ID RNT2_HUMAN Reviewed; 256 AA. AC O00584; B2RDA7; E1P5C3; Q5T8Q0; Q8TCU2; Q9BZ46; Q9BZ47; DT 03-APR-2002, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 2. DT 27-MAR-2024, entry version 188. DE RecName: Full=Ribonuclease T2; DE EC=4.6.1.19 {ECO:0000255|PROSITE-ProRule:PRU10046}; DE AltName: Full=Ribonuclease 6; DE Flags: Precursor; GN Name=RNASET2; Synonyms=RNASE6PL; 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). RX PubMed=9192857; DOI=10.1006/geno.1997.4679; RA Trubia M., Sessa L., Taramelli R.; RT "Mammalian Rh/T2/S-glycoprotein ribonuclease family genes: cloning of a RT human member located in a region of chromosome 6 (6q27) frequently deleted RT in human malignancies."; RL Genomics 42:342-344(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RX PubMed=11821951; DOI=10.1038/sj.onc.1205067; RA Liu Y., Emilion G., Mungall A.J., Dunham I., Beck S., LeMeuth-Metzinger V., RA Shelling A.N., Charnock F.M., Ganesan T.S.; RT "Physical and transcript map of the region between D6S264 and D6S149 on RT chromosome 6q27, the minimal region of allele loss in sporadic epithelial RT ovarian cancer."; RL Oncogene 21:387-399(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Colon, Pancreas, and Spleen; 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. RX PubMed=15809705; RA Acquati F., Possati L., Ferrante L., Campomenosi P., Talevi S., RA Bardelli S., Margiotta C., Russo A., Bortoletto E., Rocchetti R., Calza R., RA Cinquetti R., Monti L., Salis S., Barbanti-Brodano G., Taramelli R.; RT "Tumor and metastasis suppression by the human RNASET2 gene."; RL Int. J. Oncol. 26:1159-1168(2005). RN [8] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=16620762; DOI=10.1016/j.abb.2006.02.022; RA Campomenosi P., Salis S., Lindqvist C., Mariani D., Nordstrom T., RA Acquati F., Taramelli R.; RT "Characterization of RNASET2, the first human member of the Rh/T2/S family RT of glycoproteins."; RL Arch. Biochem. Biophys. 449:17-26(2006). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANT LCWM ARG-184, RP AND CHARACTERIZATION OF VARIANT LCWM ARG-184. RX PubMed=19525954; DOI=10.1038/ng.398; RA Henneke M., Diekmann S., Ohlenbusch A., Kaiser J., Engelbrecht V., RA Kohlschutter A., Kratzner R., Madruga-Garrido M., Mayer M., Opitz L., RA Rodriguez D., Ruschendorf F., Schumacher J., Thiele H., Thoms S., RA Steinfeld R., Nurnberg P., Gartner J.; RT "RNASET2-deficient cystic leukoencephalopathy resembles congenital RT cytomegalovirus brain infection."; RL Nat. Genet. 41:773-775(2009). RN [10] 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 [11] RP SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANT LCWM ARG-184. RX PubMed=21199949; DOI=10.1073/pnas.1009811107; RA Haud N., Kara F., Diekmann S., Henneke M., Willer J.R., Hillwig M.S., RA Gregg R.G., Macintosh G.C., Gartner J., Alia A., Hurlstone A.F.; RT "rnaset2 mutant zebrafish model familial cystic leukoencephalopathy and RT reveal a role for RNase T2 in degrading ribosomal RNA."; RL Proc. Natl. Acad. Sci. U.S.A. 108:1099-1103(2011). