SMN_MOUSE
ID SMN_MOUSE Reviewed; 288 AA.
AC P97801; O09092;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Survival motor neuron protein;
GN Name=Smn1; Synonyms=Smn;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9070939; DOI=10.1006/geno.1996.4551;
RA Viollet L., Bertrandy S., Brunialti A.L.B., Lefebvre S., Burlet P.,
RA Clermont O., Cruaud C., Guenet J.-L., Munnich A., Melki J.;
RT "cDNA isolation, expression, and chromosomal localization of the mouse
RT survival motor neuron gene (Smn).";
RL Genomics 40:185-188(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9110173; DOI=10.1101/gr.7.4.339;
RA Didonato C.J., Chen X.N., Noya D., Korenberg J.R., Nadeau J.H.,
RA Simard L.R.;
RT "Cloning, characterization, and copy number of the murine survival motor
RT neuron gene: homolog of the spinal muscular atrophy-determining gene.";
RL Genome Res. 7:339-352(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=9275227; DOI=10.1073/pnas.94.18.9920;
RA Schrank B., Goetz R., Gunnersen J.M., Ure J.M., Toyka K.V., Smith A.G.,
RA Sendtner M.;
RT "Inactivation of the survival motor neuron gene, a candidate gene for human
RT spinal muscular atrophy, leads to massive cell death in early mouse
RT embryos.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:9920-9925(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N-3; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP INTERACTION WITH SYNCRIP, AND MUTAGENESIS OF GLU-131; SER-257; TYR-267;
RP THR-269 AND GLY-274.
RX PubMed=11773003; DOI=10.1093/hmg/11.1.93;
RA Rossoll W., Kroening A.-K., Ohndorf U.-M., Steegborn C., Jablonka S.,
RA Sendtner M.;
RT "Specific interaction of Smn, the spinal muscular atrophy determining gene
RT product, with hnRNP-R and gry-rbp/hnRNP-Q: a role for Smn in RNA processing
RT in motor axons?";
RL Hum. Mol. Genet. 11:93-105(2002).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=17353360; DOI=10.1083/jcb.200610053;
RA Rajendra T.K., Gonsalvez G.B., Walker M.P., Shpargel K.B., Salz H.K.,
RA Matera A.G.;
RT "A Drosophila melanogaster model of spinal muscular atrophy reveals a
RT function for SMN in striated muscle.";
RL J. Cell Biol. 176:831-841(2007).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-28, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25 AND SER-28, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-22; SER-25 AND SER-28, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [11]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=21389246; DOI=10.1523/jneurosci.3631-10.2011;
RA Fallini C., Zhang H., Su Y., Silani V., Singer R.H., Rossoll W.,
RA Bassell G.J.;
RT "The survival of motor neuron (SMN) protein interacts with the mRNA-binding
RT protein HuD and regulates localization of poly(A) mRNA in primary motor
RT neuron axons.";
RL J. Neurosci. 31:3914-3925(2011).
RN [12]
RP FUNCTION IN U12 INTRONS SPLICING.
RX PubMed=23063131; DOI=10.1016/j.cell.2012.09.012;
RA Lotti F., Imlach W.L., Saieva L., Beck E.S., Hao le T., Li D.K., Jiao W.,
RA Mentis G.Z., Beattie C.E., McCabe B.D., Pellizzoni L.;
RT "An SMN-dependent U12 splicing event essential for motor circuit
RT function.";
RL Cell 151:440-454(2012).
CC -!- FUNCTION: The SMN complex catalyzes the assembly of small nuclear
CC ribonucleoproteins (snRNPs), the building blocks of the spliceosome,
CC and thereby plays an important role in the splicing of cellular pre-
CC mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins
CC SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in
CC a heptameric protein ring on the Sm site of the small nuclear RNA to
CC form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1,
CC SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm
CC complex by the chaperone CLNS1A that controls the assembly of the core
CC snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm
CC proteins from CLNS1A forming an intermediate. Binding of snRNA inside
CC 5Sm ultimately triggers eviction of the SMN complex, thereby allowing
CC binding of SNRPD3 and SNRPB to complete assembly of the core snRNP.
