KGP_PORG3
ID KGP_PORG3 Reviewed; 1723 AA.
AC B2RLK2;
DT 13-JUL-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-2008, sequence version 1.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=Lys-gingipain {ECO:0000303|PubMed:9538207};
DE EC=3.4.22.47 {ECO:0000269|PubMed:18295742, ECO:0000269|PubMed:9538207};
DE AltName: Full=Lysine-specific cysteine proteinase Kgp {ECO:0000303|PubMed:9538207, ECO:0000312|EMBL:BAG34247.1};
DE Contains:
DE RecName: Full=Lys-gingipain catalytic subunit {ECO:0000250|UniProtKB:Q51817, ECO:0000303|PubMed:9538207};
DE Contains:
DE RecName: Full=39 kDa adhesin {ECO:0000250|UniProtKB:Q51817};
DE Contains:
DE RecName: Full=15 kDa adhesin {ECO:0000250|UniProtKB:Q51817};
DE Contains:
DE RecName: Full=44 kDa adhesin {ECO:0000250|UniProtKB:Q51817};
DE Flags: Precursor;
GN Name=kgp {ECO:0000312|EMBL:BAG34247.1}; OrderedLocusNames=PGN_1728;
OS Porphyromonas gingivalis (strain ATCC 33277 / DSM 20709 / CIP 103683 / JCM
OS 12257 / NCTC 11834 / 2561).
OC Bacteria; Bacteroidetes; Bacteroidia; Bacteroidales; Porphyromonadaceae;
OC Porphyromonas.
OX NCBI_TaxID=431947;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 33277 / DSM 20709 / CIP 103683 / JCM 12257 / NCTC 11834 / 2561;
RX PubMed=18524787; DOI=10.1093/dnares/dsn013;
RA Naito M., Hirakawa H., Yamashita A., Ohara N., Shoji M., Yukitake H.,
RA Nakayama K., Toh H., Yoshimura F., Kuhara S., Hattori M., Hayashi T.,
RA Nakayama K.;
RT "Determination of the genome sequence of Porphyromonas gingivalis strain
RT ATCC 33277 and genomic comparison with strain W83 revealed extensive genome
RT rearrangements in P. gingivalis.";
RL DNA Res. 15:215-225(2008).
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=9538207; DOI=10.1093/oxfordjournals.jbchem.a021937;
RA Abe N., Kadowaki T., Okamoto K., Nakayama K., Ohishi M., Yamamoto K.;
RT "Biochemical and functional properties of lysine-specific cysteine
RT proteinase (Lys-gingipain) as a virulence factor of Porphyromonas
RT gingivalis in periodontal disease.";
RL J. Biochem. 123:305-312(1998).
RN [3] {ECO:0000305}
RP FUNCTION.
RX PubMed=15576324; DOI=10.1515/bc.2004.135;
RA Abe N., Baba A., Takii R., Nakayama K., Kamaguchi A., Shibata Y., Abiko Y.,
RA Okamoto K., Kadowaki T., Yamamoto K.;
RT "Roles of Arg- and Lys-gingipains in coaggregation of Porphyromonas
RT gingivalis: identification of its responsible molecules in translation
RT products of rgpA, kgp, and hagA genes.";
RL Biol. Chem. 385:1041-1047(2004).
RN [4] {ECO:0000305}
RP POLYMORPHISM.
RX PubMed=15297553; DOI=10.1128/jcm.42.8.3873-3876.2004;
RA Nadkarni M.A., Nguyen K.A., Chapple C.C., DeCarlo A.A., Jacques N.A.,
RA Hunter N.;
RT "Distribution of Porphyromonas gingivalis biotypes defined by alleles of
RT the kgp (Lys-gingipain) gene.";
RL J. Clin. Microbiol. 42:3873-3876(2004).
RN [5] {ECO:0000305}
RP ACTIVE SITE, MUTAGENESIS OF CYS-476; 476-CYS-CYS-477 AND CYS-477, AND
RP CATALYTIC ACTIVITY.
RX PubMed=18295742; DOI=10.1016/j.archoralbio.2008.01.004;
RA Ishida Y., Hu J., Sakai E., Kadowaki T., Yamamoto K., Tsukuba T., Kato Y.,
RA Nakayama K., Okamoto K.;
RT "Determination of active site of lysine-specific cysteine proteinase (Lys-
RT gingipain) by use of a Porphyromonas gingivalis plasmid system.";
RL Arch. Oral Biol. 53:538-544(2008).
CC -!- FUNCTION: Cysteine proteinase with a strong preference for substrates
CC with Lys in the P1 position. Hydrolyzes bovine hemoglobin, bovine serum
CC albumin, casein, human placental type I collagen and human IgA and IgG.
CC Disrupts the functions of polymorphonuclear leukocytes. May act as a
CC virulence factor in the development of peridontal disease. Involved in
CC the coaggregation of P.gingivalis with other oral bacteria.
