XRN2_HUMAN
ID XRN2_HUMAN Reviewed; 950 AA.
AC Q9H0D6; Q3L8N4; Q6KGZ9; Q9BQL1; Q9NTW0; Q9NXS6; Q9UL53;
DT 23-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=5'-3' exoribonuclease 2;
DE EC=3.1.13.-;
DE AltName: Full=DHM1-like protein;
DE Short=DHP protein;
GN Name=XRN2;
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] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=10409438; DOI=10.1006/geno.1999.5866;
RA Zhang M., Yu L., Xin Y., Hu P., Fu Q., Yu C., Zhao S.Y.;
RT "Cloning and mapping of the XRN2 gene to human chromosome 20p11.1-p11.2.";
RL Genomics 59:252-254(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RX PubMed=16147866; DOI=10.1080/10425170500066771;
RA Li J., Zheng H., Ji C., Fei X., Zheng M., Gao Y., Ren Y., Gu S., Xie Y.,
RA Mao Y.;
RT "A novel splice variant of human XRN2 gene is mainly expressed in blood
RT leukocyte.";
RL DNA Seq. 16:143-146(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 358-950 (ISOFORMS 1/2).
RC TISSUE=Colon;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 371-950 (ISOFORMS 1/2).
RC TISSUE=Colon;
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 [7]
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 [8]
RP FUNCTION.
RX PubMed=15565158; DOI=10.1038/nature03035;
RA West S., Gromak N., Proudfoot N.J.;
RT "Human 5' -> 3' exonuclease Xrn2 promotes transcription termination at co-
RT transcriptional cleavage sites.";
RL Nature 432:522-525(2004).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-448; SER-499 AND SER-501, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [10]
RP FUNCTION.
RX PubMed=16648491; DOI=10.1128/mcb.26.10.3986-3996.2006;
RA Gromak N., West S., Proudfoot N.J.;
RT "Pause sites promote transcriptional termination of mammalian RNA
RT polymerase II.";
RL Mol. Cell. Biol. 26:3986-3996(2006).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-448, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-448, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells
RT and high confident phosphopeptide identification by cross-validation of
RT MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-448, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-439 AND SER-448, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-499 AND SER-501, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment
RT and fractionation of phosphopeptides with strong anion exchange
RT chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-448; SER-499 AND SER-501, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-448; SER-471; SER-473;
RP SER-475 AND SER-499, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-448; SER-499 AND SER-501, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [20]
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 [21]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=21700224; DOI=10.1016/j.molcel.2011.04.026;
RA Skourti-Stathaki K., Proudfoot N.J., Gromak N.;
RT "Human senataxin resolves RNA/DNA hybrids formed at transcriptional pause
RT sites to promote Xrn2-dependent termination.";
RL Mol. Cell 42:794-805(2011).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-448; SER-499 AND SER-501, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-439; SER-448; SER-487;
RP SER-499; SER-501 AND SER-678, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [24]
RP INTERACTION WITH TRIM71.
RX PubMed=23125361; DOI=10.1093/nar/gks1032;
RA Loedige I., Gaidatzis D., Sack R., Meister G., Filipowicz W.;
RT "The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor of mRNA
RT function.";
RL Nucleic Acids Res. 41:518-532(2013).
RN [25]
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 [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-439; SER-448; SER-499 AND
RP SER-501, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [27]
RP INTERACTION WITH CDKN2AIP AND NKRF.
RX PubMed=24462208; DOI=10.1016/j.molcel.2014.01.001;
RA Miki T.S., Richter H., Rueegger S., Grosshans H.;
RT "PAXT-1 promotes XRN2 activity by stabilizing it through a conserved
RT domain.";
RL Mol. Cell 53:351-360(2014).
RN [28]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-824; ARG-847; ARG-851; ARG-883;
RP ARG-895 AND ARG-946, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [29]
RP INTERACTION WITH POLR2A AND SMN1.
