LZTR1_DROME
ID LZTR1_DROME Reviewed; 975 AA.
AC Q9V410;
DT 13-FEB-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Leucine-zipper-like transcriptional regulator 1 homolog {ECO:0000303|PubMed:30442766};
GN Name=Lztr1 {ECO:0000303|PubMed:30442766, ECO:0000312|FlyBase:FBgn0040344};
GN Synonyms=night owl {ECO:0000303|PubMed:32339168},
GN nowl {ECO:0000303|PubMed:32339168};
GN ORFNames=CG3711 {ECO:0000312|FlyBase:FBgn0040344};
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.
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 GENOMIC DNA].
RC STRAIN=Oregon-R;
RX PubMed=10731137; DOI=10.1126/science.287.5461.2220;
RA Benos P.V., Gatt M.K., Ashburner M., Murphy L., Harris D., Barrell B.G.,
RA Ferraz C., Vidal S., Brun C., Demailles J., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Borkova D., Minana B., Kafatos F.C.,
RA Louis C., Siden-Kiamos I., Bolshakov S., Papagiannakis G., Spanos L.,
RA Cox S., Madueno E., de Pablos B., Modolell J., Peter A., Schoettler P.,
RA Werner M., Mourkioti F., Beinert N., Dowe G., Schaefer U., Jaeckle H.,
RA Bucheton A., Callister D.M., Campbell L.A., Darlamitsou A., Henderson N.S.,
RA McMillan P.J., Salles C., Tait E.A., Valenti P., Saunders R.D.C.,
RA Glover D.M.;
RT "From sequence to chromosome: the tip of the X chromosome of D.
RT melanogaster.";
RL Science 287:2220-2222(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30442766; DOI=10.1126/science.aap8210;
RA Bigenzahn J.W., Collu G.M., Kartnig F., Pieraks M., Vladimer G.I.,
RA Heinz L.X., Sedlyarov V., Schischlik F., Fauster A., Rebsamen M.,
RA Parapatics K., Blomen V.A., Mueller A.C., Winter G.E., Kralovics R.,
RA Brummelkamp T.R., Mlodzik M., Superti-Furga G.;
RT "LZTR1 is a regulator of RAS ubiquitination and signaling.";
RL Science 362:1171-1177(2018).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=32339168; DOI=10.1371/journal.pgen.1008727;
RA Maurer G.W., Malita A., Nagy S., Koyama T., Werge T.M., Halberg K.A.,
RA Texada M.J., Rewitz K.;
RT "Analysis of genes within the schizophrenia-linked 22q11.2 deletion
RT identifies interaction of night owl/LZTR1 and NF1 in GABAergic sleep
RT control.";
RL PLoS Genet. 16:e1008727-e1008727(2020).
CC -!- FUNCTION: Inhibitor of Ras signaling (PubMed:30442766). Acts as a
CC substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-
CC protein ligase complex that mediates ubiquitination of Ras (By
CC similarity). Together with Nf1, plays an important role for normal
CC sleep behavior, mainly during the night (PubMed:32339168). Might affect
CC sleep by modulating GABA signaling in Rdl-expressing neurons
CC (PubMed:32339168). Might play a role in the regulation of brain
CC glycogen metabolism and organismal levels of triglycerides
CC (PubMed:32339168). {ECO:0000250|UniProtKB:Q8N653,
CC ECO:0000269|PubMed:30442766, ECO:0000269|PubMed:32339168}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q8N653}.
CC -!- SUBUNIT: Component of some BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein
CC ligase complex. {ECO:0000250|UniProtKB:Q8N653}.
CC -!- TISSUE SPECIFICITY: Expressed in Rdl-expressing neurons of the mushroom
CC body, the neurons projecting to the LC9 optic glomerulus and in a
CC neuronal cluster near the subesophageal ganglion (at protein level).
CC {ECO:0000269|PubMed:32339168}.
CC -!- DISRUPTION PHENOTYPE: Flies are viable but most wings show wing vein
CC defects characterized by extra veins and vein tissue, which are caused
CC by an increase of Ras-MAPK signaling (PubMed:30442766,
CC PubMed:32339168). Decreases sleep with night-time sleep-fragmentation
CC patterns, primarily during the second part of the night
CC (PubMed:32339168). RNAi-mediated knockdown in neurons of males results
CC in reduced total sleep in combination with decreased locomotor
CC activity, increased Ras-MAPK signaling and altered metabolism including
CC reduced glycogen levels and increased levels of triglycerides
CC (PubMed:32339168). RNAi- mediated knockdown in GABAA-receptor-
CC expressing neurons causes a shortening of sleep bouts and an increase
CC in their number during night, with an effect size similar to that seen
CC with pan-neuronal knockdown (PubMed:32339168). RNAi-mediated knockdown
CC in peripheral class-IV dendritic arborization neurons does not cause
CC increased proliferation in the nervous system (PubMed:32339168). Adult-
CC specific RNAi-mediated neuronal knockdown decreases night-time sleep
CC compared to controls and caused an increased number of short sleep
CC bouts during the night (PubMed:32339168). RNAi-mediated knockdown of in
CC GABAB-receptor-expressing neurons or PDF-expressing clock neurons-had
CC no significant effect on night-time sleep-bout number or duration
CC (PubMed:32339168). Simultaneous knockdown of Lztr1 and Nf1 reduces
CC total night-time sleep, increases night-time sleep fragmentation and
CC activates the Ras pathway similarly to single knockdown
CC (PubMed:32339168). {ECO:0000269|PubMed:30442766,
CC ECO:0000269|PubMed:32339168}.
CC -!- SIMILARITY: Belongs to the LZTR1 family. {ECO:0000305}.