CC {ECO:0000269|PubMed:15576324, ECO:0000269|PubMed:9538207}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Endopeptidase with strict specificity for lysyl bonds.;
CC EC=3.4.22.47; Evidence={ECO:0000269|PubMed:18295742,
CC ECO:0000269|PubMed:9538207};
CC -!- ACTIVITY REGULATION: Activated by the thiol-reducing agents cysteine,
CC 2-mercaptoethanol and dithiothreitol. Inhibited by idoacetamide,
CC idoacetic acid, leupeptin, tosyl-L-lysine and tosyl-L-phenylalanine.
CC Not inhibited by elastatinal, chymostatin, cystatins, alpha1-
CC antichymotrypsin or the serine protease inhibitors phenylmethylsulfonyl
CC fluoride and diisopropylfluorophosphate. Not inhibited by metal ion
CC chelators. Inhibited by the heavy metal ions Fe(3+), Zn(2+), Cu(2+) and
CC Mn(2+). {ECO:0000269|PubMed:9538207}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.5. Activity remains high from pH 6.5 to 9.5. Loses
CC 60% of its activity following incubation at pH 3.5 for 5 minutes.
CC {ECO:0000269|PubMed:9538207};
CC Temperature dependence:
CC Only retains 40% of activity after incubation at 60 degrees Celsius
CC for 10 minutes. {ECO:0000269|PubMed:9538207};
CC -!- SUBCELLULAR LOCATION: [Lys-gingipain catalytic subunit]: Secreted
CC {ECO:0000250|UniProtKB:P72194}.
CC -!- PTM: Proteolytically cleaved into a catalytic subunit and three
CC adhesins. Arg-gingipain is involved in this post-translational
CC processing (By similarity). {ECO:0000250|UniProtKB:P72194,
CC ECO:0000250|UniProtKB:Q51817}.
CC -!- POLYMORPHISM: Several forms of kgp with differences at the C-terminus
CC exist in different P.gingivalis strains. {ECO:0000269|PubMed:15297553}.
CC -!- SIMILARITY: Belongs to the peptidase C25 family. {ECO:0000255}.
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DR EMBL; AP009380; BAG34247.1; -; Genomic_DNA.
DR RefSeq; WP_012458488.1; NZ_CP025930.1.
DR AlphaFoldDB; B2RLK2; -.
DR SMR; B2RLK2; -.
DR STRING; 431947.PGN_1728; -.
DR ChEMBL; CHEMBL3308977; -.
DR MEROPS; C25.002; -.
DR PRIDE; B2RLK2; -.
DR EnsemblBacteria; BAG34247; BAG34247; PGN_1728.
DR GeneID; 29256891; -.
DR KEGG; pgn:PGN_1728; -.
DR eggNOG; COG1974; Bacteria.
DR HOGENOM; CLU_240727_0_0_10; -.
DR BioCyc; MetaCyc:HMPREF1322_RS02410-MON; -.
DR BioCyc; PGIN431947:G1G2V-1940-MON; -.
DR BRENDA; 3.4.22.47; 756.
DR PHI-base; PHI:7889; -.
DR Proteomes; UP000008842; Chromosome.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0044179; P:hemolysis in another organism; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR Gene3D; 2.60.40.10; -; 4.
DR Gene3D; 2.60.40.3800; -; 1.
DR Gene3D; 3.40.50.10390; -; 1.
DR InterPro; IPR029030; Caspase-like_dom_sf.
DR InterPro; IPR011628; Cleaved_adhesin.
DR InterPro; IPR001769; Gingipain.
DR InterPro; IPR029031; Gingipain_N_sf.
DR InterPro; IPR038490; Gingipain_propep_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR018832; Pept_C25_gingipain_C.
DR InterPro; IPR005536; Peptidase_C25_Ig-like_domain.
DR InterPro; IPR012600; Propeptide_C25.
DR Pfam; PF07675; Cleaved_Adhesin; 3.
DR Pfam; PF10365; DUF2436; 1.
DR Pfam; PF01364; Peptidase_C25; 1.
DR Pfam; PF03785; Peptidase_C25_C; 1.
DR Pfam; PF08126; Propeptide_C25; 1.
DR SUPFAM; SSF52129; SSF52129; 1.
PE 1: Evidence at protein level;
KW Calcium; Hydrolase; Metal-binding; Protease; Secreted; Signal;
KW Thiol protease; Virulence; Zymogen.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PROPEP 25..228
FT /evidence="ECO:0000250|UniProtKB:Q51817, ECO:0000255"
FT /id="PRO_0000395387"
FT CHAIN 229..1723
FT /note="Lys-gingipain"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT /id="PRO_0000395388"
FT CHAIN 229..?
FT /note="Lys-gingipain catalytic subunit"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT /id="PRO_0000395389"
FT CHAIN 738..?
FT /note="39 kDa adhesin"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT /id="PRO_0000395390"
FT CHAIN 1156..?
FT /note="15 kDa adhesin"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT /id="PRO_0000395391"
FT CHAIN 1291..?
