ID EXOS9_HUMAN Reviewed; 439 AA.
AC Q06265; Q12883; Q4W5P5; Q86Y41; Q86Y48;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 3.
DT 27-MAR-2024, entry version 213.
DE RecName: Full=Exosome complex component RRP45;
DE AltName: Full=Autoantigen PM/Scl 1;
DE AltName: Full=Exosome component 9;
DE AltName: Full=P75 polymyositis-scleroderma overlap syndrome-associated autoantigen;
DE AltName: Full=Polymyositis/scleroderma autoantigen 1;
DE AltName: Full=Polymyositis/scleroderma autoantigen 75 kDa;
DE Short=PM/Scl-75;
GN Name=EXOSC9; Synonyms=PMSCL1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC TISSUE=Lymphoblastoma;
RX PubMed=2007859; DOI=10.1084/jem.173.4.941;
RA Alderuccio F., Chan E.K.L., Tan E.M.;
RT "Molecular characterization of an autoantigen of PM-Scl in the
RT polymyositis/scleroderma overlap syndrome: a unique and complete human cDNA
RT encoding an apparent 75-kD acidic protein of the nucleolar complex.";
RL J. Exp. Med. 173:941-952(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RA Stahnke G., Haubruck H.;
RT "Nucleotide sequence of an alternatively spliced cDNA coding for PM-Scl-75,
RT an autoantigen of the Polymyositis/Scleroderma overlap syndrome.";
RL Submitted (APR-1994) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, AND
RP IDENTIFICATION IN THE RNA EXOSOME COMPLEX.
RX PubMed=12788944; DOI=10.1074/jbc.m302488200;
RA Raijmakers R., Egberts W.V., van Venrooij W.J., Pruijn G.J.;
RT "The association of the human PM/Scl-75 autoantigen with the exosome is
RT dependent on a newly identified N terminus.";
RL J. Biol. Chem. 278:30698-30704(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP CHARACTERIZATION.
RX PubMed=10465791; DOI=10.1101/gad.13.16.2148;
RA Allmang C., Petfalski E., Podtelejnikov A., Mann M., Tollervey D.,
RA Mitchell P.;
RT "The yeast exosome and human PM-Scl are related complexes of 3'-->5'
RT exonucleases.";
RL Genes Dev. 13:2148-2158(1999).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE RNA EXOSOME
RP CORE COMPLEX.
RX PubMed=11719186; DOI=10.1016/s0092-8674(01)00578-5;
RA Chen C.-Y., Gherzi R., Ong S.-E., Chan E.L., Raijmakers R., Pruijn G.J.M.,
RA Stoecklin G., Moroni C., Mann M., Karin M.;
RT "AU binding proteins recruit the exosome to degrade ARE-containing mRNAs.";
RL Cell 107:451-464(2001).
RN [7]
RP FUNCTION IN ARE-CONTAINING MRNA-BINDING AND CYTOPLASMIC MRNA DEGRADATION,
RP AND SUBCELLULAR LOCATION.
RX PubMed=11782436; DOI=10.1093/emboj/21.1.165;
RA Mukherjee D., Gao M., O'Connor J.P., Raijmakers R., Pruijn G., Lutz C.S.,
RA Wilusz J.;
RT "The mammalian exosome mediates the efficient degradation of mRNAs that
RT contain AU-rich elements.";
RL EMBO J. 21:165-174(2002).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [9]
RP FUNCTION IN NUCLEAR PRE-MRNA DEGRADATION.
RX PubMed=16455498; DOI=10.1016/j.molcel.2005.12.008;
RA West S., Gromak N., Norbury C.J., Proudfoot N.J.;
RT "Adenylation and exosome-mediated degradation of cotranscriptionally
RT cleaved pre-messenger RNA in human cells.";
RL Mol. Cell 21:437-443(2006).
RN [10]
RP FUNCTION, AND ARE BINDING.
