MTREX_HUMAN
ID MTREX_HUMAN Reviewed; 1042 AA.
AC P42285; Q2M386; Q6MZZ8; Q6P170; Q8N5R0; Q8TAG2;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 3.
DT 03-AUG-2022, entry version 219.
DE RecName: Full=Exosome RNA helicase MTR4 {ECO:0000305};
DE EC=3.6.4.13 {ECO:0000269|PubMed:29844170};
DE AltName: Full=ATP-dependent RNA helicase DOB1 {ECO:0000303|PubMed:16782053};
DE AltName: Full=ATP-dependent RNA helicase SKIV2L2;
DE AltName: Full=Superkiller viralicidic activity 2-like 2;
DE AltName: Full=TRAMP-like complex helicase;
GN Name=MTREX {ECO:0000312|HGNC:HGNC:18734};
GN Synonyms=DOB1 {ECO:0000303|PubMed:16782053}, KIAA0052,
GN MTR4 {ECO:0000303|PubMed:26456651}, SKIV2L2;
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 MRNA].
RC TISSUE=Myelomonocyte;
RX PubMed=7584044; DOI=10.1093/dnares/1.5.223;
RA Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S., Seki N.,
RA Kawarabayasi Y., Ishikawa K., Tabata S.;
RT "Prediction of the coding sequences of unidentified human genes. II. The
RT coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 1:223-229(1994).
RN [2]
RP SEQUENCE REVISION TO C-TERMINUS.
RA Ohara O., Nagase T., Kikuno R., Nomura N.;
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND INTERACTION WITH NVL.
RC TISSUE=Kidney;
RX PubMed=16782053; DOI=10.1016/j.bbrc.2006.06.017;
RA Nagahama M., Yamazoe T., Hara Y., Tani K., Tsuji A., Tagaya M.;
RT "The AAA-ATPase NVL2 is a component of pre-ribosomal particles that
RT interacts with the DExD/H-box RNA helicase DOB1.";
RL Biochem. Biophys. Res. Commun. 346:1075-1082(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Endometrium;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus, Natural killer cell, Prostate, and Retina;
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 [6]
RP PROTEIN SEQUENCE OF 2-24; 82-98; 135-145; 185-192; 340-351; 385-396;
RP 409-418; 438-449; 451-464; 495-502; 533-542; 554-604; 681-701; 724-743;
RP 844-852; 861-873; 924-933; 985-995 AND 1013-1022, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.;
RL Submitted (DEC-2008) to UniProtKB.
RN [7]
RP ASSOCIATION WITH THE RNA EXOSOME COMPLEX, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
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 [8]
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 [9]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE SPLICEOSOMAL
RP C COMPLEX.
RX PubMed=11991638; DOI=10.1017/s1355838202021088;
RA Jurica M.S., Licklider L.J., Gygi S.P., Grigorieff N., Moore M.J.;
RT "Purification and characterization of native spliceosomes suitable for
RT three-dimensional structural analysis.";
RL RNA 8:426-439(2002).
RN [10]
RP INTERACTION WITH ZCCHC8.
RX PubMed=16263084; DOI=10.1016/j.bbrc.2005.10.090;
RA Gustafson M.P., Welcker M., Hwang H.C., Clurman B.E.;
RT "Zcchc8 is a glycogen synthase kinase-3 substrate that interacts with RNA-
RT binding proteins.";
RL Biochem. Biophys. Res. Commun. 338:1359-1367(2005).
RN [11]
RP FUNCTION, AND INTERACTION WITH MPHOSPH6.
RX PubMed=17412707; DOI=10.1093/nar/gkm082;
RA Schilders G., van Dijk E., Pruijn G.J.M.;
RT "C1D and hMtr4p associate with the human exosome subunit PM/Scl-100 and are
RT involved in pre-rRNA processing.";
RL Nucleic Acids Res. 35:2564-2572(2007).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-51, 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 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 [15]
RP IDENTIFICATION IN A TRAMP-LIKE COMPLEX, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=21855801; DOI=10.1016/j.molcel.2011.06.028;
RA Lubas M., Christensen M.S., Kristiansen M.S., Domanski M., Falkenby L.G.,
RA Lykke-Andersen S., Andersen J.S., Dziembowski A., Jensen T.H.;
RT "Interaction profiling identifies the human nuclear exosome targeting
RT complex.";
RL Mol. Cell 43:624-637(2011).
