EXOS5_HUMAN
ID EXOS5_HUMAN Reviewed; 235 AA.
AC Q9NQT4; Q32Q81; Q8NG16; Q96I89;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Exosome complex component RRP46;
DE AltName: Full=Chronic myelogenous leukemia tumor antigen 28;
DE AltName: Full=Exosome component 5;
DE AltName: Full=Ribosomal RNA-processing protein 46;
DE AltName: Full=p12B;
GN Name=EXOSC5; Synonyms=CML28, RRP46;
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], 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 [MRNA].
RX PubMed=12359762;
RA Yang X.-F., Wu C.J., Chen L., Alyea E.P., Canning C., Kantoff P.,
RA Soiffer R.J., Dranoff G., Ritz J.;
RT "CML28 is a broadly immunogenic antigen, which is overexpressed in tumor
RT cells.";
RL Cancer Res. 62:5517-5522(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-5.
RC TISSUE=B-cell;
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 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 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 [8]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH EXOSC1.
RX PubMed=11812149; DOI=10.1006/jmbi.2001.5265;
RA Raijmakers R., Noordman Y.E., van Venrooij W.J., Pruijn G.J.M.;
RT "Protein-protein interactions of hCsl4p with other human exosome
RT subunits.";
RL J. Mol. Biol. 315:809-818(2002).
RN [9]
RP INTERACTION WITH ZC3HAV1.
RX PubMed=17185417; DOI=10.1073/pnas.0607063104;
RA Guo X., Ma J., Sun J., Gao G.;
RT "The zinc-finger antiviral protein recruits the RNA processing exosome to
RT degrade the target mRNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:151-156(2007).
RN [10]
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 [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, AND IDENTIFICATION BY
RP 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 [13]
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 [14]
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 [15]
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 [16]
RP IDENTIFICATION BY 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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, AND IDENTIFICATION BY
RP 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 [18]
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 [19]
RP ERRATUM OF PUBMED:17174896.
RA Liu Q., Greimann J.C., Lima C.D.;
RL Cell 131:188-189(2007).
RN [20] {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 [21]
RP INVOLVEMENT IN CABAC, AND VARIANT CABAC ILE-114.
RX PubMed=30950035; DOI=10.1111/cge.13549;
RA Beheshtian M., Fattahi Z., Fadaee M., Vazehan R., Jamali P., Parsimehr E.,
RA Kamgar M., Zonooz M.F., Mahdavi S.S., Kalhor Z., Arzhangi S., Abedini S.S.,
RA Kermani F.S., Mojahedi F., Kalscheuer V.M., Ropers H.H., Kariminejad A.,
RA Najmabadi H., Kahrizi K.;
RT "Identification of disease-causing variants in the EXOSC gene family
RT underlying autosomal recessive intellectual disability in Iranian
RT families.";
RL Clin. Genet. 95:718-725(2019).
RN [22]
RP INVOLVEMENT IN CABAC, VARIANTS CABAC ILE-114; THR-148 AND HIS-206, AND
RP CHARACTERIZATION OF VARIANTS CABAC ILE-114; THR-148 AND HIS-206.
RX PubMed=32504085; DOI=10.1093/hmg/ddaa108;
RA Slavotinek A., Misceo D., Htun S., Mathisen L., Frengen E., Foreman M.,
RA Hurtig J.E., Enyenihi L., Sterrett M.C., Leung S.W., Schneidman-Duhovny D.,
RA Estrada-Veras J., Duncan J.L., Haaxma C.A., Kamsteeg E.J., Xia V.,
RA Beleford D., Si Y., Douglas G., Treidene H.E., van Hoof A., Fasken M.B.,
RA Corbett A.H.;
RT "Biallelic variants in the RNA exosome gene EXOSC5 are associated with
RT developmental delays, short stature, cerebellar hypoplasia and motor
RT weakness.";
RL Hum. Mol. Genet. 29:2218-2239(2020).
RN [23]
RP INVOLVEMENT IN CABAC, AND VARIANTS CABAC LYS-101 AND ILE-114.
RX PubMed=34089229; DOI=10.1002/ajmg.a.62352;
RA Calame D.G., Herman I., Fatih J.M., Du H., Akay G., Jhangiani S.N.,
RA Coban-Akdemir Z., Milewicz D.M., Gibbs R.A., Posey J.E., Marafi D.,
RA Hunter J.V., Fan Y., Lupski J.R., Miyake C.Y.;
RT "Risk of sudden cardiac death in EXOSC5-related disease.";
RL Am. J. Med. Genet. A 185:2532-2540(2021).
