ID RRP44_HUMAN Reviewed; 958 AA. AC Q9Y2L1; A6NI21; B2RBL2; Q5W0P7; Q5W0P8; Q658Z7; Q7Z481; Q8WWI2; Q9UG36; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 16-AUG-2005, sequence version 2. DT 27-MAR-2024, entry version 222. DE RecName: Full=Exosome complex exonuclease RRP44; DE EC=3.1.13.-; DE EC=3.1.26.-; DE AltName: Full=Protein DIS3 homolog; DE AltName: Full=Ribosomal RNA-processing protein 44; GN Name=DIS3; Synonyms=KIAA1008, RRP44; 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=9562621; DOI=10.1093/oxfordjournals.jbchem.a022020; RA Shiomi T., Fukushima K., Suzuki N., Nakashima N., Noguchi E., Nishimoto T.; RT "Human dis3p, which binds to either GTP- or GDP-Ran, complements RT Saccharomyces cerevisiae dis3."; RL J. Biochem. 123:883-890(1998). RN [2] RP ERRATUM OF PUBMED:9562621. RA Shiomi T., Fukushima K., Suzuki N., Nakashima N., Noguchi E., Nishimoto T.; RL J. Biochem. 124:250-250(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT SER-269. RC TISSUE=Brain, and Peripheral blood leukocyte; RX PubMed=11935316; DOI=10.1007/s00439-001-0646-6; RA Rozenblum E., Vahteristo P., Sandberg T., Bergthorsson J.T., Syrjakoski K., RA Weaver D., Haraldsson K., Johannsdottir H.K., Vehmanen P., Nigam S., RA Golberger N., Robbins C., Pak E., Dutra A., Gillander E., Stephan D.A., RA Bailey-Wilson J., Juo S.-H.H., Kainu T., Arason A., Barkardottir R.B., RA Nevanlinna H., Borg A., Kallioniemi O.-P.; RT "A genomic map of a 6-Mb region at 13q21-q22 implicated in cancer RT development: identification and characterization of candidate genes."; RL Hum. Genet. 110:111-121(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT ARG-326. RC TISSUE=Brain; RX PubMed=10231032; DOI=10.1093/dnares/6.1.63; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., RA Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XIII. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 6:63-70(1999). RN [5] RP SEQUENCE REVISION. RX PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT SER-269. RC TISSUE=Trachea; 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT SER-269. RC TISSUE=Lymph node, and Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057823; DOI=10.1038/nature02379; RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L., RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., RA Frankish A.G., Frankland J., French L., Garner P., Garnett J., RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., RA Rogers J., Ross M.T.; RT "The DNA sequence and analysis of human chromosome 13."; RL Nature 428:522-528(2004). RN [9] 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-326. RC TISSUE=Lymph; 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 [11] 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 [12] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=12429849; DOI=10.1091/mbc.e02-05-0271; RA Scherl A., Coute Y., Deon C., Calle A., Kindbeiter K., Sanchez J.-C., RA Greco A., Hochstrasser D.F., Diaz J.-J.; RT "Functional proteomic analysis of human nucleolus."; RL Mol. Biol. Cell 13:4100-4109(2002). RN [13] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-18, 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 [14] RP ASSOCIATION WITH THE RNA EXOSOME COMPLEX, IDENTIFICATION BY MASS RP SPECTROMETRY, FUNCTION, COFACTOR, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP ASP-146 AND ASP-487. RX PubMed=20531386; DOI=10.1038/emboj.2010.121; RA Tomecki R., Kristiansen M.S., Lykke-Andersen S., Chlebowski A., RA Larsen K.M., Szczesny R.J., Drazkowska K., Pastula A., Andersen J.S., RA Stepien P.P., Dziembowski A., Jensen T.H.; RT "The human core exosome interacts with differentially localized processive RT RNases: hDIS3 and hDIS3L."; RL EMBO J. 29:2342-2357(2010). RN [15] RP ASSOCIATION WITH THE RNA EXOSOME COMPLEX, IDENTIFICATION BY MASS RP SPECTROMETRY, SUBCELLULAR LOCATION, AND INTERACTION WITH EXOSC3. 