ULIL_METAC
ID ULIL_METAC Reviewed; 342 AA.
AC Q8TL28;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Ulilysin;
DE EC=3.4.24.-;
DE Flags: Precursor;
GN OrderedLocusNames=MA_3214;
OS Methanosarcina acetivorans (strain ATCC 35395 / DSM 2834 / JCM 12185 /
OS C2A).
OC Archaea; Euryarchaeota; Stenosarchaea group; Methanomicrobia;
OC Methanosarcinales; Methanosarcinaceae; Methanosarcina.
OX NCBI_TaxID=188937;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 35395 / DSM 2834 / JCM 12185 / C2A;
RX PubMed=11932238; DOI=10.1101/gr.223902;
RA Galagan J.E., Nusbaum C., Roy A., Endrizzi M.G., Macdonald P., FitzHugh W.,
RA Calvo S., Engels R., Smirnov S., Atnoor D., Brown A., Allen N., Naylor J.,
RA Stange-Thomann N., DeArellano K., Johnson R., Linton L., McEwan P.,
RA McKernan K., Talamas J., Tirrell A., Ye W., Zimmer A., Barber R.D.,
RA Cann I., Graham D.E., Grahame D.A., Guss A.M., Hedderich R.,
RA Ingram-Smith C., Kuettner H.C., Krzycki J.A., Leigh J.A., Li W., Liu J.,
RA Mukhopadhyay B., Reeve J.N., Smith K., Springer T.A., Umayam L.A.,
RA White O., White R.H., de Macario E.C., Ferry J.G., Jarrell K.F., Jing H.,
RA Macario A.J.L., Paulsen I.T., Pritchett M., Sowers K.R., Swanson R.V.,
RA Zinder S.H., Lander E., Metcalf W.W., Birren B.;
RT "The genome of Methanosarcina acetivorans reveals extensive metabolic and
RT physiological diversity.";
RL Genome Res. 12:532-542(2002).
RN [2]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, CHARACTERIZATION, AUTOCATALYTIC
RP CLEAVAGES, SUBSTRATE SPECIFICITY, COFACTOR, SUBUNIT, MASS SPECTROMETRY,
RP ACTIVITY REGULATION, DISULFIDE BONDS, AND X-RAY CRYSTALLOGRAPHY (1.7
RP ANGSTROMS) OF 61-322 OF MUTANT ALA-269 IN COMPLEX WITH DIPEPTIDE PRODUCT
RP AND ZINC.
RC STRAIN=ATCC 35395 / DSM 2834 / JCM 12185 / C2A;
RX PubMed=16627477; DOI=10.1074/jbc.m600907200;
RA Tallant C., Garcia-Castellanos R., Seco J., Baumann U., Gomis-Rueth F.X.;
RT "Molecular analysis of ulilysin, the structural prototype of a new family
RT of metzincin metalloproteases.";
RL J. Biol. Chem. 281:17920-17928(2006).
RN [3]
RP PH DEPENDENCE.
RA Gomis-Rueth F.X.;
RL Unpublished observations (FEB-2007).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 61-322 OF MUTANT ALA-269 IN
RP COMPLEX WITH INHIBITOR AND ZINC, DISULFIDE BONDS, AND ACTIVITY REGULATION.
RC STRAIN=ATCC 35395 / DSM 2834 / JCM 12185 / C2A;
RX PubMed=17097044; DOI=10.1016/j.abb.2006.10.004;
RA Garcia-Castellanos R., Tallant C., Marrero A., Sola M., Baumann U.,
RA Gomis-Rueth F.X.;
RT "Substrate specificity of a metalloprotease of the pappalysin family
RT revealed by an inhibitor and a product complex.";
RL Arch. Biochem. Biophys. 457:57-72(2007).
CC -!- FUNCTION: Metalloprotease which in vitro specifically cleaves IGFBP-2
CC to -6, insulin, and extracellular matrix proteins but not IGFBP-1 or
CC IGF-II. Shows a preference for substrates with an arginine in the P1'
CC position, the first position downstream of the scissile bond.