RX PubMed=16912217; DOI=10.1261/rna.144606;
RA Anderson J.R., Mukherjee D., Muthukumaraswamy K., Moraes K.C., Wilusz C.J.,
RA Wilusz J.;
RT "Sequence-specific RNA binding mediated by the RNase PH domain of
RT components of the exosome.";
RL RNA 12:1810-1816(2006).
RN [11]
RP FUNCTION IN MRNA DEGRADATION, AND SUBCELLULAR LOCATION.
RX PubMed=17545563; DOI=10.1261/rna.575107;
RA van Dijk E.L., Schilders G., Pruijn G.J.;
RT "Human cell growth requires a functional cytoplasmic exosome, which is
RT involved in various mRNA decay pathways.";
RL RNA 13:1027-1035(2007).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306; SER-392 AND SER-394, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-297, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
RP IDENTIFICATION IN THE RNA EXOSOME COMPLEX, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=20531389; DOI=10.1038/emboj.2010.122;
RA Staals R.H., Bronkhorst A.W., Schilders G., Slomovic S., Schuster G.,
RA Heck A.J., Raijmakers R., Pruijn G.J.;
RT "Dis3-like 1: a novel exoribonuclease associated with the human exosome.";
RL EMBO J. 29:2358-2367(2010).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306; SER-392 AND SER-394, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [21]
RP INTERACTION WITH SETX, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 388-PRO--LEU-391; 390-ILE-LEU-391 AND 395-GLU--GLU-398.
RX PubMed=24105744; DOI=10.1101/gad.224923.113;
RA Richard P., Feng S., Manley J.L.;
RT "A SUMO-dependent interaction between Senataxin and the exosome, disrupted
RT in the neurodegenerative disease AOA2, targets the exosome to sites of
RT transcription-induced DNA damage.";
RL Genes Dev. 27:2227-2232(2013).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65 AND SER-306, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306 AND SER-346,
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-409 AND SER-411 (ISOFORM 2),
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-325 AND SER-327 (ISOFORM 4),
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [24]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-297, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [25]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-297, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [26]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-297, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [27]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-297 AND LYS-419, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [28]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-297 AND LYS-419, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [29]
RP INVOLVEMENT IN PCH1D, AND VARIANTS PCH1D PRO-14 AND 161-ARG--ASN-439 DEL.
RX PubMed=29727687; DOI=10.1016/j.ajhg.2018.03.011;
RA Burns D.T., Donkervoort S., Mueller J.S., Knierim E., Bharucha-Goebel D.,
RA Faqeih E.A., Bell S.K., Alfaifi A.Y., Monies D., Millan F., Retterer K.,
RA Dyack S., MacKay S., Morales-Gonzalez S., Giunta M., Munro B., Hudson G.,
RA Scavina M., Baker L., Massini T.C., Lek M., Hu Y., Ezzo D., Alkuraya F.S.,
RA Kang P.B., Griffin H., Foley A.R., Schuelke M., Horvath R.,
RA Boennemann C.G.;
RT "Variants in EXOSC9 disrupt the RNA exosome and result in cerebellar
RT atrophy with spinal motor neuronopathy.";
RL Am. J. Hum. Genet. 102:858-873(2018).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (3.35 ANGSTROMS), LACK OF CATALYTIC ACTIVITY, AND
RP RECONSTITUTION OF THE RNA EXOSOME CORE COMPLEX.
RX PubMed=17174896; DOI=10.1016/j.cell.2006.10.037;
RA Liu Q., Greimann J.C., Lima C.D.;
RT "Reconstitution, activities, and structure of the eukaryotic RNA exosome.";
RL Cell 127:1223-1237(2006).
RN [31]
RP ERRATUM OF PUBMED:17174896.
RA Liu Q., Greimann J.C., Lima C.D.;
RL Cell 131:188-189(2007).
RN [32] {ECO:0007744|PDB:6D6Q, ECO:0007744|PDB:6D6R}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.45 ANGSTROMS), AND SUBUNIT.
