P07998 (RNAS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ribonuclease pancreatic
EC=3.1.27.5

Alternative name(s):
HP-RNase
RIB-1
RNase UpI-1
Ribonuclease 1
Short name=RNase 1
Ribonuclease A
Short name=RNase A

Gene names

Name:	RNASE1
Synonyms:	RIB1, RNS1

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	156 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	Endonuclease that catalyzes the cleavage of RNA on the 3' side of pyrimidine nucleotides. Acts on single stranded and double stranded RNA. Ref.19
Catalytic activity	Endonucleolytic cleavage to nucleoside 3'-phosphates and 3'-phosphooligonucleotides ending in Cp or Up with 2',3'-cyclic phosphate intermediates.
Subunit structure	Monomer. Interacts with and forms tight 1:1 complexes with RNH1. Dimerization of two such complexes may occur. Interaction with RNH1 inhibits this protein. Ref.19
Subcellular location	Secreted.
Tissue specificity	Pancreas and other tissues and body fluids (indicating it may have other physiological functions besides its role in digestion).
Post-translational modification	N-linked glycans are of complex type.
Sequence similarities	Belongs to the pancreatic ribonuclease family.

Ontologies

Keywords
Cellular component	Secreted
Domain	Signal
Molecular function	Endonuclease Hydrolase Nuclease
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	nucleic acid binding Inferred from electronic annotation. Source: InterPro pancreatic ribonuclease activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RNH1	P13489	2	EBI-2823523,EBI-1237106

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 28

28

Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15

Chain

29 – 156

128

Ribonuclease pancreatic

PRO_0000030921

Regions

Region

69 – 73

5

Substrate binding By similarity

Sites

Active site

40

1

Proton acceptor

Active site

147

1

Proton donor

Binding site

35

1

Substrate By similarity

Binding site

38

1

Substrate By similarity

Binding site

94

1

Substrate By similarity

Binding site

113

1

Substrate By similarity

Amino acid modifications

Glycosylation

62

1

N-linked (GlcNAc...); partial Ref.11

Glycosylation

104

1

N-linked (GlcNAc...) Ref.11

Glycosylation

116

1

N-linked (GlcNAc...) Ref.11

Disulfide bond

54 ↔ 112

Ref.18 Ref.19 Ref.20

Disulfide bond

68 ↔ 123

Ref.18 Ref.19 Ref.20

Disulfide bond

86 ↔ 138

Ref.18 Ref.19 Ref.20

Disulfide bond

93 ↔ 100

Ref.18 Ref.19 Ref.20

Experimental info

Mutagenesis

67

1

R → D: Substantially decreases binding affinity for RNH1 but maintains high conformational stability; when associated with D-95, A-116, D-117 and D-119. Ref.16 Ref.19

Mutagenesis

95

1

N → D: Substantially decreases binding affinity for RNH1 but maintains high conformational stability; when associated with D-67, A-116, D-117 and D-119. Ref.16 Ref.19

Mutagenesis

116 – 117

2

NG → RS: No effect on inhibition by RNH1. Ref.16 Ref.19

Mutagenesis

116

1

N → A: Substantially decreases binding affinity for RNH1 but maintains high conformational stability; when associated with D-67, D-95, D-117 and D-119. Ref.16 Ref.19

Mutagenesis

117

1

G → D: Substantially decreases binding affinity for RNH1 but maintains high conformational stability; when associated with D-67, D-95, A-116 and D-119. Ref.16 Ref.19

Mutagenesis

119

1

R → D: Substantially decreases binding affinity for RNH1 but maintains high conformational stability; when associated with D-67, D-95, A-116 and D-117. Ref.16 Ref.19

Sequence conflict

2

1

A → G in CAA55817. Ref.7

Sequence conflict

4

1

Missing in AAB35096. Ref.8

Sequence conflict

9 – 11

3

RLL → VLP in AAB35096. Ref.8

Sequence conflict

16 – 22

7

ILLVLGW → VLLLVR in AAB35096. Ref.8

Sequence conflict

67

1

R → L in CAG29314. Ref.4

Sequence conflict

151

1

S → T in CAA55817. Ref.7

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

156

Helix Strand Turn

Details...

