ID DIMM_DROME Reviewed; 390 AA. AC B6VQA1; Q0IGR9; Q9VID2; DT 19-OCT-2011, integrated into UniProtKB/Swiss-Prot. DT 16-DEC-2008, sequence version 1. DT 03-MAY-2023, entry version 101. DE RecName: Full=Protein dimmed {ECO:0000312|EMBL:AAF53991.1}; GN Name=dimm; ORFNames=CG8667; 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] {ECO:0000312|EMBL:AAF53991.1} 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 [2] {ECO:0000305, ECO:0000312|EMBL:AAF53991.1} 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 [3] {ECO:0000312|EMBL:ABI34200.4} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Berkeley; RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.E.; RL Submitted (JUN-2010) to the EMBL/GenBank/DDBJ databases. RN [4] {ECO:0000305} RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=10973473; DOI=10.1073/pnas.170301897; RA Moore A.W., Barbel S., Jan L.Y., Jan Y.N.; RT "A genomewide survey of basic helix-loop-helix factors in Drosophila."; RL Proc. Natl. Acad. Sci. U.S.A. 97:10436-10441(2000). RN [5] {ECO:0000305} RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RC TISSUE=Head {ECO:0000269|PubMed:15748845}; RX PubMed=12642483; DOI=10.1242/dev.00404; RA Hewes R.S., Park D., Gauthier S.A., Schaefer A.M., Taghert P.H.; RT "The bHLH protein Dimmed controls neuroendocrine cell differentiation in RT Drosophila."; RL Development 130:1771-1781(2003). RN [6] {ECO:0000305} RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=15081360; DOI=10.1016/j.ydbio.2004.01.015; RA Park D., Han M., Kim Y.C., Han K.A., Taghert P.H.; RT "Ap-let neurons--a peptidergic circuit potentially controlling ecdysial RT behavior in Drosophila."; RL Dev. Biol. 269:95-108(2004). RN [7] {ECO:0000305} RP FUNCTION, SUBUNIT, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=15748845; DOI=10.1016/j.neuron.2005.01.026; RA Allan D.W., Park D., St Pierre S.E., Taghert P.H., Thor S.; RT "Regulators acting in combinatorial codes also act independently in single RT differentiating neurons."; RL Neuron 45:689-700(2005). RN [8] {ECO:0000305} RP FUNCTION. RX PubMed=16651547; DOI=10.1242/jeb.02202; RA Gauthier S.A., Hewes R.S.; RT "Transcriptional regulation of neuropeptide and peptide hormone expression RT by the Drosophila dimmed and cryptocephal genes."; RL J. Exp. Biol. 209:1803-1815(2006). RN [9] {ECO:0000305} RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL RP STAGE. RC TISSUE=Head {ECO:0000269|PubMed:15081360}; RX PubMed=16870731; DOI=10.1523/jneurosci.1759-06.2006; RA Hewes R.S., Gu T., Brewster J.A., Qu C., Zhao T.; RT "Regulation of secretory protein expression in mature cells by DIMM, a RT basic helix-loop-helix neuroendocrine differentiation factor."; RL J. Neurosci. 26:7860-7869(2006). RN [10] {ECO:0000305} RP FUNCTION, SUBUNIT, DOMAIN, AND MUTAGENESIS OF 164-ARG--ARG-166. RX PubMed=17967878; DOI=10.1128/mcb.01104-07; RA Park D., Shafer O.T., Shepherd S.P., Suh H., Trigg J.S., Taghert P.H.; RT "The Drosophila basic helix-loop-helix protein DIMMED directly activates RT PHM, a gene encoding a neuropeptide-amidating enzyme."; RL Mol. Cell. Biol. 28:410-421(2008). RN [11] {ECO:0000305} RP FUNCTION. RX PubMed=20045330; DOI=10.1016/j.cub.2009.11.065; RA Hamanaka Y., Park D., Yin P., Annangudi S.P., Edwards T.N., Sweedler J., RA Meinertzhagen I.A., Taghert P.H.; RT "Transcriptional orchestration of the regulated secretory pathway in RT neurons by the bHLH protein DIMM."; RL Curr. Biol. 20:9-18(2010). CC -!