EXOS3_HUMAN
ID EXOS3_HUMAN Reviewed; 275 AA.
AC Q9NQT5; A8K0K6; Q5QP85; Q9Y3A8;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Exosome complex component RRP40;
DE AltName: Full=Exosome component 3;
DE AltName: Full=Ribosomal RNA-processing protein 40;
DE AltName: Full=p10;
GN Name=EXOSC3; Synonyms=RRP40; ORFNames=CGI-102;
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 1), AND CHARACTERIZATION.
RX PubMed=11110791; DOI=10.1074/jbc.m007603200;
RA Brouwer R., Allmang C., Raijmakers R., van Aarssen Y., Egberts W.V.,
RA Petfalski E., van Venrooij W.J., Tollervey D., Pruijn G.J.M.;
RT "Three novel components of the human exosome.";
RL J. Biol. Chem. 276:6177-6184(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin, and Uterus;
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 [6]
RP PROTEIN SEQUENCE OF 2-16 AND 202-208, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT ALA-2, SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RA Bienvenut W.V.;
RL Submitted (AUG-2005) to UniProtKB.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 56-275 (ISOFORM 1).
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [8]
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 [9]
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 [10]
RP FUNCTION IN CYTOPLASMIC MRNA DEGRADATION.
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 [11]
RP INTERACTION WITH DHX36.
RX PubMed=14731398; DOI=10.1016/s1097-2765(03)00481-7;
RA Tran H., Schilling M., Wirbelauer C., Hess D., Nagamine Y.;
RT "Facilitation of mRNA deadenylation and decay by the exosome-bound, DExH
RT protein RHAU.";
RL Mol. Cell 13:101-111(2004).
RN [12]
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 [13]
RP INTERACTION WITH DDX17.
RX PubMed=18334637; DOI=10.1073/pnas.0712276105;
RA Chen G., Guo X., Lv F., Xu Y., Gao G.;
RT "p72 DEAD box RNA helicase is required for optimal function of the zinc-
RT finger antiviral protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:4352-4357(2008).
RN [14]
RP FUNCTION IN PROMPT DEGRADATION.
RX PubMed=19056938; DOI=10.1126/science.1164096;
RA Preker P., Nielsen J., Kammler S., Lykke-Andersen S., Christensen M.S.,
RA Mapendano C.K., Schierup M.H., Jensen T.H.;
RT "RNA exosome depletion reveals transcription upstream of active human
RT promoters.";
RL Science 322:1851-1854(2008).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [16]
RP IDENTIFICATION IN THE RNA EXOSOME COMPLEX, IDENTIFICATION BY MASS
RP SPECTROMETRY, SUBCELLULAR LOCATION, AND INTERACTION WITH DIS3L.
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 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 [18]
RP FUNCTION IN DEAMINATION OF TRANSCRIBED DNA SUBSTRATE.
RX PubMed=21255825; DOI=10.1016/j.cell.2011.01.001;
RA Basu U., Meng F.L., Keim C., Grinstein V., Pefanis E., Eccleston J.,
RA Zhang T., Myers D., Wasserman C.R., Wesemann D.R., Januszyk K.,
RA Gregory R.I., Deng H., Lima C.D., Alt F.W.;
RT "The RNA exosome targets the AID cytidine deaminase to both strands of
RT transcribed duplex DNA substrates.";
RL Cell 144:353-363(2011).
RN [19]
RP INTERACTION WITH GTPBP1.
RX PubMed=21515746; DOI=10.1096/fj.10-178715;
RA Woo K.C., Kim T.D., Lee K.H., Kim D.Y., Kim S., Lee H.R., Kang H.J.,
RA Chung S.J., Senju S., Nishimura Y., Kim K.T.;
RT "Modulation of exosome-mediated mRNA turnover by interaction of GTP-binding
RT protein 1 (GTPBP1) with its target mRNAs.";
RL FASEB J. 25:2757-2769(2011).
RN [20]
RP INTERACTION WITH ZC3HAV1.
RX PubMed=21876179; DOI=10.1073/pnas.1101676108;
RA Zhu Y., Chen G., Lv F., Wang X., Ji X., Xu Y., Sun J., Wu L., Zheng Y.T.,
RA Gao G.;
RT "Zinc-finger antiviral protein inhibits HIV-1 infection by selectively
RT targeting multiply spliced viral mRNAs for degradation.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:15834-15839(2011).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [24]
RP INTERACTION WITH ISOFORM 2 OF HBS1L.
