ID SPPA_ECOLI Reviewed; 618 AA.
AC P08395; P77752; Q46723; Q46724; Q46725; Q46726; Q57183;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 29-AUG-2003, sequence version 2.
DT 24-JAN-2024, entry version 176.
DE RecName: Full=Protease 4;
DE EC=3.4.21.-;
DE AltName: Full=Endopeptidase IV;
DE AltName: Full=Protease IV;
DE AltName: Full=Signal peptide peptidase;
GN Name=sppA; OrderedLocusNames=b1766, JW1755;
OS Escherichia coli (strain K12).
OC Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, ACTIVITY REGULATION, SUBUNIT,
RP AND SUBCELLULAR LOCATION.
RC STRAIN=K12 / CS520;
RX PubMed=3522590; DOI=10.1016/s0021-9258(18)67669-0;
RA Ichihara S., Suzuki T., Suzuki M., Mizushima S.;
RT "Molecular cloning and sequencing of the sppA gene and characterization of
RT the encoded protease IV, a signal peptide peptidase, of Escherichia coli.";
RL J. Biol. Chem. 261:9405-9411(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=9097039; DOI=10.1093/dnares/3.6.363;
RA Aiba H., Baba T., Fujita K., Hayashi K., Inada T., Isono K., Itoh T.,
RA Kasai H., Kashimoto K., Kimura S., Kitakawa M., Kitagawa M., Makino K.,
RA Miki T., Mizobuchi K., Mori H., Mori T., Motomura K., Nakade S.,
RA Nakamura Y., Nashimoto H., Nishio Y., Oshima T., Saito N., Sampei G.,
RA Seki Y., Sivasundaram S., Tagami H., Takeda J., Takemoto K., Takeuchi Y.,
RA Wada C., Yamamoto Y., Horiuchi T.;
RT "A 570-kb DNA sequence of the Escherichia coli K-12 genome corresponding to
RT the 28.0-40.1 min region on the linkage map.";
RL DNA Res. 3:363-377(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 110-433.
RC STRAIN=Various ECOR strains;
RX PubMed=7973728; DOI=10.1126/science.7973728;
RA Guttman D.S., Dykhuizen D.E.;
RT "Clonal divergence in Escherichia coli as a result of recombination, not
RT mutation.";
RL Science 266:1380-1383(1994).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, ACTIVE SITE, TOPOLOGY, AND MUTAGENESIS OF
RP LYS-209; LYS-366; SER-409; GLY-410; TYR-412; HIS-510 AND ASP-524.
RC STRAIN=K12 / MC1061 / ATCC 53338 / DSM 7140;
RX PubMed=18476724; DOI=10.1021/bi800657p;
RA Wang P., Shim E., Cravatt B., Jacobsen R., Schoeniger J., Kim A.C.,
RA Paetzel M., Dalbey R.E.;
RT "Escherichia coli signal peptide peptidase A is a serine-lysine protease
RT with a lysine recruited to the nonconserved amino-terminal domain in the
RT S49 protease family.";
RL Biochemistry 47:6361-6369(2008).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12;
RX PubMed=21810987; DOI=10.1073/pnas.1108376108;
RA Saito A., Hizukuri Y., Matsuo E., Chiba S., Mori H., Nishimura O., Ito K.,
RA Akiyama Y.;
RT "Post-liberation cleavage of signal peptides is catalyzed by the site-2
RT protease (S2P) in bacteria.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:13740-13745(2011).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 47-618, FUNCTION, ACTIVE SITE,
RP TOPOLOGY, AND SUBUNIT.
RC STRAIN=K12;
RX PubMed=18164727; DOI=10.1016/j.jmb.2007.11.080;
RA Kim A.C., Oliver D.C., Paetzel M.;
RT "Crystal structure of a bacterial signal peptide peptidase.";
RL J. Mol. Biol. 376:352-366(2008).
CC -!- FUNCTION: Digests cleaved signal peptides in vitro, its in vivo
CC function is unknown. This activity is necessary to maintain proper
CC secretion of mature proteins across the membrane.
CC {ECO:0000269|PubMed:18164727, ECO:0000269|PubMed:18476724,
CC ECO:0000269|PubMed:21810987, ECO:0000269|PubMed:3522590}.
