Full text data of RNASE2
RNASE2
(EDN, RNS2)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Non-secretory ribonuclease; 3.1.27.5 (Eosinophil-derived neurotoxin; RNase UpI-2; Ribonuclease 2; RNase 2; Ribonuclease US; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Non-secretory ribonuclease; 3.1.27.5 (Eosinophil-derived neurotoxin; RNase UpI-2; Ribonuclease 2; RNase 2; Ribonuclease US; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P10153
ID RNAS2_HUMAN Reviewed; 161 AA.
AC P10153; Q52M39; Q9H2B7; Q9UCG7;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JAN-1990, sequence version 2.
DT 22-JAN-2014, entry version 159.
DE RecName: Full=Non-secretory ribonuclease;
DE EC=3.1.27.5;
DE AltName: Full=Eosinophil-derived neurotoxin;
DE AltName: Full=RNase UpI-2;
DE AltName: Full=Ribonuclease 2;
DE Short=RNase 2;
DE AltName: Full=Ribonuclease US;
DE Flags: Precursor;
GN Name=RNASE2; Synonyms=EDN, RNS2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2591744; DOI=10.1016/0378-1119(89)90414-9;
RA Hamann K.J., Barker R.L., Loegering D.A., Pease L.R., Gleich G.J.;
RT "Sequence of human eosinophil-derived neurotoxin cDNA: identity of
RT deduced amino acid sequence with human nonsecretory ribonucleases.";
RL Gene 83:161-167(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2745977;
RA Barker R.L., Loegering D.A., Ten R.M., Hamann K.J., Pease L.R.,
RA Gleich G.J.;
RT "Eosinophil cationic protein cDNA. Comparison with other toxic
RT cationic proteins and ribonucleases.";
RL J. Immunol. 143:952-955(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2734298; DOI=10.1073/pnas.86.12.4460;
RA Rosenberg H.F., Tenen D.G., Ackerman S.J.;
RT "Molecular cloning of the human eosinophil-derived neurotoxin: a
RT member of the ribonuclease gene family.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:4460-4464(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2387583; DOI=10.1016/0888-7543(90)90197-3;
RA Hamann K.J., Ten R.M., Loegering D.A., Jenkins R.B., Heise M.T.,
RA Schad C.R., Pease L.R., Gleich G.J., Barker R.L.;
RT "Structure and chromosome localization of the human eosinophil-derived
RT neurotoxin and eosinophil cationic protein genes: evidence for
RT intronless coding sequences in the ribonuclease gene superfamily.";
RL Genomics 7:535-546(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASN-156.
RX PubMed=11102386;
RA Zhang J., Rosenberg H.F.;
RT "Sequence variation at two eosinophil-associated ribonuclease loci in
RT humans.";
RL Genetics 156:1949-1958(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC TISSUE=Colon, and Leukemia;
RA Simonsen C.C., Kennedy J., Comstock L., Ashton N., McGrogan M.;
RL Submitted (OCT-1990) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 28-161.
RX PubMed=3166997; DOI=10.1021/bi00412a046;
RA Beintema J.J., Hofsteenge J., Iwama M., Morita T., Ohgi K., Irie M.,
RA Sugiyama R.H., Schieven G.L., Dekker C.A., Glitz D.G.;
RT "Amino acid sequence of the nonsecretory ribonuclease of human
RT urine.";
RL Biochemistry 27:4530-4538(1988).
RN [9]
RP PROTEIN SEQUENCE OF 28-82, AND FUNCTION.
RX PubMed=3458170; DOI=10.1073/pnas.83.10.3146;
RA Gleich G.J., Loegering D.A., Bell M.P., Checkel J.L., Ackerman S.J.,
RA McKean D.J.;
RT "Biochemical and functional similarities between human eosinophil-
RT derived neurotoxin and eosinophil cationic protein: homology with
RT ribonuclease.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:3146-3150(1986).
RN [10]
RP PROTEIN SEQUENCE OF 28-55.
RX PubMed=3926759;
RA Niwata Y., Ohgi K., Sanda A., Takizawa Y., Irie M.;
RT "Purification and properties of bovine kidney ribonucleases.";
RL J. Biochem. 97:923-934(1985).
RN [11]
RP PROTEIN SEQUENCE OF 28-53.
RC TISSUE=Liver;
RX PubMed=3182786;
RA Sorrentino S., Tucker G.K., Glitz D.G.;
RT "Purification and characterization of a ribonuclease from human
RT liver.";
RL J. Biol. Chem. 263:16125-16131(1988).
RN [12]
RP PROTEIN SEQUENCE OF 24-43.
RC TISSUE=Urine;
RX PubMed=1587793;
RA Sakakibara R., Hashida K., Kitahara T., Ishiguro M.;
RT "Characterization of a unique nonsecretory ribonuclease from urine of
RT pregnant women.";
RL J. Biochem. 111:325-330(1992).
RN [13]
RP PROTEIN SEQUENCE OF 28-45.
RC TISSUE=Urine;
RX PubMed=8471426;
RA Kardana A., Bagshawe K.D., Coles B., Read D., Taylor M.;
RT "Characterisation of UGP and its relationship with beta-core
RT fragment.";
RL Br. J. Cancer 67:686-692(1993).
RN [14]
RP GLYCOSYLATION AT TRP-34.
RX PubMed=7947762; DOI=10.1021/bi00250a003;
RA Hofsteenge J., Mueller D.R., de Beer T., Loeffler A., Richter W.J.,
RA Vliegenthart J.F.G.;
RT "New type of linkage between a carbohydrate and a protein: C-
RT glycosylation of a specific tryptophan residue in human RNase Us.";
RL Biochemistry 33:13524-13530(1994).
RN [15]
RP STRUCTURE OF C-GLYCOSYLATED GROUP.
RX PubMed=7547911; DOI=10.1021/bi00037a016;
RA de Beer T., Vliegenthart J.F.G., Loeffler A., Hofsteenge J.;
RT "The hexopyranosyl residue that is C-glycosidically linked to the side
RT chain of tryptophan-7 in human RNase Us is alpha-mannopyranose.";
RL Biochemistry 34:11785-11789(1995).
RN [16]
RP GLYCOSYLATION AT TRP-34.
RX PubMed=9450956; DOI=10.1091/mbc.9.2.301;
RA Krieg J., Hartmann S., Vicentini A., Glasner W., Hess D.,
RA Hofsteenge J.;
RT "Recognition signal for C-mannosylation of Trp-7 in RNase 2 consists
RT of sequence Trp-x-x-Trp.";
RL Mol. Biol. Cell 9:301-309(1998).
