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   27-MAR-2024, entry version 159.
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}.
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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   EMDB; EMD-0127; -.
DR   EMDB; EMD-0128; -.
DR   EMDB; EMD-14515; -.
DR   EMDB; EMD-7808; -.
DR   EMDB; EMD-7809; -.
DR   EMDB; EMD-7818; -.
DR   EMDB; EMD-7819; -.
DR   SMR; Q5RKV6; -.
DR   BioGRID; 125608; 119.
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; 30.
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; 9606-ENSP00000398597; -.
DR   PeptideAtlas; Q5RKV6; -.
DR   ProteomicsDB; 63753; -.
DR   Pumba; Q5RKV6; -.
DR   TopDownProteomics; Q5RKV6; -.
DR   Antibodypedia; 29956; 112 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   AGR; HGNC:19055; -.
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; KLMCCVY; -.
DR   OrthoDB; 4642487at2759; -.
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; 811 hits in 1171 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 169 other cell types or tissues.
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); NAS: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   CDD; cd11371; RNase_PH_MTR3; 1.
DR   Gene3D; 3.30.230.70; GHMP Kinase, N-terminal domain; 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_Su5_D2-typ_SF.
DR   PANTHER; PTHR11953; EXOSOME COMPLEX COMPONENT; 1.
DR   PANTHER; PTHR11953:SF2; EXOSOME COMPLEX COMPONENT MTR3; 1.
DR   Pfam; PF01138; RNase_PH; 1.
DR   SUPFAM; SSF55666; Ribonuclease PH domain 2-like; 1.
DR   SUPFAM; SSF54211; Ribosomal protein S5 domain 2-like; 1.
DR   Genevisible; Q5RKV6; HS.
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
//