COLG_HATHI
ID COLG_HATHI Reviewed; 1118 AA.
AC Q9X721; Q9S0X0;
DT 28-MAR-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Collagenase ColG {ECO:0000303|PubMed:9922257};
DE EC=3.4.24.3 {ECO:0000269|PubMed:3002446};
DE AltName: Full=Class I collagenase {ECO:0000303|PubMed:6087888, ECO:0000303|PubMed:9922257};
DE AltName: Full=Gelatinase ColG {ECO:0000303|PubMed:9922257};
DE AltName: Full=Microbial collagenase;
DE Flags: Precursor;
GN Name=colG {ECO:0000303|PubMed:9922257};
OS Hathewaya histolytica (Clostridium histolyticum).
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Clostridiaceae; Hathewaya.
OX NCBI_TaxID=1498;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 111-150, FUNCTION,
RP SUBCELLULAR LOCATION, INDUCTION, DOMAIN, AND PROTEIN CLEAVAGE.
RC STRAIN=ATCC 19401 / DSM 2158 / JCM 1403 / NCIMB 503 / NCTC 503;
RX PubMed=9922257; DOI=10.1128/jb.181.3.923-933.1999;
RA Matsushita O., Jung C.-M., Katayama S., Minami J., Takahashi Y., Okabe A.;
RT "Gene duplication and multiplicity of collagenases in Clostridium
RT histolyticum.";
RL J. Bacteriol. 181:923-933(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 19401 / DSM 2158 / JCM 1403 / NCIMB 503 / NCTC 503;
RA Hosaka T., Yamato I.;
RT "Class 1 collagenase.";
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP COFACTOR, AND CLASSIFICATION.
RX PubMed=6087888; DOI=10.1021/bi00308a036;
RA Bond M.D., Van Wart H.E.;
RT "Characterization of the individual collagenases from Clostridium
RT histolyticum.";
RL Biochemistry 23:3085-3091(1984).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=3002446; DOI=10.1021/bi00344a033;
RA Mookhtiar K.A., Steinbrink D.R., Van Wart H.E.;
RT "Mode of hydrolysis of collagen-like peptides by class I and class II
RT Clostridium histolyticum collagenases: evidence for both endopeptidase and
RT tripeptidylcarboxypeptidase activities.";
RL Biochemistry 24:6527-6533(1985).
RN [5]
RP PRELIMINARY STUDIES FOR PHARMACEUTICAL USE FOR TREATMENT OF PEYRONIE
RP DISEASE.
RX PubMed=8417217; DOI=10.1016/s0022-5347(17)35998-0;
RA Gelbard M.K., James K., Riach P., Dorey F.;
RT "Collagenase versus placebo in the treatment of Peyronie's disease: a
RT double-blind study.";
RL J. Urol. 149:56-58(1993).
RN [6]
RP BIOTECHNOLOGY USE IN TREATING RETAINED PLACENTA.
RX PubMed=9699958; DOI=10.1016/s0143-4004(98)90077-7;
RA Fecteau K.A., Haffner J.C., Eiler H.;
RT "The potential of collagenase as a new therapy for separation of human
RT retained placenta: hydrolytic potency on human, equine and bovine
RT placentae.";
RL Placenta 19:379-383(1998).
RN [7]
RP PHARMACEUTICAL USE FOR TREATMENT OF DUPUYTREN DISEASE.
RX PubMed=10913202; DOI=10.1053/jhsu.2000.6918;
RA Badalamente M.A., Hurst L.C.;
RT "Enzyme injection as nonsurgical treatment of Dupuytren's disease.";
RL J. Hand Surg. Am. 25:629-636(2000).
RN [8]
RP FUNCTION, DOMAIN, AND COLLAGEN-BINDING.
RX PubMed=11913772; DOI=10.3109/03008200109016842;
RA Toyoshima T., Matsushita O., Minami J., Nishi N., Okabe A., Itano T.;
RT "Collagen-binding domain of a Clostridium histolyticum collagenase exhibits
RT a broad substrate spectrum both in vitro and in vivo.";
RL Connect. Tissue Res. 42:281-290(2001).
RN [9]
RP FUNCTION, POSSIBLE ACTIVE SITE, DOMAIN, COLLAGEN-BINDING, AND MUTAGENESIS
RP OF GLU-524.
RX PubMed=11121400; DOI=10.1074/jbc.m003450200;
RA Matsushita O., Koide T., Kobayashi R., Nagata K., Okabe A.;
RT "Substrate recognition by the collagen-binding domain of Clostridium
RT histolyticum class I collagenase.";
RL J. Biol. Chem. 276:8761-8770(2001).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND BIOTECHNOLOGY FOR ISOLATION OF PANCREAS
RP ISLET CELLS.
RX PubMed=18374061; DOI=10.1016/j.transproceed.2008.01.041;
RA McCarthy R.C., Spurlin B., Wright M.J., Breite A.G., Sturdevant L.K.,
RA Dwulet C.S., Dwulet F.E.;
RT "Development and characterization of a collagen degradation assay to assess
RT purified collagenase used in islet isolation.";
RL Transplant. Proc. 40:339-342(2008).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND DOMAIN.
RX PubMed=18937627; DOI=10.1515/bc.2009.004;
RA Eckhard U., Schoenauer E., Ducka P., Briza P., Nuess D., Brandstetter H.;
RT "Biochemical characterization of the catalytic domains of three different
RT Clostridial collagenases.";
RL Biol. Chem. 390:11-18(2009).
RN [12]
RP COLLAGEN BINDING BY S3B DOMAIN.
RX PubMed=19208618; DOI=10.1074/jbc.m807684200;
RA Philominathan S.T., Koide T., Hamada K., Yasui H., Seifert S.,
RA Matsushita O., Sakon J.;
RT "Unidirectional binding of clostridial collagenase to triple helical
RT substrates.";
RL J. Biol. Chem. 284:10868-10876(2009).
RN [13]
RP PHARMACEUTICAL USES FOR WOUND TREATMENT AND BURN DEBRIDEMENT.
