CRERF_DROME
ID CRERF_DROME Reviewed; 755 AA.
AC Q9VC61; Q0KI17; Q8T9A9;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Protein CREBRF homolog {ECO:0000305};
DE AltName: Full=Protein Repressed by Tor {ECO:0000303|PubMed:25920570};
GN Name=REPTOR {ECO:0000303|PubMed:25920570, ECO:0000312|FlyBase:FBgn0039209};
GN ORFNames=CG13624 {ECO:0000312|FlyBase:FBgn0039209};
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]
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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC STRAIN=Berkeley; TISSUE=Embryo;
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 [4]
RP FUNCTION, INTERACTION WITH REPTOR-BP; RAPTOR AND 14-3-3ZETA, SUBCELLULAR
RP LOCATION, PHOSPHORYLATION AT SER-442; SER-443; SER-505; SER-527; SER-530;
RP THR-589; SER-595; SER-596 AND THR-665, DEPHOSPHORYLATION, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF SER-527 AND SER-530.
RX PubMed=25920570; DOI=10.1016/j.devcel.2015.03.013;
RA Tiebe M., Lutz M., De La Garza A., Buechling T., Boutros M., Teleman A.A.;
RT "REPTOR and REPTOR-BP regulate organismal metabolism and transcription
RT downstream of TORC1.";
RL Dev. Cell 33:272-284(2015).
CC -!- FUNCTION: Transcriptional regulator that acts in the TORC1 signaling
CC pathway to regulate energy homeostasis and promote survival during
CC nutrient deprivation. Interacts with REPTOR to form a transcriptional
CC activator complex that functions downstream of TORC1 to up-regulate the
CC expression of most target genes induced by TORC1 inhibition. In the
CC complex, acts as the transcriptional activator. Under normal conditions
CC TORC1 is active, inhibiting the formation of the REPTOR/REPTOR-BP
CC complex by phosphorylating REPTOR and mediates its cytoplasmic
CC retention by forming a docking site for 14-3-3 proteins. Upon TORC1
CC inhibition resulting from nutrient stress, REPTOR is recruited into the
CC nucleus where it interacts with REPTOR-BP and together they maintain
CC organismal metabolism by activating the expression of target stress
CC response genes including those involved in glycogenesis and
CC triglyceride biosynthesis. The complex also appears to negatively
CC regulate some aspects of TORC1-dependent larval growth.
CC {ECO:0000269|PubMed:25920570}.
CC -!- SUBUNIT: Interacts (via C-terminus) with REPTOR-BP (via C-terminus).
CC Interacts with the TORC1 complex component raptor. Interacts (when
CC phosphorylated) with 14-3-3zeta, this interaction may assist its
CC cytoplasmic retention. {ECO:0000269|PubMed:25920570}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:25920570}. Cytoplasm
CC {ECO:0000269|PubMed:25920570}. Chromosome
CC {ECO:0000269|PubMed:25920570}. Note=Translocation from the cytoplasm to
CC the nucleus is promoted by dephosphorylation and inhibited by
CC phosphorylation. Binds to chromatin. {ECO:0000269|PubMed:25920570}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A {ECO:0000312|FlyBase:FBgn0039209}; Synonyms=B
CC {ECO:0000312|FlyBase:FBgn0039209}, C {ECO:0000312|FlyBase:FBgn0039209},
CC D {ECO:0000312|FlyBase:FBgn0039209}, G
CC {ECO:0000312|FlyBase:FBgn0039209};
CC IsoId=Q9VC61-1; Sequence=Displayed;
CC Name=E {ECO:0000312|FlyBase:FBgn0039209}; Synonyms=F
CC {ECO:0000312|FlyBase:FBgn0039209};
CC IsoId=Q9VC61-2; Sequence=VSP_027604;
CC -!- PTM: Phosphorylation by the TORC1 kinase complex at Ser-527 and Ser-530
CC abolishes nuclear localization. Upon TORC1 inhibition, dephosphorylated
CC in a mts/PP2a-dependent manner leading to nuclear localization.
CC {ECO:0000269|PubMed:25920570}.
