ORB2_DROME
ID ORB2_DROME Reviewed; 704 AA.
AC Q9VSR3; Q95T31; Q9VSR2;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Translational regulator orb2;
GN Name=orb2 {ECO:0000312|EMBL:AAF50350.1}; ORFNames=CG43782;
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:0000312|EMBL:AAF50350.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:10731132};
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] {ECO:0000312|EMBL:AAF50350.1}
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 [3] {ECO:0000312|EMBL:AAK93467.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAK93467.1};
RC TISSUE=Head {ECO:0000269|PubMed:12537569},
RC Larva {ECO:0000269|PubMed:12537569}, and
RC Pupae {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 [4]
RP FUNCTION, TISSUE SPECIFICITY, AND DOMAIN (ISOFORM A).
RX PubMed=17965711; DOI=10.1038/nn1996;
RA Keleman K., Kruettner S., Alenius M., Dickson B.J.;
RT "Function of the Drosophila CPEB protein Orb2 in long-term courtship
RT memory.";
RL Nat. Neurosci. 10:1587-1593(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-74; SER-88; SER-100; SER-425
RP AND SER-428, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [6]
RP FUNCTION.
RX PubMed=20547833; DOI=10.1073/pnas.1004433107;
RA Mastushita-Sakai T., White-Grindley E., Samuelson J., Seidel C., Si K.;
RT "Drosophila Orb2 targets genes involved in neuronal growth, synapse
RT formation, and protein turnover.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:11987-11992(2010).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=21900268; DOI=10.1534/genetics.110.123646;
RA Hafer N., Xu S., Bhat K.M., Schedl P.;
RT "The Drosophila CPEB protein Orb2 has a novel expression pattern and is
RT important for asymmetric cell division and nervous system function.";
RL Genetics 189:907-921(2011).
RN [8]
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=22284910; DOI=10.1016/j.cell.2012.01.004;
RA Majumdar A., Cesario W.C., White-Grindley E., Jiang H., Ren F., Khan M.R.,
RA Li L., Choi E.M., Kannan K., Guo F., Unruh J., Slaughter B., Si K.;
RT "Critical role of amyloid-like oligomers of Drosophila Orb2 in the
RT persistence of memory.";
RL Cell 148:515-529(2012).
RN [9]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DOMAIN
RP (ISOFORMS A AND B).
RX PubMed=23083740; DOI=10.1016/j.neuron.2012.08.028;
RA Kruettner S., Stepien B., Noordermeer J.N., Mommaas M.A., Mechtler K.,
RA Dickson B.J., Keleman K.;
RT "Drosophila CPEB Orb2A mediates memory independent of its RNA-binding
RT domain.";
RL Neuron 76:383-395(2012).
RN [10]
RP FUNCTION, INTERACTION WITH BOL, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=23209437; DOI=10.1371/journal.pgen.1003079;
RA Xu S., Hafer N., Agunwamba B., Schedl P.;
RT "The CPEB protein Orb2 has multiple functions during spermatogenesis in
RT Drosophila melanogaster.";
RL PLoS Genet. 8:E1003079-E1003079(2012).
RN [11]
RP INTERACTION WITH TOB, SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=24523662; DOI=10.1371/journal.pbio.1001786;
RA White-Grindley E., Li L., Mohammad Khan R., Ren F., Saraf A., Florens L.,
RA Si K.;
RT "Contribution of Orb2A stability in regulated amyloid-like oligomerization
RT of Drosophila Orb2.";
RL PLoS Biol. 12:E1001786-E1001786(2014).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24830287; DOI=10.1371/journal.pgen.1004380;
RA Xu S., Tyagi S., Schedl P.;
RT "Spermatid cyst polarization in Drosophila depends upon apkc and the CPEB
RT family translational regulator orb2.";
RL PLoS Genet. 10:E1004380-E1004380(2014).
RN [13]
RP FUNCTION.