FT /note="44 kDa adhesin"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT /id="PRO_0000395392"
FT REGION 964..985
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 444
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P95493"
FT ACT_SITE 477
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:18295742"
FT BINDING 313
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 337
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 339
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 341
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 343
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 482
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 491
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 987
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 989
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 1000
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 1002
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 1004
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 1006
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 1021
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 1023
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 1042
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 1145
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 1146
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 1430
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 1432
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 1444
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 1446
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 1448
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 1450
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 1480
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 1495
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT BINDING 1585
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT SITE 228..229
FT /note="Cleavage; site 1"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT SITE 737..738
FT /note="Cleavage; site 2"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT SITE 1155..1156
FT /note="Cleavage; site 3"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT SITE 1290..1291
FT /note="Cleavage; site 4"
FT /evidence="ECO:0000250|UniProtKB:Q51817"
FT MUTAGEN 476..477
FT /note="CC->AA: Loss of activity."
FT /evidence="ECO:0000269|PubMed:18295742"
FT MUTAGEN 476
FT /note="C->A: No effect on activity."
FT /evidence="ECO:0000269|PubMed:18295742"
FT MUTAGEN 477
FT /note="C->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:18295742"
SQ SEQUENCE 1723 AA; 187262 MW; 5628963D251493EB CRC64;
MRKLLLLIAA SLLGVGLYAQ SAKIKLDAPT TRTTCTNNSF KQFDASFSFN EVELTKVETK
GGTFASVSIP GAFPTGEVGS PEVPAVRKLI AVPVGATPVV RVKSFTEQVY SLNQYGSEKL
MPHQPSMSKS DDPEKVPFVY NAAAYARKGF VGQELTQVEM LGTMRGVRIA ALTINPVQYD
VVANQLKVRN NIEIEVSFQG ADEVATQRLY DASFSPYFET AYKQLFNRDV YTDHGDLYNT
PVRMLVVAGA KFKEALKPWL TWKAQKGFYL DVHYTDEAEV GTTNASIKAF IHKKYNDGLA
ASAAPVFLAL VGDTDVISGE KGKKTKKVTD LYYSAVDGDY FPEMYTFRMS ASSPEELTNI
IDKVLMYEKA TMPDKSYLEK ALLIAGADSY WNPKIGQQTI KYAVQYYYNQ DHGYTDVYSY
PKAPYTGCYS HLNTGVGFAN YTAHGSETSW ADPSLTATQV KALTNKDKYF LAIGNCCVTA
QFDYPQPCFG EVMTRVKEKG AYAYIGSSPN SYWGEDYYWS VGANAVFGVQ PTFEGTSMGS
YDATFLEDSY NTVNSIMWAG NLAATHAGNI GNITHIGAHY YWEAYHVLGD GSVMPYRAMP
KTNTYTLPAS LPQNQASYSI QASAGSYVAI SKDGVLYGTG VANASGVATV NMTKQITENG
NYDVVITRSN YLPVIKQIQA GEPSPYQPVS NLTATTQGQK VTLKWDAPSA KKAEASREVK
RIGDGLFVTI EPANDVRANE AKVVLAADNV WGDNTGYQFL LDADHNTFGS VIPATGPLFT
GTASSNLYSA NFEYLIPANA DPVVTTQNII VTGQGEVVIP GGVYDYCITN PEPASGKMWI
AGDGGNQPAR YDDFTFEAGK KYTFTMRRAG MGDGTDMEVE DDSPASYTYT VYRDGTKIQE
GLTATTFEED GVAAGNHEYC VEVKYTAGVS PKVCKDVTVE GSNEFAPVQN LTGSAVGQKV
TLKWDAPNGT PNPNPNPNPG TTTLSESFEN GIPASWKTID ADGDGHGWKP GNAPGIAGYN
SNGCVYSESF GLGGIGVLTP DNYLITPALD LPNGGKLTFW VCAQDANYAS EHYAVYASST
GNDASNFTNA LLEETITAKG VRSPEAIRGR IQGTWRQKTV DLPAGTKYVA FRHFQSTDMF
YIDLDEVEIK ANGKRADFTE TFESSTHGEA PAEWTTIDAD GDGQDWLCLS SGQLDWLTAH
GGTNVVASFS WNGMALNPDN YLISKDVTGA TKVKYYYAVN DGFPGDHYAV MISKTGTNAG
DFTVVFEETP NGINKGGARF GLSTEANGAK PQSVWIERTV DLPAGTKYVA FRHYNCSDLN
YILLDDIQFT MGGSPTPTDY TYTVYRDGTK IKEGLTETTF EEDGVATGNH EYCVEVKYTA
GVSPKVCVNV TINPTQFNPV KNLKAQPDGG DVVLKWEAPS GKRGELLNED FEGDAIPTGW
TALDADGDGN NWDITLNEFT RGERHVLSPL RASNVAISYS SLLQGQEYLP LTPNNFLITP
KVEGAKKITY KVGSPGLPQW SHDHYALCIS KSGTAAADFE VIFEETMTYT QGGANLTREK
DLPAGTKYVA FRHYNCTDVL GIMIDDVVIT GEGEGPSYTY TVYRDGTKIQ EGLTETTYRD
AGMSAQSHEY CVEVKYAAGV SPKVCVDYIP DGVADVTAQK PYTLTVVGKT ITVTCQGEAM
IYDMNGRRLA AGRNTVVYTA QGGYYAVMVV VDGKSYVEKL AIK