RN [17]
RP FUNCTION, AND INTERACTION WITH RNH1.
RX PubMed=12578357; DOI=10.1021/bi026852o;
RA Teufel D.P., Kao R.Y., Acharya K.R., Shapiro R.;
RT "Mutational analysis of the complex of human RNase inhibitor and human
RT eosinophil-derived neurotoxin (RNase 2).";
RL Biochemistry 42:1451-1459(2003).
RN [18]
RP INVOLVEMENT IN CHEMOTAXIS.
RX PubMed=12855582; DOI=10.1182/blood-2003-01-0151;
RA Yang D., Rosenberg H.F., Chen Q., Dyer K.D., Kurosaka K.,
RA Oppenheim J.J.;
RT "Eosinophil-derived neurotoxin (EDN), an antimicrobial protein with
RT chemotactic activities for dendritic cells.";
RL Blood 102:3396-3403(2003).
RN [19]
RP NITRATION AT TYR-60.
RX PubMed=18694936; DOI=10.1074/jbc.M801196200;
RA Ulrich M., Petre A., Youhnovski N., Proemm F., Schirle M., Schumm M.,
RA Pero R.S., Doyle A., Checkel J., Kita H., Thiyagarajan N.,
RA Acharya K.R., Schmid-Grendelmeier P., Simon H.-U., Schwarz H.,
RA Tsutsui M., Shimokawa H., Bellon G., Lee J.J., Przybylski M.,
RA Doering G.;
RT "Post-translational tyrosine nitration of eosinophil granule toxins
RT mediated by eosinophil peroxidase.";
RL J. Biol. Chem. 283:28629-28640(2008).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS).
RX PubMed=8759319; DOI=10.1006/jmbi.1996.0420;
RA Mosimann S.C., Newton D.L., Youle R.J., James M.N.G.;
RT "X-ray crystallographic structure of recombinant eosinophil-derived
RT neurotoxin at 1.83-A resolution.";
RL J. Mol. Biol. 260:540-552(1996).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
RX PubMed=11154698; DOI=10.1074/jbc.M010585200;
RA Leonidas D.D., Boix E., Prill R., Suzuki M., Turton R., Minson K.,
RA Swaminathan G.J., Youle R.J., Acharya K.R.;
RT "Mapping the ribonucleolytic active site of eosinophil-derived
RT neurotoxin (EDN). High resolution crystal structures of EDN complexes
RT with adenylic nucleotide inhibitors.";
RL J. Biol. Chem. 276:15009-15017(2001).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 28-161 IN COMPLEX WITH RNH1,
RP AND SUBUNIT.
RX PubMed=15755456; DOI=10.1016/j.jmb.2005.01.035;
RA Iyer S., Holloway D.E., Kumar K., Shapiro R., Acharya K.R.;
RT "Molecular recognition of human eosinophil-derived neurotoxin (RNase
RT 2) by placental ribonuclease inhibitor.";
RL J. Mol. Biol. 347:637-655(2005).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (0.98 ANGSTROMS) OF 28-161 IN COMPLEX WITH ADP
RP AND ATP.
RX PubMed=16401072; DOI=10.1021/bi0518592;
RA Baker M.D., Holloway D.E., Swaminathan G.J., Acharya K.R.;
RT "Crystal structures of eosinophil-derived neurotoxin (EDN) in complex
RT with the inhibitors 5'-ATP, Ap3A, Ap4A, and Ap5A.";
RL Biochemistry 45:416-426(2006).
CC -!- FUNCTION: This is a non-secretory ribonuclease. It is a pyrimidine
CC specific nuclease with a slight preference for U. Cytotoxin and
CC helminthotoxin. Selectively chemotactic for dendritic cells.
CC Possesses a wide variety of biological activities.
CC -!- CATALYTIC ACTIVITY: Endonucleolytic cleavage to nucleoside 3'-
CC phosphates and 3'-phosphooligonucleotides ending in Cp or Up with
CC 2',3'-cyclic phosphate intermediates.
CC -!- SUBUNIT: Interacts with and forms a tight 1:1 complex with RNH1.
CC Dimerization of two such complexes may occur.
CC -!- SUBCELLULAR LOCATION: Lysosome (Probable). Cytoplasmic granule.
CC Note=Matrix of eosinophil's large specific granule.
CC -!- TISSUE SPECIFICITY: Liver, lung, spleen, leukocytes and body
CC fluids.
CC -!- DOMAIN: The N-terminal region is necessary for mediating
CC chemotactic activity.
CC -!- PTM: A particular signal processing and glycosylation pattern may
CC differentiate the UpI2 RNase, found specifically in pregnant women
CC urine, from other nonsecretory RNases.
CC -!- SIMILARITY: Belongs to the pancreatic ribonuclease family.
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DR EMBL; M30510; AAC82505.1; -; mRNA.
DR EMBL; M28129; AAA50284.1; -; mRNA.
DR EMBL; M24157; AAA52337.1; -; mRNA.
DR EMBL; X16546; CAA34546.1; -; Genomic_DNA.
DR EMBL; AF294007; AAG31577.1; -; Genomic_DNA.
DR EMBL; AF294008; AAG31578.1; -; Genomic_DNA.
DR EMBL; AF294009; AAG31579.1; -; Genomic_DNA.
DR EMBL; AF294010; AAG31580.1; -; Genomic_DNA.
DR EMBL; AF294011; AAG31581.1; -; Genomic_DNA.
DR EMBL; AF294012; AAG31582.1; -; Genomic_DNA.
DR EMBL; AF294013; AAG31583.1; -; Genomic_DNA.
DR EMBL; AF294014; AAG31584.1; -; Genomic_DNA.
DR EMBL; AF294015; AAG31585.1; -; Genomic_DNA.
DR EMBL; X55987; CAA39459.1; -; Genomic_DNA.
DR EMBL; X55988; CAA39460.1; -; mRNA.
DR EMBL; BC093678; AAH93678.1; -; mRNA.
DR EMBL; BC093680; AAH93680.1; -; mRNA.
DR EMBL; BC096059; AAH96059.1; -; mRNA.
DR PIR; A35328; A33922.
DR RefSeq; NP_002925.1; NM_002934.2.
DR UniGene; Hs.728; -.
DR PDB; 1GQV; X-ray; 0.98 A; A=28-161.
DR PDB; 1HI2; X-ray; 1.60 A; A=28-161.
