ID SIM_DROME Reviewed; 697 AA.
AC P05709; O96521; Q7KSL7; Q8MQI7; Q9VFZ3;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-MAY-2003, sequence version 3.
DT 27-MAR-2024, entry version 211.
DE RecName: Full=Protein single-minded;
GN Name=sim; ORFNames=CG7771;
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 [GENOMIC DNA] (ISOFORM B), FUNCTION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=9840810;
RA Kasai Y., Stahl S., Crews S.;
RT "Specification of the Drosophila CNS midline cell lineage: direct control
RT of single-minded transcription by dorsal/ventral patterning genes.";
RL Gene Expr. 7:171-189(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE (ALLELE SIM-J1-47), FUNCTION, SUBUNIT, TISSUE
RP SPECIFICITY, AND MUTAGENESIS OF SER-65.
RX PubMed=12221007; DOI=10.1006/dbio.2002.0770;
RA Pielage J., Steffes G., Lau D.C., Parente B.A., Crews S.T., Strauss R.,
RA Klambt C.;
RT "Novel behavioral and developmental defects associated with Drosophila
RT single-minded.";
RL Dev. Biol. 249:283-299(2002).
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, AND ALTERNATIVE SPLICING.
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] (ISOFORM A).
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 [6]
RP NUCLEOTIDE SEQUENCE OF 25-42, SIMILARITY TO HLH PROTEINS, AND FUNCTION.
RX PubMed=1760843; DOI=10.1016/0092-8674(91)90292-7;
RA Nambu J.R., Lewis J.O., Wharton K.A. Jr., Crews S.T.;
RT "The Drosophila single-minded gene encodes a helix-loop-helix protein that
RT acts as a master regulator of CNS midline development.";
RL Cell 67:1157-1167(1991).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 43-697, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=3345560; DOI=10.1016/0092-8674(88)90538-7;
RA Crews S.T., Thomas J.B., Goodman C.S.;
RT "The Drosophila single-minded gene encodes a nuclear protein with sequence
RT similarity to the per gene product.";
RL Cell 52:143-151(1988).
RN [8]
RP FUNCTION IN SYNAPSE DEVELOPMENT.
RX PubMed=23644463; DOI=10.1136/jmedgenet-2012-101490;
RA Willemsen M.H., Nijhof B., Fenckova M., Nillesen W.M., Bongers E.M.,
RA Castells-Nobau A., Asztalos L., Viragh E., van Bon B.W., Tezel E.,
RA Veltman J.A., Brunner H.G., de Vries B.B., de Ligt J., Yntema H.G.,
RA van Bokhoven H., Isidor B., Le Caignec C., Lorino E., Asztalos Z.,
RA Koolen D.A., Vissers L.E., Schenck A., Kleefstra T.;
RT "GATAD2B loss-of-function mutations cause a recognisable syndrome with
RT intellectual disability and are associated with learning deficits and
RT synaptic undergrowth in Drosophila.";
RL J. Med. Genet. 50:507-514(2013).
CC -!- FUNCTION: Transcription factor that functions as a master developmental
CC regulator controlling midline development of the ventral nerve cord
CC (PubMed:1760843, PubMed:12221007, PubMed:9840810). Required to
CC correctly specify the formation of the central brain complex, which
CC controls walking behavior (PubMed:1760843, PubMed:12221007,
CC PubMed:9840810). Also required for correct patterning of the embryonic
CC genital disk and anal pad anlage (PubMed:1760843, PubMed:12221007,
CC PubMed:9840810). Plays a role in synapse development (PubMed:23644463).
CC {ECO:0000269|PubMed:12221007, ECO:0000269|PubMed:1760843,
CC ECO:0000269|PubMed:23644463, ECO:0000269|PubMed:9840810}.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC protein. {ECO:0000269|PubMed:12221007}.
CC -!- INTERACTION:
CC P05709; O15945: tgo; NbExp=3; IntAct=EBI-88929, EBI-172695;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981,
CC ECO:0000269|PubMed:3345560}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A;
CC IsoId=P05709-1; Sequence=Displayed;
CC Name=B;
CC IsoId=P05709-2; Sequence=VSP_011812;
CC -!- TISSUE SPECIFICITY: Embryonic nerve cord.
CC {ECO:0000269|PubMed:12221007}.
CC -!- POLYMORPHISM: Berkeley strain has 11 A-A-Q repeats.
CC {ECO:0000269|PubMed:1760843}.
CC -!- DISRUPTION PHENOTYPE: Mutations result in the loss of the precursor
CC cells that give rise to midline cells of the embryonic central nervous
CC system. {ECO:0000269|PubMed:3345560, ECO:0000269|PubMed:9840810}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC64519.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; AF071934; AAC64519.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AE014297; AAF54902.3; -; Genomic_DNA.
DR EMBL; AE014297; AAN14343.3; -; Genomic_DNA.
DR EMBL; AY129457; AAM76199.1; -; mRNA.
DR EMBL; M19020; AAA28900.1; -; mRNA.
DR PIR; A29945; A29945.
DR PIR; A41647; A41647.
DR RefSeq; NP_524340.2; NM_079616.4.
DR RefSeq; NP_731771.3; NM_169495.4.
DR AlphaFoldDB; P05709; -.
DR SMR; P05709; -.
DR BioGRID; 66699; 10.
DR IntAct; P05709; 4.
DR STRING; 7227.FBpp0082178; -.
DR PaxDb; 7227-FBpp0082178; -.
DR DNASU; 41612; -.
