDB:ENSMUSG00000002812; -.
DR eggNOG; KOG0444; Eukaryota.
DR GeneTree; ENSGT00940000156643; -.
DR HOGENOM; CLU_002568_1_0_1; -.
DR InParanoid; Q9JJ28; -.
DR OMA; CFHGWSA; -.
DR OrthoDB; 1376537at2759; -.
DR PhylomeDB; Q9JJ28; -.
DR TreeFam; TF313468; -.
DR BioGRID-ORCS; 14248; 8 hits in 72 CRISPR screens.
DR ChiTaRS; Flii; mouse.
DR PRO; PR:Q9JJ28; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q9JJ28; protein.
DR Bgee; ENSMUSG00000002812; Expressed in ileal epithelium and 262 other tissues.
DR Genevisible; Q9JJ28; MM.
DR GO; GO:0015629; C:actin cytoskeleton; IBA:GO_Central.
DR GO; GO:0005903; C:brush border; IDA:UniProtKB.
DR GO; GO:0034451; C:centriolar satellite; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003779; F:actin binding; ISO:MGI.
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:0030036; P:actin cytoskeleton organization; TAS:MGI.
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 Gene3D; 3.40.20.10; -; 6.
DR Gene3D; 3.80.10.10; -; 3.
DR InterPro; IPR029006; ADF-H/Gelsolin-like_dom_sf.
DR InterPro; IPR029919; FliI.
DR InterPro; IPR007123; Gelsolin-like_dom.
DR InterPro; IPR036180; Gelsolin-like_dom_sf.
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; PTHR11977; 1.
DR PANTHER; PTHR11977:SF85; PTHR11977:SF85; 1.
DR Pfam; PF00626; Gelsolin; 4.
DR Pfam; PF12799; LRR_4; 1.
DR Pfam; PF13855; LRR_8; 2.
DR PRINTS; PR00597; GELSOLIN.
DR SMART; SM00262; GEL; 6.
DR SMART; SM00369; LRR_TYP; 9.
DR SUPFAM; SSF82754; SSF82754; 1.
DR PROSITE; PS51450; LRR; 11.
PE 1: Evidence at protein level;
KW Acetylation; Actin-binding; Activator; Cell junction; Cytoplasm;
KW Cytoskeleton; Developmental protein; Leucine-rich repeat; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Transcription;
KW Transcription regulation.
FT CHAIN 1..1271
FT /note="Protein flightless-1 homolog"
FT /id="PRO_0000218751"
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 1070..1117
FT /note="Gelsolin-like 4"
FT REPEAT 1178..1220
FT /note="Gelsolin-like 5"
FT REGION 1..427
FT /note="Interaction with LRRFIP1 and LRRFIP2"
FT /evidence="ECO:0000250"
FT REGION 495..827
FT /note="Interaction with ACTL6A"
FT /evidence="ECO:0000250"
FT REGION 951..977
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q13045"
FT MOD_RES 21
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q13045"
FT MOD_RES 406
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13045"
FT MOD_RES 436
FT /note="Phosphoserine; by SGK3"
FT /evidence="ECO:0000250|UniProtKB:Q13045"
FT MOD_RES 860
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13045"
FT CONFLICT 849
FT /note="N -> D (in Ref. 1; AAL36557)"
FT /evidence="ECO:0000305"
FT CONFLICT 1057
FT /note="T -> I (in Ref. 3; AAH32282)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1271 AA; 144803 MW; A9642B10FEBF8769 CRC64;
MEATGVLPFV RGVDLSGNDF KGGYFPENVK AMTSLRWLKL NRTGLCYLPE ELAALQKLEH
LSVSHNHLTT LHGELSSLPS LRAIVARANS LKNSGVPDDI FKLDDLSVLD LSHNQLTECP
RELENAKNML VLNLSHNGID SIPNQLFINL TDLLYLDLSE NRLESLPPQM RRLVHLQTLV
LNGNPLLHAQ LRQLPAMMAL QTLHLRNTQR TQSNLPTSLE GLSNLSDVDL SCNDLTRVPE
CLYTLPSLRR LNLSSNQIAE LSLCIDQWVH LETLNLSRNQ LTSLPSAICK LTKLKKLYLN
SNKLDFDGLP SGIGKLTSLE EFMAANNNLE LIPESLCRCP KLKKLVLNKN RLVTLPEAIH
FLTEIQVLDV RENPSLVMPP KPADRTAEWY NIDFSLQNQL RLAGASPATV AAAAAVGSGS
KDPLARKMRL RRRKDSAQDV QAKQVLKGMS DVAQEKNKNQ EESIDARAPG GKVRRWDQGL
EKPRLDYSEF FTEDVGQLPG LTIWQIENFV PVLVEEAFHG KFYEADCYIV LKTFLDDSGS
LNWEIYYWIG GEATLDKKAC SAIHAVNLRN YLGAECRTVR EEMGDESEEF LQVFDNDISY
IEGGTASGFY TVEDTHYVTR MYRVYGKKNI KLEPVPLKGS SLDPRFVFLL DQGLDIYVWR
GAQATLSNTT KARLFAEKIN KNERKGKAEI TLLVQGQEPP GFWDVLGGEP SEIKNHVPDD
FWPPQPKLYK VGLGLGYLEL PQINYKLSVE HKKRPKVELM PGMRLLQSLL DTRCVYILDC
WSDVFIWLGR KSPRLVRAAA LKLGQELCGM LHRPRHTVVS RSLEGTEAQV FKAKFKNWDD
VLTVDYTRNA EAVLQGQGLS GKVKRDTEKT DQMKADLTAL FLPRQPPMPL AEAEQLMEEW
NEDLDGMEGF VLEGRKFTRL PEEEFGHFYT QDCYVFLCRY WVPVEYEEEE KTEDKEGKAS
AEAREGEEAA AEAEEKQPEE DFQCIVYFWQ GREASNMGWL TFTFSLQKKF ESLFPGKLEV
VRMTQQQENP KFLSHFKRKF IIHRGKRKVT QGTLQPTLYQ IRTNGSALCT RCIQINTDSS
LLNSEFCFIL KVPFESEDNQ GIVYAWVGRA SDPDEAKLAE DILNTMFDAS YSKQVINEGE
EPENFFWVGI GAQKPYDDDA EYMKHTRLFR CSNEKGYFAV TEKCSDFCQD DLADDDIMLL
DNGQEVYMWV GTQTSQVEIK LSLKACQVYI QHTRSKEHER PRRLRLVRKG NEQRAFTRCF
HAWSTFRQAP A