- FUNCTION: Transcription factor that regulates neurosecretory (NS) cell CC function and neuroendocrine cell fate. Acts as a master regulator of CC common NS functions such as Phm expression and neuropeptide production. CC Plays a role as a regulator of peptide-containing large dense-core CC vesicle (LDCV) production and peptidergic cell differentiation. CC Controls transcription of FMRFamide in Tv neuronal cells and Fur1 in CC Ap-let cells (Tvb and dorsal apterous cells). Also required for up- CC regulation of Phm in Tv and Ap-let cells, and expression of three CC neuropeptide genes, Ms, FMRFamide and Lk. Influences both regulated and CC constitutive secretory activity in neuroendocrine cells at embryonic CC and postembryonic level. Loss of function studies show reduced cellular CC levels of various neuropeptides and neuropeptide biosynthetic enzymes. CC {ECO:0000269|PubMed:12642483, ECO:0000269|PubMed:15081360, CC ECO:0000269|PubMed:15748845, ECO:0000269|PubMed:16651547, CC ECO:0000269|PubMed:16870731, ECO:0000269|PubMed:17967878, CC ECO:0000269|PubMed:20045330}. CC -!- SUBUNIT: Forms homodimers via the bHLH domain. These dimers bind the CC core E-box sequence. {ECO:0000269|PubMed:15748845, CC ECO:0000269|PubMed:17967878}. CC -!- INTERACTION: CC B6VQA1; P23792: disco; NbExp=3; IntAct=EBI-166061, EBI-152064; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16870731}. CC -!- TISSUE SPECIFICITY: Detected in the developing nervous system in the CC bilateral domains in the cephalic region that later on forms part of CC the ring gland. Concomitantly expressed in the larval central nervous CC system (CNS), including the dorsal chain neurons as well as several CC bilateral clusters of neurons: large, midline protocerebral brain cells CC (MC), lateral protocerebral brain cells (LC), ventral subesophageal CC neurons (SE) and lateral abdominal neurons, and the transverse nerves. CC Outside the CNS, detected in at least three classes of endocrine cells: CC intrinsic cells of the corpora cardiaca, midgut cells, the Inka cells, CC lateral Bipolar neurons associated with the segmental transverse nerve, CC and several peptidergic cells of the enteric nervous system. Expressed CC only in central and peripheral neuroendocrine secretory cells and CC neurosecretory neurons but not in sensory or motor neurons. CC {ECO:0000269|PubMed:10973473, ECO:0000269|PubMed:12642483, CC ECO:0000269|PubMed:15081360, ECO:0000269|PubMed:15748845, CC ECO:0000269|PubMed:16870731}. CC -!- DEVELOPMENTAL STAGE: First detected in the embryonic ectoderm at early CC stage 11, but this expression is transient. Zygotic expression is first CC detected in stage 12 embryos and cytoplasmic expression is detected in CC many cells around stage 14. Embryonic cells maintain expression CC throughout their lifetime and expression continues into hatchling CC larvae less than 24 hours old. {ECO:0000269|PubMed:10973473, CC ECO:0000269|PubMed:12642483, ECO:0000269|PubMed:15748845, CC ECO:0000269|PubMed:16870731}. CC -!- DOMAIN: The basic domain binds to the canonical E-box (5'-CANNTG-3'), CC with a particular preference for TA relative to AT or CG in the CC variable central nucleotide positions. {ECO:0000269|PubMed:17967878}. CC -!- SEQUENCE CAUTION: CC Sequence=ABI34200.4; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=ABI34232.3; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; 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; AE014134; AAF53991.1; -; Genomic_DNA. DR EMBL; BT028819; ABI34200.4; ALT_INIT; mRNA. DR EMBL; BT028851; ABI34232.3; ALT_INIT; mRNA. DR RefSeq; NP_001260674.1; NM_001273745.1. DR RefSeq; NP_523611.1; NM_078887.3. DR AlphaFoldDB; B6VQA1; -. DR SMR; B6VQA1; -. DR BioGRID; 61353; 41. DR IntAct; B6VQA1; 32. DR STRING; 7227.FBpp0305546; -. DR GlyCosmos; B6VQA1; 7 sites, No reported glycans. DR GlyGen; B6VQA1; 7 sites. DR PaxDb; B6VQA1; -. DR DNASU; 35404; -. DR EnsemblMetazoa; FBtr0081514; FBpp0081042; FBgn0023091. DR