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 24-JAN-2024, entry version 197. 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] RP FUNCTION, AND SUBUNIT. RX PubMed=20660080; DOI=10.1261/rna.2180810; RA Yang C.C., Wang Y.T., Hsiao Y.Y., Doudeva L.G., Kuo P.H., Chow S.Y., RA Yuan H.S.; RT "Structural and biochemical characterization of CRN-5 and Rrp46: an exosome RT component participating in apoptotic DNA degradation."; RL RNA 16:1748-1759(2010). RN [21] {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 [22] 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 [23] 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 [24] 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 (PubMed:11782436, PubMed:21269460). In vitro, EXOSC5 does not bind or CC digest single-stranded RNA and binds to double-stranded DNA without CC detectable DNase activity (PubMed:20660080). CC {ECO:0000269|PubMed:11782436, ECO:0000269|PubMed:20660080, CC ECO:0000269|PubMed:21269460}. CC -!- SUBUNIT: Homodimer (PubMed:20660080). Component of the RNA exosome CC complex (PubMed:20660080, PubMed:29906447). Specifically part of the CC catalytically inactive RNA exosome core (Exo-9) complex which is CC believed to associate with catalytic subunits EXOSC10, and DIS3 or CC DIS3L in cytoplasmic- and nuclear-specific RNA exosome complex forms. CC Exo-9 is formed by a hexameric ring of RNase PH domain-containing CC subunits specifically containing the heterodimers EXOSC4-EXOSC9, CC EXOSC5-EXOSC8 and EXOSC6-EXOSC7, and peripheral S1 domain-containing CC components EXOSC1, EXOSC2 and EXOSC3 located on the top of the ring CC structure. Interacts with EXOSC1. Interacts with GTPBP1. Interacts with CC ZC3HAV1. Interacts with DDX17 only in the presence of ZC3HAV1 in an CC RNA-independent manner. {ECO:0000269|PubMed:11719186, CC ECO:0000269|PubMed:11812149, ECO:0000269|PubMed:17185417, CC ECO:0000269|PubMed:18334637, ECO:0000269|PubMed:20531389, CC ECO:0000269|PubMed:20660080, 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 EMDB; EMD-0127; -. DR EMDB; EMD-0128; -. DR EMDB; EMD-14515; -. DR EMDB; EMD-7808; -. DR EMDB; EMD-7809; -. DR SMR; Q9NQT4; -. DR BioGRID; 121243; 164. 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; 9606-ENSP00000221233; -. DR PeptideAtlas; Q9NQT4; -. DR ProteomicsDB; 82183; -. DR Pumba; Q9NQT4; -. DR Antibodypedia; 30775; 221 antibodies from 25 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 AGR; HGNC:24662; -. DR CTD; 56915; -. DR DisGeNET; 56915; -. DR GeneCards; EXOSC5; -. DR HGNC; HGNC:24662; EXOSC5. DR HPA; ENSG00000077348; Low tissue specificity. DR MalaCards; EXOSC5; -. DR MIM; 606492; gene. DR MIM; 619576; phenotype. DR neXtProt; NX_Q9NQT4; -. DR OpenTargets; ENSG00000077348; -. DR Orphanet; 641361; Neurodevelopmental delay-hypotonia-cerebellar ataxia-cardiac conduction defects syndrome. 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; 2996330at2759; -. 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; 693 hits in 1142 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 135 other cell types or tissues. DR ExpressionAtlas; Q9NQT4; baseline and differential. 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); NAS: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'-RNA exonuclease activity; NAS:UniProtKB. DR GO; GO:0003677; F:DNA 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 CDD; cd11372; RNase_PH_RRP46; 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 PANTHER; PTHR11953; EXOSOME COMPLEX COMPONENT; 1. DR PANTHER; PTHR11953:SF1; EXOSOME COMPLEX COMPONENT RRP46; 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. DR Genevisible; Q9NQT4; HS. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; Disease variant; DNA-binding; Exosome; KW Intellectual disability; Nucleus; Phosphoprotein; Reference proteome; KW 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; uncertain significance; no FT 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 //