P10153 (RNAS2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Non-secretory ribonuclease
EC=3.1.27.5

Alternative name(s):
Eosinophil-derived neurotoxin
RNase UpI-2
Ribonuclease 2
Short name=RNase 2
Ribonuclease US

Gene names

Name:	RNASE2
Synonyms:	EDN, RNS2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	161 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	This is a non-secretory ribonuclease. It is a pyrimidine specific nuclease with a slight preference for U. Cytotoxin and helminthotoxin. Selectively chemotactic for dendritic cells. Possesses a wide variety of biological activities. Ref.9 Ref.17
Catalytic activity	Endonucleolytic cleavage to nucleoside 3'-phosphates and 3'-phosphooligonucleotides ending in Cp or Up with 2',3'-cyclic phosphate intermediates.
Subunit structure	Interacts with and forms a tight 1:1 complex with RNH1. Dimerization of two such complexes may occur. Ref.17 Ref.22
Subcellular location	Lysosome Probable. Cytoplasmic granule. Note: Matrix of eosinophil's large specific granule.
Tissue specificity	Liver, lung, spleen, leukocytes and body fluids.
Domain	The N-terminal region is necessary for mediating chemotactic activity.
Post-translational modification	A particular signal processing and glycosylation pattern may differentiate the UpI2 RNase, found specifically in pregnant women urine, from other nonsecretory RNases.
Sequence similarities	Belongs to the pancreatic ribonuclease family.

Ontologies

Keywords
Biological process	Chemotaxis
Cellular component	Lysosome
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Endonuclease Hydrolase Nuclease
PTM	Disulfide bond Glycoprotein Nitration
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	RNA catabolic process Traceable author statement Ref.3. Source: ProtInc chemotaxis Inferred from direct assay Ref.18. Source: UniProtKB
Cellular_component	extracellular region Traceable author statement Ref.3. Source: ProtInc lysosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	nucleic acid binding Inferred from electronic annotation. Source: InterPro pancreatic ribonuclease activity Inferred from electronic annotation. Source: EC ribonuclease activity Traceable author statement Ref.3. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 27

27

Ref.8 Ref.9 Ref.10 Ref.11 Ref.13

Chain

28 – 161

134

Non-secretory ribonuclease

PRO_0000030874

Regions

Region

65 – 69

5

Substrate binding

Sites

Active site

42

1

Proton acceptor

Active site

156

1

Proton donor

Amino acid modifications

Modified residue

60

1

Nitrated tyrosine Ref.19

Glycosylation

34

1

C-linked (Man) Ref.14 Ref.16

CAR_000004

Glycosylation

44

1

N-linked (GlcNAc...)

Glycosylation

86

1

N-linked (GlcNAc...)

Glycosylation

92

1

N-linked (GlcNAc...)

Glycosylation

111

1

N-linked (GlcNAc...)

Glycosylation

119

1

N-linked (GlcNAc...)

Disulfide bond

50 ↔ 110

Disulfide bond

64 ↔ 123

Disulfide bond

82 ↔ 138

Disulfide bond

89 ↔ 98

Natural variations

Natural variant

100

1

H → Q.
Corresponds to variant rs8012891 [ dbSNP | Ensembl ].

VAR_059820

Natural variant

156

1

H → N Probably inactive. Ref.5

VAR_013150

Experimental info

Sequence conflict

37

1

W → R AA sequence Ref.10

Sequence conflict

39 – 40

2

ET → QE AA sequence Ref.10

Sequence conflict

46

1

T → V AA sequence Ref.10

Sequence conflict

47

1

S → T AA sequence Ref.11

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

161

Helix Strand Turn

Details...

Helix

34 – 42

9

Beta strand

46 – 49

4

Helix

50 – 61

12

Beta strand

66 – 73

8

Helix

75 – 82

8

Beta strand

98 – 100

3

Beta strand

105 – 114

10

Helix

120 – 122

3

Beta strand

124 – 140

17

Turn

143 – 145

3

Beta strand

151 – 161

11

Sequences

	Sequence		Length	Mass (Da)
	P10153 [UniParc]. Last modified January 1, 1990. Version 2. Checksum: 9406C4596CA69038	FASTA	161	18,354
	10 20 30 40 50 60 MVPKLFTSQI CLLLLLGLLA VEGSLHVKPP QFTWAQWFET QHINMTSQQC TNAMQVINNY 70 80 90 100 110 120 QRRCKNQNTF LLTTFANVVN VCGNPNMTCP SNKTRKNCHH SGSQVPLIHC NLTTPSPQNI 130 140 150 160 SNCRYAQTPA NMFYIVACDN RDQRRDPPQY PVVPVHLDRI I