RX PubMed=29906447; DOI=10.1016/j.cell.2018.05.041;
RA Weick E.M., Puno M.R., Januszyk K., Zinder J.C., DiMattia M.A., Lima C.D.;
RT "Helicase-Dependent RNA Decay Illuminated by a Cryo-EM Structure of a Human
RT Nuclear RNA Exosome-MTR4 Complex.";
RL Cell 173:1663-1677.e21(2018).
CC -!- FUNCTION: Non-catalytic component of the RNA exosome complex which has
CC 3'->5' exoribonuclease activity and participates in a multitude of
CC cellular RNA processing and degradation events. In the nucleus, the RNA
CC exosome complex is involved in proper maturation of stable RNA species
CC such as rRNA, snRNA and snoRNA, in the elimination of RNA processing
CC by-products and non-coding 'pervasive' transcripts, such as antisense
CC RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs
CC with processing defects, thereby limiting or excluding their export to
CC the cytoplasm. The RNA exosome may be involved in Ig class switch
CC recombination (CSR) and/or Ig variable region somatic hypermutation
CC (SHM) by targeting AICDA deamination activity to transcribed dsDNA
CC substrates. In the cytoplasm, the RNA exosome complex is involved in
CC general mRNA turnover and specifically degrades inherently unstable
CC mRNAs containing AU-rich elements (AREs) within their 3' untranslated
CC regions, and in RNA surveillance pathways, preventing translation of
CC aberrant mRNAs. It seems to be involved in degradation of histone mRNA.
CC The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9)
CC is proposed to play a pivotal role in the binding and presentation of
CC RNA for ribonucleolysis, and to serve as a scaffold for the association
CC with catalytic subunits and accessory proteins or complexes. EXOSC9
CC binds to ARE-containing RNAs. {ECO:0000269|PubMed:11782436,
CC ECO:0000269|PubMed:16455498, ECO:0000269|PubMed:16912217,
CC ECO:0000269|PubMed:17545563}.
CC -!- SUBUNIT: Component of the RNA exosome complex (PubMed:29906447).
CC Specifically part of the catalytically inactive RNA exosome core (Exo-
CC 9) complex which is believed to associate with catalytic subunits
CC EXOSC10, and DIS3 or DIS3L in cytoplasmic- and nuclear-specific RNA
CC exosome complex forms. Exo-9 is formed by a hexameric ring of RNase PH
CC domain-containing subunits specifically containing the heterodimers
CC EXOSC4-EXOSC9, EXOSC5-EXOSC8 and EXOSC6-EXOSC7, and peripheral S1
CC domain-containing components EXOSC1, EXOSC2 and EXOSC3 located on the
CC top of the ring structure (PubMed:11719186, PubMed:12788944,
CC PubMed:20531389). Interacts (via C-terminus region) with SETX (via N-
CC terminus domain); the interaction enhances SETX sumoylation
CC (PubMed:24105744). {ECO:0000269|PubMed:11719186,
CC ECO:0000269|PubMed:12788944, ECO:0000269|PubMed:20531389,
CC ECO:0000269|PubMed:24105744, ECO:0000269|PubMed:29906447}.
CC -!- INTERACTION:
CC Q06265; Q9NPD3: EXOSC4; NbExp=7; IntAct=EBI-347966, EBI-371823;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11782436}. Nucleus
CC {ECO:0000269|PubMed:24105744}. Nucleus, nucleolus
CC {ECO:0000269|PubMed:24105744}. Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:24105744}. Note=Colocalizes with SETX in nuclear
CC foci upon induction of transcription-related DNA damage at the S phase
CC (PubMed:24105744). {ECO:0000269|PubMed:24105744}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus, nucleolus.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus, nucleolus.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Nucleus. Note=Excluded from the
CC nucleolus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=PM/SCL-75c-alpha;
CC IsoId=Q06265-1; Sequence=Displayed;
CC Name=2; Synonyms=PM/SCL-75c-beta;
CC IsoId=Q06265-2; Sequence=VSP_025556;
CC Name=3; Synonyms=PM/SCL-75a-alpha;
CC IsoId=Q06265-3; Sequence=VSP_025555;
CC Name=4; Synonyms=PM/SCL-75a-beta;
CC IsoId=Q06265-4; Sequence=VSP_025555, VSP_025556;
CC -!- DISEASE: Pontocerebellar hypoplasia 1D (PCH1D) [MIM:618065]: An
CC autosomal recessive neurologic disorder with onset at birth or in
CC infancy, and characterized by progressive axonal motor neuronopathy,
CC severe generalized hypotonia, respiratory insufficiency, and cerebellar
CC atrophy. Death in childhood may occur. {ECO:0000269|PubMed:29727687}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the RNase PH family. {ECO:0000305}.