RX PubMed=28204585; DOI=10.1093/nar/gkw862;
RA Kalisiak K., Kulinski T.M., Tomecki R., Cysewski D., Pietras Z.,
RA Chlebowski A., Kowalska K., Dziembowski A.;
RT "A short splicing isoform of HBS1L links the cytoplasmic exosome and SKI
RT complexes in humans.";
RL Nucleic Acids Res. 45:2068-2080(2017).
RN [25]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-151, AND IDENTIFICATION BY MASS
RP 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 [26]
RP X-RAY CRYSTALLOGRAPHY (3.35 ANGSTROMS), AND RECONSTITUTION OF THE RNA
RP 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 [27]
RP ERRATUM OF PUBMED:17174896.
RA Liu Q., Greimann J.C., Lima C.D.;
RL Cell 131:188-189(2007).
RN [28] {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).
RN [29]
RP VARIANTS PCH1B ALA-31; ALA-132; PRO-139 AND ARG-238.
RX PubMed=22544365; DOI=10.1038/ng.2254;
RA Wan J., Yourshaw M., Mamsa H., Rudnik-Schoneborn S., Menezes M.P.,
RA Hong J.E., Leong D.W., Senderek J., Salman M.S., Chitayat D., Seeman P.,
RA von Moers A., Graul-Neumann L., Kornberg A.J., Castro-Gago M.,
RA Sobrido M.J., Sanefuji M., Shieh P.B., Salamon N., Kim R.C., Vinters H.V.,
RA Chen Z., Zerres K., Ryan M.M., Nelson S.F., Jen J.C.;
RT "Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar
RT hypoplasia and spinal motor neuron degeneration.";
RL Nat. Genet. 44:704-708(2012).
RN [30]
RP VARIANT PHE-80.
RX PubMed=25841024; DOI=10.1212/wnl.0000000000001524;
RA Coutelier M., Burglen L., Mundwiller E., Abada-Bendib M., Rodriguez D.,
RA Chantot-Bastaraud S., Rougeot C., Cournelle M.A., Milh M., Toutain A.,
RA Bacq D., Meyer V., Afenjar A., Deleuze J.F., Brice A., Heron D.,
RA Stevanin G., Durr A.;
RT "GRID2 mutations span from congenital to mild adult-onset cerebellar
RT ataxia.";
RL Neurology 84:1751-1759(2015).
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. EXOSC3 as
CC peripheral part of the Exo-9 complex stabilizes the hexameric ring of
CC RNase PH-domain subunits through contacts with EXOSC9 and EXOSC5.
CC {ECO:0000269|PubMed:11782436, ECO:0000269|PubMed:17545563,
CC ECO:0000269|PubMed:19056938, ECO:0000269|PubMed:21255825}.
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. Interacts with GTPBP1. Interacts with
CC ZC3HAV1. Interacts with DDX17 only in the presence of ZC3HAV1 in an
CC RNA-independent manner. Interacts with DHX36; this interaction occurs
CC in a RNase-insensitive manner (PubMed:14731398). Interacts with HBS1L
CC isoform 2 (PubMed:28204585). {ECO:0000269|PubMed:11719186,
CC ECO:0000269|PubMed:14731398, ECO:0000269|PubMed:18334637,
CC ECO:0000269|PubMed:20531389, ECO:0000269|PubMed:21515746,
CC ECO:0000269|PubMed:21876179, ECO:0000269|PubMed:28204585,
CC ECO:0000269|PubMed:29906447}.