RX PubMed=19918145; DOI=10.1097/won.0b013e3181bfdd1a;
RA Shi L., Carson D.;
RT "Collagenase Santyl ointment: a selective agent for wound debridement.";
RL J. Wound Ostomy Continence Nurs. 36:S12-S16(2009).
RN [14]
RP PHARMACEUTICAL USES FOR TREATMENT OF DUPUYTREN DISEASE.
RX PubMed=19726771; DOI=10.1056/nejmoa0810866;
RG CORD I Study Group;
RA Hurst L.C., Badalamente M.A., Hentz V.R., Hotchkiss R.N., Kaplan F.T.,
RA Meals R.A., Smith T.M., Rodzvilla J.;
RT "Injectable collagenase clostridium histolyticum for Dupuytren's
RT contracture.";
RL N. Engl. J. Med. 361:968-979(2009).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION,
RP PROTEIN CLEAVAGE, AND BIOTECHNOLOGY FOR ISOLATION OF PANCREAS ISLET CELLS.
RX PubMed=22099748; DOI=10.1016/j.transproceed.2011.09.059;
RA Breite A.G., McCarthy R.C., Dwulet F.E.;
RT "Characterization and functional assessment of Clostridium histolyticum
RT class I (C1) collagenases and the synergistic degradation of native
RT collagen in enzyme mixtures containing class II (C2) collagenase.";
RL Transplant. Proc. 43:3171-3175(2011).
RN [16]
RP COLLAGEN BINDING BY S3B DOMAIN.
RX PubMed=22898990; DOI=10.1002/pro.2145;
RA Philominathan S.T., Koide T., Matsushita O., Sakon J.;
RT "Bacterial collagen-binding domain targets undertwisted regions of
RT collagen.";
RL Protein Sci. 21:1554-1565(2012).
RN [17]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=24125730; DOI=10.1016/j.jprot.2013.10.004;
RA Eckhard U., Huesgen P.F., Brandstetter H., Overall C.M.;
RT "Proteomic protease specificity profiling of clostridial collagenases
RT reveals their intrinsic nature as dedicated degraders of collagen.";
RL J. Proteomics 100:102-114(2014).
RN [18]
RP PHARMACEUTICAL USE FOR TREATMENT OF PEYRONIE DISEASE.
RX PubMed=25711400; DOI=10.1111/bju.13096;
RA Lipshultz L.I., Goldstein I., Seftel A.D., Kaufman G.J., Smith T.M.,
RA Tursi J.P., Burnett A.L.;
RT "Clinical efficacy of collagenase Clostridium histolyticum in the treatment
RT of Peyronie's disease by subgroup: results from two large, double-blind,
RT randomized, placebo-controlled, phase III studies.";
RL BJU Int. 116:650-656(2015).
RN [19]
RP FUNCTION, ACTIVITY REGULATION, AND BIOTECHNOLOGY FOR ANTI-INFECTIVE AGENTS.
RX PubMed=28820255; DOI=10.1021/jacs.7b06935;
RA Schoenauer E., Kany A.M., Haupenthal J., Huesecken K., Hoppe I.J., Voos K.,
RA Yahiaoui S., Elsaesser B., Ducho C., Brandstetter H., Hartmann R.W.;
RT "Discovery of a potent inhibitor class with high selectivity toward
RT clostridial collagenases.";
RL J. Am. Chem. Soc. 139:12696-12703(2017).
RN [20] {ECO:0007744|PDB:1NQD, ECO:0007744|PDB:1NQJ}
RP X-RAY CRYSTALLOGRAPHY (1.00 ANGSTROMS) OF 1003-1118 IN THE PRESENCE AND
RP ABSENCE OF CALCIUM, CALCIUM COFACTOR, DOMAIN, COLLAGEN-BINDING, AND
RP MUTAGENESIS OF ARG-1039; PHE-1062; THR-1067; TYR-1080; VAL-1088; LEU-1102;
RP TYR-1104 AND TYR-1106.
RX PubMed=12682007; DOI=10.1093/emboj/cdg172;
RA Wilson J.J., Matsushita O., Okabe A., Sakon J.;
RT "A bacterial collagen-binding domain with novel calcium-binding motif
RT controls domain orientation.";
RL EMBO J. 22:1743-1752(2003).
RN [21] {ECO:0007744|PDB:2O8O}
RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 1003-1118 IN COMPLEX WITH
RP CALCIUM.
RA Philominathan S.T.L., Wilson J.J., Matsushita O., Sakon J.;
RT "Induction of stable beta-sheet by Ca2+ in Clostridial collagen binding
RT domain.";
RL Submitted (DEC-2006) to the PDB data bank.
RN [22] {ECO:0007744|PDB:2Y72}
RP X-RAY CRYSTALLOGRAPHY (1.18 ANGSTROMS) OF 799-880, AND DOMAIN.
RX PubMed=21871007; DOI=10.1515/bc.2011.099;
RA Eckhard U., Brandstetter H.;
RT "Polycystic kidney disease-like domains of clostridial collagenases and
RT their role in collagen recruitment.";
RL Biol. Chem. 392:1039-1045(2011).
RN [23] {ECO:0007744|PDB:2Y3U, ECO:0007744|PDB:2Y50, ECO:0007744|PDB:2Y6I, ECO:0007744|PDB:2Y72}
RP X-RAY CRYSTALLOGRAPHY (1.18 ANGSTROMS) OF 799-880, X-RAY CRYSTALLOGRAPHY
RP (2.80 ANGSTROMS) OF 119-880 IN COMPLEX WITH AND WITHOUT ZINC, X-RAY
RP CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 119-880 IN COMPLEX WITH ZINC AND AN
RP INHIBITOR, FUNCTION, REACTION MECHANISM, ZINC COFACTOR, ACTIVITY
RP REGULATION, DOMAIN, AND MUTAGENESIS OF 389-GLY--VAL-397.
RX PubMed=21947205; DOI=10.1038/nsmb.2127;
RA Eckhard U., Schonauer E., Nuss D., Brandstetter H.;
RT "Structure of collagenase G reveals a chew-and-digest mechanism of
RT bacterial collagenolysis.";
RL Nat. Struct. Mol. Biol. 18:1109-1114(2011).
