RNAS7_HUMAN
ID RNAS7_HUMAN Reviewed; 156 AA.
AC Q9H1E1; P80927; P83685; Q546N3;
DT 19-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Ribonuclease 7;
DE Short=RNase 7;
DE EC=3.1.27.- {ECO:0000269|PubMed:12244054, ECO:0000269|PubMed:12527768, ECO:0000269|PubMed:17150966};
DE AltName: Full=Skin-derived antimicrobial protein 2;
DE Short=SAP-2;
DE Flags: Precursor;
GN Name=RNASE7; ORFNames=UNQ2516/PRO6006;
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], PROTEIN SEQUENCE OF 29-52, FUNCTION, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, INDUCTION, VARIANTS PRO-103 AND TYR-116, AND MASS
RP SPECTROMETRY.
RX PubMed=12244054; DOI=10.1074/jbc.m207587200;
RA Harder J., Schroeder J.M.;
RT "RNase 7, a novel innate immune defense antimicrobial protein of healthy
RT human skin.";
RL J. Biol. Chem. 277:46779-46784(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, TISSUE
RP SPECIFICITY, AND VARIANTS PRO-103 AND TYR-116.
RC TISSUE=Kidney;
RX PubMed=12527768; DOI=10.1093/nar/gkg157;
RA Zhang J., Dyer K.D., Rosenberg H.F.;
RT "Human RNase 7: a new cationic ribonuclease of the RNase A superfamily.";
RL Nucleic Acids Res. 31:602-607(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS PRO-103 AND TYR-116.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS PRO-103 AND TYR-116.
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 [6]
RP PRELIMINARY PROTEIN SEQUENCE OF 30-70.
RC TISSUE=Keratinocyte;
RA Harder J., Bartels J., Christophers E., Schroeder J.M.;
RL Submitted (MAR-1997) to UniProtKB.
RN [7]
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 [8]
RP STRUCTURE BY NMR OF 29-156, FUNCTION, CATALYTIC ACTIVITY, DISULFIDE BONDS,
RP AND MUTAGENESIS OF 29-LYS--GLY-32; LYS-29; LYS-31; HIS-43; 60-LYS--LYS-63;
RP LYS-66; 124-LYS--LYS-128; 139-LYS-LYS-140 AND HIS-151.
RX PubMed=17150966; DOI=10.1074/jbc.m607321200;
RA Huang Y.-C., Lin Y.-M., Chang T.-W., Wu S.-J., Lee Y.-S., Chang M.D.-S.,
RA Chen C., Wu S.-H., Liao Y.-D.;
RT "The flexible and clustered lysine residues of human ribonuclease 7 are
RT critical for membrane permeability and antimicrobial activity.";
RL J. Biol. Chem. 282:4626-4633(2007).
CC -!- FUNCTION: Exhibits a potent RNase activity (PubMed:12244054,
CC PubMed:12527768, PubMed:17150966). Has broad-spectrum antimicrobial
CC activity against many pathogenic microorganisms and remarkably potent
CC activity (lethal dose of 90% < 30 nM) against a vancomycin resistant
CC Enterococcus faecium (PubMed:12244054, PubMed:12527768,
CC PubMed:25075772, PubMed:17150966). Causes loss of bacterial membrane
CC integrity (PubMed:17150966). Probably contributes to urinary tract
CC sterility (PubMed:25075772). Bactericidal activity is independent of
CC RNase activity (PubMed:17150966). {ECO:0000269|PubMed:12244054,
CC ECO:0000269|PubMed:12527768, ECO:0000269|PubMed:17150966,
CC ECO:0000269|PubMed:25075772}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.2 uM for tRNA {ECO:0000269|PubMed:12244054};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12244054,
CC ECO:0000269|PubMed:25075772}. Note=Detected in urine.
CC {ECO:0000269|PubMed:25075772}.
CC -!- TISSUE SPECIFICITY: Expressed in collecting ducts in kidney, and in
CC apical uroepithelium in bladder (at protein level) (PubMed:25075772).
CC Expressed in various epithelial tissues including skin, respiratory
CC tract, genito-urinary tract and, at a low level, in the gut
CC (PubMed:12244054). Expressed in liver, kidney, skeletal muscle and
CC heart (PubMed:12527768). {ECO:0000269|PubMed:12244054,
CC ECO:0000269|PubMed:12527768, ECO:0000269|PubMed:25075772}.
CC -!- INDUCTION: Up-regulated in response to the cytokines IL1B, IFNG and TNF
CC (PubMed:12244054). Strongly up-regulated in response to the bacterium
CC P.aeruginosa (PubMed:12244054). Moderately up-regulated in response to
CC S.aureus, E.coli and S.pyogenes (PubMed:12244054). Up-regulated in
CC kidney in response to infection (PubMed:25075772).