CC -!- CAUTION: The six exosome core subunits containing a RNase PH-domain are
CC not phosphorolytically active. {ECO:0000305}.
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DR EMBL; M58460; AAA58384.1; -; mRNA.
DR EMBL; U09215; AAA18832.1; -; mRNA.
DR EMBL; AJ505989; CAD44530.1; -; mRNA.
DR EMBL; AJ517294; CAD56889.1; -; mRNA.
DR EMBL; AC079341; AAY40968.1; -; Genomic_DNA.
DR CCDS; CCDS34057.1; -. [Q06265-2]
DR CCDS; CCDS3722.2; -. [Q06265-1]
DR PIR; G01425; G01425.
DR RefSeq; NP_001029366.1; NM_001034194.1. [Q06265-2]
DR RefSeq; NP_005024.2; NM_005033.2. [Q06265-1]
DR PDB; 2NN6; X-ray; 3.35 A; A=1-302.
DR PDB; 6D6Q; EM; 3.45 A; A=1-439.
DR PDB; 6D6R; EM; 3.45 A; A=1-439.
DR PDB; 6H25; EM; 3.80 A; A=1-439.
DR PDBsum; 2NN6; -.
DR PDBsum; 6D6Q; -.
DR PDBsum; 6D6R; -.
DR PDBsum; 6H25; -.
DR AlphaFoldDB; Q06265; -.
DR EMDB; EMD-0127; -.
DR EMDB; EMD-0128; -.
DR EMDB; EMD-14515; -.
DR EMDB; EMD-7808; -.
DR EMDB; EMD-7809; -.
DR SMR; Q06265; -.
DR BioGRID; 111402; 143.
DR ComplexPortal; CPX-476; Nuclear exosome complex, DIS3-EXOSC10 variant.
DR ComplexPortal; CPX-591; Nucleolar exosome complex, EXOSC10 variant.
DR ComplexPortal; CPX-592; Cytoplasmic exosome complex, DIS3L variant.
DR ComplexPortal; CPX-593; Exosome complex, DIS3 variant.
DR ComplexPortal; CPX-600; Cytoplasmic exosome complex, DIS3L-EXOSC10 variant.
DR CORUM; Q06265; -.
DR DIP; DIP-31286N; -.
DR IntAct; Q06265; 54.
DR MINT; Q06265; -.
DR STRING; 9606.ENSP00000368984; -.
DR GlyGen; Q06265; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q06265; -.
DR PhosphoSitePlus; Q06265; -.
DR SwissPalm; Q06265; -.
DR BioMuta; EXOSC9; -.
DR DMDM; 147744559; -.
DR EPD; Q06265; -.
DR jPOST; Q06265; -.
DR MassIVE; Q06265; -.
DR MaxQB; Q06265; -.
DR PaxDb; 9606-ENSP00000368984; -.
DR PeptideAtlas; Q06265; -.
DR ProteomicsDB; 58426; -. [Q06265-1]
DR ProteomicsDB; 58427; -. [Q06265-2]
DR ProteomicsDB; 58428; -. [Q06265-3]
DR ProteomicsDB; 58429; -. [Q06265-4]
DR Pumba; Q06265; -.