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 [16] 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 [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP 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 [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-215, AND IDENTIFICATION BY RP 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 [19] RP INTERACTION WITH DHX34. RX PubMed=25220460; DOI=10.1016/j.celrep.2014.08.020; RA Hug N., Caceres J.F.; RT "The RNA helicase DHX34 activates NMD by promoting a transition from the RT surveillance to the decay-inducing complex."; RL Cell Rep. 8:1845-1856(2014). 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). CC -!- FUNCTION: Putative catalytic component of the RNA exosome complex which CC has 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 DIS3 has both 3'-5' exonuclease and endonuclease activities. CC {ECO:0000269|PubMed:19056938, ECO:0000269|PubMed:20531386}. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:20531386}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000269|PubMed:20531386}; CC -!- SUBUNIT: Component of the RNA exosome complex (PubMed:29906447). The CC catalytically inactive RNA exosome core (Exo-9) complex is believed to CC associate with catalytic subunits EXOSC10, and DIS3 or DIS3L in CC cytoplasmic- and nuclear-specific RNA exosome complex forms CC (PubMed:29906447). Interacts with DHX34; the interaction is RNA- CC independent (PubMed:25220460). {ECO:0000269|PubMed:25220460, CC ECO:0000269|PubMed:29906447}. CC -!- INTERACTION: CC Q9Y2L1; Q01780: EXOSC10; NbExp=4; IntAct=EBI-373539, EBI-358236; CC Q9Y2L1; Q9NQT5: EXOSC3; NbExp=3; IntAct=EBI-373539, EBI-371866; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20531386}. Nucleus, CC nucleolus {ECO:0000269|PubMed:12429849}. Nucleus, nucleoplasm CC {ECO:0000269|PubMed:20531389}. Nucleus {ECO:0000269|PubMed:20531386}. CC Note=Predominantly located in the nucleus (PubMed:20531386). According CC to PubMed:12429849, found in the nucleolus (PubMed:12429849). According CC to PubMed:20531386, excluded from nucleolus supporting the existence of CC a nucleolar RNA exosome complex devoid of DIS3 (PubMed:20531386). CC {ECO:0000269|PubMed:12429849, ECO:0000269|PubMed:20531386}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9Y2L1-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9Y2L1-2; Sequence=VSP_014971; CC -!- TISSUE SPECIFICITY: Widely expressed. CC -!- MISCELLANEOUS: The association of DIS3 with the RNA exosome complex CC appears to be weak explaining its absence in some complex CC purifications. CC -!- SIMILARITY: Belongs to the RNR ribonuclease family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA76852.2; 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; AF330044; AAL37479.1; -; mRNA. DR EMBL; AB023225; BAA76852.2; ALT_INIT; mRNA. DR EMBL; AL832266; CAH56266.1; -; mRNA. DR EMBL; AK314715; BAG37259.1; -; mRNA. DR EMBL; AL080158; CAB45749.1; -; mRNA. DR EMBL; AL138695; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL391384; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471093; EAW80517.1; -; Genomic_DNA. DR EMBL; BC056143; AAH56143.1; -; mRNA. DR CCDS; CCDS45057.1; -. [Q9Y2L1-2] DR CCDS; CCDS9447.1; -. [Q9Y2L1-1] DR PIR; JE0110; JE0110. DR RefSeq; NP_001121698.1; NM_001128226.2. [Q9Y2L1-2] DR RefSeq; NP_055768.3; NM_014953.4. [Q9Y2L1-1] DR