ID FTSH_THET8 Reviewed; 624 AA.
AC Q5SI82; Q9LCZ4;
DT 02-NOV-2010, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 27-MAR-2024, entry version 120.
DE RecName: Full=ATP-dependent zinc metalloprotease FtsH {ECO:0000255|HAMAP-Rule:MF_01458};
DE EC=3.4.24.- {ECO:0000255|HAMAP-Rule:MF_01458};
GN Name=ftsH {ECO:0000255|HAMAP-Rule:MF_01458}; OrderedLocusNames=TTHA1492;
OS Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8).
OC Bacteria; Deinococcota; Deinococci; Thermales; Thermaceae; Thermus.
OX NCBI_TaxID=300852;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION, ATPASE ACTIVITY,
RP PROCESSIVE PROTEASE ACTIVITY, ACTIVITY REGULATION, AND ZINC COFACTOR.
RX PubMed=10788805; DOI=10.1093/oxfordjournals.jbchem.a022689;
RA Asahara Y., Atsuta K., Motohashi K., Taguchi H., Yohda M., Yoshida M.;
RT "FtsH recognizes proteins with unfolded structure and hydrolyzes the
RT carboxyl side of hydrophobic residues.";
RL J. Biochem. 127:931-937(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 27634 / DSM 579 / HB8;
RA Masui R., Kurokawa K., Nakagawa N., Tokunaga F., Koyama Y., Shibata T.,
RA Oshima T., Yokoyama S., Yasunaga T., Kuramitsu S.;
RT "Complete genome sequence of Thermus thermophilus HB8.";
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-61.
RX PubMed=10377389; DOI=10.1073/pnas.96.13.7184;
RA Motohashi K., Watanabe Y.H., Yohda M., Yoshida M.;
RT "Heat-inactivated proteins are rescued by the DnaK/J-GrpE set and ClpB
RT chaperones.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:7184-7189(1999).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 146-393 WITHOUT NUCLEOTIDE,
RP COMPLEXED WITH ADP OR AMP-PNP, X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF
RP 126-393, AND POSSIBLE SUBUNIT.
RX PubMed=12377127; DOI=10.1016/s0969-2126(02)00855-9;
RA Niwa H., Tsuchiya D., Makyio H., Yoshida M., Morikawa K.;
RT "Hexameric ring structure of the ATPase domain of the membrane-integrated
RT metalloprotease FtsH from Thermus thermophilus HB8.";
RL Structure 10:1415-1423(2002).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (3.9 ANGSTROMS) OF 126-624, SUBUNIT, MUTAGENESIS OF
RP GLY-399, PROTEOLYTIC ACTIVITY, AND ATP-DEPENDENCE.
RX PubMed=16762831; DOI=10.1016/j.molcel.2006.04.020;
RA Suno R., Niwa H., Tsuchiya D., Zhang X., Yoshida M., Morikawa K.;
RT "Structure of the whole cytosolic region of ATP-dependent protease FtsH.";
RL Mol. Cell 22:575-585(2006).
CC -!- FUNCTION: Acts as a processive, ATP-dependent zinc metallopeptidase for
CC both cytoplasmic and membrane proteins. Plays a role in the quality
CC control of integral membrane proteins. {ECO:0000255|HAMAP-
CC Rule:MF_01458}.
CC -!- FUNCTION: Degrades preferentially unfolded substrates in a processive,
CC ATP-dependent manner, usually after hydrophobic residues.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01458};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|HAMAP-Rule:MF_01458};
CC -!- ACTIVITY REGULATION: The proteolytic activity is dependent on ATP, both
CC the ATPase and protease activities are inhibited by ADP.
CC {ECO:0000269|PubMed:10788805}.
CC -!- SUBUNIT: The isolated soluble domain (residues 126-624) forms a stable
CC hexamer in which the AAA+ domains (residues 126-400) are alternatively
CC open or closed. {ECO:0000269|PubMed:16762831}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane
CC {ECO:0000305|PubMed:10788805}; Multi-pass membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_01458}; Cytoplasmic side {ECO:0000255|HAMAP-
CC Rule:MF_01458}.
CC -!- DOMAIN: The open AAA+ domain (residues 126-400) probably allows
CC nucleotide exchange and has the protease active site, while the closed
CC domain is the active ATPase domain but the protease is inactive.
