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Identification
HMDB Protein ID HMDBP08807
Secondary Accession Numbers
  • 14532
Name 2-5A-dependent ribonuclease
Synonyms
  1. 2-5A-dependent RNase
  2. RNase L
  3. Ribonuclease 4
  4. Ribonuclease L
Gene Name RNASEL
Protein Type Unknown
Biological Properties
General Function Involved in endoribonuclease activity, producing 5'-phosphomonoesters
Specific Function Endoribonuclease that functions in the interferon (IFN) antiviral response. In INF treated and virus infected cells, RNASEL probably mediates its antiviral effects through a combination of direct cleavage of single-stranded viral RNAs, inhibition of protein synthesis through the degradation of rRNA, induction of apoptosis, and induction of other antiviral genes. RNASEL mediated apoptosis is the result of a JNK-dependent stress- response pathway leading to cytochrome c release from mitochondria and caspase-dependent apoptosis. Therefore, activation of RNASEL could lead to elimination of virus infected cells under some circumstances. Might play a central role in the regulation of mRNA. turnover
Pathways Not Available
Reactions Not Available
GO Classification
Function
hydrolase activity, acting on ester bonds
binding
catalytic activity
endoribonuclease activity, producing 5'-phosphomonoesters
hydrolase activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
protein kinase activity
nuclease activity
endonuclease activity
endoribonuclease activity
Process
rna metabolic process
phosphorus metabolic process
phosphate metabolic process
metabolic process
macromolecule metabolic process
cellular macromolecule metabolic process
rna processing
cellular metabolic process
protein amino acid phosphorylation
mrna processing
phosphorylation
Cellular Location
  1. Cytoplasm
  2. Mitochondrion
Gene Properties
Chromosome Location Chromosome:1
Locus 1q25
SNPs RNASEL
Gene Sequence
>2226 bp
ATGGAGAGCAGGGATCATAACAACCCCCAGGAGGGACCCACGTCCTCCAGCGGTAGAAGG
GCTGCAGTGGAAGACAATCACTTGCTGATTAAAGCTGTTCAAAACGAAGATGTTGACCTG
GTCCAGCAATTGCTGGAAGGTGGAGCCAATGTTAATTTCCAGGAAGAGGAAGGGGGCTGG
ACACCTCTGCATAACGCAGTACAAATGAGCAGGGAGGACATTGTGGAACTTCTGCTTCGT
CATGGTGCTGACCCTGTTCTGAGGAAGAAGAATGGGGCCACGCCTTTTATCCTCGCAGCG
ATTGCGGGGAGCGTGAAGCTGCTGAAACTTTTCCTTTCTAAAGGAGCAGATGTCAATGAG
TGTGATTTTTATGGCTTCACAGCCTTCATGGAAGCCGCTGTGTATGGTAAGGTCAAAGCC
CTAAAATTCCTTTATAAGAGAGGAGCAAATGTGAATTTGAGGCGAAAGACAAAGGAGGAT
CAAGAGCGGCTGAGGAAAGGAGGGGCCACAGCTCTCATGGACGCTGCTGAAAAAGGACAC
GTAGAGGTCTTGAAGATTCTCCTTGATGAGATGGGGGCAGATGTAAACGCCTGTGACAAT
ATGGGCAGAAATGCCTTGATCCATGCTCTCCTGAGCTCTGACGATAGTGATGTGGAGGCT
ATTACGCATCTGCTGCTGGACCATGGGGCTGATGTCAATGTGAGGGGAGAAAGAGGGAAG
ACTCCCCTGATCCTGGCAGTGGAGAAGAAGCACTTGGGTTTGGTGCAGAGGCTTCTGGAG
CAAGAGCACATAGAGATTAATGACACAGACAGTGATGGCAAAACAGCACTGCTGCTTGCT
GTTGAACTCAAACTGAAGAAAATCGCCGAGTTGCTGTGCAAACGTGGAGCCAGTACAGAT
TGTGGGGATCTTGTTATGACAGCGAGGCGGAATTATGACCATTCCCTTGTGAAGGTTCTT
