CPG2_PORGI
ID CPG2_PORGI Reviewed; 736 AA.
AC P95493; O33441;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Gingipain R2;
DE EC=3.4.22.37 {ECO:0000269|PubMed:11179305, ECO:0000269|PubMed:9705298};
DE AltName: Full=Arg-gingipain;
DE AltName: Full=Gingipain 2;
DE AltName: Full=RGP-2;
DE Flags: Precursor;
GN Name=rgpB; Synonyms=prtRII, rgp2; OrderedLocusNames=PG_0506;
OS Porphyromonas gingivalis (strain ATCC BAA-308 / W83).
OC Bacteria; Bacteroidetes; Bacteroidia; Bacteroidales; Porphyromonadaceae;
OC Porphyromonas.
OX NCBI_TaxID=242619;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 230-651, PROPEPTIDE,
RP SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
RC STRAIN=HG66;
RX PubMed=9705298; DOI=10.1074/jbc.273.34.21648;
RA Potempa J., Mikolajczyk-Pawlinska J., Brassell D., Nelson D.,
RA Thoegersen I.B., Enghild J.J., Travis J.;
RT "Comparative properties of two cysteine proteinases (gingipains R), the
RT products of two related but individual genes of Porphyromonas gingivalis.";
RL J. Biol. Chem. 273:21648-21657(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 53978 / W50;
RX PubMed=9639929; DOI=10.1099/00221287-144-6-1583;
RA Slakeski N., Bhogal P.S., O'Brien-Simpson N.M., Reynolds E.C.;
RT "Characterization of a second cell-associated Arg-specific cysteine
RT proteinase of Porphyromonas gingivalis and identification of an adhesin-
RT binding motif involved in association of the prtR and prtK proteinases and
RT adhesins into large complexes.";
RL Microbiology 144:1583-1592(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-308 / W83;
RX PubMed=12949112; DOI=10.1128/jb.185.18.5591-5601.2003;
RA Nelson K.E., Fleischmann R.D., DeBoy R.T., Paulsen I.T., Fouts D.E.,
RA Eisen J.A., Daugherty S.C., Dodson R.J., Durkin A.S., Gwinn M.L.,
RA Haft D.H., Kolonay J.F., Nelson W.C., Mason T.M., Tallon L., Gray J.,
RA Granger D., Tettelin H., Dong H., Galvin J.L., Duncan M.J., Dewhirst F.E.,
RA Fraser C.M.;
RT "Complete genome sequence of the oral pathogenic bacterium Porphyromonas
RT gingivalis strain W83.";
RL J. Bacteriol. 185:5591-5601(2003).
RN [4]
RP ACTIVITY REGULATION, AND CATALYTIC ACTIVITY.
RX PubMed=11179305; DOI=10.1128/iai.69.3.1402-1408.2001;
RA Gusman H., Travis J., Helmerhorst E.J., Potempa J., Troxler R.F.,
RA Oppenheim F.G.;
RT "Salivary histatin 5 is an inhibitor of both host and bacterial enzymes
RT implicated in periodontal disease.";
RL Infect. Immun. 69:1402-1408(2001).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 230-664, AND ACTIVE SITE.
RX PubMed=10523290; DOI=10.1093/emboj/18.20.5453;
RA Eichinger A., Beisel H.-G., Jacob U., Huber R., Medrano F.-J., Banbula A.,
RA Potempa J., Travis J., Bode W.;
RT "Crystal structure of gingipain R: an Arg-specific bacterial cysteine
RT proteinase with a caspase-like fold.";
RL EMBO J. 18:5453-5462(1999).
RN [6] {ECO:0007744|PDB:4IEF}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 25-229 AND 230-662 IN COMPLEX
RP WITH CALCIUM, AND ACTIVE SITE.