CC {ECO:0000269|PubMed:16627477}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:16627477};
CC Note=Binds 2 calcium ions per subunit. {ECO:0000269|PubMed:16627477};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:16627477};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:16627477};
CC -!- ACTIVITY REGULATION: Inhibited by EDTA, excess zinc, and also
CC significantly by batimastat in vitro. Is not inhibited by other
CC metalloprotease inhibitors like phosphoramidon, captopril and galardine
CC or those targeting other classes of proteases.
CC {ECO:0000269|PubMed:16627477, ECO:0000269|PubMed:17097044}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.5. {ECO:0000269|Ref.3};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:16627477,
CC ECO:0000269|PubMed:17097044}.
CC -!- DOMAIN: Consists of two subdomains separated by an active site cleft
CC containing the catalytic zinc ion.
CC -!- PTM: The inactive zymogen pro-ulilysin undergoes calcium-mediated
CC autolytic activation to the mature ulilysin. Autoproteolytic activation
CC entails removal of the first 60 residues and of a highly charged 20-
CC residue C-terminal tail.
CC -!- MASS SPECTROMETRY: Mass=28885; Mass_error=50; Method=Unknown;
CC Evidence={ECO:0000269|PubMed:16627477};
CC -!- SIMILARITY: Belongs to the peptidase M43B family. {ECO:0000305}.
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DR EMBL; AE010299; AAM06585.1; -; Genomic_DNA.
DR RefSeq; WP_011023149.1; NC_003552.1.
DR PDB; 2CKI; X-ray; 1.70 A; A/B=61-322.
DR PDB; 2J83; X-ray; 2.00 A; A/B=61-322.
DR PDB; 3LUM; X-ray; 1.70 A; A/B/C/D=61-322.
DR PDB; 3LUN; X-ray; 1.80 A; A/B=61-322.
DR PDBsum; 2CKI; -.
DR PDBsum; 2J83; -.
DR PDBsum; 3LUM; -.
DR PDBsum; 3LUN; -.
DR AlphaFoldDB; Q8TL28; -.
DR SMR; Q8TL28; -.
DR STRING; 188937.MA_3214; -.
DR MEROPS; M43.007; -.
DR EnsemblBacteria; AAM06585; AAM06585; MA_3214.
DR GeneID; 1475107; -.
DR KEGG; mac:MA_3214; -.
DR HOGENOM; CLU_011684_0_0_2; -.
DR InParanoid; Q8TL28; -.
DR OrthoDB; 133018at2157; -.
DR PhylomeDB; Q8TL28; -.
DR EvolutionaryTrace; Q8TL28; -.
DR Proteomes; UP000002487; Chromosome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008237; F:metallopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd04275; ZnMc_pappalysin_like; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR008754; Peptidase_M43.
DR Pfam; PF05572; Peptidase_M43; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Direct protein sequencing; Disulfide bond;
KW Hydrolase; Metal-binding; Metalloprotease; Protease; Reference proteome;
KW Signal; Zinc; Zymogen.
FT SIGNAL 1..?
