Q05823 · RN5A_HUMAN
- Protein2-5A-dependent ribonuclease
- GeneRNASEL
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids741 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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. In the crosstalk between autophagy and apoptosis proposed to induce autophagy as an early stress response to small double-stranded RNA and at later stages of prolonged stress to activate caspase-dependent proteolytic cleavage of BECN1 to terminate autophagy and promote apoptosis (PubMed:26263979).
Might play a central role in the regulation of mRNA turnover (PubMed:11585831).
Cleaves 3' of UpNp dimers, with preference for UU and UA sequences, to sets of discrete products ranging from between 4 and 22 nucleotides in length
Might play a central role in the regulation of mRNA turnover (PubMed:11585831).
Cleaves 3' of UpNp dimers, with preference for UU and UA sequences, to sets of discrete products ranging from between 4 and 22 nucleotides in length
Cofactor
Mg2+ (UniProtKB | Rhea| CHEBI:18420 )
Note: Manganese or magnesium. Required for optimal RNA cleavage rates.
Activity regulation
After binding to 2-5A (5'-phosphorylated 2',5'-linked oligoadenylates) the homodimerization and subsequent activation occurs. Inhibited by RNASEL inhibitor ABCE1/RLI, a cytoplasmic member of the ATP-binding cassette (ABC) transporter family.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | mitochondrial matrix | |
Cellular Component | nuclear matrix | |
Molecular Function | ATP binding | |
Molecular Function | identical protein binding | |
Molecular Function | metal ion binding | |
Molecular Function | protein kinase activity | |
Molecular Function | ribonucleoprotein complex binding | |
Molecular Function | RNA binding | |
Molecular Function | RNA endonuclease activity | |
Molecular Function | RNA nuclease activity | |
Molecular Function | rRNA binding | |
Biological Process | defense response to virus | |
Biological Process | fat cell differentiation | |
Biological Process | mRNA processing | |
Biological Process | negative regulation of viral genome replication | |
Biological Process | positive regulation of glucose import | |
Biological Process | positive regulation of transcription by RNA polymerase II | |
Biological Process | protein phosphorylation | |
Biological Process | regulation of mRNA stability | |
Biological Process | RNA processing | |
Biological Process | rRNA processing |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended name2-5A-dependent ribonuclease
- EC number
- Short names2-5A-dependent RNase
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ05823
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Prostate cancer, hereditary, 1 (HPC1)
- Note
- DescriptionA condition associated with familial predisposition to cancer of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma.
- See alsoMIM:601518
