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 27-MAR-2024, entry version 198. 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; Q9NXV6: CDKN2AIP; NbExp=4; IntAct=EBI-372110, EBI-2559836; CC Q9H0D6; Q96HQ2: CDKN2AIPNL; NbExp=3; 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}; 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; 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; 366. DR CORUM; Q9H0D6; -. DR DIP; DIP-31166N; -. DR IntAct; Q9H0D6; 90. 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 EPD; Q9H0D6; -. DR jPOST; Q9H0D6; -. DR MassIVE; Q9H0D6; -. DR MaxQB; Q9H0D6; -. DR PaxDb; 9606-ENSP00000366396; -. DR PeptideAtlas; Q9H0D6; -. DR ProteomicsDB; 80258; -. [Q9H0D6-1] DR ProteomicsDB; 80259; -. [Q9H0D6-2] DR Pumba; Q9H0D6; -. DR Antibodypedia; 24812; 222 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 AGR; HGNC:12836; -. 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 InParanoid; Q9H0D6; -. DR OMA; CLHYYVH; -. DR OrthoDB; 167745at2759; -. 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; 750 hits in 1136 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 180 other cell types or tissues. DR GO; GO:0016235; C:aggresome; IDA:HPA. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0000175; F:3'-5'-RNA exonuclease activity; EXP:Reactome. DR GO; GO:0008409; F:5'-3' exonuclease activity; IDA:UniProtKB. DR GO; GO:0004534; F:5'-3' RNA exonuclease 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: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 GO; GO:0006369; P:termination of RNA polymerase II transcription; IMP:UniProtKB. DR CDD; cd18673; PIN_XRN1-2-like; 1. DR Gene3D; 1.25.40.1050; -; 1. DR Gene3D; 3.40.50.12390; -; 2. DR InterPro; IPR027073; 5_3_exoribonuclease. DR InterPro; IPR041412; Xrn1_helical. DR InterPro; IPR004859; Xrn1_N. DR InterPro; IPR017151; Xrn2/3/4. DR PANTHER; PTHR12341:SF77; 5'-3' EXORIBONUCLEASE 2; 1. DR PANTHER; PTHR12341; 5'->3' EXORIBONUCLEASE; 1. DR Pfam; PF17846; XRN_M; 1. DR Pfam; PF03159; XRN_N; 1. DR PIRSF; PIRSF037239; Exonuclease_Xrn2; 1. DR SWISS-2DPAGE; Q9H0D6; -. DR Genevisible; Q9H0D6; HS. 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 //