RC STRAIN=ATCC BAA-308 / W83 {ECO:0000303|PubMed:23558682};
RX PubMed=23558682; DOI=10.1074/jbc.m112.444927;
RA de Diego I., Veillard F.T., Guevara T., Potempa B., Sztukowska M.,
RA Potempa J., Gomis-Ruth F.X.;
RT "Porphyromonas gingivalis virulence factor gingipain RgpB shows a unique
RT zymogenic mechanism for cysteine peptidases.";
RL J. Biol. Chem. 288:14287-14296(2013).
RN [7] {ECO:0007744|PDB:5AG8, ECO:0007744|PDB:5AG9, ECO:0007744|PDB:5HFS}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 577-736.
RC STRAIN=ATCC BAA-308 / W83 {ECO:0000303|PubMed:27005013};
RX PubMed=27005013; DOI=10.1038/srep23123;
RA de Diego I., Ksiazek M., Mizgalska D., Koneru L., Golik P., Szmigielski B.,
RA Nowak M., Nowakowska Z., Potempa B., Houston J.A., Enghild J.J.,
RA Thogersen I.B., Gao J., Kwan A.H., Trewhella J., Dubin G., Gomis-Ruth F.X.,
RA Nguyen K.A., Potempa J.;
RT "The outer-membrane export signal of Porphyromonas gingivalis type IX
RT secretion system (T9SS) is a conserved C-terminal beta-sandwich domain.";
RL Sci. Rep. 6:23123-23123(2016).
CC -!- FUNCTION: Thiol protease. Acts synergistically with RgpA to catalyze
CC the maturation of fimbrial subunits, such as FimA (By similarity). Its
CC proteolytic activity is a major factor in both periodontal tissue
CC destruction and in evasion of host defense mechanisms (Probable).
CC {ECO:0000250|UniProtKB:B2RKU0, ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of proteins and small molecule substrates, with a
CC preference for Arg in P1.; EC=3.4.22.37;
CC Evidence={ECO:0000269|PubMed:11179305, ECO:0000269|PubMed:9705298};
CC -!- ACTIVITY REGULATION: Inhibited by human histatin-3 1/24 (histatin-5).
CC {ECO:0000269|PubMed:11179305}.
CC -!- INTERACTION:
CC P95493; P15516: HTN3; Xeno; NbExp=7; IntAct=EBI-8505881, EBI-738783;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:9705298}.
CC -!- SIMILARITY: Belongs to the peptidase C25 family. {ECO:0000305}.
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DR EMBL; U85038; AAB41892.1; -; Genomic_DNA.
DR EMBL; AF007124; AAC26371.1; -; Genomic_DNA.
DR EMBL; AE015924; AAQ65700.1; -; Genomic_DNA.
DR RefSeq; WP_010956050.1; NC_002950.2.
DR PDB; 1CVR; X-ray; 2.00 A; A=230-664.
DR PDB; 4IEF; X-ray; 2.30 A; A/C/E/G=25-229, B/D/F/H=230-662.
DR PDB; 5AG8; X-ray; 1.90 A; A/B=577-736.
DR PDB; 5AG9; X-ray; 2.11 A; A/B=577-736.
DR PDB; 5HFS; X-ray; 1.97 A; A/B=665-736.
DR PDBsum; 1CVR; -.
DR PDBsum; 4IEF; -.
DR PDBsum; 5AG8; -.
DR PDBsum; 5AG9; -.
DR PDBsum; 5HFS; -.
DR AlphaFoldDB; P95493; -.
DR SMR; P95493; -.
DR IntAct; P95493; 1.
DR MINT; P95493; -.
DR STRING; 242619.PG_0506; -.
DR MEROPS; C25.001; -.
DR MEROPS; C25.003; -.
DR PRIDE; P95493; -.
DR EnsemblBacteria; AAQ65700; AAQ65700; PG_0506.
DR KEGG; pgi:PG_0506; -.
DR PATRIC; fig|242619.8.peg.464; -.
DR eggNOG; COG2957; Bacteria.
DR HOGENOM; CLU_376783_0_0_10; -.
DR OMA; KENGRMI; -.
