INT13_DROME
ID INT13_DROME Reviewed; 689 AA.
AC Q9VEX5; Q27924; Q7JP08;
DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Protein asunder {ECO:0000303|PubMed:19357193};
DE AltName: Full=Cell cycle regulator Mat89Bb {ECO:0000303|PubMed:15737938};
DE AltName: Full=Integrator complex subunit 13 {ECO:0000303|PubMed:23097424};
DE AltName: Full=Maternal transcript 89Bb {ECO:0000312|EMBL:AAF55290.1};
DE AltName: Full=Set apart in position or space protein {ECO:0000303|PubMed:19357193};
GN Name=Asun {ECO:0000312|FlyBase:FBgn0020407};
GN Synonyms=IntS13 {ECO:0000303|PubMed:23097424},
GN Mat89Bb {ECO:0000303|PubMed:15737938},
GN ovary2 {ECO:0000312|EMBL:AAA90971.1};
GN ORFNames=CG6814 {ECO:0000312|FlyBase:FBgn0020407};
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:0000305, ECO:0000312|EMBL:AAA90971.1}
RP NUCLEOTIDE SEQUENCE [MRNA], NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 413-689,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=9799434; DOI=10.1007/s004270050211;
RA Stebbings L.A., Grimes B.R., Bownes M.;
RT "A testis-specifically expressed gene is embedded within a cluster of
RT maternally expressed genes at 89B in Drosophila melanogaster.";
RL Dev. Genes Evol. 208:523-530(1998).
RN [2] {ECO:0000312|EMBL:AAF55290.1}
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 [3] {ECO:0000305, ECO:0000312|EMBL:AAF55290.1}
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 [4] {ECO:0000312|EMBL:AAM49919.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAM49919.1};
RC TISSUE=Embryo {ECO:0000269|PubMed:12537569};
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] {ECO:0000305}
RP FUNCTION, PHOSPHORYLATION, AND DISRUPTION PHENOTYPE.
RX PubMed=15737938; DOI=10.1016/j.devcel.2004.12.008;
RA Lee L.A., Lee E., Anderson M.A., Vardy L., Tahinci E., Ali S.M.,
RA Kashevsky H., Benasutti M., Kirschner M.W., Orr-Weaver T.L.;
RT "Drosophila genome-scale screen for PAN GU kinase substrates identifies
RT Mat89Bb as a cell cycle regulator.";
RL Dev. Cell 8:435-442(2005).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19357193; DOI=10.1091/mbc.e08-12-1165;
RA Anderson M.A., Jodoin J.N., Lee E., Hales K.G., Hays T.S., Lee L.A.;
RT "Asunder is a critical regulator of dynein-dynactin localization during
RT Drosophila spermatogenesis.";
RL Mol. Biol. Cell 20:2709-2721(2009).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE INTEGRATOR
RP COMPLEX.
RX PubMed=23097424; DOI=10.1261/rna.035725.112;
RA Chen J., Ezzeddine N., Waltenspiel B., Albrecht T.R., Warren W.D.,
RA Marzluff W.F., Wagner E.J.;
RT "An RNAi screen identifies additional members of the Drosophila Integrator
RT complex and a requirement for cyclin C/Cdk8 in snRNA 3'-end formation.";
RL RNA 18:2148-2156(2012).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF
RP 617-LYS--ARG-619.
RX PubMed=23904267; DOI=10.1091/mbc.e13-05-0254;
RA Jodoin J.N., Sitaram P., Albrecht T.R., May S.B., Shboul M., Lee E.,
RA Reversade B., Wagner E.J., Lee L.A.;
RT "Nuclear-localized Asunder regulates cytoplasmic dynein localization via
RT its role in the integrator complex.";
RL Mol. Biol. Cell 24:2954-2965(2013).
CC -!- FUNCTION: Component of the Integrator complex, a complex involved in
CC the transcription of small nuclear RNAs (snRNA) and their 3'-box-
CC dependent processing (PubMed:23097424). Involved in the 3'-end
CC processing of the U7 snRNA, and also the spliceosomal snRNAs U1 and U5
CC (PubMed:23097424). Plays a role as a regulator of spermatogenesis
CC (PubMed:19357193). Crucial regulator of the mitotic cell cycle and
CC development (PubMed:15737938, PubMed:19357193). Required for the
CC correct dynein-dynactin perinuclear localization important for nucleus-
CC centrosome coupling that occur upon meiotic progression of primary
CC spermatocytes (PubMed:19357193,PubMed:23904267). Plays a role in sperm
CC motility and fertility (PubMed:19357193). May have a role in the
CC PNG/PLU/GNU pathway (PubMed:15737938). {ECO:0000269|PubMed:15737938,
CC ECO:0000269|PubMed:19357193, ECO:0000269|PubMed:23097424,
CC ECO:0000269|PubMed:23904267}.
