DPN_DROME
ID DPN_DROME Reviewed; 435 AA.
AC Q26263; Q9V384;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2001, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Protein deadpan;
GN Name=dpn; ORFNames=CG8704;
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, SUBCELLULAR LOCATION, DEVELOPMENTAL
RP STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=1427077; DOI=10.1101/gad.6.11.2137;
RA Bier E., Vaessin H., Younger-Shepherd S., Jan L.Y., Jan Y.N.;
RT "Deadpan, an essential pan-neural gene in Drosophila, encodes a helix-loop-
RT helix protein similar to the hairy gene product.";
RL Genes Dev. 6:2137-2151(1992).
RN [2]
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
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 [5]
RP FUNCTION, INTERACTION WITH GRO, AND DOMAIN WRPW MOTIF.
RX PubMed=8001118; DOI=10.1016/0092-8674(94)90070-1;
RA Paroush Z., Finley R.L. Jr., Kidd T., Wainwright S.M., Ingham P.W.,
RA Brent R., Ish-Horowicz D.;
RT "Groucho is required for Drosophila neurogenesis, segmentation, and sex
RT determination and interacts directly with hairy-related bHLH proteins.";
RL Cell 79:805-815(1994).
RN [6]
RP FUNCTION, SUBUNIT, AND INTERACTION WITH SISA AND DA.
RX PubMed=7651341; DOI=10.1007/bf02190799;
RA Liu Y., Belote J.M.;
RT "Protein-protein interactions among components of the Drosophila primary
RT sex determination signal.";
RL Mol. Gen. Genet. 248:182-189(1995).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407; SER-408 AND SER-411, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21262215; DOI=10.1016/j.ydbio.2011.01.019;
RA San-Juan B.P., Baonza A.;
RT "The bHLH factor deadpan is a direct target of Notch signaling and
RT regulates neuroblast self-renewal in Drosophila.";
RL Dev. Biol. 352:70-82(2011).
RN [9]
RP FUNCTION, SUBUNIT, INTERACTION WITH E(SPL)MGAMMA-HLH, DEVELOPMENTAL STAGE,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=22357926; DOI=10.1242/dev.071779;
RA Zacharioudaki E., Magadi S.S., Delidakis C.;
RT "bHLH-O proteins are crucial for Drosophila neuroblast self-renewal and
RT mediate Notch-induced overproliferation.";
RL Development 139:1258-1269(2012).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23056424; DOI=10.1371/journal.pone.0046724;
RA Zhu S., Wildonger J., Barshow S., Younger S., Huang Y., Lee T.;
RT "The bHLH repressor Deadpan regulates the self-renewal and specification of
RT Drosophila larval neural stem cells independently of Notch.";
RL PLoS ONE 7:E46724-E46724(2012).
RN [11]
RP FUNCTION.
RX PubMed=24618901; DOI=10.7554/elife.01906;
RA Koe C.T., Li S., Rossi F., Wong J.J., Wang Y., Zhang Z., Chen K., Aw S.S.,
RA Richardson H.E., Robson P., Sung W.K., Yu F., Gonzalez C., Wang H.;
RT "The Brm-HDAC3-Erm repressor complex suppresses dedifferentiation in
RT Drosophila type II neuroblast lineages.";
RL Elife 3:E01906-E01906(2014).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28899667; DOI=10.1016/j.ydbio.2017.09.011;
RA Li X., Chen R., Zhu S.;
RT "bHLH-O proteins balance the self-renewal and differentiation of Drosophila
RT neural stem cells by regulating Earmuff expression.";
RL Dev. Biol. 431:239-251(2017).