RX PubMed=26638074; DOI=10.1016/j.cell.2015.11.020;
RA Khan M.R., Li L., Perez-Sanchez C., Saraf A., Florens L., Slaughter B.D.,
RA Unruh J.R., Si K.;
RT "Amyloidogenic oligomerization transforms Drosophila Orb2 from a
RT translation repressor to an activator.";
RL Cell 163:1468-1483(2015).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION (ISOFORMS A AND B).
RX PubMed=26095367; DOI=10.1016/j.celrep.2015.05.037;
RA Kruettner S., Traunmueller L., Dag U., Jandrasits K., Stepien B., Iyer N.,
RA Fradkin L.G., Noordermeer J.N., Mensh B.D., Keleman K.;
RT "Synaptic Orb2A bridges memory acquisition and late memory consolidation in
RT Drosophila.";
RL Cell Rep. 11:1953-1965(2015).
RN [15]
RP SUBUNIT.
RX PubMed=26812143; DOI=10.1371/journal.pbio.1002361;
RA Hervas R., Li L., Majumdar A., Fernandez-Ramirez M.C., Unruh J.R.,
RA Slaughter B.D., Galera-Prat A., Santana E., Suzuki M., Nagai Y., Bruix M.,
RA Casas-Tinto S., Menendez M., Laurents D.V., Si K., Carrion-Vazquez M.;
RT "Molecular basis of Orb2 amyloidogenesis and blockade of memory
RT consolidation.";
RL PLoS Biol. 14:E1002361-E1002361(2016).
RN [16]
RP DOMAIN (ISOFORM A).
RX PubMed=28763009; DOI=10.3390/biom7030057;
RA Bajakian T.H., Cervantes S.A., Soria M.A., Beaugrand M., Kim J.Y.,
RA Service R.J., Siemer A.B.;
RT "Metal Binding Properties of the N-Terminus of the Functional Amyloid
RT Orb2.";
RL Biomolecules 7:0-0(2017).
RN [17]
RP DOMAIN (ISOFORM A).
RX PubMed=28700922; DOI=10.1016/j.bpj.2017.05.039;
RA Soria M.A., Cervantes S.A., Bajakian T.H., Siemer A.B.;
RT "The Functional Amyloid Orb2A Binds to Lipid Membranes.";
RL Biophys. J. 113:37-47(2017).
RN [18]
RP FUNCTION, FUNCTION (ISOFORM A), AND DISRUPTION PHENOTYPE (ISOFORM A).
RX PubMed=28525754; DOI=10.1016/j.cell.2017.05.006;
RA Gill J., Park Y., McGinnis J.P., Perez-Sanchez C., Blanchette M., Si K.;
RT "Regulated Intron Removal Integrates Motivational State and Experience.";
RL Cell 169:836-848.e15(2017).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE,
RP AND DISRUPTION PHENOTYPE (ISOFORM A).
RX PubMed=29105522; DOI=10.1080/01677063.2017.1393539;
RA Santana E., Casas-Tinto S.;
RT "Orb2 as modulator of Brat and their role at the neuromuscular junction.";
RL J. Neurogenet. 31:181-188(2017).
RN [20] {ECO:0007744|PDB:6VPS}
RP STRUCTURE BY ELECTRON MICROSCOPY (2.60 ANGSTROMS) OF 176-206, FUNCTION,
RP SUBUNIT, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=32165583; DOI=10.1126/science.aba3526;
RA Hervas R., Rau M.J., Park Y., Zhang W., Murzin A.G., Fitzpatrick J.A.J.,
RA Scheres S.H.W., Si K.;
RT "Cryo-EM structure of a neuronal functional amyloid implicated in memory
RT persistence in Drosophila.";
RL Science 367:1230-1234(2020).
CC -!- FUNCTION: RNA-binding protein involved in translational regulation and
CC required for long-term memory (PubMed:28525754, PubMed:29105522).
CC Required in mushroom body gamma neurons for long-term memory in male
CC courtship (PubMed:17965711, PubMed:23083740). Binds to mRNA 3'-UTRs
CC (PubMed:20547833, PubMed:26638074, PubMed:24830287, PubMed:26095367,
CC PubMed:32165583). In its monomeric form, acts as a translational
CC repressor of genes involved in neuronal growth, synapse formation and
CC protein turnover (PubMed:20547833, PubMed:26638074, PubMed:32165583).