CC -!- SIMILARITY: In the central section; belongs to the AAA ATPase family.
CC {ECO:0000255|HAMAP-Rule:MF_01458}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the peptidase M41
CC family. {ECO:0000255|HAMAP-Rule:MF_01458}.
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DR EMBL; AB032368; BAA96090.1; -; Genomic_DNA.
DR EMBL; AP008226; BAD71315.1; -; Genomic_DNA.
DR EMBL; AB012390; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; WP_011173542.1; NC_006461.1.
DR RefSeq; YP_144758.1; NC_006461.1.
DR PDB; 1IXZ; X-ray; 2.20 A; A=146-393.
DR PDB; 1IY0; X-ray; 2.95 A; A=146-393.
DR PDB; 1IY1; X-ray; 2.80 A; A=146-393.
DR PDB; 1IY2; X-ray; 3.20 A; A=126-393.
DR PDB; 2DHR; X-ray; 3.90 A; A/B/C/D/E/F=126-624.
DR PDB; 4EIW; X-ray; 3.90 A; A/B/C/D/E/F=126-624.
DR PDBsum; 1IXZ; -.
DR PDBsum; 1IY0; -.
DR PDBsum; 1IY1; -.
DR PDBsum; 1IY2; -.
DR PDBsum; 2DHR; -.
DR PDBsum; 4EIW; -.
DR AlphaFoldDB; Q5SI82; -.
DR SMR; Q5SI82; -.
DR MEROPS; M41.013; -.
DR EnsemblBacteria; BAD71315; BAD71315; BAD71315.
DR GeneID; 3170023; -.
DR KEGG; ttj:TTHA1492; -.
DR PATRIC; fig|300852.9.peg.1467; -.
DR eggNOG; COG0465; Bacteria.
DR HOGENOM; CLU_000688_16_2_0; -.
DR PhylomeDB; Q5SI82; -.
DR BRENDA; 3.4.24.B17; 2305.
DR EvolutionaryTrace; Q5SI82; -.
DR Proteomes; UP000000532; Chromosome.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:UniProtKB-UniRule.
DR GO; GO:0004176; F:ATP-dependent peptidase activity; IEA:InterPro.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0030163; P:protein catabolic process; IEA:UniProtKB-UniRule.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd19501; RecA-like_FtsH; 1.
DR Gene3D; 1.10.8.60; -; 1.
DR Gene3D; 3.30.720.210; -; 1.
DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR Gene3D; 1.20.58.760; Peptidase M41; 1.
DR HAMAP; MF_01458; FtsH; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR041569; AAA_lid_3.
DR InterPro; IPR003959; ATPase_AAA_core.
DR InterPro; IPR003960; ATPase_AAA_CS.
DR InterPro; IPR005936; FtsH.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR011546; Pept_M41_FtsH_extracell.
DR InterPro; IPR000642; Peptidase_M41.
DR InterPro; IPR037219; Peptidase_M41-like.
DR NCBIfam; TIGR01241; FtsH_fam; 1.
DR PANTHER; PTHR23076:SF97; ATP-DEPENDENT ZINC METALLOPROTEASE FTSH 2, CHLOROPLASTIC-RELATED; 1.
DR PANTHER; PTHR23076; METALLOPROTEASE M41 FTSH; 1.
DR Pfam; PF00004; AAA; 1.
DR Pfam; PF17862; AAA_lid_3; 1.
DR Pfam; PF06480; FtsH_ext; 1.
DR Pfam; PF01434; Peptidase_M41; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF140990; FtsH protease domain-like; 1.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR PROSITE; PS00674; AAA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell inner membrane; Cell membrane; Hydrolase;
KW Membrane; Metal-binding; Metalloprotease; Nucleotide-binding; Protease;
KW Reference proteome; Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..624
FT /note="ATP-dependent zinc metalloprotease FtsH"
FT /id="PRO_0000400413"
FT TOPO_DOM 1..7
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01458"
FT TRANSMEM 8..28
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01458"
FT TOPO_DOM 29..103
FT /note="Periplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01458"
FT TRANSMEM 104..124
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01458"
FT TOPO_DOM 125..624
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01458"
FT REGION 595..624
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 596..612
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 419
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01458"
FT BINDING 159
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 199..203
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 204
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 418
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01458"
FT BINDING 422
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01458"
FT BINDING 493
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01458"
FT MUTAGEN 399
FT /note="G->L: No effect on protease activity against alpha-
FT casein."
