DSK_DROME
ID DSK_DROME Reviewed; 141 AA.
AC P09040; B2ZB94; Q8MYU9; Q9VMY4;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 15-AUG-2003, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Drosulfakinins;
DE Contains:
DE RecName: Full=Drosulfakinin-0;
DE Short=DSK-0;
DE Contains:
DE RecName: Full=Drosulfakinin-1;
DE AltName: Full=Drosulfakinin I;
DE Short=DSK-I;
DE Contains:
DE RecName: Full=Drosulfakinin-2;
DE AltName: Full=Drosulfakinin II;
DE Short=DSK-II;
DE Flags: Precursor;
GN Name=Dsk; ORFNames=CG18090;
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 [GENOMIC DNA], AND TISSUE SPECIFICITY.
RC STRAIN=Canton-S;
RX PubMed=2842322; DOI=10.1016/s0021-9258(18)37731-7;
RA Nichols R., Schneuwly S.A., Dixon J.E.;
RT "Identification and characterization of a Drosophila homologue to the
RT vertebrate neuropeptide cholecystokinin.";
RL J. Biol. Chem. 263:12167-12170(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Ke F.;
RT "A molecular phylogeny for the Drosophila melanogaster subgroup.";
RL Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
RN [3]
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]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Head;
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]
RP PROTEIN SEQUENCE OF 126-139, SULFATION AT TYR-134, AND AMIDATION AT
RP PHE-139.
RC TISSUE=Larva;
RX PubMed=12171930; DOI=10.1074/jbc.m206257200;
RA Baggerman G., Cerstiaens A., De Loof A., Schoofs L.;
RT "Peptidomics of the larval Drosophila melanogaster central nervous
RT system.";
RL J. Biol. Chem. 277:40368-40374(2002).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=8350979; DOI=10.1016/0143-4179(93)90002-r;
RA Tibbetts M.F., Nichols R.;
RT "Immunocytochemistry of sequence-related neuropeptides in Drosophila.";
RL Neuropeptides 24:321-325(1993).
RN [8]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=8581950; DOI=10.1007/s004410050518;
RA Nichols R., Lim I.A.;
RT "Spatial and temporal immunocytochemical analysis of drosulfakinin (Dsk)
RT gene products in the Drosophila melanogaster central nervous system.";
RL Cell Tissue Res. 283:107-116(1996).
RN [9]
RP FUNCTION, AND TISSUE SPECIFICITY.
RC STRAIN=Oregon-R;
RX PubMed=17632121; DOI=10.1016/j.jinsphys.2007.06.001;
RA Palmer G.C., Tran T., Duttlinger A., Nichols R.;
RT "The drosulfakinin 0 (DSK 0) peptide encoded in the conserved Dsk gene
RT affects adult Drosophila melanogaster crop contractions.";
RL J. Insect Physiol. 53:1125-1133(2007).
RN [10]
RP FUNCTION.
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 [11]
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).
CC -!- FUNCTION: Involved in diverse biological roles including regulating
CC aspects of gut function, satiety and food ingestion, hyperactivity, and
CC aggression (PubMed:17632121, PubMed:24142897, PubMed:25187989).
CC Regulates gut muscle contraction in adults but not in larvae
CC (PubMed:17632121). Functions downstream of TfAP-2 and twz in octopamine
CC signaling pathways to modulate feeding and male aggression
CC (PubMed:24142897, PubMed:25187989). Inhibits consummatory behavior in
CC adults and functions as part of a negative feedback loop with TfAP-2
CC and twz to prevent overeating; TfAP-2 and twz regulate octopamine
CC signaling to initiate feeding, then octopamine activates expression of
CC Dsk in insulin-producing cells (IPCs) to inhibit feeding
CC (PubMed:25187989). {ECO:0000269|PubMed:17632121,
CC ECO:0000269|PubMed:24142897, ECO:0000269|PubMed:25187989}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed in larval brain tissue localizing to
CC cells in the anterior and medial protocerebrum. Expressed in cells in
CC the brain lobe, optic lobe, subesophageal ganglion, thoracic ganglia
CC and the eighth abdominal neuromere. Drosulfakinin-0 is expressed in the
CC central nervous system including the subesophageal ganglion and an
CC abdominal ganglion. {ECO:0000269|PubMed:17632121,
CC ECO:0000269|PubMed:2842322, ECO:0000269|PubMed:8350979,
CC ECO:0000269|PubMed:8581950}.
CC -!- DEVELOPMENTAL STAGE: Expressed at all developmental stages.
CC {ECO:0000269|PubMed:8581950}.
CC -!- INDUCTION: Up-regulated 24 hours after starvation and then appears to
CC return to normal expression levels 48 hours after nutritional
CC starvation. {ECO:0000269|PubMed:25187989}.
CC -!- DISRUPTION PHENOTYPE: In adults, RNAi-mediated knockdown in insulin-
CC producing cells or all Dsk-expressing cells, increases total food
CC intake and the number of feeding bouts over a 24 hour period
CC (PubMed:25187989). However, feeding them the CCK antagonist SR 27897
CC does not result in a further increase in total food intake and feeding
CC bouts, as in wild-type adults (PubMed:25187989).