DR PDB; 1HI3; X-ray; 1.80 A; A=28-161.
DR PDB; 1HI4; X-ray; 1.80 A; A=28-161.
DR PDB; 1HI5; X-ray; 1.80 A; A=28-161.
DR PDB; 1K2A; X-ray; 1.00 A; A=26-160.
DR PDB; 2BEX; X-ray; 1.99 A; C/D=28-161.
DR PDB; 2BZZ; X-ray; 0.98 A; A=28-161.
DR PDB; 2C01; X-ray; 1.24 A; X=28-161.
DR PDB; 2C02; X-ray; 2.00 A; A=28-161.
DR PDB; 2C05; X-ray; 1.86 A; A=28-161.
DR PDBsum; 1GQV; -.
DR PDBsum; 1HI2; -.
DR PDBsum; 1HI3; -.
DR PDBsum; 1HI4; -.
DR PDBsum; 1HI5; -.
DR PDBsum; 1K2A; -.
DR PDBsum; 2BEX; -.
DR PDBsum; 2BZZ; -.
DR PDBsum; 2C01; -.
DR PDBsum; 2C02; -.
DR PDBsum; 2C05; -.
DR ProteinModelPortal; P10153; -.
DR SMR; P10153; 26-161.
DR STRING; 9606.ENSP00000303276; -.
DR BindingDB; P10153; -.
DR ChEMBL; CHEMBL5120; -.
DR PhosphoSite; P10153; -.
DR UniCarbKB; P10153; -.
DR DMDM; 133168; -.
DR PaxDb; P10153; -.
DR PeptideAtlas; P10153; -.
DR PRIDE; P10153; -.
DR Ensembl; ENST00000304625; ENSP00000303276; ENSG00000169385.
DR GeneID; 6036; -.
DR KEGG; hsa:6036; -.
DR UCSC; uc001vyl.1; human.
DR CTD; 6036; -.
DR GeneCards; GC14P021423; -.
DR HGNC; HGNC:10045; RNASE2.
DR HPA; HPA044983; -.
DR MIM; 131410; gene.
DR neXtProt; NX_P10153; -.
DR PharmGKB; PA34413; -.
DR eggNOG; NOG39501; -.
DR HOGENOM; HOG000276882; -.
DR HOVERGEN; HBG008396; -.
DR InParanoid; P10153; -.
DR KO; K01168; -.
DR OMA; RDPPQYP; -.
DR OrthoDB; EOG7KDFCP; -.
DR PhylomeDB; P10153; -.
DR EvolutionaryTrace; P10153; -.
DR GeneWiki; Eosinophil-derived_neurotoxin; -.
DR GenomeRNAi; 6036; -.
DR NextBio; 23525; -.
DR PRO; PR:P10153; -.
DR Bgee; P10153; -.
DR CleanEx; HS_RNASE2; -.
DR Genevestigator; P10153; -.
DR GO; GO:0005576; C:extracellular region; TAS:ProtInc.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0004522; F:pancreatic ribonuclease activity; IEA:UniProtKB-EC.
DR GO; GO:0004540; F:ribonuclease activity; TAS:ProtInc.
DR GO; GO:0006935; P:chemotaxis; IDA:UniProtKB.
DR GO; GO:0006401; P:RNA catabolic process; TAS:ProtInc.
DR Gene3D; 3.10.130.10; -; 1.
DR InterPro; IPR001427; RNaseA.
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 ProDom; PD000535; RNaseA; 1.
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; Chemotaxis; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Endonuclease; Glycoprotein;
KW Hydrolase; Lysosome; Nitration; Nuclease; Polymorphism;
KW Reference proteome; Signal.
FT SIGNAL 1 27
FT CHAIN 28 161 Non-secretory ribonuclease.
FT /FTId=PRO_0000030874.
FT REGION 65 69 Substrate binding.
FT ACT_SITE 42 42 Proton acceptor.
FT ACT_SITE 156 156 Proton donor.
FT MOD_RES 60 60 Nitrated tyrosine.
FT CARBOHYD 34 34 C-linked (Man).
FT /FTId=CAR_000004.
FT CARBOHYD 44 44 N-linked (GlcNAc...).
FT CARBOHYD 86 86 N-linked (GlcNAc...).
FT CARBOHYD 92 92 N-linked (GlcNAc...).
FT CARBOHYD 111 111 N-linked (GlcNAc...).
FT CARBOHYD 119 119 N-linked (GlcNAc...).
FT DISULFID 50 110
FT DISULFID 64 123
FT DISULFID 82 138
FT DISULFID 89 98
FT VARIANT 100 100 H -> Q (in dbSNP:rs8012891).
FT /FTId=VAR_059820.
FT VARIANT 156 156 H -> N (probably inactive;
FT dbSNP:rs146887874).
FT /FTId=VAR_013150.
FT CONFLICT 37 37 W -> R (in Ref. 10; AA sequence).
FT CONFLICT 39 40 ET -> QE (in Ref. 10; AA sequence).
FT CONFLICT 46 46 T -> V (in Ref. 10; AA sequence).
FT CONFLICT 47 47 S -> T (in Ref. 11; AA sequence).
FT HELIX 34 42
FT STRAND 46 49
FT HELIX 50 61
FT STRAND 66 73
FT HELIX 75 82
FT STRAND 98 100
FT STRAND 105 114
FT HELIX 120 122
FT STRAND 124 140
FT TURN 143 145
FT STRAND 151 161
SQ SEQUENCE 161 AA; 18354 MW; 9406C4596CA69038 CRC64;
MVPKLFTSQI CLLLLLGLLA VEGSLHVKPP QFTWAQWFET QHINMTSQQC TNAMQVINNY
QRRCKNQNTF LLTTFANVVN VCGNPNMTCP SNKTRKNCHH SGSQVPLIHC NLTTPSPQNI
SNCRYAQTPA NMFYIVACDN RDQRRDPPQY PVVPVHLDRI I
//
ID RNAS2_HUMAN Reviewed; 161 AA.
AC P10153; Q52M39; Q9H2B7; Q9UCG7;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JAN-1990, sequence version 2.
DT 22-JAN-2014, entry version 159.
