INSV_DROME
ID INSV_DROME Reviewed; 376 AA.
AC Q8SYK5; Q9VQD5;
DT 11-NOV-2015, integrated into UniProtKB/Swiss-Prot.
DT 11-NOV-2015, sequence version 2.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Protein insensitive;
GN Name=insv; ORFNames=CG3227;
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 [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]
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]
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 [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.;
RL Submitted (JAN-2009) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND INTERACTION WITH
RP SU(H).
RX PubMed=21765394; DOI=10.1038/emboj.2011.218;
RA Duan H., Dai Q., Kavaler J., Bejarano F., Medranda G., Negre N., Lai E.C.;
RT "Insensitive is a corepressor for Suppressor of Hairless and regulates
RT Notch signalling during neural development.";
RL EMBO J. 30:3120-3133(2011).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, INTERACTION WITH
RP CP190, DNA-BINDING, AND DOMAIN BEN.
RX PubMed=25561495; DOI=10.1101/gad.252122.114;
RA Dai Q., Ren A., Westholm J.O., Duan H., Patel D.J., Lai E.C.;
RT "Common and distinct DNA-binding and regulatory activities of the BEN-solo
RT transcription factor family.";
RL Genes Dev. 29:48-62(2015).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 251-365, FUNCTION, SUBUNIT,
RP SUBCELLULAR LOCATION, DOMAIN BEN, DNA-BINDING, AND MUTAGENESIS OF SER-304;
RP LYS-315; ARG-342; ASP-351 AND LYS-354.
RX PubMed=23468431; DOI=10.1101/gad.213314.113;
RA Dai Q., Ren A., Westholm J.O., Serganov A.A., Patel D.J., Lai E.C.;
RT "The BEN domain is a novel sequence-specific DNA-binding domain conserved
RT in neural transcriptional repressors.";
RL Genes Dev. 27:602-614(2013).
CC -!- FUNCTION: Can act as both a transcriptional repressor and corepressor.
CC Represses the expression of genes involved in neural development and
CC preferentially binds palindromic sequence 5'-CCAATTGG-3' to mediate
CC transcriptional repression (PubMed:25561495, PubMed:23468431). Acts as
CC a corepressor for suppressor of hairless (Su(H)) and inhibits Notch
CC signaling during peripheral nervous system development
CC (PubMed:21765394, PubMed:25561495). {ECO:0000269|PubMed:21765394,
CC ECO:0000269|PubMed:23468431, ECO:0000269|PubMed:25561495}.
CC -!- SUBUNIT: Homodimer. Interacts (via BEN domain) with Su(H). Interacts
CC with Cp190. {ECO:0000269|PubMed:21765394, ECO:0000269|PubMed:25561495,
CC ECO:0000303|PubMed:23468431}.
CC -!- INTERACTION:
CC Q8SYK5; Q24117: ctp; NbExp=3; IntAct=EBI-192407, EBI-156442;
CC Q8SYK5; P28159: Su(H); NbExp=4; IntAct=EBI-192407, EBI-92180;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21765394,
CC ECO:0000269|PubMed:23468431, ECO:0000269|PubMed:25561495}.
CC -!- DEVELOPMENTAL STAGE: Initially expressed ubiquitously in the early
CC embryo and later throughout the developing ectoderm but becomes highly
CC restricted to the developing CNS and PNS. Peak expression seen at the
CC blastoderm stage (2-4 hours) (at protein level).
CC {ECO:0000269|PubMed:21765394, ECO:0000269|PubMed:25561495}.
CC -!- DOMAIN: The BEN domain mediates DNA-binding.
CC {ECO:0000269|PubMed:23468431, ECO:0000269|PubMed:25561495}.
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DR EMBL; AE014134; AAF51240.1; -; Genomic_DNA.
DR EMBL; AE014134; AHN54081.1; -; Genomic_DNA.
DR EMBL; AY071488; AAL49110.1; -; mRNA.
DR EMBL; BT056232; ACL68679.1; -; mRNA.
DR RefSeq; NP_001285566.1; NM_001298637.1.
DR RefSeq; NP_608690.2; NM_134846.3.
DR PDB; 4IX7; X-ray; 1.58 A; A/B=251-365.
DR PDBsum; 4IX7; -.
DR AlphaFoldDB; Q8SYK5; -.
DR SMR; Q8SYK5; -.
DR IntAct; Q8SYK5; 4.
DR MINT; Q8SYK5; -.
DR STRING; 7227.FBpp0077426; -.
DR PaxDb; Q8SYK5; -.
DR DNASU; 33441; -.
