Q9VV74 (SMN_DROME) Reviewed, UniProtKB/Swiss-Prot
Last modified July 9, 2014. Version 120. History...
Names and origin
|Protein names||Recommended name:|
Survival motor neuron protein
|Organism||Drosophila melanogaster (Fruit fly) [Reference proteome]|
|Taxonomic identifier||7227 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Ecdysozoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora ›|
|Sequence length||226 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
The SMN complex plays an essential role in spliceosomal snRNP assembly in the cytoplasm, is required for pre-mRNA splicing in the nucleus and acts as a chaperone that discriminates target and non-target RNAs of Sm proteins. Required for normal expression of spliceosomal snRNAs and for U12 intron splicing. Required in cholinergic neurons, but not in motor neurons, to ensure correct splicing and proper levels of stas mRNA and normal neurotransmitter release by motor neurons (Ref.18 and Ref.19). However, Smn is required in motor neurons, but not in cholinergic neurons, for normal motor behavior but plays no role in synaptic transmission according to Ref.17. In both muscle and neurons, required for the formation of a normal neuromuscular junction (NMJ) structure. Plays a neuron-specific role in long-term homeostatic compensation at the larval NMJ. In the thorax of adult flies, required for Act88F, an indirect flight muscle (IFM)-specific actin, expression and for proper IFM myofibril formation. In nurse cells, oocytes and follicle cells, required to maintain normal organization of nuclear compartments including chromosomes, nucleoli, Cajal bodies, histone locus bodies and heterochromatin. Required for the functional integrity of the cytoplasmic U snRNP body (U body) and P body. Required in dividing postembryonic neuroblasts (pNBs) for the correct basal localization of mira. The tight regulation of its expression is critical for stem cell division, proliferation and differentiation in male germline and developing central nervous system (CNS). Required for tracheal terminal cell lumen formation. Ref.5 Ref.9 Ref.11 Ref.12 Ref.14 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.23
Homodimer (via C-terminal region). Part of the core SMN complex, which seems to be composed of Smn and Gem2 only. The SMN complex associates with the entire set of spliceosomal snRNP Sm proteins, SmB, SmD1, SmD2, SmD3, SmE, SmF and SmG, and with the snRNP-specific proteins snRNP-U1-70K, U2A, snf/U1A and U5-116KD. Associates weakly with Gem3. Interacts with SmB and SmD1; the interaction is favored by methylation of the Sm proteins. Interacts with Actn; the interaction occurs in thoracic tissues and in adult flies. Interacts with Rpp20, msk and snupn. Ref.1 Ref.5 Ref.6 Ref.7 Ref.9 Ref.12 Ref.13 Ref.19 Ref.20 Ref.22 Ref.23
Cytoplasm. Nucleus › gem. Cytoplasm › myofibril › sarcomere › I band. Cytoplasm › myofibril › sarcomere › Z line. Note: Component of U bodies. High expression detected in the cytoplasm of female germline stem cells and cystoblast which persists up to stage 10 egg chambers. Accumulates in the cytoplasm of dividing pNBs. Colocalizes with Actn at the Z-line of IFMs. Expression concentrates at the post-synaptic region of NMJs in larval brain. Ref.8 Ref.9 Ref.10 Ref.11 Ref.14 Ref.15 Ref.16
In late first instar larvae, expressed in pNBs. Expression increases as the pNBs enlarge, with the highest accumulation observed in dividing pNBs of second and third instar larvae. Enriched in type ID (thoracic and brain lobe), type IA and all the mira-expressing NBs of the brain lobes. In larvae, also expressed in muscle fibers. In larval and adult testis, expressed in germline stem cells and gonialblast, expression decreases as cells differentiate into cysts and spermatocytes. In adult fly thorax, expressed in the IFMs. In adult ovary, expressed in germline stem cells, cystoblasts, follicle cells, nurse cells and oocyte (at protein level). Also expressed in larval salivary glands. Ref.5 Ref.8 Ref.9 Ref.10 Ref.14 Ref.16
Expressed both maternally and zygotically. Expressed ubiquitously throughout development. Expression is high during embryogenesis but decreases 30-fold in adult flies (at protein level). Ref.1 Ref.5 Ref.8 Ref.9 Ref.11
Embryos lacking maternal and zygotic Smn die between 0 and 4 hours after egg laying. Zygotic mutants never initiate pupation but instead persist as third instar larvae, often surviving at this stage for several days. Mutant larvae exhibit reduced CNS, testes and muscle size, decreased locomotion and altered rhythmic motor activity. At the NMJ, mutant larvae show an overall decrease in the number of synaptic boutons, but an increase in enlarged ones, loss of large glutamate receptor clusters and an aberrant increase in evoked excitatory postsynaptic potential (eEPSP) amplitude and in miniature EPSP frequency. Mutant larvae also show defective mira subcellular localization in pNBs. Mutant larvae show a decrease of spliceosomal snRNA levels and splicing defects in U12 intron-containing genes (Ref.19). But appreciable splicing defects in U12 intron-containing genes are not observed in mutant larvae, although a decrease in spliceosomal snRNA levels is detected, in Ref.20. Ref.5 Ref.9 Ref.11 Ref.14 Ref.16 Ref.18 Ref.19 Ref.20
Belongs to the SMN family.
