RNAS6_HUMAN
ID RNAS6_HUMAN Reviewed; 150 AA.
AC Q93091;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Ribonuclease K6;
DE Short=RNase K6;
DE EC=3.1.27.- {ECO:0000269|PubMed:27013146, ECO:0000269|PubMed:8836175};
DE Flags: Precursor;
GN Name=RNASE6; Synonyms=RNS6;
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 [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RX PubMed=8836175; DOI=10.1093/nar/24.18.3507;
RA Rosenberg H.F., Dyer K.D.;
RT "Molecular cloning and characterization of a novel human ribonuclease
RT (RNase k6): increasing diversity in the enlarging ribonuclease gene
RT family.";
RL Nucleic Acids Res. 24:3507-3513(1996).
RN [2]
RP SEQUENCE REVISION TO 76.
RA Rosenberg H.F.;
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=25075772; DOI=10.1038/ki.2014.268;
RA Becknell B., Eichler T.E., Beceiro S., Li B., Easterling R.S.,
RA Carpenter A.R., James C.L., McHugh K.M., Hains D.S., Partida-Sanchez S.,
RA Spencer J.D.;
RT "Ribonucleases 6 and 7 have antimicrobial function in the human and murine
RT urinary tract.";
RL Kidney Int. 87:151-161(2015).
RN [5]
RP FUNCTION, INTERACTION WITH LPS, AND MUTAGENESIS OF TRP-24; ILE-36 AND
RP HIS-38.
RX PubMed=27089320; DOI=10.3390/ijms17040552;
RA Pulido D., Arranz-Trullen J., Prats-Ejarque G., Velazquez D., Torrent M.,
RA Moussaoui M., Boix E.;
RT "Insights into the antimicrobial mechanism of action of human RNase6:
RT structural determinants for bacterial cell agglutination and membrane
RT permeation.";
RL Int. J. Mol. Sci. 17:552-552(2016).
RN [6] {ECO:0007744|PDB:4X09}
RP X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 24-150, FUNCTION, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, DISULFIDE BONDS, AND MUTAGENESIS
RP OF HIS-38 AND HIS-59.
RX PubMed=27013146; DOI=10.1042/bcj20160245;
RA Prats-Ejarque G., Arranz-Trullen J., Blanco J.A., Pulido D., Nogues M.V.,
RA Moussaoui M., Boix E.;
RT "The first crystal structure of human RNase 6 reveals a novel substrate-
RT binding and cleavage site arrangement.";
RL Biochem. J. 473:1523-1536(2016).
CC -!- FUNCTION: Ribonuclease which shows a preference for the pyrimidines
CC uridine and cytosine (PubMed:8836175, PubMed:27013146). Has potent
CC antibacterial activity against a range of Gram-positive and Gram-
CC negative bacteria, including P.aeruginosa, A.baumanii, M.luteus,
CC S.aureus, E.faecalis, E.faecium, S.saprophyticus and E.coli
CC (PubMed:25075772, PubMed:27089320). Causes loss of bacterial membrane
CC integrity, and also promotes agglutination of Gram-negative bacteria
CC (PubMed:27089320). Probably contributes to urinary tract sterility
CC (PubMed:25075772). Bactericidal activity is independent of RNase
CC activity (PubMed:27089320). {ECO:0000269|PubMed:25075772,
CC ECO:0000269|PubMed:27013146, ECO:0000269|PubMed:27089320,
CC ECO:0000269|PubMed:8836175}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5.0 uM for tRNA {ECO:0000269|PubMed:8836175};
CC KM=2.63 mM for UpA dinucleotide {ECO:0000269|PubMed:27013146};
CC KM=1.22 mM for CpA dinucleotide {ECO:0000269|PubMed:27013146};
CC KM=2.06 mM for cytidine 2,3-cyclic phosphate
CC {ECO:0000269|PubMed:27013146};
CC -!- SUBUNIT: Interacts (via N-terminus) with bacterial lipopolysaccharide
CC (LPS). {ECO:0000269|PubMed:27089320}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:25075772}. Lysosome
CC {ECO:0000305|PubMed:25075772}. Cytoplasmic granule
CC {ECO:0000269|PubMed:25075772}.
CC -!- TISSUE SPECIFICITY: Highly expressed in spleen (at protein level)
CC (PubMed:8836175, PubMed:25075772). Has little or no expression in
CC healthy kidneys (at protein level) (PubMed:25075772). Detected in
CC interstitial leukocytes in infected kidneys (at protein level)
CC (PubMed:25075772). Expressed in ureter where it localizes to urothelial
CC and submucosal leukocytes (at protein level) (PubMed:25075772). Strong
CC expression in lung and thymus, and lower expression in heart, placenta,
CC pancreas, liver, brain and skeletal muscle (PubMed:8836175,
CC PubMed:25075772). Also expressed in monocytes and neutrophils
CC (PubMed:8836175). {ECO:0000269|PubMed:25075772,
CC ECO:0000269|PubMed:8836175}.