RN [16]
RP REVIEW ON RNA EXOSOMES.
RX PubMed=22817747; DOI=10.1042/bst20120061;
RA Sloan K.E., Schneider C., Watkins N.J.;
RT "Comparison of the yeast and human nuclear exosome complexes.";
RL Biochem. Soc. Trans. 40:850-855(2012).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
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 THE RNA EXOSOME COMPLEX, AND INTERACTION WITH EXOSC10.
RX PubMed=26166824; DOI=10.1016/j.bbrc.2015.07.032;
RA Yoshikatsu Y., Ishida Y., Sudo H., Yuasa K., Tsuji A., Nagahama M.;
RT "NVL2, a nucleolar AAA-ATPase, is associated with the nuclear exosome and
RT is involved in pre-rRNA processing.";
RL Biochem. Biophys. Res. Commun. 464:780-786(2015).
RN [20]
RP INTERACTION WITH WDR74.
RX PubMed=26456651; DOI=10.1016/j.bbrc.2015.09.160;
RA Hiraishi N., Ishida Y., Nagahama M.;
RT "AAA-ATPase NVL2 acts on MTR4-exosome complex to dissociate the nucleolar
RT protein WDR74.";
RL Biochem. Biophys. Res. Commun. 467:534-540(2015).
RN [21]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-684, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [22]
RP SUBUNIT, INTERACTION WITH ZFC3H1; ZCCHC8 AND RBM7, AND FUNCTION.
RX PubMed=27871484; DOI=10.1016/j.molcel.2016.09.025;
RA Meola N., Domanski M., Karadoulama E., Chen Y., Gentil C., Pultz D.,
RA Vitting-Seerup K., Lykke-Andersen S., Andersen J.S., Sandelin A.,
RA Jensen T.H.;
RT "Identification of a nuclear exosome decay pathway for processed
RT transcripts.";
RL Mol. Cell 64:520-533(2016).
RN [23]
RP SUBUNIT, AND INTERACTION WITH ZCCHC8.
RX PubMed=27905398; DOI=10.1038/ncomms13573;
RA Falk S., Finogenova K., Melko M., Benda C., Lykke-Andersen S., Jensen T.H.,
RA Conti E.;
RT "Structure of the RBM7-ZCCHC8 core of the NEXT complex reveals connections
RT to splicing factors.";
RL Nat. Commun. 7:13573-13573(2016).
RN [24]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-24; LYS-358; LYS-684 AND LYS-723,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [25]
RP FUNCTION, AND INTERACTION WITH WDR74.
RX PubMed=29107693; DOI=10.1016/j.bbrc.2017.10.148;
RA Hiraishi N., Ishida Y.I., Sudo H., Nagahama M.;
RT "WDR74 participates in an early cleavage of the pre-rRNA processing pathway
RT in cooperation with the nucleolar AAA-ATPase NVL2.";
RL Biochem. Biophys. Res. Commun. 495:116-123(2018).
RN [26]
RP FUNCTION, AND INTERACTION WITH NRDE2.
RX PubMed=29902117; DOI=10.1080/15476286.2018.1467180;
RA Richard P., Ogami K., Chen Y., Feng S., Moresco J.J., Yates J.R. III,
RA Manley J.L.;
RT "NRDE-2, the human homolog of fission yeast Nrl1, prevents DNA damage
RT accumulation in human cells.";
RL RNA Biol. 15:868-876(2018).
RN [27]
RP INTERACTION WITH NRDE2.
RX PubMed=30538148; DOI=10.1261/rna.069773.118;
RA Jiao A.L., Perales R., Umbreit N.T., Haswell J.R., Piper M.E., Adams B.D.,
RA Pellman D., Kennedy S., Slack F.J.;
RT "Human nuclear RNAi-defective 2 (NRDE2) is an essential RNA splicing
RT factor.";
RL RNA 25:352-363(2019).
RN [28] {ECO:0007744|PDB:6D6Q, ECO:0007744|PDB:6D6R}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.45 ANGSTROMS) IN COMPLEX WITH NUCLEAR
RP RNA EXOSOME COMPLEX AND DNA/RNA HETERODUPLEX, CATALYTIC ACTIVITY, FUNCTION,
RP AND ACTIVITY REGULATION.
