TIWAZ_DROME
ID TIWAZ_DROME Reviewed; 367 AA.
AC D5SHR0; Q9W2F9;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 13-JUL-2010, sequence version 1.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=BTB/POZ domain-containing protein Tiwaz {ECO:0000303|PubMed:24142897};
DE AltName: Full=Potassium channel tetramerization domain-containing protein Tiwaz {ECO:0000303|PubMed:30231996};
GN Name=twz {ECO:0000303|PubMed:24142897, ECO:0000312|FlyBase:FBgn0034636};
GN ORFNames=CG10440 {ECO:0000312|FlyBase:FBgn0034636};
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 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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] {ECO:0000312|EMBL:AAM48388.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAM48388.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAM48388.1};
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] {ECO:0000312|EMBL:ADG03446.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC STRAIN=Berkeley {ECO:0000312|EMBL:ADG03446.1};
RA Carlson J., Booth B., Frise E., Sandler J., Wan K., Yu C., Celniker S.;
RL Submitted (APR-2010) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24142897; DOI=10.1534/genetics.113.158402;
RA Williams M.J., Goergen P., Rajendran J., Klockars A., Kasagiannis A.,
RA Fredriksson R., Schioeth H.B.;
RT "Regulation of aggression by obesity-linked genes TfAP-2 and Twz through
RT octopamine signaling in Drosophila.";
RL Genetics 196:349-362(2014).
RN [6] {ECO:0000305}
RP FUNCTION, INDUCTION BY STARVATION, AND DISRUPTION PHENOTYPE.
RX PubMed=25187989; DOI=10.1371/journal.pgen.1004499;
RA Williams M.J., Goergen P., Rajendran J., Zheleznyakova G., Haegglund M.G.,
RA Perland E., Bagchi S., Kalogeropoulou A., Khan Z., Fredriksson R.,
RA Schioeth H.B.;
RT "Obesity-linked homologues TfAP-2 and Twz establish meal frequency in
RT Drosophila melanogaster.";
RL PLoS Genet. 10:e1004499-e1004499(2014).
RN [7] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30231996; DOI=10.1016/j.celrep.2018.08.070;
RA Walcott K.C.E., Mauthner S.E., Tsubouchi A., Robertson J., Tracey W.D.;
RT "The Drosophila Small Conductance Calcium-Activated Potassium Channel
RT Negatively Regulates Nociception.";
RL Cell Rep. 24:3125-3132(2018).
CC -!- FUNCTION: Functions with the transcription factor TfAP-2 to regulate
CC octopamine neuronal signaling pathways that control behaviors such as
CC male aggression, male mating, and the initiation of feeding
CC (PubMed:30231996, PubMed:24142897, PubMed:25187989). Required for TfAP-
CC 2 transcriptional activity in octopaminergic neurons (PubMed:24142897,
CC PubMed:25187989). Functions with TfAP-2 to regulate expression of genes
CC which are involved in promoting octopamine production and secretion
CC from octopaminergic neurons, such as Tbh and Vmat (PubMed:24142897,
CC PubMed:25187989). Octopamine then modulates feeding and male aggression
CC by regulating the expression of the satiation hormone Dsk in insulin-
CC producing cells (IPCs) (PubMed:24142897, PubMed:25187989). Functions
CC with octopamine and Dsk as part of a negative feedback loop to prevent
CC overeating; acts with TfAP-2 to regulate octopamine signaling pathways
CC that initiate feeding, then octopamine activates expression of Dsk
CC which inhibits consummatory behavior (PubMed:25187989). May also be
CC involved in negatively regulating nociception in larvae to prevent
CC spontaneous pain and hyperalgesia (PubMed:30231996).
CC {ECO:0000269|PubMed:24142897, ECO:0000269|PubMed:25187989,
CC ECO:0000269|PubMed:30231996}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=B {ECO:0000312|FlyBase:FBgn0034636};
CC IsoId=D5SHR0-1; Sequence=Displayed;
CC Name=A {ECO:0000312|FlyBase:FBgn0034636};
CC IsoId=D5SHR0-2; Sequence=VSP_061346;
CC -!- INDUCTION: Up-regulated in adults by starvation for 48 hours, whereas
CC no up-regulation was detected at 24 hours.
CC {ECO:0000269|PubMed:25187989}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in adult octopaminergic
CC neurons, disrupts TfAP-2 expression resulting in behavioral
CC abnormalities such as increased male aggression, reduced walking pace
CC and overeating (PubMed:24142897, PubMed:25187989). Males display an
CC increase in low-intensity fighting, with males performing more wing
CC flicks and shoves during a 20 min fighting bout (PubMed:24142897).