CC {ECO:0000269|PubMed:12244054, ECO:0000269|PubMed:25075772}.
CC -!- MASS SPECTROMETRY: Mass=14546.06; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:12244054};
CC -!- SIMILARITY: Belongs to the pancreatic ribonuclease family.
CC {ECO:0000305}.
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DR EMBL; AJ131212; CAC20410.1; -; mRNA.
DR EMBL; AJ306608; CAC84462.1; -; mRNA.
DR EMBL; AJ306609; CAC84457.1; -; mRNA.
DR EMBL; AJ306610; CAC84458.1; -; mRNA.
DR EMBL; AY170392; AAO12510.1; -; mRNA.
DR EMBL; AY359097; AAQ89455.1; -; mRNA.
DR EMBL; AL161668; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC074960; AAH74960.1; -; mRNA.
DR EMBL; BC112334; AAI12335.1; -; mRNA.
DR CCDS; CCDS41914.1; -.
DR RefSeq; NP_115961.2; NM_032572.3.
DR PDB; 2HKY; NMR; -; A=29-156.
DR PDBsum; 2HKY; -.
DR AlphaFoldDB; Q9H1E1; -.
DR BMRB; Q9H1E1; -.
DR SMR; Q9H1E1; -.
DR BioGRID; 124179; 101.
DR IntAct; Q9H1E1; 21.
DR STRING; 9606.ENSP00000298690; -.
DR GlyGen; Q9H1E1; 1 site.
DR iPTMnet; Q9H1E1; -.
DR PhosphoSitePlus; Q9H1E1; -.
DR BioMuta; RNASE7; -.
DR DMDM; 296452879; -.
DR MassIVE; Q9H1E1; -.
DR MaxQB; Q9H1E1; -.
DR PaxDb; Q9H1E1; -.
DR PeptideAtlas; Q9H1E1; -.
DR PRIDE; Q9H1E1; -.
DR ProteomicsDB; 80403; -.
DR Antibodypedia; 69; 69 antibodies from 13 providers.
DR DNASU; 84659; -.
DR Ensembl; ENST00000298690.5; ENSP00000298690.3; ENSG00000165799.5.
DR Ensembl; ENST00000481538.1; ENSP00000431382.1; ENSG00000165799.5.
DR GeneID; 84659; -.
DR KEGG; hsa:84659; -.
DR MANE-Select; ENST00000298690.5; ENSP00000298690.3; NM_032572.4; NP_115961.3.
DR UCSC; uc001vzk.4; human.
DR CTD; 84659; -.
DR DisGeNET; 84659; -.
DR GeneCards; RNASE7; -.
DR HGNC; HGNC:19278; RNASE7.
DR HPA; ENSG00000165799; Group enriched (esophagus, lymphoid tissue, skin).
DR MIM; 612484; gene.
DR neXtProt; NX_Q9H1E1; -.
DR OpenTargets; ENSG00000165799; -.
DR PharmGKB; PA134939592; -.
DR VEuPathDB; HostDB:ENSG00000165799; -.
DR eggNOG; ENOG502TDZ3; Eukaryota.
DR GeneTree; ENSGT00940000164606; -.
DR HOGENOM; CLU_117006_0_1_1; -.
DR InParanoid; Q9H1E1; -.
DR OMA; RVATTCQ; -.
DR OrthoDB; 1549558at2759; -.
DR PhylomeDB; Q9H1E1; -.
DR TreeFam; TF333393; -.
DR PathwayCommons; Q9H1E1; -.
DR Reactome; R-HSA-6803157; Antimicrobial peptides.
DR SignaLink; Q9H1E1; -.
DR BioGRID-ORCS; 84659; 9 hits in 1065 CRISPR screens.
DR EvolutionaryTrace; Q9H1E1; -.
DR GenomeRNAi; 84659; -.
DR Pharos; Q9H1E1; Tbio.
DR PRO; PR:Q9H1E1; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q9H1E1; protein.
DR Bgee; ENSG00000165799; Expressed in upper arm skin and 74 other tissues.
DR Genevisible; Q9H1E1; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0001530; F:lipopolysaccharide binding; IDA:UniProtKB.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0042834; F:peptidoglycan binding; IDA:UniProtKB.
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:0050832; P:defense response to fungus; IDA:UniProtKB.
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:0045087; P:innate immune response; IDA:UniProtKB.