Helix

32 – 40

9

Turn

47 – 50

4

Helix

53 – 60

8

Turn

61 – 64

4

Beta strand

65 – 67

3

Beta strand

70 – 75

6

Helix

79 – 83

5

Helix

84 – 87

4

Beta strand

88 – 92

5

Beta strand

96 – 102

7

Beta strand

107 – 114

8

Beta strand

120 – 122

3

Beta strand

125 – 139

15

Turn

140 – 143

4

Beta strand

144 – 152

9

Sequences

	Sequence		Length	Mass (Da)
	P07998 [UniParc]. Last modified February 1, 1996. Version 4. Checksum: F63B17B8B55115F9	FASTA	156	17,644
	10 20 30 40 50 60 MALEKSLVRL LLLVLILLVL GWVQPSLGKE SRAKKFQRQH MDSDSSPSSS STYCNQMMRR 70 80 90 100 110 120 RNMTQGRCKP VNTFVHEPLV DVQNVCFQEK VTCKNGQGNC YKSNSSMHIT DCRLTNGSRY 130 140 150 PNCAYRTSPK ERHIIVACEG SPYVPVHFDA SVEDST

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence encoding human pancreatic ribonuclease." Seno M., Fatami J.I., Kosaka M., Seno S., Yamada H. Biochim. Biophys. Acta 1218:466-468(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Pancreas.
[2]	"Duplication and divergence of two distinct pancreatic ribonuclease genes in leaf-eating African and Asian colobine monkeys." Schienman J.E., Holt R.A., Auerbach M.R., Stewart C.B. Mol. Biol. Evol. 23:1465-1479(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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]. Tissue: Pancreas and Prostate.
[7]	"Primary structure of the coding part of the gene for human pancreatic ribonuclease and its chromosomal location." Kochetov A.V., Lukasheva V.V., Filipenko M.L., Mertvetsov N.P., Rivkin M.I. Bioorg. Khim. 21:691-694(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-152. Tissue: Placenta.
[8]	"Expression in mammalian cells, purification and characterization of recombinant human pancreatic ribonuclease." Russo N., de Nigris M., Ciardiello A., Di Donato A., D'Alessio G. FEBS Lett. 369:352-352(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-155.
[9]	"The DNA sequences of the human and hamster secretory ribonucleases determined with the polymerase chain reaction (PCR)." Haugg M., Schein C.H. Nucleic Acids Res. 20:612-612(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 23-149. Tissue: Placenta.
[10]	"The amino acid sequence of human pancreatic ribonuclease." Beintema J.J., Wietzes P., Weickmann J.L., Glitz D.G. Anal. Biochem. 136:48-64(1984) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 29-156. Tissue: Pancreas.
[11]	"Differences in glycosylation pattern of human secretory ribonucleases." Beintema J.J., Blank A., Schieven G.L., Dekker C.A., Sorrentino S., Libonati M. Biochem. J. 255:501-505(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 29-156, GLYCOSYLATION AT ASN-62; ASN-104 AND ASN-116.
[12]	"Purification and characterization of three ribonucleases from human kidney: comparison with urine ribonucleases." Mizuta K., Awazu S., Yasuda T., Kishi K. Arch. Biochem. Biophys. 281:144-151(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 29-47.
[13]	"A putative mouse oocyte maturation inhibitory protein from urine of pregnant women: N-terminal sequence homology with human nonsecretory ribonuclease." Sakakibara R., Hashida K., Tominaga N., Sakai K., Ishiguro M., Imamura S., Ohmatsu F., Sato E. Chem. Pharm. Bull. 39:146-149(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 29-43.
[14]	"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 29-48. Tissue: Urine.
[15]	"Two distinct secretory ribonucleases from human cerebrum: purification, characterization and relationships to other ribonucleases." Yasuda T., Nadano D., Takeshita H., Kishi K. Biochem. J. 296:617-625(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 29-49.
[16]	"Three-dimensional structure of a human pancreatic ribonuclease variant, a step forward in the design of cytotoxic ribonucleases." Pous J., Canals A., Terzyan S.S., Guasch A., Benito A., Ribo M., Vilanova M., Coll M. J. Mol. Biol. 303:49-60(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 29-156, MUTAGENESIS OF 116-ASN-GLY-117.
[17]	"Three-dimensional structure of human RNase 1 delta N7 at 1.9 A resolution." Pous J., Mallorqui-Fernandez G., Peracaula R., Terzyan S.S., Futami J., Tada H., Yamada H., Seno M., de Llorens R., Gomis-Rueth F.-X., Coll M. Acta Crystallogr. D 57:498-505(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 29-156.
[18]	"The structure of an engineered domain-swapped ribonuclease dimer and its implications for the evolution of proteins toward oligomerization." Canals A., Pous J., Guasch A., Benito A., Ribo M., Vilanova M., Coll M. Structure 9:967-976(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 29-156, DISULFIDE BONDS.
[19]	"Inhibition of human pancreatic ribonuclease by the human ribonuclease inhibitor protein." Johnson R.J., McCoy J.G., Bingman C.A., Phillips G.N. Jr., Raines R.T. J. Mol. Biol. 368:434-449(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 29-156 IN COMPLEX WITH RNH1, FUNCTION, SUBUNIT, INTERACTION WITH RNH1, DISULFIDE BONDS, MUTAGENESIS OF ARG-67; ASN-95; ASN-116; GLY-117 AND ARG-119.
[20]	"'Crystal lattice engineering,' an approach to engineer protein crystal contacts by creating intermolecular symmetry: crystallization and structure determination of a mutant human RNase 1 with a hydrophobic interface of leucines." Yamada H., Tamada T., Kosaka M., Miyata K., Fujiki S., Tano M., Moriya M., Yamanishi M., Honjo E., Tada H., Ino T., Yamaguchi H., Futami J., Seno M., Nomoto T., Hirata T., Yoshimura M., Kuroki R. Protein Sci. 16:1389-1397(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 29-156, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D26129 mRNA. Translation: BAA05124.1.
DQ494867 Genomic DNA. Translation: ABF00144.1.
AK312100 mRNA. Translation: BAG35036.1.
CR450318 mRNA. Translation: CAG29314.1.
CH471078 Genomic DNA. Translation: EAW66437.1.
CH471078 Genomic DNA. Translation: EAW66438.1.
BC005324 mRNA. Translation: AAH05324.1.
BC022882 mRNA. Translation: AAH22882.1.
X79235 Genomic DNA. Translation: CAA55817.1.
S79281 mRNA. Translation: AAB35096.1.
X62946 Genomic DNA. Translation: CAA44718.1.