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 [29] {ECO:0007744|PDB:6C90}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 71-600 AND 843-1042 IN COMPLEX
RP WITH ZCCHC8 AND ATP, INTERACTION WITH ZCCHC8, CATALYTIC ACTIVITY, FUNCTION,
RP MUTAGENESIS OF GLU-253, ATP BINDING, AND ACTIVITY REGULATION.
RX PubMed=29844170; DOI=10.1073/pnas.1803530115;
RA Puno M.R., Lima C.D.;
RT "Structural basis for MTR4-ZCCHC8 interactions that stimulate the MTR4
RT helicase in the nuclear exosome-targeting complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E5506-E5515(2018).
RN [30] {ECO:0007744|PDB:6IEG, ECO:0007744|PDB:6IEH}
RP X-RAY CRYSTALLOGRAPHY (2.89 ANGSTROMS) OF 71-1042 IN COMPLEX WITH NRDE2,
RP INTERACTION WITH NCBP1; NRDE2; SRRT; ZFC3H1, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF ARG-658; GLU-697; ARG-743 AND 989-PHE-GLU-990.
RX PubMed=30842217; DOI=10.1101/gad.322602.118;
RA Wang J., Chen J., Wu G., Zhang H., Du X., Chen S., Zhang L., Wang K.,
RA Fan J., Gao S., Wu X., Zhang S., Kuai B., Zhao P., Chi B., Wang L., Li G.,
RA Wong C.C.L., Zhou Y., Li J., Yun C., Cheng H.;
RT "NRDE2 negatively regulates exosome functions by inhibiting MTR4
RT recruitment and exosome interaction.";
RL Genes Dev. 33:536-549(2019).
RN [31] {ECO:0007744|PDB:6RO1}
RP X-RAY CRYSTALLOGRAPHY (3.07 ANGSTROMS) OF 70-1042 IN COMPLEXES WITH NVL AND
RP ATP, INTERACTION WITH NVL AND ZCCHC8, ATP BINDING, AND MUTAGENESIS OF
RP ARG-743.
RX PubMed=31358741; DOI=10.1038/s41467-019-11339-x;
RA Lingaraju M., Johnsen D., Schlundt A., Langer L.M., Basquin J., Sattler M.,
RA Heick Jensen T., Falk S., Conti E.;
RT "The MTR4 helicase recruits nuclear adaptors of the human RNA exosome using
RT distinct arch-interacting motifs.";
RL Nat. Commun. 10:3393-3393(2019).
CC -!- FUNCTION: Catalyzes the ATP-dependent unwinding of RNA duplexes with a
CC single-stranded 3' RNA extension (PubMed:27871484, PubMed:29844170,
CC PubMed:29906447). Central subunit of many protein complexes, namely
CC TRAMP-like, nuclear exosome targeting (NEXT) and poly(A) tail exosome
CC targeting (PAXT) (PubMed:27871484, PubMed:29844170, PubMed:21855801).
CC NEXT functions as an RNA exosome cofactor that directs a subset of non-
CC coding short-lived RNAs for exosomal degradation. NEXT is involved in
CC surveillance and turnover of aberrant transcripts and non-coding RNAs
CC (PubMed:27871484, PubMed:29844170). PAXT directs a subset of long and
CC polyadenylated poly(A) RNAs for exosomal degradation. The RNA exosome
CC is fundamental for the degradation of RNA in eukaryotic nuclei.