RX PubMed=26700805; DOI=10.1038/nature16469;
RA Yanling Zhao D., Gish G., Braunschweig U., Li Y., Ni Z., Schmitges F.W.,
RA Zhong G., Liu K., Li W., Moffat J., Vedadi M., Min J., Pawson T.J.,
RA Blencowe B.J., Greenblatt J.F.;
RT "SMN and symmetric arginine dimethylation of RNA polymerase II C-terminal
RT domain control termination.";
RL Nature 529:48-53(2016).
RN [30]
RP INTERACTION WITH CDKN2AIPNL.
RX PubMed=26779609; DOI=10.1038/nsmb.3155;
RA Richter H., Katic I., Gut H., Grosshans H.;
RT "Structural basis and function of XRN2 binding by XTB domains.";
RL Nat. Struct. Mol. Biol. 23:164-171(2016).
CC -!- FUNCTION: Possesses 5'->3' exoribonuclease activity (By similarity).
CC May promote the termination of transcription by RNA polymerase II.
CC During transcription termination, cleavage at the polyadenylation site
CC liberates a 5' fragment which is subsequently processed to form the
CC mature mRNA and a 3' fragment which remains attached to the elongating
CC polymerase. The processive degradation of this 3' fragment by this
CC protein may promote termination of transcription. Binds to RNA
CC polymerase II (RNAp II) transcription termination R-loops formed by G-
CC rich pause sites (PubMed:21700224). {ECO:0000250,
CC ECO:0000269|PubMed:15565158, ECO:0000269|PubMed:16648491,
CC ECO:0000269|PubMed:21700224}.
CC -!- SUBUNIT: Interacts with POLR2A and SMN1/SMN2 (PubMed:26700805).
CC Interacts with CDKN2AIP and NKRF (PubMed:24462208). Interacts with
CC CDKN2AIPNL; the interaction is direct (PubMed:26779609). Interacts with
CC TRIM71 (via NHL repeats) in an RNA-dependent manner (PubMed:23125361).
CC Interacts with DHX34; the interaction is RNA-independent
CC (PubMed:25220460). {ECO:0000269|PubMed:23125361,
CC ECO:0000269|PubMed:24462208, ECO:0000269|PubMed:25220460,
CC ECO:0000269|PubMed:26700805, ECO:0000269|PubMed:26779609}.
CC -!- INTERACTION:
CC Q9H0D6; Q96HQ2: CDKN2AIPNL; NbExp=2; IntAct=EBI-372110, EBI-10038935;
CC Q9H0D6; Q49AN0: CRY2; NbExp=3; IntAct=EBI-372110, EBI-2212355;
CC Q9H0D6; Q9NRI5: DISC1; NbExp=3; IntAct=EBI-372110, EBI-529989;
CC Q9H0D6; P80188: LCN2; NbExp=3; IntAct=EBI-372110, EBI-11911016;
CC Q9H0D6; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-372110, EBI-742388;
CC Q9H0D6; Q13148: TARDBP; NbExp=7; IntAct=EBI-372110, EBI-372899;
CC Q9H0D6; Q5W5X9-3: TTC23; NbExp=3; IntAct=EBI-372110, EBI-9090990;
CC Q9H0D6; Q9H0D6: XRN2; NbExp=3; IntAct=EBI-372110, EBI-372110;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:12429849}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=XRN2a;
CC IsoId=Q9H0D6-1; Sequence=Displayed;
CC Name=2; Synonyms=XRN2b;
CC IsoId=Q9H0D6-2; Sequence=VSP_020596;
CC -!- TISSUE SPECIFICITY: Expressed in the spleen, thymus, prostate, testis,
CC ovary, small intestine, colon, peripheral blood leukocytes, heart,
CC brain, placenta, lung, liver, skeletal muscle, kidney, and pancreas.
CC Isoform 2 is expressed predominantly in peripheral blood leukocytes.
