RIP1_MYCTU
ID RIP1_MYCTU Reviewed; 404 AA.
AC P9WHS3; L0TB42; O33351;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 43.
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 protease Rip1;
DE Short=S2P protease Rip1;
DE AltName: Full=Site-2-type intramembrane protease;
GN Name=rip1; OrderedLocusNames=Rv2869c; ORFNames=MTV003.15c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [3]
RP FUNCTION, SUBSTRATE, COFACTOR, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP HIS-21; 21-HIS--HIS-25; GLU-22 AND HIS-25.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19496931; DOI=10.1111/j.1365-2958.2009.06750.x;
RA Mukherjee P., Sureka K., Datta P., Hossain T., Barik S., Das K.P.,
RA Kundu M., Basu J.;
RT "Novel role of Wag31 in protection of mycobacteria under oxidative
RT stress.";
RL Mol. Microbiol. 73:103-119(2009).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
CC -!- FUNCTION: A probable intramembrane site-2 protease (S2P) that cleaves
CC type-2 transmembrane proteins within their membrane-spanning domains.
CC Cleaves PbpB (PBP3, FtsI) near 'Ala-102' and 'Ala-103' in response to
CC oxidative stress; cleavage is inhibited by Wag31-PbpB interaction.
CC Probably also cleaves anti-sigma factors RskA, RslA and RsmA but not
CC RsdA. {ECO:0000269|PubMed:19496931}.
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 in
CC M.tuberculosis) is first cut extracytoplasmically (site-1 protease,
CC S1P), then within the membrane itself (site-2 protease, S2P, this
CC entry), while cytoplasmic proteases finish degrading the regulatory
CC protein, liberating the effector protein (ECF sigma factors SigK, SigL
CC and SigM). {ECO:0000269|PubMed:19496931}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000305|PubMed:19496931};
CC -!- ACTIVITY REGULATION: Inhibited by metal chelator o-phenanthroline.
CC {ECO:0000269|PubMed:19496931}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the peptidase M50B family. {ECO:0000305}.
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DR EMBL; AL123456; CCP45671.1; -; Genomic_DNA.
DR PIR; G70886; G70886.
DR RefSeq; NP_217385.1; NC_000962.3.
DR RefSeq; WP_003899518.1; NZ_NVQJ01000006.1.
DR AlphaFoldDB; P9WHS3; -.
DR SMR; P9WHS3; -.
DR STRING; 83332.Rv2869c; -.
DR PaxDb; P9WHS3; -.
DR DNASU; 887449; -.
DR GeneID; 887449; -.
DR KEGG; mtu:Rv2869c; -.
DR TubercuList; Rv2869c; -.
DR eggNOG; COG0750; Bacteria.
DR OMA; GPTQYNP; -.
DR PhylomeDB; P9WHS3; -.
DR Proteomes; UP000001584; 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:0004175; F:endopeptidase activity; IDA:UniProtKB.
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; IDA:UniProtKB.
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; Reference proteome; Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..404
FT /note="Zinc metalloprotease Rip1"
FT /id="PRO_0000088449"
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..25
FT /note="Missing: Loss of PbpB (PBP3, FtsI) processing."
FT /evidence="ECO:0000269|PubMed:19496931"
FT MUTAGEN 21
FT /note="H->A: No effect on PbpB (PBP3, FtsI) processing."
FT /evidence="ECO:0000269|PubMed:19496931"
FT MUTAGEN 22
FT /note="E->G: No effect on PbpB (PBP3, FtsI) processing."
FT /evidence="ECO:0000269|PubMed:19496931"
FT MUTAGEN 25
FT /note="H->A: No effect on PbpB (PBP3, FtsI) processing."
FT /evidence="ECO:0000269|PubMed:19496931"
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