CC -!- FUNCTION: Transcriptional repressor of genes that require a bHLH
CC protein for their transcription (PubMed:1427077, PubMed:28899667,
CC PubMed:24618901). In the larval brain, required to maintain the self-
CC renewal and identity of type II neuroblasts by regulating the
CC expression of the transcriptional repressor erm together with other
CC self-renewal transcriptional repressors such as klu and E(spl)mgamma-
CC HLH (PubMed:28899667, PubMed:23056424, PubMed:21262215,
CC PubMed:24618901, PubMed:22357926). As part of its role in neuroblasts
CC development, has been shown to be a direct target of the Notch
CC signaling pathway, however might work also independently of N/Notch
CC (PubMed:21262215, PubMed:22357926, PubMed:23056424). In the developing
CC larval and pupal brain, required for mushroom body differentiation
CC (PubMed:22357926). Involved in sex determination and SXL transcription
CC repression when in complex with the corepressor protein Groucho
CC (PubMed:8001118, PubMed:7651341). {ECO:0000269|PubMed:1427077,
CC ECO:0000269|PubMed:21262215, ECO:0000269|PubMed:22357926,
CC ECO:0000269|PubMed:23056424, ECO:0000269|PubMed:24618901,
CC ECO:0000269|PubMed:28899667, ECO:0000269|PubMed:7651341,
CC ECO:0000269|PubMed:8001118}.
CC -!- SUBUNIT: Homodimer (PubMed:22357926, PubMed:7651341). Heterodimer with
CC E(spl)mgamma-HLH and E(spl) (PubMed:22357926). Transcription repression
CC requires formation of a complex with the corepressor protein Groucho
CC (PubMed:8001118). Interacts (via bHLH motif) with sisA
CC (PubMed:7651341). Interacts with da (PubMed:7651341).
CC {ECO:0000269|PubMed:22357926, ECO:0000269|PubMed:7651341,
CC ECO:0000269|PubMed:8001118}.
CC -!- INTERACTION:
CC Q26263; Q86PA6: da; NbExp=3; IntAct=EBI-144502, EBI-367267;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:1427077}.
CC -!- DEVELOPMENTAL STAGE: In larvae, expressed in primary neural precursors
CC (at protein level) (PubMed:1427077). In leg imaginal disks, expressed
CC in stripes at the distal edge of each leg segment primordium (at
CC protein level) (PubMed:1427077). In stage 9 embryo, detected in the
CC first neuroblasts delaminating from the ectoderm (at protein level)
CC (PubMed:22357926). In newly hatched larvae, detected in dividing
CC neuroblasts (at protein level) (PubMed:22357926). First detected in
CC preblastoderm cycle 12 in all nuclei (PubMed:1427077). During middle to
CC late cycle 13, expressed in eight stripes that overlap those of the
CC hairy protein (PubMed:1427077). {ECO:0000269|PubMed:1427077,
CC ECO:0000269|PubMed:22357926}.
CC -!- DOMAIN: Has a particular type of basic domain (presence of a helix-
CC interrupting proline) that binds to the N-box (CACNAG), rather than the
CC canonical E-box (CANNTG). {ECO:0000269|PubMed:8001118}.
CC -!- DOMAIN: The C-terminal WRPW motif is a transcriptional repression
CC domain necessary for the interaction with Groucho, a transcriptional
CC corepressor recruited to specific target DNA by Hairy-related proteins.
CC {ECO:0000269|PubMed:8001118}.
CC -!- DISRUPTION PHENOTYPE: Lethal at different developmental stages
CC (PubMed:1427077). In late third instar larval brains, results in a
CC complete absence of type II neuroblasts (NBs) and a reduction of type I
CC NBs; after larval hatching, loss of neuroblasts in the ventral nerve
CC cord and specific loss of type I neuroblasts within 48 hours; in the
CC pupae, results in a premature loss of mushroom body NBs
CC (PubMed:23056424, PubMed:21262215, PubMed:22357926). Escaper adult
CC flies display weak motor activity, lethargic behavior, and shortened
CC life span (PubMed:1427077). RNAi-mediated knockdown of the protein in
CC type II neuroblasts lineage results in an increase in the number of
CC type II neuroblasts (PubMed:28899667). Simultaneous RNAi-mediated
CC knockdown of the ETS protein pnt or the transcriptional repressor Erm
CC restores normal neuroblast numbers (PubMed:28899667).
CC {ECO:0000269|PubMed:1427077, ECO:0000269|PubMed:21262215,
CC ECO:0000269|PubMed:22357926, ECO:0000269|PubMed:23056424,
CC ECO:0000269|PubMed:28899667}.
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DR EMBL; S48025; AAB24149.1; -; mRNA.
DR EMBL; AE013599; AAF59113.1; -; Genomic_DNA.
