EXOS6_HUMAN
ID EXOS6_HUMAN Reviewed; 272 AA.
AC Q5RKV6;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Exosome complex component MTR3;
DE AltName: Full=Exosome component 6;
DE AltName: Full=mRNA transport regulator 3 homolog;
DE Short=hMtr3;
DE AltName: Full=p11;
GN Name=EXOSC6; Synonyms=MTR3;
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 [LARGE SCALE GENOMIC DNA].
RC TISSUE=Salivary gland;
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Salivary gland;
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 [3]
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 [4]
RP PROTEIN INTERACTION.
RX PubMed=12419256; DOI=10.1016/s0022-2836(02)00947-6;
RA Raijmakers R., Vree Egberts W., van Venrooij W.J., Pruijn G.J.M.;
RT "Protein-protein interactions between human exosome components support the
RT assembly of RNase PH-type subunits into a six-membered PNPase-like ring.";
RL J. Mol. Biol. 323:653-663(2002).
RN [5]
RP PROTEIN INTERACTION.
RX PubMed=15231747; DOI=10.1101/gr.2122004;
RA Lehner B., Sanderson C.M.;
RT "A protein interaction framework for human mRNA degradation.";
RL Genome Res. 14:1315-1323(2004).
RN [6]
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 [7]
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 [8]
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 [9]
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 [10]
RP ERRATUM OF PUBMED:17174896.
RA Liu Q., Greimann J.C., Lima C.D.;
RL Cell 131:188-189(2007).
RN [11] {ECO:0007744|PDB:6D6Q, ECO:0007744|PDB:6D6R}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.45 ANGSTROMS), AND SUBUNIT.
RX PubMed=29906447; DOI=10.1016/j.cell.2018.05.041;
RA Weick E.M., Puno M.R., Januszyk K., Zinder J.C., DiMattia M.A., Lima C.D.;
RT "Helicase-Dependent RNA Decay Illuminated by a Cryo-EM Structure of a Human
RT Nuclear RNA Exosome-MTR4 Complex.";
RL Cell 173:1663-1677.e21(2018).
CC -!- FUNCTION: Non-catalytic component of the RNA exosome complex which has
CC 3'->5' exoribonuclease activity and participates in a multitude of
CC cellular RNA processing and degradation events. In the nucleus, the RNA
CC exosome complex is involved in proper maturation of stable RNA species
CC such as rRNA, snRNA and snoRNA, in the elimination of RNA processing
CC by-products and non-coding 'pervasive' transcripts, such as antisense
CC RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs
CC with processing defects, thereby limiting or excluding their export to
CC the cytoplasm. The RNA exosome may be involved in Ig class switch
CC recombination (CSR) and/or Ig variable region somatic hypermutation
CC (SHM) by targeting AICDA deamination activity to transcribed dsDNA
CC substrates. In the cytoplasm, the RNA exosome complex is involved in
CC general mRNA turnover and specifically degrades inherently unstable
CC mRNAs containing AU-rich elements (AREs) within their 3' untranslated
CC regions, and in RNA surveillance pathways, preventing translation of
CC aberrant mRNAs. It seems to be involved in degradation of histone mRNA.
CC The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9)
CC is proposed to play a pivotal role in the binding and presentation of
CC RNA for ribonucleolysis, and to serve as a scaffold for the association
CC with catalytic subunits and accessory proteins or complexes.
CC {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. {ECO:0000269|PubMed:11719186,
CC ECO:0000269|PubMed:20531389, ECO:0000269|PubMed:29906447}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Nucleus, nucleolus
CC {ECO:0000305}. Nucleus {ECO:0000305}.
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 ---------------------------------------------------------------------------
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; AC009060; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC052252; AAH52252.1; -; mRNA.
DR CCDS; CCDS10887.1; -.
DR RefSeq; NP_478126.1; NM_058219.2.
DR PDB; 2NN6; X-ray; 3.35 A; F=1-272.
DR PDB; 6D6Q; EM; 3.45 A; F=1-272.
DR PDB; 6D6R; EM; 3.45 A; F=1-272.
DR PDB; 6H25; EM; 3.80 A; F=1-272.
DR PDBsum; 2NN6; -.
DR PDBsum; 6D6Q; -.
DR PDBsum; 6D6R; -.
DR PDBsum; 6H25; -.
DR AlphaFoldDB; Q5RKV6; -.
DR SMR; Q5RKV6; -.
DR BioGRID; 125608; 98.
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; Q5RKV6; -.
DR DIP; DIP-61038N; -.
DR IntAct; Q5RKV6; 28.
DR MINT; Q5RKV6; -.
DR STRING; 9606.ENSP00000398597; -.
DR GlyGen; Q5RKV6; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q5RKV6; -.
DR PhosphoSitePlus; Q5RKV6; -.
DR SwissPalm; Q5RKV6; -.
DR BioMuta; EXOSC6; -.
DR DMDM; 74736141; -.
DR EPD; Q5RKV6; -.
DR jPOST; Q5RKV6; -.
DR MassIVE; Q5RKV6; -.
DR MaxQB; Q5RKV6; -.
