THADA_DROME
ID THADA_DROME Reviewed; 1746 AA.
AC Q9VWB9; Q8MQL6;
DT 25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 3.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Thyroid adenoma-associated protein homolog {ECO:0000303|PubMed:28399403};
GN Name=THADA {ECO:0000303|PubMed:28399403, ECO:0000312|FlyBase:FBgn0031077};
GN ORFNames=CG15618 {ECO:0000312|FlyBase:FBgn0031077};
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:AAM75097.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAM75097.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAM75097.1};
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K., Yu C., Lewis S.E., Rubin G.M., Celniker S.;
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305}
RP FUNCTION, INTERACTION WITH SERCA, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=28399403; DOI=10.1016/j.devcel.2017.03.016;
RA Moraru A., Cakan-Akdogan G., Strassburger K., Males M., Mueller S.,
RA Jabs M., Muelleder M., Frejno M., Braeckman B.P., Ralser M., Teleman A.A.;
RT "THADA regulates the organismal balance between energy storage and heat
RT production.";
RL Dev. Cell 41:72-81(2017).
CC -!- FUNCTION: Plays a key role in energy homeostasis by regulating the
CC balance between energy storage and heat production. Functions by
CC negatively regulating Ca(2+) signaling pathways that are involved in
CC heat production and maintaining correct lipid storage in the fat body.
CC Regulates Ca(2+) signaling pathways by reducing the activity of the
CC calcium-transporting ATPase SERCA possibly by promoting uncoupling of
CC SERCA ATP hydrolysis from calcium pumping. May also function in the
CC nervous system to control feeding behavior.
CC {ECO:0000269|PubMed:28399403}.
CC -!- SUBUNIT: Interacts with SERCA. {ECO:0000269|PubMed:28399403}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:28399403}.
CC -!- TISSUE SPECIFICITY: Detected in the larval fat body, salivary glands
CC and wing imaginal disks (at protein level).
CC {ECO:0000269|PubMed:28399403}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. However, flies are
CC hypersensitive to the cold, hyperphagic and display elevated
CC triglyceride stores resulting in an increased resistance to starvation.
CC Heat production is impaired and flies are slow to recover after cold
CC treatment. The size of the lipid droplets in larval fat bodies are
CC significantly increased and flies display increased feeding. Total body
CC glycogen is also significantly increased in adult females but not in
CC males. Mutants also display an increase in calcium-dependent SERCA
CC activity. No effect on levels of circulating sugars, glucose and
CC trehalose. {ECO:0000269|PubMed:28399403}.
CC -!- SIMILARITY: Belongs to the THADA family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAM75097.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AE014298; AAF49027.3; -; Genomic_DNA.
DR EMBL; AY128504; AAM75097.1; ALT_FRAME; mRNA.
DR RefSeq; NP_608361.3; NM_134517.3.
DR AlphaFoldDB; Q9VWB9; -.
DR IntAct; Q9VWB9; 2.
DR STRING; 7227.FBpp0288416; -.
DR PaxDb; Q9VWB9; -.
DR PRIDE; Q9VWB9; -.
DR EnsemblMetazoa; FBtr0289978; FBpp0288416; FBgn0031077.
DR GeneID; 33001; -.
DR KEGG; dme:Dmel_CG15618; -.
DR UCSC; CG15618-RB; d. melanogaster.
DR CTD; 63892; -.
DR FlyBase; FBgn0031077; THADA.
DR VEuPathDB; VectorBase:FBgn0031077; -.
DR eggNOG; KOG1810; Eukaryota.
DR GeneTree; ENSGT00390000015500; -.
DR HOGENOM; CLU_240100_0_0_1; -.
DR InParanoid; Q9VWB9; -.
DR OMA; ACLQNFP; -.
DR PhylomeDB; Q9VWB9; -.
DR BioGRID-ORCS; 33001; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 33001; -.
DR PRO; PR:Q9VWB9; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0031077; Expressed in eye disc (Drosophila) and 20 other tissues.
DR ExpressionAtlas; Q9VWB9; baseline and differential.
DR Genevisible; Q9VWB9; DM.
DR GO; GO:0098554; C:cytoplasmic side of endoplasmic reticulum membrane; IDA:FlyBase.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:FlyBase.
DR GO; GO:1990845; P:adaptive thermogenesis; IMP:FlyBase.
DR GO; GO:1901895; P:negative regulation of ATPase-coupled calcium transmembrane transporter activity; IPI:FlyBase.
DR GO; GO:0032471; P:negative regulation of endoplasmic reticulum calcium ion concentration; IDA:FlyBase.
DR GO; GO:0010888; P:negative regulation of lipid storage; IMP:FlyBase.
DR GO; GO:0030488; P:tRNA methylation; IBA:GO_Central.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR019442; THADA/TRM732_DUF2428.
DR Pfam; PF10350; DUF2428; 1.
