STOPP_PYRHO
ID STOPP_PYRHO Reviewed; 441 AA.
AC O59179;
DT 14-MAY-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Membrane-bound protease PH1510;
DE EC=3.4.21.-;
DE AltName: Full=NfeD homolog;
DE AltName: Full=Stomatin operon partner protein;
DE Short=STOPP;
DE Flags: Precursor;
GN OrderedLocusNames=PH1510;
OS Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC
OS 100139 / OT-3).
OC Archaea; Euryarchaeota; Thermococci; Thermococcales; Thermococcaceae;
OC Pyrococcus.
OX NCBI_TaxID=70601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3;
RX PubMed=9679194; DOI=10.1093/dnares/5.2.55;
RA Kawarabayasi Y., Sawada M., Horikawa H., Haikawa Y., Hino Y., Yamamoto S.,
RA Sekine M., Baba S., Kosugi H., Hosoyama A., Nagai Y., Sakai M., Ogura K.,
RA Otsuka R., Nakazawa H., Takamiya M., Ohfuku Y., Funahashi T., Tanaka T.,
RA Kudoh Y., Yamazaki J., Kushida N., Oguchi A., Aoki K., Yoshizawa T.,
RA Nakamura Y., Robb F.T., Horikoshi K., Masuchi Y., Shizuya H., Kikuchi H.;
RT "Complete sequence and gene organization of the genome of a hyper-
RT thermophilic archaebacterium, Pyrococcus horikoshii OT3.";
RL DNA Res. 5:55-76(1998).
RN [2]
RP FUNCTION, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF THR-62;
RP SER-97; LYS-138 AND ASP-168, AND ACTIVITY REGULATION.
RC STRAIN=ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3;
RX PubMed=15611110; DOI=10.1074/jbc.m411748200;
RA Yokoyama H., Matsui I.;
RT "A novel thermostable membrane protease forming an operon with a stomatin
RT homolog from the hyperthermophilic archaebacterium Pyrococcus horikoshii.";
RL J. Biol. Chem. 280:6588-6594(2005).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 16-236, SUBUNIT, AND FUNCTION.
RC STRAIN=ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3;
RX PubMed=16574150; DOI=10.1016/j.jmb.2006.02.052;
RA Yokoyama H., Matsui E., Akiba T., Harata K., Matsui I.;
RT "Molecular structure of a novel membrane protease specific for a stomatin
RT homolog from the hyperthermophilic archaeon Pyrococcus horikoshii.";
RL J. Mol. Biol. 358:1152-1164(2006).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 16-236 OF MUTANT ALA-138, AND
RP SUBUNIT.
RC STRAIN=ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3;
RX PubMed=18421152; DOI=10.1107/s0909049507068471;
RA Yokoyama H., Hamamatsu S., Fujii S., Matsui I.;
RT "Novel dimer structure of a membrane-bound protease with a catalytic Ser-
RT Lys dyad and its linkage to stomatin.";
RL J. Synchrotron Radiat. 15:254-257(2008).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 16-236 OF MUTANT ALA-138 IN
RP COMPLEX WITH SUBSTRATE PEPTIDE, AND SUBUNIT.
RC STRAIN=ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3;
RX PubMed=22475127; DOI=10.1021/bi300098k;
RA Yokoyama H., Takizawa N., Kobayashi D., Matsui I., Fujii S.;
RT "Crystal structure of a membrane stomatin-specific protease in complex with
RT a substrate peptide.";
RL Biochemistry 51:3872-3880(2012).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 16-236 OF MUTANT ALA-138, AND
RP FUNCTION.
RC STRAIN=ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3;
RX PubMed=24121343; DOI=10.1107/s0909049513021328;
RA Yokoyama H., Kobayashi D., Takizawa N., Fujii S., Matsui I.;
RT "Structural and biochemical analysis of a thermostable membrane-bound
RT stomatin-specific protease.";
RL J. Synchrotron Radiat. 20:933-937(2013).
CC -!- FUNCTION: Protease that cleaves its substrates preferentially near
CC hydrophobic or aromatic amino acid residues. Can degrade casein and the
CC stomatin homolog PH1511 (in vitro). {ECO:0000269|PubMed:15611110,
CC ECO:0000269|PubMed:16574150, ECO:0000269|PubMed:24121343}.
CC -!- ACTIVITY REGULATION: Inhibited by divalent metal cations, including
CC Mg(2+), Mn(2+), Ca(2+) and Zn(2+). Mildly inhibited by 0.01 % SDS and
CC 0.1% dodecyl-beta-D-maltoside. Activity is nearly abolished by 1 % SDS.
CC {ECO:0000269|PubMed:15611110}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 5-6. {ECO:0000269|PubMed:15611110};
CC Temperature dependence:
CC Optimum temperature is above 90 degrees Celsius.
CC {ECO:0000269|PubMed:15611110};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:15611110,
CC ECO:0000269|PubMed:16574150, ECO:0000269|PubMed:18421152,
CC ECO:0000269|PubMed:22475127}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the peptidase S14 family. {ECO:0000305}.
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; BA000001; BAA30618.1; -; Genomic_DNA.
DR PIR; B71027; B71027.
DR RefSeq; WP_010885587.1; NC_000961.1.
DR PDB; 2DEO; X-ray; 3.00 A; A/B=16-236.
DR PDB; 3BPP; X-ray; 2.30 A; A=16-236.
DR PDB; 3VIV; X-ray; 2.25 A; A/B=16-236.
DR PDB; 3WG5; X-ray; 2.40 A; A/B=16-236.
DR PDB; 3WWV; X-ray; 2.40 A; A=371-441.
DR PDB; 6M4B; X-ray; 2.25 A; A/B=16-236.