RN [24] {ECO:0007744|PDB:4HPK}
RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 1006-1118 AND 1002-1118 IN
RP COMPLEX WITH CALCIUM, COFACTOR, DOMAIN, AND COLLAGEN-BINDING.
RX PubMed=23144249; DOI=10.1128/jb.00010-12;
RA Bauer R., Wilson J.J., Philominathan S.T., Davis D., Matsushita O.,
RA Sakon J.;
RT "Structural comparison of ColH and ColG collagen-binding domains from
RT Clostridium histolyticum.";
RL J. Bacteriol. 195:318-327(2013).
RN [25] {ECO:0007744|PDB:4AQO, ECO:0007744|PDB:4ARE}
RP X-RAY CRYSTALLOGRAPHY (0.99 ANGSTROMS) OF 792-880 IN COMPLEX WITH CALCIUM,
RP X-RAY CRYSTALLOGRAPHY (2.19 ANGSTROMS) OF 119-789 IN COMPLEX WITH ZINC,
RP FUNCTION, COFACTOR, AND DOMAIN.
RX PubMed=23703618; DOI=10.1074/jbc.m112.448548;
RA Eckhard U., Schonauer E., Brandstetter H.;
RT "Structural basis for activity regulation and substrate preference of
RT clostridial collagenases G, H, and T.";
RL J. Biol. Chem. 288:20184-20194(2013).
RN [26] {ECO:0007744|PDB:4JRW, ECO:0007744|PDB:4TN9}
RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 797-881, AND DOMAIN.
RX PubMed=25760606; DOI=10.1107/s1399004714027722;
RA Bauer R., Janowska K., Taylor K., Jordan B., Gann S., Janowski T.,
RA Latimer E.C., Matsushita O., Sakon J.;
RT "Structures of three polycystic kidney disease-like domains from
RT Clostridium histolyticum collagenases ColG and ColH.";
RL Acta Crystallogr. D 71:565-577(2015).
RN [27] {ECO:0007744|PDB:5IKU}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 883-1118 IN COMPLEX WITH CALCIUM,
RP COFACTOR, AND DOMAIN.
RA Janowska K., Bauer R., Roeser R., Sakon J., Matsushita O.;
RT "Crystal structure of the Clostridium histolyticum ColG tandem collagen-
RT binding domain s3as3b in the presence of calcium at 1.9 Angstrom
RT resolution.";
RL Submitted (MAR-2016) to the PDB data bank.
CC -!- FUNCTION: Clostridial collagenases are among the most efficient
CC degraders of eukaryotic collagen known; saprophytes use collagen as a
CC carbon source while pathogens additionally digest collagen to aid in
CC host colonization. Has both tripeptidylcarboxypeptidase on Gly-X-Y and
CC endopeptidase activities; the endopeptidase cuts within the triple
CC helix region of collagen while tripeptidylcarboxypeptidase successively
CC digests the exposed ends, thus clostridial collagenases can digest
CC large sections of collagen (PubMed:3002446). Active on soluble type I
CC collagen, insoluble collagen, azocoll, soluble PZ-peptide (all
CC collagenase substrates) and gelatin (PubMed:9922257). The full-length
CC protein has collagenase activity, while the in vivo derived C-
CC terminally truncated shorter versions only act on gelatin
CC (PubMed:9922257). In vitro digestion of soluble calf skin collagen
CC fibrils requires both ColG and ColH; ColG forms missing the second
CC collagen-binding domain are also synergistic with ColH, although their
CC overall efficiency is decreased (PubMed:18374061, PubMed:22099748). The
CC activator domain (residues 119-388) and catalytic subdomain (389-670)
CC open and close around substrate using a Gly-rich hinge (387-397),
CC allowing digestion when the protein is closed (PubMed:21947205,
CC PubMed:23703618). Binding of collagen requires Ca(2+) and is inhibited
CC by EGTA; the collagen-binding domain (CBD, S3a plus S3b) specifically
CC recognizes the triple-helical conformation made by 3 collagen protein
CC chains in the triple-helical region (PubMed:11121400). Isolated CBD
CC (S3a plus S3b) binds collagen fibrils and sheets of many tissues
CC (PubMed:11913772). {ECO:0000269|PubMed:11121400,
CC ECO:0000269|PubMed:11913772, ECO:0000269|PubMed:18374061,
CC ECO:0000269|PubMed:18937627, ECO:0000269|PubMed:21947205,
CC ECO:0000269|PubMed:22099748, ECO:0000269|PubMed:23703618,
CC ECO:0000269|PubMed:24125730, ECO:0000269|PubMed:28820255,
CC ECO:0000269|PubMed:3002446, ECO:0000269|PubMed:9922257}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Digestion of native collagen in the triple helical region at
CC Xaa-|-Gly bonds. With synthetic peptides, a preference is shown for
CC Gly at P3 and P1', Pro and Ala at P2 and P2', and hydroxyproline, Ala
CC or Arg at P3'.; EC=3.4.24.3; Evidence={ECO:0000269|PubMed:24125730,
CC ECO:0000269|PubMed:3002446, ECO:0000305|PubMed:18937627};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:12682007, ECO:0000269|PubMed:23144249,
CC ECO:0000269|PubMed:23703618, ECO:0000269|PubMed:6087888,
CC ECO:0000269|Ref.21, ECO:0000269|Ref.27};
CC Note=Binds about 7 Ca(2+) per subunit (PubMed:6087888). The
CC metallopeptidase and PKD domains each bind 1 Ca(2+), while each CDB
CC binds 2 (PubMed:12682007, Ref.21, PubMed:23144249, Ref.27).
