MNB_DROME
ID MNB_DROME Reviewed; 908 AA.
AC P49657; Q59E39; Q6AWJ3; Q9I7R8; Q9VX07;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2005, sequence version 2.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Serine/threonine-protein kinase minibrain;
DE EC=2.7.12.1;
GN Name=mnb; ORFNames=CG7826;
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] (ISOFORMS A; C AND D), FUNCTION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RC STRAIN=Berlin;
RX PubMed=7857639; DOI=10.1016/0896-6273(95)90286-4;
RA Tejedor F., Zhu X.R., Kaltenbach E., Ackermann A., Baumann A., Canal I.,
RA Heisenberg M., Fischbach K.F., Pongs O.;
RT "Minibrain: a new protein kinase family involved in postembryonic
RT neurogenesis in Drosophila.";
RL Neuron 14:287-301(1995).
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, 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 21-908 (ISOFORM A).
RC STRAIN=Berkeley; TISSUE=Larva, and Pupae;
RA Stapleton M., Carlson J.W., Chavez C., Frise E., George R.A., Pacleb J.M.,
RA Park S., Wan K.H., Yu C., Rubin G.M., Celniker S.E.;
RL Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Role in the specific control of proper proliferation of optic
CC lobe neuronal progeny. {ECO:0000269|PubMed:7857639}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.12.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.12.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.12.1;
CC -!- INTERACTION:
CC P49657; Q9VR53: wap; NbExp=2; IntAct=EBI-466373, EBI-92828;
CC P49657; Q9VA38: wts; NbExp=3; IntAct=EBI-466373, EBI-82717;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=A;
CC IsoId=P49657-1; Sequence=Displayed;
CC Name=C;
CC IsoId=P49657-3; Sequence=VSP_004915, VSP_004916;
CC Name=D;
CC IsoId=P49657-2; Sequence=VSP_004913, VSP_004914;
CC -!- TISSUE SPECIFICITY: In ventral nerve cord and supraesophageal ganglion
CC of embryos. Is most prominent in the mushroom body neuropil and the
CC outer proliferation center of the optic lobes in third instar larvae.
CC {ECO:0000269|PubMed:7857639}.
CC -!- DEVELOPMENTAL STAGE: Isoform A and isoform C are present mainly in
CC embryos and pupae. By contrast, isoform D appears to be expressed most
CC markedly in third instar larvae and pupae.
CC {ECO:0000269|PubMed:7857639}.
CC -!- DISRUPTION PHENOTYPE: Flies exhibit a specific and marked size
CC reduction of the optic lobes and central brain hemispheres but no major
CC alteration in neuronal architecture can be found.
CC {ECO:0000269|PubMed:7857639}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MNB/DYRK subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA50065.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA50068.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA50069.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; X70794; CAA50065.1; ALT_FRAME; mRNA.
DR EMBL; X70798; CAA50068.1; ALT_FRAME; mRNA.
DR EMBL; X70799; CAA50069.1; ALT_FRAME; mRNA.
DR EMBL; AE014298; AAF48777.3; -; Genomic_DNA.
DR EMBL; AE014298; AAN09442.1; -; Genomic_DNA.
DR EMBL; AE014298; AAX52504.1; -; Genomic_DNA.
DR EMBL; BT015255; AAT94484.1; ALT_SEQ; mRNA.
DR RefSeq; NP_001014750.1; NM_001014750.2. [P49657-2]
DR RefSeq; NP_728104.1; NM_167581.3. [P49657-1]
DR RefSeq; NP_728106.1; NM_170658.3. [P49657-3]
DR AlphaFoldDB; P49657; -.
DR SMR; P49657; -.
DR BioGRID; 59093; 21.
DR DIP; DIP-49177N; -.
DR IntAct; P49657; 49.
DR STRING; 7227.FBpp0289737; -.
DR PaxDb; P49657; -.
DR PRIDE; P49657; -.
DR DNASU; 32771; -.
DR EnsemblMetazoa; FBtr0299619; FBpp0288894; FBgn0259168. [P49657-3]
DR EnsemblMetazoa; FBtr0300508; FBpp0289735; FBgn0259168. [P49657-1]
DR EnsemblMetazoa; FBtr0300509; FBpp0289736; FBgn0259168. [P49657-2]
DR GeneID; 32771; -.
DR KEGG; dme:Dmel_CG42273; -.
DR UCSC; CG42273-RB; d. melanogaster.
DR CTD; 32771; -.
DR FlyBase; FBgn0259168; mnb.
DR VEuPathDB; VectorBase:FBgn0259168; -.
DR eggNOG; KOG0667; Eukaryota.
DR GeneTree; ENSGT00940000170191; -.
DR InParanoid; P49657; -.
DR OMA; HPFLMSM; -.
DR PhylomeDB; P49657; -.
DR BRENDA; 2.7.12.1; 1994.
DR Reactome; R-DME-1538133; G0 and Early G1.
DR BioGRID-ORCS; 32771; 0 hits in 3 CRISPR screens.
DR ChiTaRS; mnb; fly.
DR GenomeRNAi; 32771; -.
DR PRO; PR:P49657; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0259168; Expressed in saliva-secreting gland and 25 other tissues.
DR ExpressionAtlas; P49657; baseline and differential.