CC -!- INTERACTION:
CC Q9NQT5; Q92841: DDX17; NbExp=2; IntAct=EBI-371866, EBI-746012;
CC Q9NQT5; Q9Y2L1: DIS3; NbExp=3; IntAct=EBI-371866, EBI-373539;
CC Q9NQT5; Q8TF46: DIS3L; NbExp=5; IntAct=EBI-371866, EBI-3672244;
CC Q9NQT5; Q13868: EXOSC2; NbExp=8; IntAct=EBI-371866, EBI-301735;
CC Q9NQT5; Q9NPD3: EXOSC4; NbExp=7; IntAct=EBI-371866, EBI-371823;
CC Q9NQT5; Q9NQT4: EXOSC5; NbExp=10; IntAct=EBI-371866, EBI-371876;
CC Q9NQT5; Q96B26: EXOSC8; NbExp=5; IntAct=EBI-371866, EBI-371922;
CC Q9NQT5; Q969E8: TSR2; NbExp=3; IntAct=EBI-371866, EBI-746981;
CC Q9NQT5; Q8K3Y6: Zc3hav1; Xeno; NbExp=3; IntAct=EBI-371866, EBI-8860250;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17545563}. Nucleus,
CC nucleolus {ECO:0000269|PubMed:20531389}. Nucleus
CC {ECO:0000269|PubMed:17545563}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NQT5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NQT5-2; Sequence=VSP_043457;
CC -!- DISEASE: Pontocerebellar hypoplasia 1B (PCH1B) [MIM:614678]: A severe
CC autosomal recessive neurologic disorder characterized by a combination
CC of cerebellar and spinal motor neuron degeneration beginning at birth.
CC There is diffuse muscle weakness, progressive microcephaly, global
CC developmental delay, and brainstem involvement.
CC {ECO:0000269|PubMed:22544365}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the RRP40 family. {ECO:0000305}.
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DR EMBL; AF281132; AAF82133.1; -; mRNA.
DR EMBL; AK289571; BAF82260.1; -; mRNA.
DR EMBL; AK290864; BAF83553.1; -; mRNA.
DR EMBL; AL138752; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471071; EAW58264.1; -; Genomic_DNA.
DR EMBL; BC002437; AAH02437.1; -; mRNA.
DR EMBL; BC008880; AAH08880.1; -; mRNA.
DR EMBL; AF151860; AAD34097.1; -; mRNA.
DR CCDS; CCDS35016.1; -. [Q9NQT5-1]
DR CCDS; CCDS43805.1; -. [Q9NQT5-2]
DR RefSeq; NP_001002269.1; NM_001002269.2. [Q9NQT5-2]
DR RefSeq; NP_057126.2; NM_016042.3. [Q9NQT5-1]
DR PDB; 2NN6; X-ray; 3.35 A; G=1-275.
DR PDB; 6D6Q; EM; 3.45 A; G=1-275.
DR PDB; 6D6R; EM; 3.45 A; G=1-275.
DR PDB; 6H25; EM; 3.80 A; G=1-275.
DR PDBsum; 2NN6; -.
DR PDBsum; 6D6Q; -.
DR PDBsum; 6D6R; -.
DR PDBsum; 6H25; -.
DR AlphaFoldDB; Q9NQT5; -.
DR SMR; Q9NQT5; -.
DR BioGRID; 119217; 75.
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; Q9NQT5; -.
DR DIP; DIP-29847N; -.
DR IntAct; Q9NQT5; 44.
DR MINT; Q9NQT5; -.
DR STRING; 9606.ENSP00000323046; -.
DR GlyGen; Q9NQT5; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NQT5; -.
DR PhosphoSitePlus; Q9NQT5; -.
DR SwissPalm; Q9NQT5; -.
DR BioMuta; EXOSC3; -.
DR DMDM; 14285758; -.
DR EPD; Q9NQT5; -.
DR jPOST; Q9NQT5; -.
DR MassIVE; Q9NQT5; -.
DR MaxQB; Q9NQT5; -.
DR PaxDb; Q9NQT5; -.
DR PeptideAtlas; Q9NQT5; -.
DR PRIDE; Q9NQT5; -.
DR ProteomicsDB; 82184; -. [Q9NQT5-1]
DR ProteomicsDB; 82185; -. [Q9NQT5-2]
DR Antibodypedia; 12051; 296 antibodies from 28 providers.
DR DNASU; 51010; -.
DR Ensembl; ENST00000327304.10; ENSP00000323046.4; ENSG00000107371.14. [Q9NQT5-1]
DR Ensembl; ENST00000396521.3; ENSP00000379775.3; ENSG00000107371.14. [Q9NQT5-2]
DR Ensembl; ENST00000465229.5; ENSP00000418422.1; ENSG00000107371.14. [Q9NQT5-2]
DR Ensembl; ENST00000679059.1; ENSP00000503947.1; ENSG00000107371.14. [Q9NQT5-2]
DR GeneID; 51010; -.