CC {ECO:0000269|PubMed:12682007, ECO:0000269|PubMed:23144249,
CC ECO:0000269|PubMed:6087888, ECO:0000269|Ref.21, ECO:0000269|Ref.27};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:21947205, ECO:0000269|PubMed:23703618,
CC ECO:0000269|PubMed:6087888};
CC Note=Binds 1 catalytic Zn(2+) per subunit, a Zn-free form has been
CC crystallized (PubMed:21947205). {ECO:0000269|PubMed:21947205,
CC ECO:0000269|PubMed:23703618, ECO:0000269|PubMed:6087888};
CC -!- ACTIVITY REGULATION: Inhibited by 1-10-phenanthroline
CC (PubMed:18937627). Inhibited by peptidomimetic isoamyl-phosphonyl-Gly-
CC Pro-Ala, which binds to Zn(2+) (PubMed:21947205). Inhibited by broad-
CC spectrum zinc metalloprotease inhibitor batimastat (PubMed:28820255).
CC N-aryl mercaptoacetamide-based inhibitors have been isolated that act
CC on clostridial collagenases with submicromolar affinity while having
CC negligibile activity on human collagenases (PubMed:28820255).
CC {ECO:0000269|PubMed:18937627, ECO:0000269|PubMed:21947205,
CC ECO:0000269|PubMed:28820255}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.840 mM for furylacryloyl-Leu-Gly-Pro-Ala (FALGPA)
CC {ECO:0000269|PubMed:18937627};
CC Vmax=0.0852 umol/min/mg enzyme {ECO:0000269|PubMed:18937627};
CC Note=kcat is 0.11/sec, using a catalytic fragment (119-790) on an
CC artificial substrate. {ECO:0000269|PubMed:18937627};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:18374061,
CC ECO:0000269|PubMed:22099748, ECO:0000269|PubMed:9922257}.
CC -!- INDUCTION: RNA levels are high in late logarithmic phase.
CC {ECO:0000269|PubMed:9922257}.
CC -!- DOMAIN: The mature protein has 4 domains; a metalloprotease domain (S1,
CC approximately residues 111-786), S2 (877-882, equivalent to PKD), and 2
CC collagen-binding domains (CBD) S3a (997-1003) and S3b (1008-1118)
CC (PubMed:9922257, PubMed:11121400). The S1 domain has collagen
CC hydrolytic activity (PubMed:11121400, PubMed:18937627). The
CC metalloprotease S1 domain is composed of 3 subdomains which together
CC resemble a saddle; an activator domain (residues 119-388), the
CC catalytic peptidase subdomain (398-670) and a helper subdomain (679-
CC 790) joined by a Gly-rich hinge (387-397) (PubMed:21947205,
CC PubMed:23703618). The S2 domain (799-880, PKD) is flexible within a
CC larger structure (S1 plus S2, residues 119-880) (PubMed:21947205,
CC PubMed:21871007). Binding to Ca(2+) renders the midsection of S2 more
CC flexible; Ca(2+) binding confers thermostability (PubMed:25760606). S3a
CC and S3b each have collagen-binding activity; collagen is bound more
CC efficiently when both S3a and S3b are present (PubMed:11121400). CBD
CC S3a plus S3b binds to many types of collagen in vitro and in vivo
CC (PubMed:11913772). The structure of CBD S3b becomes more compact and
CC thermostable when it is bound to Ca(2+) and its N-terminal linker
CC (approximately residues 1008-1020) changes from an extended alpha-helix
CC to a beta-sheet anchored to the rest of the CBD (PubMed:12682007,
CC PubMed:23144249). S3b may act as a Ca(2+)-activated molecular switch to
CC trigger domain reorientation (PubMed:12682007). Isolated CBD S3b binds
CC unidirectionally to the C-terminus of the collagen triple helix via a
CC surface cleft (PubMed:19208618, PubMed:23144249). The S3b domain binds
CC preferentially to undertwisted segions of collagen (PubMed:22898990).
CC {ECO:0000269|PubMed:11121400, ECO:0000269|PubMed:11913772,
CC ECO:0000269|PubMed:12682007, ECO:0000269|PubMed:18937627,
CC ECO:0000269|PubMed:19208618, ECO:0000269|PubMed:21947205,
CC ECO:0000269|PubMed:22898990, ECO:0000269|PubMed:23144249,
CC ECO:0000269|PubMed:23703618, ECO:0000269|PubMed:25760606,
CC ECO:0000305|PubMed:11121400, ECO:0000305|PubMed:21871007,
CC ECO:0000305|PubMed:23144249, ECO:0000305|PubMed:9922257}.
CC -!- PTM: Upon purification gives 67 kDa, 78 kDa, 82 kDa and 116 kDa (full-
CC length) proteins all of which have the same N-terminus; only the
CC longest form digests insoluble collagen (PubMed:9922257). At least 2 in
CC vivo isolated forms (C1b and C1c) are missing the second collagen-
CC binding domain, ending on Lys-1006 and Lys-1018 respectively
CC (PubMed:22099748). {ECO:0000269|PubMed:22099748,
CC ECO:0000269|PubMed:9922257}.
CC -!- BIOTECHNOLOGY: Widely used for tissue dissociation due to their potent
CC activity on connective tissue. {ECO:0000305}.
CC -!- BIOTECHNOLOGY: A mix of ColG and ColH is used for isolation of
CC pancreatic islet cells for subsequent transplantation.
CC {ECO:0000269|PubMed:18374061, ECO:0000269|PubMed:22099748}.
CC -!- BIOTECHNOLOGY: A mix of ColG and ColH has been used to allow release of
CC retained placenta in cows and mares, and its use in humans has been
CC proposed. {ECO:0000269|PubMed:9699958}.
CC -!- BIOTECHNOLOGY: N-aryl mercaptoacetamide-based inhibitors with
CC submicromolar affinity for clostridial collagenases but negligibile
CC activity on human collagenases have been discovered that may lead to
CC promising anti-infective drugs against Clostridia (PubMed:28820255).
CC {ECO:0000269|PubMed:28820255}.
CC -!- PHARMACEUTICAL: SANTYL Ointment (Smith and Nephew, Inc.) is indicated
CC for debriding chronic dermal ulcers and severely burned areas. It is
CC unclear which of the collagenases from this bacteria is in the
CC ointment. {ECO:0000269|PubMed:19918145}.