DR PDBsum; 2DEO; -.
DR PDBsum; 3BPP; -.
DR PDBsum; 3VIV; -.
DR PDBsum; 3WG5; -.
DR PDBsum; 3WWV; -.
DR PDBsum; 6M4B; -.
DR AlphaFoldDB; O59179; -.
DR SMR; O59179; -.
DR STRING; 70601.3257935; -.
DR MEROPS; S49.005; -.
DR TCDB; 8.A.21.2.1; the stomatin/podocin/band 7/nephrosis,2/spfh (stomatin) family.
DR EnsemblBacteria; BAA30618; BAA30618; BAA30618.
DR GeneID; 1443826; -.
DR KEGG; pho:PH1510; -.
DR eggNOG; arCOG01910; Archaea.
DR OMA; QMDTPGG; -.
DR OrthoDB; 38523at2157; -.
DR BRENDA; 3.4.21.B56; 5244.
DR EvolutionaryTrace; O59179; -.
DR Proteomes; UP000000752; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0008236; F:serine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd07015; Clp_protease_NfeD; 1.
DR Gene3D; 2.40.50.140; -; 1.
DR InterPro; IPR029045; ClpP/crotonase-like_dom_sf.
DR InterPro; IPR023562; ClpP/TepA.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR002810; NfeD-like_C.
DR InterPro; IPR033853; PH1510-N.
DR Pfam; PF00574; CLP_protease; 1.
DR Pfam; PF01957; NfeD; 1.
DR SUPFAM; SSF52096; SSF52096; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Membrane; Protease; Serine protease; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..441
FT /note="Membrane-bound protease PH1510"
FT /id="PRO_0000429022"
FT TRANSMEM 239..259
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 271..291
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 307..327
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 344..364
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 97
FT /note="Nucleophile"
FT ACT_SITE 138
FT /note="Proton donor/acceptor"
FT BINDING 64..67
FT /ligand="substrate"
FT BINDING 119..124
FT /ligand="substrate"
FT MUTAGEN 62
FT /note="T->A: Reduces enzyme activity by over 90%."
FT /evidence="ECO:0000269|PubMed:15611110"
FT MUTAGEN 97
FT /note="S->A: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:15611110"
FT MUTAGEN 138
FT /note="K->A: Reduces enzyme activity by 99%."
FT /evidence="ECO:0000269|PubMed:15611110"
FT MUTAGEN 168
FT /note="D->A: Reduces enzyme activity by 97%."
FT /evidence="ECO:0000269|PubMed:15611110"
FT STRAND 23..31
FT /evidence="ECO:0007829|PDB:3VIV"
FT HELIX 35..50
FT /evidence="ECO:0007829|PDB:3VIV"
FT STRAND 54..63
FT /evidence="ECO:0007829|PDB:3VIV"
FT HELIX 67..78
FT /evidence="ECO:0007829|PDB:3VIV"
FT STRAND 84..88
FT /evidence="ECO:0007829|PDB:3VIV"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:3VIV"
FT HELIX 98..104
FT /evidence="ECO:0007829|PDB:3VIV"
FT STRAND 106..111
FT /evidence="ECO:0007829|PDB:3VIV"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:3VIV"
FT STRAND 122..126
FT /evidence="ECO:0007829|PDB:3VIV"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:6M4B"
FT STRAND 132..134
FT /evidence="ECO:0007829|PDB:3VIV"
FT HELIX 137..153
FT /evidence="ECO:0007829|PDB:3VIV"
FT HELIX 158..166
FT /evidence="ECO:0007829|PDB:3VIV"
FT HELIX 173..178
FT /evidence="ECO:0007829|PDB:3VIV"
FT STRAND 183..185
FT /evidence="ECO:0007829|PDB:3VIV"
FT HELIX 189..196
FT /evidence="ECO:0007829|PDB:3VIV"
FT STRAND 218..221
FT /evidence="ECO:0007829|PDB:3VIV"
FT HELIX 226..236
FT /evidence="ECO:0007829|PDB:3VIV"
FT HELIX 376..379
FT /evidence="ECO:0007829|PDB:3WWV"
FT STRAND 383..388
FT /evidence="ECO:0007829|PDB:3WWV"
FT STRAND 390..398
FT /evidence="ECO:0007829|PDB:3WWV"
FT STRAND 401..409
FT /evidence="ECO:0007829|PDB:3WWV"
FT STRAND 418..425
FT /evidence="ECO:0007829|PDB:3WWV"
FT STRAND 428..433
FT /evidence="ECO:0007829|PDB:3WWV"
SQ SEQUENCE 441 AA; 48281 MW; 2E16ECFC4529C4E6 CRC64;
MRRILLSMIV LIFLASPILA KNIVYVAQIK GQITSYTYDQ FDRYITIAEQ DNAEAIIIEL
DTPGGRADAM MNIVQRIQQS KIPVIIYVYP PGASAASAGT YIALGSHLIA MAPGTSIGAC
RPILGYSQNG SIIEAPPKIT NYFIAYIKSL AQESGRNATI AEEFITKDLS LTPEEALKYG
VIEVVARDIN ELLKKSNGMK TKIPVNGRYV TLNFTNVEVR YLAPSFKDKL ISYITDPNVA
YLLLTLGIWA LIIGFLTPGW HVPETVGAIM IILAIIGFGY FGYNSAGILL IIVAMLFFIA
EALTPTFGLF TVAGLITFII GGILLFGGGE EYLVRKEVFS QLRILIITVG AILAAFFAFG
MAAVIRAHKK KARTGKEEMI GLIGTVVEEL NPEGMIKVRG ELWKARSKFN GKIEKGEKVR
VVDMDGLTLI VVRERKEGGE K
