KLK2_RAT
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 03-AUG-2022, entry version 169.
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}.
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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 GlyGen; P00759; 2 sites.
DR iPTMnet; P00759; -.
DR PaxDb; P00759; -.
DR Ensembl; ENSRNOT00000107012; ENSRNOP00000081904; ENSRNOG00000068685.
DR GeneID; 24841; -.
DR KEGG; rno:24841; -.
DR UCSC; RGD:3888; rat.
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 OMA; WIQDTIM; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; P00759; -.
DR TreeFam; TF331065; -.
DR Reactome; R-RNO-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR EvolutionaryTrace; P00759; -.
DR PRO; PR:P00759; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000029237; Expressed in thymus and 3 other tissues.
DR ExpressionAtlas; P00759; baseline and differential.
DR Genevisible; P00759; RN.
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; -; 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 Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
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
