RIP1_MYCTE
ID RIP1_MYCTE Reviewed; 404 AA.
AC H8EW46;
DT 26-JUN-2013, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2012, sequence version 1.
DT 03-AUG-2022, entry version 55.
DE RecName: Full=Zinc metalloprotease Rip1;
DE EC=3.4.24.-;
DE AltName: Full=Regulator of sigma KLM proteases;
DE AltName: Full=S2P endopeptidase;
DE AltName: Full=Site-2-type intramembrane protease;
DE AltName: Full=site-2 protease Rip1;
DE Short=S2P protease Rip1;
GN Name=rip1; OrderedLocusNames=ERDMAN_3146;
OS Mycobacterium tuberculosis (strain ATCC 35801 / TMC 107 / Erdman).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=652616;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=22535945; DOI=10.1128/jb.00353-12;
RA Miyoshi-Akiyama T., Matsumura K., Iwai H., Funatogawa K., Kirikae T.;
RT "Complete annotated genome sequence of Mycobacterium tuberculosis Erdman.";
RL J. Bacteriol. 194:2770-2770(2012).
RN [2]
RP DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=16034419; DOI=10.1038/nature03713;
RA Makinoshima H., Glickman M.S.;
RT "Regulation of Mycobacterium tuberculosis cell envelope composition and
RT virulence by intramembrane proteolysis.";
RL Nature 436:406-409(2005).
RN [3]
RP FUNCTION, SUBSTRATES, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF HIS-21.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=20545848; DOI=10.1111/j.1365-2958.2010.07232.x;
RA Sklar J.G., Makinoshima H., Schneider J.S., Glickman M.S.;
RT "M. tuberculosis intramembrane protease Rip1 controls transcription through
RT three anti-sigma factor substrates.";
RL Mol. Microbiol. 77:605-617(2010).
CC -!- FUNCTION: A probable site-2 protease (S2P) that cleaves type-2
CC transmembrane proteins within their membrane-spanning domains. Degrades
CC anti-sigma factors RskA, RslA and RsmA, releasing sigma factors SigK,
CC SigL and SigM from the cellular membrane, activating signaling
CC pathways. Does not act on RsdA. Regulates the composition of
CC extractable mycolic acids in the cell envelope in response to changes
CC in membrane fluidity. Mediates transcriptional regulation of mycolic
CC acid biosynthetic genes in response to detergent. Probably also cleaves
CC PbpB (PBP3, FtsI); this cleavage is inhibited by Wag31-PbpBI
CC interaction. {ECO:0000269|PubMed:20545848}.
CC -!- FUNCTION: Regulated intramembrane proteolysis (RIP) occurs when an
CC extracytoplasmic signal (possibly oxidative stress) triggers a
CC concerted proteolytic cascade to transmit information and elicit
CC cellular responses. The membrane-spanning regulatory substrate protein
CC (includes anti-sigma factors RskA, RslA, RsmA, and PbpB) is first cut
CC extracytoplasmically (site-1 protease, S1P), then within the membrane
CC itself (site-2 protease, S2P, this entry), while cytoplasmic proteases
CC finish degrading the regulatory protein, liberating the effector
CC protein (ECF sigma factors SigK, SigL and SigM).
CC {ECO:0000269|PubMed:20545848}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: Not essential. Altered processing of anti-sigma
CC factors RskA, RslA and RslM. Cells have altered colony morphology,
CC lacking cording associated with virulence. Down-regulates extractable
CC alpha-mycolate synthesis 4.6-fold, methoxymycolates 3.5-fold and
CC ketomycolates 2.3-fold; has no effect on covalently esterified cell
CC wall mycolates. Decreased abundance of hexamannosylated
CC phosphatidylinositol mannoside. Decreased abundance of rpfC. Impairment
CC of bacterial growth in a mouse (C57BL/6) aerosol infection. Bacterial
CC titers in the lung after 3 weeks of infection were about 100-fold lower
CC than in the wild-type; by 22 weeks they are 10,000-fold lower in the
CC lung and fully cleared from the liver. {ECO:0000269|PubMed:16034419,
CC ECO:0000269|PubMed:20545848}.
CC -!- SIMILARITY: Belongs to the peptidase M50B family. {ECO:0000305}.
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DR EMBL; AP012340; BAL66925.1; -; Genomic_DNA.
DR RefSeq; WP_003899518.1; NZ_KK339487.1.
DR AlphaFoldDB; H8EW46; -.
DR SMR; H8EW46; -.
DR MEROPS; M50.005; -.
DR EnsemblBacteria; BAL66925; BAL66925; ERDMAN_3146.
DR KEGG; mtn:ERDMAN_3146; -.
DR PATRIC; fig|652616.3.peg.3204; -.
DR HOGENOM; CLU_025778_1_2_11; -.
DR Proteomes; UP000007568; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR041489; PDZ_6.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR004387; Pept_M50_Zn.
DR InterPro; IPR008915; Peptidase_M50.
DR PANTHER; PTHR42837; PTHR42837; 1.
DR Pfam; PF17820; PDZ_6; 1.
DR Pfam; PF02163; Peptidase_M50; 1.
DR SMART; SM00228; PDZ; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR PROSITE; PS50106; PDZ; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Hydrolase; Membrane; Metal-binding; Metalloprotease;
KW Protease; Transmembrane; Transmembrane helix; Virulence; Zinc.
FT CHAIN 1..404
FT /note="Zinc metalloprotease Rip1"
FT /id="PRO_0000422674"
FT TRANSMEM 1..21
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 104..124
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 313..333
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 373..393
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 121..203
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT ACT_SITE 22
FT /evidence="ECO:0000255"
FT BINDING 21
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 25
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 202
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT MUTAGEN 21
FT /note="H->A: No cleavage of RskA or RskL."
FT /evidence="ECO:0000269|PubMed:20545848"
SQ SEQUENCE 404 AA; 42834 MW; 918565A46B152F98 CRC64;
MMFVTGIVLF ALAILISVAL HECGHMWVAR RTGMKVRRYF VGFGPTLWST RRGETEYGVK
AVPLGGFCDI AGMTPVEELD PDERDRAMYK QATWKRVAVL FAGPGMNLAI CLVLIYAIAL
VWGLPNLHPP TRAVIGETGC VAQEVSQGKL EQCTGPGPAA LAGIRSGDVV VKVGDTPVSS
FDEMAAAVRK SHGSVPIVVE RDGTAIVTYV DIESTQRWIP NGQGGELQPA TVGAIGVGAA
RVGPVRYGVF SAMPATFAVT GDLTVEVGKA LAALPTKVGA LVRAIGGGQR DPQTPISVVG
ASIIGGDTVD HGLWVAFWFF LAQLNLILAA INLLPLLPFD GGHIAVAVFE RIRNMVRSAR
GKVAAAPVNY LKLLPATYVV LVLVVGYMLL TVTADLVNPI RLFQ