CC {ECO:0000269|PubMed:10409438, ECO:0000269|PubMed:16147866}.
CC -!- SIMILARITY: Belongs to the 5'-3' exonuclease family. XRN2/RAT1
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAR24369.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAA90934.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF064257; AAD55138.1; -; mRNA.
DR EMBL; AF152169; AAQ13577.1; -; mRNA.
DR EMBL; AY382900; AAR24369.1; ALT_FRAME; mRNA.
DR EMBL; AL136841; CAB66775.1; -; mRNA.
DR EMBL; AL117332; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL158013; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK000084; BAA90934.1; ALT_INIT; mRNA.
DR EMBL; BC006417; AAH06417.2; -; mRNA.
DR CCDS; CCDS13144.1; -. [Q9H0D6-1]
DR RefSeq; NP_001304889.1; NM_001317960.1.
DR RefSeq; NP_036387.2; NM_012255.4. [Q9H0D6-1]
DR AlphaFoldDB; Q9H0D6; -.
DR SMR; Q9H0D6; -.
DR BioGRID; 116483; 311.
DR CORUM; Q9H0D6; -.
DR DIP; DIP-31166N; -.
DR IntAct; Q9H0D6; 80.
DR MINT; Q9H0D6; -.
DR STRING; 9606.ENSP00000366396; -.
DR GlyGen; Q9H0D6; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9H0D6; -.
DR MetOSite; Q9H0D6; -.
DR PhosphoSitePlus; Q9H0D6; -.
DR SwissPalm; Q9H0D6; -.
DR BioMuta; XRN2; -.
DR DMDM; 30173484; -.
DR SWISS-2DPAGE; Q9H0D6; -.
DR EPD; Q9H0D6; -.
DR jPOST; Q9H0D6; -.
DR MassIVE; Q9H0D6; -.
DR MaxQB; Q9H0D6; -.
DR PaxDb; Q9H0D6; -.
DR PeptideAtlas; Q9H0D6; -.
DR PRIDE; Q9H0D6; -.
DR ProteomicsDB; 80258; -. [Q9H0D6-1]
DR ProteomicsDB; 80259; -. [Q9H0D6-2]
DR Antibodypedia; 24812; 192 antibodies from 28 providers.
DR DNASU; 22803; -.
DR Ensembl; ENST00000377191.5; ENSP00000366396.3; ENSG00000088930.8. [Q9H0D6-1]
DR GeneID; 22803; -.
DR KEGG; hsa:22803; -.
DR MANE-Select; ENST00000377191.5; ENSP00000366396.3; NM_012255.5; NP_036387.2.
DR UCSC; uc002wsf.2; human. [Q9H0D6-1]
DR CTD; 22803; -.
DR DisGeNET; 22803; -.
DR GeneCards; XRN2; -.
DR HGNC; HGNC:12836; XRN2.
DR HPA; ENSG00000088930; Low tissue specificity.
DR MIM; 608851; gene.
DR neXtProt; NX_Q9H0D6; -.
DR OpenTargets; ENSG00000088930; -.
DR PharmGKB; PA37427; -.
DR VEuPathDB; HostDB:ENSG00000088930; -.
DR eggNOG; KOG2044; Eukaryota.
DR GeneTree; ENSGT00670000098098; -.
DR HOGENOM; CLU_006038_1_2_1; -.
DR OMA; CLHYYVH; -.
DR OrthoDB; 685597at2759; -.
DR PhylomeDB; Q9H0D6; -.
DR TreeFam; TF105977; -.
DR BRENDA; 3.1.13.1; 2681.
DR PathwayCommons; Q9H0D6; -.
DR Reactome; R-HSA-390471; Association of TriC/CCT with target proteins during biosynthesis.
DR Reactome; R-HSA-6791226; Major pathway of rRNA processing in the nucleolus and cytosol.
