NITO_DROME
ID NITO_DROME Reviewed; 793 AA.
AC Q7KMJ6; Q8T0B2;
DT 20-JUN-2018, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=RNA-binding protein spenito {ECO:0000305};
GN Name=nito {ECO:0000312|FlyBase:FBgn0027548};
GN ORFNames=CG2910 {ECO:0000312|FlyBase:FBgn0027548};
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, and Head;
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 FUNCTION.
RX PubMed=16547102; DOI=10.1534/genetics.106.055558;
RA Jemc J., Rebay I.;
RT "Characterization of the split ends-like gene spenito reveals functional
RT antagonism between SPOC family members during Drosophila eye development.";
RL Genetics 173:279-286(2006).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=18174108; DOI=10.1016/j.ydbio.2007.11.023;
RA Chang J.L., Lin H.V., Blauwkamp T.A., Cadigan K.M.;
RT "Spenito and Split ends act redundantly to promote Wingless signaling.";
RL Dev. Biol. 314:100-111(2008).
RN [6]
RP TISSUE SPECIFICITY, PHOSPHORYLATION, INTERACTION WITH HIPK, AND MUTAGENESIS
RP OF 23-SER--SER-27 AND 32-SER--SER-37.
RX PubMed=25040100; DOI=10.1111/imb.12117;
RA Dewald D.N., Steinmetz E.L., Walldorf U.;
RT "Homeodomain-interacting protein kinase (Hipk) phosphorylates the small
RT SPOC family protein Spenito.";
RL Insect Mol. Biol. 23:706-719(2014).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, RNA-BINDING, AND
RP INTERACTION WITH SXL.
RX PubMed=26324914; DOI=10.1073/pnas.1515891112;
RA Yan D., Perrimon N.;
RT "spenito is required for sex determination in Drosophila melanogaster.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:11606-11611(2015).
RN [8]
RP FUNCTION, RNA-BINDING, AND IDENTIFICATION IN THE WMM COMPLEX.
RX PubMed=27919077; DOI=10.1038/nature20568;
RA Lence T., Akhtar J., Bayer M., Schmid K., Spindler L., Ho C.H., Kreim N.,
RA Andrade-Navarro M.A., Poeck B., Helm M., Roignant J.Y.;
RT "m(6)A modulates neuronal functions and sex determination in Drosophila.";
RL Nature 540:242-247(2016).
RN [9]
RP FUNCTION, AND IDENTIFICATION IN THE WMM COMPLEX.
RX PubMed=29535189; DOI=10.1101/gad.309146.117;
RA Knuckles P., Lence T., Haussmann I.U., Jacob D., Kreim N., Carl S.H.,
RA Masiello I., Hares T., Villasenor R., Hess D., Andrade-Navarro M.A.,
RA Biggiogera M., Helm M., Soller M., Buehler M., Roignant J.Y.;
RT "Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA-
RT binding factor Rbm15/Spenito to the m6A machinery component Wtap/Fl(2)d.";
RL Genes Dev. 32:415-429(2018).
RN [10]
RP SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE WMM COMPLEX.
RX PubMed=28675155; DOI=10.1038/ncomms15737;
RA Kan L., Grozhik A.V., Vedanayagam J., Patil D.P., Pang N., Lim K.S.,
RA Huang Y.C., Joseph B., Lin C.J., Despic V., Guo J., Yan D., Kondo S.,
RA Deng W.M., Dedon P.C., Jaffrey S.R., Lai E.C.;
RT "The m6A pathway facilitates sex determination in Drosophila.";
RL Nat. Commun. 8:15737-15737(2017).
RN [11]
RP FUNCTION, AND IDENTIFICATION IN THE WMM COMPLEX.
RX PubMed=29555755; DOI=10.1073/pnas.1720945115;
RA Guo J., Tang H.W., Li J., Perrimon N., Yan D.;
RT "Xio is a component of the Drosophila sex determination pathway and RNA N6-
RT methyladenosine-methyladenosine methyltransferase complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:3674-3679(2018).
CC -!- FUNCTION: RNA-binding protein that acts as an associated component of
CC the WMM complex, a complex that mediates N6-methyladenosine (m6A)
CC methylation of mRNAs (PubMed:27919077, PubMed:29535189,
CC PubMed:29555755). M6a modification plays a role in the efficiency of
CC mRNA splicing and is required for sex determination (PubMed:27919077,
CC PubMed:29535189, PubMed:29555755). In the WMM complex, may act by
CC binding target RNAs and recruiting the WMM complex (PubMed:29535189).
