FOXO_DROME
ID FOXO_DROME Reviewed; 613 AA.
AC Q95V55; Q7KF42; Q95TK1; Q9VFN8;
DT 16-JUN-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Forkhead box protein O {ECO:0000303|PubMed:12893776};
DE Short=dFOXO {ECO:0000303|PubMed:12893776};
DE AltName: Full=Protein FKHR;
GN Name=foxo {ECO:0000312|EMBL:AAS65148.1}; Synonyms=Afx; ORFNames=CG3143;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAL28078.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), FUNCTION, SUBCELLULAR LOCATION,
RP DISRUPTION PHENOTYPE, PHOSPHORYLATION AT THR-44; SER-190 AND SER-259, AND
RP MUTAGENESIS OF THR-44; SER-190 AND SER-259.
RX PubMed=12893776; DOI=10.1101/gad.1098703;
RA Puig O., Marr M.T., Ruhf M.L., Tjian R.;
RT "Control of cell number by Drosophila FOXO: downstream and feedback
RT regulation of the insulin receptor pathway.";
RL Genes Dev. 17:2006-2020(2003).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAL09043.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM E).
RC TISSUE=Oocyte {ECO:0000269|Ref.2};
RA Zhang H.;
RT "A Drosophila FKHR highly expressed in oocyte and early embryo.";
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000312|EMBL:AAS65147.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [4] {ECO:0000305, ECO:0000312|EMBL:AAS65147.1}
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [5] {ECO:0000305, ECO:0000312|EMBL:AAL90280.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAL90280.1};
RC TISSUE=Embryo {ECO:0000269|PubMed:12537569};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=12908874; DOI=10.1186/1475-4924-2-20;
RA Juenger M.A., Rintelen F., Stocker H., Wasserman J.D., Vegh M.,
RA Radimerski T., Greenberg M.E., Hafen E.;
RT "The Drosophila forkhead transcription factor FOXO mediates the reduction
RT in cell number associated with reduced insulin signaling.";
RL J. Biol. 2:20.1-20.17(2003).
RN [7] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15175753; DOI=10.1038/nature02549;
RA Hwangbo D.S., Gershman B., Tu M.-P., Palmer M., Tatar M.;
RT "Drosophila dFOXO controls lifespan and regulates insulin signalling in
RT brain and fat body.";
RL Nature 429:562-566(2004).
RN [8] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH MELT.
RX PubMed=16054033; DOI=10.1016/j.devcel.2005.07.004;
RA Teleman A.A., Chen Y.-W., Cohen S.M.;
RT "Drosophila Melted modulates FOXO and TOR activity.";
RL Dev. Cell 9:271-281(2005).
RN [9] {ECO:0000305}
RP FUNCTION.
RX PubMed=18234213; DOI=10.1016/j.jmb.2007.12.042;
RA Vihervaara T., Puig O.;
RT "dFOXO regulates transcription of a Drosophila acid lipase.";
RL J. Mol. Biol. 376:1215-1223(2008).
RN [10] {ECO:0000305}
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-75; SER-262; SER-263 AND
RP SER-268, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo {ECO:0000269|PubMed:18327897};
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
CC -!- FUNCTION: Transcription factor involved in the regulation of the
CC insulin signaling pathway. Consistently activates both the downstream
CC target Thor\d4EBP and the feedback control target InR. Involved in
CC negative regulation of the cell cycle, modulating cell growth and
CC proliferation. In response to cellular stresses, such as nutrient
CC deprivation or increased levels of reactive oxygen species, foxo is
CC activated and inhibits growth through the action of target genes such
CC as Thor. Foxo activated in the adult fat body can regulate lifespan in
CC adults; an insulin peptide itself may function as one secondary
CC messenger of insulin-regulated aging. Also regulates Lip4, homolog of
CC human acid lipases, thereby acting as a key modulator of lipid
CC metabolism by insulin signaling and integrates insulin responses to
CC glucose and lipid homeostasis. {ECO:0000269|PubMed:12893776,
CC ECO:0000269|PubMed:12908874, ECO:0000269|PubMed:15175753,
CC ECO:0000269|PubMed:16054033, ECO:0000269|PubMed:18234213}.
CC -!- SUBUNIT: Interacts with melt. {ECO:0000269|PubMed:16054033}.