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.
CC {ECO:0000269|PubMed:11782436, 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 EXOSC1. Interacts with
CC GTPBP1. Interacts with ZC3HAV1. Interacts with DDX17 only in the
CC presence of ZC3HAV1 in an RNA-independent manner.
CC {ECO:0000269|PubMed:11719186, ECO:0000269|PubMed:11812149,
CC ECO:0000269|PubMed:17185417, ECO:0000269|PubMed:18334637,
CC ECO:0000269|PubMed:20531389, ECO:0000269|PubMed:21515746,
CC ECO:0000269|PubMed:29906447}.
CC -!- INTERACTION:
CC Q9NQT4; Q8WXI4-2: ACOT11; NbExp=3; IntAct=EBI-371876, EBI-17721098;
CC Q9NQT4; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-371876, EBI-10173507;
CC Q9NQT4; Q13490: BIRC2; NbExp=6; IntAct=EBI-371876, EBI-514538;
CC Q9NQT4; Q96GS4: BORCS6; NbExp=3; IntAct=EBI-371876, EBI-10193358;
CC Q9NQT4; Q13137: CALCOCO2; NbExp=3; IntAct=EBI-371876, EBI-739580;
CC Q9NQT4; A6NC98: CCDC88B; NbExp=3; IntAct=EBI-371876, EBI-347573;
CC Q9NQT4; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-371876, EBI-742054;
CC Q9NQT4; Q8NF50-2: DOCK8; NbExp=3; IntAct=EBI-371876, EBI-10174653;
CC Q9NQT4; Q5JST6: EFHC2; NbExp=3; IntAct=EBI-371876, EBI-2349927;
CC Q9NQT4; Q9Y3B2: EXOSC1; NbExp=33; IntAct=EBI-371876, EBI-371892;
CC Q9NQT4; Q01780: EXOSC10; NbExp=4; IntAct=EBI-371876, EBI-358236;
CC Q9NQT4; Q9NQT5: EXOSC3; NbExp=10; IntAct=EBI-371876, EBI-371866;
CC Q9NQT4; Q96B26: EXOSC8; NbExp=22; IntAct=EBI-371876, EBI-371922;
CC Q9NQT4; A0A0C3SFZ9: FCHO1; NbExp=3; IntAct=EBI-371876, EBI-11977403;
CC Q9NQT4; O14526: FCHO1; NbExp=4; IntAct=EBI-371876, EBI-719823;
CC Q9NQT4; P07954: FH; NbExp=3; IntAct=EBI-371876, EBI-1050358;
CC Q9NQT4; Q08379: GOLGA2; NbExp=3; IntAct=EBI-371876, EBI-618309;
CC Q9NQT4; P09017: HOXC4; NbExp=3; IntAct=EBI-371876, EBI-3923226;
CC Q9NQT4; Q9UKT9: IKZF3; NbExp=7; IntAct=EBI-371876, EBI-747204;
CC Q9NQT4; Q8WZ19: KCTD13; NbExp=3; IntAct=EBI-371876, EBI-742916;
CC Q9NQT4; A1A4E9: KRT13; NbExp=3; IntAct=EBI-371876, EBI-10171552;
CC Q9NQT4; Q7Z3Y8: KRT27; NbExp=3; IntAct=EBI-371876, EBI-3044087;
CC Q9NQT4; Q15323: KRT31; NbExp=3; IntAct=EBI-371876, EBI-948001;
CC Q9NQT4; O76011: KRT34; NbExp=3; IntAct=EBI-371876, EBI-1047093;
CC Q9NQT4; Q92764: KRT35; NbExp=3; IntAct=EBI-371876, EBI-1058674;
CC Q9NQT4; O95447: LCA5L; NbExp=3; IntAct=EBI-371876, EBI-8473670;
CC Q9NQT4; A0A087WWI0: LRMDA; NbExp=3; IntAct=EBI-371876, EBI-18393842;
CC Q9NQT4; Q9BRK4: LZTS2; NbExp=3; IntAct=EBI-371876, EBI-741037;
CC Q9NQT4; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-371876, EBI-16439278;
CC Q9NQT4; Q13615: MTMR3; NbExp=3; IntAct=EBI-371876, EBI-371938;
CC Q9NQT4; Q8WY64: MYLIP; NbExp=3; IntAct=EBI-371876, EBI-6952711;
CC Q9NQT4; Q6ZUT1: NKAPD1; NbExp=3; IntAct=EBI-371876, EBI-3920396;
CC Q9NQT4; Q86TG7-2: PEG10; NbExp=3; IntAct=EBI-371876, EBI-6259410;
CC Q9NQT4; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-371876, EBI-79165;