CC -!- INDUCTION: Up-regulated in CD14+ monocytes in response to the
CC uropathogenic E.coli strain CFT073. {ECO:0000269|PubMed:25075772}.
CC -!- SIMILARITY: Belongs to the pancreatic ribonuclease family.
CC {ECO:0000305}.
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DR EMBL; U64998; AAC51848.1; -; Genomic_DNA.
DR EMBL; BC020848; AAH20848.1; -; mRNA.
DR CCDS; CCDS9558.1; -.
DR PIR; S72361; S72361.
DR RefSeq; NP_005606.1; NM_005615.4.
DR RefSeq; XP_016877055.1; XM_017021566.1.
DR RefSeq; XP_016877056.1; XM_017021567.1.
DR PDB; 4X09; X-ray; 1.72 A; A=24-150.
DR PDB; 5OAB; X-ray; 1.11 A; A=24-150.
DR PDB; 6ENP; X-ray; 1.04 A; A=24-150.
DR PDB; 6MV6; X-ray; 1.50 A; A=26-150.
DR PDB; 6MV7; X-ray; 2.59 A; A=24-150.
DR PDBsum; 4X09; -.
DR PDBsum; 5OAB; -.
DR PDBsum; 6ENP; -.
DR PDBsum; 6MV6; -.
DR PDBsum; 6MV7; -.
DR AlphaFoldDB; Q93091; -.
DR BMRB; Q93091; -.
DR SMR; Q93091; -.
DR BioGRID; 111968; 1.
DR IntAct; Q93091; 1.
DR STRING; 9606.ENSP00000302046; -.
DR GlyGen; Q93091; 2 sites.
DR BioMuta; RNASE6; -.
DR DMDM; 3123285; -.
DR EPD; Q93091; -.
DR jPOST; Q93091; -.
DR MassIVE; Q93091; -.
DR PaxDb; Q93091; -.
DR PeptideAtlas; Q93091; -.
DR PRIDE; Q93091; -.
DR ProteomicsDB; 75720; -.
DR Antibodypedia; 3; 64 antibodies from 17 providers.
DR DNASU; 6039; -.
DR Ensembl; ENST00000304677.3; ENSP00000302046.2; ENSG00000169413.3.
DR GeneID; 6039; -.
DR KEGG; hsa:6039; -.
DR MANE-Select; ENST00000304677.3; ENSP00000302046.2; NM_005615.5; NP_005606.1.
DR UCSC; uc001vye.4; human.
DR CTD; 6039; -.
DR DisGeNET; 6039; -.
DR GeneCards; RNASE6; -.
DR HGNC; HGNC:10048; RNASE6.
DR HPA; ENSG00000169413; Tissue enhanced (lymphoid).
DR MIM; 601981; gene.
DR neXtProt; NX_Q93091; -.
DR OpenTargets; ENSG00000169413; -.
DR PharmGKB; PA34416; -.
DR VEuPathDB; HostDB:ENSG00000169413; -.
DR eggNOG; ENOG502TDZ3; Eukaryota.
DR GeneTree; ENSGT00940000161733; -.
DR HOGENOM; CLU_117006_0_1_1; -.
DR InParanoid; Q93091; -.
DR OMA; LTKAHWF; -.
DR OrthoDB; 1549558at2759; -.
DR PhylomeDB; Q93091; -.
DR TreeFam; TF333393; -.
DR PathwayCommons; Q93091; -.
DR Reactome; R-HSA-6803157; Antimicrobial peptides.
DR SignaLink; Q93091; -.
DR BioGRID-ORCS; 6039; 8 hits in 1067 CRISPR screens.
DR GenomeRNAi; 6039; -.
DR Pharos; Q93091; Tbio.
DR PRO; PR:Q93091; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q93091; protein.
DR Bgee; ENSG00000169413; Expressed in monocyte and 144 other tissues.
DR ExpressionAtlas; Q93091; baseline and differential.
DR Genevisible; Q93091; HS.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0004540; F:ribonuclease activity; IDA:UniProtKB.
DR GO; GO:0019731; P:antibacterial humoral response; IDA:UniProtKB.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR GO; GO:0006952; P:defense response; TAS:ProtInc.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IDA:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB.
DR GO; GO:0006401; P:RNA catabolic process; TAS:ProtInc.
DR GO; GO:0090501; P:RNA phosphodiester bond hydrolysis; IDA:UniProtKB.
DR Gene3D; 3.10.130.10; -; 1.