DE RecName: Full=Non-secretory ribonuclease;
DE EC=3.1.27.5;
DE AltName: Full=Eosinophil-derived neurotoxin;
DE AltName: Full=RNase UpI-2;
DE AltName: Full=Ribonuclease 2;
DE Short=RNase 2;
DE AltName: Full=Ribonuclease US;
DE Flags: Precursor;
GN Name=RNASE2; Synonyms=EDN, RNS2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2591744; DOI=10.1016/0378-1119(89)90414-9;
RA Hamann K.J., Barker R.L., Loegering D.A., Pease L.R., Gleich G.J.;
RT "Sequence of human eosinophil-derived neurotoxin cDNA: identity of
RT deduced amino acid sequence with human nonsecretory ribonucleases.";
RL Gene 83:161-167(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2745977;
RA Barker R.L., Loegering D.A., Ten R.M., Hamann K.J., Pease L.R.,
RA Gleich G.J.;
RT "Eosinophil cationic protein cDNA. Comparison with other toxic
RT cationic proteins and ribonucleases.";
RL J. Immunol. 143:952-955(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2734298; DOI=10.1073/pnas.86.12.4460;
RA Rosenberg H.F., Tenen D.G., Ackerman S.J.;
RT "Molecular cloning of the human eosinophil-derived neurotoxin: a
RT member of the ribonuclease gene family.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:4460-4464(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2387583; DOI=10.1016/0888-7543(90)90197-3;
RA Hamann K.J., Ten R.M., Loegering D.A., Jenkins R.B., Heise M.T.,
RA Schad C.R., Pease L.R., Gleich G.J., Barker R.L.;
RT "Structure and chromosome localization of the human eosinophil-derived
RT neurotoxin and eosinophil cationic protein genes: evidence for
RT intronless coding sequences in the ribonuclease gene superfamily.";
RL Genomics 7:535-546(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASN-156.
RX PubMed=11102386;
RA Zhang J., Rosenberg H.F.;
RT "Sequence variation at two eosinophil-associated ribonuclease loci in
RT humans.";
RL Genetics 156:1949-1958(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC TISSUE=Colon, and Leukemia;
RA Simonsen C.C., Kennedy J., Comstock L., Ashton N., McGrogan M.;
RL Submitted (OCT-1990) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 28-161.
RX PubMed=3166997; DOI=10.1021/bi00412a046;
RA Beintema J.J., Hofsteenge J., Iwama M., Morita T., Ohgi K., Irie M.,
RA Sugiyama R.H., Schieven G.L., Dekker C.A., Glitz D.G.;
RT "Amino acid sequence of the nonsecretory ribonuclease of human
RT urine.";
RL Biochemistry 27:4530-4538(1988).
RN [9]
RP PROTEIN SEQUENCE OF 28-82, AND FUNCTION.
RX PubMed=3458170; DOI=10.1073/pnas.83.10.3146;
RA Gleich G.J., Loegering D.A., Bell M.P., Checkel J.L., Ackerman S.J.,
RA McKean D.J.;
RT "Biochemical and functional similarities between human eosinophil-
RT derived neurotoxin and eosinophil cationic protein: homology with
RT ribonuclease.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:3146-3150(1986).
RN [10]
RP PROTEIN SEQUENCE OF 28-55.
RX PubMed=3926759;
RA Niwata Y., Ohgi K., Sanda A., Takizawa Y., Irie M.;
RT "Purification and properties of bovine kidney ribonucleases.";
RL J. Biochem. 97:923-934(1985).
RN [11]
RP PROTEIN SEQUENCE OF 28-53.
RC TISSUE=Liver;
RX PubMed=3182786;
RA Sorrentino S., Tucker G.K., Glitz D.G.;
RT "Purification and characterization of a ribonuclease from human
RT liver.";
RL J. Biol. Chem. 263:16125-16131(1988).
RN [12]
RP PROTEIN SEQUENCE OF 24-43.
RC TISSUE=Urine;
RX PubMed=1587793;
RA Sakakibara R., Hashida K., Kitahara T., Ishiguro M.;
RT "Characterization of a unique nonsecretory ribonuclease from urine of
RT pregnant women.";
RL J. Biochem. 111:325-330(1992).
RN [13]
RP PROTEIN SEQUENCE OF 28-45.
RC TISSUE=Urine;
RX PubMed=8471426;
RA Kardana A., Bagshawe K.D., Coles B., Read D., Taylor M.;
RT "Characterisation of UGP and its relationship with beta-core
RT fragment.";
RL Br. J. Cancer 67:686-692(1993).
RN [14]
RP GLYCOSYLATION AT TRP-34.
RX PubMed=7947762; DOI=10.1021/bi00250a003;
RA Hofsteenge J., Mueller D.R., de Beer T., Loeffler A., Richter W.J.,
RA Vliegenthart J.F.G.;
RT "New type of linkage between a carbohydrate and a protein: C-
RT glycosylation of a specific tryptophan residue in human RNase Us.";
RL Biochemistry 33:13524-13530(1994).
RN [15]
RP STRUCTURE OF C-GLYCOSYLATED GROUP.
RX PubMed=7547911; DOI=10.1021/bi00037a016;
RA de Beer T., Vliegenthart J.F.G., Loeffler A., Hofsteenge J.;
RT "The hexopyranosyl residue that is C-glycosidically linked to the side
RT chain of tryptophan-7 in human RNase Us is alpha-mannopyranose.";
RL Biochemistry 34:11785-11789(1995).
RN [16]
RP GLYCOSYLATION AT TRP-34.
RX PubMed=9450956; DOI=10.1091/mbc.9.2.301;
RA Krieg J., Hartmann S., Vicentini A., Glasner W., Hess D.,
RA Hofsteenge J.;
RT "Recognition signal for C-mannosylation of Trp-7 in RNase 2 consists
RT of sequence Trp-x-x-Trp.";
RL Mol. Biol. Cell 9:301-309(1998).
RN [17]
RP FUNCTION, AND INTERACTION WITH RNH1.
RX PubMed=12578357; DOI=10.1021/bi026852o;
RA Teufel D.P., Kao R.Y., Acharya K.R., Shapiro R.;
RT "Mutational analysis of the complex of human RNase inhibitor and human
RT eosinophil-derived neurotoxin (RNase 2).";
RL Biochemistry 42:1451-1459(2003).
RN [18]
RP INVOLVEMENT IN CHEMOTAXIS.
RX PubMed=12855582; DOI=10.1182/blood-2003-01-0151;
RA Yang D., Rosenberg H.F., Chen Q., Dyer K.D., Kurosaka K.,
RA Oppenheim J.J.;
RT "Eosinophil-derived neurotoxin (EDN), an antimicrobial protein with
RT chemotactic activities for dendritic cells.";
RL Blood 102:3396-3403(2003).