CC Required for sex determination and dosage compensation via Sxl
CC alternative splicing: m6A methylation acts as a key regulator of Sxl
CC pre-mRNA and promotes female-specific alternative splicing of Sxl,
CC which determines female physiognomy (PubMed:26324914, PubMed:29535189,
CC PubMed:29555755). M6A methylation is also required for neuronal
CC functions (PubMed:27919077). Acts as a positive regulator of canonical
CC Wg signaling during wing disk and eye development (PubMed:16547102,
CC PubMed:18174108). {ECO:0000269|PubMed:16547102,
CC ECO:0000269|PubMed:18174108, ECO:0000269|PubMed:26324914,
CC ECO:0000269|PubMed:27919077, ECO:0000269|PubMed:29535189,
CC ECO:0000269|PubMed:29555755}.
CC -!- SUBUNIT: Component of the WMM complex, a N6-methyltransferase complex
CC composed of a catalytic subcomplex, named MAC, and of an associated
CC subcomplex, named MACOM (PubMed:27919077, PubMed:29535189,
CC PubMed:28675155, PubMed:29555755). The MAC subcomplex is composed of
CC Ime4/Mettl3 and Mettl14 (PubMed:27919077, PubMed:29535189,
CC PubMed:28675155, PubMed:29555755). The MACOM subcomplex is composed of
CC fl(2)d, Flacc/Xio, Hakai, vir, and, in some cases of nito
CC (PubMed:27919077, PubMed:29535189, PubMed:29555755). Interacts with Sxl
CC (PubMed:26324914). Interacts with Hipk; leading to phosphorylation
CC (PubMed:25040100). {ECO:0000269|PubMed:25040100,
CC ECO:0000269|PubMed:26324914, ECO:0000269|PubMed:27919077,
CC ECO:0000269|PubMed:28675155, ECO:0000269|PubMed:29535189,
CC ECO:0000269|PubMed:29555755}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18174108,
CC ECO:0000269|PubMed:26324914, ECO:0000269|PubMed:28675155}.
CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:18174108,
CC PubMed:25040100). Shows some enrichment in the central nervous system
CC (PubMed:25040100). {ECO:0000269|PubMed:18174108,
CC ECO:0000269|PubMed:25040100}.
CC -!- PTM: Phosphorylated by Hipk at Ser-23, Ser-25 and/or Ser-27; the
CC precise position if phosphorylation sites is unknown (PubMed:25040100).
CC {ECO:0000269|PubMed:25040100}.
CC -!- DISRUPTION PHENOTYPE: Female flies show stem cell tumors in the female
CC germ line as well as female-to-male somatic transformations
CC (PubMed:26324914). {ECO:0000269|PubMed:26324914}.
CC -!- SIMILARITY: Belongs to the RRM Spen family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL39579.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AE013599; AAF59160.1; -; Genomic_DNA.
DR EMBL; AE013599; AAM68878.1; -; Genomic_DNA.
DR EMBL; AE013599; AHN55972.1; -; Genomic_DNA.
DR EMBL; AF145664; AAD38639.1; -; mRNA.
DR EMBL; AY069434; AAL39579.1; ALT_INIT; mRNA.
DR RefSeq; NP_001286174.1; NM_001299245.1.
DR RefSeq; NP_610339.1; NM_136495.3.
DR RefSeq; NP_724633.1; NM_165579.2.
DR AlphaFoldDB; Q7KMJ6; -.
DR SMR; Q7KMJ6; -.
DR IntAct; Q7KMJ6; 6.
DR STRING; 7227.FBpp0087934; -.
DR PaxDb; Q7KMJ6; -.
DR PRIDE; Q7KMJ6; -.
DR EnsemblMetazoa; FBtr0088857; FBpp0087933; FBgn0027548.
DR EnsemblMetazoa; FBtr0088858; FBpp0087934; FBgn0027548.
DR EnsemblMetazoa; FBtr0339122; FBpp0308267; FBgn0027548.
DR GeneID; 35756; -.
DR KEGG; dme:Dmel_CG2910; -.
DR UCSC; CG2910-RA; d. melanogaster.
DR CTD; 35756; -.
DR FlyBase; FBgn0027548; nito.
DR VEuPathDB; VectorBase:FBgn0027548; -.
DR eggNOG; KOG0112; Eukaryota.
DR GeneTree; ENSGT00940000172749; -.
DR HOGENOM; CLU_012724_1_0_1; -.
DR InParanoid; Q7KMJ6; -.
DR OMA; YVCFRTP; -.
DR OrthoDB; 367857at2759; -.
DR PhylomeDB; Q7KMJ6; -.
DR SignaLink; Q7KMJ6; -.