CC Substrate targeting is facilitated by its cofactor ZCCHC8, which links
CC to RNA-binding protein adapters (PubMed:27871484). Associated with the
CC RNA exosome complex and involved in the 3'-processing of the 7S pre-RNA
CC to the mature 5.8S rRNA (PubMed:17412707, PubMed:29107693). May be
CC involved in pre-mRNA splicing. In the context of NEXT complex can also
CC in vitro unwind DNA:RNA heteroduplexes with a 3' poly (A) RNA tracking
CC strand (PubMed:29844170). Can promote unwinding and degradation of
CC structured RNA substrates when associated with the nuclear exosome and
CC its cofactors. Can displace a DNA strand while translocating on RNA to
CC ultimately degrade the RNA within a DNA/RNA heteroduplex
CC (PubMed:29906447). Plays a role in DNA damage response
CC (PubMed:29902117). {ECO:0000269|PubMed:17412707,
CC ECO:0000269|PubMed:21855801, ECO:0000269|PubMed:27871484,
CC ECO:0000269|PubMed:29107693, ECO:0000269|PubMed:29844170,
CC ECO:0000269|PubMed:29902117, ECO:0000269|PubMed:29906447}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
CC Evidence={ECO:0000269|PubMed:29844170, ECO:0000269|PubMed:29906447};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066;
CC Evidence={ECO:0000269|PubMed:29844170};
CC -!- ACTIVITY REGULATION: Activated when MTREX is incorporated into NEXT
CC complex an the nuclear RNA exosome complex.
CC {ECO:0000269|PubMed:29844170, ECO:0000269|PubMed:29906447}.
CC -!- SUBUNIT: Component of a TRAMP-like complex, an ATP-dependent exosome
CC regulatory complex consisting of a helicase (MTREX), an oligadenylate
CC polymerase (TENT4B or TENT4A), and a substrate specific RNA-binding
CC factor (ZCCHC7 or ZCCHC8). Several TRAMP-like complexes exist with
CC specific compositions and are associated with nuclear, or nucleolar RNA
CC exosomes (PubMed:21855801). Identified in the spliceosome C complex.
CC Component of the poly(A) tail exosome targeting (PAXT) complex made of
CC PABPN1, ZFC3H1 and MTREX that directs a subset of long and
CC polyadenylated poly(A) RNAs for exosomal degradation (PubMed:27871484).
CC Component of the nuclear exosome targeting (NEXT) complex composed of
CC MTREX, ZCCHC8, and RBM7 that directs a subset of non-coding short-lived
CC RNAs for exosomal degradation (PubMed:27905398, PubMed:27871484).
CC Interacts with ZCCHC8; this interaction bridges the interaction between
CC RBM7 and MTREX (PubMed:27905398, PubMed:16263084, PubMed:29844170,
CC PubMed:31358741). Binds to ZFC3H1 and RBM7 in a RNase-insensitive
CC manner (PubMed:27871484). Interacts with EXOSC10; the interaction
CC mediates the association of MTREX with nuclear RNA exosomes
CC (PubMed:26166824). Interacts with isoform 1 of NVL in an ATP-dependent
CC manner; the interaction is required to associate NVL with nuclear RNA
CC exosome (PubMed:16782053, PubMed:26166824, PubMed:11991638,
CC PubMed:16263084, PubMed:21855801, PubMed:27871484, PubMed:27905398,
CC PubMed:31358741). Interacts with WDR74; the interaction dissociation in
CC a late stage of rRNA synthesis is required for appropriate maturation
CC of pre-60S particles and depends on the ATPase activity of NVL
CC (PubMed:26456651, PubMed:29107693). Interacts with MPHOSPH6
CC (PubMed:17412707). Interacts with the RNA cap-binding complex proteins
CC NCBP1 and SRRT (PubMed:30842217). Interacts with NRDE2; the interaction
CC is direct and negatively regulates MTREX function in exosomal
CC degradation by changing its conformation precluding interaction with
CC ZFC3H1, the RNA cap-binding complex proteins NCBP1 and SRRT, and
CC association with the exosome (PubMed:30842217, PubMed:30538148,
CC PubMed:29902117). Interacts with the nuclear RNA exosome complex
CC (PubMed:29906447). {ECO:0000269|PubMed:11991638,
CC ECO:0000269|PubMed:16263084, ECO:0000269|PubMed:16782053,
CC ECO:0000269|PubMed:17412707, ECO:0000269|PubMed:21855801,
CC ECO:0000269|PubMed:26166824, ECO:0000269|PubMed:26456651,
CC ECO:0000269|PubMed:27871484, ECO:0000269|PubMed:27905398,
CC ECO:0000269|PubMed:29107693, ECO:0000269|PubMed:29844170,
CC ECO:0000269|PubMed:29902117, ECO:0000269|PubMed:29906447,
CC ECO:0000269|PubMed:30538148, ECO:0000269|PubMed:30842217,
CC ECO:0000269|PubMed:31358741}.
