MIP_DROME
ID MIP_DROME Reviewed; 211 AA.
AC Q9VVF7;
DT 10-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Allatostatins MIP;
DE AltName: Full=B-type Allostatin preprohormone;
DE AltName: Full=Myoinhibitory-like protein;
DE Contains:
DE RecName: Full=Drostatin-B1;
DE AltName: Full=MIP-1;
DE Contains:
DE RecName: Full=Drostatin-B2;
DE AltName: Full=MIP-2;
DE Contains:
DE RecName: Full=Drostatin-B3;
DE AltName: Full=MIP-3;
DE Contains:
DE RecName: Full=Drostatin-B4;
DE AltName: Full=MIP-4;
DE Contains:
DE RecName: Full=Drostatin-B5;
DE AltName: Full=MIP-5;
DE Flags: Precursor;
GN Name=Mip; ORFNames=CG6456;
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 [MRNA], FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RC STRAIN=Canton-S;
RX PubMed=11181081; DOI=10.1006/bbrc.2001.4402;
RA Williamson M., Lenz C., Winther M.E., Naessel D.R.,
RA Grimmelikhuijzen C.J.P.;
RT "Molecular cloning, genomic organization, and expression of a B-type
RT (cricket-type) allatostatin preprohormone from Drosophila melanogaster.";
RL Biochem. Biophys. Res. Commun. 281:544-550(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Vanden Broeck J., Schoofs L., De Loof A.;
RT "Evolution of developmental peptide hormones and their receptors.";
RL (In) Adiyodi K.G., Adiyodi R.G., Dorn A. (eds.);
RL Reproductive biology of invertebrates. Vol. X - part B. Progress in
RL developmental endocrinology, pp.41-69, John Wiley & Sons, Chichester
RL (2000).
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;
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J.W., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.A.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M., Celniker S.E.;
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP PROTEIN SEQUENCE OF 151-159 AND 193-202, AND AMIDATION.
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 PROTEIN SEQUENCE OF 151-159; 163-175; 179-189 AND 193-202, IDENTIFICATION
RP BY MASS SPECTROMETRY, MASS SPECTROMETRY, AND AMIDATION AT TRP-159; TRP-175;
RP TRP-189 AND TRP-202.
RC TISSUE=Midgut {ECO:0000303|PubMed:21214272};
RX PubMed=21214272; DOI=10.1021/pr101116g;
RA Reiher W., Shirras C., Kahnt J., Baumeister S., Isaac R.E., Wegener C.;
RT "Peptidomics and peptide hormone processing in the Drosophila midgut.";
RL J. Proteome Res. 10:1881-1892(2011).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=19319573; DOI=10.1007/s00441-009-0769-y;
RA Veenstra J.A.;
RT "Peptidergic paracrine and endocrine cells in the midgut of the fruit fly
RT maggot.";
RL Cell Tissue Res. 336:309-323(2009).
RN [9]
RP FUNCTION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF TRP-195 AND TRP-202.
RX PubMed=20458515; DOI=10.1007/s00018-010-0393-8;
RA Poels J., Van Loy T., Vandersmissen H.P., Van Hiel B., Van Soest S.,
RA Nachman R.J., Vanden Broeck J.;
RT "Myoinhibiting peptides are the ancestral ligands of the promiscuous
RT Drosophila sex peptide receptor.";
RL Cell. Mol. Life Sci. 67:3511-3522(2010).
RN [10]
RP FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF TRP-67 AND TRP-74, AND
RP SYNTHESIS OF 66-74.
RX PubMed=20308537; DOI=10.1073/pnas.0914764107;
RA Kim Y.J., Bartalska K., Audsley N., Yamanaka N., Yapici N., Lee J.Y.,
RA Kim Y.C., Markovic M., Isaac E., Tanaka Y., Dickson B.J.;
RT "MIPs are ancestral ligands for the sex peptide receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:6520-6525(2010).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=21174124; DOI=10.1007/s00441-010-1100-7;
RA Kolodziejczyk A., Nassel D.R.;
RT "A novel wide-field neuron with branches in the lamina of the Drosophila
RT visual system expresses myoinhibitory peptide and may be associated with
RT the clock.";
RL Cell Tissue Res. 343:357-369(2011).