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [13] RP FUNCTION, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANT ARG-184. RX PubMed=28730546; DOI=10.1007/s13238-017-0448-9; RA Liu P., Huang J., Zheng Q., Xie L., Lu X., Jin J., Wang G.; RT "Mammalian mitochondrial RNAs are degraded in the mitochondrial RT intermembrane space by RNASET2."; RL Protein Cell 8:735-749(2017). RN [14] RP FUNCTION, MUTAGENESIS OF HIS-65 AND HIS-118, AND SUBCELLULAR LOCATION. RX PubMed=30385512; DOI=10.1074/jbc.ra118.005433; RA Huang J., Liu P., Wang G.; RT "Regulation of mitochondrion-associated cytosolic ribosomes by mammalian RT mitochondrial ribonuclease T2 (RNASET2)."; RL J. Biol. Chem. 293:19633-19644(2018). RN [15] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=30184494; DOI=10.1016/j.celrep.2018.08.003; RA Cheng Y., Liu P., Zheng Q., Gao G., Yuan J., Wang P., Huang J., Xie L., RA Lu X., Tong T., Chen J., Lu Z., Guan J., Wang G.; RT "Mitochondrial Trafficking and Processing of Telomerase RNA TERC."; RL Cell Rep. 24:2589-2595(2018). RN [16] RP FUNCTION. RX PubMed=31778653; DOI=10.1016/j.cell.2019.11.001; RA Greulich W., Wagner M., Gaidt M.M., Stafford C., Cheng Y., Linder A., RA Carell T., Hornung V.; RT "TLR8 Is a Sensor of RNase T2 Degradation Products."; RL Cell 179:1264-1275.E13(2019). RN [17] RP X-RAY CRYSTALLOGRAPHY (1.59 ANGSTROMS) OF 25-256, GLYCOSYLATION AT ASN-76; RP ASN-106 AND ASN-212, FUNCTION, ACTIVITY REGULATION, DISULFIDE BONDS, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=22735700; DOI=10.1093/nar/gks614; RA Thorn A., Steinfeld R., Ziegenbein M., Grapp M., Hsiao H.H., Urlaub H., RA Sheldrick G.M., Gartner J., Kratzner R.; RT "Structure and activity of the only human RNase T2."; RL Nucleic Acids Res. 40:8733-8742(2012). CC -!- FUNCTION: Ribonuclease that plays an essential role in innate immune CC response by recognizing and degrading RNAs from microbial pathogens CC that are subsequently sensed by TLR8 (PubMed:31778653). Cleaves CC preferentially single-stranded RNA molecules between purine and uridine CC residues, which critically contributes to the supply of catabolic CC uridine and the generation of purine-2',3'-cyclophosphate-terminated CC oligoribonucleotides (PubMed:31778653). In turn, RNase T2 degradation CC products promote the RNA-dependent activation of TLR8 CC (PubMed:31778653). Also plays a key role in degradation of CC mitochondrial RNA and processing of non-coding RNA imported from the CC cytosol into mitochondria (PubMed:28730546, PubMed:30184494). CC Participates as well in degradation of mitochondrion-associated CC cytosolic rRNAs (PubMed:30385512). {ECO:0000269|PubMed:16620762, CC ECO:0000269|PubMed:19525954, ECO:0000269|PubMed:22735700, CC ECO:0000269|PubMed:28730546, ECO:0000269|PubMed:30184494, CC ECO:0000269|PubMed:30385512, ECO:0000269|PubMed:31778653}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a ribonucleotidyl-ribonucleotide-RNA + H2O = a 3'-end 3'- CC phospho-ribonucleotide-RNA + a 5'-end dephospho-ribonucleoside-RNA + CC H(+); Xref=Rhea:RHEA:68052, Rhea:RHEA-COMP:10463, Rhea:RHEA- CC COMP:13936, Rhea:RHEA-COMP:17355, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:83062, ChEBI:CHEBI:138284, CC ChEBI:CHEBI:173118; EC=4.6.1.19; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU10046}; CC -!