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_013509 | 59 | in dbSNP:rs151296858 | |||
Sequence: G → S | ||||||
Natural variant | VAR_042358 | 97 | in dbSNP:rs56250729 | |||
Sequence: I → L | ||||||
Mutagenesis | 240 | Reduced 2-5A binding activity; almost complete loss of 2-5A binding activity; when associated with N-274. | ||||
Sequence: K → N | ||||||
Mutagenesis | 274 | Reduced 2-5A binding activity; almost complete loss of 2-5A binding activity; when associated with N-240. | ||||
Sequence: K → N | ||||||
Natural variant | VAR_042359 | 289 | in dbSNP:rs35553278 | |||
Sequence: A → T | ||||||
Mutagenesis | 392 | Complete loss of enzymatic activity and enzyme dimerization. No change in binding to 2-5A and RNA. | ||||
Sequence: K → R | ||||||
Natural variant | VAR_013510 | 406 | in dbSNP:rs145787003 | |||
Sequence: S → F | ||||||
Natural variant | VAR_012056 | 462 | risk factor for prostate cancer; reduced enzymatic activity; dbSNP:rs486907 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_012057 | 541 | no change in enzymatic activity; dbSNP:rs627928 | |||
Sequence: D → E | ||||||
Mutagenesis | 583 | No change in enzymatic activity. | ||||
Sequence: H → A | ||||||
Mutagenesis | 584 | No change in enzymatic activity. | ||||
Sequence: P → A | ||||||
Natural variant | VAR_042360 | 592 | in dbSNP:rs35896902 | |||
Sequence: R → H | ||||||
Mutagenesis | 632 | No change in enzymatic activity. | ||||
Sequence: W → A | ||||||
Mutagenesis | 661 | Complete loss of enzymatic activity. | ||||
Sequence: D → A | ||||||
Mutagenesis | 667 | Complete loss of enzymatic activity. No change in 2-5A binding and enzyme dimerization. | ||||
Sequence: R → A | ||||||
Mutagenesis | 672 | Complete loss of enzymatic activity. No change in 2-5A binding activity and enzyme dimerization. | ||||
Sequence: H → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,354 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000067051 | 1-741 | 2-5A-dependent ribonuclease | |||
Sequence: MESRDHNNPQEGPTSSSGRRAAVEDNHLLIKAVQNEDVDLVQQLLEGGANVNFQEEEGGWTPLHNAVQMSREDIVELLLRHGADPVLRKKNGATPFILAAIAGSVKLLKLFLSKGADVNECDFYGFTAFMEAAVYGKVKALKFLYKRGANVNLRRKTKEDQERLRKGGATALMDAAEKGHVEVLKILLDEMGADVNACDNMGRNALIHALLSSDDSDVEAITHLLLDHGADVNVRGERGKTPLILAVEKKHLGLVQRLLEQEHIEINDTDSDGKTALLLAVELKLKKIAELLCKRGASTDCGDLVMTARRNYDHSLVKVLLSHGAKEDFHPPAEDWKPQSSHWGAALKDLHRIYRPMIGKLKFFIDEKYKIADTSEGGIYLGFYEKQEVAVKTFCEGSPRAQREVSCLQSSRENSHLVTFYGSESHRGHLFVCVTLCEQTLEACLDVHRGEDVENEEDEFARNVLSSIFKAVQELHLSCGYTHQDLQPQNILIDSKKAAHLADFDKSIKWAGDPQEVKRDLEDLGRLVLYVVKKGSISFEDLKAQSNEEVVQLSPDEETKDLIHRLFHPGEHVRDCLSDLLGHPFFWTWESRYRTLRNVGNESDIKTRKSESEILRLLQPGPSEHSKSFDKWTTKINECVMKKMNKFYEKRGNFYQNTVGDLLKFIRNLGEHIDEEKHKKMKLKIGDPSLYFQKTFPDLVIYVYTKLQNTEYRKHFPQTHSPNKPQCDGAGGASGLASPGC | ||||||
Modified residue | 684 | N6-acetyllysine | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in spleen and thymus followed by prostate, testis, uterus, small intestine, colon and peripheral blood leukocytes.