PDB; 6D6Q; EM; 3.45 A; K=1-958. DR PDB; 6D6R; EM; 3.45 A; K=1-958. DR PDB; 6H25; EM; 3.80 A; J=1-958. DR PDBsum; 6D6Q; -. DR PDBsum; 6D6R; -. DR PDBsum; 6H25; -. DR AlphaFoldDB; Q9Y2L1; -. DR EMDB; EMD-0127; -. DR EMDB; EMD-0128; -. DR EMDB; EMD-14515; -. DR EMDB; EMD-7808; -. DR EMDB; EMD-7809; -. DR SMR; Q9Y2L1; -. DR BioGRID; 116559; 201. DR ComplexPortal; CPX-476; Nuclear exosome complex, DIS3-EXOSC10 variant. DR ComplexPortal; CPX-593; Exosome complex, DIS3 variant. DR CORUM; Q9Y2L1; -. DR IntAct; Q9Y2L1; 54. DR MINT; Q9Y2L1; -. DR STRING; 9606.ENSP00000366997; -. DR GlyGen; Q9Y2L1; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9Y2L1; -. DR MetOSite; Q9Y2L1; -. DR PhosphoSitePlus; Q9Y2L1; -. DR SwissPalm; Q9Y2L1; -. DR BioMuta; DIS3; -. DR DMDM; 73620993; -. DR EPD; Q9Y2L1; -. DR jPOST; Q9Y2L1; -. DR MassIVE; Q9Y2L1; -. DR MaxQB; Q9Y2L1; -. DR PaxDb; 9606-ENSP00000366997; -. DR PeptideAtlas; Q9Y2L1; -. DR ProteomicsDB; 85832; -. [Q9Y2L1-1] DR ProteomicsDB; 85833; -. [Q9Y2L1-2] DR Pumba; Q9Y2L1; -. DR Antibodypedia; 24401; 250 antibodies from 30 providers. DR DNASU; 22894; -. DR Ensembl; ENST00000377767.9; ENSP00000366997.4; ENSG00000083520.15. [Q9Y2L1-1] DR Ensembl; ENST00000377780.8; ENSP00000367011.4; ENSG00000083520.15. [Q9Y2L1-2] DR GeneID; 22894; -. DR KEGG; hsa:22894; -. DR MANE-Select; ENST00000377767.9; ENSP00000366997.4; NM_014953.5; NP_055768.3. DR UCSC; uc001vix.6; human. [Q9Y2L1-1] DR AGR; HGNC:20604; -. DR CTD; 22894; -. DR DisGeNET; 22894; -. DR GeneCards; DIS3; -. DR HGNC; HGNC:20604; DIS3. DR HPA; ENSG00000083520; Low tissue specificity. DR MIM; 607533; gene. DR neXtProt; NX_Q9Y2L1; -. DR OpenTargets; ENSG00000083520; -. DR PharmGKB; PA162383628; -. DR VEuPathDB; HostDB:ENSG00000083520; -. DR eggNOG; KOG2102; Eukaryota. DR GeneTree; ENSGT00530000063106; -. DR InParanoid; Q9Y2L1; -. DR OMA; VKVHMDS; -. DR OrthoDB; 945235at2759; -. DR PhylomeDB; Q9Y2L1; -. DR TreeFam; TF105755; -. DR PathwayCommons; Q9Y2L1; -. 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; Q9Y2L1; -. DR BioGRID-ORCS; 22894; 602 hits in 1175 CRISPR screens. DR ChiTaRS; DIS3; human. DR GeneWiki; DIS3; -. DR GenomeRNAi; 22894; -. DR Pharos; Q9Y2L1; Tbio. DR PRO; PR:Q9Y2L1; -. DR Proteomes; UP000005640; Chromosome 13. DR RNAct; Q9Y2L1; Protein. DR Bgee; ENSG00000083520; Expressed in sperm and 191 other cell types or tissues. DR ExpressionAtlas; Q9Y2L1; baseline and differential. DR GO; GO:0000177; C:cytoplasmic exosome (RNase complex); IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0000178; C:exosome (RNase complex); TAS:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0000176; C:nuclear exosome (RNase complex); IDA:UniProtKB. 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; IMP:UniProtKB. DR GO; GO:0004519; F:endonuclease activity; IMP:UniProtKB. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB. DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW. DR GO; GO:0071034; P:CUT catabolic process; IMP:UniProtKB. DR GO; GO:0043928; P:exonucleolytic catabolism of deadenylated mRNA; TAS:Reactome. 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; IMP:UniProtKB. DR GO; GO:0006364; P:rRNA processing; TAS:UniProtKB. DR CDD; cd09862; PIN_Rrp44-like; 1. DR Gene3D; 2.40.50.690; -; 1. DR Gene3D; 2.40.50.700; -; 1. DR Gene3D; 3.40.50.1010; 5'-nuclease; 1. DR Gene3D; 2.40.50.140; Nucleic acid-binding proteins; 1. DR InterPro; IPR041505; Dis3_CSD2. DR InterPro; IPR012340; NA-bd_OB-fold. DR InterPro; IPR029060; PIN-like_dom_sf. DR InterPro; IPR002716; PIN_dom. DR InterPro; IPR001900; RNase_II/R. DR InterPro; IPR022966; RNase_II/R_CS. DR