RN [19]
RP NITRATION AT TYR-60.
RX PubMed=18694936; DOI=10.1074/jbc.M801196200;
RA Ulrich M., Petre A., Youhnovski N., Proemm F., Schirle M., Schumm M.,
RA Pero R.S., Doyle A., Checkel J., Kita H., Thiyagarajan N.,
RA Acharya K.R., Schmid-Grendelmeier P., Simon H.-U., Schwarz H.,
RA Tsutsui M., Shimokawa H., Bellon G., Lee J.J., Przybylski M.,
RA Doering G.;
RT "Post-translational tyrosine nitration of eosinophil granule toxins
RT mediated by eosinophil peroxidase.";
RL J. Biol. Chem. 283:28629-28640(2008).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS).
RX PubMed=8759319; DOI=10.1006/jmbi.1996.0420;
RA Mosimann S.C., Newton D.L., Youle R.J., James M.N.G.;
RT "X-ray crystallographic structure of recombinant eosinophil-derived
RT neurotoxin at 1.83-A resolution.";
RL J. Mol. Biol. 260:540-552(1996).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
RX PubMed=11154698; DOI=10.1074/jbc.M010585200;
RA Leonidas D.D., Boix E., Prill R., Suzuki M., Turton R., Minson K.,
RA Swaminathan G.J., Youle R.J., Acharya K.R.;
RT "Mapping the ribonucleolytic active site of eosinophil-derived
RT neurotoxin (EDN). High resolution crystal structures of EDN complexes
RT with adenylic nucleotide inhibitors.";
RL J. Biol. Chem. 276:15009-15017(2001).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 28-161 IN COMPLEX WITH RNH1,
RP AND SUBUNIT.
RX PubMed=15755456; DOI=10.1016/j.jmb.2005.01.035;
RA Iyer S., Holloway D.E., Kumar K., Shapiro R., Acharya K.R.;
RT "Molecular recognition of human eosinophil-derived neurotoxin (RNase
RT 2) by placental ribonuclease inhibitor.";
RL J. Mol. Biol. 347:637-655(2005).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (0.98 ANGSTROMS) OF 28-161 IN COMPLEX WITH ADP
RP AND ATP.
RX PubMed=16401072; DOI=10.1021/bi0518592;
RA Baker M.D., Holloway D.E., Swaminathan G.J., Acharya K.R.;
RT "Crystal structures of eosinophil-derived neurotoxin (EDN) in complex
RT with the inhibitors 5'-ATP, Ap3A, Ap4A, and Ap5A.";
RL Biochemistry 45:416-426(2006).
CC -!- FUNCTION: This is a non-secretory ribonuclease. It is a pyrimidine
CC specific nuclease with a slight preference for U. Cytotoxin and
CC helminthotoxin. Selectively chemotactic for dendritic cells.
CC Possesses a wide variety of biological activities.
CC -!- CATALYTIC ACTIVITY: Endonucleolytic cleavage to nucleoside 3'-
CC phosphates and 3'-phosphooligonucleotides ending in Cp or Up with
CC 2',3'-cyclic phosphate intermediates.
CC -!- SUBUNIT: Interacts with and forms a tight 1:1 complex with RNH1.
CC Dimerization of two such complexes may occur.
CC -!- SUBCELLULAR LOCATION: Lysosome (Probable). Cytoplasmic granule.
CC Note=Matrix of eosinophil's large specific granule.
CC -!- TISSUE SPECIFICITY: Liver, lung, spleen, leukocytes and body
CC fluids.
CC -!- DOMAIN: The N-terminal region is necessary for mediating
CC chemotactic activity.
CC -!- PTM: A particular signal processing and glycosylation pattern may
CC differentiate the UpI2 RNase, found specifically in pregnant women
CC urine, from other nonsecretory RNases.
CC -!- SIMILARITY: Belongs to the pancreatic ribonuclease family.
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; M30510; AAC82505.1; -; mRNA.
DR EMBL; M28129; AAA50284.1; -; mRNA.
DR EMBL; M24157; AAA52337.1; -; mRNA.
DR EMBL; X16546; CAA34546.1; -; Genomic_DNA.
DR EMBL; AF294007; AAG31577.1; -; Genomic_DNA.
DR EMBL; AF294008; AAG31578.1; -; Genomic_DNA.
DR EMBL; AF294009; AAG31579.1; -; Genomic_DNA.
DR EMBL; AF294010; AAG31580.1; -; Genomic_DNA.
DR EMBL; AF294011; AAG31581.1; -; Genomic_DNA.
DR EMBL; AF294012; AAG31582.1; -; Genomic_DNA.
DR EMBL; AF294013; AAG31583.1; -; Genomic_DNA.
DR EMBL; AF294014; AAG31584.1; -; Genomic_DNA.
DR EMBL; AF294015; AAG31585.1; -; Genomic_DNA.
DR EMBL; X55987; CAA39459.1; -; Genomic_DNA.
DR EMBL; X55988; CAA39460.1; -; mRNA.
DR EMBL; BC093678; AAH93678.1; -; mRNA.
DR EMBL; BC093680; AAH93680.1; -; mRNA.
DR EMBL; BC096059; AAH96059.1; -; mRNA.
DR PIR; A35328; A33922.
DR RefSeq; NP_002925.1; NM_002934.2.
DR UniGene; Hs.728; -.
DR PDB; 1GQV; X-ray; 0.98 A; A=28-161.
DR PDB; 1HI2; X-ray; 1.60 A; A=28-161.
DR PDB; 1HI3; X-ray; 1.80 A; A=28-161.
DR PDB; 1HI4; X-ray; 1.80 A; A=28-161.
DR PDB; 1HI5; X-ray; 1.80 A; A=28-161.
DR PDB; 1K2A; X-ray; 1.00 A; A=26-160.
DR PDB; 2BEX; X-ray; 1.99 A; C/D=28-161.
DR PDB; 2BZZ; X-ray; 0.98 A; A=28-161.
DR PDB; 2C01; X-ray; 1.24 A; X=28-161.
DR PDB; 2C02; X-ray; 2.00 A; A=28-161.
DR PDB; 2C05; X-ray; 1.86 A; A=28-161.
DR PDBsum; 1GQV; -.
DR PDBsum; 1HI2; -.
DR PDBsum; 1HI3; -.
DR PDBsum; 1HI4; -.
DR PDBsum; 1HI5; -.
DR PDBsum; 1K2A; -.
