CCHA2_DROME
ID CCHA2_DROME Reviewed; 136 AA.
AC Q8SXL2; Q9VFV7;
DT 09-DEC-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Neuropeptide CCHamide-2 {ECO:0000303|PubMed:21110953};
DE Flags: Precursor;
GN Name=CCHa2 {ECO:0000312|FlyBase:FBgn0038147};
GN ORFNames=CG14375 {ECO:0000312|FlyBase:FBgn0038147};
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|EMBL:AAL90314.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 27-39, FUNCTION, MASS
RP SPECTROMETRY, AMIDATION AT HIS-39, AND DISULFIDE BOND.
RX PubMed=23293632; DOI=10.3389/fendo.2012.00177;
RA Ida T., Takahashi T., Tominaga H., Sato T., Sano H., Kume K., Ozaki M.,
RA Hiraguchi T., Shiotani H., Terajima S., Nakamura Y., Mori K., Yoshida M.,
RA Kato J., Murakami N., Miyazato M., Kangawa K., Kojima M.;
RT "Isolation of the bioactive peptides CCHamide-1 and CCHamide-2 from
RT Drosophila and their putative role in appetite regulation as ligands for G
RT protein-coupled receptors.";
RL Front. Endocrinol. 3:177-177(2012).
RN [2] {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 [3] {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 [4] {ECO:0000312|EMBL:AAL90314.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAL90314.1};
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 (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP PROTEIN SEQUENCE OF 27-39, IDENTIFICATION BY MASS SPECTROMETRY, MASS
RP SPECTROMETRY, AMIDATION AT HIS-39, AND DISULFIDE BOND.
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 [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=21110953; DOI=10.1016/j.bbrc.2010.11.089;
RA Hansen K.K., Hauser F., Williamson M., Weber S.B., Grimmelikhuijzen C.J.;
RT "The Drosophila genes CG14593 and CG30106 code for G-protein-coupled
RT receptors specifically activated by the neuropeptides CCHamide-1 and
RT CCHamide-2.";
RL Biochem. Biophys. Res. Commun. 404:184-189(2011).
RN [7] {ECO:0000305}
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=Canton-S;
RX PubMed=24098432; DOI=10.1371/journal.pone.0076131;
RA Li S., Torre-Muruzabal T., Soegaard K.C., Ren G.R., Hauser F.,
RA Engelsen S.M., Poedenphanth M.D., Desjardins A., Grimmelikhuijzen C.J.;
RT "Expression patterns of the Drosophila neuropeptide CCHamide-2 and its
RT receptor may suggest hormonal signaling from the gut to the brain.";
RL PLoS ONE 8:E76131-E76131(2013).
RN [8] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=24850274; DOI=10.1007/s00441-014-1880-2;
RA Veenstra J.A., Ida T.;
RT "More Drosophila enteroendocrine peptides: Orcokinin B and the CCHamides 1
RT and 2.";
RL Cell Tissue Res. 357:607-621(2014).
RN [9] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=26168160; DOI=10.1371/journal.pone.0133017;
RA Ren G.R., Hauser F., Rewitz K.F., Kondo S., Engelbrecht A.F.,
RA Didriksen A.K., Schjoett S.R., Sembach F.E., Li S., Soegaard K.C.,
RA Soendergaard L., Grimmelikhuijzen C.J.;
RT "CCHamide-2 is an orexigenic brain-gut peptide in Drosophila.";
RL PLoS ONE 10:E0133017-E0133017(2015).
RN [10] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26020940; DOI=10.1371/journal.pgen.1005209;
RA Sano H., Nakamura A., Texada M.J., Truman J.W., Ishimoto H., Kamikouchi A.,
RA Nibu Y., Kume K., Ida T., Kojima M.;
RT "The nutrient-responsive hormone CCHamide-2 controls growth by regulating
RT insulin-like peptides in the brain of Drosophila melanogaster.";
RL PLoS Genet. 11:E1005209-E1005209(2015).
RN [11]
RP ERRATUM OF PUBMED:26020940.
RX PubMed=26394035; DOI=10.1371/journal.pgen.1005481;
RA Sano H., Nakamura A., Texada M.J., Truman J.W., Ishimoto H., Kamikouchi A.,
RA Nibu Y., Kume K., Ida T., Kojima M.;
RL PLoS Genet. 11:E1005481-E1005481(2015).
CC -!- FUNCTION: Ligand for the CCHamide-2 receptor CCHa2-R (PubMed:23293632,
CC PubMed:21110953). In one study, shown to be an orexigenic peptide which
CC induces appetite and stimulates food intake, leading to the release of
CC insulin-like peptides which stimulate growth (PubMed:26168160). In
CC another study, shown to be a nutrient-sensitive peptide derived from
CC peripheral tissues which controls growth by directly regulating the
CC production and release of insulin-like peptides (PubMed:26020940).