DR GeneID; 41612; -.
DR KEGG; dme:Dmel_CG7771; -.
DR AGR; FB:FBgn0004666; -.
DR CTD; 41612; -.
DR FlyBase; FBgn0004666; sim.
DR VEuPathDB; VectorBase:FBgn0004666; -.
DR eggNOG; KOG3559; Eukaryota.
DR InParanoid; P05709; -.
DR OrthoDB; 5396877at2759; -.
DR PhylomeDB; P05709; -.
DR SignaLink; P05709; -.
DR BioGRID-ORCS; 41612; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 41612; -.
DR PRO; PR:P05709; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR ExpressionAtlas; P05709; baseline and differential.
DR Genevisible; P05709; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IEA:InterPro.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IPI:FlyBase.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:FlyBase.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:FlyBase.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:FlyBase.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:FlyBase.
DR GO; GO:0007628; P:adult walking behavior; IMP:FlyBase.
DR GO; GO:0007409; P:axonogenesis; IMP:FlyBase.
DR GO; GO:0007420; P:brain development; IMP:FlyBase.
DR GO; GO:0035225; P:determination of genital disc primordium; IMP:FlyBase.
DR GO; GO:0007398; P:ectoderm development; TAS:FlyBase.
DR GO; GO:0040011; P:locomotion; TAS:FlyBase.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:FlyBase.
DR GO; GO:0006355; P:regulation of DNA-templated transcription; NAS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007419; P:ventral cord development; IMP:FlyBase.
DR GO; GO:0007418; P:ventral midline development; IMP:UniProtKB.
DR CDD; cd19740; bHLH-PAS_dSIM_like; 1.
DR CDD; cd00130; PAS; 2.
DR Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1.
DR Gene3D; 3.30.450.20; PAS domain; 2.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR001067; Nuc_translocat.
DR InterPro; IPR001610; PAC.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR013767; PAS_fold.
DR InterPro; IPR013655; PAS_fold_3.
DR NCBIfam; TIGR00229; sensory_box; 1.
DR PANTHER; PTHR23043; HYPOXIA-INDUCIBLE FACTOR 1 ALPHA; 1.
DR PANTHER; PTHR23043:SF36; SIM BHLH TRANSCRIPTION FACTOR 1B-RELATED; 1.
DR Pfam; PF00010; HLH; 1.
DR Pfam; PF00989; PAS; 1.
DR Pfam; PF08447; PAS_3; 1.
DR PRINTS; PR00785; NCTRNSLOCATR.
DR SMART; SM00353; HLH; 1.
DR SMART; SM00086; PAC; 1.
DR SMART; SM00091; PAS; 2.
DR SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 1.
DR SUPFAM; SSF55785; PYP-like sensor domain (PAS domain); 2.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS50112; PAS; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Developmental protein; Differentiation; DNA-binding;
KW Neurogenesis; Nucleus; Reference proteome; Repeat; Transcription;
KW Transcription regulation.
FT CHAIN 1..697
FT /note="Protein single-minded"
FT /id="PRO_0000127438"
FT DOMAIN 24..77
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 100..172
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 266..336
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT REGION 406..446
FT /note="14 X 3 AA repeats of A-A-Q (approximate)"
FT REGION 496..537
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 554..584
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 621..655
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 502..537
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..24
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000305"
FT /id="VSP_011812"
FT VARIANT 406..414
FT /note="Missing (in strain: Berkeley)"
FT MUTAGEN 65
FT /note="S->F: In allele sim-J1-47; temperature sensitive
FT embryonic midline axon phenotype."
FT /evidence="ECO:0000269|PubMed:12221007"
FT CONFLICT 151
FT /note="I -> Y (in Ref. 1; AAC64519)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 697 AA; 76475 MW; 588414A4A17101AD CRC64;
MTNHRRVRKD CYESRLHDIA KTCAMKEKSK NAARTRREKE NTEFCELAKL LPLPAAITSQ
LDKASVIRLT TSYLKMRQVF PDGLGEAWGS SPAMQRGATI KELGSHLLQT LDGFIFVVAP
DGKIMYISET ASVHLGLSQV ELTGNSIFEY IHNYDQDEMN AILSLHPHIN QHPLAQTHTP
IGSPNGVQHP SAYDHDRGSH TIEIEKTFFL RMKCVLAKRN AGLTTSGFKV IHCSGYLKAR
IYPDRGDGQG SLIQNLGLVA VGHSLPSSAI TEIKLHQNMF MFRAKLDMKL IFFDARVSQL
TGYEPQDLIE KTLYQYIHAA DIMAMRCSHQ ILLYKGQVTT KYYRFLTKGG GWVWVQSYAT
LVHNSRSSRE VFIVSVNYVL SEREVKDLVL NEIQTGVVKR EPISPAAQAA QAAQAAQAAQ
AAQAAQAAQA AQAAQAAHVA QAVQAQVVVV PQQSVVVQPQ CAGATGQPVG PGTPVSLALS
ASPKLDPYFE PELPLQPAVT PVPPTNNSSS SSNNNNGVWH HHHVQQQQQS GSMDHDSLSY
TQLYPPLNDL VVSSSSSVGG GTASSAGGGS SASASSSGVY STEMQYPDTT TGNLYYNNNN
HYYYDYDATV DVATSMIRPF SANSNSCSSS SESERQLSTG NASIVNETSP SQTTYSDLSH
NFELSYFSDN SSQQHQHQQQ QQHLMEQQHL QYQYATW
//