CC -!- INTERACTION:
CC Q95V55; Q8I9J6: HDAC4; NbExp=3; IntAct=EBI-500849, EBI-4288282;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12893776,
CC ECO:0000269|PubMed:15175753}. Nucleus {ECO:0000255|PROSITE-
CC ProRule:PRU00089, ECO:0000269|PubMed:12893776,
CC ECO:0000269|PubMed:15175753}. Note=When phosphorylated, translocated
CC from nucleus to cytoplasm. Dephosphorylation triggers nuclear
CC translocation. {ECO:0000269|PubMed:12893776,
CC ECO:0000269|PubMed:15175753}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=B {ECO:0000269|PubMed:12893776}; Synonyms=C
CC {ECO:0000269|PubMed:10731132};
CC IsoId=Q95V55-1; Sequence=Displayed;
CC Name=A {ECO:0000269|PubMed:10731132};
CC IsoId=Q95V55-2; Sequence=VSP_053041;
CC Name=D {ECO:0000269|PubMed:10731132};
CC IsoId=Q95V55-3; Sequence=VSP_053040, VSP_053042;
CC Name=E {ECO:0000269|Ref.2};
CC IsoId=Q95V55-4; Sequence=VSP_053039, VSP_053043;
CC -!- DISRUPTION PHENOTYPE: Mutant foxo lacking Akt1 phosphorylation sites no
CC longer responds to insulin inhibition, remains in the nucleus, and is
CC constitutively active, inducing cell arrest.
CC {ECO:0000269|PubMed:12893776}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL13947.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF426831; AAL28078.1; -; mRNA.
DR EMBL; AF416728; AAL09043.1; -; mRNA.
DR EMBL; AE014297; AAF55012.2; -; Genomic_DNA.
DR EMBL; AE014297; AAS65147.1; -; Genomic_DNA.
DR EMBL; AE014297; AAS65148.1; -; Genomic_DNA.
DR EMBL; AE014297; ACL83512.1; -; Genomic_DNA.
DR EMBL; AY058718; AAL13947.1; ALT_INIT; mRNA.
DR EMBL; AY089542; AAL90280.1; -; mRNA.
DR RefSeq; NP_001262557.1; NM_001275628.1.
DR RefSeq; NP_650330.3; NM_142073.5.
DR RefSeq; NP_996204.1; NM_206482.3. [Q95V55-1]
DR RefSeq; NP_996205.1; NM_206483.3. [Q95V55-1]
DR AlphaFoldDB; Q95V55; -.
DR SMR; Q95V55; -.
DR BioGRID; 66786; 241.
DR IntAct; Q95V55; 60.
DR STRING; 7227.FBpp0293589; -.
DR iPTMnet; Q95V55; -.
DR PaxDb; Q95V55; -.
DR EnsemblMetazoa; FBtr0082886; FBpp0089343; FBgn0038197. [Q95V55-1]
DR EnsemblMetazoa; FBtr0082887; FBpp0089344; FBgn0038197. [Q95V55-1]
DR GeneID; 41709; -.
DR KEGG; dme:Dmel_CG3143; -.
DR UCSC; CG3143-RA; d. melanogaster.
DR UCSC; CG3143-RB; d. melanogaster. [Q95V55-1]
DR CTD; 41709; -.
DR FlyBase; FBgn0038197; foxo.
DR VEuPathDB; VectorBase:FBgn0038197; -.
DR eggNOG; KOG2294; Eukaryota.
DR GeneTree; ENSGT00940000170843; -.
DR InParanoid; Q95V55; -.
DR OMA; EWMMQNI; -.
DR PhylomeDB; Q95V55; -.
DR Reactome; R-DME-110478; Insulin signaling pathway.
DR Reactome; R-DME-1181150; Signaling by NODAL.
DR Reactome; R-DME-198693; AKT phosphorylates targets in the nucleus.
DR Reactome; R-DME-211163; AKT-mediated inactivation of FOXO1A.
DR Reactome; R-DME-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-DME-5689880; Ub-specific processing proteases.
DR Reactome; R-DME-9607240; FLT3 Signaling.
DR Reactome; R-DME-9614399; Regulation of localization of FOXO transcription factors.
DR Reactome; R-DME-9617629; Regulation of FOXO transcriptional activity by acetylation.
DR Reactome; R-DME-9617828; FOXO-mediated transcription of cell cycle genes.
DR Reactome; R-DME-9634638; Estrogen-dependent nuclear events downstream of ESR-membrane signaling.
DR SignaLink; Q95V55; -.
DR BioGRID-ORCS; 41709; 0 hits in 3 CRISPR screens.
DR ChiTaRS; foxo; fly.
DR GenomeRNAi; 41709; -.
DR PRO; PR:Q95V55; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0038197; Expressed in embryonic labral segment (Drosophila) and 43 other tissues.
DR ExpressionAtlas; Q95V55; baseline and differential.
DR Genevisible; Q95V55; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:FlyBase.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IMP:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:FlyBase.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IDA:FlyBase.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:FlyBase.
DR GO; GO:0009267; P:cellular response to starvation; IMP:FlyBase.