CC -!- ACTIVITY REGULATION: Inhibited by serine hydrolase inhibitor FP-biotin
CC and by antipain. {ECO:0000269|PubMed:3522590}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:18164727,
CC ECO:0000269|PubMed:3522590}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000269|PubMed:18476724,
CC ECO:0000269|PubMed:3522590}; Single-pass membrane protein
CC {ECO:0000269|PubMed:18476724, ECO:0000269|PubMed:3522590}.
CC -!- DOMAIN: A tandem duplication in the protein fold creates an intact
CC active site between the repeated domains of each monomer.
CC -!- DISRUPTION PHENOTYPE: No effect on processing of liberated signal
CC peptides in vivo. {ECO:0000269|PubMed:21810987}.
CC -!- SIMILARITY: Belongs to the peptidase S49 family. {ECO:0000305}.
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DR EMBL; M13359; AAA24648.1; -; Genomic_DNA.
DR EMBL; U00096; AAC74836.1; -; Genomic_DNA.
DR EMBL; AP009048; BAA15557.1; -; Genomic_DNA.
DR EMBL; U13772; AAA57008.1; -; Genomic_DNA.
DR EMBL; U13773; AAA57009.1; -; Genomic_DNA.
DR EMBL; U13774; AAA57010.1; -; Genomic_DNA.
DR EMBL; U13775; AAA57011.1; -; Genomic_DNA.
DR EMBL; U13776; AAA57012.1; -; Genomic_DNA.
DR EMBL; U13777; AAA57013.1; -; Genomic_DNA.
DR EMBL; U13778; AAA57014.1; -; Genomic_DNA.
DR EMBL; U13779; AAA57015.1; -; Genomic_DNA.
DR EMBL; U13780; AAA57016.1; -; Genomic_DNA.
DR EMBL; U13782; AAA57017.1; -; Genomic_DNA.
DR EMBL; U13833; AAA57030.1; -; Genomic_DNA.
DR EMBL; U13834; AAA57031.1; -; Genomic_DNA.
DR PIR; F64936; PRECT4.
DR PIR; I81191; I81191.
DR RefSeq; NP_416280.1; NC_000913.3.
DR RefSeq; WP_001259810.1; NZ_SSZK01000001.1.
DR PDB; 3BEZ; X-ray; 2.76 A; A/B/C/D=47-618.
DR PDB; 3BF0; X-ray; 2.55 A; A/B/C/D=47-618.
DR PDBsum; 3BEZ; -.
DR PDBsum; 3BF0; -.
DR AlphaFoldDB; P08395; -.
DR SMR; P08395; -.
DR BioGRID; 4259140; 22.
DR IntAct; P08395; 1.
DR STRING; 511145.b1766; -.
DR MEROPS; S49.001; -.
DR jPOST; P08395; -.
DR PaxDb; 511145-b1766; -.
DR EnsemblBacteria; AAC74836; AAC74836; b1766.
DR GeneID; 946281; -.
DR KEGG; ecj:JW1755; -.
DR KEGG; eco:b1766; -.
DR PATRIC; fig|1411691.4.peg.488; -.
DR EchoBASE; EB0961; -.
DR eggNOG; COG0616; Bacteria.
DR HOGENOM; CLU_008856_1_1_6; -.
DR InParanoid; P08395; -.
DR OMA; KGQYLYC; -.
DR OrthoDB; 9764363at2; -.
DR PhylomeDB; P08395; -.
DR BioCyc; EcoCyc:EG10968-MONOMER; -.
DR BioCyc; MetaCyc:EG10968-MONOMER; -.
DR EvolutionaryTrace; P08395; -.
DR PRO; PR:P08395; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:EcoCyc.
DR GO; GO:0004175; F:endopeptidase activity; IDA:EcoCyc.
DR GO; GO:0008236; F:serine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0006465; P:signal peptide processing; IMP:EcoliWiki.
DR CDD; cd07019; S49_SppA_1; 1.
DR CDD; cd07018; S49_SppA_67K_type; 1.
DR Gene3D; 6.20.330.10; -; 1.
DR InterPro; IPR029045; ClpP/crotonase-like_dom_sf.
DR InterPro; IPR004634; Pept_S49_pIV.
DR InterPro; IPR004635; Pept_S49_SppA.
DR InterPro; IPR002142; Peptidase_S49.