CC {ECO:0000269|PubMed:21110953, ECO:0000269|PubMed:23293632,
CC ECO:0000269|PubMed:26020940, ECO:0000269|PubMed:26168160}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in endocrine cells of the larval midgut
CC (at protein level) (PubMed:24098432, PubMed:24850274). Also expressed
CC in endocrine cells of the midgut of adult males and females (at protein
CC level) (PubMed:24098432). In the midgut, expression occurs mainly in
CC the anterior region (at protein level) (PubMed:24098432). In the larval
CC central nervous system, expressed in about 40 neurons in the brain
CC hemispheres and ventral nerve cord (at protein level)
CC (PubMed:24098432). Highly expressed in larval and adult gut with low
CC levels in larval and adult brain (PubMed:24098432). Very little
CC expression in the larval fat body (PubMed:26168160). However, another
CC study shows high levels of expression in the larval fat body as well as
CC the larval gut with low levels in the larval central nervous system
CC (PubMed:26020940). {ECO:0000269|PubMed:24098432,
CC ECO:0000269|PubMed:24850274, ECO:0000269|PubMed:26020940,
CC ECO:0000269|PubMed:26168160}.
CC -!- DEVELOPMENTAL STAGE: Very low expression in eggs. Expression increases
CC during the first instar larval stage, decreases gradually during the
CC second and third instar larval stages and in pupae and increases in
CC adults. {ECO:0000269|PubMed:24098432}.
CC -!- INDUCTION: Repressed in larvae by starvation for 18 hours with levels
CC recovering when larvae are refed with yeast or glucose.
CC {ECO:0000269|PubMed:26020940}.
CC -!- MASS SPECTROMETRY: Mass=1347.69; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:23293632};
CC -!- MASS SPECTROMETRY: Mass=1348.53; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:21214272};
CC -!- DISRUPTION PHENOTYPE: Reduced food intake in adults and larvae, reduced
CC locomotor activity, delayed development with mutants taking 200 hours
CC to develop from egg to pupa compared to 130 hours for wild-type flies,
CC reduced levels of the insulin-like peptides Ilp2 and Ilp3, and reduced
CC wing size (PubMed:26168160). Reduced levels of insulin-like peptide
CC Ilp5 and reduced body weight of mid-third instar larvae
CC (PubMed:26020940). {ECO:0000269|PubMed:26020940,
CC ECO:0000269|PubMed:26168160}.
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DR EMBL; AE014297; AAF54942.2; -; Genomic_DNA.
DR EMBL; AE014297; ADV37307.1; -; Genomic_DNA.
DR EMBL; AE014297; ADV37308.1; -; Genomic_DNA.
DR EMBL; AY089576; AAL90314.1; -; mRNA.
DR RefSeq; NP_001189216.1; NM_001202287.1.
DR RefSeq; NP_001189217.1; NM_001202288.1.
DR RefSeq; NP_650285.1; NM_142028.3.
DR AlphaFoldDB; Q8SXL2; -.
DR STRING; 7227.FBpp0082230; -.
DR PaxDb; Q8SXL2; -.
DR DNASU; 41648; -.
DR EnsemblMetazoa; FBtr0082762; FBpp0082230; FBgn0038147.
DR EnsemblMetazoa; FBtr0303262; FBpp0292354; FBgn0038147.
DR EnsemblMetazoa; FBtr0303263; FBpp0292355; FBgn0038147.
DR GeneID; 41648; -.
DR KEGG; dme:Dmel_CG14375; -.
DR UCSC; CG14375-RA; d. melanogaster.
DR CTD; 41648; -.
DR FlyBase; FBgn0038147; CCHa2.
DR VEuPathDB; VectorBase:FBgn0038147; -.
DR eggNOG; ENOG502SFM9; Eukaryota.
DR HOGENOM; CLU_1898380_0_0_1; -.
DR InParanoid; Q8SXL2; -.
DR OMA; QAKKGCQ; -.
DR OrthoDB; 1436024at2759; -.
DR PhylomeDB; Q8SXL2; -.
DR BioGRID-ORCS; 41648; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 41648; -.
DR PRO; PR:Q8SXL2; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0038147; Expressed in arthropod fat body and 25 other tissues.
DR ExpressionAtlas; Q8SXL2; baseline and differential.
DR GO; GO:0005615; C:extracellular space; IDA:FlyBase.
DR GO; GO:0005184; F:neuropeptide hormone activity; IDA:FlyBase.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IDA:FlyBase.
DR InterPro; IPR037729; CCHa1/2.
DR PANTHER; PTHR35980; PTHR35980; 1.
PE 1: Evidence at protein level;
KW Amidation; Direct protein sequencing; Disulfide bond; Hormone;
KW Neuropeptide; Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000269|PubMed:21214272,
FT ECO:0000269|PubMed:23293632"
FT PEPTIDE 27..39
FT /note="Neuropeptide CCHamide-2"
FT /evidence="ECO:0000269|PubMed:21214272,
FT ECO:0000269|PubMed:23293632"
FT /id="PRO_0000435027"
FT PROPEP 43..136
FT /evidence="ECO:0000269|PubMed:21214272,
FT ECO:0000269|PubMed:23293632"
FT /id="PRO_0000435028"
FT REGION 42..78
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 39
FT /note="Histidine amide"
FT /evidence="ECO:0000269|PubMed:21214272,
FT ECO:0000269|PubMed:23293632"
FT DISULFID 28..35
FT /evidence="ECO:0000269|PubMed:21214272,
FT ECO:0000269|PubMed:23293632"
SQ SEQUENCE 136 AA; 14410 MW; C6EA5FC76303EF8F CRC64;
MKSTISLLLV VICTVVLAAQ QSQAKKGCQA YGHVCYGGHG KRSLSPGSGS GTGVGGGMGE
AASGGQEPDY VRPNGLLPMM APNEQVPLEG DFNDYPARQV LYKIMKSWFN RPRRPASRLG
ELDYPLANSA ELNGVN