DR Genevisible; P49657; DM.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0043195; C:terminal bouton; IDA:FlyBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IDA:FlyBase.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:FlyBase.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IEA:RHEA.
DR GO; GO:0003713; F:transcription coactivator activity; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007623; P:circadian rhythm; IGI:FlyBase.
DR GO; GO:0045786; P:negative regulation of cell cycle; IMP:FlyBase.
DR GO; GO:0035331; P:negative regulation of hippo signaling; IMP:FlyBase.
DR GO; GO:0007399; P:nervous system development; IMP:FlyBase.
DR GO; GO:0008355; P:olfactory learning; IMP:FlyBase.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IBA:GO_Central.
DR GO; GO:2000253; P:positive regulation of feeding behavior; IMP:FlyBase.
DR GO; GO:0045927; P:positive regulation of growth; IMP:FlyBase.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IEP:FlyBase.
DR GO; GO:0046622; P:positive regulation of organ growth; IMP:FlyBase.
DR GO; GO:0045887; P:positive regulation of synaptic assembly at neuromuscular junction; IMP:FlyBase.
DR GO; GO:1900244; P:positive regulation of synaptic vesicle endocytosis; IMP:FlyBase.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0046777; P:protein autophosphorylation; IEA:InterPro.
DR GO; GO:0007632; P:visual behavior; IMP:FlyBase.
DR CDD; cd14226; PKc_DYRK1; 1.
DR InterPro; IPR028318; DYRK1A/B_MNB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR044131; PKc_DYR1A/1B.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24058:SF121; PTHR24058:SF121; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Developmental protein; Differentiation;
KW Kinase; Neurogenesis; Nucleotide-binding; Nucleus; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..908
FT /note="Serine/threonine-protein kinase minibrain"
FT /id="PRO_0000086340"
FT DOMAIN 164..484
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 119..143
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 552..592
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 623..669
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 863..895
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 121..139
FT /note="Bipartite nuclear localization signal"
FT COMPBIAS 11..33
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 552..574
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 865..895
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 292
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 170..178
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 193
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 243..246
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 601..607
FT /note="GLLMHSV -> VRRIVRI (in isoform C)"
FT /evidence="ECO:0000303|PubMed:7857639"
FT /id="VSP_004915"
FT VAR_SEQ 601..604
FT /note="GLLM -> DDRR (in isoform D)"
FT /evidence="ECO:0000303|PubMed:7857639"
FT /id="VSP_004913"
FT VAR_SEQ 605..908
FT /note="Missing (in isoform D)"
FT /evidence="ECO:0000303|PubMed:7857639"
FT /id="VSP_004914"
FT VAR_SEQ 608..908
FT /note="Missing (in isoform C)"
FT /evidence="ECO:0000303|PubMed:7857639"
FT /id="VSP_004916"
FT VARIANT 191
FT /note="A -> T (in mnb1; reduced brain volume)"
FT CONFLICT 45..46
FT /note="HA -> S (in Ref. 1; CAA50065/CAA50068/CAA50069)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 908 AA; 95903 MW; FFE6841F42F0BAD8 CRC64;
MYRLEDTNSG GVMDKNKQKL SAYGSSGGSV DAAQGSGSGG GRQRHAPLYG RFVDAEDLPA
THRDVMHHHS SPSSSSEVRA MQARIPNHFR EPASGPLRKL SVDLIKTYKH INEVYYAKKK
RRAQQTQGDD DSSNKKERKL YNDGYDDDNH DYIIKNGEKF LDRYEIDSLI GKGSFGQVVK
AYDHEEQCHV AIKIIKNKKP FLNQAQIEVK LLEMMNRADA ENKYYIVKLK RHFMWRNHLC
LVFELLSYNL YDLLRNTNFR GVSLNLTRKF AQQLCTALLF LSTPELNIIH CDLKPENILL
CNPKRSAIKI VDFGSSCQLG QRIYHYIQSR FYRSPEVLLG IQYDLAIDMW SLGCILVEMH
TGEPLFSGCN EVDQMNKIVE VLGMPPKYLL DQAHKTRKFF DKIVADGSYV LKKNQNGRKY
KPPGSRKLHD ILGVETGGPG GRRLDEPGHS VSDYLKFKDL ILRMLDFDPK TRVTPYYALQ
HNFFKRTADE ATNTSGAGAT ANAGAGGSGS SGAGGSSGGG VGGGLGASNS SSGAVSSSSA
AAPTAATAAA TAAGSSGSGS SVGGGSSAAQ QQQAMPLPLP LPLPLPPLAG PGGASDGQCH
GLLMHSVAAN AMNNFSALSL QSNAHPPPSL ANSHHSTNSL GSLNHISPGS TGCHNNNSNS
SNNNTRHSRL YGSNMVNMVG HHNSGSSNNH NSISYPHAME CDPPQMPPPP PNGHGRMRVP
AIMQLQPNSY APNSVPYYGN MSSSSVAAAA AAAAAAASHL MMTDSSVISA SAAGGGQGGG
NPGQNPVTPS AAAFLFPSQP AGTLYGTALG SLSDLPLPMP LPMSVPLQLP PSSSSSVSSG
SASVGSGGVG VGVVGQRRHI TGPAAQVGIS QSVGSGSSGS ATGASSSDAS SSSPMVGVCV
QQNPVVIH