DR BioGRID-ORCS; 35756; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 35756; -.
DR PRO; PR:Q7KMJ6; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0027548; Expressed in eye disc (Drosophila) and 27 other tissues.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0071011; C:precatalytic spliceosome; HDA:FlyBase.
DR GO; GO:0036396; C:RNA N6-methyladenosine methyltransferase complex; IDA:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; ISS:FlyBase.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0048749; P:compound eye development; IMP:FlyBase.
DR GO; GO:0080009; P:mRNA methylation; IC:FlyBase.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IC:FlyBase.
DR GO; GO:2000737; P:negative regulation of stem cell differentiation; IMP:FlyBase.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IGI:FlyBase.
DR GO; GO:0010628; P:positive regulation of gene expression; IGI:FlyBase.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IMP:FlyBase.
DR GO; GO:0007548; P:sex differentiation; IEA:UniProtKB-KW.
DR GO; GO:0035222; P:wing disc pattern formation; IMP:FlyBase.
DR Gene3D; 2.40.290.10; -; 1.
DR Gene3D; 3.30.70.330; -; 3.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR InterPro; IPR016194; SPOC-like_C_dom_sf.
DR InterPro; IPR012921; SPOC_C.
DR InterPro; IPR010912; SPOC_met.
DR Pfam; PF00076; RRM_1; 2.
DR Pfam; PF07744; SPOC; 1.
DR SMART; SM00360; RRM; 3.
DR SUPFAM; SSF100939; SSF100939; 1.
DR SUPFAM; SSF54928; SSF54928; 2.
DR PROSITE; PS50102; RRM; 2.
DR PROSITE; PS50917; SPOC; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Differentiation; mRNA processing; mRNA splicing;
KW Nucleus; Phosphoprotein; Reference proteome; RNA-binding;
KW Sexual differentiation.
FT CHAIN 1..793
FT /note="RNA-binding protein spenito"
FT /id="PRO_0000444612"
FT DOMAIN 314..391
FT /note="RRM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 395..469
FT /note="RRM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 624..791
FT /note="SPOC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00249"
FT REGION 1..93
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 243..296
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 507..623
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..18
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 25..46
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 60..78
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 567..609
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 23..27
FT /note="SASRS->AAARA: Decreased phosphorylation by Hipk."
FT /evidence="ECO:0000269|PubMed:25040100"
FT MUTAGEN 32..37
FT /note="SRSSLS->ARAALA: Does not affect phosphorylation by
FT Hipk."
FT /evidence="ECO:0000269|PubMed:25040100"
SQ SEQUENCE 793 AA; 89053 MW; CF8F7BBB1774B35B CRC64;
MSSHRDGAGA DRITIKIHNM KRSASRSPGP ASRSSLSRNS RSMGRGYDNG SGVPGDSPER
LSPERMRRRL DRSPSRYGSP HREPYMRGPP PAERPAGYKV LCVSALPPKA PDDFIEETLY
REYKKFGDFS VRLAHDLDER VAYVCFRTPE DAREAKHHKP RLIIYDKMAI VEPVYKSTTR
PEYRPRGHSM SPPDYERYHY SRSPMGQGVP LDHRRPPIDP YDRYGPPHMH PHAVHPRDYR
PLHHDYPHPP RGPPLHRGGH PHHLHGHAPP HQYAPMRPLA PRPHAPYEKP ESKKDKFPNY
LHHVQPEDDP LSTRTLFAGN LEVTIADDEL RRIFGKYGVV DDIDIKRPPP GTGNAFAFVR
YQNLDMAHRA KIELSGQYIG KFQCKIGYGK VTPATRMWIG GLGAWTSVTQ LEREFDRFGA
IKKIEYQKGE PYAYIQYETV EAATAAVKEM RGFPLGGPER RLRTDFAELP GATPAAPFKS
SKPPYDESAL EYRRPEYDPY YEESAAYAPR GGYSPYPPRG GYRGRGGYRG RGRGMYHYHN
DVHRPPHPGS LAGSSSSVPP PGGVEDEWRR PPGESYDRGA RSSSREPGVE RSRSRSPLKR
ARSPGSDSDT STRRNDALAS ASTVPDVARK CSTVWTGALI LKSSLFPAKF HLTDGDTDIV
ESLMRDEEGK HNLRITQRLR LDPPKLDDVQ KRIASSSSHA IFMGLAGSTN DTNCDDASVQ
TRPLRNLVSY LKQKEAAGVI SLLNKETEAT GVLYAFPPCD FSTELLKRTC HSLTEEGLKE
DHLVIVVVRG GTA