DR SignaLink; Q9H0D6; -.
DR SIGNOR; Q9H0D6; -.
DR BioGRID-ORCS; 22803; 716 hits in 1058 CRISPR screens.
DR ChiTaRS; XRN2; human.
DR GeneWiki; 5%27-3%27_exoribonuclease_2; -.
DR GenomeRNAi; 22803; -.
DR Pharos; Q9H0D6; Tbio.
DR PRO; PR:Q9H0D6; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9H0D6; protein.
DR Bgee; ENSG00000088930; Expressed in monocyte and 178 other tissues.
DR Genevisible; Q9H0D6; HS.
DR GO; GO:0016235; C:aggresome; IDA:HPA.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000175; F:3'-5'-exoribonuclease activity; EXP:Reactome.
DR GO; GO:0008409; F:5'-3' exonuclease activity; IDA:UniProtKB.
DR GO; GO:0004534; F:5'-3' exoribonuclease activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004518; F:nuclease activity; TAS:ProtInc.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0001147; F:transcription termination site sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0000738; P:DNA catabolic process, exonucleolytic; IDA:UniProtKB.
DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0030182; P:neuron differentiation; IEA:Ensembl.
DR GO; GO:0000956; P:nuclear-transcribed mRNA catabolic process; IBA:GO_Central.
DR GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl.
DR GO; GO:0006401; P:RNA catabolic process; TAS:ProtInc.
DR GO; GO:0016070; P:RNA metabolic process; ISS:UniProtKB.
DR GO; GO:0006396; P:RNA processing; TAS:ProtInc.
DR GO; GO:0006364; P:rRNA processing; TAS:Reactome.
DR GO; GO:0007283; P:spermatogenesis; IEP:UniProtKB.
DR InterPro; IPR027073; 5_3_exoribonuclease.
DR InterPro; IPR004859; Put_53exo.
DR InterPro; IPR041412; Xrn1_helical.
DR InterPro; IPR017151; Xrn2/3/4.
DR PANTHER; PTHR12341; PTHR12341; 1.
DR Pfam; PF17846; XRN_M; 1.
DR Pfam; PF03159; XRN_N; 1.
DR PIRSF; PIRSF037239; Exonuclease_Xrn2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; DNA-binding; Exonuclease; Hydrolase;
KW Metal-binding; Methylation; mRNA processing; Nuclease; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Transcription termination; Zinc; Zinc-finger.
FT CHAIN 1..950
FT /note="5'-3' exoribonuclease 2"
FT /id="PRO_0000071396"
FT ZN_FING 262..278
FT /note="CCHC-type"
FT REGION 408..508
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 911..950
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 440..486
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 493..508
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 286
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBR1"
FT MOD_RES 439
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 448
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:17924679,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 471
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 473
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 475
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 482
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBR1"
FT MOD_RES 487
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 499
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18318008, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 501
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18318008, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 678
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 824