DR GO; GO:0051673; P:membrane disruption in another organism; 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; Direct protein sequencing;
KW Disulfide bond; Endonuclease; Glycoprotein; Hydrolase; Nuclease;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..28
FT /evidence="ECO:0000269|PubMed:12244054"
FT CHAIN 29..156
FT /note="Ribonuclease 7"
FT /id="PRO_0000030901"
FT REGION 29..32
FT /note="Important for antibacterial activity"
FT /evidence="ECO:0000269|PubMed:17150966"
FT REGION 139..140
FT /note="Important for antibacterial activity"
FT /evidence="ECO:0000269|PubMed:17150966"
FT ACT_SITE 43
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:17150966"
FT ACT_SITE 151
FT /note="Proton donor"
FT /evidence="ECO:0000305|PubMed:17150966"
FT BINDING 66..70
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 91
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT SITE 66
FT /note="Critical for catalytic activity"
FT /evidence="ECO:0000269|PubMed:17150966"
FT CARBOHYD 127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 51..109
FT /evidence="ECO:0000269|PubMed:17150966,
FT ECO:0007744|PDB:2HKY"
FT DISULFID 65..119
FT /evidence="ECO:0000269|PubMed:17150966,
FT ECO:0007744|PDB:2HKY"
FT DISULFID 83..134
FT /evidence="ECO:0000269|PubMed:17150966,
FT ECO:0007744|PDB:2HKY"
FT DISULFID 90..97
FT /evidence="ECO:0000269|PubMed:17150966,
FT ECO:0007744|PDB:2HKY"
FT VARIANT 103
FT /note="A -> P (in dbSNP:rs1263872)"
FT /evidence="ECO:0000269|PubMed:12244054,
FT ECO:0000269|PubMed:12527768, ECO:0000269|PubMed:12975309,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_024619"
FT VARIANT 116
FT /note="H -> Y (in dbSNP:rs1243469)"
FT /evidence="ECO:0000269|PubMed:12244054,
FT ECO:0000269|PubMed:12527768, ECO:0000269|PubMed:12975309,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_024620"
FT MUTAGEN 29..32
FT /note="Missing: Significant loss of bactericidal activity.
FT No effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:17150966"
FT MUTAGEN 29
FT /note="K->A: Slight loss of bactericidal activity. No
FT effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:17150966"
FT MUTAGEN 31
FT /note="K->A: Significant loss of bactericidal activity. No
FT effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:17150966"
FT MUTAGEN 43
FT /note="H->A: Loss of catalytic activity. No effect on
FT bactericidal activity."
FT /evidence="ECO:0000269|PubMed:17150966"
FT MUTAGEN 60..63
FT /note="KHTK->NHTQ: No significant effect on bactericidal
FT activity or catalytic activity."
FT /evidence="ECO:0000269|PubMed:17150966"
FT MUTAGEN 66
FT /note="K->A: Loss of catalytic activity. No effect on
FT bactericidal activity."
FT /evidence="ECO:0000269|PubMed:17150966"
FT MUTAGEN 124..128
FT /note="KRQNK->AAQNT: No significant effect on bactericidal
FT activity or catalytic activity."
FT /evidence="ECO:0000269|PubMed:17150966"
FT MUTAGEN 139..140
FT /note="KK->QQ: Moderate loss of bactericidal activity. No
FT effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:17150966"
FT MUTAGEN 151
FT /note="H->A: Loss of catalytic activity. No effect on
FT bactericidal activity."
FT /evidence="ECO:0000269|PubMed:17150966"
FT HELIX 35..43
FT /evidence="ECO:0007829|PDB:2HKY"
FT HELIX 50..62
FT /evidence="ECO:0007829|PDB:2HKY"
FT STRAND 67..72
FT /evidence="ECO:0007829|PDB:2HKY"
FT HELIX 76..82
FT /evidence="ECO:0007829|PDB:2HKY"
FT STRAND 90..93
FT /evidence="ECO:0007829|PDB:2HKY"
FT STRAND 97..99
FT /evidence="ECO:0007829|PDB:2HKY"
FT STRAND 104..114
FT /evidence="ECO:0007829|PDB:2HKY"
FT STRAND 120..128
FT /evidence="ECO:0007829|PDB:2HKY"
FT STRAND 130..135
FT /evidence="ECO:0007829|PDB:2HKY"
FT STRAND 146..155
FT /evidence="ECO:0007829|PDB:2HKY"
SQ SEQUENCE 156 AA; 17419 MW; A8659D3EECEF4054 CRC64;
MAPARAGFCP LLLLLLLGLW VAEIPVSAKP KGMTSSQWFK IQHMQPSPQA CNSAMKNINK
HTKRCKDLNT FLHEPFSSVA ATCQTPKIAC KNGDKNCHQS HGAVSLTMCK LTSGKHPNCR
YKEKRQNKSY VVACKPPQKK DSQQFHLVPV HLDRVL