CC In its amyloid-like oligomeric form, acts as a translational activator
CC (PubMed:26638074, PubMed:32165583). The monomeric form reduces poly(A)
CC tail length and destabilizes mRNA while the oligomeric form protects
CC and elongates the poly(A) tail and stabilizes mRNA (PubMed:26638074).
CC Involved in asymmetric cell division in the central nervous system
CC (PubMed:21900268). Plays a role in synapse formation and morphology at
CC neuromuscular junctions by modulating the translation of the tumor
CC suppressor brat (PubMed:29105522). Required for the progression of
CC spermatogenesis through meiosis and for sperm differentiation
CC (PubMed:23209437). During sperm differentiation, required to
CC asymmetrically localize and activate the translation of protein kinase
CC aPKC mRNAs which is necessary for spermatid cyst polarization
CC (PubMed:24830287). Also required during spermatid cyst polarization for
CC localization and translation of its own mRNA (PubMed:24830287).
CC {ECO:0000269|PubMed:17965711, ECO:0000269|PubMed:20547833,
CC ECO:0000269|PubMed:21900268, ECO:0000269|PubMed:23083740,
CC ECO:0000269|PubMed:23209437, ECO:0000269|PubMed:24830287,
CC ECO:0000269|PubMed:26095367, ECO:0000269|PubMed:26638074,
CC ECO:0000269|PubMed:28525754, ECO:0000269|PubMed:29105522,
CC ECO:0000269|PubMed:32165583}.
CC -!- FUNCTION: [Isoform A]: Required for initial memory acquisition
CC (PubMed:26095367, PubMed:28525754). Following subsequent late
CC dopaminergic pathway activation, recruits isoform B into a complex to
CC activate translation of CaMKII which is required for long-term memory
CC consolidation (PubMed:26095367). {ECO:0000269|PubMed:26095367,
CC ECO:0000269|PubMed:28525754}.
CC -!- SUBUNIT: Monomer (PubMed:22284910, PubMed:23083740, PubMed:32165583).
CC Upon neuronal stimulation, forms stable amyloid-like oligomers composed
CC of isoform A and isoform B which are required for formation of
CC persistent long-term memory (PubMed:22284910, PubMed:23083740,
CC PubMed:32165583). Isoform A is critical for oligomer formation
CC (PubMed:22284910, PubMed:23083740). Phe-5 of isoform A is required for
CC amyloid-like oligomerization (PubMed:22284910, PubMed:26812143).
CC Rapidly forms amyloids and toxic intermediates are extremely transient
CC (PubMed:26812143). Unlike in the adult nervous system, remains
CC monomeric in the early embryo (PubMed:32165583). Interacts with the
CC translational regulator bol (PubMed:23209437). Interacts with Tob; the
CC interaction is enhanced by neuronal stimulation, stabilizes isoform A
CC and induces oligomerization (PubMed:24523662).
CC {ECO:0000269|PubMed:22284910, ECO:0000269|PubMed:23083740,
CC ECO:0000269|PubMed:23209437, ECO:0000269|PubMed:24523662,
CC ECO:0000269|PubMed:26812143, ECO:0000269|PubMed:32165583}.
CC -!- INTERACTION:
CC Q9VSR3-1; Q9VSR3-1: orb2; NbExp=2; IntAct=EBI-16193700, EBI-16193700;
CC Q9VSR3-2; Q9VSR3-2: orb2; NbExp=3; IntAct=EBI-16193628, EBI-16193628;
CC -!- SUBCELLULAR LOCATION: Perikaryon {ECO:0000269|PubMed:21900268}. Cell
CC projection, axon {ECO:0000269|PubMed:21900268}. Cell projection,
CC dendrite {ECO:0000269|PubMed:21900268}. Synapse
CC {ECO:0000269|PubMed:22284910, ECO:0000269|PubMed:23083740,
CC ECO:0000269|PubMed:24523662}. Cytoplasm {ECO:0000269|PubMed:21900268,
CC ECO:0000269|PubMed:23209437}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:23209437}. Note=In embryonic and larval nervous
CC system, concentrated in the perikaryon (PubMed:21900268). In the adult
CC central nervous system, localizes to synaptic terminals
CC (PubMed:21900268). In the ovary, localizes to the cytoplasm of nurse
CC cells (PubMed:21900268). Localizes to neuromuscular junctions
CC (PubMed:29105522). In spermatocytes, localizes throughout the cytoplasm
CC with higher levels concentrated in a ring around the nucleus
CC (PubMed:23209437). The oligomeric form is enriched in the synaptic
CC region (PubMed:22284910). {ECO:0000269|PubMed:21900268,
CC ECO:0000269|PubMed:22284910, ECO:0000269|PubMed:29105522}.