InterPro; IPR033771; Rrp44_CSD1. DR InterPro; IPR033770; RRP44_S1. DR PANTHER; PTHR23355:SF35; EXOSOME COMPLEX EXONUCLEASE RRP44; 1. DR PANTHER; PTHR23355; RIBONUCLEASE; 1. DR Pfam; PF17849; OB_Dis3; 1. DR Pfam; PF13638; PIN_4; 1. DR Pfam; PF00773; RNB; 1. DR Pfam; PF17216; Rrp44_CSD1; 1. DR Pfam; PF17215; Rrp44_S1; 1. DR SMART; SM00670; PINc; 1. DR SMART; SM00955; RNB; 1. DR SUPFAM; SSF50249; Nucleic acid-binding proteins; 3. DR SUPFAM; SSF88723; PIN domain-like; 1. DR PROSITE; PS01175; RIBONUCLEASE_II; 1. DR SWISS-2DPAGE; Q9Y2L1; -. DR Genevisible; Q9Y2L1; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; Endonuclease; KW Exonuclease; Exosome; Hydrolase; Magnesium; Manganese; Nuclease; Nucleus; KW Phosphoprotein; Reference proteome; RNA-binding; rRNA processing. FT CHAIN 1..958 FT /note="Exosome complex exonuclease RRP44" FT /id="PRO_0000166419" FT DOMAIN 64..182 FT /note="PINc" FT REGION 938..958 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES 18 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 215 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 78..129 FT /note="DVLEDPAIRNVIVLQTVLQEVRNRSAPVYKRIRDVTNNQEKHFYTFTNEHHR FT -> VSAWRPGTWASVASSLRLPGSL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10231032" FT /id="VSP_014971" FT VARIANT 269 FT /note="N -> S (in dbSNP:rs4883918)" FT /evidence="ECO:0000269|PubMed:11935316, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:17974005" FT /id="VAR_023099" FT VARIANT 326 FT /note="T -> R (in dbSNP:rs7332388)" FT /evidence="ECO:0000269|PubMed:10231032, FT ECO:0000269|PubMed:15489334" FT /id="VAR_023100" FT MUTAGEN 146 FT /note="D->N: Loss of endonuclease activity; when associated FT with N-487." FT /evidence="ECO:0000269|PubMed:20531386" FT MUTAGEN 487 FT /note="D->N: Loss of exonuclease activity. Loss of FT endonuclease activity; when associated with N-146." FT /evidence="ECO:0000269|PubMed:20531386" FT CONFLICT 635 FT /note="P -> S (in Ref. 7; CAH56266)" FT /evidence="ECO:0000305" FT STRAND 2..10 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 12..14 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 16..24 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 70..75 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 77..81 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 82..84 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 87..90 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 93..101 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 103..113 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 116..122 FT /evidence="ECO:0007829|PDB:6D6Q" FT TURN 129..131 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 141..163 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 166..168 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 173..177 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 178..186 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 194..200 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 206..209 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 234..243 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 247..252 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 261..265 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 274..277 FT /evidence="ECO:0007829|PDB:6D6Q" FT TURN 280..282 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 291..296 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 342..350 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 356..361 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 371..377 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 383..385 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 