CC -!- DISRUPTION PHENOTYPE: Sensitive to nutrient stress. Larvae display no
CC obvious phenotype under normal feeding conditions; larval growth and
CC development is normal, and there is no effect on triglyceride and
CC glycogen levels. However when mutants pupate and become adults they
CC display reduced triglyceride and glycogen stores leading to adults
CC dying within 18 hours of starvation whereas controls survive 2.5 days
CC without food. Larvae are also sensitive to nutrient stress displaying
CC 50% lethality when fed a low nutrient diet. Double knockouts of REPTOR
CC with a hypomorphic Tor, rescue the Tor-mediated increase in
CC triglyceride levels and partially rescue the larval growth defect.
CC {ECO:0000269|PubMed:25920570}.
CC -!- SIMILARITY: Belongs to the bZIP family. CREBRF subfamily.
CC {ECO:0000305}.
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DR EMBL; AE014297; AAF56314.2; -; Genomic_DNA.
DR EMBL; AE014297; AAN14001.1; -; Genomic_DNA.
DR EMBL; AE014297; AAN14002.1; -; Genomic_DNA.
DR EMBL; AE014297; AAN14003.1; -; Genomic_DNA.
DR EMBL; AE014297; ABI31203.1; -; Genomic_DNA.
DR EMBL; AE014297; ABI31204.1; -; Genomic_DNA.
DR EMBL; AY069850; AAL39995.1; -; mRNA.
DR RefSeq; NP_001036752.1; NM_001043287.2. [Q9VC61-2]
DR RefSeq; NP_001036753.1; NM_001043288.2. [Q9VC61-2]
DR RefSeq; NP_001287505.1; NM_001300576.1. [Q9VC61-1]
DR RefSeq; NP_651271.1; NM_143014.3. [Q9VC61-1]
DR RefSeq; NP_733012.1; NM_170150.2. [Q9VC61-1]
DR RefSeq; NP_733013.1; NM_170151.2. [Q9VC61-1]
DR RefSeq; NP_733014.1; NM_170152.2. [Q9VC61-1]
DR AlphaFoldDB; Q9VC61; -.
DR SMR; Q9VC61; -.
DR BioGRID; 67856; 20.
DR IntAct; Q9VC61; 4.
DR STRING; 7227.FBpp0110092; -.
DR iPTMnet; Q9VC61; -.
DR PaxDb; Q9VC61; -.
DR PRIDE; Q9VC61; -.
DR DNASU; 42930; -.
DR EnsemblMetazoa; FBtr0084672; FBpp0084052; FBgn0039209. [Q9VC61-1]
DR EnsemblMetazoa; FBtr0084673; FBpp0084053; FBgn0039209. [Q9VC61-1]
DR EnsemblMetazoa; FBtr0084674; FBpp0084054; FBgn0039209. [Q9VC61-1]
DR EnsemblMetazoa; FBtr0084675; FBpp0084055; FBgn0039209. [Q9VC61-1]
DR EnsemblMetazoa; FBtr0110795; FBpp0110092; FBgn0039209. [Q9VC61-2]
DR EnsemblMetazoa; FBtr0110796; FBpp0110093; FBgn0039209. [Q9VC61-2]
DR EnsemblMetazoa; FBtr0345204; FBpp0311399; FBgn0039209. [Q9VC61-1]
DR GeneID; 42930; -.
DR KEGG; dme:Dmel_CG13624; -.
DR UCSC; CG13624-RA; d. melanogaster. [Q9VC61-1]
DR CTD; 42930; -.
DR FlyBase; FBgn0039209; REPTOR.
DR VEuPathDB; VectorBase:FBgn0039209; -.
DR eggNOG; ENOG502QTAK; Eukaryota.
DR GeneTree; ENSGT00390000007125; -.
DR InParanoid; Q9VC61; -.
DR OMA; YFAPDMS; -.
DR BioGRID-ORCS; 42930; 0 hits in 1 CRISPR screen.
DR ChiTaRS; REPTOR; fly.
DR GenomeRNAi; 42930; -.
DR PRO; PR:Q9VC61; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0039209; Expressed in brain and 51 other tissues.
DR ExpressionAtlas; Q9VC61; baseline and differential.