EnsemblMetazoa; FBtr0333354; FBpp0305546; FBgn0023091. DR GeneID; 35404; -. DR KEGG; dme:Dmel_CG8667; -. DR UCSC; CG8667-RA; d. melanogaster. DR AGR; FB:FBgn0023091; -. DR CTD; 35404; -. DR FlyBase; FBgn0023091; dimm. DR VEuPathDB; VectorBase:FBgn0023091; -. DR eggNOG; KOG3898; Eukaryota. DR HOGENOM; CLU_704527_0_0_1; -. DR InParanoid; B6VQA1; -. DR OMA; NGGAFDC; -. DR OrthoDB; 5406208at2759; -. DR PhylomeDB; B6VQA1; -. DR SignaLink; B6VQA1; -. DR BioGRID-ORCS; 35404; 0 hits in 1 CRISPR screen. DR GenomeRNAi; 35404; -. DR PRO; PR:B6VQA1; -. DR Proteomes; UP000000803; Chromosome 2L. DR Bgee; FBgn0023091; Expressed in embryonic/larval neuron (Drosophila) and 17 other tissues. DR ExpressionAtlas; B6VQA1; baseline and differential. DR Genevisible; B6VQA1; DM. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IDA:FlyBase. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central. DR GO; GO:0070888; F:E-box binding; IBA:GO_Central. DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro. DR GO; GO:0061564; P:axon development; IBA:GO_Central. DR GO; GO:0061101; P:neuroendocrine cell differentiation; IMP:FlyBase. DR GO; GO:0048663; P:neuron fate commitment; IBA:GO_Central. DR GO; GO:0046887; P:positive regulation of hormone secretion; IMP:FlyBase. DR GO; GO:0002793; P:positive regulation of peptide secretion; IMP:FlyBase. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:FlyBase. DR GO; GO:0006355; P:regulation of DNA-templated transcription; ISS:FlyBase. DR GO; GO:0007423; P:sensory organ development; IBA:GO_Central. DR GO; GO:0007419; P:ventral cord development; HMP:FlyBase. DR CDD; cd19712; bHLH_TS_dimmed_like; 1. DR Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1. DR InterPro; IPR011598; bHLH_dom. DR InterPro; IPR036638; HLH_DNA-bd_sf. DR PANTHER; PTHR19290; BASIC HELIX-LOOP-HELIX PROTEIN NEUROGENIN-RELATED; 1. DR PANTHER; PTHR19290:SF160; CLASS A BASIC HELIX-LOOP-HELIX PROTEIN 15; 1. DR Pfam; PF00010; HLH; 1. DR SMART; SM00353; HLH; 1. DR SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 1. DR PROSITE; PS50888; BHLH; 1. PE 1: Evidence at protein level; KW Cytoplasm; Developmental protein; Differentiation; DNA-binding; KW Glycoprotein; Reference proteome; Transcription; Transcription regulation. FT CHAIN 1..390 FT /note="Protein dimmed" FT /id="PRO_0000412993" FT DOMAIN 156..208 FT /note="bHLH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981" FT REGION 24..163 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 312..339 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 24..101 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 108..143 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 146..163 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 61 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 128 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 133 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 140 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 207 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 237 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 347 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT MUTAGEN 164..166 FT /note="RER->GGG: Reduced DNA-binding activity." FT /evidence="ECO:0000269|PubMed:17967878" SQ SEQUENCE 390 AA; 40980 MW; C877F99770EDDCF8 CRC64; MDATQLTELM GSHDFMQLQH QLHHNNNNYN TDGHNGLSSE SAEGSSRPVR RATRRTSQLS NNTYDLEMTD SSSQSDDTSG GGGSSNGGGS TTNTGHPSGC SLGGQGPSGR GRVQQASSGA CPSTIAPNST SSNSSNANGN ASRRRKGALN AKERNMRRLE SNERERMRMH SLNDAFQSLR EVIPHVEMER RLSKIETLTL AKNYIINLTH IILSKRNEEA AALELNSGAV GGVLLSNLSS ESGGPVASGI PANSNAATIC FEDTLASGGA FDCAILAATD GSLLNAATVT TSPAMQSIQS QAIHLQTPME QQQQQASHLP HHQQAMHGHG HLGASIQSQQ QPSLVLNGTT SVGLGIGIGV GVGVGVGVCN NAPSFADIND NFDEPFREFL //