391..393 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 396..404 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 413..422 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 426..436 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 446..451 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 463..465 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 466..469 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 489..494 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 500..506 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 509..511 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 518..525 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 542..546 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 555..566 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 574..585 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 590..598 FT /evidence="ECO:0007829|PDB:6D6Q" FT TURN 604..606 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 607..626 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 658..681 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 683..685 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 688..691 FT /evidence="ECO:0007829|PDB:6D6Q" FT TURN 696..699 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 700..708 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 718..725 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 737..745 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 752..754 FT /evidence="ECO:0007829|PDB:6D6Q" FT TURN 756..758 FT /evidence="ECO:0007829|PDB:6D6Q" FT TURN 765..767 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 783..795 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 802..804 FT /evidence="ECO:0007829|PDB:6D6Q" FT HELIX 807..842 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 846..848 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 857..859 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 862..864 FT /evidence="ECO:0007829|PDB:6D6Q" FT TURN 865..868 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 869..871 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 886..888 FT /evidence="ECO:0007829|PDB:6D6R" FT TURN 889..892 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 893..895 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 908..911 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 916..918 FT /evidence="ECO:0007829|PDB:6D6Q" FT STRAND 925..928 FT /evidence="ECO:0007829|PDB:6D6Q" SQ SEQUENCE 958 AA; 109003 MW; 92336BA0D06247FE CRC64; MLKSKTFLKK TRAGGVMKIV REHYLRDDIG CGAPGCAACG GAHEGPALEP QPQDPASSVC PQPHYLLPDT NVLLHQIDVL EDPAIRNVIV LQTVLQEVRN RSAPVYKRIR DVTNNQEKHF YTFTNEHHRE TYVEQEQGEN ANDRNDRAIR VAAKWYNEHL KKMSADNQLQ VIFITNDRRN KEKAIEEGIP AFTCEEYVKS LTANPELIDR LACLSEEGNE IESGKIIFSE HLPLSKLQQG IKSGTYLQGT FRASRENYLE ATVWIHGDNE ENKEIILQGL KHLNRAVHED IVAVELLPKS QWVAPSSVVL HDEGQNEEDV EKEEETERML KTAVSEKMLK PTGRVVGIIK RNWRPYCGML SKSDIKESRR HLFTPADKRI PRIRIETRQA STLEGRRIIV AIDGWPRNSR YPNGHFVRNL GDVGEKETET EVLLLEHDVP HQPFSQAVLS FLPKMPWSIT EKDMKNREDL RHLCICSVDP PGCTDIDDAL HCRELENGNL EVGVHIADVS HFIRPGNALD QESARRGTTV YLCEKRIDMV PELLSSNLCS LKCDVDRLAF SCIWEMNHNA EILKTKFTKS VINSKASLTY AEAQLRIDSA NMNDDITTSL RGLNKLAKIL KKRRIEKGAL TLSSPEVRFH MDSETHDPID LQTKELRETN SMVEEFMLLA NISVAKKIHE EFSEHALLRK HPAPPPSNYE ILVKAARSRN LEIKTDTAKS LAESLDQAES PTFPYLNTLL RILATRCMMQ AVYFCSGMDN DFHHYGLASP IYTHFTSPIR RYADVIVHRL LAVAIGADCT YPELTDKHKL ADICKNLNFR HKMAQYAQRA SVAFHTQLFF KSKGIVSEEA YILFVRKNAI VVLIPKYGLE GTVFFEEKDK PNPQLIYDDE IPSLKIEDTV FHVFDKVKVK IMLDSSNLQH QKIRMSLVEP QIPGISIPTD TSNMDLNGPK KKKMKLGK //