RNSL3_DANRE
ID RNSL3_DANRE Reviewed; 149 AA.
AC A5HAK0;
DT 15-JUN-2010, integrated into UniProtKB/Swiss-Prot.
DT 15-JUN-2010, sequence version 2.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Ribonuclease-like 3 {ECO:0000303|PubMed:16861230};
DE Short=RNase ZF-3 {ECO:0000303|PubMed:18508078};
DE Short=RNase-like 3 {ECO:0000303|PubMed:16861230};
DE Short=ZF-RNase-3 {ECO:0000303|PubMed:16861230};
DE EC=3.1.27.-;
DE AltName: Full=Dr-RNase 1 {ECO:0000303|PubMed:17347156};
DE Contains:
DE RecName: Full=N-terminal peptide {ECO:0000303|PubMed:20214681};
DE Contains:
DE RecName: Full=LF-ZF3 {ECO:0000303|PubMed:20214681};
DE Flags: Precursor;
GN Name=rnasel3 {ECO:0000312|ZFIN:ZDB-GENE-050809-5};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1] {ECO:0000305, ECO:0000312|EMBL:ABQ23783.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE ZF-3C), FUNCTION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND VARIANTS GLY-56; GLU-93 AND SER-137.
RC STRAIN=AB {ECO:0000269|PubMed:17347156};
RX PubMed=17347156; DOI=10.1093/molbev/msm047;
RA Cho S., Zhang J.;
RT "Zebrafish ribonucleases are bactericidal: implications for the origin of
RT the vertebrate RNase A superfamily.";
RL Mol. Biol. Evol. 24:1259-1268(2007).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELES ZF-3D AND ZF-3E), FUNCTION, X-RAY
RP CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 23-149 (ALLELE ZF-3E), AND VARIANTS
RP ARG-5; ASP-102; ALA-141 AND ARG-145.
RX PubMed=18508078; DOI=10.1016/j.jmb.2008.04.070;
RA Kazakou K., Holloway D.E., Prior S.H., Subramanian V., Acharya K.R.;
RT "Ribonuclease A homologues of the zebrafish: polymorphism, crystal
RT structures of two representatives and their evolutionary implications.";
RL J. Mol. Biol. 380:206-222(2008).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ALLELE ZF-3A), AND VARIANT
RP GLY-56.
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [4] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 25-148 (ALLELE ZF-3B), AND FUNCTION.
RX PubMed=16861230; DOI=10.1074/jbc.m605505200;
RA Pizzo E., Buonanno P., Di Maro A., Ponticelli S., De Falco S., Quarto N.,
RA Cubellis M.V., D'Alessio G.;
RT "Ribonucleases and angiogenins from fish.";
RL J. Biol. Chem. 281:27454-27460(2006).
RN [5] {ECO:0000305}
RP PROTEIN SEQUENCE OF 56-63 (ALLELE ZF-3B), FUNCTION, AND PROTEOLYTIC
RP CLEAVAGE AT ARG-55.
RX PubMed=20214681; DOI=10.1111/j.1742-4658.2010.07614.x;
RA Zanfardino A., Pizzo E., Di Maro A., Varcamonti M., D'Alessio G.;
RT "The bactericidal action on Escherichia coli of ZF-RNase-3 is triggered by
RT the suicidal action of the bacterium OmpT protease.";
RL FEBS J. 277:1921-1928(2010).
RN [6] {ECO:0000305}
RP REVIEW.
RX PubMed=17616268; DOI=10.1016/j.gene.2007.05.006;
RA Pizzo E., D'Alessio G.;
RT "The success of the RNase scaffold in the advance of biosciences and in
RT evolution.";
RL Gene 406:8-12(2007).
CC -!- FUNCTION: Ribonuclease. Angiogenic. Plays a role in host defense.
CC Exhibits strong antibacterial activity against Gram-negative bacteria
CC but mild antibacterial activity against Gram-positive bacteria. The
CC RNase activity is not required for the bactericidal activity.
CC {ECO:0000269|PubMed:16861230, ECO:0000269|PubMed:17347156,
CC ECO:0000269|PubMed:18508078, ECO:0000269|PubMed:20214681}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P34096}.
CC -!- TISSUE SPECIFICITY: Strongly expressed in the adult liver and gut, and
CC weakly in the heart and testis. {ECO:0000269|PubMed:17347156}.
CC -!- DEVELOPMENTAL STAGE: Only expressed in adults.
CC {ECO:0000269|PubMed:17347156}.
CC -!- PTM: Cleavage between Arg-55 and Arg-56 is catalyzed by a membrane-
CC localized Gram-negative bacterium protease (OmpT in E.coli). The
CC excised fragment is then transported to the bacterium cytosol for
CC cleavage of the disulfide bridge linking Cys-48 and Cys-109, thus
CC separating the N-terminal and LF-ZF3. LF-ZF3 but not the N-terminal
CC peptide possesses bactericidal activity. {ECO:0000269|PubMed:20214681}.
CC -!- MISCELLANEOUS: Although the OmpT protease is absent in Gram-positive
CC bacteria, LF-ZF3 generated by a Gram-negative bacterium can penetrate a
CC Gram-positive bacterium and exert its cytotoxicity.
CC {ECO:0000269|PubMed:20214681}.
CC -!- SIMILARITY: Belongs to the pancreatic ribonuclease family.
CC {ECO:0000255}.
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DR EMBL; EF382669; ABQ23783.1; -; mRNA.
