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 22-JUL-2015, entry version 49. DE RecName: Full=Lys-gingipain {ECO:0000303|PubMed:9538207}; DE EC=3.4.22.47; 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 / JCM 12257). OC Bacteria; Bacteroidetes; Bacteroidia; Bacteroidales; OC Porphyromonadaceae; Porphyromonas. OX NCBI_TaxID=431947; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 33277 / DSM 20709 / JCM 12257; 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 RT strain ATCC 33277 and genomic comparison with strain W83 revealed RT extensive genome rearrangements in P. gingivalis."; RL DNA Res. 15:215-225(2008). RN [2] {ECO:0000305} RP FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, AND RP BIOPHYSICOCHEMICAL 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., RA Abiko Y., 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 RT of the kgp (Lys-gingipain) gene."; RL J. Clin. Microbiol. 42:3873-3876(2004). RN [5] {ECO:0000305} RP ACTIVE SITE, AND MUTAGENESIS OF CYS-476; 476-CYS-CYS-477 AND CYS-477. RX PubMed=18295742; DOI=10.1016/j.archoralbio.2008.01.004; RA Ishida Y., Hu J., Sakai E., Kadowaki T., Yamamoto K., Tsukuba T., RA Kato Y., Nakayama K., Okamoto K.; RT "Determination of active site of lysine-specific cysteine proteinase RT (Lys-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 CC substrates with Lys in the P1 position. Hydrolyzes bovine CC hemoglobin, bovine serum albumin, casein, human placental type I CC collagen and human IgA and IgG. Disrupts the functions of CC polymorphonuclear leukocytes. May act as a virulence factor in the CC development of peridontal disease. Involved in the coaggregation CC of P.gingivalis with other oral bacteria. CC {ECO:0000269|PubMed:15576324, ECO:0000269|PubMed:9538207}. CC -!- CATALYTIC ACTIVITY: Endopeptidase with strict specificity for CC lysyl bonds. {ECO:0000269|PubMed:9538207}. CC -!- ENZYME REGULATION: Activated by the thiol-reducing agents CC cysteine, 2-mercaptoethanol and dithiothreitol. Inhibited by CC idoacetamide, idoacetic acid, leupeptin, tosyl-L-lysine and tosyl- CC L-phenylalanine. Not inhibited by elastatinal, chymostatin, CC cystatins, alpha1-antichymotrypsin or the serine protease CC inhibitors phenylmethylsulfonyl fluoride and CC diisopropylfluorophosphate. Not inhibited by metal ion chelators. CC 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. CC Loses 60% of its activity following incubation at pH 3.5 for 5 CC minutes. {ECO:0000269|PubMed:9538207}; CC Temperature dependence: CC Only retains 40% of activity after incubation at 60 degrees CC Celsius for 10 minutes. {ECO:0000269|PubMed:9538207}; CC -!- SUBCELLULAR LOCATION: Lys-gingipain catalytic subunit: Secreted, CC extracellular space {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- CC terminus exist in different P.gingivalis strains. CC {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; NC_010729.1. DR ProteinModelPortal; B2RLK2; -. DR STRING; 431947.PGN_1728; -. DR MEROPS; C25.002; -. DR EnsemblBacteria; BAG34247; BAG34247; PGN_1728. DR KEGG; pgn:PGN_1728; -. DR PATRIC; 22976425; VBIPorGin26334_1703. DR eggNOG; NOG12793; -. DR HOGENOM; HOG000060004; -. DR KO; K19237; -. DR OrthoDB; EOG6GJBWJ; -. DR BioCyc; PGIN431947:GC9J-1781-MONOMER; -. DR BRENDA; 3.4.22.47; 756. DR Proteomes; UP000008842; Chromosome. DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell. DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro. DR GO; GO:0009405; P:pathogenesis; IEA:UniProtKB-KW. DR Gene3D; 3.40.50.10390; -; 1. DR Gene3D; 3.40.50.1460; -; 1. DR InterPro; IPR029030; Caspase-like_dom. DR InterPro; IPR011628; Cleaved_adhesin. DR InterPro; IPR001769; Gingipain. DR InterPro; IPR029031; Gingipain_N. 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. PE 1: Evidence at protein level; KW Complete proteome; Hydrolase; Protease; Secreted; Signal; KW Thiol protease; Virulence; Zymogen. FT SIGNAL 1 24 {ECO:0000255}. FT PROPEP 25 228 {ECO:0000250|UniProtKB:Q51817, FT ECO:0000255}. FT /FTId=PRO_0000395387. FT CHAIN 229 1723 Lys-gingipain. FT {ECO:0000250|UniProtKB:Q51817}. FT /FTId=PRO_0000395388. FT CHAIN 229 ? Lys-gingipain catalytic subunit. FT {ECO:0000250|UniProtKB:Q51817}. FT /FTId=PRO_0000395389. FT CHAIN 738 ? 39 kDa adhesin. FT {ECO:0000250|UniProtKB:Q51817}. FT /FTId=PRO_0000395390. FT CHAIN 1156 ? 15 kDa adhesin. FT {ECO:0000250|UniProtKB:Q51817}. FT /FTId=PRO_0000395391. FT CHAIN 1291 ? 44 kDa adhesin. FT {ECO:0000250|UniProtKB:Q51817}. FT /FTId=PRO_0000395392. FT ACT_SITE 444 444 Proton donor. FT {ECO:0000250|UniProtKB:P95493}. FT ACT_SITE 477 477 Nucleophile. FT {ECO:0000269|PubMed:18295742}. FT MUTAGEN 476 477 CC->AA: Loss of activity. FT {ECO:0000269|PubMed:18295742}. FT MUTAGEN 476 476 C->A: No effect on activity. FT {ECO:0000269|PubMed:18295742}. FT MUTAGEN 477 477 C->A: Loss of activity. FT {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 //