DR GO; GO:0007623; P:circadian rhythm; IMP:FlyBase.
DR GO; GO:0001745; P:compound eye morphogenesis; IMP:FlyBase.
DR GO; GO:0048813; P:dendrite morphogenesis; IMP:FlyBase.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:FlyBase.
DR GO; GO:0036099; P:female germ-line stem cell population maintenance; IMP:FlyBase.
DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IMP:FlyBase.
DR GO; GO:0045475; P:locomotor rhythm; IGI:FlyBase.
DR GO; GO:0048542; P:lymph gland development; IMP:FlyBase.
DR GO; GO:0030308; P:negative regulation of cell growth; IMP:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0045792; P:negative regulation of cell size; IMP:FlyBase.
DR GO; GO:0070345; P:negative regulation of fat cell proliferation; IMP:FlyBase.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0010888; P:negative regulation of lipid storage; IDA:FlyBase.
DR GO; GO:0040015; P:negative regulation of multicellular organism growth; IMP:FlyBase.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:FlyBase.
DR GO; GO:0061045; P:negative regulation of wound healing; IMP:FlyBase.
DR GO; GO:0061057; P:peptidoglycan recognition protein signaling pathway; IMP:FlyBase.
DR GO; GO:0010508; P:positive regulation of autophagy; IMP:FlyBase.
DR GO; GO:0061965; P:positive regulation of entry into reproductive diapause; IMP:FlyBase.
DR GO; GO:2000253; P:positive regulation of feeding behavior; IMP:FlyBase.
DR GO; GO:2000130; P:positive regulation of octopamine signaling pathway; IMP:FlyBase.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:FlyBase.
DR GO; GO:0010898; P:positive regulation of triglyceride catabolic process; IMP:FlyBase.
DR GO; GO:0010506; P:regulation of autophagy; IMP:FlyBase.
DR GO; GO:0040008; P:regulation of growth; IGI:FlyBase.
DR GO; GO:0035206; P:regulation of hemocyte proliferation; IMP:FlyBase.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IMP:UniProtKB.
DR GO; GO:0016241; P:regulation of macroautophagy; IMP:FlyBase.
DR GO; GO:0046620; P:regulation of organ growth; IMP:FlyBase.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; IDA:FlyBase.
DR GO; GO:0006979; P:response to oxidative stress; IMP:FlyBase.
DR GO; GO:0042594; P:response to starvation; IDA:FlyBase.
DR CDD; cd00059; FH; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR001766; Fork_head_dom.
DR InterPro; IPR030456; TF_fork_head_CS_2.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00250; Forkhead; 1.
DR PRINTS; PR00053; FORKHEAD.
DR SMART; SM00339; FH; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS00658; FORK_HEAD_2; 1.
DR PROSITE; PS50039; FORK_HEAD_3; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Cell cycle; Cytoplasm;
KW Developmental protein; Differentiation; DNA-binding; Growth regulation;
KW Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..613
FT /note="Forkhead box protein O"
FT /id="PRO_0000371436"
FT DNA_BIND 95..201
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 39..90
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 182..205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 217..269
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 317..360
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 59..90
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 182..198
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 219..233
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 252..267
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 339..360
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 44
FT /note="Phosphothreonine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:12893776"