CC Within the SMN complex, SMN1 acts as a structural backbone and together
CC with GEMIN2 it gathers the Sm complex subunits (By similarity). Ensures
CC the correct splicing of U12 intron-containing genes that may be
CC important for normal motor and proprioceptive neurons development
CC (PubMed:23063131). Also required for resolving RNA-DNA hybrids created
CC by RNA polymerase II, that form R-loop in transcription terminal
CC regions, an important step in proper transcription termination. May
CC also play a role in the metabolism of small nucleolar ribonucleoprotein
CC (snoRNPs) (By similarity). {ECO:0000250|UniProtKB:Q16637,
CC ECO:0000269|PubMed:23063131}.
CC -!- SUBUNIT: Homooligomer; may form higher order homooligomers in the dimer
CC to octamer range. Part of the core SMN complex that contains SMN1,
CC GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8 and
CC STRAP/UNRIP. Part of the SMN-Sm complex that contains SMN1,
CC GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8,
CC STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE,
CC SNRPF and SNRPG. Component of an import snRNP complex composed of
CC KPNB1, RNUT1, SMN1 and ZNF259. Interacts with DDX20, FBL, NOLA1, RNUT1
CC and with several spliceosomal snRNP core Sm proteins, including SNRPB,
CC SNRPD1, SNRPD2, SNRPD3, SNRPE and ILF3. Interacts with GEMIN2; the
CC interaction is direct. Interacts with GEMIN3; the interaction is
CC direct. Interacts with GEMIN8; the interaction is direct. Interacts
CC with SNRPB; the interaction is direct. Interacts (via Tudor domain)
CC with SNRPD1 (via C-terminus); the interaction is direct. Interacts with
CC SNRPD2; the interaction is direct. Interacts (via Tudor domain) with
CC SNRPD3 (via C-terminus); the interaction is direct. Interacts with
CC SNRPE; the interaction is direct. Interacts with OSTF1, LSM10, LSM11
CC and RPP20/POP7. Interacts (via C-terminal region) with ZPR1 (via C-
CC terminal region). Interacts (via Tudor domain) with COIL. Interacts
CC with SETX; recruits SETX to POLR2A. Interacts with POLR2A (via the C-
CC terminal domain (CTD)). Interacts with PRMT5. Interacts with XRN2.
CC Interacts (via C-terminus) with FMR1 (via C-terminus); the interaction
CC is direct and occurs in a RNA-independent manner (By similarity).
CC Interacts with SYNCRIP (PubMed:11773003). Interacts (via Tudor domain)
CC with SF3B2 (methylated form). Interacts with WRAP53/TCAB1 (By
CC similarity). Interacts (via Tudor domain) with ELAVL4 in an RNA-
CC independent manner; the interaction is required for localization of
CC ELAVL4 to RNA granules (By similarity). Interacts with GEMIN2; the
CC interaction is direct (By similarity). Interacts with FRG1 (By
CC similarity). {ECO:0000250|UniProtKB:Q16637,
CC ECO:0000269|PubMed:11773003}.
CC -!- INTERACTION:
CC P97801; P56959: Fus; NbExp=4; IntAct=EBI-309807, EBI-400452;
CC P97801; P35637: FUS; Xeno; NbExp=5; IntAct=EBI-309807, EBI-400434;
CC P97801; P03134: NS1; Xeno; NbExp=3; IntAct=EBI-309807, EBI-9515229;
CC -!- SUBCELLULAR LOCATION: Nucleus, gem {ECO:0000250|UniProtKB:Q16637}.