CC Q9NQT4; Q8WWB5: PIH1D2; NbExp=3; IntAct=EBI-371876, EBI-10232538;
CC Q9NQT4; Q9NQX0: PRDM6; NbExp=3; IntAct=EBI-371876, EBI-11320284;
CC Q9NQT4; Q04864: REL; NbExp=3; IntAct=EBI-371876, EBI-307352;
CC Q9NQT4; Q04864-2: REL; NbExp=3; IntAct=EBI-371876, EBI-10829018;
CC Q9NQT4; Q6ZSJ9: SHISA6; NbExp=3; IntAct=EBI-371876, EBI-12037847;
CC Q9NQT4; Q13573: SNW1; NbExp=3; IntAct=EBI-371876, EBI-632715;
CC Q9NQT4; P02549: SPTA1; NbExp=3; IntAct=EBI-371876, EBI-375617;
CC Q9NQT4; Q9UBB9: TFIP11; NbExp=3; IntAct=EBI-371876, EBI-1105213;
CC Q9NQT4; Q08117-2: TLE5; NbExp=3; IntAct=EBI-371876, EBI-11741437;
CC Q9NQT4; Q13829: TNFAIP1; NbExp=6; IntAct=EBI-371876, EBI-2505861;
CC Q9NQT4; Q96RU7: TRIB3; NbExp=3; IntAct=EBI-371876, EBI-492476;
CC Q9NQT4; Q9BYV2: TRIM54; NbExp=6; IntAct=EBI-371876, EBI-2130429;
CC Q9NQT4; Q9BVG3: TRIM62; NbExp=3; IntAct=EBI-371876, EBI-6929619;
CC Q9NQT4; Q8TF47: ZFP90; NbExp=3; IntAct=EBI-371876, EBI-11419867;
CC Q9NQT4; Q8TAQ5: ZNF420; NbExp=3; IntAct=EBI-371876, EBI-3923307;
CC Q9NQT4; Q6ZNG0: ZNF620; NbExp=3; IntAct=EBI-371876, EBI-4395669;
CC Q9NQT4; Q8N720: ZNF655; NbExp=5; IntAct=EBI-371876, EBI-625509;
CC Q9NQT4; Q3KQV3: ZNF792; NbExp=3; IntAct=EBI-371876, EBI-10240849;
CC Q9NQT4; Q8K3Y6: Zc3hav1; Xeno; NbExp=6; IntAct=EBI-371876, EBI-8860250;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:11812149}.
CC Cytoplasm {ECO:0000305|PubMed:11812149}. Nucleus
CC {ECO:0000305|PubMed:11812149}.
CC -!- TISSUE SPECIFICITY: Highly expressed in a variety of hematopoietic and
CC epithelial tumor cell lines, but not in normal hematopoietic tissues or
CC other normal tissue, with the exception of testis.
CC -!- DISEASE: Cerebellar ataxia, brain abnormalities, and cardiac conduction
CC defects (CABAC) [MIM:619576]: An autosomal recessive disorder
CC characterized by global developmental delay, impaired intellectual
CC development and speech delay that are observed in most patients.
CC Disease manifestations are variable and include infantile-onset
CC hypotonia, poor motor development, poor feeding and overall growth, and
CC ataxic gait due to cerebellar ataxia. Additional variable features are
CC dysarthria, nystagmus, variable ocular anomalies, spasticity,
CC hyperreflexia, and non-specific dysmorphic features. Brain imaging
CC shows cerebellar hypoplasia, often with brainstem hypoplasia, enlarged
CC ventricles, delayed myelination, and thin corpus callosum. A
CC significant number of patients develop cardiac conduction defects in
CC childhood or adolescence. {ECO:0000269|PubMed:30950035,
CC ECO:0000269|PubMed:32504085, ECO:0000269|PubMed:34089229}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC 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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAM75154.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF281134; AAF82135.1; -; mRNA.