DR Genevisible; Q9VC61; DM.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:FlyBase.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:FlyBase.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0042594; P:response to starvation; IMP:FlyBase.
DR GO; GO:0006986; P:response to unfolded protein; IEA:InterPro.
DR GO; GO:0038202; P:TORC1 signaling; IMP:FlyBase.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR039165; CREBRF.
DR PANTHER; PTHR21552; PTHR21552; 1.
DR PROSITE; PS00036; BZIP_BASIC; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Chromosome; Cytoplasm; DNA-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..755
FT /note="Protein CREBRF homolog"
FT /id="PRO_0000299308"
FT DOMAIN 697..755
FT /note="bZIP"
FT REGION 51..80
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 99..154
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 368..422
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 438..483
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 538..596
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 699..708
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 709..716
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT COMPBIAS 99..119
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 126..154
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 368..406
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 445..483
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 552..566
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 442
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:25920570"
FT MOD_RES 443
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:25920570"
FT MOD_RES 505
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:25920570"
FT MOD_RES 527
FT /note="Phosphoserine; by TORC1"
FT /evidence="ECO:0000269|PubMed:25920570"
FT MOD_RES 530
FT /note="Phosphoserine; by TORC1"
FT /evidence="ECO:0000269|PubMed:25920570"
FT MOD_RES 589
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:25920570"
FT MOD_RES 595
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:25920570"
FT MOD_RES 596
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:25920570"
FT MOD_RES 665
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:25920570"
FT VAR_SEQ 737..755
FT /note="SEFNVKAVEISYNPSIFVL -> KRLMNGIAELKQALVVKHRTKNLGESTEE
FT VDQQIARIYATASSGIRIAGGSTDFVNKVLENMRGGMPNGGLEELRKSS (in
FT isoform E)"
FT /evidence="ECO:0000305"
FT /id="VSP_027604"
FT MUTAGEN 527
FT /note="S->A: Nuclear localization and induces
FT transcriptional activity; when associated with A-530."
FT /evidence="ECO:0000269|PubMed:25920570"
FT MUTAGEN 530
FT /note="S->A: Nuclear localization and induces
FT transcriptional activity; when associated with A-527."
FT /evidence="ECO:0000269|PubMed:25920570"
SQ SEQUENCE 755 AA; 82263 MW; D851D42235FF10E5 CRC64;
MTENQLYPMS SEFFDTGSNS SSNTLKYDLY SLGSTVVGAA LPTLTINTGY GSSSSNNNNT
NNNNNNSSSH SSSSNCSTST TNTCNVMLST TAITIPRSSN HNQIHHHPYQ QSDLQTPRHH
PSPLHTLPSM THQQNQLQQQ QQQQHHNQQQ QLQQSHLALG ELSDFGLDAL DAASLSPTLL
QDVSLSAVSP LSTTLYNGNT SGAGSSNGIG SGSGGYFTPD MSHSLSLNVV SEQVLLQEAT
TPNELLYEMT PNSNAMWSDI SSAIIHTKHE PFSLDDDYIF PNDKAEIQAA DLSDLNGGDF
LDVIGNIEDF LPQTAVTQSV NFLLSPQAQG QDALVAPPME LLQQQQQNHQ QLQVGSLPQL
QTLLTLSQQQ QSNSSSTSPY EIYHSTPQKP QQQQLSASFS PGSQASQSPL TPPPPPHANR
PQYQMVKSRN MQELIKKGFP MSSPPERSIL SQSAALSPGG SSGFGSSASG NSTTTSNQTS
GSAVRKSFGY QSAVENSQLS RLSSSAPTHL GLEHIWMRRE PRQHLLSTGS LAEAESFSSL
STGSVLSPDG IDFSQDDEDD NSSENSDNYD DCSSDNGLSE DEDETRTSTP NHLSSSKGKE
RFFWQYNVQA KGPKGKRLVF QSKLEDPHVL NEVTDPVFSP TCSVRGIKVY KHSGKARKGD
GNDLTPNARK LHNIGKELDK LSRTINDMTP VSELPFNVRP KSRKEKNKLA SRACRLKKKA
QHEANKIKLF GLEIEHSEFN VKAVEISYNP SIFVL