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DR EMBL; AE014298; AAF45563.1; -; Genomic_DNA.
DR EMBL; AL109630; CAB65872.1; -; Genomic_DNA.
DR RefSeq; NP_569869.2; NM_130513.4.
DR AlphaFoldDB; Q9V410; -.
DR SMR; Q9V410; -.
DR IntAct; Q9V410; 6.
DR STRING; 7227.FBpp0070184; -.
DR DNASU; 31037; -.
DR EnsemblMetazoa; FBtr0343361; FBpp0310018; FBgn0040344.
DR GeneID; 31037; -.
DR KEGG; dme:Dmel_CG3711; -.
DR UCSC; CG3711-RA; d. melanogaster.
DR CTD; 8216; -.
DR FlyBase; FBgn0040344; Lztr1.
DR VEuPathDB; VectorBase:FBgn0040344; -.
DR GeneTree; ENSGT00940000158190; -.
DR HOGENOM; CLU_012081_0_0_1; -.
DR InParanoid; Q9V410; -.
DR OMA; ILEDHVI; -.
DR OrthoDB; 1263405at2759; -.
DR PhylomeDB; Q9V410; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 31037; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 31037; -.
DR PRO; PR:Q9V410; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0040344; Expressed in eye disc (Drosophila) and 20 other tissues.
DR ExpressionAtlas; Q9V410; baseline and differential.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; IMP:UniProtKB.
DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; IMP:UniProtKB.
DR GO; GO:0070875; P:positive regulation of glycogen metabolic process; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0030431; P:sleep; IGI:UniProtKB.
DR GO; GO:0070328; P:triglyceride homeostasis; IMP:UniProtKB.
DR Gene3D; 2.120.10.80; -; 2.
DR Gene3D; 3.30.710.10; -; 2.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR015915; Kelch-typ_b-propeller.
DR InterPro; IPR006652; Kelch_1.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR Pfam; PF00651; BTB; 2.
DR Pfam; PF01344; Kelch_1; 2.
DR SMART; SM00225; BTB; 2.
DR SUPFAM; SSF117281; SSF117281; 1.
DR SUPFAM; SSF54695; SSF54695; 2.
DR PROSITE; PS50097; BTB; 2.
PE 1: Evidence at protein level;
KW Kelch repeat; Reference proteome; Repeat; Ubl conjugation pathway.
FT CHAIN 1..975
FT /note="Leucine-zipper-like transcriptional regulator 1
FT homolog"
FT /id="PRO_0000446385"
FT REPEAT 263..312
FT /note="Kelch 1"
FT /evidence="ECO:0000255"
FT REPEAT 314..369
FT /note="Kelch 2"
FT /evidence="ECO:0000255"
FT REPEAT 370..417
FT /note="Kelch 3"
FT /evidence="ECO:0000255"
FT REPEAT 421..467
FT /note="Kelch 4"
FT /evidence="ECO:0000255"
FT REPEAT 478..524
FT /note="Kelch 5"
FT /evidence="ECO:0000255"
FT REPEAT 530..581
FT /note="Kelch 6"
FT /evidence="ECO:0000255"
FT DOMAIN 574..670
FT /note="BTB 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT DOMAIN 801..870
FT /note="BTB 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT REGION 16..41
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 158..186
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 975 AA; 106435 MW; 2FE9909DE1C3F70D CRC64;
MLKSISGGVG VASTERGGGG GGCGGGGAGG SASGSRSTSG SGRASCGLGS SSISSGLSAV
CGFVTGASGG GGFERDRDRD RGLANISGGS TPAGILYCPA CMAAANQQSP SQNSSPHHES
FFLRSSFKSS KRNKARKSAS TAGCLDAQHI RANLRMSMSS SMRSSRGNGG GGAASSSHPP
GSSCSSGPGG SGCSMAYDAA SNASSGSGSG SGKATSPGSY SCNALNVDFT SYTATHQWTR
MLECAEFVGA KRSKHTVVAY KDAMFVFGGD NGKNMLNDLI RFGVKDKSWG RACATGTPPA
PRYHHSAVVA GSSMFIFGGY TGDIHSNSNL TNKNDLFEYK FQSAMWVEWK FSGRQPVPRS
AHGAAVYDNK MWIYAGYDGN ARLNDMWTLN LTGENQWEEV DQLGDRPPTC CNFPVAVARD
AMYVFSGQSG LQITNSLFEF HFKTRTWRRI SNEPVLRGAT SAPPSRRYGH TMVHHDRFLY
VFGGSADSTL PNDLHCYDLD SQVWSVIQPE QNSDVPSGRV FHASAVICDA MYIFGGTVDN
SVRRGDTYRF QFSSYPKCTL RDDFGKFFQD KQFCDIQFIV GAEEIRILAH IAFVAARSKY
LRNKILAARE ARQQQMEKVY GVGQVDALAL NAGAGGDRGP MLEVRLANAS PEAFEIILNY
IYTDRIDLKD TYSKNIIILI TDIYQLAGLF TMPRLAHGCI QYLDYKINKL NVLEALYNAD
KSNIKIIKDH CMQFIIKEEN FTDVVMSSEF SDLDKPLLVE IIRKRLYPSK LVIDTSYEGN
IGTTLEIDLC AFLESTGKDF CDISLVLEDH VIPAHKSVLS SRCTYFQGMF RSFMPPDNTV
NIQIGEISPS LEAFHSLLRY IYYGETKMPP QDALYLFQAP CFYGLANNRL HAFCKYSLEH
NITFENVLQT LEASDITKIY DIKEYALKLI VKDFAKVARL PKIAGLSREL LLEIIRAVAD
SHGEFLTRIN INTDI