DR Antibodypedia; 26749; 171 antibodies from 28 providers.
DR DNASU; 5393; -.
DR Ensembl; ENST00000243498.10; ENSP00000243498.5; ENSG00000123737.13. [Q06265-1]
DR Ensembl; ENST00000379663.7; ENSP00000368984.3; ENSG00000123737.13. [Q06265-2]
DR GeneID; 5393; -.
DR KEGG; hsa:5393; -.
DR MANE-Select; ENST00000243498.10; ENSP00000243498.5; NM_005033.3; NP_005024.2.
DR UCSC; uc003idz.4; human. [Q06265-1]
DR AGR; HGNC:9137; -.
DR CTD; 5393; -.
DR DisGeNET; 5393; -.
DR GeneCards; EXOSC9; -.
DR HGNC; HGNC:9137; EXOSC9.
DR HPA; ENSG00000123737; Low tissue specificity.
DR MalaCards; EXOSC9; -.
DR MIM; 606180; gene.
DR MIM; 618065; phenotype.
DR neXtProt; NX_Q06265; -.
DR OpenTargets; ENSG00000123737; -.
DR Orphanet; 2254; Pontocerebellar hypoplasia type 1.
DR PharmGKB; PA33463; -.
DR VEuPathDB; HostDB:ENSG00000123737; -.
DR eggNOG; KOG1614; Eukaryota.
DR GeneTree; ENSGT00950000183130; -.
DR HOGENOM; CLU_038194_7_0_1; -.
DR InParanoid; Q06265; -.
DR OMA; GPQFENG; -.
DR OrthoDB; 128403at2759; -.
DR PhylomeDB; Q06265; -.
DR TreeFam; TF300092; -.
DR PathwayCommons; Q06265; -.
DR Reactome; R-HSA-380994; ATF4 activates genes in response to endoplasmic reticulum stress.
DR Reactome; R-HSA-429958; mRNA decay by 3' to 5' exoribonuclease.
DR Reactome; R-HSA-450385; Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA.
DR Reactome; R-HSA-450513; Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA.
DR Reactome; R-HSA-450604; KSRP (KHSRP) binds and destabilizes mRNA.
DR Reactome; R-HSA-6791226; Major pathway of rRNA processing in the nucleolus and cytosol.
DR SignaLink; Q06265; -.
DR SIGNOR; Q06265; -.
DR BioGRID-ORCS; 5393; 687 hits in 1173 CRISPR screens.
DR ChiTaRS; EXOSC9; human.
DR EvolutionaryTrace; Q06265; -.
DR GeneWiki; Exosome_component_9; -.
DR GenomeRNAi; 5393; -.
DR Pharos; Q06265; Tbio.
DR PRO; PR:Q06265; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q06265; Protein.
DR Bgee; ENSG00000123737; Expressed in secondary oocyte and 198 other cell types or tissues.
DR ExpressionAtlas; Q06265; baseline and differential.
DR Genevisible; Q06265; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0000177; C:cytoplasmic exosome (RNase complex); IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:ComplexPortal.
DR GO; GO:0000178; C:exosome (RNase complex); IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0000228; C:nuclear chromosome; IDA:UniProtKB.
DR GO; GO:0000176; C:nuclear exosome (RNase complex); IDA:UniProtKB.
DR GO; GO:0101019; C:nucleolar exosome (RNase complex); NAS:ComplexPortal.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000175; F:3'-5'-RNA exonuclease activity; NAS:UniProtKB.
DR GO; GO:0035925; F:mRNA 3'-UTR AU-rich region binding; IDA:GO_Central.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IEA:Ensembl.
DR GO; GO:0043928; P:exonucleolytic catabolism of deadenylated mRNA; IMP:UniProtKB.
DR GO; GO:0000467; P:exonucleolytic trimming to generate mature 3'-end of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA); IBA:GO_Central.
DR GO; GO:0006955; P:immune response; NAS:UniProtKB.