DR EnsemblMetazoa; FBtr0077746; FBpp0077426; FBgn0031434.
DR EnsemblMetazoa; FBtr0344854; FBpp0311169; FBgn0031434.
DR GeneID; 33441; -.
DR KEGG; dme:Dmel_CG3227; -.
DR UCSC; CG3227-RA; d. melanogaster.
DR CTD; 33441; -.
DR FlyBase; FBgn0031434; insv.
DR VEuPathDB; VectorBase:FBgn0031434; -.
DR eggNOG; ENOG502S4GE; Eukaryota.
DR GeneTree; ENSGT00530000069528; -.
DR HOGENOM; CLU_736238_0_0_1; -.
DR OMA; PKPLKQM; -.
DR OrthoDB; 983061at2759; -.
DR PhylomeDB; Q8SYK5; -.
DR SignaLink; Q8SYK5; -.
DR BioGRID-ORCS; 33441; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 33441; -.
DR PRO; PR:Q8SYK5; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0031434; Expressed in egg chamber and 34 other tissues.
DR Genevisible; Q8SYK5; DM.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0043035; F:chromatin insulator sequence binding; IDA:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IPI:FlyBase.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; IMP:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR InterPro; IPR018379; BEN_domain.
DR Pfam; PF10523; BEN; 1.
DR SMART; SM01025; BEN; 1.
DR PROSITE; PS51457; BEN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Coiled coil; DNA-binding; Nucleus; Reference proteome;
KW Repressor; Transcription; Transcription regulation.
FT CHAIN 1..376
FT /note="Protein insensitive"
FT /id="PRO_0000434573"
FT DOMAIN 258..356
FT /note="BEN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00784"
FT COILED 50..79
FT /evidence="ECO:0000255"
FT MUTAGEN 304
FT /note="S->A: Partial loss of DNA-binding and
FT transcriptional repressor activity."
FT /evidence="ECO:0000269|PubMed:23468431"
FT MUTAGEN 315
FT /note="K->A: Complete loss of DNA-binding."
FT /evidence="ECO:0000269|PubMed:23468431"
FT MUTAGEN 342
FT /note="R->A: Complete loss of DNA-binding."
FT /evidence="ECO:0000269|PubMed:23468431"
FT MUTAGEN 351
FT /note="D->A: Partial loss of DNA-binding and significant
FT decrease in transcriptional repressor activity. Complete
FT loss of repressor activity; when associated with A-354."
FT /evidence="ECO:0000269|PubMed:23468431"
FT MUTAGEN 354
FT /note="K->A: Significant loss of DNA-binding and
FT transcriptional repressor activity. Complete loss of
FT repressor activity; when associated with A-351."
FT /evidence="ECO:0000269|PubMed:23468431"
FT CONFLICT 299
FT /note="M -> V (in Ref. 3; AAL49110)"
FT STRAND 254..256
FT /evidence="ECO:0007829|PDB:4IX7"
FT STRAND 263..265
FT /evidence="ECO:0007829|PDB:4IX7"
FT HELIX 266..269
FT /evidence="ECO:0007829|PDB:4IX7"
FT HELIX 277..288
FT /evidence="ECO:0007829|PDB:4IX7"
FT HELIX 291..296
FT /evidence="ECO:0007829|PDB:4IX7"
FT STRAND 297..300
FT /evidence="ECO:0007829|PDB:4IX7"
FT HELIX 305..307
FT /evidence="ECO:0007829|PDB:4IX7"
FT HELIX 320..334
FT /evidence="ECO:0007829|PDB:4IX7"
FT HELIX 338..362
FT /evidence="ECO:0007829|PDB:4IX7"
SQ SEQUENCE 376 AA; 42215 MW; 26BD1410E8332F85 CRC64;
MENQYQRIVS ATAREDSQAR RSKPLFLNAW SQTSSVDFEV LRSISAPDPQ VEVENRALRD
KVRYLEAKLQ QHKDLLSQIH ATSARMQQAS SLLAESRPPT PPAVQSHHIL TPPSSEICAP
AQNPQILDYK IISAPDDADA IEIRLAAESL NSLSTSADSD RLEICLGDEN HQQSNHHNSQ
QQYRISNGIK RDGSSESADT PLQFIKRRKL QEIQLQEEIP RQNIKLPAKP QVKARNGSFT
DLNKGQQQNM DNVMVSIGPN NTCVPASVFE NINWSVCSLA TRKLLVTIFD RETLATHSMT
GKPSPAFKDQ DKPLKRMLDP GKIQDIIFAV THKCNASEKE VRNAITTKCA DENKMMKIQN
VKRRSSGIKH EKENII