DR InterPro; IPR001427; RNaseA.
DR InterPro; IPR036816; RNaseA-like_dom_sf.
DR InterPro; IPR023411; RNaseA_AS.
DR InterPro; IPR023412; RNaseA_domain.
DR PANTHER; PTHR11437; PTHR11437; 1.
DR Pfam; PF00074; RnaseA; 1.
DR PRINTS; PR00794; RIBONUCLEASE.
DR SMART; SM00092; RNAse_Pc; 1.
DR SUPFAM; SSF54076; SSF54076; 1.
DR PROSITE; PS00127; RNASE_PANCREATIC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic; Antimicrobial; Disulfide bond; Endonuclease;
KW Glycoprotein; Hydrolase; Lysosome; Nuclease; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000250|UniProtKB:P81649"
FT CHAIN 24..150
FT /note="Ribonuclease K6"
FT /id="PRO_0000030892"
FT ACT_SITE 38
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q64438"
FT ACT_SITE 145
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q64438"
FT BINDING 61..65
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 86
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 105
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT SITE 24
FT /note="Important for bactericidal activity, bacterial
FT agglutination activity and binding to bacterial
FT lipopolysaccharide (LPS)"
FT /evidence="ECO:0000269|PubMed:27089320"
FT SITE 36
FT /note="Important for bactericidal activity, bacterial
FT agglutination activity and binding to bacterial
FT lipopolysaccharide (LPS)"
FT /evidence="ECO:0000269|PubMed:27089320"
FT SITE 59
FT /note="Facilitates cleavage of polynucleotide substrates"
FT /evidence="ECO:0000269|PubMed:27013146"
FT SITE 61
FT /note="Critical for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:Q9H1E1"
FT CARBOHYD 55
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 46..104
FT /evidence="ECO:0007744|PDB:4X09"
FT DISULFID 60..114
FT /evidence="ECO:0007744|PDB:4X09"
FT DISULFID 78..129
FT /evidence="ECO:0007744|PDB:4X09"
FT DISULFID 85..92
FT /evidence="ECO:0007744|PDB:4X09"
FT VARIANT 89
FT /note="R -> Q (in dbSNP:rs1045922)"
FT /id="VAR_012048"
FT MUTAGEN 24
FT /note="W->A: Moderately impairs bactericidal activity,
FT bacterial agglutination activity and binding to bacterial
FT lipopolysaccharide (LPS)."
FT /evidence="ECO:0000269|PubMed:27089320"
FT MUTAGEN 36
FT /note="I->A: Strongly impairs bactericidal activity,
FT bacterial agglutination activity and binding to bacterial
FT lipopolysaccharide (LPS)."
FT /evidence="ECO:0000269|PubMed:27089320"
FT MUTAGEN 38
FT /note="H->A: Significantly reduced activity towards
FT dinucleotides UpA and CpA. Slightly reduced activity
FT towards polymeric substrates poly(U) and poly(U):poly(A).
FT No effect on bactericidal activity. Significantly reduced
FT activity towards poly(U) and poly(U):poly(A); when
FT associated with R-59."
FT /evidence="ECO:0000269|PubMed:27013146,
FT ECO:0000269|PubMed:27089320"
FT MUTAGEN 59
FT /note="H->R: No significant effect on activity towards
FT dinucleotides UpA and CpA. Reduced activity towards
FT polymeric substrates poly(U) and poly(U):poly(A).
FT Significantly reduced activity towards poly(U) and
FT poly(U):poly(A); when associated with A-38."
FT /evidence="ECO:0000269|PubMed:27013146"
FT HELIX 30..38
FT /evidence="ECO:0007829|PDB:6ENP"
FT HELIX 46..57
FT /evidence="ECO:0007829|PDB:6ENP"
FT STRAND 62..67
FT /evidence="ECO:0007829|PDB:6ENP"
FT HELIX 71..77
FT /evidence="ECO:0007829|PDB:6ENP"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:6ENP"
FT STRAND 99..108
FT /evidence="ECO:0007829|PDB:6ENP"
FT STRAND 115..130
FT /evidence="ECO:0007829|PDB:6ENP"
FT STRAND 142..150
FT /evidence="ECO:0007829|PDB:6ENP"
SQ SEQUENCE 150 AA; 17196 MW; 4C1F722066BCC13A CRC64;
MVLCFPLLLL LLVLWGPVCP LHAWPKRLTK AHWFEIQHIQ PSPLQCNRAM SGINNYTQHC
KHQNTFLHDS FQNVAAVCDL LSIVCKNRRH NCHQSSKPVN MTDCRLTSGK YPQCRYSAAA
QYKFFIVACD PPQKSDPPYK LVPVHLDSIL
