ID   KLK2_RAT                Reviewed;         259 AA.
AC   P00759;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1988, sequence version 1.
DT   24-JAN-2024, entry version 177.
DE   RecName: Full=Tonin;
DE            EC=3.4.21.35;
DE   AltName: Full=Esterase 1;
DE   AltName: Full=Glandular kallikrein-2;
DE            Short=rGK-2;
DE   AltName: Full=RSKG-5;
DE   AltName: Full=S2 kallikrein;
DE   Flags: Precursor;
GN   Name=Klk2; Synonyms=Klk-2, Ton;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2998455; DOI=10.1021/bi00338a005;
RA   Ashley P.L., MacDonald R.J.;
RT   "Kallikrein-related mRNAs of the rat submaxillary gland: nucleotide
RT   sequences of four distinct types including tonin.";
RL   Biochemistry 24:4512-4520(1985).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2708383; DOI=10.1016/s0021-9258(18)83284-7;
RA   Wines D.R., Brady J.M., Pritchett D.B., Roberts J.L., MacDonald R.J.;
RT   "Organization and expression of the rat kallikrein gene family.";
RL   J. Biol. Chem. 264:7653-7662(1989).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2550051; DOI=10.1021/bi00439a005;
RA   Shai S.Y., Woodley-Miller C., Chao J., Chao L.;
RT   "Characterization of genes encoding rat tonin and a kallikrein-like serine
RT   protease.";
RL   Biochemistry 28:5334-5343(1989).
RN   [4]
RP   PROTEIN SEQUENCE OF 25-259.
RX   PubMed=3038148; DOI=10.1139/o87-042;
RA   Lazure C., Leduc R., Seidah N.G., Thibault G., Genest J., Chretien M.;
RT   "The complete amino acid sequence of rat submaxillary gland tonin does
RT   contain the aspartic acid at the active site: confirmation by protein
RT   sequence analysis.";
RL   Biochem. Cell Biol. 65:321-337(1987).
RN   [5]
RP   PROTEIN SEQUENCE OF 25-103 AND 120-259.
RX   PubMed=6320014; DOI=10.1038/307555a0;
RA   Lazure C., Leduc R., Seidah N.G., Thibault G., Genest J., Chretien M.;
RT   "Amino acid sequence of rat submaxillary tonin reveals similarities to
RT   serine proteases.";
RL   Nature 307:555-558(1984).
RN   [6]
RP   PROTEIN SEQUENCE OF 25-34.
RX   PubMed=2302205; DOI=10.1016/0006-291x(90)91935-l;
RA   Kamada M., Furuhata N., Yamaguchi T., Ikekita M., Kizuki K., Moriya H.;
RT   "Observation of tissue prokallikrein activation by some serine proteases,
RT   arginine esterases in rat submandibular gland.";
RL   Biochem. Biophys. Res. Commun. 166:231-237(1990).
RN   [7]
RP   PROTEIN SEQUENCE OF 25-50, AND CHARACTERIZATION.
RX   PubMed=1315752; DOI=10.1016/s0021-9258(19)50197-1;
RA   Moreau T., Brillard-Bourdet M., Bouhnik J., Gauthier F.;
RT   "Protein products of the rat kallikrein gene family. Substrate
RT   specificities of kallikrein rK2 (tonin) and kallikrein rK9.";
RL   J. Biol. Chem. 267:10045-10051(1992).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
RX   PubMed=2821276; DOI=10.1016/0022-2836(87)90658-9;
RA   Fujinaga M., James M.N.G.;
RT   "Rat submaxillary gland serine protease, tonin. Structure solution and
RT   refinement at 1.8-A resolution.";
RL   J. Mol. Biol. 195:373-396(1987).
CC   -!- FUNCTION: This protein has both trypsin- and chymotrypsin-like
CC       activities, being able to release angiotensin II from angiotensin I or
CC       angiotensinogen.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Preferential cleavage of Arg-|-Xaa bonds in small molecule
CC         substrates. Highly selective action to release kallidin (lysyl-
CC         bradykinin) from kininogen involves hydrolysis of Met-|-Xaa or Leu-|-
CC         Xaa.; EC=3.4.21.35;
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC       Note=Binds 1 zinc ion per subunit.;
CC   -!- SUBUNIT: Monomer.