DR EMBL; AY071330; AAL48952.1; -; mRNA.
DR RefSeq; NP_476923.1; NM_057575.3.
DR AlphaFoldDB; Q26263; -.
DR SMR; Q26263; -.
DR BioGRID; 61654; 26.
DR DIP; DIP-19436N; -.
DR ELM; Q26263; -.
DR IntAct; Q26263; 9.
DR STRING; 7227.FBpp0087879; -.
DR iPTMnet; Q26263; -.
DR PaxDb; Q26263; -.
DR EnsemblMetazoa; FBtr0088803; FBpp0087879; FBgn0010109.
DR GeneID; 35800; -.
DR KEGG; dme:Dmel_CG8704; -.
DR UCSC; CG8704-RA; d. melanogaster.
DR CTD; 35800; -.
DR FlyBase; FBgn0010109; dpn.
DR VEuPathDB; VectorBase:FBgn0010109; -.
DR eggNOG; KOG4304; Eukaryota.
DR GeneTree; ENSGT00940000166705; -.
DR HOGENOM; CLU_036128_0_0_1; -.
DR InParanoid; Q26263; -.
DR OMA; RYVSQMD; -.
DR OrthoDB; 1427802at2759; -.
DR PhylomeDB; Q26263; -.
DR SignaLink; Q26263; -.
DR BioGRID-ORCS; 35800; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 35800; -.
DR PRO; PR:Q26263; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0010109; Expressed in wing disc and 38 other tissues.
DR Genevisible; Q26263; DM.
DR GO; GO:0005829; C:cytosol; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:FlyBase.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IMP:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:FlyBase.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:UniProtKB.
DR GO; GO:0008344; P:adult locomotory behavior; IMP:FlyBase.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IBA:GO_Central.
DR GO; GO:0007549; P:dosage compensation; IMP:FlyBase.
DR GO; GO:0008345; P:larval locomotory behavior; IMP:FlyBase.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:FlyBase.
DR GO; GO:0014019; P:neuroblast development; IMP:UniProtKB.
DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IMP:FlyBase.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IMP:UniProtKB.
DR GO; GO:0007465; P:R7 cell fate commitment; IMP:FlyBase.
DR GO; GO:1902692; P:regulation of neuroblast proliferation; IMP:UniProtKB.
DR GO; GO:0050767; P:regulation of neurogenesis; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007540; P:sex determination, establishment of X:A ratio; IMP:FlyBase.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR003650; Orange_dom.
DR Pfam; PF07527; Hairy_orange; 1.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SMART; SM00511; ORANGE; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS51054; ORANGE; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Differentiation; DNA-binding; Neurogenesis; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..435
FT /note="Protein deadpan"
FT /id="PRO_0000127168"
FT DOMAIN 40..97
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 116..149
FT /note="Orange"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00380"
FT REGION 18..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 305..334
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 349..416
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 432..435
FT /note="WRPW motif"
FT COMPBIAS 18..38
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 305..330
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 349..396
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 397..413
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 407
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 408
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 411
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT CONFLICT 339
FT /note="M -> L (in Ref. 1; AAB24149)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 435 AA; 46551 MW; 9511A6C5F5019A29 CRC64;
MDYKNDINSD DDFDCSNGYS DSYGSNGRMS NPNGLSKAEL RKTNKPIMEK RRRARINHCL
NELKSLILEA MKKDPARHTK LEKADILEMT VKHLQSVQRQ QLNMAIQSDP SVVQKFKTGF
VECAEEVNRY VSQMDGIDTG VRQRLSAHLN QCANSLEQIG SMSNFSNGYR GGLFPATAVT
AAPTPLFPSL PQDLNNNSRT ESSAPAIQMG GLQLIPSRLP SGEFALIMPN TGSAAPPPGP
FAWPGSAAGV AAGTASAALA SIANPTHLND YTQSFRMSAF SKPVNTSVPA NLPENLIHTL
PGQTQLPVKN STSPPLSPIS SISSHCEESR AASPTVDVMS KHSFAGVFST PPPTSAETSF
NTSGSLNLSA GSHDSSGCSR PLAHLQQQQV SSTSGIAKRD REAEAESSDC SLDEPSSKKF
LAGAIEKSSS AWRPW