CC -!- PHARMACEUTICAL: Xiaflex (Endo Pharmaceuticals, Inc.) is a mix of
CC H.histolytica collagenases (ColG and ColH) used to treat both Dupuytren
CC disease and Peyronie disease. Dupuytren disease is a progressive
CC genetic disorder of pathologic collagen production and deposition under
CC the skin of the hand that causes the fingers to be drawn into the palm,
CC leading to flexion contractures of the joints, which can severely limit
CC hand function. Injections of collagenase reduce these joint
CC contractures (PubMed:10913202, PubMed:19726771). Peyronie disease (PD)
CC is characterized by a disorganized, excessive deposition of collagen
CC that forms a plaque within the penis. The plaque restricts lengthening
CC on the affected side during erection, which can lead to penile
CC curvature deformity, discomfort and erectile dysfunction, and can
CC eventually lead to psychosocial effects such as depression and
CC relationship difficulties. Studies have shown the clinical efficacy of
CC collagenase injection for reducing penile curvature deformity and
CC psychosocial symptoms (PubMed:8417217, PubMed:25711400).
CC {ECO:0000269|PubMed:10913202, ECO:0000269|PubMed:19726771,
CC ECO:0000269|PubMed:25711400, ECO:0000269|PubMed:8417217}.
CC -!- MISCELLANEOUS: Clostridial collagenases enable the bacteria to
CC infiltrate and colonize host tissue, and contribute to gas gangrene
CC (myonecrosis) pathogenesis. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the peptidase M9B family. Collagenase subfamily.
CC {ECO:0000305|PubMed:6087888, ECO:0000305|PubMed:9922257}.
CC -!- WEB RESOURCE: Name=Worthington enzyme manual;
CC URL="https://www.worthington-biochem.com/CLS/";
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DR EMBL; D87215; BAA77453.1; -; Genomic_DNA.
DR EMBL; AB026889; BAA86030.1; -; Genomic_DNA.
DR PDB; 1NQD; X-ray; 1.65 A; A/B=1003-1118.
DR PDB; 1NQJ; X-ray; 1.00 A; A/B=1003-1118.
DR PDB; 2O8O; X-ray; 1.35 A; A/B=1003-1118.
DR PDB; 2Y3U; X-ray; 2.55 A; A=119-880.
DR PDB; 2Y50; X-ray; 2.80 A; A=119-880.
DR PDB; 2Y6I; X-ray; 3.25 A; A=119-880.
DR PDB; 2Y72; X-ray; 1.18 A; A/B=799-880.
DR PDB; 4AQO; X-ray; 0.99 A; A=792-880.
DR PDB; 4ARE; X-ray; 2.19 A; A=119-789.
DR PDB; 4HPK; X-ray; 1.35 A; A=1006-1118, B=1003-1118.
DR PDB; 4JRW; X-ray; 1.60 A; A/B=797-881.
DR PDB; 4TN9; X-ray; 1.40 A; A/B=797-881.
DR PDB; 5IKU; X-ray; 1.90 A; A=883-1118.
DR PDBsum; 1NQD; -.
DR PDBsum; 1NQJ; -.
DR PDBsum; 2O8O; -.
DR PDBsum; 2Y3U; -.
DR PDBsum; 2Y50; -.
DR PDBsum; 2Y6I; -.
DR PDBsum; 2Y72; -.
DR PDBsum; 4AQO; -.
DR PDBsum; 4ARE; -.
DR PDBsum; 4HPK; -.
DR PDBsum; 4JRW; -.
DR PDBsum; 4TN9; -.
DR PDBsum; 5IKU; -.
DR AlphaFoldDB; Q9X721; -.
DR SASBDB; Q9X721; -.
DR SMR; Q9X721; -.
DR BindingDB; Q9X721; -.
DR ChEMBL; CHEMBL2268009; -.
DR Allergome; 5989; Clo hi Collagenase.
DR MEROPS; M09.002; -.
DR PRIDE; Q9X721; -.
DR BRENDA; 3.4.24.3; 1481.
DR EvolutionaryTrace; Q9X721; -.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0005518; F:collagen binding; IDA:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0004222; F:metalloendopeptidase activity; IMP:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0034701; F:tripeptidase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0032963; P:collagen metabolic process; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR041379; ColG_subdomain.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013661; Peptidase_M9_N_dom.
DR InterPro; IPR002169; Peptidase_M9A/M9B.
DR InterPro; IPR022409; PKD/Chitinase_dom.
DR InterPro; IPR000601; PKD_dom.
DR InterPro; IPR035986; PKD_dom_sf.
DR Pfam; PF18496; ColG_sub; 1.
DR Pfam; PF01752; Peptidase_M9; 1.
DR Pfam; PF08453; Peptidase_M9_N; 1.
DR PRINTS; PR00931; MICOLLPTASE.
DR SMART; SM00089; PKD; 1.
DR SUPFAM; SSF49299; SSF49299; 1.
DR PROSITE; PS50093; PKD; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Direct protein sequencing; Hydrolase; Metal-binding;
KW Metalloprotease; Pharmaceutical; Protease; Repeat; Secreted; Signal;
KW Virulence; Zinc; Zymogen.