DR KEGG; hsa:51010; -.
DR MANE-Select; ENST00000327304.10; ENSP00000323046.4; NM_016042.4; NP_057126.2.
DR UCSC; uc004aal.4; human. [Q9NQT5-1]
DR CTD; 51010; -.
DR DisGeNET; 51010; -.
DR GeneCards; EXOSC3; -.
DR GeneReviews; EXOSC3; -.
DR HGNC; HGNC:17944; EXOSC3.
DR HPA; ENSG00000107371; Low tissue specificity.
DR MalaCards; EXOSC3; -.
DR MIM; 606489; gene.
DR MIM; 614678; phenotype.
DR neXtProt; NX_Q9NQT5; -.
DR OpenTargets; ENSG00000107371; -.
DR Orphanet; 2254; Pontocerebellar hypoplasia type 1.
DR PharmGKB; PA134926550; -.
DR VEuPathDB; HostDB:ENSG00000107371; -.
DR eggNOG; KOG1004; Eukaryota.
DR GeneTree; ENSGT00940000153596; -.
DR HOGENOM; CLU_069847_3_0_1; -.
DR InParanoid; Q9NQT5; -.
DR OMA; SYMAFPN; -.
DR OrthoDB; 1284731at2759; -.
DR PhylomeDB; Q9NQT5; -.
DR TreeFam; TF314927; -.
DR PathwayCommons; Q9NQT5; -.
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; Q9NQT5; -.
DR SIGNOR; Q9NQT5; -.
DR BioGRID-ORCS; 51010; 757 hits in 1088 CRISPR screens.
DR ChiTaRS; EXOSC3; human.
DR EvolutionaryTrace; Q9NQT5; -.
DR GeneWiki; Exosome_component_3; -.
DR GenomeRNAi; 51010; -.
DR Pharos; Q9NQT5; Tbio.
DR PRO; PR:Q9NQT5; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q9NQT5; protein.
DR Bgee; ENSG00000107371; Expressed in oocyte and 178 other tissues.
DR Genevisible; Q9NQT5; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0000177; C:cytoplasmic exosome (RNase complex); IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:ComplexPortal.
DR GO; GO:0000791; C:euchromatin; IMP:UniProtKB.
DR GO; GO:0000178; C:exosome (RNase complex); IDA:UniProtKB.
DR GO; GO:0000176; C:nuclear exosome (RNase complex); IDA:UniProtKB.
DR GO; GO:0101019; C:nucleolar exosome (RNase complex); IC:ComplexPortal.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000175; F:3'-5'-exoribonuclease activity; NAS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IBA:GO_Central.
DR GO; GO:0071034; P:CUT catabolic process; IMP:UniProtKB.
DR GO; GO:0045006; P:DNA deamination; IDA:UniProtKB.
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:0045190; P:isotype switching; ISS:UniProtKB.
DR GO; GO:0071035; P:nuclear polyadenylation-dependent rRNA catabolic process; IBA:GO_Central.
DR GO; GO:0071038; P:nuclear polyadenylation-dependent tRNA catabolic process; IBA:GO_Central.
DR GO; GO:0034427; P:nuclear-transcribed mRNA catabolic process, exonucleolytic, 3'-5'; IBA:GO_Central.
DR GO; GO:0071051; P:polyadenylation-dependent snoRNA 3'-end processing; IBA:GO_Central.
DR GO; GO:0045830; P:positive regulation of isotype switching; 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; IDA:UniProtKB.
DR GO; GO:0034475; P:U4 snRNA 3'-end processing; IBA:GO_Central.
DR CDD; cd05790; S1_Rrp40; 1.
DR Gene3D; 2.40.50.140; -; 1.
DR Gene3D; 3.30.1370.10; -; 1.
DR InterPro; IPR026699; Exosome_RNA_bind1/RRP40/RRP4.
DR InterPro; IPR004088; KH_dom_type_1.
DR InterPro; IPR036612; KH_dom_type_1_sf.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR037319; Rrp40_S1.
DR PANTHER; PTHR21321; PTHR21321; 1.
DR Pfam; PF15985; KH_6; 1.