CC -!- INTERACTION:
CC P42285; Q99547: MPHOSPH6; NbExp=2; IntAct=EBI-347612, EBI-373187;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:30842217}. Nucleus, nucleolus
CC {ECO:0000269|PubMed:12429849}. Nucleus {ECO:0000269|PubMed:16782053}.
CC Nucleus speckle {ECO:0000269|PubMed:30842217}.
CC -!- SIMILARITY: Belongs to the helicase family. SKI2 subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH65258.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA06124.2; 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; D29641; BAA06124.2; ALT_INIT; mRNA.
DR EMBL; BX640789; CAE45877.1; -; mRNA.
DR EMBL; BC014669; AAH14669.2; -; mRNA.
DR EMBL; BC028604; AAH28604.3; -; mRNA.
DR EMBL; BC031779; AAH31779.1; -; mRNA.
DR EMBL; BC065258; AAH65258.1; ALT_INIT; mRNA.
DR EMBL; BC104996; AAI04997.1; -; mRNA.
DR EMBL; BC113509; AAI13510.1; -; mRNA.
DR CCDS; CCDS3967.1; -.
DR RefSeq; NP_056175.3; NM_015360.4.
DR PDB; 6C90; X-ray; 2.20 A; A=71-600, A=843-1042.
DR PDB; 6D6Q; EM; 3.45 A; M=1-1042.
DR PDB; 6D6R; EM; 3.45 A; M=1-1042.
DR PDB; 6IEG; X-ray; 3.55 A; A/B=71-1042.
DR PDB; 6IEH; X-ray; 2.89 A; B=71-1042.
DR PDB; 6RO1; X-ray; 3.07 A; A=70-1042.
DR PDBsum; 6C90; -.
DR PDBsum; 6D6Q; -.
DR PDBsum; 6D6R; -.
DR PDBsum; 6IEG; -.
DR PDBsum; 6IEH; -.
DR PDBsum; 6RO1; -.
DR AlphaFoldDB; P42285; -.
DR SMR; P42285; -.
DR BioGRID; 117064; 181.
DR CORUM; P42285; -.
DR ELM; P42285; -.
DR IntAct; P42285; 71.
DR MINT; P42285; -.
DR STRING; 9606.ENSP00000230640; -.
DR ChEMBL; CHEMBL4105889; -.
DR GlyGen; P42285; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P42285; -.
DR MetOSite; P42285; -.
DR PhosphoSitePlus; P42285; -.
DR SwissPalm; P42285; -.
DR BioMuta; SKIV2L2; -.
DR DMDM; 71153172; -.
DR SWISS-2DPAGE; P42285; -.
DR EPD; P42285; -.
DR jPOST; P42285; -.
DR MassIVE; P42285; -.
DR MaxQB; P42285; -.
DR PaxDb; P42285; -.
DR PeptideAtlas; P42285; -.
DR PRIDE; P42285; -.
DR ProteomicsDB; 55503; -.
DR Antibodypedia; 23424; 222 antibodies from 29 providers.
DR DNASU; 23517; -.
DR Ensembl; ENST00000230640.10; ENSP00000230640.5; ENSG00000039123.16.
DR GeneID; 23517; -.
DR KEGG; hsa:23517; -.
DR MANE-Select; ENST00000230640.10; ENSP00000230640.5; NM_015360.5; NP_056175.3.
DR UCSC; uc003jpy.5; human.
DR CTD; 23517; -.
DR DisGeNET; 23517; -.
DR GeneCards; MTREX; -.
DR HGNC; HGNC:18734; MTREX.
DR HPA; ENSG00000039123; Low tissue specificity.
DR MIM; 618122; gene.
DR neXtProt; NX_P42285; -.
DR OpenTargets; ENSG00000039123; -.
DR PharmGKB; PA134901921; -.
DR VEuPathDB; HostDB:ENSG00000039123; -.
DR eggNOG; KOG0948; Eukaryota.
DR GeneTree; ENSGT00940000156183; -.
DR HOGENOM; CLU_002902_0_1_1; -.
DR InParanoid; P42285; -.
DR OMA; IMLKNYN; -.
DR OrthoDB; 176060at2759; -.
DR PhylomeDB; P42285; -.
DR TreeFam; TF300597; -.
DR PathwayCommons; P42285; -.