DR GO; GO:0071028; P:nuclear mRNA surveillance; IMP:UniProtKB.
DR GO; GO:0071042; P:nuclear polyadenylation-dependent mRNA catabolic process; IBA:GO_Central.
DR GO; GO:0071035; P:nuclear polyadenylation-dependent rRNA catabolic process; IMP:UniProtKB.
DR GO; GO:0071038; P:nuclear polyadenylation-dependent tRNA catabolic process; IBA:GO_Central.
DR GO; GO:0000956; P:nuclear-transcribed mRNA catabolic process; IMP:UniProtKB.
DR GO; GO:0034427; P:nuclear-transcribed mRNA catabolic process, exonucleolytic, 3'-5'; IBA:GO_Central.
DR GO; GO:0030307; P:positive regulation of cell growth; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0006401; P:RNA catabolic process; IDA:ComplexPortal.
DR GO; GO:0006396; P:RNA processing; IDA:ComplexPortal.
DR GO; GO:0006364; P:rRNA processing; NAS:UniProtKB.
DR GO; GO:0034473; P:U1 snRNA 3'-end processing; IBA:GO_Central.
DR GO; GO:0034475; P:U4 snRNA 3'-end processing; IBA:GO_Central.
DR GO; GO:0034476; P:U5 snRNA 3'-end processing; IBA:GO_Central.
DR CDD; cd11368; RNase_PH_RRP45; 1.
DR Gene3D; 3.30.230.70; GHMP Kinase, N-terminal domain; 1.
DR InterPro; IPR001247; ExoRNase_PH_dom1.
DR InterPro; IPR015847; ExoRNase_PH_dom2.
DR InterPro; IPR036345; ExoRNase_PH_dom2_sf.
DR InterPro; IPR027408; PNPase/RNase_PH_dom_sf.
DR InterPro; IPR020568; Ribosomal_Su5_D2-typ_SF.
DR InterPro; IPR033100; Rrp45.
DR PANTHER; PTHR11097:SF14; EXOSOME COMPLEX COMPONENT RRP45; 1.
DR PANTHER; PTHR11097; EXOSOME COMPLEX EXONUCLEASE RIBOSOMAL RNA PROCESSING PROTEIN; 1.
DR Pfam; PF01138; RNase_PH; 1.
DR Pfam; PF03725; RNase_PH_C; 1.
DR SUPFAM; SSF55666; Ribonuclease PH domain 2-like; 1.
DR SUPFAM; SSF54211; Ribosomal protein S5 domain 2-like; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Disease variant; Exosome; Isopeptide bond; Neurodegeneration; Nucleus;
KW Phosphoprotein; Reference proteome; RNA-binding; rRNA processing;
KW Ubl conjugation.
FT CHAIN 1..439
FT /note="Exosome complex component RRP45"
FT /id="PRO_0000139971"
FT REGION 1..268
FT /note="ARE binding"
FT /evidence="ECO:0000269|PubMed:16912217"
FT REGION 335..363
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 391..439
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 401..416
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 425..439
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 65
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 297
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 306
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 346
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 392
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 394
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT CROSSLNK 297
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 297
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 419
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..84
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:2007859, ECO:0000303|Ref.2"
FT /id="VSP_025555"
FT VAR_SEQ 385
FT /note="Q -> QELGFHHVGQTGLEFLTS (in isoform 2 and isoform
FT 4)"
FT /evidence="ECO:0000303|PubMed:12788944, ECO:0000303|Ref.2"
FT /id="VSP_025556"
FT VARIANT 14
FT /note="L -> P (in PCH1D; reduced EXOSC9 and exosome levels
FT in patient cells; dbSNP:rs139632595)"
FT /evidence="ECO:0000269|PubMed:29727687"
FT /id="VAR_081052"
FT VARIANT 161..439
FT /note="Missing (in PCH1D; reduced EXOSC9 and exosome levels
FT in patient cells)"
FT /evidence="ECO:0000269|PubMed:29727687"
FT /id="VAR_081053"
FT VARIANT 366
FT /note="I -> V (in dbSNP:rs1803183)"
FT /id="VAR_051867"
FT VARIANT 425
FT /note="S -> T (in dbSNP:rs1051881)"
FT /id="VAR_014924"
FT MUTAGEN 388..391
FT /note="PIIL->EECP: Abolishes interaction with SETX."