Contains 1 Tudor domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 226||226||Survival motor neuron protein||PRO_0000424374|
|Domain||69 – 128||60||Tudor|
|Region||159 – 226||68||Required for homodimerization Ref.1|
|Mutagenesis||20||1||D → V: Does not affect homodimer formation. Ref.20|
|Mutagenesis||70||1||F → S: Does not affect homodimer formation. Ref.20|
|Mutagenesis||201||1||S → F in allele Smn-B; homozygous lethal at late larval stages and abolishes homodimerization. Ref.5|
|Mutagenesis||202||1||G → S in allele Smn-73Ao; homozygous lethal at late larval stages and abolishes homodimerization. Ref.5|
|Mutagenesis||203||1||Y → C: Weakly inhibits homodimer formation. Ref.20|
|Mutagenesis||205||1||T → I: Rescues larval viability and locomotion defects and only partially restores U5 and U12 snRNA levels in the null mutant. Weakly inhibits homodimer formation. Does not affect protein stability. Ref.20|
|Mutagenesis||206||1||G → S: Inhibits homodimer formation. Ref.20|
Helix Strand Turn
|Helix||15 – 23||9|
|||"Disruption of SMN function by ectopic expression of the human SMN gene in Drosophila."|
Miguel-Aliaga I., Chan Y.B., Davies K.E., van den Heuvel M.
FEBS Lett. 486:99-102(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBUNIT, DEVELOPMENTAL STAGE.
|||"The genome sequence of Drosophila melanogaster."|
Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. Venter J.C.
Science 287:2185-2195(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
|||"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review."|
Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. Lewis S.E.
Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: GENOME REANNOTATION.
|||"A Drosophila full-length cDNA resource."|
Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E.
Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Larva and Pupae.
|||"Neuromuscular defects in a Drosophila survival motor neuron gene mutant."|
Chan Y.B., Miguel-Aliaga I., Franks C., Thomas N., Trulzsch B., Sattelle D.B., Davies K.E., van den Heuvel M.
Hum. Mol. Genet. 12:1367-1376(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, MUTAGENESIS OF SER-201 AND GLY-202.
|||"Rpp20 interacts with SMN and is re-distributed into SMN granules in response to stress."|
Hua Y., Zhou J.
Biochem. Biophys. Res. Commun. 314:268-276(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, INTERACTION WITH RPP20.
|||"The Sm-protein methyltransferase, dart5, is essential for germ-cell specification and maintenance."|
Gonsalvez G.B., Rajendra T.K., Tian L., Matera A.G.
Curr. Biol. 16:1077-1089(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SMB.
|||"The Drosophila melanogaster Cajal body."|
Liu J.L., Murphy C., Buszczak M., Clatterbuck S., Goodman R., Gall J.G.
J. Cell Biol. 172:875-884(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
|||"A Drosophila melanogaster model of spinal muscular atrophy reveals a function for SMN in striated muscle."|
Rajendra T.K., Gonsalvez G.B., Walker M.P., Shpargel K.B., Salz H.K., Matera A.G.
J. Cell Biol. 176:831-841(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, INTERACTION WITH ACTN, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
|||"U bodies are cytoplasmic structures that contain uridine-rich small nuclear ribonucleoproteins and associate with P bodies."|
Liu J.L., Gall J.G.
Proc. Natl. Acad. Sci. U.S.A. 104:11655-11659(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
|||"Modeling spinal muscular atrophy in Drosophila."|
Chang H.C., Dimlich D.N., Yokokura T., Mukherjee A., Kankel M.W., Sen A., Sridhar V., Fulga T.A., Hart A.C., Van Vactor D., Artavanis-Tsakonas S.