DR Reactome; R-HSA-6791226; Major pathway of rRNA processing in the nucleolus and cytosol.
DR Reactome; R-HSA-72163; mRNA Splicing - Major Pathway.
DR SignaLink; P42285; -.
DR BioGRID-ORCS; 23517; 766 hits in 1079 CRISPR screens.
DR ChiTaRS; SKIV2L2; human.
DR GeneWiki; SKIV2L2; -.
DR GenomeRNAi; 23517; -.
DR Pharos; P42285; Tbio.
DR PRO; PR:P42285; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P42285; protein.
DR Bgee; ENSG00000039123; Expressed in calcaneal tendon and 208 other tissues.
DR ExpressionAtlas; P42285; baseline and differential.
DR Genevisible; P42285; HS.
DR GO; GO:0071013; C:catalytic step 2 spliceosome; IDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0031499; C:TRAMP complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0003724; F:RNA helicase activity; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0000460; P:maturation of 5.8S rRNA; IMP:UniProtKB.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IC:UniProtKB.
DR GO; GO:0006401; P:RNA catabolic process; IDA:UniProtKB.
DR GO; GO:0006364; P:rRNA processing; IMP:UniProtKB.
DR GO; GO:0016076; P:snRNA catabolic process; ISS:UniProtKB.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR011545; DEAD/DEAH_box_helicase_dom.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR025696; rRNA_proc-arch_dom.
DR InterPro; IPR016438; Ski2-like.
DR InterPro; IPR012961; Ski2_C.
DR Pfam; PF00270; DEAD; 1.
DR Pfam; PF08148; DSHCT; 1.
DR Pfam; PF00271; Helicase_C; 1.
DR Pfam; PF13234; rRNA_proc-arch; 1.
DR PIRSF; PIRSF005198; Antiviral_helicase_SKI2; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM01142; DSHCT; 1.
DR SMART; SM00490; HELICc; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Direct protein sequencing;
KW DNA damage; Helicase; Hydrolase; Isopeptide bond; mRNA processing;
KW mRNA splicing; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; rRNA processing; Spliceosome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895"
FT CHAIN 2..1042
FT /note="Exosome RNA helicase MTR4"
FT /id="PRO_0000102094"
FT DOMAIN 148..304
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 405..577
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT REGION 16..74
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 252..255
FT /note="DEIH box"
FT COMPBIAS 20..50
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 58..74
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 139
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:31358741,
FT ECO:0007744|PDB:6RO1"
FT BINDING 161..168
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT BINDING 164
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:29844170,
FT ECO:0000269|PubMed:31358741, ECO:0007744|PDB:6C90,
FT ECO:0007744|PDB:6RO1"
FT BINDING 166
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:29844170,
FT ECO:0000269|PubMed:31358741, ECO:0007744|PDB:6C90,
FT ECO:0007744|PDB:6RO1"
FT BINDING 167
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:29844170,
FT ECO:0000269|PubMed:31358741, ECO:0007744|PDB:6C90,
FT ECO:0007744|PDB:6RO1"
FT BINDING 168
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:29844170,
FT ECO:0000269|PubMed:31358741, ECO:0007744|PDB:6C90,
FT ECO:0007744|PDB:6RO1"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895"
FT MOD_RES 40
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 51
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 78
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9CZU3"
FT CROSSLNK 24
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 358
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 684
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 723
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 346
FT /note="A -> P (in dbSNP:rs35643285)"
FT /id="VAR_049343"
FT MUTAGEN 253
FT /note="E->Q: Abolishes RNA helicase activity."
FT /evidence="ECO:0000269|PubMed:29844170"
FT MUTAGEN 658
FT /note="R->A: Decreased interaction with NRDE2."
FT /evidence="ECO:0000269|PubMed:30842217"
FT MUTAGEN 697
FT /note="E->R: Decreased interaction with NRDE2."
FT /evidence="ECO:0000269|PubMed:30842217"
FT MUTAGEN 743
FT /note="R->E: Decreased interaction with NRDE2. Impairs the
FT binding of both NVL and NOP53."
FT /evidence="ECO:0000269|PubMed:30842217,
FT ECO:0000269|PubMed:31358741"
FT MUTAGEN 989..990
FT /note="FE->AK: Loss of interaction with NRDE2."