DR PaxDb; Q5RKV6; -.
DR PeptideAtlas; Q5RKV6; -.
DR PRIDE; Q5RKV6; -.
DR ProteomicsDB; 63753; -.
DR TopDownProteomics; Q5RKV6; -.
DR Antibodypedia; 29956; 97 antibodies from 16 providers.
DR DNASU; 118460; -.
DR Ensembl; ENST00000435634.3; ENSP00000398597.1; ENSG00000223496.3.
DR GeneID; 118460; -.
DR KEGG; hsa:118460; -.
DR MANE-Select; ENST00000435634.3; ENSP00000398597.1; NM_058219.3; NP_478126.1.
DR UCSC; uc002eym.2; human.
DR CTD; 118460; -.
DR DisGeNET; 118460; -.
DR GeneCards; EXOSC6; -.
DR HGNC; HGNC:19055; EXOSC6.
DR HPA; ENSG00000223496; Low tissue specificity.
DR MIM; 606490; gene.
DR neXtProt; NX_Q5RKV6; -.
DR OpenTargets; ENSG00000223496; -.
DR PharmGKB; PA134932096; -.
DR VEuPathDB; HostDB:ENSG00000223496; -.
DR eggNOG; KOG1068; Eukaryota.
DR GeneTree; ENSGT00940000153348; -.
DR HOGENOM; CLU_063514_1_3_1; -.
DR InParanoid; Q5RKV6; -.
DR OMA; RCGLVSQ; -.
DR OrthoDB; 1101132at2759; -.
DR PhylomeDB; Q5RKV6; -.
DR TreeFam; TF323886; -.
DR PathwayCommons; Q5RKV6; -.
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; Q5RKV6; -.
DR SIGNOR; Q5RKV6; -.
DR BioGRID-ORCS; 118460; 772 hits in 1088 CRISPR screens.
DR ChiTaRS; EXOSC6; human.
DR EvolutionaryTrace; Q5RKV6; -.
DR GenomeRNAi; 118460; -.
DR Pharos; Q5RKV6; Tbio.
DR PRO; PR:Q5RKV6; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q5RKV6; protein.
DR Bgee; ENSG00000223496; Expressed in buccal mucosa cell and 167 other tissues.
DR Genevisible; Q5RKV6; HS.
DR GO; GO:0000177; C:cytoplasmic exosome (RNase complex); IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:ComplexPortal.
DR GO; GO:0000178; C:exosome (RNase complex); IDA:UniProtKB.
DR GO; GO: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:ComplexPortal.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0045006; P:DNA deamination; IDA:UniProtKB.
DR GO; GO:0045190; P:isotype switching; ISS: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: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:0016075; P:rRNA catabolic process; IBA:GO_Central.
DR GO; GO:0006364; P:rRNA processing; IEA:UniProtKB-KW.
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; 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 SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF55666; SSF55666; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Exosome; Nucleus; Reference proteome; RNA-binding;
KW rRNA processing.
FT CHAIN 1..272
FT /note="Exosome complex component MTR3"
FT /id="PRO_0000287478"
FT REGION 1..36
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT HELIX 18..20
FT /evidence="ECO:0007829|PDB:6D6Q"
FT STRAND 39..43
FT /evidence="ECO:0007829|PDB:6D6Q"
FT STRAND 47..53
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 61..70
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 95..102
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 106..109
FT /evidence="ECO:0007829|PDB:2NN6"
FT HELIX 116..130
FT /evidence="ECO:0007829|PDB:2NN6"
FT TURN 131..133
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 143..152
FT /evidence="ECO:0007829|PDB:2NN6"
FT HELIX 157..172
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 176..178
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 181..184
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 190..192
FT /evidence="ECO:0007829|PDB:6D6Q"
FT STRAND 195..198
FT /evidence="ECO:0007829|PDB:6D6Q"
FT TURN 201..203
FT /evidence="ECO:0007829|PDB:2NN6"
FT HELIX 204..206
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 208..216
FT /evidence="ECO:0007829|PDB:2NN6"
FT TURN 217..220
FT /evidence="ECO:0007829|PDB:2NN6"
FT STRAND 221..228
FT /evidence="ECO:0007829|PDB:2NN6"
FT TURN 234..237
FT /evidence="ECO:0007829|PDB:2NN6"
FT HELIX 238..267
FT /evidence="ECO:0007829|PDB:2NN6"
SQ SEQUENCE 272 AA; 28235 MW; F31729E0D1545F94 CRC64;
MPGDHRRIRG PEESQPPQLY AADEEEAPGT RDPTRLRPVY ARAGLLSQAK GSAYLEAGGT
KVLCAVSGPR QAEGGERGGG PAGAGGEAPA ALRGRLLCDF RRAPFAGRRR RAPPGGCEER
ELALALQEAL EPAVRLGRYP RAQLEVSALL LEDGGSALAA ALTAAALALA DAGVEMYDLV
VGCGLSLAPG PAPTWLLDPT RLEEERAAAG LTVALMPVLN QVAGLLGSGE GGLTESWAEA
VRLGLEGCQR LYPVLQQSLV RAARRRGAAA QP