DR InterPro; IPR033854; S49_SppA_1.
DR InterPro; IPR047217; S49_SppA_67K_type_N.
DR NCBIfam; TIGR00705; SppA_67K; 1.
DR NCBIfam; TIGR00706; SppA_dom; 1.
DR PANTHER; PTHR33209; PROTEASE 4; 1.
DR PANTHER; PTHR33209:SF1; SERINE PROTEASE SPPA, CHLOROPLASTIC; 1.
DR Pfam; PF01343; Peptidase_S49; 2.
DR PIRSF; PIRSF001217; Protease_4_SppA; 1.
DR SUPFAM; SSF52096; ClpP/crotonase; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Cell inner membrane; Cell membrane; Hydrolase; Membrane;
KW Protease; Reference proteome; Serine protease; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..618
FT /note="Protease 4"
FT /id="PRO_0000171438"
FT TOPO_DOM 1..24
FT /note="Cytoplasmic"
FT TRANSMEM 25..45
FT /note="Helical"
FT TOPO_DOM 46..618
FT /note="Periplasmic"
FT ACT_SITE 209
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000305"
FT ACT_SITE 409
FT /note="Nucleophile"
FT VARIANT 151
FT /note="V -> I (in strain: ECOR 49 and ECOR 50)"
FT VARIANT 186
FT /note="G -> S (in strain: ECOR 16)"
FT VARIANT 252
FT /note="E -> H (in strain: ECOR 16)"
FT VARIANT 252
FT /note="E -> K (in strain: ECOR 49)"
FT VARIANT 252
FT /note="E -> Q (in strain: ECOR 38, ECOR 39, ECOR 40, ECOR
FT 50, ECOR 65 and ECOR 68)"
FT VARIANT 294
FT /note="A -> T (in strain: ECOR 38, ECOR 39, ECOR 40, ECOR
FT 49, ECOR 50 and ECOR 65)"
FT MUTAGEN 209
FT /note="K->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:18476724"
FT MUTAGEN 366
FT /note="K->A: Reduced activity."
FT /evidence="ECO:0000269|PubMed:18476724"
FT MUTAGEN 409
FT /note="S->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:18476724"
FT MUTAGEN 410
FT /note="G->A: Reduced activity."
FT /evidence="ECO:0000269|PubMed:18476724"
FT MUTAGEN 412
FT /note="Y->F: No effect on activity."
FT /evidence="ECO:0000269|PubMed:18476724"
FT MUTAGEN 510
FT /note="H->A: Reduced activity."
FT /evidence="ECO:0000269|PubMed:18476724"
FT MUTAGEN 524
FT /note="D->N: Increased activity."
FT /evidence="ECO:0000269|PubMed:18476724"
FT CONFLICT 378
FT /note="S -> T (in Ref. 1; AAA24648 and 5; AAA57009)"
FT /evidence="ECO:0000305"
FT STRAND 58..61
FT /evidence="ECO:0007829|PDB:3BF0"
FT STRAND 64..69
FT /evidence="ECO:0007829|PDB:3BF0"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:3BF0"
FT HELIX 97..109
FT /evidence="ECO:0007829|PDB:3BF0"
FT STRAND 116..119
FT /evidence="ECO:0007829|PDB:3BF0"
FT STRAND 122..125
FT /evidence="ECO:0007829|PDB:3BF0"
FT HELIX 128..143
FT /evidence="ECO:0007829|PDB:3BF0"
FT STRAND 148..153
FT /evidence="ECO:0007829|PDB:3BF0"
FT HELIX 157..163
FT /evidence="ECO:0007829|PDB:3BF0"
FT STRAND 166..171
FT /evidence="ECO:0007829|PDB:3BF0"
FT STRAND 186..188
FT /evidence="ECO:0007829|PDB:3BF0"