PLoS ONE 3:E3209-E3209(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
|||"Evolution of an RNP assembly system: a minimal SMN complex facilitates formation of UsnRNPs in Drosophila melanogaster."|
Kroiss M., Schultz J., Wiesner J., Chari A., Sickmann A., Fischer U.
Proc. Natl. Acad. Sci. U.S.A. 105:10045-10050(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN THE SMN COMPLEX, INTERACTION WITH THE SPLICEOSOME USNRNP PROTEINS SNRNP-U1-70K, U2A, SNF/U1A AND U5-116KD, INTERACTION WITH THE SNRNP SM PROTEINS, INTERACTION WITH GEM3.
|||"Sm protein methylation is dispensable for snRNP assembly in Drosophila melanogaster."|
Gonsalvez G.B., Praveen K., Hicks A.J., Tian L., Matera A.G.
RNA 14:878-887(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SMD1.
|||"The spinal muscular atrophy protein SMN affects Drosophila germline nuclear organization through the U body-P body pathway."|
Lee L., Davies S.E., Liu J.L.
Dev. Biol. 332:142-155(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
|||"Drosophila SMN complex proteins Gemin2, Gemin3, and Gemin5 are components of U bodies."|
Cauchi R.J., Sanchez-Pulido L., Liu J.L.
Exp. Cell Res. 316:2354-2364(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
|||"Survival motor neuron protein regulates stem cell division, proliferation, and differentiation in Drosophila."|
Grice S.J., Liu J.L.
PLoS Genet. 7:E1002030-E1002030(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
|||"Behavioral and electrophysiological outcomes of tissue-specific Smn knockdown in Drosophila melanogaster."|
Timmerman C., Sanyal S.
Brain Res. 1489:66-80(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"SMN is required for sensory-motor circuit function in Drosophila."|
Imlach W.L., Beck E.S., Choi B.J., Lotti F., Pellizzoni L., McCabe B.D.
Cell 151:427-439(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
|||"An SMN-dependent U12 splicing event essential for motor circuit function."|
Lotti F., Imlach W.L., Saieva L., Beck E.S., Hao le T., Li D.K., Jiao W., Mentis G.Z., Beattie C.E., McCabe B.D., Pellizzoni L.
Cell 151:440-454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, DISRUPTION PHENOTYPE.
|||"A Drosophila model of spinal muscular atrophy uncouples snRNP biogenesis functions of survival motor neuron from locomotion and viability defects."|
Praveen K., Wen Y., Matera A.G.
Cell Rep. 1:624-631(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, DISRUPTION PHENOTYPE, MUTAGENESIS OF ASP-20; PHE-70; TYR-203; THR-205 AND GLY-206.
|||"Drosophila Zpr1 (Zinc finger protein 1) is required downstream of both EGFR and FGFR signaling in tracheal subcellular lumen formation."|
Ruiz O.E., Nikolova L.S., Metzstein M.M.
PLoS ONE 7:E45649-E45649(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"Identification and characterization of Drosophila Snurportin reveals a role for the import receptor Moleskin/Importin7 in snRNP biogenesis."|
Natalizio A.H., Matera A.G.
Mol. Biol. Cell 24:2932-2942(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MSK AND SNUPN.
|||"Structural basis of assembly chaperone-mediated snRNP formation."|
Grimm C., Chari A., Pelz J.P., Kuper J., Kisker C., Diederichs K., Stark H., Schindelin H., Fischer U.
Mol. Cell 49:692-703(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 1-122, FUNCTION, SUBUNIT.
|+||Additional computationally mapped references.|
|AF296281 mRNA. Translation: AAG17893.1.|
AE014296 Genomic DNA. Translation: AAF49446.1.
AE014296 Genomic DNA. Translation: AGB94647.1.
AY058529 mRNA. Translation: AAL13758.1.
|RefSeq||NP_001261954.1. NM_001275025.1. |
3D structure databases
|SMR||Q9VV74. Positions 2-27, 68-121. |
Protein-protein interaction databases
|IntAct||Q9VV74. 8 interactions.|
Protocols and materials databases
Genome annotation databases
|EnsemblMetazoa||FBtr0075395; FBpp0075153; FBgn0036641. |
FBtr0329921; FBpp0302954; FBgn0036641.
|UCSC||CG16725-RA. d. melanogaster. |
|FlyBase||FBgn0036641. Smn. |
Family and domain databases
|InterPro||IPR010304. Survival_motor_neuron. |
|Pfam||PF06003. SMN. 1 hit. |
|SMART||SM00333. TUDOR. 1 hit. |
|Accession||Primary (citable) accession number: Q9VV74|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Drosophila annotation project|