FT /evidence="ECO:0000269|PubMed:30842217"
FT CONFLICT 342
FT /note="N -> K (in Ref. 5; AAH14669)"
FT /evidence="ECO:0000305"
FT CONFLICT 722
FT /note="E -> G (in Ref. 4; CAE45877)"
FT /evidence="ECO:0000305"
FT CONFLICT 900
FT /note="L -> I (in Ref. 5; AAH28604)"
FT /evidence="ECO:0000305"
FT CONFLICT 927
FT /note="Q -> R (in Ref. 4; CAE45877)"
FT /evidence="ECO:0000305"
FT STRAND 99..104
FT /evidence="ECO:0007829|PDB:6C90"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:6C90"
FT STRAND 111..117
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 142..152
FT /evidence="ECO:0007829|PDB:6C90"
FT STRAND 156..160
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 168..180
FT /evidence="ECO:0007829|PDB:6C90"
FT STRAND 184..191
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 192..206
FT /evidence="ECO:0007829|PDB:6C90"
FT STRAND 209..212
FT /evidence="ECO:0007829|PDB:6C90"
FT STRAND 223..228
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 229..237
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 241..243
FT /evidence="ECO:0007829|PDB:6C90"
FT STRAND 246..251
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 254..256
FT /evidence="ECO:0007829|PDB:6C90"
FT TURN 257..261
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 263..272
FT /evidence="ECO:0007829|PDB:6C90"
FT STRAND 278..284
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 289..300
FT /evidence="ECO:0007829|PDB:6C90"
FT STRAND 304..308
FT /evidence="ECO:0007829|PDB:6C90"
FT STRAND 316..322
FT /evidence="ECO:0007829|PDB:6C90"
FT STRAND 329..332
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 340..348
FT /evidence="ECO:0007829|PDB:6C90"
FT TURN 355..357
FT /evidence="ECO:0007829|PDB:6RO1"
FT HELIX 371..383
FT /evidence="ECO:0007829|PDB:6C90"
FT STRAND 388..392
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 396..405
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 406..408
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 414..428
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 433..436
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 439..449
FT /evidence="ECO:0007829|PDB:6C90"
FT STRAND 452..455
FT /evidence="ECO:0007829|PDB:6C90"
FT STRAND 457..459
FT /evidence="ECO:0007829|PDB:6IEH"
FT HELIX 461..472
FT /evidence="ECO:0007829|PDB:6C90"
FT STRAND 477..481
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 483..487
FT /evidence="ECO:0007829|PDB:6C90"
FT STRAND 488..490
FT /evidence="ECO:0007829|PDB:6C90"
FT STRAND 493..499
FT /evidence="ECO:0007829|PDB:6C90"
FT STRAND 501..504
FT /evidence="ECO:0007829|PDB:6C90"
FT STRAND 509..511
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 514..521
FT /evidence="ECO:0007829|PDB:6C90"
FT TURN 527..529
FT /evidence="ECO:0007829|PDB:6C90"
FT STRAND 531..539
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 545..553
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 567..575
FT /evidence="ECO:0007829|PDB:6C90"
FT STRAND 576..578
FT /evidence="ECO:0007829|PDB:6RO1"
FT HELIX 581..587
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 589..597
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 598..604
FT /evidence="ECO:0007829|PDB:6IEH"