- ACTIVITY REGULATION: Inhibited by Zn(2+) and Cu(2+). CC {ECO:0000269|PubMed:22735700}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15809705, CC ECO:0000269|PubMed:16620762}. Lysosome lumen CC {ECO:0000269|PubMed:16620762}. Endoplasmic reticulum lumen CC {ECO:0000269|PubMed:16620762}. Mitochondrion intermembrane space CC {ECO:0000269|PubMed:28730546, ECO:0000269|PubMed:30184494, CC ECO:0000269|PubMed:30385512}. Note=Full-length RNASET2 is found in the CC endoplasmic reticulum while smaller RNASET2 proteolytic products are CC found in the lysosome fraction. {ECO:0000269|PubMed:16620762}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O00584-1; Sequence=Displayed; CC Name=2; CC IsoId=O00584-2; Sequence=VSP_008405, VSP_008406; CC -!- TISSUE SPECIFICITY: Ubiquitous. Higher expression levels observed in CC the temporal lobe and fetal brain. {ECO:0000269|PubMed:19525954}. CC -!- DISEASE: Leukoencephalopathy, cystic, without megalencephaly (LCWM) CC [MIM:612951]: An infantile-onset syndrome of cerebral CC leukoencephalopathy. Affected newborns develop microcephaly and CC neurologic abnormalities including psychomotor impairment, seizures and CC sensorineural hearing impairment. The brain shows multifocal white CC matter lesions, anterior temporal lobe subcortical cysts, pericystic CC abnormal myelination, ventriculomegaly and intracranial calcifications. CC {ECO:0000269|PubMed:19525954, ECO:0000269|PubMed:21199949}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the RNase T2 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/518/RNASET2"; 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; U85625; AAC51363.2; -; mRNA. DR EMBL; AJ419865; CAD12030.1; -; mRNA. DR EMBL; AJ419866; CAD12031.1; -; mRNA. DR EMBL; AK315467; BAG37854.1; -; mRNA. DR EMBL; AL133458; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL159163; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471051; EAW47512.1; -; Genomic_DNA. DR EMBL; CH471051; EAW47513.1; -; Genomic_DNA. DR EMBL; CH471051; EAW47514.1; -; Genomic_DNA. DR EMBL; BC001660; AAH01660.1; -; mRNA. DR EMBL; BC001819; AAH01819.1; -; mRNA. DR EMBL; BC039713; AAH39713.1; -; mRNA. DR EMBL; BC051912; AAH51912.1; -; mRNA. DR CCDS; CCDS5295.1; -. [O00584-1] DR PIR; S78046; S78046. DR RefSeq; NP_003721.2; NM_003730.4. [O00584-1] DR PDB; 3T0O; X-ray; 1.59 A; A=25-256. DR PDBsum; 3T0O; -. DR AlphaFoldDB; O00584; -. DR SMR; O00584; -. DR BioGRID; 114188; 20. DR IntAct; O00584; 7. DR STRING; 9606.ENSP00000426455; -. DR GlyConnect; 1719; 7 N-Linked glycans (2 sites). DR GlyCosmos; O00584; 4 sites, 9 glycans. DR GlyGen; O00584; 4 sites, 7 N-linked glycans (2 sites), 2 O-linked glycans (1 site). DR iPTMnet; O00584; -. DR PhosphoSitePlus; O00584; -. DR SwissPalm; O00584; -. DR BioMuta; RNASET2; -. DR EPD; O00584; -. DR jPOST; O00584; -. DR MassIVE; O00584; -. DR MaxQB; O00584; -. DR PaxDb; 9606-ENSP00000426455; -. DR PeptideAtlas; O00584; -. DR ProteomicsDB; 47985; -. [O00584-1] DR ProteomicsDB; 47986; -. [O00584-2] DR Pumba; O00584; -. DR Antibodypedia; 33528; 219 antibodies from 