Reviewed, UniProtKB/Swiss-Prot P00759 (KLK2_RAT)

Names and origin

Protein names

Recommended name:
    Tonin
    EC=3.4.21.35
Alternative name(s):
    Esterase 1
    S2 kallikrein
    RGK-2
    RSKG-5

Gene names

Name:	Klk2
Synonyms:	Klk-2, Ton

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	259 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 protein has both trypsin- and chymotrypsin-like activities, being able to release angiotensin II from angiotensin I or angiotensinogen.
Catalytic activity	Preferential cleavage of Arg-|-Xaa bonds in small molecule substrates. Highly selective action to release kallidin (lysyl-bradykinin) from kininogen involves hydrolysis of Met-|-Xaa or Leu-|-Xaa.
Cofactor	Binds 1 zinc ion per subunit.
Subunit structure	Monomer.
Tissue specificity	Found in submaxillary gland.
Sequence similarities	Belongs to the peptidase S1 family. Kallikrein subfamily. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	proteolysis Inferred from electronic annotation. Source: InterPro
Molecular function	serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Propeptide

19 – 24

6

Activation peptide Ref.4 Ref.5 Ref.6 Ref.7

PRO_0000028003

Chain

25 – 259

235

Tonin

PRO_0000028004

Regions

Domain

25 – 256

232

Peptidase S1

Sites

Active site

63

1

Charge relay system

Active site

118

1

Charge relay system

Active site

211

1

Charge relay system

Metal binding

63

1

Zinc

Metal binding

113

1

Zinc

Metal binding

115

1

Zinc

Amino acid modifications

Glycosylation

106

1

N-linked (GlcNAc...) Ref.4

Glycosylation

189

1

N-linked (GlcNAc...) Ref.4

Disulfide bond

31 ↔ 171

Disulfide bond

48 ↔ 64

Disulfide bond

150 ↔ 217

Disulfide bond

182 ↔ 196

Disulfide bond

207 ↔ 232

Secondary structure

1

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259

Helix Strand Turn

Details...

Beta strand

39 – 54

16

Beta strand

57 – 60

4

Helix

62 – 64

3

Beta strand

70 – 74

5

Beta strand

86 – 88

3

Beta strand

90 – 95

6

Beta strand

120 – 126

7

Beta strand

149 – 156

8

Beta strand

158 – 162

5

Beta strand

170 – 177

8

Helix

179 – 181

3

Helix

183 – 186

4

Helix

190 – 193

4

Beta strand

194 – 198

5

Beta strand

214 – 217

4

Beta strand

220 – 225

6

Beta strand

239 – 243

5

Helix

244 – 247

4

Helix

248 – 257

10

Sequences

	Sequence		Length	Mass (Da)
	P00759-1 [UniParc]. Last modified April 1, 1988. Version 1. Checksum: 3D6E60D011F926B4	FASTA	259	28,248
	10 20 30 40 50 60 MWLQILSLVL SVGRIDAAPP GQSRIVGGYK CEKNSQPWQV AVINEYLCGG VLIDPSWVIT 70 80 90 100 110 120 AAHCYSNNYQ VLLGRNNLFK DEPFAQRRLV RQSFRHPDYI PLIVTNDTEQ PVHDHSNDLM 130 140 150 160 170 180 LLHLSEPADI TGGVKVIDLP TKEPKVGSTC LASGWGSTNP SEMVVSHDLQ CVNIHLLSNE 190 200 210 220 230 240 KCIETYKDNV TDVMLCAGEM EGGKDTCAGD SGGPLICDGV LQGITSGGAT PCAKPKTPAI 250 YAKLIKFTSW IKKVMKENP

References

[1]	"Kallikrein-related mRNAs of the rat submaxillary gland: nucleotide sequences of four distinct types including tonin." Ashley P.L., MacDonald R.J. Biochemistry 24:4512-4520(1985) [PubMed: 2998455] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Organization and expression of the rat kallikrein gene family." Wines D.R., Brady J.M., Pritchett D.B., Roberts J.L., MacDonald R.J. J. Biol. Chem. 264:7653-7662(1989) [PubMed: 2708383] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Characterization of genes encoding rat tonin and a kallikrein-like serine protease." Shai S.Y., Woodley-Miller C., Chao J., Chao L. Biochemistry 28:5334-5343(1989) [PubMed: 2550051] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The complete amino acid sequence of rat submaxillary gland tonin does contain the aspartic acid at the active site: confirmation by protein sequence analysis." Lazure C., Leduc R., Seidah N.G., Thibault G., Genest J., Chretien M. Biochem. Cell Biol. 65:321-337(1987) [PubMed: 3038148] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-259.
[5]	"Amino acid sequence of rat submaxillary tonin reveals similarities to serine proteases." Lazure C., Leduc R., Seidah N.G., Thibault G., Genest J., Chretien M. Nature 307:555-558(1984) [PubMed: 6320014] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-103 AND 120-259.
[6]	"Observation of tissue prokallikrein activation by some serine proteases, arginine esterases in rat submandibular gland." Kamada M., Furuhata N., Yamaguchi T., Ikekita M., Kizuki K., Moriya H. Biochem. Biophys. Res. Commun. 166:231-237(1990) [PubMed: 2302205] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-34.
[7]	"Protein products of the rat kallikrein gene family. Substrate specificities of kallikrein rK2 (tonin) and kallikrein rK9." Moreau T., Brillard-Bourdet M., Bouhnik J., Gauthier F. J. Biol. Chem. 267:10045-10051(1992) [PubMed: 1315752] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-50, CHARACTERIZATION.
[8]	"Rat submaxillary gland serine protease, tonin. Structure solution and refinement at 1.8-A resolution." Fujinaga M., James M.N.G. J. Mol. Biol. 195:373-396(1987) [PubMed: 2821276] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).

Cross-references

Sequence databases

EMBLGenBankDDBJ

M11565 mRNA. Translation: AAA41466.1.
M23878, M23877 Genomic DNA. Translation: AAA42259.1.
M26533 Genomic DNA. Translation: AAA42081.1.

IPI

IPI00212752.

PIR

KQRTTN. B33359.

RefSeq

NP_036809.1.

UniGene

Rn.9882

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TON	X-ray	1.80	A	25-259	[»]

ModBase

Search...

Protein family/group databases

MEROPS

S01.172.

Genome annotation databases

Ensembl

ENSRNOG00000029237. Rattus norvegicus. [Contig view]

GeneID

24841.

KEGG

rno:24841.

Organism-specific databases

RGD

3888. Ton.

Phylogenomic databases

HOVERGEN

P00759.

OMA

P00759. EDIMIAN.

Enzyme and pathway databases

BRENDA

3.4.21.35. 248.

Gene expression databases

ArrayExpress

P00759.

GermOnline

ENSRNOG00000029237. Rattus norvegicus.

Family and domain databases

InterPro

IPR018114. Peptidase_S1/S6_AS.
IPR001254. Peptidase_S1_S6.
IPR001314. Peptidase_S1A.
[Graphical view]

Pfam

PF00089. Trypsin. 1 hit.
[Graphical view]

PRINTS

PR00722. CHYMOTRYPSIN.

SMART

SM00020. Tryp_SPc. 1 hit.
[Graphical view]

PROSITE

PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

604592.

Entry information

Entry name

KLK2_RAT

Accession

Primary (citable) accession number: P00759

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	April 1, 1988
Last modified:	June 16, 2009
This is version 88 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)