DR OrthoDB; 1558380at2; -.
DR BioCyc; PGIN242619:G1G02-466-MON; -.
DR BRENDA; 3.4.22.37; 756.
DR SABIO-RK; P95493; -.
DR EvolutionaryTrace; P95493; -.
DR Proteomes; UP000000588; Chromosome.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0004198; F:calcium-dependent cysteine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR CDD; cd10913; Peptidase_C25_N_gingipain; 1.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 2.60.40.3800; -; 1.
DR Gene3D; 3.40.50.10390; -; 1.
DR InterPro; IPR029030; Caspase-like_dom_sf.
DR InterPro; IPR001769; Gingipain.
DR InterPro; IPR039392; Gingipain_N.
DR InterPro; IPR029031; Gingipain_N_sf.
DR InterPro; IPR038490; Gingipain_propep_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR041333; M60_C.
DR InterPro; IPR005536; Peptidase_C25_Ig-like_domain.
DR InterPro; IPR012600; Propeptide_C25.
DR InterPro; IPR026444; Secre_tail.
DR Pfam; PF01364; Peptidase_C25; 1.
DR Pfam; PF03785; Peptidase_C25_C; 1.
DR Pfam; PF18630; Peptidase_M60_C; 1.
DR Pfam; PF08126; Propeptide_C25; 1.
DR SUPFAM; SSF52129; SSF52129; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR TIGRFAMs; TIGR04183; Por_Secre_tail; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Direct protein sequencing; Hydrolase; Metal-binding;
KW Protease; Reference proteome; Secreted; Signal; Thiol protease; Virulence;
KW Zymogen.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PROPEP 25..229
FT /evidence="ECO:0000269|PubMed:9705298"
FT /id="PRO_0000026535"
FT CHAIN 230..736
FT /note="Gingipain R2"
FT /id="PRO_0000026536"
FT ACT_SITE 440
FT /note="Proton donor"
FT /evidence="ECO:0000305|PubMed:10523290,
FT ECO:0007744|PDB:1CVR"
FT ACT_SITE 473
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:23558682,
FT ECO:0000305|PubMed:10523290, ECO:0007744|PDB:1CVR"
FT BINDING 307
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:1CVR"
FT BINDING 329
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:1CVR, ECO:0007744|PDB:4IEF"
FT BINDING 332
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:1CVR, ECO:0007744|PDB:4IEF"
FT BINDING 334
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:1CVR, ECO:0007744|PDB:4IEF"
FT BINDING 336
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:1CVR, ECO:0007744|PDB:4IEF"
FT BINDING 390
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0007744|PDB:1CVR"
FT BINDING 395
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0007744|PDB:1CVR"
FT BINDING 478
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:1CVR"
FT BINDING 487
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:1CVR"
FT BINDING 521
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0007744|PDB:1CVR"
FT BINDING 522
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0007744|PDB:1CVR"
FT BINDING 525