CC -!- SUBUNIT: Belongs to the multiprotein complex Integrator, at least
CC composed of IntS1, IntS2, IntS3, IntS4, omd/IntS5, IntS6, defl/IntS7,
CC IntS8, IntS9, IntS10, IntS11, IntS12, asun/IntS13 and IntS14.
CC {ECO:0000305|PubMed:23097424}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19357193,
CC ECO:0000269|PubMed:23097424}. Cytoplasm {ECO:0000269|PubMed:19357193,
CC ECO:0000269|PubMed:23097424, ECO:0000269|PubMed:9799434}. Cytoplasm,
CC perinuclear region {ECO:0000269|PubMed:19357193}. Note=Colocalizes with
CC dynein-dynactin on the nuclear surface at the meiotic G2/prophase
CC transition in primary spermatocytes (PubMed:19357193). Nuclear location
CC is required for recruitment of dynein motors to nuclear envelope at
CC G2/M (PubMed:23904267). {ECO:0000269|PubMed:19357193,
CC ECO:0000269|PubMed:23904267}.
CC -!- TISSUE SPECIFICITY: Expressed in nurse cells at stages 9-10 of
CC oogenesis and exported to the oocyte. Also expressed in the follicle
CC cells surrounding the oocyte. {ECO:0000269|PubMed:9799434}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC Expressed in the nucleus during the G2 phase of primary spermatocytes
CC at stages S3-S4. Distributed between the nucleus and the cytoplasm in
CC G2 phase of primary spermatocytes at stage S5. Localized in the
CC cytoplasm in G2 phase of primary spermatocytes at stage S6. Remains
CC dispersed throughout the cell until the completion of meiosis when it
CC becomes restricted from nuclei of onion-stage spermatides.
CC {ECO:0000269|PubMed:9799434}.
CC -!- PTM: Phosphorylated. {ECO:0000269|PubMed:15737938}.
CC -!- DISRUPTION PHENOTYPE: Results in almost complete steril males. Mature
CC sperm formed in small amounts in testes are immotile or weakly motile;
CC seminal vesicles are largely empty. Primary spermatocytes appeared
CC normal (Cysts of 16 cells); however, spermatids show irregularities in
CC nuclear size and number. Spermatocytes I exhibit failure of nucleus-
CC centrosome coupling that normally occur upon meiotic phase entry; those
CC that progress through meiotic divisions exhibit defects in spindle
CC assembly and chromosome segregation. When injected into Xenopus
CC embryos, causes developmental arrest with gastrulation defects and
CC defective cell cycles resulting in polyploid nuclei. RNAi injection
CC into HeLa cells or Drosophila syncytial embryos causes mitotic cell
CC cycle, giving rise to multinucleated polyploidy cells.
CC {ECO:0000269|PubMed:15737938}.
CC -!- SIMILARITY: Belongs to the asunder family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA90969.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=AAA90969.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAA90971.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=AAA90971.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U47618; AAA90969.1; ALT_SEQ; Genomic_DNA.
DR EMBL; U47619; AAA90971.1; ALT_SEQ; mRNA.
DR EMBL; AE014297; AAF55290.1; -; Genomic_DNA.
DR EMBL; AY118550; AAM49919.1; -; mRNA.
DR RefSeq; NP_524379.2; NM_079655.4.
DR AlphaFoldDB; Q9VEX5; -.
DR SMR; Q9VEX5; -.
DR BioGRID; 67019; 8.
DR IntAct; Q9VEX5; 1.
DR STRING; 7227.FBpp0082713; -.
DR PaxDb; Q9VEX5; -.
DR PRIDE; Q9VEX5; -.
DR DNASU; 41971; -.
DR EnsemblMetazoa; FBtr0083259; FBpp0082713; FBgn0020407.
DR GeneID; 41971; -.
DR KEGG; dme:Dmel_CG6814; -.
DR UCSC; CG6814-RA; d. melanogaster.
DR CTD; 41971; -.
DR FlyBase; FBgn0020407; asun.
DR VEuPathDB; VectorBase:FBgn0020407; -.
DR eggNOG; KOG3711; Eukaryota.
DR GeneTree; ENSGT00390000002793; -.
DR HOGENOM; CLU_012654_1_0_1; -.
DR InParanoid; Q9VEX5; -.
DR OMA; CMDEAPS; -.
DR OrthoDB; 676663at2759; -.
DR PhylomeDB; Q9VEX5; -.