CTCTCTCATGGAGCCAAAGAAGATTTTCACCCTCCTGCTGAAGACTGGAAGCCTCAGAGC
TCACACTGGGGGGCAGCCCTGAAGGATCTCCACAGAATATACCGCCCTATGATTGGCAAA
CTCAAGTTCTTTATTGATGAAAAATACAAAATTGCTGATACTTCAGAAGGAGGCATCTAC
CTGGGGTTCTATGAGAAGCAAGAAGTAGCTGTGAAGACGTTCTGTGAGGGCAGCCCACGT
GCACAGCGGGAAGTCTCTTGTCTGCAAAGCAGCCGAGAGAACAGTCACTTGGTGACATTC
TATGGGAGTGAGAGCCACAGGGGCCACTTGTTTGTGTGTGTCACCCTCTGTGAGCAGACT
CTGGAAGCGTGTTTGGATGTGCACAGAGGGGAAGATGTGGAAAATGAGGAAGATGAATTT
GCCCGAAATGTCCTGTCATCTATATTTAAGGCTGTTCAAGAACTACACTTGTCCTGTGGA
TACACCCACCAGGATCTGCAACCACAAAACATCTTAATAGATTCTAAGAAAGCTGCTCAC
CTGGCAGATTTTGATAAGAGCATCAAGTGGGCTGGAGATCCACAGGAAGTCAAGAGAGAT
CTAGAGGACCTTGGACGGCTGGTCCTCTATGTGGTAAAGAAGGGAAGCATCTCATTTGAG
GATCTGAAAGCTCAAAGTAATGAAGAGGTGGTTCAACTTTCTCCAGATGAGGAAACTAAG
GACCTCATTCATCGTCTCTTCCATCCTGGGGAACATGTGAGGGACTGTCTGAGTGACCTG
CTGGGTCATCCCTTCTTTTGGACTTGGGAGAGCCGCTATAGGACGCTTCGGAATGTGGGA
AATGAATCCGACATCAAAACACGAAAATCTGAAAGTGAGATCCTCAGACTACTGCAACCT
GGGCCTTCTGAACATTCCAAAAGTTTTGACAAGTGGACGACTAAGATTAATGAATGTGTT
ATGAAAAAAATGAATAAGTTTTATGAAAAAAGAGGCAATTTCTACCAGAACACTGTGGGT
GATCTGCTAAAGTTCATCCGGAATTTGGGAGAACACATTGATGAAGAAAAGCATAAAAAG
ATGAAATTAAAAATTGGAGACCCTTCCCTGTATTTTCAGAAGACATTTCCAGATCTGGTG
ATCTATGTCTACACAAAACTACAGAACACAGAATATAGAAAGCATTTCCCCCAAACCCAC
AGTCCAAACAAACCTCAGTGTGATGGAGCTGGTGGGGCCAGTGGGTTGGCCAGCCCTGGG
TGCTGA
Protein Properties
Number of Residues 741
Molecular Weight 83532.1
Theoretical pI 6.64
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>2-5A-dependent ribonuclease
MESRDHNNPQEGPTSSSGRRAAVEDNHLLIKAVQNEDVDLVQQLLEGGANVNFQEEEGGW
TPLHNAVQMSREDIVELLLRHGADPVLRKKNGATPFILAAIAGSVKLLKLFLSKGADVNE
CDFYGFTAFMEAAVYGKVKALKFLYKRGANVNLRRKTKEDQERLRKGGATALMDAAEKGH
VEVLKILLDEMGADVNACDNMGRNALIHALLSSDDSDVEAITHLLLDHGADVNVRGERGK
TPLILAVEKKHLGLVQRLLEQEHIEINDTDSDGKTALLLAVELKLKKIAELLCKRGASTD
CGDLVMTARRNYDHSLVKVLLSHGAKEDFHPPAEDWKPQSSHWGAALKDLHRIYRPMIGK
LKFFIDEKYKIADTSEGGIYLGFYEKQEVAVKTFCEGSPRAQREVSCLQSSRENSHLVTF
YGSESHRGHLFVCVTLCEQTLEACLDVHRGEDVENEEDEFARNVLSSIFKAVQELHLSCG
YTHQDLQPQNILIDSKKAAHLADFDKSIKWAGDPQEVKRDLEDLGRLVLYVVKKGSISFE
DLKAQSNEEVVQLSPDEETKDLIHRLFHPGEHVRDCLSDLLGHPFFWTWESRYRTLRNVG
NESDIKTRKSESEILRLLQPGPSEHSKSFDKWTTKINECVMKKMNKFYEKRGNFYQNTVG
DLLKFIRNLGEHIDEEKHKKMKLKIGDPSLYFQKTFPDLVIYVYTKLQNTEYRKHFPQTH
SPNKPQCDGAGGASGLASPGC
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q05823
UniProtKB/Swiss-Prot Entry Name RN5A_HUMAN
PDB IDs
GenBank Gene ID L10381
GeneCard ID RNASEL
GenAtlas ID RNASEL
HGNC ID HGNC:10050
References
General References
  1. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  2. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [PubMed:17344846 ]
  3. Zhou A, Hassel BA, Silverman RH: Expression cloning of 2-5A-dependent RNAase: a uniquely regulated mediator of interferon action. Cell. 1993 Mar 12;72(5):753-65. [PubMed:7680958 ]