CC -!- SUBCELLULAR LOCATION: [Isoform A]: Synapse
CC {ECO:0000269|PubMed:26095367}.
CC -!- SUBCELLULAR LOCATION: [Isoform B]: Perikaryon
CC {ECO:0000269|PubMed:26095367}. Cell projection, axon
CC {ECO:0000269|PubMed:26095367}. Synapse {ECO:0000269|PubMed:26095367}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=B {ECO:0000312|FlyBase:FBgn0264307}; Synonyms=C
CC {ECO:0000312|FlyBase:FBgn0264307}, Orb2B {ECO:0000303|PubMed:22284910};
CC IsoId=Q9VSR3-1; Sequence=Displayed;
CC Name=A {ECO:0000312|FlyBase:FBgn0264307}; Synonyms=Orb2A
CC {ECO:0000303|PubMed:22284910};
CC IsoId=Q9VSR3-2; Sequence=VSP_051999, VSP_052000;
CC -!- TISSUE SPECIFICITY: Broadly expressed throughout the nervous system of
CC embryo, larva and adult including the ventral nerve cord and brain (at
CC protein level) (PubMed:23083740, PubMed:32165583). In early embryos,
CC deposited maternally and distributed uniformly throughout the embryo
CC until the extended germband stage (PubMed:21900268). By mid-
CC embryogenesis, highest levels are found in the central and peripheral
CC nervous systems with lower expression also detected in the ectoderm and
CC mesoderm (PubMed:21900268). In adults, high levels are present in the
CC head and body of both sexes with higher expression in testis than ovary
CC (PubMed:21900268). In the ovary, expressed in both germ and follicle
CC cells (PubMed:21900268). In adult head, predominantly neuronal with
CC broad expression throughout the brain and ventral ganglia including the
CC mushroom body (PubMed:17965711, PubMed:21900268).
CC {ECO:0000269|PubMed:17965711, ECO:0000269|PubMed:21900268,
CC ECO:0000269|PubMed:23083740, ECO:0000269|PubMed:32165583}.
CC -!- DEVELOPMENTAL STAGE: Expressed in 0- to 2-hour-old embryos (at protein
CC level) (PubMed:32165583). Expressed in the larval motor neuron cells in
CC the brain (at protein level) (PubMed:29105522). Expressed throughout
CC development in both the soma and germline. Widely expressed in early
CC embryos with levels dropping during mid-embryogenesis and increasing
CC again in late embryogenesis. Expression is relatively low during larval
CC stages with lowest levels in the first and second instars and an
CC increase during the third instar. Levels increase substantially during
CC the pupal stage and remain relatively high in the adult. In the ovary,
CC little expression in the germarium or previtellogenic stage chambers
CC with levels increasing midway through oogenesis and remaining high
CC until stage 10 (PubMed:21900268). In the testis, there is substantial
CC up-regulation after mitosis is finished and the interconnected
CC spermatocytes begin to grow (PubMed:23209437). Expression peaks as the
CC mature spermatocytes go through meiosis and high levels are found in
CC 32- and 64-cell spermatid cysts with expression persisting after the
CC spermatids in the 64-cell cysts start differentiation and disappearing
CC once elongation and nuclear condensation are completed
CC (PubMed:23209437). {ECO:0000269|PubMed:21900268,
CC ECO:0000269|PubMed:23209437, ECO:0000269|PubMed:29105522,
CC ECO:0000269|PubMed:32165583}.