FT SIGNAL 1..45
FT /evidence="ECO:0000255"
FT PROPEP 46..110
FT /evidence="ECO:0000305|PubMed:9922257"
FT /id="PRO_0000443545"
FT CHAIN 111..1118
FT /note="Collagenase ColG"
FT /id="PRO_0000443546"
FT DOMAIN 797..885
FT /note="PKD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00151"
FT REGION 111..786
FT /note="S1 metalloprotease domain, degrades both FALGPA
FT (furylacryloyl-Leu-Gly-Pro-Ala) and type I collagen"
FT /evidence="ECO:0000269|PubMed:21947205,
FT ECO:0000305|PubMed:11121400, ECO:0000305|PubMed:9922257"
FT REGION 119..388
FT /note="Activator domain required for full activity on
FT collagen"
FT /evidence="ECO:0000269|PubMed:21947205,
FT ECO:0000305|PubMed:23703618"
FT REGION 389..670
FT /note="Catalytic subdomain"
FT /evidence="ECO:0000305|PubMed:23703618"
FT REGION 396..1118
FT /note="Degrades soluble FALGPA peptide (furylacryloyl-Leu-
FT Gly-Pro-Ala) but not type I collagen"
FT /evidence="ECO:0000269|PubMed:21947205"
FT REGION 679..790
FT /note="Helper subdomain"
FT /evidence="ECO:0000305|PubMed:23703618"
FT REGION 787..882
FT /note="S2 domain"
FT /evidence="ECO:0000305|PubMed:11121400,
FT ECO:0000305|PubMed:9922257"
FT REGION 886..1003
FT /note="S3a collagen-binding domain"
FT /evidence="ECO:0000305|PubMed:11121400,
FT ECO:0000305|PubMed:9922257"
FT REGION 1008..1118
FT /note="S3b collagen-binding domain"
FT /evidence="ECO:0000269|PubMed:12682007,
FT ECO:0000305|PubMed:11121400, ECO:0000305|PubMed:9922257"
FT REGION 1102..1106
FT /note="Collagen-binding"
FT /evidence="ECO:0000269|PubMed:12682007,
FT ECO:0000269|PubMed:19208618"
FT ACT_SITE 524
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000305|PubMed:11121400"
FT BINDING 498
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q899Y1,
FT ECO:0000303|PubMed:23703618"
FT BINDING 523
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000269|PubMed:21947205, ECO:0000269|PubMed:23703618,
FT ECO:0007744|PDB:2Y50, ECO:0007744|PDB:2Y6I,
FT ECO:0007744|PDB:4ARE"
FT BINDING 527
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000269|PubMed:21947205, ECO:0000269|PubMed:23703618,
FT ECO:0007744|PDB:2Y50, ECO:0007744|PDB:2Y6I,
FT ECO:0007744|PDB:4ARE"
FT BINDING 531
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q899Y1,
FT ECO:0000303|PubMed:23703618"
FT BINDING 535
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q899Y1,
FT ECO:0000303|PubMed:23703618"
FT BINDING 537
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q899Y1,
FT ECO:0000303|PubMed:23703618"
FT BINDING 555
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:21947205,
FT ECO:0000269|PubMed:23703618, ECO:0007744|PDB:2Y50,
FT ECO:0007744|PDB:2Y6I, ECO:0007744|PDB:4ARE"
FT BINDING 795
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:23703618,
FT ECO:0007744|PDB:4AQO"
FT BINDING 796
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:23703618,
FT ECO:0007744|PDB:4AQO"
FT BINDING 823
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:23703618,
FT ECO:0007744|PDB:4AQO"
FT BINDING 825
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:23703618,
FT ECO:0007744|PDB:4AQO"
FT BINDING 864
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:23703618,
FT ECO:0007744|PDB:4AQO"
FT BINDING 890
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0007744|PDB:5IKU"
FT BINDING 892
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0007744|PDB:5IKU"
FT BINDING 892
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0007744|PDB:5IKU"
FT BINDING 894
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0007744|PDB:5IKU"
FT BINDING 913
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0007744|PDB:5IKU"
FT BINDING 918
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0007744|PDB:5IKU"
FT BINDING 918
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0007744|PDB:5IKU"
FT BINDING 920
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0007744|PDB:5IKU"
FT BINDING 921
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0007744|PDB:5IKU"
FT BINDING 921
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0007744|PDB:5IKU"
FT BINDING 1009
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000269|PubMed:12682007,
FT ECO:0000269|PubMed:23144249, ECO:0007744|PDB:1NQD,
FT ECO:0007744|PDB:2O8O, ECO:0007744|PDB:4HPK,
FT ECO:0007744|PDB:5IKU"
FT BINDING 1011
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000269|PubMed:12682007,
FT ECO:0000269|PubMed:23144249, ECO:0007744|PDB:1NQD,
FT ECO:0007744|PDB:2O8O, ECO:0007744|PDB:4HPK,
FT ECO:0007744|PDB:5IKU"
FT BINDING 1011
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000269|PubMed:12682007,
FT ECO:0000269|PubMed:23144249, ECO:0007744|PDB:1NQD,
FT ECO:0007744|PDB:2O8O, ECO:0007744|PDB:4HPK,
FT ECO:0007744|PDB:5IKU"
FT BINDING 1013
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000269|PubMed:12682007,
FT ECO:0000269|PubMed:23144249, ECO:0007744|PDB:1NQD,
FT ECO:0007744|PDB:2O8O, ECO:0007744|PDB:4HPK,
FT ECO:0007744|PDB:5IKU"
FT BINDING 1014
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000269|PubMed:12682007,
FT ECO:0000269|PubMed:23144249, ECO:0007744|PDB:1NQD,
FT ECO:0007744|PDB:2O8O, ECO:0007744|PDB:4HPK"
FT BINDING 1032
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000269|PubMed:12682007,
FT ECO:0000269|PubMed:23144249, ECO:0007744|PDB:1NQD,
FT ECO:0007744|PDB:2O8O, ECO:0007744|PDB:4HPK,
FT ECO:0007744|PDB:5IKU"
FT BINDING 1037
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000269|PubMed:12682007,
FT ECO:0000269|PubMed:23144249, ECO:0007744|PDB:1NQD,
FT ECO:0007744|PDB:2O8O, ECO:0007744|PDB:4HPK,
FT ECO:0007744|PDB:5IKU"
FT BINDING 1037
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000269|PubMed:12682007,
FT ECO:0000269|PubMed:23144249, ECO:0007744|PDB:1NQD,
FT ECO:0007744|PDB:2O8O, ECO:0007744|PDB:4HPK,
FT ECO:0007744|PDB:5IKU"
FT BINDING 1039
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000269|PubMed:12682007,
FT ECO:0000269|PubMed:23144249, ECO:0007744|PDB:1NQD,
FT ECO:0007744|PDB:2O8O, ECO:0007744|PDB:4HPK,
FT ECO:0007744|PDB:5IKU"
FT BINDING 1040
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000269|PubMed:12682007,
FT ECO:0000269|PubMed:23144249, ECO:0007744|PDB:1NQD,
FT ECO:0007744|PDB:2O8O, ECO:0007744|PDB:4HPK,
FT ECO:0007744|PDB:5IKU"
FT BINDING 1040
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000269|PubMed:12682007,
FT ECO:0000269|PubMed:23144249, ECO:0007744|PDB:1NQD,
FT ECO:0007744|PDB:2O8O, ECO:0007744|PDB:4HPK,
FT ECO:0007744|PDB:5IKU"
FT SITE 1006
FT /note="C-terminus of form C1b"
FT /evidence="ECO:0000269|PubMed:22099748"
FT SITE 1018
FT /note="C-terminus of form C1c"
FT /evidence="ECO:0000269|PubMed:22099748"
FT SITE 1067
FT /note="Collagen binding"
FT /evidence="ECO:0000269|PubMed:12682007,
FT ECO:0000269|PubMed:19208618"
FT SITE 1080
FT /note="Collagen binding"
FT /evidence="ECO:0000269|PubMed:12682007,
FT ECO:0000269|PubMed:19208618"
FT MUTAGEN 389..397
FT /note="Missing: Degrades soluble FALGPA peptide
FT (furylacryloyl-Leu-Gly-Pro-Ala) but only 40% active on type
FT I collagen."