CC   -!- TISSUE SPECIFICITY: Found in submaxillary gland.
CC   -!- SIMILARITY: Belongs to the peptidase S1 family. Kallikrein subfamily.
CC       {ECO:0000255|PROSITE-ProRule:PRU00274}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; M11565; AAA41466.1; -; mRNA.
DR   EMBL; M23878; AAA42259.1; -; Genomic_DNA.
DR   EMBL; M23877; AAA42259.1; JOINED; Genomic_DNA.
DR   EMBL; M26533; AAA42081.1; -; Genomic_DNA.
DR   PIR; B33359; KQRTTN.
DR   RefSeq; NP_036809.1; NM_012677.1.
DR   PDB; 1TON; X-ray; 1.80 A; A=25-259.
DR   PDBsum; 1TON; -.
DR   AlphaFoldDB; P00759; -.
DR   SMR; P00759; -.
DR   STRING; 10116.ENSRNOP00000025701; -.
DR   MEROPS; S01.172; -.
DR   GlyCosmos; P00759; 2 sites, No reported glycans.
DR   GlyGen; P00759; 2 sites.
DR   iPTMnet; P00759; -.
DR   PhosphoSitePlus; P00759; -.
DR   PaxDb; 10116-ENSRNOP00000025701; -.
DR   Ensembl; ENSRNOT00000107012.1; ENSRNOP00000081904.1; ENSRNOG00000068685.1.
DR   Ensembl; ENSRNOT00055009379; ENSRNOP00055007207; ENSRNOG00055005801.
DR   Ensembl; ENSRNOT00060018708; ENSRNOP00060014580; ENSRNOG00060011050.
DR   Ensembl; ENSRNOT00065051642; ENSRNOP00065042517; ENSRNOG00065029884.
DR   GeneID; 24841; -.
DR   KEGG; rno:24841; -.
DR   UCSC; RGD:3888; rat.
DR   AGR; RGD:3888; -.
DR   CTD; 24841; -.
DR   RGD; 3888; Ton.
DR   eggNOG; KOG3627; Eukaryota.
DR   GeneTree; ENSGT01020000230389; -.
DR   HOGENOM; CLU_006842_1_1_1; -.
DR   InParanoid; P00759; -.
DR   OrthoDB; 4629979at2759; -.
DR   PhylomeDB; P00759; -.
DR   TreeFam; TF331065; -.
DR   EvolutionaryTrace; P00759; -.
DR   PRO; PR:P00759; -.
DR   Proteomes; UP000002494; Chromosome 1.
DR   Bgee; ENSRNOG00000029237; Expressed in thymus and 3 other cell types or tissues.
DR   ExpressionAtlas; P00759; differential.
DR   GO; GO:0030141; C:secretory granule; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; IEA:UniProtKB-EC.
DR   GO; GO:0008236; F:serine-type peptidase activity; IDA:RGD.
DR   GO; GO:0003073; P:regulation of systemic arterial blood pressure; IBA:GO_Central.
DR   GO; GO:0031638; P:zymogen activation; IBA:GO_Central.
DR   CDD; cd00190; Tryp_SPc; 1.
DR   Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR   InterPro; IPR001314; Peptidase_S1A.
DR   InterPro; IPR001254; Trypsin_dom.
DR   InterPro; IPR018114; TRYPSIN_HIS.
DR   InterPro; IPR033116; TRYPSIN_SER.
DR   PANTHER; PTHR24271:SF47; KALLIKREIN-1; 1.
DR   PANTHER; PTHR24271; KALLIKREIN-RELATED; 1.
DR   Pfam; PF00089; Trypsin; 1.
DR   PRINTS; PR00722; CHYMOTRYPSIN.
DR   SMART; SM00020; Tryp_SPc; 1.
DR   SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR   PROSITE; PS50240; TRYPSIN_DOM; 1.