CC -!- INDUCTION: [Isoform A]: In the adult brain the mRNA is expressed as an
CC unspliced non-protein coding mRNA; inclusion of isoform A-specific exon
CC in the mature transcript is important for long-term memory; mRNA levels
CC depends on behavioral stimulus and splicing depends on the activity of
CC the splicing regulator ps. {ECO:0000305|PubMed:28525754}.
CC -!- DOMAIN: [Isoform A]: The RNA-binding region is not essential for long-
CC term memory. {ECO:0000269|PubMed:23083740}.
CC -!- DOMAIN: [Isoform B]: The RNA-binding region is essential for long-term
CC memory. {ECO:0000269|PubMed:23083740}.
CC -!- DOMAIN: [Isoform A]: The N-terminal Gln/His-rich domain is necessary
CC and sufficient for long-term memory and is required for formation of
CC amyloid-like oligomers with isoform B (PubMed:17965711,
CC PubMed:23083740). Binds transition metals (PubMed:28763009). Might bind
CC lipid membranes (PubMed:28700922). {ECO:0000269|PubMed:17965711,
CC ECO:0000269|PubMed:23083740, ECO:0000269|PubMed:28700922,
CC ECO:0000269|PubMed:28763009}.
CC -!- DOMAIN: [Isoform B]: The N-terminal Gln/His-rich domain is both
CC dispensable and insufficient for long-term memory and for formation of
CC amyloid-like oligomers with isoform A. {ECO:0000269|PubMed:23083740}.
CC -!- PTM: Phosphorylation regulates interaction with Tob and
CC oligomerization. Protein phosphatase 2A keeps both Orb2 and Tob in an
CC unphosphorylated form. Following synaptic activation, unphosphorylated
CC Orb2 is bound and stabilized by unphosphorylated Tob. Tob recruits
CC activated LimK which phosphorylates both Orb2 and Tob and enhances Orb2
CC oligomerization. {ECO:0000269|PubMed:24523662}.
CC -!- DISRUPTION PHENOTYPE: Substantially reduced viability with surviving
CC males being completely sterile due to a failure of spermatocytes to
CC complete meiosis with arrest happening at the G2-M transition
CC (PubMed:23209437). Defective spermatid cyst polarization
CC (PubMed:24830287). RNAi-mediated knockdown in motor neurons decreases
CC number of synapses and accumulation of the tumor suppressor brat at
CC neuromuscular junctions (NMJ) (PubMed:29105522). Simultaneous knockdown
CC of the tumor suppressor brat restablishes the number of synapses at NMJ
CC (PubMed:29105522). {ECO:0000269|PubMed:23209437,
CC ECO:0000269|PubMed:24830287, ECO:0000269|PubMed:29105522}.
CC -!- DISRUPTION PHENOTYPE: [Isoform A]: Fails to form stable long-term
CC memory during male courtship suppression, in which a male fly, upon
CC repeated exposure to an unreceptive female, suppresses its courting
CC behavior for days (PubMed:28525754). In neurons, increases levels of
CC the tumor suppressor brat (PubMed:29105522).
CC {ECO:0000269|PubMed:28525754, ECO:0000269|PubMed:29105522}.
CC -!- MISCELLANEOUS: Lowering pH destabilizes the protein filaments.
CC {ECO:0000305|PubMed:32165583}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL25391.1; Type=Erroneous translation; Note=Wrong choice of frame.; Evidence={ECO:0000305};
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DR EMBL; AE014296; AAF50350.1; -; Genomic_DNA.
DR EMBL; AE014296; AAF50352.1; -; Genomic_DNA.
DR EMBL; AY052043; AAK93467.1; -; mRNA.
DR EMBL; AY060352; AAL25391.1; ALT_SEQ; mRNA.