IPI

IPI00014048.

PIR

I53530.
NRHU1. S45003.

RefSeq

NP_002924.1. NM_002933.4.
NP_937875.1. NM_198232.2.
NP_937877.1. NM_198234.2.
NP_937878.1. NM_198235.2.

UniGene

Hs.78224.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DZA	X-ray	1.65	A/B	29-156	[»]
1E21	X-ray	1.90	A	29-156	[»]
1H8X	X-ray	2.00	A/B	29-156	[»]
1Z7X	X-ray	1.95	X/Z	29-156	[»]
2E0J	X-ray	1.60	A/B	29-156	[»]
2E0L	X-ray	1.60	A/B	29-156	[»]
2E0M	X-ray	1.70	A/B	29-156	[»]
2E0O	X-ray	2.00	A/B	29-156	[»]
2K11	NMR	-	A	29-155	[»]
2Q4G	X-ray	1.95	X/Z	29-156	[»]
3F8G	X-ray	2.60	A/B	29-153	[»]

ProteinModelPortal

P07998.

ModBase

Search...

Protein-protein interaction databases

IntAct

P07998. 5 interactions.

STRING

9606.ENSP00000344193.

PTM databases

PhosphoSite

P07998.

Polymorphism databases

DMDM

1350818.

Proteomic databases

PaxDb

P07998.

PeptideAtlas

P07998.

PRIDE

P07998.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000340900; ENSP00000344193; ENSG00000129538.
ENST00000397967; ENSP00000381057; ENSG00000129538.
ENST00000397970; ENSP00000381060; ENSG00000129538.
ENST00000412779; ENSP00000399493; ENSG00000129538.

GeneID

6035.

KEGG

hsa:6035.

UCSC

uc001vyf.3. human.

Organism-specific databases

CTD

6035.

GeneCards

GC14M021269.

HGNC

HGNC:10044. RNASE1.

HPA

HPA001140.

MIM

180440. gene.

neXtProt

NX_P07998.

PharmGKB

PA34412.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG40319.

HOVERGEN

HBG008396.

InParanoid

P07998.

KO

K01168.

OMA

NCAYRTS.

OrthoDB

EOG4TMR3F.

PhylomeDB

P07998.

Gene expression databases

ArrayExpress

P07998.

Bgee

P07998.

CleanEx

HS_RNASE1.

Genevestigator

P07998.

GermOnline

ENSG00000129538. 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

P07998.

ChEMBL

CHEMBL5425.

ChiTaRS

RNASE1. human.

EvolutionaryTrace

P07998.

GenomeRNAi

6035.

NextBio

23515.

SOURCE

Search...

Entry information

Entry name

RNAS1_HUMAN

Accession

Primary (citable) accession number: P07998
Secondary accession number(s): B2R589 , D3DS06, Q16830, Q16869, Q1KHR2, Q6ICS5, Q9UCB4, Q9UCB5

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	February 1, 1996
Last modified:	May 1, 2013
This is version 148 of the entry and version 4 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.