  4. Zhou A, Nie H, Silverman RH: Analysis and origins of the human and mouse RNase L genes: mediators of interferon action. Mamm Genome. 2000 Nov;11(11):989-92. [PubMed:11063255 ]
  5. Dong B, Xu L, Zhou A, Hassel BA, Lee X, Torrence PF, Silverman RH: Intrinsic molecular activities of the interferon-induced 2-5A-dependent RNase. J Biol Chem. 1994 May 13;269(19):14153-8. [PubMed:7514601 ]
  6. Bisbal C, Martinand C, Silhol M, Lebleu B, Salehzada T: Cloning and characterization of a RNAse L inhibitor. A new component of the interferon-regulated 2-5A pathway. J Biol Chem. 1995 Jun 2;270(22):13308-17. [PubMed:7539425 ]
  7. Le Roy F, Bisbal C, Silhol M, Martinand C, Lebleu B, Salehzada T: The 2-5A/RNase L/RNase L inhibitor (RLI) [correction of (RNI)] pathway regulates mitochondrial mRNAs stability in interferon alpha-treated H9 cells. J Biol Chem. 2001 Dec 21;276(51):48473-82. Epub 2001 Oct 3. [PubMed:11585831 ]
  8. Castelli J, Wood KA, Youle RJ: The 2-5A system in viral infection and apoptosis. Biomed Pharmacother. 1998;52(9):386-90. [PubMed:9856285 ]
  9. Dong B, Silverman RH: Alternative function of a protein kinase homology domain in 2', 5'-oligoadenylate dependent RNase L. Nucleic Acids Res. 1999 Jan 15;27(2):439-45. [PubMed:9862963 ]
  10. Dong B, Niwa M, Walter P, Silverman RH: Basis for regulated RNA cleavage by functional analysis of RNase L and Ire1p. RNA. 2001 Mar;7(3):361-73. [PubMed:11333017 ]
  11. Tanaka N, Nakanishi M, Kusakabe Y, Goto Y, Kitade Y, Nakamura KT: Structural basis for recognition of 2',5'-linked oligoadenylates by human ribonuclease L. EMBO J. 2004 Oct 13;23(20):3929-38. Epub 2004 Sep 23. [PubMed:15385955 ]
  12. Rokman A, Ikonen T, Seppala EH, Nupponen N, Autio V, Mononen N, Bailey-Wilson J, Trent J, Carpten J, Matikainen MP, Koivisto PA, Tammela TL, Kallioniemi OP, Schleutker J: Germline alterations of the RNASEL gene, a candidate HPC1 gene at 1q25, in patients and families with prostate cancer. Am J Hum Genet. 2002 May;70(5):1299-304. Epub 2002 Apr 8. [PubMed:11941539 ]
  13. Carpten J, Nupponen N, Isaacs S, Sood R, Robbins C, Xu J, Faruque M, Moses T, Ewing C, Gillanders E, Hu P, Bujnovszky P, Makalowska I, Baffoe-Bonnie A, Faith D, Smith J, Stephan D, Wiley K, Brownstein M, Gildea D, Kelly B, Jenkins R, Hostetter G, Matikainen M, Schleutker J, Klinger K, Connors T, Xiang Y, Wang Z, De Marzo A, Papadopoulos N, Kallioniemi OP, Burk R, Meyers D, Gronberg H, Meltzer P, Silverman R, Bailey-Wilson J, Walsh P, Isaacs W, Trent J: Germline mutations in the ribonuclease L gene in families showing linkage with HPC1. Nat Genet. 2002 Feb;30(2):181-4. Epub 2002 Jan 22. [PubMed:11799394 ]
  14. Casey G, Neville PJ, Plummer SJ, Xiang Y, Krumroy LM, Klein EA, Catalona WJ, Nupponen N, Carpten JD, Trent JM, Silverman RH, Witte JS: RNASEL Arg462Gln variant is implicated in up to 13% of prostate cancer cases. Nat Genet. 2002 Dec;32(4):581-3. Epub 2002 Nov 4. [PubMed:12415269 ]