DR   PROSITE; PS00134; TRYPSIN_HIS; 1.
DR   PROSITE; PS00135; TRYPSIN_SER; 1.
DR   Genevisible; P00759; RN.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW   Hydrolase; Metal-binding; Protease; Reference proteome; Serine protease;
KW   Signal; Zinc; Zymogen.
FT   SIGNAL          1..18
FT   PROPEP          19..24
FT                   /note="Activation peptide"
FT                   /evidence="ECO:0000269|PubMed:1315752,
FT                   ECO:0000269|PubMed:2302205, ECO:0000269|PubMed:3038148,
FT                   ECO:0000269|PubMed:6320014"
FT                   /id="PRO_0000028003"
FT   CHAIN           25..259
FT                   /note="Tonin"
FT                   /id="PRO_0000028004"
FT   DOMAIN          25..256
FT                   /note="Peptidase S1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   ACT_SITE        63
FT                   /note="Charge relay system"
FT   ACT_SITE        118
FT                   /note="Charge relay system"
FT   ACT_SITE        211
FT                   /note="Charge relay system"
FT   BINDING         63
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT   BINDING         113
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT   BINDING         115
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT   CARBOHYD        106
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:3038148"
FT   CARBOHYD        189
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:3038148"
FT   DISULFID        31..171
FT   DISULFID        48..64
FT   DISULFID        150..217
FT   DISULFID        182..196
FT   DISULFID        207..232
FT   STRAND          39..54
FT                   /evidence="ECO:0007829|PDB:1TON"
FT   STRAND          57..60
FT                   /evidence="ECO:0007829|PDB:1TON"
FT   HELIX           62..64
FT                   /evidence="ECO:0007829|PDB:1TON"
FT   STRAND          70..74
FT                   /evidence="ECO:0007829|PDB:1TON"
FT   STRAND          86..88
FT                   /evidence="ECO:0007829|PDB:1TON"
FT   STRAND          90..95
FT                   /evidence="ECO:0007829|PDB:1TON"
FT   STRAND          120..126
FT                   /evidence="ECO:0007829|PDB:1TON"
FT   STRAND          149..156
FT                   /evidence="ECO:0007829|PDB:1TON"
FT   STRAND          158..162
FT                   /evidence="ECO:0007829|PDB:1TON"
FT   STRAND          170..177
FT                   /evidence="ECO:0007829|PDB:1TON"
FT   HELIX           179..181
FT                   /evidence="ECO:0007829|PDB:1TON"
FT   HELIX           183..186
FT                   /evidence="ECO:0007829|PDB:1TON"
FT   HELIX           190..193
FT                   /evidence="ECO:0007829|PDB:1TON"
FT   STRAND          194..198
FT                   /evidence="ECO:0007829|PDB:1TON"
FT   STRAND          214..217
FT                   /evidence="ECO:0007829|PDB:1TON"
FT   STRAND          220..225
FT                   /evidence="ECO:0007829|PDB:1TON"
FT   STRAND          239..243
FT                   /evidence="ECO:0007829|PDB:1TON"
FT   HELIX           244..247
FT                   /evidence="ECO:0007829|PDB:1TON"
FT   HELIX           248..257
FT                   /evidence="ECO:0007829|PDB:1TON"
SQ   SEQUENCE   259 AA;  28248 MW;  3D6E60D011F926B4 CRC64;
     MWLQILSLVL SVGRIDAAPP GQSRIVGGYK CEKNSQPWQV AVINEYLCGG VLIDPSWVIT
     AAHCYSNNYQ VLLGRNNLFK DEPFAQRRLV RQSFRHPDYI PLIVTNDTEQ PVHDHSNDLM
     LLHLSEPADI TGGVKVIDLP TKEPKVGSTC LASGWGSTNP SEMVVSHDLQ CVNIHLLSNE
     KCIETYKDNV TDVMLCAGEM EGGKDTCAGD SGGPLICDGV LQGITSGGAT PCAKPKTPAI
     YAKLIKFTSW IKKVMKENP
//