DR Reactome; R-DME-6807505; RNA polymerase II transcribes snRNA genes.
DR BioGRID-ORCS; 41971; 1 hit in 1 CRISPR screen.
DR GenomeRNAi; 41971; -.
DR PRO; PR:Q9VEX5; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0020407; Expressed in egg cell and 20 other tissues.
DR Genevisible; Q9VEX5; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0032039; C:integrator complex; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0051642; P:centrosome localization; IMP:FlyBase.
DR GO; GO:0046843; P:dorsal appendage formation; IMP:FlyBase.
DR GO; GO:0030317; P:flagellated sperm motility; IMP:UniProtKB.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051663; P:oocyte nucleus localization involved in oocyte dorsal/ventral axis specification; IMP:FlyBase.
DR GO; GO:0060814; P:posterior mRNA localization involved in anterior/posterior axis specification; IMP:FlyBase.
DR GO; GO:0080154; P:regulation of fertilization; IMP:UniProtKB.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0034472; P:snRNA 3'-end processing; IDA:FlyBase.
DR GO; GO:0007283; P:spermatogenesis; IMP:FlyBase.
DR InterPro; IPR019355; Cell_cycle_regulator_Mat89Bb.
DR PANTHER; PTHR12955; PTHR12955; 2.
DR Pfam; PF10221; DUF2151; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Coiled coil; Cytoplasm; Developmental protein;
KW Differentiation; Meiosis; Mitosis; Nucleus; Phosphoprotein;
KW Reference proteome; Spermatogenesis.
FT CHAIN 1..689
FT /note="Protein asunder"
FT /id="PRO_0000385342"
FT REGION 592..619
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 665..689
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 521..550
FT /evidence="ECO:0000255"
FT MOTIF 613..619
FT /note="Nuclear localization signal (NLS)"
FT /evidence="ECO:0000269|PubMed:23904267"
FT COMPBIAS 600..619
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 670..689
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 617..619
FT /note="KRR->AAA: Loss of nuclear location. Location is
FT mainly cytoplasmic or diffuse."
FT /evidence="ECO:0000269|PubMed:23904267"
FT CONFLICT 54
FT /note="S -> T (in Ref. 1; AAA90971)"
FT /evidence="ECO:0000305"
FT CONFLICT 147..151
FT /note="TDEQL -> PMSSW (in Ref. 1; AAA90971)"
FT /evidence="ECO:0000305"
FT CONFLICT 199
FT /note="T -> S (in Ref. 1; AAA90971)"
FT /evidence="ECO:0000305"
FT CONFLICT 257..258
FT /note="KL -> NV (in Ref. 1; AAA90971)"
FT /evidence="ECO:0000305"
FT CONFLICT 438
FT /note="V -> M (in Ref. 1; AAA90969/AAA90971)"
FT /evidence="ECO:0000305"
FT CONFLICT 602
FT /note="G -> V (in Ref. 1; AAA90969/AAA90971)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 689 AA; 75728 MW; E02C1F79DA88AE79 CRC64;
MFERNQKTIF VLDHTRYFSI ASEEYISMDF LKGKPSADGG ATGAAGNATG SGGSQFSKSL
WTCACESSIE YCRVVWDLFP GKKHVRFIVS DTAAHIVNTW RPSTQNMAHV MNAMLIVGVP
SRNVPTSSDY SVIHGLRAAI EALAEPTDEQ LAAMADFGTD ELPRIPNKGR VICITSARDN
TSMKSLEDIF NTVLVQQNTL AAPPSKKGLV IDHCHLVILN IVPLGVESLV TNRSLLKISP
LLDVEIHTVS APDISYKLTH LILNHYDLAS TTVTNIPMKE EQNANSSANY DVEILHSRRA
HSITCGPDFS LPTSIKQGAT YETVTLKWCT PRGCGSADLQ PCLGQFLVTP VDVTSRPSSC
LINFLLNGRS VLLEMPRKTG SKATSHMLSA RGGEIFVHSL CITRSCMDEA PSITDGPGGR
VSDYRTAELG QLIKMSRVVP LKVKDPSAPP LTRRLPRYFP LTTSSSILFH LQRHISWLPH
FLHLLVKEDM DKQDEVRCQQ HIHELYKSAS RGDVLPFTHT NGARLKLSKA KDQYRLLYRE
LEQLIQLNAT TMHHKNLLES LQSLRAAYGD APLKSEPGAS LLRTYTESPL SPERLEPISS
VGASGSSSSN SLLKASKRRM SSCGQRSLLD IISSAERSQS NKRLDFSGRL CTPLGQVAKL
YPDFGTKDKD TVTTGASITP NVKEESVRS