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 824
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 847
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 847
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 851
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 851
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 880
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBR1"
FT MOD_RES 883
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBR1"
FT MOD_RES 883
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 895
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 946
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 946
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT VAR_SEQ 1..76
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16147866"
FT /id="VSP_020596"
FT VARIANT 743
FT /note="R -> M (in dbSNP:rs6137324)"
FT /id="VAR_027516"
FT VARIANT 925
FT /note="R -> C (in dbSNP:rs6047420)"
FT /id="VAR_053002"
FT CONFLICT 14
FT /note="Y -> C (in Ref. 1; AAQ13577)"
FT /evidence="ECO:0000305"
FT CONFLICT 109
FT /note="A -> V (in Ref. 1; AAD55138/AAQ13577)"
FT /evidence="ECO:0000305"
FT CONFLICT 122..124
FT /note="SKE -> IKR (in Ref. 1; AAD55138)"
FT /evidence="ECO:0000305"
FT CONFLICT 240..245
FT /note="GLATHE -> AFPHMN (in Ref. 1; AAQ13577)"
FT /evidence="ECO:0000305"
FT CONFLICT 259
FT /note="K -> R (in Ref. 1; AAD55138/AAQ13577)"
FT /evidence="ECO:0000305"
FT CONFLICT 280
FT /note="P -> S (in Ref. 1; AAD55138/AAQ13577)"
FT /evidence="ECO:0000305"
FT CONFLICT 313
FT /note="L -> V (in Ref. 1; AAQ13577)"
FT /evidence="ECO:0000305"
FT CONFLICT 463
FT /note="E -> D (in Ref. 1; AAD55138)"
FT /evidence="ECO:0000305"
FT CONFLICT 582
FT /note="P -> S (in Ref. 1; AAQ13577)"
FT /evidence="ECO:0000305"
FT CONFLICT 584
FT /note="D -> E (in Ref. 1; AAD55138)"
FT /evidence="ECO:0000305"
FT CONFLICT 737
FT /note="S -> A (in Ref. 1; AAD55138)"
FT /evidence="ECO:0000305"
FT CONFLICT 760
FT /note="F -> L (in Ref. 2; AAR24369)"
FT /evidence="ECO:0000305"
FT CONFLICT 787
FT /note="E -> G (in Ref. 1; AAD55138)"
FT /evidence="ECO:0000305"
FT CONFLICT 874
FT /note="P -> L (in Ref. 2; AAR24369)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 950 AA; 108582 MW; 763B5E0E628F97A8 CRC64;
MGVPAFFRWL SRKYPSIIVN CVEEKPKECN GVKIPVDASK PNPNDVEFDN LYLDMNGIIH
PCTHPEDKPA PKNEDEMMVA IFEYIDRLFS IVRPRRLLYM AIDGVAPRAK MNQQRSRRFR
ASKEGMEAAV EKQRVREEIL AKGGFLPPEE IKERFDSNCI TPGTEFMDNL AKCLRYYIAD
RLNNDPGWKN LTVILSDASA PGEGEHKIMD YIRRQRAQPN HDPNTHHCLC GADADLIMLG
LATHEPNFTI IREEFKPNKP KPCGLCNQFG HEVKDCEGLP REKKGKHDEL ADSLPCAEGE
FIFLRLNVLR EYLERELTMA SLPFTFDVER SIDDWVFMCF FVGNDFLPHL PSLEIRENAI
DRLVNIYKNV VHKTGGYLTE SGYVNLQRVQ MIMLAVGEVE DSIFKKRKDD EDSFRRRQKE
KRKRMKRDQP AFTPSGILTP HALGSRNSPG SQVASNPRQA AYEMRMQNNS SPSISPNTSF
TSDGSPSPLG GIKRKAEDSD SEPEPEDNVR LWEAGWKQRY YKNKFDVDAA DEKFRRKVVQ
SYVEGLCWVL RYYYQGCASW KWYYPFHYAP FASDFEGIAD MPSDFEKGTK PFKPLEQLMG
VFPAASGNFL PPSWRKLMSD PDSSIIDFYP EDFAIDLNGK KYAWQGVALL PFVDERRLRA
ALEEVYPDLT PEETRRNSLG GDVLFVGKHH PLHDFILELY QTGSTEPVEV PPELCHGIQG
KFSLDEEAIL PDQIVCSPVP MLRDLTQNTV VSINFKDPQF AEDYIFKAVM LPGARKPAAV
LKPSDWEKSS NGRQWKPQLG FNRDRRPVHL DQAAFRTLGH VMPRGSGTGI YSNAAPPPVT
YQGNLYRPLL RGQAQIPKLM SNMRPQDSWR GPPPLFQQQR FDRGVGAEPL LPWNRMLQTQ
NAAFQPNQYQ MLAGPGGYPP RRDDRGGRQG YPREGRKYPL PPPSGRYNWN
