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 25-MAY-2022, entry version 84. 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}. 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; 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 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 METAL 313 FT /note="Calcium 1" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 337 FT /note="Calcium 2" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 339 FT /note="Calcium 2" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 341 FT /note="Calcium 2; via carbonyl oxygen" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 343 FT /note="Calcium 2" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 482 FT /note="Calcium 1; via carbonyl oxygen" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 491 FT /note="Calcium 1" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 987 FT /note="Calcium 3; via carbonyl oxygen" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 989 FT /note="Calcium 3" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 1000 FT /note="Calcium 4" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 1002 FT /note="Calcium 4" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 1004 FT /note="Calcium 4" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 1006 FT /note="Calcium 4; via carbonyl oxygen" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 1021 FT /note="Calcium 3" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 1023 FT /note="Calcium 3; via carbonyl oxygen" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 1042 FT /note="Calcium 4" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 1145 FT /note="Calcium 3" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 1146 FT /note="Calcium 3" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 1430 FT /note="Calcium 5; via carbonyl oxygen" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 1432 FT /note="Calcium 5" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 1444 FT /note="Calcium 6" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 1446 FT /note="Calcium 6" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 1448 FT /note="Calcium 6" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 1450 FT /note="Calcium 6; via carbonyl oxygen" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 1480 FT /note="Calcium 5" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 1495 FT /note="Calcium 6" FT /evidence="ECO:0000250|UniProtKB:Q51817" FT METAL 1585 FT /note="Calcium 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 //