DR RefSeq; NP_001261608.1; NM_001274679.1. [Q9VSR3-1]
DR RefSeq; NP_648266.1; NM_140009.3. [Q9VSR3-1]
DR RefSeq; NP_729427.1; NM_168300.3. [Q9VSR3-1]
DR RefSeq; NP_729428.1; NM_168301.3. [Q9VSR3-1]
DR RefSeq; NP_729429.1; NM_168302.3. [Q9VSR3-2]
DR PDB; 6VPS; EM; 2.60 A; A/B/C/D/E/F/G/H/I=176-206.
DR PDBsum; 6VPS; -.
DR AlphaFoldDB; Q9VSR3; -.
DR SMR; Q9VSR3; -.
DR BioGRID; 64423; 80.
DR DIP; DIP-49224N; -.
DR IntAct; Q9VSR3; 13.
DR STRING; 7227.FBpp0303905; -.
DR iPTMnet; Q9VSR3; -.
DR PaxDb; Q9VSR3; -.
DR DNASU; 39018; -.
DR EnsemblMetazoa; FBtr0331511; FBpp0303901; FBgn0264307. [Q9VSR3-2]
DR EnsemblMetazoa; FBtr0331512; FBpp0303902; FBgn0264307. [Q9VSR3-1]
DR EnsemblMetazoa; FBtr0331513; FBpp0303903; FBgn0264307. [Q9VSR3-1]
DR EnsemblMetazoa; FBtr0331514; FBpp0303904; FBgn0264307. [Q9VSR3-1]
DR EnsemblMetazoa; FBtr0331515; FBpp0303905; FBgn0264307. [Q9VSR3-1]
DR GeneID; 39018; -.
DR KEGG; dme:Dmel_CG43782; -.
DR UCSC; CG5735-RA; d. melanogaster. [Q9VSR3-1]
DR CTD; 39018; -.
DR FlyBase; FBgn0264307; orb2.
DR VEuPathDB; VectorBase:FBgn0264307; -.
DR eggNOG; KOG0129; Eukaryota.
DR GeneTree; ENSGT00940000169843; -.
DR InParanoid; Q9VSR3; -.
DR OMA; SDYMRGM; -.
DR PhylomeDB; Q9VSR3; -.
DR SignaLink; Q9VSR3; -.
DR BioGRID-ORCS; 39018; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 39018; -.
DR PRO; PR:Q9VSR3; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0264307; Expressed in testis and 33 other tissues.
DR ExpressionAtlas; Q9VSR3; baseline and differential.
DR Genevisible; Q9VSR3; DM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:0043679; C:axon terminus; IDA:FlyBase.
DR GO; GO:0044297; C:cell body; IDA:FlyBase.
DR GO; GO:0005938; C:cell cortex; IDA:FlyBase.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0005829; C:cytosol; HDA:FlyBase.
DR GO; GO:0044292; C:dendrite terminus; IDA:FlyBase.
DR GO; GO:1990124; C:messenger ribonucleoprotein complex; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:FlyBase.
DR GO; GO:0098794; C:postsynapse; IDA:SynGO.
DR GO; GO:0098793; C:presynapse; IDA:SynGO.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IDA:FlyBase.
DR GO; GO:0097060; C:synaptic membrane; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; IDA:UniProtKB.
DR GO; GO:0000900; F:mRNA regulatory element binding translation repressor activity; IDA:FlyBase.
DR GO; GO:0043022; F:ribosome binding; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; ISM:FlyBase.
DR GO; GO:0008494; F:translation activator activity; IMP:UniProtKB.
DR GO; GO:0008135; F:translation factor activity, RNA binding; IBA:GO_Central.
DR GO; GO:0008356; P:asymmetric cell division; IMP:FlyBase.
DR GO; GO:0007616; P:long-term memory; IMP:UniProtKB.
DR GO; GO:0008049; P:male courtship behavior; IMP:FlyBase.
DR GO; GO:0007141; P:male meiosis I; IMP:FlyBase.
DR GO; GO:2000766; P:negative regulation of cytoplasmic translation; IBA:GO_Central.
DR GO; GO:0017148; P:negative regulation of translation; IDA:FlyBase.
DR GO; GO:0045727; P:positive regulation of translation; IDA:FlyBase.
DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB.
DR GO; GO:0007288; P:sperm axoneme assembly; IMP:FlyBase.