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0007744|PDB:1CVR"
FT BINDING 531
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0007744|PDB:1CVR"
FT BINDING 613
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0007744|PDB:4IEF"
FT BINDING 639
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0007744|PDB:4IEF"
FT CONFLICT 58
FT /note="G -> D (in Ref. 1; AAB41892)"
FT /evidence="ECO:0000305"
FT CONFLICT 246
FT /note="P -> A (in Ref. 1; AAB41892)"
FT /evidence="ECO:0000305"
FT CONFLICT 251
FT /note="E -> G (in Ref. 1; AAB41892)"
FT /evidence="ECO:0000305"
FT CONFLICT 254
FT /note="E -> K (in Ref. 1; AAB41892)"
FT /evidence="ECO:0000305"
FT CONFLICT 398
FT /note="I -> V (in Ref. 1; AAB41892)"
FT /evidence="ECO:0000305"
FT CONFLICT 435
FT /note="A -> V (in Ref. 1; AAB41892)"
FT /evidence="ECO:0000305"
FT CONFLICT 480..482
FT /note="YNV -> FSM (in Ref. 1; AAB41892)"
FT /evidence="ECO:0000305"
FT CONFLICT 510
FT /note="N -> D (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 512
FT /note="S -> Y (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 515
FT /note="S -> P (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 560
FT /note="K -> N (in Ref. 1; AAB41892)"
FT /evidence="ECO:0000305"
FT CONFLICT 582
FT /note="K -> E (in Ref. 1; AAB41892)"
FT /evidence="ECO:0000305"
FT STRAND 36..41
FT /evidence="ECO:0007829|PDB:4IEF"
FT STRAND 44..50
FT /evidence="ECO:0007829|PDB:4IEF"
FT STRAND 55..61
FT /evidence="ECO:0007829|PDB:4IEF"
FT STRAND 64..70
FT /evidence="ECO:0007829|PDB:4IEF"
FT STRAND 87..93
FT /evidence="ECO:0007829|PDB:4IEF"
FT STRAND 96..112
FT /evidence="ECO:0007829|PDB:4IEF"
FT HELIX 130..132
FT /evidence="ECO:0007829|PDB:4IEF"
FT HELIX 139..142
FT /evidence="ECO:0007829|PDB:4IEF"
FT STRAND 151..154
FT /evidence="ECO:0007829|PDB:4IEF"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:4IEF"
FT STRAND 163..170
FT /evidence="ECO:0007829|PDB:4IEF"
FT STRAND 173..176
FT /evidence="ECO:0007829|PDB:4IEF"
FT TURN 177..180
FT /evidence="ECO:0007829|PDB:4IEF"
FT STRAND 181..198
FT /evidence="ECO:0007829|PDB:4IEF"
FT HELIX 215..221
FT /evidence="ECO:0007829|PDB:4IEF"
FT STRAND 240..245
FT /evidence="ECO:0007829|PDB:1CVR"
FT HELIX 247..252
FT /evidence="ECO:0007829|PDB:1CVR"
FT HELIX 254..262
FT /evidence="ECO:0007829|PDB:1CVR"
FT STRAND 266..271
FT /evidence="ECO:0007829|PDB:1CVR"
FT HELIX 272..275
FT /evidence="ECO:0007829|PDB:1CVR"
FT HELIX 281..293
FT /evidence="ECO:0007829|PDB:1CVR"
FT STRAND 299..306
FT /evidence="ECO:0007829|PDB:1CVR"
FT TURN 308..310
FT /evidence="ECO:0007829|PDB:1CVR"
FT STRAND 314..316
FT /evidence="ECO:0007829|PDB:1CVR"
FT STRAND 319..322
FT /evidence="ECO:0007829|PDB:1CVR"
FT HELIX 323..326
FT /evidence="ECO:0007829|PDB:1CVR"
FT STRAND 329..333