DR EMBL; AF285785; AAM75154.1; ALT_INIT; mRNA.
DR EMBL; AC011462; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC007742; AAH07742.1; -; mRNA.
DR EMBL; BC107696; AAI07697.1; -; mRNA.
DR CCDS; CCDS12580.1; -.
DR RefSeq; NP_064543.3; NM_020158.3.
DR PDB; 2NN6; X-ray; 3.35 A; D=1-235.
DR PDB; 6D6Q; EM; 3.45 A; D=1-235.
DR PDB; 6D6R; EM; 3.45 A; D=1-235.
DR PDB; 6H25; EM; 3.80 A; D=1-235.
DR PDBsum; 2NN6; -.
DR PDBsum; 6D6Q; -.
DR PDBsum; 6D6R; -.
DR PDBsum; 6H25; -.
DR AlphaFoldDB; Q9NQT4; -.
DR SMR; Q9NQT4; -.
DR BioGRID; 121243; 150.
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; Q9NQT4; -.
DR DIP; DIP-29846N; -.
DR IntAct; Q9NQT4; 107.
DR MINT; Q9NQT4; -.
DR STRING; 9606.ENSP00000221233; -.
DR GlyGen; Q9NQT4; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NQT4; -.
DR PhosphoSitePlus; Q9NQT4; -.
DR SwissPalm; Q9NQT4; -.
DR BioMuta; EXOSC5; -.
DR DMDM; 14285757; -.
DR EPD; Q9NQT4; -.
DR jPOST; Q9NQT4; -.
DR MassIVE; Q9NQT4; -.
DR MaxQB; Q9NQT4; -.
DR PaxDb; Q9NQT4; -.
DR PeptideAtlas; Q9NQT4; -.
DR PRIDE; Q9NQT4; -.
DR ProteomicsDB; 82183; -.
DR Antibodypedia; 30775; 204 antibodies from 24 providers.
DR DNASU; 56915; -.
DR Ensembl; ENST00000221233.9; ENSP00000221233.3; ENSG00000077348.10.
DR GeneID; 56915; -.
DR KEGG; hsa:56915; -.
DR MANE-Select; ENST00000221233.9; ENSP00000221233.3; NM_020158.4; NP_064543.3.
DR UCSC; uc002oqo.4; human.
DR CTD; 56915; -.
DR DisGeNET; 56915; -.
DR GeneCards; EXOSC5; -.
DR HGNC; HGNC:24662; EXOSC5.
DR HPA; ENSG00000077348; Low tissue specificity.
DR MIM; 606492; gene.
DR MIM; 619576; phenotype.
DR neXtProt; NX_Q9NQT4; -.
DR OpenTargets; ENSG00000077348; -.
DR PharmGKB; PA134890468; -.
DR VEuPathDB; HostDB:ENSG00000077348; -.
DR eggNOG; KOG1069; Eukaryota.
DR GeneTree; ENSGT00940000153348; -.
DR HOGENOM; CLU_063514_2_3_1; -.
DR InParanoid; Q9NQT4; -.
DR OMA; CIINEQG; -.
DR OrthoDB; 1129417at2759; -.
DR PhylomeDB; Q9NQT4; -.
DR TreeFam; TF315920; -.
DR PathwayCommons; Q9NQT4; -.
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; Q9NQT4; -.
DR SIGNOR; Q9NQT4; -.
DR BioGRID-ORCS; 56915; 659 hits in 1063 CRISPR screens.
DR EvolutionaryTrace; Q9NQT4; -.
DR GeneWiki; Exosome_component_5; -.
DR GenomeRNAi; 56915; -.
DR Pharos; Q9NQT4; Tbio.
DR PRO; PR:Q9NQT4; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9NQT4; protein.
DR Bgee; ENSG00000077348; Expressed in monocyte and 133 other tissues.
DR ExpressionAtlas; Q9NQT4; baseline and differential.
DR Genevisible; Q9NQT4; HS.
DR GO; GO:0005737; C:cytoplasm; NAS:UniProtKB.
DR GO; GO:0000177; C:cytoplasmic exosome (RNase complex); IBA:GO_Central.
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); IBA:GO_Central.
DR GO; GO:0101019; C:nucleolar exosome (RNase complex); IC:ComplexPortal.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal.
DR GO; GO:0000175; F:3'-5'-exoribonuclease activity; NAS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0051607; P:defense response to virus; IMP:MGI.