RN [12]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25333796; DOI=10.1371/journal.pbio.1001974;
RA Oh Y., Yoon S.E., Zhang Q., Chae H.S., Daubnerova I., Shafer O.T., Choe J.,
RA Kim Y.J.;
RT "A homeostatic sleep-stabilizing pathway in Drosophila composed of the sex
RT peptide receptor and its ligand, the myoinhibitory peptide.";
RL PLoS Biol. 12:E1001974-E1001974(2014).
CC -!- FUNCTION: Ligand for the sex peptide receptor (SPR) (PubMed:20308537,
CC PubMed:20458515, PubMed:25333796). Stabilizes sleep and maintains sleep
CC homeostasis to inhibit the activity of wake-promoting circuits, such as
CC those that involve the pigment dispersing factor (pdf) neurons.
CC Regulated by the circadian clock network and pathways associated with a
CC sleep homeostat (PubMed:25333796). May also have a regulatory role in
CC gut motility (PubMed:11181081). {ECO:0000269|PubMed:20308537,
CC ECO:0000269|PubMed:20458515, ECO:0000269|PubMed:25333796,
CC ECO:0000305|PubMed:11181081}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: In larvae, strongly expressed in the midgut region
CC before and in between the copper cells, and in a group of cells in the
CC posterior part of the larval midgut (PubMed:11181081, PubMed:19319573).
CC Expressed in the neurons of many areas including the subesophageal
CC ganglion/tritocerebrum (SOG), olfactory glomeruli, lateral ventral
CC protocerebrum, mushroom body, the optic lobe medulla and in the
CC antennal lobes (PubMed:11181081, PubMed:20308537,PubMed:21174124).
CC {ECO:0000269|PubMed:11181081, ECO:0000269|PubMed:19319573,
CC ECO:0000269|PubMed:21174124}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout development, with higher
CC expression in larvae than in embryos (at protein level)
CC (PubMed:11181081). Higher expression in males than females, with
CC strongest expression at the third instar larval stage
CC (PubMed:20458515). {ECO:0000269|PubMed:11181081,
CC ECO:0000269|PubMed:20458515}.
CC -!- INDUCTION: Up-regulated by sleep deprivation.
CC {ECO:0000269|PubMed:25333796}.
CC -!- MASS SPECTROMETRY: [Drostatin-B2]: Mass=1091.55; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:21214272};
CC -!- MASS SPECTROMETRY: [Drostatin-B3]: Mass=1603.84; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:21214272};
CC -!- MASS SPECTROMETRY: [Drostatin-B4]: Mass=1374.66; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:21214272};
CC -!- MASS SPECTROMETRY: [Drostatin-B5]: Mass=1253.62; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:21214272};
CC -!- DISRUPTION PHENOTYPE: In both sexes RNA-mediated knockdown results in
CC decreased day- and night-time sleep due to reduced sleep-bout duration.
CC The number of sleep-bouts is not affected.
CC {ECO:0000269|PubMed:25333796}.
CC -!- MISCELLANEOUS: All five Drostatin-B peptides activate SPR with
CC comparable efficiency, however Drostatin-B4 is a slightly more potent
CC ligand. {ECO:0000305|PubMed:20458515}.
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DR EMBL; AF312379; AAK29381.1; -; mRNA.
DR EMBL; AJ291725; CAC17604.1; -; mRNA.
DR EMBL; AE014296; AAF49354.1; -; Genomic_DNA.
DR EMBL; AY118306; AAM48335.1; -; mRNA.
DR PIR; JC7617; JC7617.
DR RefSeq; NP_648971.1; NM_140714.4.
DR AlphaFoldDB; Q9VVF7; -.
DR BioGRID; 65223; 2.
DR STRING; 7227.FBpp0075003; -.
DR PaxDb; Q9VVF7; -.
DR PRIDE; Q9VVF7; -.
DR DNASU; 39933; -.
DR EnsemblMetazoa; FBtr0075241; FBpp0075003; FBgn0036713.
DR GeneID; 39933; -.
DR KEGG; dme:Dmel_CG6456; -.
DR CTD; 4284; -.
DR FlyBase; FBgn0036713; Mip.
DR VEuPathDB; VectorBase:FBgn0036713; -.
DR eggNOG; ENOG502SDZD; Eukaryota.
DR GeneTree; ENSGT00940000176783; -.
DR HOGENOM; CLU_1306026_0_0_1; -.