CC Nucleus, Cajal body {ECO:0000250|UniProtKB:Q16637}. Cytoplasm
CC {ECO:0000269|PubMed:21389246}. Cytoplasmic granule
CC {ECO:0000250|UniProtKB:Q16637}. Perikaryon
CC {ECO:0000250|UniProtKB:Q16637}. Cell projection, neuron projection
CC {ECO:0000250|UniProtKB:Q16637}. Cell projection, axon
CC {ECO:0000269|PubMed:21389246}. Cytoplasm, myofibril, sarcomere, Z line
CC {ECO:0000269|PubMed:17353360}. Note=Colocalizes with actin and at the
CC Z-line of skeletal muscle (PubMed:17353360). Under stress conditions
CC colocalizes with RPP20/POP7 in punctuated cytoplasmic granules.
CC Colocalized and redistributed with ZPR1 from the cytoplasm to nuclear
CC gems (Gemini of coiled bodies) and Cajal bodies. Colocalizes with FMR1
CC in cytoplasmic granules in the soma and neurite cell processes (By
CC similarity). {ECO:0000250|UniProtKB:Q16637,
CC ECO:0000269|PubMed:17353360}.
CC -!- TISSUE SPECIFICITY: Expressed in motor neurons.
CC {ECO:0000269|PubMed:21389246}.
CC -!- DOMAIN: The Tudor domain mediates association with dimethylarginines,
CC which are common in snRNP proteins. {ECO:0000250|UniProtKB:Q16637}.
CC -!- SIMILARITY: Belongs to the SMN family. {ECO:0000305}.
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DR EMBL; U63294; AAC53057.1; -; mRNA.
DR EMBL; U77714; AAC53144.1; -; mRNA.
DR EMBL; Y12835; CAA73356.1; -; mRNA.
DR EMBL; BC045158; AAH45158.1; -; mRNA.
DR CCDS; CCDS26725.1; -.
DR RefSeq; NP_001239558.1; NM_001252629.1.
DR RefSeq; NP_035550.1; NM_011420.2.
DR AlphaFoldDB; P97801; -.
DR BMRB; P97801; -.
DR SMR; P97801; -.
DR BioGRID; 203344; 84.
DR IntAct; P97801; 80.
DR MINT; P97801; -.
DR STRING; 10090.ENSMUSP00000022147; -.
DR iPTMnet; P97801; -.
DR PhosphoSitePlus; P97801; -.
DR EPD; P97801; -.
DR jPOST; P97801; -.
DR PaxDb; P97801; -.
DR PeptideAtlas; P97801; -.
DR PRIDE; P97801; -.
DR ProteomicsDB; 258701; -.
DR DNASU; 20595; -.
DR Ensembl; ENSMUST00000022147; ENSMUSP00000022147; ENSMUSG00000021645.
DR GeneID; 20595; -.
DR KEGG; mmu:20595; -.
DR UCSC; uc007rqh.1; mouse.
DR CTD; 6606; -.
DR MGI; MGI:109257; Smn1.
DR VEuPathDB; HostDB:ENSMUSG00000021645; -.
DR eggNOG; KOG4327; Eukaryota.
DR GeneTree; ENSGT00940000153352; -.
DR HOGENOM; CLU_077852_0_0_1; -.
DR InParanoid; P97801; -.
DR OMA; LMAWYMS; -.
DR OrthoDB; 1316275at2759; -.
DR PhylomeDB; P97801; -.
DR TreeFam; TF318390; -.
DR Reactome; R-MMU-191859; snRNP Assembly.
DR BioGRID-ORCS; 20595; 15 hits in 76 CRISPR screens.
DR ChiTaRS; Smn1; mouse.
DR PRO; PR:P97801; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; P97801; protein.
DR Bgee; ENSMUSG00000021645; Expressed in animal zygote and 254 other tissues.
DR ExpressionAtlas; P97801; baseline and differential.
DR Genevisible; P97801; MM.
DR GO; GO:0015030; C:Cajal body; IDA:MGI.
DR GO; GO:0030137; C:COPI-coated vesicle; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0097504; C:Gemini of coiled bodies; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0030426; C:growth cone; IDA:MGI.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0043204; C:perikaryon; ISS:UniProtKB.