FT /evidence="ECO:0000255"
FT PROPEP ?..60
FT /note="Removed in mature form"
FT /id="PRO_0000280823"
FT CHAIN 61..322
FT /note="Ulilysin"
FT /id="PRO_0000280824"
FT PROPEP 323..342
FT /note="Removed in mature form"
FT /id="PRO_0000280825"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 323..342
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 229
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:16627477,
FT ECO:0000269|PubMed:17097044"
FT BINDING 188..189
FT /ligand="substrate"
FT BINDING 225
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:16627477"
FT BINDING 228
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:16627477, ECO:0000269|PubMed:17097044"
FT BINDING 232
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:16627477, ECO:0000269|PubMed:17097044"
FT BINDING 238
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:16627477, ECO:0000269|PubMed:17097044"
FT BINDING 240
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:16627477,
FT ECO:0000269|PubMed:17097044"
FT BINDING 243
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:16627477,
FT ECO:0000269|PubMed:17097044"
FT BINDING 249
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:16627477,
FT ECO:0000269|PubMed:17097044"
FT BINDING 254
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:16627477,
FT ECO:0000269|PubMed:17097044"
FT BINDING 256
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:16627477,
FT ECO:0000269|PubMed:17097044"
FT BINDING 259
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:16627477,
FT ECO:0000269|PubMed:17097044"
FT BINDING 262
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:16627477,
FT ECO:0000269|PubMed:17097044"
FT BINDING 263
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:16627477,
FT ECO:0000269|PubMed:17097044"
FT BINDING 295
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:16627477"
FT DISULFID 250..277
FT /evidence="ECO:0000269|PubMed:16627477,
FT ECO:0000269|PubMed:17097044"
FT DISULFID 269..297
FT /evidence="ECO:0000305"
FT STRAND 65..77
FT /evidence="ECO:0007829|PDB:2CKI"
FT HELIX 78..80
FT /evidence="ECO:0007829|PDB:2CKI"
FT HELIX 84..97
FT /evidence="ECO:0007829|PDB:2CKI"
FT TURN 98..100
FT /evidence="ECO:0007829|PDB:2CKI"
FT HELIX 103..107
FT /evidence="ECO:0007829|PDB:2CKI"
FT HELIX 110..115
FT /evidence="ECO:0007829|PDB:2CKI"
FT STRAND 121..125
FT /evidence="ECO:0007829|PDB:2CKI"
FT STRAND 137..142
FT /evidence="ECO:0007829|PDB:2CKI"
FT HELIX 153..155
FT /evidence="ECO:0007829|PDB:2CKI"
FT HELIX 157..159
FT /evidence="ECO:0007829|PDB:2CKI"
FT TURN 167..169
FT /evidence="ECO:0007829|PDB:2CKI"
FT STRAND 171..177
FT /evidence="ECO:0007829|PDB:2CKI"
FT STRAND 188..191
FT /evidence="ECO:0007829|PDB:2CKI"
FT HELIX 198..200
FT /evidence="ECO:0007829|PDB:2CKI"
FT STRAND 202..206
FT /evidence="ECO:0007829|PDB:2CKI"
FT HELIX 207..209
FT /evidence="ECO:0007829|PDB:2CKI"
FT STRAND 210..213
FT /evidence="ECO:0007829|PDB:2CKI"
FT HELIX 224..233
FT /evidence="ECO:0007829|PDB:2CKI"
FT TURN 280..282
FT /evidence="ECO:0007829|PDB:2CKI"
FT TURN 295..297
FT /evidence="ECO:0007829|PDB:2CKI"
FT HELIX 303..314
FT /evidence="ECO:0007829|PDB:2CKI"
FT TURN 315..317
FT /evidence="ECO:0007829|PDB:2CKI"
FT HELIX 318..320
FT /evidence="ECO:0007829|PDB:2CKI"
SQ SEQUENCE 342 AA; 38371 MW; B2480CD7BB2B9574 CRC64;
MAEKFESRGI EEASSEVPTQ RRCGAMEVHH RLLRSASYVR ERDQIENLAL KYKQGFRAIS
RMEIVKIPVV VHVVWNEEEE NISDAQIQSQ IDILNKDFRK LNSDVSQVPS VWSNLIADLG
IEFFLATKDP NGNQTTGITR TQTSVTFFTT SDEVKFASSG GEDAWPADRY LNIWVCHVLK
SEIGQDILGY AQFPGGPAET DGVVIVDAAF GTTGTALPPF DKGRTATHEI GHWLNLYHIW
GDELRFEDPC SRSDEVDDTP NQADPNFGCP SYPHVSCSNG PNGDMFMNYM DYVDDKCMVM
FTQGQATRVN ACLDGPRSSF LARVEETEKK EAPSKREMPM PR