DR PDBsum; 2BEX; -.
DR PDBsum; 2BZZ; -.
DR PDBsum; 2C01; -.
DR PDBsum; 2C02; -.
DR PDBsum; 2C05; -.
DR ProteinModelPortal; P10153; -.
DR SMR; P10153; 26-161.
DR STRING; 9606.ENSP00000303276; -.
DR BindingDB; P10153; -.
DR ChEMBL; CHEMBL5120; -.
DR PhosphoSite; P10153; -.
DR UniCarbKB; P10153; -.
DR DMDM; 133168; -.
DR PaxDb; P10153; -.
DR PeptideAtlas; P10153; -.
DR PRIDE; P10153; -.
DR Ensembl; ENST00000304625; ENSP00000303276; ENSG00000169385.
DR GeneID; 6036; -.
DR KEGG; hsa:6036; -.
DR UCSC; uc001vyl.1; human.
DR CTD; 6036; -.
DR GeneCards; GC14P021423; -.
DR HGNC; HGNC:10045; RNASE2.
DR HPA; HPA044983; -.
DR MIM; 131410; gene.
DR neXtProt; NX_P10153; -.
DR PharmGKB; PA34413; -.
DR eggNOG; NOG39501; -.
DR HOGENOM; HOG000276882; -.
DR HOVERGEN; HBG008396; -.
DR InParanoid; P10153; -.
DR KO; K01168; -.
DR OMA; RDPPQYP; -.
DR OrthoDB; EOG7KDFCP; -.
DR PhylomeDB; P10153; -.
DR EvolutionaryTrace; P10153; -.
DR GeneWiki; Eosinophil-derived_neurotoxin; -.
DR GenomeRNAi; 6036; -.
DR NextBio; 23525; -.
DR PRO; PR:P10153; -.
DR Bgee; P10153; -.
DR CleanEx; HS_RNASE2; -.
DR Genevestigator; P10153; -.
DR GO; GO:0005576; C:extracellular region; TAS:ProtInc.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0004522; F:pancreatic ribonuclease activity; IEA:UniProtKB-EC.
DR GO; GO:0004540; F:ribonuclease activity; TAS:ProtInc.
DR GO; GO:0006935; P:chemotaxis; IDA:UniProtKB.
DR GO; GO:0006401; P:RNA catabolic process; TAS:ProtInc.
DR Gene3D; 3.10.130.10; -; 1.
DR InterPro; IPR001427; RNaseA.
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 ProDom; PD000535; RNaseA; 1.
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; Chemotaxis; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Endonuclease; Glycoprotein;
KW Hydrolase; Lysosome; Nitration; Nuclease; Polymorphism;
KW Reference proteome; Signal.
FT SIGNAL 1 27
FT CHAIN 28 161 Non-secretory ribonuclease.
FT /FTId=PRO_0000030874.
FT REGION 65 69 Substrate binding.
FT ACT_SITE 42 42 Proton acceptor.
FT ACT_SITE 156 156 Proton donor.
FT MOD_RES 60 60 Nitrated tyrosine.
FT CARBOHYD 34 34 C-linked (Man).
FT /FTId=CAR_000004.
FT CARBOHYD 44 44 N-linked (GlcNAc...).
FT CARBOHYD 86 86 N-linked (GlcNAc...).
FT CARBOHYD 92 92 N-linked (GlcNAc...).
FT CARBOHYD 111 111 N-linked (GlcNAc...).
FT CARBOHYD 119 119 N-linked (GlcNAc...).
FT DISULFID 50 110
FT DISULFID 64 123
FT DISULFID 82 138
FT DISULFID 89 98
FT VARIANT 100 100 H -> Q (in dbSNP:rs8012891).
FT /FTId=VAR_059820.
FT VARIANT 156 156 H -> N (probably inactive;
FT dbSNP:rs146887874).
FT /FTId=VAR_013150.
FT CONFLICT 37 37 W -> R (in Ref. 10; AA sequence).
FT CONFLICT 39 40 ET -> QE (in Ref. 10; AA sequence).
FT CONFLICT 46 46 T -> V (in Ref. 10; AA sequence).
FT CONFLICT 47 47 S -> T (in Ref. 11; AA sequence).
FT HELIX 34 42
FT STRAND 46 49
FT HELIX 50 61
FT STRAND 66 73
FT HELIX 75 82
FT STRAND 98 100
FT STRAND 105 114
FT HELIX 120 122
FT STRAND 124 140
FT TURN 143 145
FT STRAND 151 161
SQ SEQUENCE 161 AA; 18354 MW; 9406C4596CA69038 CRC64;
MVPKLFTSQI CLLLLLGLLA VEGSLHVKPP QFTWAQWFET QHINMTSQQC TNAMQVINNY
QRRCKNQNTF LLTTFANVVN VCGNPNMTCP SNKTRKNCHH SGSQVPLIHC NLTTPSPQNI
SNCRYAQTPA NMFYIVACDN RDQRRDPPQY PVVPVHLDRI I
//
MIM
131410
*RECORD*
*FIELD* NO
131410
*FIELD* TI
*131410 RIBONUCLEASE A FAMILY, 2; RNASE2
;;RNS2;;
EOSINOPHIL-DERIVED NEUROTOXIN; EDN
read more*FIELD* TX
CLONING
Eosinophil-derived neurotoxin is a distinct cationic protein of the
eosinophil's large specific granule known primarily for its ability to
induce ataxia, paralysis, and central nervous system cellular
degeneration in experimental animals (Gordon phenomenon). Rosenberg et
al. (1989) isolated a 725-bp cDNA clone for EDN. The open reading frame
encodes a 134-amino acid polypeptide with a molecular mass of 15.5 kD
and a 27-residue N-terminal hydrophobic leader sequence. The sequence of
the mature polypeptide was identical to that reported for human urinary
ribonuclease and to the N-terminal sequence of human liver ribonuclease.
Similarities to the ribonucleases of pancreas (180440) and angiogenin
(105850) indicate that EDN belongs to the ribonuclease multigene family.
This gene is also symbolized RNS2 for ribonuclease 2. Hamann et al.
(1990) demonstrated the close similarities between the genes encoding
eosinophil-derived neurotoxin and another eosinophil granule protein,
eosinophil cationic protein (RNS3; 131398).
MAPPING
By analysis of somatic cell hybrids and in situ hybridization, Hamann et
al. (1990) showed that both genes are located in the 14q24-q31 region.