DR SUPFAM; SSF50249; SSF50249; 1.
DR SUPFAM; SSF54791; SSF54791; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Direct protein sequencing; Disease variant; Exosome; Isopeptide bond;
KW Neurodegeneration; Nucleus; Reference proteome; RNA-binding;
KW rRNA processing; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT CHAIN 2..275
FT /note="Exosome complex component RRP40"
FT /id="PRO_0000087131"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT CROSSLNK 151
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 159..275
FT /note="VGDLIYGQFVVANKDMEPEMVCIDSCGRANGMGVIGQDGLLFKVTLGLIRKL
FT LAPDCEIIQEVGKLYPLEIVFGMNGRIWVKAKTIQQTLILANILEACEHMTSDQRKQIF
FT SRLAES -> AISSRL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043457"
FT VARIANT 31
FT /note="G -> A (in PCH1B; dbSNP:rs387907196)"
FT /evidence="ECO:0000269|PubMed:22544365"
FT /id="VAR_068505"
FT VARIANT 80
FT /note="V -> F (in dbSNP:rs374550999)"
FT /evidence="ECO:0000269|PubMed:25841024"
FT /id="VAR_074169"
FT VARIANT 132
FT /note="D -> A (in PCH1B; dbSNP:rs141138948)"
FT /evidence="ECO:0000269|PubMed:22544365"
FT /id="VAR_068506"
FT VARIANT 139
FT /note="A -> P (in PCH1B; dbSNP:rs387907195)"
FT /evidence="ECO:0000269|PubMed:22544365"
FT /id="VAR_068507"
FT VARIANT 225
FT /note="Y -> H (in dbSNP:rs3208406)"
FT /id="VAR_054098"
FT VARIANT 238
FT /note="W -> R (in PCH1B; dbSNP:rs672601332)"
FT /evidence="ECO:0000269|PubMed:22544365"
FT /id="VAR_068508"
FT CONFLICT 56..65
FT /note="NARACSRVRV -> MLERARGCAF (in Ref. 7; AAD34097)"
FT /evidence="ECO:0000305"
FT CONFLICT 95
FT /note="S -> G (in Ref. 7; AAD34097)"
FT /evidence="ECO:0000305"
FT HELIX 22..24
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 25..27
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 30..34
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 45..49
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:6D6Q"
FT STRAND 69..74
FT /evidence="ECO:0007829|PDB:6D6Q"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 85..89
FT /evidence="ECO:0007829|PDB:2NN6"
FT TURN 92..94
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 99..103
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 113..125
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 128..132
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 134..137
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 141..143
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 153..157
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 162..169
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 172..174
FT /evidence="ECO:0007829|PDB:6D6Q"
FT STRAND 177..179
FT /evidence="ECO:0007829|PDB:2NN6"
FT TURN 183..185
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 198..200
FT /evidence="ECO:0007829|PDB:2NN6"
FT HELIX 204..211
FT /evidence="ECO:0007829|PDB:2NN6"
FT HELIX 217..220
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 224..226
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 230..232
FT /evidence="ECO:0007829|PDB:2NN6"
FT TURN 233..235
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 236..239
FT /evidence="ECO:0007829|PDB:2NN6"
FT HELIX 244..256
FT /evidence="ECO:0007829|PDB:2NN6"
FT TURN 262..264
FT /evidence="ECO:0007829|PDB:2NN6"
FT HELIX 265..274
FT /evidence="ECO:0007829|PDB:2NN6"
SQ SEQUENCE 275 AA; 29572 MW; 264322144A199166 CRC64;
MAEPASVAAE SLAGSRARAA RTVLGQVVLP GEELLLPEQE DAEGPGGAVE RPLSLNARAC
SRVRVVCGPG LRRCGDRLLV TKCGRLRHKE PGSGSGGGVY WVDSQQKRYV PVKGDHVIGI
VTAKSGDIFK VDVGGSEPAS LSYLSFEGAT KRNRPNVQVG DLIYGQFVVA NKDMEPEMVC
IDSCGRANGM GVIGQDGLLF KVTLGLIRKL LAPDCEIIQE VGKLYPLEIV FGMNGRIWVK
AKTIQQTLIL ANILEACEHM TSDQRKQIFS RLAES