Induction
By interferons. Virus replication in higher vertebrates is restrained by IFNs that cause cells to transcribe genes encoding antiviral proteins, such as 2'-5' oligoadenylate synthetases (OASs). oligoadenylate synthetase is stimulated by dsRNA to produce 5'-phosphorylated, 2'-5'-linked oligoadenylates (2-5A), whose function is to activate RNASEL.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Monomer (inactive form) or homodimer. Interacts with ABCE1; this interaction inhibits the RNASEL.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q05823 | IQGAP1 P46940 | 2 | EBI-8390477, EBI-297509 | |
BINARY | Q05823-1 | RNASEL Q05823-1 | 2 | EBI-16094551, EBI-16094551 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, repeat, domain, zinc finger.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-21 | Disordered | ||||
Sequence: MESRDHNNPQEGPTSSSGRRA | ||||||
Repeat | 24-53 | ANK 1 | ||||
Sequence: EDNHLLIKAVQNEDVDLVQQLLEGGANVNF | ||||||
Repeat | 58-87 | ANK 2 | ||||
Sequence: GGWTPLHNAVQMSREDIVELLLRHGADPVL | ||||||
Repeat | 91-120 | ANK 3 | ||||
Sequence: NGATPFILAAIAGSVKLLKLFLSKGADVNE | ||||||
Repeat | 124-153 | ANK 4 | ||||
Sequence: YGFTAFMEAAVYGKVKALKFLYKRGANVNL | ||||||
Repeat | 167-197 | ANK 5 | ||||
Sequence: GGATALMDAAEKGHVEVLKILLDEMGADVNA | ||||||
Repeat | 201-234 | ANK 6 | ||||
Sequence: MGRNALIHALLSSDDSDVEAITHLLLDHGADVNV | ||||||
Region | 229-242 | 2-5A binding (P-loop) 1 | ||||
Sequence: GADVNVRGERGKTP | ||||||
Repeat | 238-268 | ANK 7 | ||||
Sequence: RGKTPLILAVEKKHLGLVQRLLEQEHIEIND | ||||||
Region | 253-275 | 2-5A binding (P-loop) 2 | ||||
Sequence: GLVQRLLEQEHIEINDTDSDGKT | ||||||
Repeat | 272-301 | ANK 8 | ||||
Sequence: DGKTALLLAVELKLKKIAELLCKRGASTDC | ||||||
Repeat | 303-329 | ANK 9 | ||||
Sequence: DLVMTARRNYDHSLVKVLLSHGAKEDF | ||||||
Domain | 365-586 | Protein kinase | ||||
Sequence: IDEKYKIADTSEGGIYLGFYEKQEVAVKTFCEGSPRAQREVSCLQSSRENSHLVTFYGSESHRGHLFVCVTLCEQTLEACLDVHRGEDVENEEDEFARNVLSSIFKAVQELHLSCGYTHQDLQPQNILIDSKKAAHLADFDKSIKWAGDPQEVKRDLEDLGRLVLYVVKKGSISFEDLKAQSNEEVVQLSPDEETKDLIHRLFHPGEHVRDCLSDLLGHPFF | ||||||
Zinc finger | 395-444 | C6-type; atypical | ||||
Sequence: CEGSPRAQREVSCLQSSRENSHLVTFYGSESHRGHLFVCVTLCEQTLEAC | ||||||
Domain | 589-723 | KEN | ||||
Sequence: WESRYRTLRNVGNESDIKTRKSESEILRLLQPGPSEHSKSFDKWTTKINECVMKKMNKFYEKRGNFYQNTVGDLLKFIRNLGEHIDEEKHKKMKLKIGDPSLYFQKTFPDLVIYVYTKLQNTEYRKHFPQTHSPN | ||||||
Region | 715-741 | Disordered | ||||
Sequence: HFPQTHSPNKPQCDGAGGASGLASPGC |
Domain
The nine ankyrin repeats also called 2-5A sensor constitute the N-terminus 2-5A binding domain.
The protein kinase domain is predicted to be catalytically inactive. It allows the homodimerization.
The ribonuclease domain is located in the C-terminus. A single active nuclease domain in a dimer is sufficient for ribonuclease activity (By similarity).
Sequence similarities
Belongs to the protein kinase superfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q05823-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length741
- Mass (Da)83,533
- Last updated1996-02-01 v2
- Checksum91385EA307E3CE1D
Q05823-2
- Name2
Features
Showing features for alternative sequence.
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L10381 EMBL· GenBank· DDBJ | AAA18032.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CR627369 EMBL· GenBank· DDBJ | CAH10468.1 EMBL· GenBank· DDBJ | mRNA | ||
AL138776 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471067 EMBL· GenBank· DDBJ | EAW91128.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC090934 EMBL· GenBank· DDBJ | AAH90934.1 EMBL· GenBank· DDBJ | mRNA | ||
BC114433 EMBL· GenBank· DDBJ | AAI14434.1 EMBL· GenBank· DDBJ | mRNA |