FT /evidence="ECO:0000269|PubMed:16762831"
FT CONFLICT 21..25
FT /note="AFSLA -> PSASR (in Ref. 1; BAA96090 and 2;
FT AB012390)"
FT /evidence="ECO:0000305"
FT HELIX 155..157
FT /evidence="ECO:0007829|PDB:1IXZ"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:1IY2"
FT HELIX 162..176
FT /evidence="ECO:0007829|PDB:1IXZ"
FT HELIX 178..183
FT /evidence="ECO:0007829|PDB:1IXZ"
FT STRAND 190..195
FT /evidence="ECO:0007829|PDB:1IXZ"
FT STRAND 198..201
FT /evidence="ECO:0007829|PDB:1IY1"
FT HELIX 202..212
FT /evidence="ECO:0007829|PDB:1IXZ"
FT STRAND 217..221
FT /evidence="ECO:0007829|PDB:1IXZ"
FT HELIX 222..227
FT /evidence="ECO:0007829|PDB:1IXZ"
FT TURN 229..231
FT /evidence="ECO:0007829|PDB:1IY2"
FT HELIX 232..244
FT /evidence="ECO:0007829|PDB:1IXZ"
FT STRAND 247..255
FT /evidence="ECO:0007829|PDB:1IXZ"
FT HELIX 257..261
FT /evidence="ECO:0007829|PDB:1IXZ"
FT HELIX 273..287
FT /evidence="ECO:0007829|PDB:1IXZ"
FT STRAND 295..302
FT /evidence="ECO:0007829|PDB:1IXZ"
FT HELIX 304..306
FT /evidence="ECO:0007829|PDB:1IXZ"
FT HELIX 309..312
FT /evidence="ECO:0007829|PDB:1IXZ"
FT STRAND 319..322
FT /evidence="ECO:0007829|PDB:1IXZ"
FT HELIX 328..339
FT /evidence="ECO:0007829|PDB:1IXZ"
FT HELIX 350..355
FT /evidence="ECO:0007829|PDB:1IXZ"
FT HELIX 362..378
FT /evidence="ECO:0007829|PDB:1IXZ"
FT STRAND 382..384
FT /evidence="ECO:0007829|PDB:1IXZ"
FT HELIX 386..392
FT /evidence="ECO:0007829|PDB:1IXZ"
SQ SEQUENCE 624 AA; 68452 MW; A2000075F32E3A6F CRC64;
MPRAPFSLLA LVLGLAFLAW AFSLAGTVGA PSGTVNYTTF LEDLKAGRVK EVVVRAGDTR
IQGVLEDGSA FTTYAASPPD NATLEGWMAR GVSVRVEPPQ GQNALGFLWP LLLVGLLIGA
LYYFSRNGRA GPSDSAFSFT KSRARVLTEA PKVTFKDVAG AEEAKEELKE IVEFLKNPSR
FHEMGARIPK GVLLVGPPGV GKTHLARAVA GEARVPFITA SGSDFVEMFV GVGAARVRDL
FETAKRHAPC IVFIDEIDAV GRKRGSGVGG GNDEREQTLN QLLVEMDGFE KDTAIVVMAA
TNRPDILDPA LLRPGRFDRQ IAIDAPDVKG REQILRIHAR GKPLAEDVDL ALLAKRTPGF
VGADLENLLN EAALLAAREG RRKITMKDLE EAADRVMMGP AKKSLVLSPR DRRITAYHEA
GHALAAHFLE HADGVHKVTI VPRGRALGFM MPRREDMLHW SRKRLLDQIA VALAGRAAEE
IVFDDVTTGA ENDFRQATEL ARRMITEWGM HPEFGPVAYA VREDTYLGGY DVRQYSEETA
KRIDEAVRRL IEEQYQRVKA LLLEKREVLE RVAETLLERE TLTAEEFQRV VEGLPLEAPE
EAREEREPPR VVPKVKPGGA LGGA
//