FT /evidence="ECO:0000269|PubMed:21947205"
FT MUTAGEN 524
FT /note="E->D: Retains 4% digestion of collagen, still bind
FT collagen."
FT /evidence="ECO:0000269|PubMed:11121400"
FT MUTAGEN 1039
FT /note="R->A: S3b fragment has 2.3-fold increased affinity
FT for collagen."
FT /evidence="ECO:0000269|PubMed:12682007"
FT MUTAGEN 1062
FT /note="F->A: S3b fragment has 2.4-fold increased affinity
FT for collagen."
FT /evidence="ECO:0000269|PubMed:12682007"
FT MUTAGEN 1067
FT /note="T->A: S3b fragment has 10-fold decreased affinity
FT for collagen."
FT /evidence="ECO:0000269|PubMed:12682007"
FT MUTAGEN 1080
FT /note="Y->A: S3b fragment has 12-fold decreased affinity
FT for collagen."
FT /evidence="ECO:0000269|PubMed:12682007"
FT MUTAGEN 1088
FT /note="V->A: S3b fragment has 2.2-fold increased affinity
FT for collagen."
FT /evidence="ECO:0000269|PubMed:12682007"
FT MUTAGEN 1102
FT /note="L->A: S3b fragment has 5-fold decreased affinity for
FT collagen."
FT /evidence="ECO:0000269|PubMed:12682007"
FT MUTAGEN 1104
FT /note="Y->A,S: S3b fragment has no collagen binding."
FT /evidence="ECO:0000269|PubMed:12682007"
FT MUTAGEN 1104
FT /note="Y->F: S3b fragment has 12-fold decreased affinity
FT for collagen."
FT /evidence="ECO:0000269|PubMed:12682007"
FT MUTAGEN 1106
FT /note="Y->A: S3b fragment has 40-fold decreased affinity
FT for collagen."
FT /evidence="ECO:0000269|PubMed:12682007"
FT CONFLICT 606
FT /note="F -> V (in Ref. 2; BAA86030)"
FT /evidence="ECO:0000305"
FT CONFLICT 656..659
FT /note="EYQN -> DYQT (in Ref. 2; BAA86030)"
FT /evidence="ECO:0000305"
FT CONFLICT 836..837
FT /note="GD -> VY (in Ref. 2; BAA86030)"
FT /evidence="ECO:0000305"
FT HELIX 121..124
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 129..137
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 141..143
FT /evidence="ECO:0007829|PDB:4ARE"
FT TURN 145..148
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 152..157
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 161..177
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 186..202
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 204..206
FT /evidence="ECO:0007829|PDB:2Y6I"
FT HELIX 207..210
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 212..215
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 216..218
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 219..227
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 229..231
FT /evidence="ECO:0007829|PDB:2Y6I"
FT HELIX 236..251
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 256..260
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 263..271
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 273..276
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 280..301
FT /evidence="ECO:0007829|PDB:4ARE"
FT STRAND 302..304
FT /evidence="ECO:0007829|PDB:2Y3U"
FT HELIX 306..308
FT /evidence="ECO:0007829|PDB:4ARE"
FT TURN 310..313
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 316..326
FT /evidence="ECO:0007829|PDB:4ARE"
FT TURN 333..335
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 336..349
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 350..352
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 356..370
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 374..386
FT /evidence="ECO:0007829|PDB:4ARE"
FT STRAND 394..396
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 399..410
FT /evidence="ECO:0007829|PDB:4ARE"
FT STRAND 413..417
FT /evidence="ECO:0007829|PDB:4ARE"
FT TURN 418..421
FT /evidence="ECO:0007829|PDB:4ARE"
FT STRAND 422..426
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 432..453
FT /evidence="ECO:0007829|PDB:4ARE"
FT STRAND 459..462
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 464..466
FT /evidence="ECO:0007829|PDB:4ARE"
FT STRAND 467..475
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 476..479
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 481..486
FT /evidence="ECO:0007829|PDB:4ARE"
FT STRAND 491..497
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 498..500
FT /evidence="ECO:0007829|PDB:4ARE"
FT STRAND 502..506
FT /evidence="ECO:0007829|PDB:4ARE"
FT TURN 510..512