DR GO; GO:0032797; C:SMN complex; ISS:UniProtKB.
DR GO; GO:0034719; C:SMN-Sm protein complex; ISS:UniProtKB.
DR GO; GO:0030018; C:Z disc; IEA:UniProtKB-SubCell.
DR GO; GO:0017134; F:fibroblast growth factor binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0007409; P:axonogenesis; IMP:MGI.
DR GO; GO:0006353; P:DNA-templated transcription, termination; ISS:UniProtKB.
DR GO; GO:0007019; P:microtubule depolymerization; IMP:MGI.
DR GO; GO:0033120; P:positive regulation of RNA splicing; IMP:MGI.
DR GO; GO:0010975; P:regulation of neuron projection development; IGI:MGI.
DR GO; GO:0000387; P:spliceosomal snRNP assembly; ISS:UniProtKB.
DR CDD; cd04508; TUDOR; 1.
DR InterPro; IPR010304; SMN_Tudor.
DR InterPro; IPR002999; Tudor.
DR Pfam; PF06003; SMN; 1.
DR SMART; SM00333; TUDOR; 1.
DR PROSITE; PS50304; TUDOR; 1.
PE 1: Evidence at protein level;
KW Cell projection; Cytoplasm; Isopeptide bond; mRNA processing;
KW mRNA splicing; Neurogenesis; Nucleus; Phosphoprotein; Reference proteome;
KW RNA-binding; Ubl conjugation.
FT CHAIN 1..288
FT /note="Survival motor neuron protein"
FT /id="PRO_0000218904"
FT DOMAIN 88..148
FT /note="Tudor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00211"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 10..41
FT /note="P1 (binding site for GEMIN2)"
FT /evidence="ECO:0000250"
FT REGION 54..85
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 94..204
FT /note="Required for interaction with RPP20/POP7"
FT /evidence="ECO:0000250"
FT REGION 146..216
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 235..262
FT /note="P2 (binding site for SNRPB)"
FT /evidence="ECO:0000250"
FT REGION 274..288
FT /note="Required for interaction with SYNCRIP"
FT /evidence="ECO:0000250"
FT COMPBIAS 186..200
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 5
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16637"
FT MOD_RES 22
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:15345747,
FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"
FT MOD_RES 66
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q16637"
FT CROSSLNK 48
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q16637"
FT CROSSLNK 204
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q16637"
FT MUTAGEN 131
FT /note="E->K: Loss of interaction with SYNCRIP."
FT /evidence="ECO:0000269|PubMed:11773003"
FT MUTAGEN 257
FT /note="S->I: Loss of interaction with SYNCRIP."
FT /evidence="ECO:0000269|PubMed:11773003"
FT MUTAGEN 267
FT /note="Y->C: Loss of interaction with SYNCRIP."
FT /evidence="ECO:0000269|PubMed:11773003"
FT MUTAGEN 269
FT /note="T->I: Loss of interaction with SYNCRIP."
FT /evidence="ECO:0000269|PubMed:11773003"
FT MUTAGEN 274
FT /note="G->V: Loss of interaction with SYNCRIP."
FT /evidence="ECO:0000269|PubMed:11773003"
SQ SEQUENCE 288 AA; 31254 MW; 757B3074649F7458 CRC64;
MAMGSGGAGS EQEDTVLFRR GTGQSDDSDI WDDTALIKAY DKAVASFKHA LKNGDICETP
DKPKGTARRK PAKKNKSQKK NATTPLKQWK VGDKCSAVWS EDGCIYPATI TSIDFKRETC
VVVYTGYGNR EEQNLSDLLS PTCEVANSTE QNTQENESQV STDDSEHSSR SLRSKAHSKS
KAAPWTSFLP PPPPMPGSGL GPGKPGLKFN GPPPPPPLPP PPFLPCWMPP FPSGPPIIPP
PPPISPDCLD DTDALGSMLI SWYMSGYHTG YYMGFRQNKK EGKCSHTN