FT MOD_RES 75
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 190
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:12893776"
FT MOD_RES 259
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:12893776"
FT MOD_RES 262
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 263
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 268
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT VAR_SEQ 146..447
FT /note="NSIRHNLSLHNRFMRVQNEGTGKSSWWMLNPEAKPGKSVRRRAASMETSRYE
FT KRRGRAKKRVEALRQAGVVGLNDATPSPSSSVSEGLDHFPESPLHSGGGFQLSPDFRQR
FT ASSNASSCGRLSPIRAQDLEPDWGFPVDYQNTTMTQAHAQALEELTGTMADELTLCNQQ
FT QQGFSAASGLPSQPPPPPYQPPQHQQAQQQQQQQSPYALNGPASGYNTLQPQSQCLLHR
FT SLNCSCMHNARDGLSPNSVTTTMSPAYPNSEPSSDSLNTYSNVVLDGPADTAALMVQQQ
FT QQQQQQQQLSASLE -> SFAINALLSSDRFSFCLHRSIPPLAVIKDQRLLKNSLRWLR
FT RNRRRLFHLIPETLFFADSALPANFSFFLRRLVVVRWFRGLADRWFGGSVARVFIIENS
FT SSQSGDLAIEPVPKFYELSTNQSECKWQSGMAVDKTWIIGGDPVSATCRDSVSPISRSN
FT GPMKYAYLIRDDSVSWGSNELHTSQSVAAQPLYEGPKRGHRQVILVDAQPGGQARQVCA
FT PPCRFHGDVPVREAARQGQEAGGGTASGGRGGPQRCHALAQQQRQRGAGSLSRESAPQW
FT RWLPIIARFPATRLIQCQFLRTPEPH (in isoform E)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_053039"
FT VAR_SEQ 146..304
FT /note="NSIRHNLSLHNRFMRVQNEGTGKSSWWMLNPEAKPGKSVRRRAASMETSRYE
FT KRRGRAKKRVEALRQAGVVGLNDATPSPSSSVSEGLDHFPESPLHSGGGFQLSPDFRQR
FT ASSNASSCGRLSPIRAQDLEPDWGFPVDYQNTTMTQAHAQALEELTGT -> DLQILQF
FT FYIQYISVFAKYIYLYVHICFSLVLVTELHTSQSVAAQPLYEGPKRGHRQVILVDAQPG
FT GQARQVCAPPCRFHGDVPVREAARQGQEAGGGTASGGRGGPQRCHALAQQQRQRGAGSL
FT SRESAPQWRWLPIIARFPATRLIQCQFLRTPEPH (in isoform D)"
FT /evidence="ECO:0000303|PubMed:10731132"
FT /id="VSP_053040"
FT VAR_SEQ 146..243
FT /note="NSIRHNLSLHNRFMRVQNEGTGKSSWWMLNPEAKPGKSVRRRAASMETSRYE
FT KRRGRAKKRVEALRQAGVVGLNDATPSPSSSVSEGLDHFPESPLHS -> SFAINALLS
FT SDRFSFCLHRSIPPLAVIKDQRLLKNSLRWLRRNRRRLFHLIPETLFFADSALPANFSF
FT FLRRLVVVRWFRGLADRWFGGSVARVFIIENSSSQSGDLAIEPVPKFYELSTNQSECKW
FT QSGMAVDKTWIIGGDPVSATCRDSVSPISRSNGPMKYAYLIRDDSVSWGSNELHTSQSV
FT AAQPLYEGPKRGHRQVILVDAQPGGQARQVCAPPCRFHGDVPVREAARQGQEAGGGTAS
FT GGRGGPQRCHALAQQQRQRGAGSLSRESAPQVTINCDD (in isoform A)"
FT /evidence="ECO:0000303|PubMed:10731132"
FT /id="VSP_053041"
FT VAR_SEQ 305..613
FT /note="Missing (in isoform D)"
FT /evidence="ECO:0000303|PubMed:10731132"
FT /id="VSP_053042"
FT VAR_SEQ 448..613
FT /note="Missing (in isoform E)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_053043"
FT MUTAGEN 44
FT /note="T->A: Abolishes phosphorylation; when associated
FT with A-190 and A-259."
FT /evidence="ECO:0000269|PubMed:12893776"
FT MUTAGEN 190
FT /note="S->A: Abolishes phosphorylation; when associated
FT with A-44 and A-259."
FT /evidence="ECO:0000269|PubMed:12893776"
FT MUTAGEN 259
FT /note="S->A: Abolishes phosphorylation; when associated
FT with A-44 and A-190."
FT /evidence="ECO:0000269|PubMed:12893776"
SQ SEQUENCE 613 AA; 67413 MW; B472822ACA169BF9 CRC64;
MMDGYAQEWP RLTHTDNGLA MDQLGGDLPL DVGFEPQTRA RSNTWPCPRP ENFVEPTDEL
DSTKASNQQL APGDSQQAIQ NANAAKKNSS RRNAWGNLSY ADLITHAIGS ATDKRLTLSQ
IYEWMVQNVP YFKDKGDSNS SAGWKNSIRH NLSLHNRFMR VQNEGTGKSS WWMLNPEAKP
GKSVRRRAAS METSRYEKRR GRAKKRVEAL RQAGVVGLND ATPSPSSSVS EGLDHFPESP
LHSGGGFQLS PDFRQRASSN ASSCGRLSPI RAQDLEPDWG FPVDYQNTTM TQAHAQALEE
LTGTMADELT LCNQQQQGFS AASGLPSQPP PPPYQPPQHQ QAQQQQQQQS PYALNGPASG
YNTLQPQSQC LLHRSLNCSC MHNARDGLSP NSVTTTMSPA YPNSEPSSDS LNTYSNVVLD
GPADTAALMV QQQQQQQQQQ QLSASLEGQC LEVLNNEAQP IDEFNLENFP VGNLECNVEE
LLQQEMSYGG LLDINIPLAT VNTNLVNSSS GPLSISNISN LSNISSNSGS SLSLNQLQAQ
LQQQQQQQQA QQQQQAQQQQ QQHQQHQQQL LLNNNNNSSS SLELATQTAT TNLNARVQYS
QPSVVTSPPS WVH