DR InParanoid; Q9VVF7; -.
DR OMA; NIYMTGH; -.
DR OrthoDB; 1344573at2759; -.
DR PhylomeDB; Q9VVF7; -.
DR BioGRID-ORCS; 39933; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 39933; -.
DR PRO; PR:Q9VVF7; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0036713; Expressed in head capsule and 21 other tissues.
DR Genevisible; Q9VVF7; DM.
DR GO; GO:0005615; C:extracellular space; IDA:FlyBase.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IPI:FlyBase.
DR GO; GO:0005184; F:neuropeptide hormone activity; NAS:FlyBase.
DR GO; GO:0005102; F:signaling receptor binding; IDA:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:FlyBase.
DR GO; GO:1903999; P:negative regulation of eating behavior; IMP:FlyBase.
DR GO; GO:0045968; P:negative regulation of juvenile hormone biosynthetic process; NAS:UniProtKB.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IDA:UniProtKB.
PE 1: Evidence at protein level;
KW Amidation; Cleavage on pair of basic residues; Direct protein sequencing;
KW Neuropeptide; Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PROPEP 25..63
FT /id="PRO_0000001156"
FT PEPTIDE 66..74
FT /note="Drostatin-B1"
FT /evidence="ECO:0000255"
FT /id="PRO_0000001157"
FT PROPEP 78..148
FT /id="PRO_0000001158"
FT PEPTIDE 151..159
FT /note="Drostatin-B2"
FT /evidence="ECO:0000269|PubMed:12171930,
FT ECO:0000269|PubMed:21214272"
FT /id="PRO_0000001159"
FT PEPTIDE 163..175
FT /note="Drostatin-B3"
FT /evidence="ECO:0000269|PubMed:21214272"
FT /id="PRO_0000001160"
FT PEPTIDE 179..189
FT /note="Drostatin-B4"
FT /evidence="ECO:0000269|PubMed:21214272"
FT /id="PRO_0000001161"
FT PEPTIDE 193..202
FT /note="Drostatin-B5"
FT /evidence="ECO:0000269|PubMed:12171930,
FT ECO:0000269|PubMed:21214272"
FT /id="PRO_0000001162"
FT PROPEP 206..211
FT /id="PRO_0000001163"
FT REGION 115..142
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 168..190
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 115..137
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 74
FT /note="Tryptophan amide"
FT /evidence="ECO:0000255"
FT MOD_RES 159
FT /note="Tryptophan amide"
FT /evidence="ECO:0000269|PubMed:12171930,
FT ECO:0000269|PubMed:21214272"
FT MOD_RES 175
FT /note="Tryptophan amide"
FT /evidence="ECO:0000269|PubMed:21214272"
FT MOD_RES 189
FT /note="Tryptophan amide"
FT /evidence="ECO:0000269|PubMed:21214272"
FT MOD_RES 202
FT /note="Tryptophan amide"
FT /evidence="ECO:0000269|PubMed:12171930,
FT ECO:0000269|PubMed:21214272"
FT MUTAGEN 67
FT /note="W->A: Complete loss of activity; when associated
FT with A-74."
FT /evidence="ECO:0000269|PubMed:20308537"
FT MUTAGEN 74
FT /note="W->A: Complete loss of activity; when associated
FT with A-67."
FT /evidence="ECO:0000269|PubMed:20308537"
FT MUTAGEN 195
FT /note="W->A: Reduced activation of SPR; when associated
FT with A-202."
FT /evidence="ECO:0000269|PubMed:20458515"
FT MUTAGEN 202
FT /note="W->A: Reduced activation of SPR."
FT /evidence="ECO:0000269|PubMed:20458515"
SQ SEQUENCE 211 AA; 23412 MW; 616C8BDEA4D4DADB CRC64;
MAHTKTRRTY GFLMVLLILG SACGNLVASG SAGSPPSNEP GGGGLSEQVV LDQLSESDLY
GNNKRAWQSL QSSWGKRSSS GDVSDPDIYM TGHFVPLVIT DGTNTIDWDT FERLASGQSA
QQQQQQPLQQ QSQSGEDFDD LAGEPDVEKR AWKSMNVAWG KRRQAQGWNK FRGAWGKREP
TWNNLKGMWG KRDQWQKLHG GWGKRSQLPS N