FT HELIX 608..614
FT /evidence="ECO:0007829|PDB:6IEH"
FT HELIX 623..644
FT /evidence="ECO:0007829|PDB:6IEH"
FT HELIX 647..650
FT /evidence="ECO:0007829|PDB:6IEH"
FT HELIX 651..653
FT /evidence="ECO:0007829|PDB:6IEH"
FT STRAND 658..664
FT /evidence="ECO:0007829|PDB:6IEH"
FT STRAND 667..680
FT /evidence="ECO:0007829|PDB:6IEH"
FT STRAND 693..702
FT /evidence="ECO:0007829|PDB:6IEH"
FT HELIX 704..707
FT /evidence="ECO:0007829|PDB:6IEH"
FT STRAND 720..722
FT /evidence="ECO:0007829|PDB:6RO1"
FT STRAND 725..732
FT /evidence="ECO:0007829|PDB:6IEH"
FT HELIX 733..735
FT /evidence="ECO:0007829|PDB:6IEH"
FT STRAND 736..743
FT /evidence="ECO:0007829|PDB:6IEH"
FT HELIX 753..769
FT /evidence="ECO:0007829|PDB:6IEH"
FT TURN 779..782
FT /evidence="ECO:0007829|PDB:6IEH"
FT HELIX 788..806
FT /evidence="ECO:0007829|PDB:6IEH"
FT HELIX 808..811
FT /evidence="ECO:0007829|PDB:6IEH"
FT STRAND 812..814
FT /evidence="ECO:0007829|PDB:6IEH"
FT HELIX 815..840
FT /evidence="ECO:0007829|PDB:6IEH"
FT TURN 841..843
FT /evidence="ECO:0007829|PDB:6IEH"
FT HELIX 848..860
FT /evidence="ECO:0007829|PDB:6C90"
FT STRAND 863..865
FT /evidence="ECO:0007829|PDB:6D6Q"
FT TURN 866..868
FT /evidence="ECO:0007829|PDB:6D6Q"
FT HELIX 872..877
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 885..894
FT /evidence="ECO:0007829|PDB:6C90"
FT TURN 895..899
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 902..909
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 910..912
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 926..948
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 955..960
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 967..974
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 979..983
FT /evidence="ECO:0007829|PDB:6C90"
FT STRAND 986..988
FT /evidence="ECO:0007829|PDB:6D6Q"
FT HELIX 990..1013
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 1017..1030
FT /evidence="ECO:0007829|PDB:6C90"
FT HELIX 1033..1036
FT /evidence="ECO:0007829|PDB:6C90"
SQ SEQUENCE 1042 AA; 117805 MW; 49F47BEC753FBEE7 CRC64;
MADAFGDELF SVFEGDSTTA AGTKKDKEKD KGKWKGPPGS ADKAGKRFDG KLQSESTNNG
KNKRDVDFEG TDEPIFGKKP RIEESITEDL SLADLMPRVK VQSVETVEGC THEVALPAEE
DYLPLKPRVG KAAKEYPFIL DAFQREAIQC VDNNQSVLVS AHTSAGKTVC AEYAIALALR
EKQRVIFTSP IKALSNQKYR EMYEEFQDVG LMTGDVTINP TASCLVMTTE ILRSMLYRGS
EVMREVAWVI FDEIHYMRDS ERGVVWEETI ILLPDNVHYV FLSATIPNAR QFAEWICHLH
KQPCHVIYTD YRPTPLQHYI FPAGGDGLHL VVDENGDFRE DNFNTAMQVL RDAGDLAKGD
QKGRKGGTKG PSNVFKIVKM IMERNFQPVI IFSFSKKDCE AYALQMTKLD FNTDEEKKMV
EEVFSNAIDC LSDEDKKLPQ VEHVLPLLKR GIGIHHGGLL PILKETIEIL FSEGLIKALF
ATETFAMGIN MPARTVLFTN ARKFDGKDFR WISSGEYIQM SGRAGRRGMD DRGIVILMVD
EKMSPTIGKQ LLKGSADPLN SAFHLTYNMV LNLLRVEEIN PEYMLEKSFY QFQHYRAIPG
VVEKVKNSEE QYNKIVIPNE ESVVIYYKIR QQLAKLGKEI EEYIHKPKYC LPFLQPGRLV
KVKNEGDDFG WGVVVNFSKK SNVKPNSGEL DPLYVVEVLL RCSKESLKNS ATEAAKPAKP
DEKGEMQVVP VLVHLLSAIS SVRLYIPKDL RPVDNRQSVL KSIQEVQKRF PDGIPLLDPI
DDMGIQDQGL KKVIQKVEAF EHRMYSHPLH NDPNLETVYT LCEKKAQIAI DIKSAKRELK
KARTVLQMDE LKCRKRVLRR LGFATSSDVI EMKGRVACEI SSADELLLTE MMFNGLFNDL
SAEQATALLS CFVFQENSSE MPKLTEQLAG PLRQMQECAK RIAKVSAEAK LEIDEETYLS
SFKPHLMDVV YTWATGATFA HICKMTDVFE GSIIRCMRRL EELLRQMCQA AKAIGNTELE
NKFAEGITKI KRDIVFAASL YL