29 providers. DR DNASU; 8635; -. DR Ensembl; ENST00000421787.5; ENSP00000390833.1; ENSG00000026297.17. [O00584-2] DR Ensembl; ENST00000476238.6; ENSP00000422846.1; ENSG00000026297.17. [O00584-1] DR Ensembl; ENST00000508775.6; ENSP00000426455.2; ENSG00000026297.17. [O00584-1] DR GeneID; 8635; -. DR KEGG; hsa:8635; -. DR MANE-Select; ENST00000508775.6; ENSP00000426455.2; NM_003730.6; NP_003721.2. DR UCSC; uc003qve.4; human. [O00584-1] DR AGR; HGNC:21686; -. DR CTD; 8635; -. DR DisGeNET; 8635; -. DR GeneCards; RNASET2; -. DR HGNC; HGNC:21686; RNASET2. DR HPA; ENSG00000026297; Low tissue specificity. DR MalaCards; RNASET2; -. DR MIM; 612944; gene. DR MIM; 612951; phenotype. DR neXtProt; NX_O00584; -. DR OpenTargets; ENSG00000026297; -. DR Orphanet; 85136; Cystic leukoencephalopathy without megalencephaly. DR PharmGKB; PA128394541; -. DR VEuPathDB; HostDB:ENSG00000026297; -. DR eggNOG; KOG1642; Eukaryota. DR GeneTree; ENSGT00640000091563; -. DR HOGENOM; CLU_2037289_0_0_1; -. DR InParanoid; O00584; -. DR OrthoDB; 878940at2759; -. DR PhylomeDB; O00584; -. DR TreeFam; TF315063; -. DR BRENDA; 4.6.1.19; 2681. DR PathwayCommons; O00584; -. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR SignaLink; O00584; -. DR BioGRID-ORCS; 8635; 16 hits in 1146 CRISPR screens. DR ChiTaRS; RNASET2; human. DR GeneWiki; RNASET2; -. DR GenomeRNAi; 8635; -. DR Pharos; O00584; Tbio. DR PRO; PR:O00584; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; O00584; Protein. DR Bgee; ENSG00000026297; Expressed in right uterine tube and 202 other cell types or tissues. DR ExpressionAtlas; O00584; baseline and differential. DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome. DR GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; IBA:GO_Central. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0043202; C:lysosomal lumen; IEA:UniProtKB-SubCell. DR GO; GO:0005764; C:lysosome; IDA:UniProtKB. DR GO; GO:0005758; C:mitochondrial intermembrane space; IEA:UniProtKB-SubCell. DR GO; GO:0033897; F:ribonuclease T2 activity; IEA:UniProtKB-EC. DR GO; GO:0003723; F:RNA binding; IEA:InterPro. DR GO; GO:0004521; F:RNA endonuclease activity; IBA:GO_Central. DR GO; GO:0004540; F:RNA nuclease activity; IDA:UniProtKB. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0006401; P:RNA catabolic process; IDA:UniProtKB. DR CDD; cd01061; RNase_T2_euk; 1. DR Gene3D; 3.90.730.10; Ribonuclease T2-like; 1. DR InterPro; IPR033697; Ribonuclease_T2_eukaryotic. DR InterPro; IPR001568; RNase_T2-like. DR InterPro; IPR036430; RNase_T2-like_sf. DR InterPro; IPR018188; RNase_T2_His_AS_1. DR InterPro; IPR033130; RNase_T2_His_AS_2. DR PANTHER; PTHR11240; RIBONUCLEASE T2; 1. DR PANTHER; PTHR11240:SF83; RIBONUCLEASE T2; 1. DR Pfam; PF00445; Ribonuclease_T2; 1. DR SUPFAM; SSF55895; Ribonuclease Rh-like; 1. DR PROSITE; PS00530; RNASE_T2_1; 1. DR PROSITE; PS00531; RNASE_T2_2; 1. DR Genevisible; O00584; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Disease variant; Disulfide bond; KW Endonuclease; Endoplasmic reticulum; Glycoprotein; Hydrolase; Immunity; KW Innate immunity; Lyase; Lysosome; Mitochondrion; Nuclease; KW Reference