DR GO; GO:0045006; P:DNA deamination; IDA:UniProtKB.
DR GO; GO:0043928; P:exonucleolytic catabolism of deadenylated mRNA; IMP:UniProtKB.
DR GO; GO:0071028; P:nuclear mRNA surveillance; 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:0006401; P:RNA catabolic process; IDA:ComplexPortal.
DR GO; GO:0006396; P:RNA processing; IDA:ComplexPortal.
DR GO; GO:0016075; P:rRNA catabolic process; IBA:GO_Central.
DR GO; GO:0006364; P:rRNA processing; NAS:UniProtKB.
DR GO; GO:0034475; P:U4 snRNA 3'-end processing; IBA:GO_Central.
DR Gene3D; 3.30.230.70; -; 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_S5_D2-typ_fold.
DR Pfam; PF01138; RNase_PH; 1.
DR Pfam; PF03725; RNase_PH_C; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF55666; SSF55666; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Disease variant; Exosome; Intellectual disability;
KW Nucleus; Phosphoprotein; Reference proteome; RNA-binding; rRNA processing.
FT CHAIN 1..235
FT /note="Exosome complex component RRP46"
FT /id="PRO_0000139975"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT VARIANT 5
FT /note="T -> M (in dbSNP:rs10853751)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030788"
FT VARIANT 33
FT /note="C -> W (in dbSNP:rs34500671)"
FT /id="VAR_051868"
FT VARIANT 101
FT /note="T -> K (in CABAC; dbSNP:rs777418116)"
FT /evidence="ECO:0000269|PubMed:34089229"
FT /id="VAR_086374"
FT VARIANT 114
FT /note="T -> I (in CABAC; decreased interaction with EXOSC3,
FT EXOSC9 and EXOSC10, when assayed in a heterologous system;
FT dbSNP:rs542429051)"
FT /evidence="ECO:0000269|PubMed:30950035,
FT ECO:0000269|PubMed:32504085, ECO:0000269|PubMed:34089229"
FT /id="VAR_086375"
FT VARIANT 148
FT /note="M -> T (in CABAC; unknown pathological significance;
FT no detectable effect on interaction with EXOSC3, EXOSC9 and
FT EXOSC10, when assayed in a heterologous system;
FT dbSNP:rs367988911)"
FT /evidence="ECO:0000269|PubMed:32504085"
FT /id="VAR_086376"
FT VARIANT 206
FT /note="L -> H (in CABAC; strongly decreased interaction
FT with EXOSC3, EXOSC9 and EXOSC10, when assayed in a
FT heterologous system)"
FT /evidence="ECO:0000269|PubMed:32504085"
FT /id="VAR_086377"
FT STRAND 31..36
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 39..49
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 52..63
FT /evidence="ECO:0007829|PDB:2NN6"
FT TURN 66..68
FT /evidence="ECO:0007829|PDB:6D6Q"
FT STRAND 74..81
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 83..85
FT /evidence="ECO:0007829|PDB:2NN6"
FT HELIX 89..105
FT /evidence="ECO:0007829|PDB:2NN6"
FT HELIX 107..109
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 111..124
FT /evidence="ECO:0007829|PDB:2NN6"
FT HELIX 129..143
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 148..150
FT /evidence="ECO:0007829|PDB:6D6Q"
FT STRAND 152..159
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 165..168
FT /evidence="ECO:0007829|PDB:2NN6"
FT HELIX 171..176
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 178..186
FT /evidence="ECO:0007829|PDB:2NN6"
FT TURN 187..189
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 194..200
FT /evidence="ECO:0007829|PDB:2NN6"
FT HELIX 203..231
FT /evidence="ECO:0007829|PDB:2NN6"
SQ SEQUENCE 235 AA; 25249 MW; C3C1FCB39D85B1EE CRC64;
MEEETHTDAK IRAENGTGSS PRGPGCSLRH FACEQNLLSR PDGSASFLQG DTSVLAGVYG
PAEVKVSKEI FNKATLEVIL RPKIGLPGVA EKSRERLIRN TCEAVVLGTL HPRTSITVVL
QVVSDAGSLL ACCLNAACMA LVDAGVPMRA LFCGVACALD SDGTLVLDPT SKQEKEARAV
LTFALDSVER KLLMSSTKGL YSDTELQQCL AAAQAASQHV FRFYRESLQR RYSKS