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of human eosinophil-derived neurotoxin cDNA: identity of deduced amino acid sequence with human nonsecretory ribonucleases." Hamann K.J., Barker R.L., Loegering D.A., Pease L.R., Gleich G.J. Gene 83:161-167(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Eosinophil cationic protein cDNA. Comparison with other toxic cationic proteins and ribonucleases." Barker R.L., Loegering D.A., Ten R.M., Hamann K.J., Pease L.R., Gleich G.J. J. Immunol. 143:952-955(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Molecular cloning of the human eosinophil-derived neurotoxin: a member of the ribonuclease gene family." Rosenberg H.F., Tenen D.G., Ackerman S.J. Proc. Natl. Acad. Sci. U.S.A. 86:4460-4464(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"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." 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. Genomics 7:535-546(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Sequence variation at two eosinophil-associated ribonuclease loci in humans." Zhang J., Rosenberg H.F. Genetics 156:1949-1958(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ASN-156.
[6]	Simonsen C.C., Kennedy J., Comstock L., Ashton N., McGrogan M. Submitted (OCT-1990) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. Tissue: Colon and Leukemia.
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]	"Amino acid sequence of the nonsecretory ribonuclease of human urine." Beintema J.J., Hofsteenge J., Iwama M., Morita T., Ohgi K., Irie M., Sugiyama R.H., Schieven G.L., Dekker C.A., Glitz D.G. Biochemistry 27:4530-4538(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-161.
[9]	"Biochemical and functional similarities between human eosinophil-derived neurotoxin and eosinophil cationic protein: homology with ribonuclease." Gleich G.J., Loegering D.A., Bell M.P., Checkel J.L., Ackerman S.J., McKean D.J. Proc. Natl. Acad. Sci. U.S.A. 83:3146-3150(1986) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-82, FUNCTION.
[10]	"Purification and properties of bovine kidney ribonucleases." Niwata Y., Ohgi K., Sanda A., Takizawa Y., Irie M. J. Biochem. 97:923-934(1985) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-55.
[11]	"Purification and characterization of a ribonuclease from human liver." Sorrentino S., Tucker G.K., Glitz D.G. J. Biol. Chem. 263:16125-16131(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-53. Tissue: Liver.
[12]	"Characterization of a unique nonsecretory ribonuclease from urine of pregnant women." Sakakibara R., Hashida K., Kitahara T., Ishiguro M. J. Biochem. 111:325-330(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 24-43. Tissue: Urine.
[13]	"Characterisation of UGP and its relationship with beta-core fragment." Kardana A., Bagshawe K.D., Coles B., Read D., Taylor M. Br. J. Cancer 67:686-692(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-45. Tissue: Urine.
[14]	"New type of linkage between a carbohydrate and a protein: C-glycosylation of a specific tryptophan residue in human RNase Us." Hofsteenge J., Mueller D.R., de Beer T., Loeffler A., Richter W.J., Vliegenthart J.F.G. Biochemistry 33:13524-13530(1994) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT TRP-34.
[15]	"The hexopyranosyl residue that is C-glycosidically linked to the side chain of tryptophan-7 in human RNase Us is alpha-mannopyranose." de Beer T., Vliegenthart J.F.G., Loeffler A., Hofsteenge J. Biochemistry 34:11785-11789(1995) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE OF C-GLYCOSYLATED GROUP.
[16]	"Recognition signal for C-mannosylation of Trp-7 in RNase 2 consists of sequence Trp-x-x-Trp." Krieg J., Hartmann S., Vicentini A., Glasner W., Hess D., Hofsteenge J. Mol. Biol. Cell 9:301-309(1998) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT TRP-34.
[17]	"Mutational analysis of the complex of human RNase inhibitor and human eosinophil-derived neurotoxin (RNase 2)." Teufel D.P., Kao R.Y., Acharya K.R., Shapiro R. Biochemistry 42:1451-1459(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH RNH1.
[18]	"Eosinophil-derived neurotoxin (EDN), an antimicrobial protein with chemotactic activities for dendritic cells." Yang D., Rosenberg H.F., Chen Q., Dyer K.D., Kurosaka K., Oppenheim J.J. Blood 102:3396-3403(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN CHEMOTAXIS.
[19]	"Post-translational tyrosine nitration of eosinophil granule toxins mediated by eosinophil peroxidase." Ulrich M., Petre A., Youhnovski N., Proemm F., Schirle M., Schumm M., Pero R.S., Doyle A., Checkel J., Kita H., Thiyagarajan N., Acharya K.R., Schmid-Grendelmeier P., Simon H.-U., Schwarz H., Tsutsui M., Shimokawa H., Bellon G. , Lee J.J., Przybylski M., Doering G. J. Biol. Chem. 283:28629-28640(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NITRATION AT TYR-60.
[20]	"X-ray crystallographic structure of recombinant eosinophil-derived neurotoxin at 1.83-A resolution." Mosimann S.C., Newton D.L., Youle R.J., James M.N.G. J. Mol. Biol. 260:540-552(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS).
[21]	"Mapping the ribonucleolytic active site of eosinophil-derived neurotoxin (EDN). High resolution crystal structures of EDN complexes with adenylic nucleotide inhibitors." Leonidas D.D., Boix E., Prill R., Suzuki M., Turton R., Minson K., Swaminathan G.J., Youle R.J., Acharya K.R. J. Biol. Chem. 276:15009-15017(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
[22]	"Molecular recognition of human eosinophil-derived neurotoxin (RNase 2) by placental ribonuclease inhibitor." Iyer S., Holloway D.E., Kumar K., Shapiro R., Acharya K.R. J. Mol. Biol. 347:637-655(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 28-161 IN COMPLEX WITH RNH1, SUBUNIT.
[23]	"Crystal structures of eosinophil-derived neurotoxin (EDN) in complex with the inhibitors 5'-ATP, Ap3A, Ap4A, and Ap5A." Baker M.D., Holloway D.E., Swaminathan G.J., Acharya K.R. Biochemistry 45:416-426(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (0.98 ANGSTROMS) OF 28-161 IN COMPLEX WITH ADP AND ATP.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M30510 mRNA. Translation: AAC82505.1.
M28129 mRNA. Translation: AAA50284.1.
M24157 mRNA. Translation: AAA52337.1.
X16546 Genomic DNA. Translation: CAA34546.1.
AF294007 Genomic DNA. Translation: AAG31577.1.
AF294008 Genomic DNA. Translation: AAG31578.1.
AF294009 Genomic DNA. Translation: AAG31579.1.
AF294010 Genomic DNA. Translation: AAG31580.1.
AF294011 Genomic DNA. Translation: AAG31581.1.
AF294012 Genomic DNA. Translation: AAG31582.1.
AF294013 Genomic DNA. Translation: AAG31583.1.
AF294014 Genomic DNA. Translation: AAG31584.1.
AF294015 Genomic DNA. Translation: AAG31585.1.
X55987 Genomic DNA. Translation: CAA39459.1.
X55988 mRNA. Translation: CAA39460.1.
BC093678 mRNA. Translation: AAH93678.1.
BC093680 mRNA. Translation: AAH93680.1.
BC096059 mRNA. Translation: AAH96059.1.