CC Males also display increased courtship behaviors, such as singing,
CC circling and abdomen bends, towards males and virgin females
CC (PubMed:24142897). Adults also eat significantly more over a 24 hr
CC period and some overeat after starvation (PubMed:25187989). Inhibits
CC expression of TfAP-2 in adults fed a normal diet, and inhibits the up-
CC regulation of TfAP-2 in adults fed a low calorie diet or undergoing
CC starvation (PubMed:25187989). Adults display decreased expression of
CC the octopamine synthesis genes Tbh and Vmat, and the octopmaine
CC signaling gene Dsk (PubMed:24142897). RNAi-mediated knockdown in class
CC I, II, III, and IV md neurons, results in hypersensitive nociception
CC behaviors, with larvae displaying reduced nocifensive escape locomotion
CC (NEL) response latency to a 42 degrees Celsius heat probe
CC (PubMed:30231996). {ECO:0000269|PubMed:24142897,
CC ECO:0000269|PubMed:25187989, ECO:0000269|PubMed:30231996}.
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; AE013599; AAF46733.1; -; Genomic_DNA.
DR EMBL; AE013599; AFH08202.1; -; Genomic_DNA.
DR EMBL; AY118359; AAM48388.1; -; mRNA.
DR EMBL; BT124861; ADG03446.1; -; mRNA.
DR RefSeq; NP_001246449.1; NM_001259520.1.
DR AlphaFoldDB; D5SHR0; -.
DR SMR; D5SHR0; -.
DR IntAct; D5SHR0; 4.
DR STRING; 7227.FBpp0300865; -.
DR PaxDb; D5SHR0; -.
DR DNASU; 37456; -.
DR EnsemblMetazoa; FBtr0071692; FBpp0071609; FBgn0034636. [D5SHR0-2]
DR EnsemblMetazoa; FBtr0308642; FBpp0300865; FBgn0034636. [D5SHR0-1]
DR GeneID; 37456; -.
DR KEGG; dme:Dmel_CG10440; -.
DR UCSC; CG10440-RA; d. melanogaster.
DR CTD; 37456; -.
DR FlyBase; FBgn0034636; twz.
DR VEuPathDB; VectorBase:FBgn0034636; -.
DR eggNOG; KOG2723; Eukaryota.
DR GeneTree; ENSGT00940000170674; -.
DR HOGENOM; CLU_061268_0_0_1; -.
DR OrthoDB; 971350at2759; -.
DR PhylomeDB; D5SHR0; -.
DR Reactome; R-DME-8866904; Negative regulation of activity of TFAP2 (AP-2) family transcription factors.
DR BioGRID-ORCS; 37456; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 37456; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0034636; Expressed in wing disc and 28 other tissues.
DR ExpressionAtlas; D5SHR0; baseline and differential.
DR GO; GO:0008343; P:adult feeding behavior; IMP:FlyBase.
DR GO; GO:0008344; P:adult locomotory behavior; IMP:FlyBase.
DR GO; GO:0002121; P:inter-male aggressive behavior; IMP:FlyBase.
DR GO; GO:0008049; P:male courtship behavior; IMP:FlyBase.
DR GO; GO:2000130; P:positive regulation of octopamine signaling pathway; IMP:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR InterPro; IPR003131; T1-type_BTB.
DR Pfam; PF02214; BTB_2; 1.
DR SMART; SM00225; BTB; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Reference proteome.
FT CHAIN 1..367
FT /note="BTB/POZ domain-containing protein Tiwaz"
FT /id="PRO_0000454471"
FT DOMAIN 135..205
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT REGION 16..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 62..87
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 240..261
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 20..44
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 62..86
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..29
FT /note="Missing (in isoform A)"
FT /id="VSP_061346"
SQ SEQUENCE 367 AA; 40146 MW; 66BB5500B45221AB CRC64;
MQVRTPFVAL DQRSPLTVDS SCPKRKKCDM DRERERDVKA LEPRDLSSTG RIYARSDIKI
SSSPTVSPTI SNSSSPTPTP PASSSVTPLG LPGAVAAAAA AVGGASSAGA SSYLHGNHKP
ITGIPCVAAA SRYTAPVHID VGGTIYTSSL ETLTKYPESK LAKLFNGQIP IVLDSLKQHY
FIDRDGGMFR HILNFMRNSR LLIAEDFPDL ELLLEEARYY EVEPMIKQLE SMRKDRVRNG
NYLVAPPTPP ARHIKTSPRT SASPECNYEV VALHISPDLG ERIMLSAERA LLDELFPEAS
QATQSSRSGV SWNQGDWGQI IRFPLNGYCK LNSVQVLTRL LNAGFTIEAS VGGQQFSEYL
LARRVPM