FT HELIX 190..195
FT /evidence="ECO:0007829|PDB:3BF0"
FT STRAND 199..205
FT /evidence="ECO:0007829|PDB:3BF0"
FT HELIX 210..212
FT /evidence="ECO:0007829|PDB:3BF0"
FT HELIX 213..216
FT /evidence="ECO:0007829|PDB:3BF0"
FT HELIX 222..247
FT /evidence="ECO:0007829|PDB:3BF0"
FT HELIX 251..254
FT /evidence="ECO:0007829|PDB:3BF0"
FT HELIX 257..266
FT /evidence="ECO:0007829|PDB:3BF0"
FT TURN 267..270
FT /evidence="ECO:0007829|PDB:3BF0"
FT HELIX 272..278
FT /evidence="ECO:0007829|PDB:3BF0"
FT STRAND 281..285
FT /evidence="ECO:0007829|PDB:3BF0"
FT HELIX 288..299
FT /evidence="ECO:0007829|PDB:3BF0"
FT TURN 303..305
FT /evidence="ECO:0007829|PDB:3BF0"
FT STRAND 306..312
FT /evidence="ECO:0007829|PDB:3BF0"
FT TURN 313..315
FT /evidence="ECO:0007829|PDB:3BF0"
FT STRAND 327..342
FT /evidence="ECO:0007829|PDB:3BF0"
FT STRAND 346..348
FT /evidence="ECO:0007829|PDB:3BF0"
FT HELIX 349..361
FT /evidence="ECO:0007829|PDB:3BF0"
FT STRAND 365..377
FT /evidence="ECO:0007829|PDB:3BF0"
FT HELIX 379..394
FT /evidence="ECO:0007829|PDB:3BF0"
FT STRAND 399..408
FT /evidence="ECO:0007829|PDB:3BF0"
FT HELIX 410..413
FT /evidence="ECO:0007829|PDB:3BF0"
FT TURN 414..417
FT /evidence="ECO:0007829|PDB:3BF0"
FT STRAND 419..423
FT /evidence="ECO:0007829|PDB:3BF0"
FT STRAND 428..430
FT /evidence="ECO:0007829|PDB:3BF0"
FT STRAND 434..440
FT /evidence="ECO:0007829|PDB:3BF0"
FT HELIX 442..447
FT /evidence="ECO:0007829|PDB:3BF0"
FT STRAND 451..453
FT /evidence="ECO:0007829|PDB:3BF0"
FT HELIX 459..461
FT /evidence="ECO:0007829|PDB:3BF0"
FT HELIX 471..495
FT /evidence="ECO:0007829|PDB:3BF0"
FT HELIX 500..504
FT /evidence="ECO:0007829|PDB:3BF0"
FT STRAND 511..513
FT /evidence="ECO:0007829|PDB:3BF0"
FT HELIX 514..519
FT /evidence="ECO:0007829|PDB:3BF0"
FT STRAND 524..526
FT /evidence="ECO:0007829|PDB:3BF0"
FT HELIX 529..539
FT /evidence="ECO:0007829|PDB:3BF0"
FT STRAND 545..548
FT /evidence="ECO:0007829|PDB:3BF0"
SQ SEQUENCE 618 AA; 67219 MW; EAF00496B5946AC3 CRC64;
MRTLWRFIAG FFKWTWRLLN FVREMVLNLF FIFLVLVGVG IWMQVSGGDS KETASRGALL
LDISGVIVDK PDSSQRFSKL SRQLLGASSD RLQENSLFDI VNTIRQAKDD RNITGIVMDL
KNFAGGDQPS MQYIGKALKE FRDSGKPVYA VGENYSQGQY YLASFANKIW LSPQGVVDLH
GFATNGLYYK SLLDKLKVST HVFRVGTYKS AVEPFIRDDM SPAAREADSR WIGELWQNYL
NTVAANRQIP AEQVFPGAQG LLEGLTKTGG DTAKYALENK LVDALASSAE IEKALTKEFG
WSKTDKNYRA ISYYDYALKT PADTGDSIGV VFANGAIMDG EETQGNVGGD TTAAQIRDAR
LDPKVKAIVL RVNSPGGSVT ASEVIRAELA AARAAGKPVV VSMGGMAASG GYWISTPANY
IVANPSTLTG SIGIFGVITT VENSLDSIGV HTDGVSTSPL ADVSITRALP PEAQLMMQLS
IENGYKRFIT LVADARHSTP EQIDKIAQGH VWTGQDAKAN GLVDSLGDFD DAVAKAAELA
KVKQWHLEYY VDEPTFFDKV MDNMSGSVRA MLPDAFQAML PAPLASVAST VKSESDKLAA
FNDPQNRYAF CLTCANMR
//