FT /evidence="ECO:0007829|PDB:1CVR"
FT STRAND 336..342
FT /evidence="ECO:0007829|PDB:1CVR"
FT HELIX 347..362
FT /evidence="ECO:0007829|PDB:1CVR"
FT TURN 369..372
FT /evidence="ECO:0007829|PDB:1CVR"
FT STRAND 373..378
FT /evidence="ECO:0007829|PDB:1CVR"
FT HELIX 387..389
FT /evidence="ECO:0007829|PDB:1CVR"
FT HELIX 392..406
FT /evidence="ECO:0007829|PDB:1CVR"
FT STRAND 409..418
FT /evidence="ECO:0007829|PDB:1CVR"
FT HELIX 421..430
FT /evidence="ECO:0007829|PDB:1CVR"
FT STRAND 433..439
FT /evidence="ECO:0007829|PDB:1CVR"
FT STRAND 443..446
FT /evidence="ECO:0007829|PDB:1CVR"
FT TURN 447..449
FT /evidence="ECO:0007829|PDB:1CVR"
FT TURN 453..455
FT /evidence="ECO:0007829|PDB:1CVR"
FT HELIX 456..458
FT /evidence="ECO:0007829|PDB:1CVR"
FT STRAND 467..474
FT /evidence="ECO:0007829|PDB:1CVR"
FT STRAND 480..482
FT /evidence="ECO:0007829|PDB:1CVR"
FT HELIX 485..491
FT /evidence="ECO:0007829|PDB:1CVR"
FT STRAND 502..509
FT /evidence="ECO:0007829|PDB:1CVR"
FT STRAND 512..514
FT /evidence="ECO:0007829|PDB:4IEF"
FT HELIX 515..527
FT /evidence="ECO:0007829|PDB:1CVR"
FT HELIX 535..537
FT /evidence="ECO:0007829|PDB:4IEF"
FT HELIX 539..564
FT /evidence="ECO:0007829|PDB:1CVR"
FT STRAND 565..569
FT /evidence="ECO:0007829|PDB:1CVR"
FT STRAND 589..592
FT /evidence="ECO:0007829|PDB:5AG8"
FT STRAND 596..604
FT /evidence="ECO:0007829|PDB:5AG8"
FT STRAND 608..613
FT /evidence="ECO:0007829|PDB:5AG8"
FT STRAND 616..622
FT /evidence="ECO:0007829|PDB:5AG8"
FT STRAND 627..631
FT /evidence="ECO:0007829|PDB:5AG8"
FT STRAND 640..647
FT /evidence="ECO:0007829|PDB:5AG8"
FT STRAND 654..661
FT /evidence="ECO:0007829|PDB:5AG8"
FT STRAND 675..679
FT /evidence="ECO:0007829|PDB:5AG8"
FT STRAND 682..695
FT /evidence="ECO:0007829|PDB:5AG8"
FT STRAND 701..712
FT /evidence="ECO:0007829|PDB:5AG8"
FT STRAND 715..724
FT /evidence="ECO:0007829|PDB:5AG8"
FT STRAND 727..735
FT /evidence="ECO:0007829|PDB:5AG8"
SQ SEQUENCE 736 AA; 80967 MW; C848DD3FAB420833 CRC64;
MKKNFSRIVS IVAFSSLLGG MAFAQPAERG RNPQVRLLSA EQSMSKVQFR MDNLQFTGVQ
TSKGVAQVPT FTEGVNISEK GTPILPILSR SLAVSETRAM KVEVVSSKFI EKKDVLIAPS
KGVISRAENP DQIPYVYGQS YNEDKFFPGE IATLSDPFIL RDVRGQVVNF APLQYNPVTK
TLRIYTEIVV AVSETAEAGQ NTISLVKNST FTGFEDIYKS VFMNYEATRY TPVEEKENGR
MIVIVPKKYE EDIEDFVDWK NQRGLRTEVK VAEDIASPVT ANAIQQFVKQ EYEKEGNDLT
YVLLVGDHKD IPAKITPGIK SDQVYGQIVG NDHYNEVFIG RFSCESKEDL KTQIDRTIHY
ERNITTEDKW LGQALCIASA EGGPSADNGE SDIQHENIIA NLLTQYGYTK IIKCYDPGVT
PKNIIDAFNG GISLANYTGH GSETAWGTSH FGTTHVKQLT NSNQLPFIFD VACVNGDFLY
NVPCFAEALM RAQKDGKPTG TVAIIASTIN QSWASPMRGQ DEMNEILCEK HPNNIKRTFG
GVTMNGMFAM VEKYKKDGEK MLDTWTVFGD PSLLVRTLVP TKMQVTAPAN ISASAQTFEV
ACDYNGAIAT LSDDGDMVGT AIVKDGKAII KLNESIADET NLTLTVVGYN KVTVIKDVKV
EGTSIADVAN DKPYTVAVSG KTITVESPAA GLTIFDMNGR RVATAKNRMV FEAQNGVYAV
RIATEGKTYT EKVIVK