Mastrianni et al. (1992) confirmed the assignment to chromosome 14 by
Southern analysis of somatic cell hybrid DNAs.
By genomic sequence analysis, Zhang et al. (2002) mapped the RNASE2 gene
to chromosome 14q11.2, where it is linked to 7 other RNase A superfamily
genes. The authors noted that the entire RNase A cluster spans 368 kb.
EVOLUTION
Zhang and Rosenberg (2002) investigated the evolution of the 2 genes
RNASE2 and RNASE3 that evolved through a duplication event about 31
million years ago in the evolutionary lineage of hominoids and Old World
monkeys. Only 1 copy of the EDN/ECP (RNS3) gene exists in the genomes of
New World monkeys and prosimians. In a commentary on the work of Zhang
and Rosenberg (2002), Benner (2002) noted that the pair of proteins are
relatives of digestive ribonuclease in artiodactyls, the mammalian order
containing ox, giraffe, deer, and antelope. This digestive ribonuclease
was evidently created approximately 40 million years ago, when ruminant
digestion first emerged, to degrade the RNA from bacteria growing in the
rumen. ECP kills bacteria in vitro; EDN inactivates retroviruses in
vitro.
GENETIC VARIABILITY
Zhang and Rosenberg (2002) showed that the mother gene of the duplicated
genes had already possessed a weak antiviral activity before
duplication. After duplication, substitutions at 2 interacting sites
(arg64 to ser and thr132 to arg) resulted in a 13-fold enhancement of
the ribonucleolytic activity of eosinophil-derived neurotoxin. These
substitutions are also necessary for the potent antiviral activity, with
contributions from additional amino acid changes at interacting sites.
Zhang and Rosenberg (2002) found that change in EDN function occurred
only when both interacting sites were altered, indicating the importance
of complementary substitutions in protein evolution. Thus, neutral
substitutions are not simply 'noises' in protein evolution. They may
play constructive roles by setting the intramolecular microenvironment
for further complementary advantageous substitutions. Although
individually the 2 replacements at sites 64 and 132 have little impact
on behavior, each provided the context for the other to have a
consequence. Thus, an inconsequential replacement may set the stage for
a second adaptive replacement. Benner (2002) commented on the usefulness
of correlating events in molecular history with events in the geologic
and paleontologic records.
HISTORY
Using a series of column chromatographies, Yasuda et al. (1988) isolated
and purified to homogeneity one of the human urinary ribonucleases. The
enzyme, which they called RNase1, was found to be a glycoprotein with a
molecular mass of about 16 kD. Rabbit antibody to the purified enzyme
reacted with human urine and sera as well as with the purified enzyme.
Genetic polymorphism of the enzyme was studied by polyacrylamide gel
isoelectric focusing (IEF-PAGE) in a pH range of 5-8, followed by
immunoblotting with antisera specific for the enzyme. Two common
phenotypes were recognized. Family studies were in agreement with
autosomal codominant transmission of 2 alleles, with the 2 common
phenotypes being homozygosity for 1 and heterozygosity for the second.
The frequency of the RNASE1*1 and RNASE1*2 alleles in Japan were found
to be 0.988 and 0.012, respectively.
*FIELD* RF
1. Benner, S. A.: The past as the key to the present: resurrection
of ancient proteins from eosinophils. (Commentary) Proc. Nat. Acad.
Sci. 99: 4760-4761, 2002.
2. Hamann, K. J.; Ten, R. M.; Loegering, D. A.; Jenkins, R. B.; Heise,
M. T.; Schad, C. R.; Pease, L. R.; Gleich, G. J.; Barker, R. L.:
Structure and chromosome localization of the human eosinophil-derived
neurotoxin and eosinophil cationic protein genes: evidence for intronless
coding sequences in the ribonuclease gene superfamily. Genomics 7:
535-546, 1990.
3. Mastrianni, D. M.; Eddy, R. L.; Rosenberg, H. F.; Corrette, S.
E.; Shows, T. B.; Tenen, D. G.; Ackerman, S. J.: Localization of
the human eosinophil Charcot-Leyden crystal protein (lysophospholipase)
gene (CLC) to chromosome 19 and the human ribonuclease 2 (eosinophil-derived
neurotoxin) and ribonuclease 3 (eosinophil cationic protein) genes
(RNS2 and RNS3) to chromosome 14. Genomics 13: 240-242, 1992.
4. Rosenberg, H. F.; Tenen, D. G.; Ackerman, S. J.: Molecular cloning
of the human eosinophil-derived neurotoxin: a member of the ribonuclease
gene family. Proc. Nat. Acad. Sci. 86: 4460-4464, 1989.
5. Yasuda, T.; Sato, W.; Mizuta, K.; Kishi, K.: Genetic polymorphism
of human serum ribonuclease 1 (RNase 1). Am. J. Hum. Genet. 42:
608-614, 1988.
6. Zhang, J.; Dyer, K. D.; Rosenberg, H. F.: RNase 8, a novel RNase
A superfamily ribonuclease expressed uniquely in placenta. Nucleic
Acids Res. 30: 1169-1175, 2002.
7. Zhang, J.; Rosenberg, H. F.: Complementary advantageous substitutions
in the evolution of an antiviral RNase of higher primates. Proc.
Nat. Acad. Sci. 99: 5486-5491, 2002.
*FIELD* CN
Victor A. McKusick - updated: 5/31/2002
*FIELD* CD
Victor A. McKusick: 7/14/1989
*FIELD* ED
wwang: 12/18/2008
cwells: 6/7/2002
terry: 5/31/2002
dholmes: 9/16/1997
mark: 3/25/1997
carol: 5/22/1992
supermim: 3/16/1992
carol: 2/16/1992
carol: 8/22/1990
supermim: 3/20/1990
ddp: 10/26/1989
*RECORD*
*FIELD* NO
131410
*FIELD* TI
*131410 RIBONUCLEASE A FAMILY, 2; RNASE2
;;RNS2;;
EOSINOPHIL-DERIVED NEUROTOXIN; EDN
read more*FIELD* TX
CLONING
Eosinophil-derived neurotoxin is a distinct cationic protein of the
eosinophil's large specific granule known primarily for its ability to
induce ataxia, paralysis, and central nervous system cellular
degeneration in experimental animals (Gordon phenomenon). Rosenberg et
al. (1989) isolated a 725-bp cDNA clone for EDN. The open reading frame
encodes a 134-amino acid polypeptide with a molecular mass of 15.5 kD
and a 27-residue N-terminal hydrophobic leader sequence. The sequence of
the mature polypeptide was identical to that reported for human urinary
ribonuclease and to the N-terminal sequence of human liver ribonuclease.