DR GO; GO:0007291; P:sperm individualization; IMP:FlyBase.
DR GO; GO:0007283; P:spermatogenesis; IMP:FlyBase.
DR Gene3D; 3.30.70.330; -; 2.
DR Gene3D; 4.10.640.40; -; 1.
DR InterPro; IPR032296; CEBP_ZZ.
DR InterPro; IPR038446; CEBP_ZZ_sf.
DR InterPro; IPR034819; CPEB.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR PANTHER; PTHR12566; PTHR12566; 1.
DR Pfam; PF16366; CEBP_ZZ; 1.
DR Pfam; PF16367; RRM_7; 1.
DR SMART; SM00360; RRM; 2.
DR SUPFAM; SSF54928; SSF54928; 1.
DR PROSITE; PS50102; RRM; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Amyloid; Cell cycle;
KW Cell division; Cell projection; Cytoplasm; Differentiation; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; RNA-binding; Spermatogenesis;
KW Synapse; Translation regulation.
FT CHAIN 1..704
FT /note="Translational regulator orb2"
FT /id="PRO_0000232396"
FT DOMAIN 447..538
FT /note="RRM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 555..637
FT /note="RRM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT REGION 1..64
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 82..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 163..240
FT /note="Gln/His-rich"
FT /evidence="ECO:0000305|PubMed:28700922"
FT REGION 166..266
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 417..438
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..45
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 172..254
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 74
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 88
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 100
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 425
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 428
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT VAR_SEQ 2..9
FT /note="DSLKLPKA -> YNKFVNFI (in isoform A)"
FT /evidence="ECO:0000303|PubMed:10731132"
FT /id="VSP_051999"
FT VAR_SEQ 10..162
FT /note="Missing (in isoform A)"
FT /evidence="ECO:0000303|PubMed:10731132"
FT /id="VSP_052000"
FT STRAND 177..191
FT /evidence="ECO:0007829|PDB:6VPS"
FT STRAND 197..204
FT /evidence="ECO:0007829|PDB:6VPS"
FT REGION Q9VSR3-2:1..87
FT /note="Gln/His-rich"
FT /evidence="ECO:0000269|PubMed:28700922,
FT ECO:0000269|PubMed:28763009"
SQ SEQUENCE 704 AA; 74504 MW; A4C8BD564C5F6432 CRC64;
MDSLKLPKAN SATSSASGSN SNLSGSTSAS ASAATSPTSS GTAVGGILSG APKSPPGLGS
STPISVRFNA NEESLDDILQ SFHHSKHSPS GGASGGGDAS PTSNLLGMKN NGLGLVVGNC
DSLSSSPSQP QMHAGSASLF GNDEVSLRNN FMQAGGFFNR KSCGGLPNLN LNKPPQLHQQ
QHQQQHQQHQ QHQQQQQLHQ HQQQLSPNLS ALHHHHQQQQ QLRESGGSHS PSSPGGGGGG
SPYNGSQAGC SSGGISPIPP QMGVSPKYRR SISFPIKGNS PTAIYGNMHM DGMGSGHMNI
PTLSIGNGGG GGSTGMVSAG ATGGGDAPYL GNSYGNMMTS NGQMHHGGGL DNSLCDYMRN
MSLGGNGGGD GSNSMSLMQD RMRVMGGPKH LSEADAMAIA ASGNDPSVYL NALKMGSPSR
LSPHSPHSPI QGGNGGNVGD GTARFSRKVF VGGLPPDIDE DEITTSFRRF GPLVVDWPHK
AESKSYFPPK GYAFLLFQDE SSVQQLIDSC ITDEDKLYLC VSSPTIKDKA VQIRPWRLAD
ADYVLDATMS LDPRKTVFVG GVPRPLKAFE LAMIMDRLYG GVCYAGIDTD PELKYPKGAG
RVAFSNQQSY IAAISARFVQ LQHGDIDKRV EVKPYVLDDQ MCDECEGQRC GGKFAPFFCA
NVTCLQYYCE HCWAVIHSRP GREYHKPLVK EGADRPRAVP FRWC