proteome; Secreted; Signal. FT SIGNAL 1..24 FT /evidence="ECO:0000255" FT CHAIN 25..256 FT /note="Ribonuclease T2" FT /id="PRO_0000030987" FT ACT_SITE 65 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10045" FT ACT_SITE 114 FT /evidence="ECO:0000250|UniProtKB:P08056" FT ACT_SITE 118 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10046" FT CARBOHYD 76 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:22735700" FT CARBOHYD 106 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:22735700" FT CARBOHYD 212 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:22735700" FT DISULFID 48..55 FT /evidence="ECO:0000269|PubMed:22735700" FT DISULFID 75..121 FT /evidence="ECO:0000269|PubMed:22735700" FT DISULFID 184..241 FT /evidence="ECO:0000269|PubMed:22735700" FT DISULFID 202..213 FT /evidence="ECO:0000269|PubMed:22735700" FT VAR_SEQ 88..121 FT /note="DLLPEMRAYWPDVIHSFPNRSRFWKHEWEKHGTC -> KNWMEITDSSLPSP FT STLPIINIFYSVLHLLQLMN (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11821951" FT /id="VSP_008405" FT VAR_SEQ 122..256 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11821951" FT /id="VSP_008406" FT VARIANT 184 FT /note="C -> R (in LCWM; the loss of a disulfide bond may FT affect protein folding and stability; the protein is FT retained in the endoplasmic reticulum and the mitochondria FT while lysosomal localization is disrupted; FT dbSNP:rs121918137)" FT /evidence="ECO:0000269|PubMed:19525954, FT ECO:0000269|PubMed:21199949, ECO:0000269|PubMed:28730546" FT /id="VAR_063596" FT VARIANT 236 FT /note="R -> W (in dbSNP:rs11159)" FT /id="VAR_013004" FT MUTAGEN 65 FT /note="H->Y: Abolishes the effect on degradation of FT mitochondrion-associated cytosolic rRNAs." FT /evidence="ECO:0000269|PubMed:30385512" FT MUTAGEN 118 FT /note="H->Y: Abolishes the effect on degradation of FT mitochondrion-associated cytosolic rRNAs." FT /evidence="ECO:0000269|PubMed:30385512" FT STRAND 36..42 FT /evidence="ECO:0007829|PDB:3T0O" FT HELIX 44..47 FT /evidence="ECO:0007829|PDB:3T0O" FT STRAND 50..52 FT /evidence="ECO:0007829|PDB:3T0O" FT HELIX 53..55 FT /evidence="ECO:0007829|PDB:3T0O" FT STRAND 63..71 FT /evidence="ECO:0007829|PDB:3T0O" FT HELIX 83..89 FT /evidence="ECO:0007829|PDB:3T0O" FT HELIX 90..96 FT /evidence="ECO:0007829|PDB:3T0O" FT HELIX 108..117 FT /evidence="ECO:0007829|PDB:3T0O" FT HELIX 119..122 FT /evidence="ECO:0007829|PDB:3T0O" FT HELIX 126..128 FT /evidence="ECO:0007829|PDB:3T0O" FT HELIX 131..145 FT /evidence="ECO:0007829|PDB:3T0O" FT HELIX 147..153 FT /evidence="ECO:0007829|PDB:3T0O" FT HELIX 165..176 FT /evidence="ECO:0007829|PDB:3T0O" FT STRAND 181..185 FT /evidence="ECO:0007829|PDB:3T0O" FT STRAND 195..204 FT /evidence="ECO:0007829|PDB:3T0O" FT TURN 205..207 FT /evidence="ECO:0007829|PDB:3T0O" FT STRAND 243..247 FT /evidence="ECO:0007829|PDB:3T0O" SQ SEQUENCE 256 AA; 29481 MW; 7C8BB08B8ED853EB CRC64; MRPAALRGAL LGCLCLALLC LGGADKRLRD NHEWKKLIMV QHWPETVCEK IQNDCRDPPD YWTIHGLWPD KSEGCNRSWP FNLEEIKDLL PEMRAYWPDV IHSFPNRSRF WKHEWEKHGT CAAQVDALNS QKKYFGRSLE LYRELDLNSV LLKLGIKPSI NYYQVADFKD ALARVYGVIP KIQCLPPSQD EEVQTIGQIE LCLTKQDQQL QNCTEPGEQP SPKQEVWLAN GAAESRGLRV CEDGPVFYPP PKKTKH //