Similarities to the ribonucleases of pancreas (180440) and angiogenin
(105850) indicate that EDN belongs to the ribonuclease multigene family.
This gene is also symbolized RNS2 for ribonuclease 2. Hamann et al.
(1990) demonstrated the close similarities between the genes encoding
eosinophil-derived neurotoxin and another eosinophil granule protein,
eosinophil cationic protein (RNS3; 131398).
MAPPING
By analysis of somatic cell hybrids and in situ hybridization, Hamann et
al. (1990) showed that both genes are located in the 14q24-q31 region.
Mastrianni et al. (1992) confirmed the assignment to chromosome 14 by
Southern analysis of somatic cell hybrid DNAs.
By genomic sequence analysis, Zhang et al. (2002) mapped the RNASE2 gene
to chromosome 14q11.2, where it is linked to 7 other RNase A superfamily
genes. The authors noted that the entire RNase A cluster spans 368 kb.
EVOLUTION
Zhang and Rosenberg (2002) investigated the evolution of the 2 genes
RNASE2 and RNASE3 that evolved through a duplication event about 31
million years ago in the evolutionary lineage of hominoids and Old World
monkeys. Only 1 copy of the EDN/ECP (RNS3) gene exists in the genomes of
New World monkeys and prosimians. In a commentary on the work of Zhang
and Rosenberg (2002), Benner (2002) noted that the pair of proteins are
relatives of digestive ribonuclease in artiodactyls, the mammalian order
containing ox, giraffe, deer, and antelope. This digestive ribonuclease
was evidently created approximately 40 million years ago, when ruminant
digestion first emerged, to degrade the RNA from bacteria growing in the
rumen. ECP kills bacteria in vitro; EDN inactivates retroviruses in
vitro.
GENETIC VARIABILITY
Zhang and Rosenberg (2002) showed that the mother gene of the duplicated
genes had already possessed a weak antiviral activity before
duplication. After duplication, substitutions at 2 interacting sites
(arg64 to ser and thr132 to arg) resulted in a 13-fold enhancement of
the ribonucleolytic activity of eosinophil-derived neurotoxin. These
substitutions are also necessary for the potent antiviral activity, with
contributions from additional amino acid changes at interacting sites.
Zhang and Rosenberg (2002) found that change in EDN function occurred
only when both interacting sites were altered, indicating the importance
of complementary substitutions in protein evolution. Thus, neutral
substitutions are not simply 'noises' in protein evolution. They may
play constructive roles by setting the intramolecular microenvironment
for further complementary advantageous substitutions. Although
individually the 2 replacements at sites 64 and 132 have little impact
on behavior, each provided the context for the other to have a
consequence. Thus, an inconsequential replacement may set the stage for
a second adaptive replacement. Benner (2002) commented on the usefulness
of correlating events in molecular history with events in the geologic
and paleontologic records.
HISTORY
Using a series of column chromatographies, Yasuda et al. (1988) isolated
and purified to homogeneity one of the human urinary ribonucleases. The
enzyme, which they called RNase1, was found to be a glycoprotein with a
molecular mass of about 16 kD. Rabbit antibody to the purified enzyme
reacted with human urine and sera as well as with the purified enzyme.
Genetic polymorphism of the enzyme was studied by polyacrylamide gel
isoelectric focusing (IEF-PAGE) in a pH range of 5-8, followed by
immunoblotting with antisera specific for the enzyme. Two common
phenotypes were recognized. Family studies were in agreement with
autosomal codominant transmission of 2 alleles, with the 2 common
phenotypes being homozygosity for 1 and heterozygosity for the second.
The frequency of the RNASE1*1 and RNASE1*2 alleles in Japan were found
to be 0.988 and 0.012, respectively.
*FIELD* RF
1. Benner, S. A.: The past as the key to the present: resurrection
of ancient proteins from eosinophils. (Commentary) Proc. Nat. Acad.
Sci. 99: 4760-4761, 2002.
2. Hamann, K. J.; Ten, R. M.; Loegering, D. A.; Jenkins, R. B.; Heise,
M. T.; Schad, C. R.; Pease, L. R.; Gleich, G. J.; Barker, R. L.:
Structure and chromosome localization of the human eosinophil-derived
neurotoxin and eosinophil cationic protein genes: evidence for intronless
coding sequences in the ribonuclease gene superfamily. Genomics 7:
535-546, 1990.
3. Mastrianni, D. M.; Eddy, R. L.; Rosenberg, H. F.; Corrette, S.
E.; Shows, T. B.; Tenen, D. G.; Ackerman, S. J.: Localization of
the human eosinophil Charcot-Leyden crystal protein (lysophospholipase)
gene (CLC) to chromosome 19 and the human ribonuclease 2 (eosinophil-derived
neurotoxin) and ribonuclease 3 (eosinophil cationic protein) genes
(RNS2 and RNS3) to chromosome 14. Genomics 13: 240-242, 1992.
4. Rosenberg, H. F.; Tenen, D. G.; Ackerman, S. J.: Molecular cloning
of the human eosinophil-derived neurotoxin: a member of the ribonuclease
gene family. Proc. Nat. Acad. Sci. 86: 4460-4464, 1989.
5. Yasuda, T.; Sato, W.; Mizuta, K.; Kishi, K.: Genetic polymorphism
of human serum ribonuclease 1 (RNase 1). Am. J. Hum. Genet. 42:
608-614, 1988.
6. Zhang, J.; Dyer, K. D.; Rosenberg, H. F.: RNase 8, a novel RNase
A superfamily ribonuclease expressed uniquely in placenta. Nucleic
Acids Res. 30: 1169-1175, 2002.
7. Zhang, J.; Rosenberg, H. F.: Complementary advantageous substitutions
in the evolution of an antiviral RNase of higher primates. Proc.
Nat. Acad. Sci. 99: 5486-5491, 2002.
*FIELD* CN
Victor A. McKusick - updated: 5/31/2002
*FIELD* CD
Victor A. McKusick: 7/14/1989
*FIELD* ED
wwang: 12/18/2008
cwells: 6/7/2002
terry: 5/31/2002
dholmes: 9/16/1997
mark: 3/25/1997
carol: 5/22/1992
supermim: 3/16/1992
carol: 2/16/1992
carol: 8/22/1990
supermim: 3/20/1990
ddp: 10/26/1989