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 05-JUL-2017, entry version 109. 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; OC Pterygota; Neoptera; Holometabola; Diptera; Brachycera; Muscomorpha; OC Ephydroidea; 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., RA Ozaki M., Hiraguchi T., Shiotani H., Terajima S., Nakamura Y., RA Mori K., Yoshida M., Kato J., Murakami N., Miyazato M., Kangawa K., RA 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 RT for G 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., RA Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., RA Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., RA Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., RA Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., RA Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., RA Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., RA Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., RA Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., RA de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., RA Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., RA Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., RA Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., RA 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., RA Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., RA Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., RA Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., RA Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., RA Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., RA Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., RA Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., RA Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., RA Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., RA Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., RA 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., RA Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., RA Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., RA Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., RA Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., RA Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., RA Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., 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., RA Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., RA Lewis S.E.; RT "Annotation of the Drosophila melanogaster euchromatic genome: a RT systematic 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., RA Champe M., Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., RA George R., Gonzalez M., Guarin H., Kronmiller B., Li P., Liao G., RA Miranda A., Mungall C.J., Nunoo J., Pacleb J., Paragas V., Park S., RA Patel S., Phouanenavong S., Wan K., Yu C., Lewis S.E., Rubin G.M., RA 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., RA Wegener C.; RT "Peptidomics and peptide hormone processing in the Drosophila RT 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., RA 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., RA 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 RT CCHamides 1 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., RA Kamikouchi A., Nibu Y., Kume K., Ida T., Kojima M.; RT "The nutrient-responsive hormone CCHamide-2 controls growth by RT regulating insulin-like peptides in the brain of Drosophila RT melanogaster."; RL PLoS Genet. 11:E1005209-E1005209(2015). RN [11] RP ERRATUM. RX PubMed=26394035; DOI=10.1371/journal.pgen.1005481; RA Sano H., Nakamura A., Texada M.J., Truman J.W., Ishimoto H., RA Kamikouchi A., 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 CC (PubMed:23293632, PubMed:21110953). In one study, shown to be an CC orexigenic peptide which induces appetite and stimulates food CC intake, leading to the release of insulin-like peptides which CC stimulate growth (PubMed:26168160). In another study, shown to be CC a nutrient-sensitive peptide derived from peripheral tissues which CC controls growth by directly regulating the production and release CC 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 CC midgut (at protein level) (PubMed:24098432, PubMed:24850274). Also CC expressed in endocrine cells of the midgut of adult males and CC females (at protein level) (PubMed:24098432). In the midgut, CC expression occurs mainly in the anterior region (at protein level) CC (PubMed:24098432). In the larval central nervous system, expressed CC in about 40 neurons in the brain hemispheres and ventral nerve CC cord (at protein level) (PubMed:24098432). Highly expressed in CC larval and adult gut with low levels in larval and adult brain CC (PubMed:24098432). Very little expression in the larval fat body CC (PubMed:26168160). However, another study shows high levels of CC expression in the larval fat body as well as the larval gut with CC low levels in the larval central nervous system (PubMed:26020940). CC {ECO:0000269|PubMed:24098432, ECO:0000269|PubMed:24850274, CC ECO:0000269|PubMed:26020940, ECO:0000269|PubMed:26168160}. CC -!- DEVELOPMENTAL STAGE: Very low expression in eggs. Expression CC increases during the first instar larval stage, decreases CC gradually during the second and third instar larval stages and in CC pupae and increases in adults. {ECO:0000269|PubMed:24098432}. CC -!- INDUCTION: Repressed in larvae by starvation for 18 hours with CC levels recovering when larvae are refed with yeast or glucose. CC {ECO:0000269|PubMed:26020940}. CC -!- MASS SPECTROMETRY: Mass=1347.69; Method=MALDI; Range=27-39; CC Evidence={ECO:0000269|PubMed:23293632}; CC -!- MASS SPECTROMETRY: Mass=1348.53; Method=MALDI; Range=27-39; CC Evidence={ECO:0000269|PubMed:21214272}; CC -!- DISRUPTION PHENOTYPE: Reduced food intake in adults and larvae, CC reduced locomotor activity, delayed development with mutants CC taking 200 hours to develop from egg to pupa compared to 130 hours CC for wild-type flies, reduced levels of the insulin-like peptides CC Ilp2 and Ilp3, and reduced wing size (PubMed:26168160). Reduced CC levels of insulin-like peptide Ilp5 and reduced body weight of CC mid-third instar larvae (PubMed:26020940). CC {ECO:0000269|PubMed:26020940, ECO:0000269|PubMed:26168160}. 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; 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 UniGene; Dm.20712; -. DR STRING; 7227.FBpp0082230; -. DR PaxDb; Q8SXL2; -. DR PRIDE; Q8SXL2; -. 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 eggNOG; ENOG410KBS1; Eukaryota. DR eggNOG; ENOG4110MZY; LUCA. DR OMA; QSQAKKG; -. DR OrthoDB; EOG091G19R6; -. DR PhylomeDB; Q8SXL2; -. DR GenomeRNAi; 41648; -. DR PRO; PR:Q8SXL2; -. DR Proteomes; UP000000803; Chromosome 3R. DR Bgee; FBgn0038147; -. DR ExpressionAtlas; Q8SXL2; 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. PE 1: Evidence at protein level; KW Amidation; Complete proteome; Direct protein sequencing; KW Disulfide bond; Hormone; Neuropeptide; Reference proteome; Secreted; KW Signal. FT SIGNAL 1 24 {ECO:0000269|PubMed:21214272, FT ECO:0000269|PubMed:23293632}. FT PEPTIDE 27 39 Neuropeptide CCHamide-2. FT {ECO:0000269|PubMed:21214272, FT ECO:0000269|PubMed:23293632}. FT /FTId=PRO_0000435027. FT PROPEP 43 136 {ECO:0000269|PubMed:21214272, FT ECO:0000269|PubMed:23293632}. FT /FTId=PRO_0000435028. FT MOD_RES 39 39 Histidine amide. FT {ECO:0000269|PubMed:21214272, FT ECO:0000269|PubMed:23293632}. FT DISULFID 28 35 {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 //