DR EMBL; BX465197; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001092923.1; NM_001099453.1.
DR PDB; 2VQ9; X-ray; 1.85 A; A=23-149.
DR PDBsum; 2VQ9; -.
DR AlphaFoldDB; A5HAK0; -.
DR SMR; A5HAK0; -.
DR STRING; 7955.ENSDARP00000123932; -.
DR PaxDb; A5HAK0; -.
DR GeneID; 798787; -.
DR KEGG; dre:798787; -.
DR CTD; 798787; -.
DR ZFIN; ZDB-GENE-050809-5; rnasel3.
DR eggNOG; ENOG502S9Q1; Eukaryota.
DR InParanoid; A5HAK0; -.
DR OrthoDB; 1549558at2759; -.
DR PhylomeDB; A5HAK0; -.
DR BRENDA; 4.6.1.18; 928.
DR Reactome; R-DRE-418990; Adherens junctions interactions.
DR Reactome; R-DRE-6798695; Neutrophil degranulation.
DR Reactome; R-DRE-6803157; Antimicrobial peptides.
DR EvolutionaryTrace; A5HAK0; -.
DR PRO; PR:A5HAK0; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0004540; F:ribonuclease activity; IDA:ZFIN.
DR GO; GO:0003723; F:RNA binding; IC:ZFIN.
DR GO; GO:0001525; P:angiogenesis; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IDA:ZFIN.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:ZFIN.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
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; Angiogenesis; Antibiotic; Antimicrobial;
KW Developmental protein; Differentiation; Direct protein sequencing;
KW Disulfide bond; Endonuclease; Hydrolase; Immunity; Nuclease;
KW Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:18508078"
FT CHAIN 23..149
FT /note="Ribonuclease-like 3"
FT /evidence="ECO:0000255"
FT /id="PRO_0000394404"
FT PEPTIDE 23..55
FT /note="N-terminal peptide"
FT /evidence="ECO:0000269|PubMed:20214681"
FT /id="PRO_0000394405"
FT PEPTIDE 56..149
FT /note="LF-ZF3"
FT /evidence="ECO:0000269|PubMed:20214681"
FT /id="PRO_0000394406"
FT ACT_SITE 38
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:18508078"
FT ACT_SITE 142
FT /note="Proton donor"
FT /evidence="ECO:0000269|PubMed:18508078"
FT BINDING 67..71
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:18508078"
FT SITE 55
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:20214681"
FT MOD_RES 23
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000250|UniProtKB:P34096"
FT DISULFID 48..109
FT /evidence="ECO:0000269|PubMed:18508078"
FT DISULFID 66..120
FT /evidence="ECO:0000269|PubMed:18508078"
FT DISULFID 84..135
FT /evidence="ECO:0000269|PubMed:18508078"
FT VARIANT 5
FT /note="Q -> R (in allele ZF-3d and allele ZF-3e)"
FT /evidence="ECO:0000269|PubMed:18508078"
FT VARIANT 56
FT /note="R -> G (in allele ZF-3a and allele ZF-3c)"
FT /evidence="ECO:0000269|PubMed:17347156,
FT ECO:0000269|PubMed:23594743"
FT VARIANT 93
FT /note="D -> E (in allele ZF-3c)"
FT /evidence="ECO:0000269|PubMed:17347156"
FT VARIANT 102
FT /note="N -> D (in allele ZF-3e)"
FT /evidence="ECO:0000269|PubMed:18508078"
FT VARIANT 137
FT /note="G -> S (in allele ZF-3c)"
FT /evidence="ECO:0000269|PubMed:17347156"
FT VARIANT 141
FT /note="T -> A (in allele ZF-3e)"
FT /evidence="ECO:0000269|PubMed:18508078"
FT VARIANT 145
FT /note="K -> R (in allele ZF-3d and allele ZF-3e)"
FT /evidence="ECO:0000269|PubMed:18508078"
FT CONFLICT 25
FT /note="A -> M (in Ref. 4; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT HELIX 28..38
FT /evidence="ECO:0007829|PDB:2VQ9"
FT HELIX 48..54
FT /evidence="ECO:0007829|PDB:2VQ9"
FT STRAND 58..63
FT /evidence="ECO:0007829|PDB:2VQ9"
FT STRAND 68..75
FT /evidence="ECO:0007829|PDB:2VQ9"
FT HELIX 77..81
FT /evidence="ECO:0007829|PDB:2VQ9"
FT HELIX 82..84
FT /evidence="ECO:0007829|PDB:2VQ9"
FT STRAND 87..90
FT /evidence="ECO:0007829|PDB:2VQ9"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:2VQ9"
FT STRAND 97..102
FT /evidence="ECO:0007829|PDB:2VQ9"
FT STRAND 104..113
FT /evidence="ECO:0007829|PDB:2VQ9"
FT STRAND 121..136
FT /evidence="ECO:0007829|PDB:2VQ9"
FT STRAND 139..147
FT /evidence="ECO:0007829|PDB:2VQ9"
SQ SEQUENCE 149 AA; 17011 MW; 096E21A32D5B6479 CRC64;
MGIHQCTAVV LLLLCASLST YGQPAEIRRR YEHFLTQHVY GGITEQTCDR VMRQRRITRF
PTGNDCKEVN TFIQANGNHV RTVCTGGGTR QTDNRDLYMS NNQFTVITCT LRSGERHPNC
RYRGKESSRK IVVACEGEWP THYEKGVIV