DR SUPFAM; SSF48371; SSF48371; 3.
PE 1: Evidence at protein level;
KW Coiled coil; Endoplasmic reticulum; Phosphoprotein; Reference proteome.
FT CHAIN 1..1746
FT /note="Thyroid adenoma-associated protein homolog"
FT /id="PRO_0000441753"
FT COILED 1252..1286
FT /evidence="ECO:0000255"
FT CONFLICT 938
FT /note="Q -> QQ (in Ref. 3; AAM75097)"
FT /evidence="ECO:0000305"
FT CONFLICT 1530
FT /note="E -> V (in Ref. 3; AAM75097)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1746 AA; 197353 MW; F6AEA09778076F84 CRC64;
MNDLNLRVAA LKVCAHPKRF AELRDALVPL PNTWIAAPHD FVLQFAAAKS SAEQVQVVKD
VFYGEQAQDH EDVAHFLADL LLASPLKHAV RNQLTKLFSD NALAKQNASP HRRHSKEHLL
EALQQSLGEM ANSLAVITPP VSHERTNDVF VSANACLQNF PFGREALGKQ VHRFAPLLTT
ALERYWADIC DPTLELSPTR RNELYLYVQN ALRFLVSLLA EWSDKLRLFE DQRFPGTSNA
VAQKVARYYD TPWDVRSIAA LLIGHLARFS GTFKAYVEDC SRPKAEQDVP IQMAALLVLR
PVDYTENATL ALAILKRIVA VSELKSTVTN LLVFLSKHLF IYSKSLGEMH AHLPDDQKLL
YQRILAQLQV FALQNISSDT DSVRHMSSAL LHQVLQHAQA AGQEELFQVV YRQFEDRAAY
LNASCMALEQ LVAVAGVSKS IENCPSLFGV IFPRHLGCED CVDALFKAMM VSAHKTEPFA
EWQSRWFGLL LAAIRVPEKR RQVIEELIAQ AVQLEPTRLA QVLLPDDRLP LSCKLAAILG
VRQLSARRQN LLRGMKEEVE QALIGLDDHT RLLALRFLVE TPRPSELLNA DQMGAIELYV
RHNANNPSAH LRQLGYGLLQ KALKRVHFGL VEYRKSRTPA SQEVLQFLIR LIRTLAQNLF
PTANYGRRWL SLRLLRDCLE LSEMVGITFS ELGIELPTEA LMACLGDSYE HNKVLAAQLL
ERFQSHSLFK PDEMIELLLS LRPSDSATGA FQLQVYCKAS RVQSEMPTPT HGGTIHEPLT
FRALQWCLQH LREGLRLAQL DLGEAAKLNP LYGLLFASRH LLQQLKLKEL AKEPQWRQYI
DELVTMCLAV SSVVLPVVSS ASPEGHLPET CDQETDQPLT NVLDRQLSRE ELLQVRTTPQ
MILLCAWRSS KEVCLILGEL VQRAPLEEEE DEEQQQQQGD FLLSRAQLEA IGEHFLQLLA
ETKHRGAFEQ AYVGFTMLCR RFWHSESVRL NQLPGQWVDE AMAMVSGQEE WAGKGARLCA
TRRSAGMPFM LQALVGTELK LGTHATLYRC MNRLLEVCER RTGGAAGITA RSHALNIMRA
LFRSSELAEL VTEFMARGIQ CALDGLLLAE EWAERNSATL LLAALIVRVF GVERARLETG
ELHVRNRMTG RIFFTRYPQL FDYFHAALQR ESEQMDAGGG GSENASGKRR QAVQLEAMLL
MLSRLYPSSL EGAESTLNLS EFVPFLIRIC HSHDLMTREM AALVVANFVT QEQALAEIRR
IVVELKALQL RLKNTEAANT KLNTNVLHGQ LLLLLHLHRL VRWTRPSLTR MQLHTLAELA
APLLQHDACA FSALVAVMVA AMEDAVEPGL LDFQLLEQIG VVYLLNHKEV QSRCQQLGIS
NRFYQIFGLH LHRLRGISQG IVLHIVEDLA ETIWALDELK VELWLYILLQ RSLSEQNSLV
SEQDIEHFEF SRDIRRYFET LSREQREEVG QELYESPAVR SSVLHMMHMI KSSKNSCWSL
QLAGRLAALQ TLLRDPGLEL NQLVQRCSEE HSTHQEAGLL LGLRRLIGES KMLERKHWLP
MLNYAQRLVH PGQPVYLRHQ AAELCDSLAR NHLRDQLVAG TTDVDIGLVG RFSGLVLLLL
HDDAEWVRHR AVQLVCGAGL RTRSGAGQEQ EQSAMAPLIL PSALIPPFLD TMIGKLTFDD
FNMVQRLVDI IAEPFTTADA MELFDKQENN HYCERNHVLT ELWDARGRAD PRARTPTIPT
GYQIFK