CC {ECO:0000269|PubMed:25187989}.
CC -!- SIMILARITY: Belongs to the gastrin/cholecystokinin family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB03703.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; J03957; AAB03703.1; ALT_FRAME; Genomic_DNA.
DR EMBL; EU635459; ACC99368.1; -; Genomic_DNA.
DR EMBL; AE014297; AAF52173.2; -; Genomic_DNA.
DR EMBL; AY113595; AAM29600.1; -; mRNA.
DR PIR; A31101; A31101.
DR RefSeq; NP_524845.2; NM_080106.3.
DR AlphaFoldDB; P09040; -.
DR SMR; P09040; -.
DR BioGRID; 69923; 4.
DR DIP; DIP-19456N; -.
DR IntAct; P09040; 2.
DR STRING; 7227.FBpp0078628; -.
DR PaxDb; P09040; -.
DR DNASU; 45845; -.
DR EnsemblMetazoa; FBtr0078989; FBpp0078628; FBgn0000500.
DR GeneID; 45845; -.
DR KEGG; dme:Dmel_CG18090; -.
DR UCSC; CG18090-RA; d. melanogaster.
DR CTD; 45845; -.
DR FlyBase; FBgn0000500; Dsk.
DR VEuPathDB; VectorBase:FBgn0000500; -.
DR eggNOG; ENOG502SESC; Eukaryota.
DR HOGENOM; CLU_1847224_0_0_1; -.
DR InParanoid; P09040; -.
DR OMA; FGDRRNQ; -.
DR OrthoDB; 1534835at2759; -.
DR PhylomeDB; P09040; -.
DR BioGRID-ORCS; 45845; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 45845; -.
DR PRO; PR:P09040; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0000500; Expressed in head capsule and 9 other tissues.
DR ExpressionAtlas; P09040; baseline and differential.
DR Genevisible; P09040; DM.
DR GO; GO:0005615; C:extracellular space; IC:FlyBase.
DR GO; GO:0005184; F:neuropeptide hormone activity; IDA:FlyBase.
DR GO; GO:0071855; F:neuropeptide receptor binding; IPI:FlyBase.
DR GO; GO:0008343; P:adult feeding behavior; IMP:FlyBase.
DR GO; GO:0008344; P:adult locomotory behavior; IMP:FlyBase.
DR GO; GO:0008345; P:larval locomotory behavior; IDA:FlyBase.
DR GO; GO:0033555; P:multicellular organismal response to stress; IMP:FlyBase.
DR GO; GO:0007528; P:neuromuscular junction development; IMP:FlyBase.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IDA:FlyBase.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:FlyBase.
DR GO; GO:0006940; P:regulation of smooth muscle contraction; IDA:FlyBase.
DR GO; GO:0006939; P:smooth muscle contraction; IMP:UniProtKB.
DR InterPro; IPR013152; Gastrin/cholecystokinin_CS.
DR InterPro; IPR013259; Sulfakinin.
DR Pfam; PF08257; Sulfakinin; 2.
DR PROSITE; PS00259; GASTRIN; 2.
PE 1: Evidence at protein level;
KW Amidation; Cleavage on pair of basic residues; Direct protein sequencing;
KW Hormone; Neuropeptide; Reference proteome; Secreted; Signal; Sulfation.
FT SIGNAL 1..33
FT /evidence="ECO:0000255"
FT PROPEP 34..73
FT /id="PRO_0000010666"
FT PEPTIDE 76..82
FT /note="Drosulfakinin-0"
FT /evidence="ECO:0000255"
FT /id="PRO_0000010667"
FT PROPEP 86..111
FT /id="PRO_0000010668"
FT PEPTIDE 114..122
FT /note="Drosulfakinin-1"
FT /evidence="ECO:0000255"
FT /id="PRO_0000010669"
FT PEPTIDE 126..139
FT /note="Drosulfakinin-2"
FT /id="PRO_0000010670"
FT MOD_RES 82
FT /note="Phenylalanine amide"
FT /evidence="ECO:0000250|UniProtKB:B2ZB96"
FT MOD_RES 117
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250|UniProtKB:B2ZB96"
FT MOD_RES 122
FT /note="Phenylalanine amide"
FT /evidence="ECO:0000250|UniProtKB:B2ZB96"
FT MOD_RES 134
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000269|PubMed:12171930"
FT MOD_RES 139
FT /note="Phenylalanine amide"
FT /evidence="ECO:0000269|PubMed:12171930"
SQ SEQUENCE 141 AA; 16151 MW; 496AD66494696C88 CRC64;
MGPRSCTHFA TLFMPLWALA FCFLVVLPIP AQTTSLQNAK DDRRLQELES KIGGEIDQPI
ANLVGPSFSL FGDRRNQKTM SFGRRVPLIS RPIIPIELDL LMDNDDERTK AKRFDDYGHM
RFGKRGGDDQ FDDYGHMRFG R