FT /evidence="ECO:0000269|PubMed:24105744"
FT MUTAGEN 388..391
FT /note="Missing: Abolishes interaction with SETX."
FT /evidence="ECO:0000269|PubMed:24105744"
FT MUTAGEN 390..391
FT /note="Missing: Abolishes interaction with SETX."
FT /evidence="ECO:0000269|PubMed:24105744"
FT MUTAGEN 395..398
FT /note="EEEE->AAAA: Abolishes interaction with SETX."
FT /evidence="ECO:0000269|PubMed:24105744"
FT MUTAGEN 395..398
FT /note="Missing: Abolishes interaction with SETX."
FT /evidence="ECO:0000269|PubMed:24105744"
FT HELIX 8..19
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 24..26
FT /evidence="ECO:0007829|PDB:6D6Q"
FT STRAND 36..39
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 45..52
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 54..59
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 62..64
FT /evidence="ECO:0007829|PDB:2NN6"
FT TURN 69..72
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 76..82
FT /evidence="ECO:0007829|PDB:2NN6"
FT TURN 84..86
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:2NN6"
FT HELIX 96..99
FT /evidence="ECO:0007829|PDB:2NN6"
FT HELIX 101..113
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 118..121
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 122..124
FT /evidence="ECO:0007829|PDB:6D6Q"
FT TURN 125..127
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 128..138
FT /evidence="ECO:0007829|PDB:2NN6"
FT HELIX 146..159
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 165..168
FT /evidence="ECO:0007829|PDB:6D6Q"
FT STRAND 171..174
FT /evidence="ECO:0007829|PDB:6D6Q"
FT HELIX 176..179
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 191..198
FT /evidence="ECO:0007829|PDB:2NN6"
FT TURN 200..202
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 203..208
FT /evidence="ECO:0007829|PDB:2NN6"
FT HELIX 211..216
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 220..226
FT /evidence="ECO:0007829|PDB:2NN6"
FT TURN 227..229
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 230..238
FT /evidence="ECO:0007829|PDB:2NN6"
FT HELIX 244..277
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 284..286
FT /evidence="ECO:0007829|PDB:6D6Q"
FT HELIX 287..290
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 291..298
FT /evidence="ECO:0007829|PDB:2NN6"
FT MOD_RES Q06265-2:409
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES Q06265-2:411
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES Q06265-4:325
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES Q06265-4:327
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
SQ SEQUENCE 439 AA; 48949 MW; 7E27322F094ED3F3 CRC64;
MKETPLSNCE RRFLLRAIEE KKRLDGRQTY DYRNIRISFG TDYGCCIVEL GKTRVLGQVS
CELVSPKLNR ATEGILFFNL ELSQMAAPAF EPGRQSDLLV KLNRLMERCL RNSKCIDTES
LCVVAGEKVW QIRVDLHLLN HDGNIIDAAS IAAIVALCHF RRPDVSVQGD EVTLYTPEER
DPVPLSIHHM PICVSFAFFQ QGTYLLVDPN EREERVMDGL LVIAMNKHRE ICTIQSSGGI
MLLKDQVLRC SKIAGVKVAE ITELILKALE NDQKVRKEGG KFGFAESIAN QRITAFKMEK
APIDTSDVEE KAEEIIAEAE PPSEVVSTPV LWTPGTAQIG EGVENSWGDL EDSEKEDDEG
GGDQAIILDG IKMDTGVEVS DIGSQDAPII LSDSEEEEMI ILEPDKNPKK IRTQTTSAKQ
EKAPSKKPVK RRKKKRAAN
//