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 517..533
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 543..545
FT /evidence="ECO:0007829|PDB:4ARE"
FT TURN 546..548
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 551..561
FT /evidence="ECO:0007829|PDB:4ARE"
FT STRAND 566..568
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 574..580
FT /evidence="ECO:0007829|PDB:4ARE"
FT TURN 585..587
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 591..596
FT /evidence="ECO:0007829|PDB:4ARE"
FT STRAND 599..601
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 606..620
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 622..633
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 637..649
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 651..667
FT /evidence="ECO:0007829|PDB:4ARE"
FT TURN 668..670
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 678..681
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 689..699
FT /evidence="ECO:0007829|PDB:4ARE"
FT STRAND 703..711
FT /evidence="ECO:0007829|PDB:4ARE"
FT STRAND 716..728
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 732..750
FT /evidence="ECO:0007829|PDB:4ARE"
FT HELIX 756..760
FT /evidence="ECO:0007829|PDB:4ARE"
FT STRAND 762..770
FT /evidence="ECO:0007829|PDB:4ARE"
FT STRAND 775..786
FT /evidence="ECO:0007829|PDB:4ARE"
FT STRAND 806..809
FT /evidence="ECO:0007829|PDB:4AQO"
FT STRAND 812..817
FT /evidence="ECO:0007829|PDB:4AQO"
FT STRAND 824..826
FT /evidence="ECO:0007829|PDB:4TN9"
FT STRAND 828..834
FT /evidence="ECO:0007829|PDB:4AQO"
FT STRAND 836..838
FT /evidence="ECO:0007829|PDB:4AQO"
FT STRAND 840..849
FT /evidence="ECO:0007829|PDB:4AQO"
FT STRAND 854..864
FT /evidence="ECO:0007829|PDB:4AQO"
FT STRAND 869..879
FT /evidence="ECO:0007829|PDB:4AQO"
FT HELIX 897..899
FT /evidence="ECO:0007829|PDB:5IKU"
FT STRAND 910..915
FT /evidence="ECO:0007829|PDB:5IKU"
FT STRAND 920..927
FT /evidence="ECO:0007829|PDB:5IKU"
FT STRAND 929..941
FT /evidence="ECO:0007829|PDB:5IKU"
FT STRAND 945..951
FT /evidence="ECO:0007829|PDB:5IKU"
FT STRAND 954..957
FT /evidence="ECO:0007829|PDB:5IKU"
FT STRAND 959..961
FT /evidence="ECO:0007829|PDB:5IKU"
FT STRAND 963..965
FT /evidence="ECO:0007829|PDB:5IKU"
FT STRAND 968..975
FT /evidence="ECO:0007829|PDB:5IKU"
FT STRAND 977..987
FT /evidence="ECO:0007829|PDB:5IKU"
FT STRAND 992..1000
FT /evidence="ECO:0007829|PDB:5IKU"
FT HELIX 1007..1018
FT /evidence="ECO:0007829|PDB:1NQJ"
FT STRAND 1024..1026
FT /evidence="ECO:0007829|PDB:1NQJ"
FT STRAND 1029..1033
FT /evidence="ECO:0007829|PDB:1NQJ"
FT STRAND 1039..1048
FT /evidence="ECO:0007829|PDB:1NQJ"
FT STRAND 1050..1070
FT /evidence="ECO:0007829|PDB:1NQJ"
FT STRAND 1082..1084
FT /evidence="ECO:0007829|PDB:1NQJ"
FT STRAND 1087..1094
FT /evidence="ECO:0007829|PDB:1NQJ"
FT STRAND 1096..1108
FT /evidence="ECO:0007829|PDB:1NQJ"
FT STRAND 1110..1117
FT /evidence="ECO:0007829|PDB:1NQJ"
SQ SEQUENCE 1118 AA; 126242 MW; 770CF3F60E4D4FD4 CRC64;
MKKNILKILM DSYSKESKIQ TVRRVTSVSL LAVYLTMNTS SLVLAKPIEN TNDTSIKNVE
KLRNAPNEEN SKKVEDSKND KVEHVKNIEE AKVEQVAPEV KSKSTLRSAS IANTNSEKYD
FEYLNGLSYT ELTNLIKNIK WNQINGLFNY STGSQKFFGD KNRVQAIINA LQESGRTYTA
NDMKGIETFT EVLRAGFYLG YYNDGLSYLN DRNFQDKCIP AMIAIQKNPN FKLGTAVQDE
VITSLGKLIG NASANAEVVN NCVPVLKQFR ENLNQYAPDY VKGTAVNELI KGIEFDFSGA
AYEKDVKTMP WYGKIDPFIN ELKALGLYGN ITSATEWASD VGIYYLSKFG LYSTNRNDIV
QSLEKAVDMY KYGKIAFVAM ERITWDYDGI GSNGKKVDHD KFLDDAEKHY LPKTYTFDNG
TFIIRAGDKV SEEKIKRLYW ASREVKSQFH RVVGNDKALE VGNADDVLTM KIFNSPEEYK
FNTNINGVST DNGGLYIEPR GTFYTYERTP QQSIFSLEEL FRHEYTHYLQ ARYLVDGLWG
QGPFYEKNRL TWFDEGTAEF FAGSTRTSGV LPRKSILGYL AKDKVDHRYS LKKTLNSGYD
DSDWMFYNYG FAVAHYLYEK DMPTFIKMNK AILNTDVKSY DEIIKKLSDD ANKNTEYQNH
IQELADKYQG AGIPLVSDDY LKDHGYKKAS EVYSEISKAA SLTNTSVTAE KSQYFNTFTL
RGTYTGETSK GEFKDWDEMS KKLDGTLESL AKNSWSGYKT LTAYFTNYRV TSDNKVQYDV
VFHGVLTDNA DISNNKAPIA KVTGPSTGAV GRNIEFSGKD SKDEDGKIVS YDWDFGDGAT
SRGKNSVHAY KKAGTYNVTL KVTDDKGATA TESFTIEIKN EDTTTPITKE MEPNDDIKEA
NGPIVEGVTV KGDLNGSDDA DTFYFDVKED GDVTIELPYS GSSNFTWLVY KEGDDQNHIA
SGIDKNNSKV GTFKSTKGRH YVFIYKHDSA SNISYSLNIK GLGNEKLKEK ENNDSSDKAT
VIPNFNTTMQ GSLLGDDSRD YYSFEVKEEG EVNIELDKKD EFGVTWTLHP ESNINDRITY
GQVDGNKVSN KVKLRPGKYY LLVYKYSGSG NYELRVNK