IPI

IPI00019449.

PIR

A33922. A35328.

RefSeq

NP_002925.1. NM_002934.2.

UniGene

Hs.728.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1GQV	X-ray	0.98	A	28-161	[»]
1HI2	X-ray	1.60	A	28-161	[»]
1HI3	X-ray	1.80	A	28-161	[»]
1HI4	X-ray	1.80	A	28-161	[»]
1HI5	X-ray	1.80	A	28-161	[»]
1K2A	X-ray	1.00	A	26-160	[»]
2BEX	X-ray	1.99	C/D	28-161	[»]
2BZZ	X-ray	0.98	A	28-161	[»]
2C01	X-ray	1.24	X	28-161	[»]
2C02	X-ray	2.00	A	28-161	[»]
2C05	X-ray	1.86	A	28-161	[»]

ProteinModelPortal

P10153.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000303276.

PTM databases

GlycoSuiteDB

P10153.

PhosphoSite

P10153.

Polymorphism databases

DMDM

133168.

Proteomic databases

PaxDb

P10153.

PeptideAtlas

P10153.

PRIDE

P10153.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000304625; ENSP00000303276; ENSG00000169385.

GeneID

6036.

KEGG

hsa:6036.

UCSC

uc001vyl.1. human.

Organism-specific databases

CTD

6036.

GeneCards

GC14P021423.

HGNC

HGNC:10045. RNASE2.

HPA

HPA044983.

MIM

131410. gene.

neXtProt

NX_P10153.

PharmGKB

PA34413.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG39501.

HOGENOM

HOG000276882.

HOVERGEN

HBG008396.

InParanoid

P10153.

KO

K01168.

OMA

TWAQWFE.

OrthoDB

EOG4GXFP0.

PhylomeDB

P10153.

Gene expression databases

Bgee

P10153.

CleanEx

HS_RNASE2.

Genevestigator

P10153.

GermOnline

ENSG00000169385. Homo sapiens.

Family and domain databases

Gene3D

3.10.130.10. 1 hit.

InterPro

IPR001427. RNaseA.
IPR023411. RNaseA_AS.
IPR023412. RNaseA_domain.
[Graphical view]

PANTHER

PTHR11437. PTHR11437. 1 hit.

Pfam

PF00074. RnaseA. 1 hit.
[Graphical view]

PRINTS

PR00794. RIBONUCLEASE.

ProDom

PD000535. RNaseA. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00092. RNAse_Pc. 1 hit.
[Graphical view]

SUPFAM

SSF54076. RNaseA. 1 hit.

PROSITE

PS00127. RNASE_PANCREATIC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P10153.

ChEMBL

CHEMBL5120.

EvolutionaryTrace

P10153.

GenomeRNAi

6036.

NextBio

23525.

SOURCE

Search...

Entry information

Entry name

RNAS2_HUMAN

Accession

Primary (citable) accession number: P10153
Secondary accession number(s): Q52M39, Q9H2B7, Q9UCG7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	January 1, 1990
Last modified:	May 1, 2013
This is version 153 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.