Y3671_MYCTU
ID Y3671_MYCTU Reviewed; 397 AA.
AC P9WHR9; L0TDG7; O69639; Q7D538;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 44.
DE RecName: Full=Serine protease Rv3671c;
DE EC=3.4.21.-;
GN OrderedLocusNames=Rv3671c;
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 FUNCTION IN ACID RESISTANCE AND INTRABACTERIAL PH MAINTENANCE, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF SER-343.
RX PubMed=18641659; DOI=10.1038/nmxxxx;
RA Vandal O.H., Pierini L.M., Schnappinger D., Nathan C.F., Ehrt S.;
RT "A membrane protein preserves intrabacterial pH in intraphagosomal
RT Mycobacterium tuberculosis.";
RL Nat. Med. 14:849-854(2008).
RN [3]
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).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.30 ANGSTROMS) OF 161-397 AND OF 161-397 OF MUTANT
RP ALA-343, FUNCTION AS A SERINE PROTEASE AND IN PROTECTION AGAINST OXIDATIVE
RP STRESS, AUTOCATALYTIC CLEAVAGE, ACTIVITY REGULATION, MUTAGENESIS OF
RP CYS-214; SER-343 AND CYS-395, AND SUBUNIT.
RX PubMed=20947023; DOI=10.1016/j.str.2010.06.017;
RA Biswas T., Small J., Vandal O., Odaira T., Deng H., Ehrt S., Tsodikov O.V.;
RT "Structural insight into serine protease Rv3671c that Protects M.
RT tuberculosis from oxidative and acidic stress.";
RL Structure 18:1353-1363(2010).
CC -!- FUNCTION: Required for M.tuberculosis resistance to oxidative stress in
CC addition to its role in resistance to acid, which is essential for
CC virulence. It protects M.tuberculosis against phagolysosomal
CC concentrations of acid and maintains its intrabacterial pH when
CC phagocytosed by IFN-gamma-activated macrophages.
CC {ECO:0000269|PubMed:18641659, ECO:0000269|PubMed:20947023}.
CC -!- ACTIVITY REGULATION: Inhibited by reducing agents and activated during
CC exposure to oxidative stress. {ECO:0000269|PubMed:20947023}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:20947023}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- PTM: Autocleaved. The autocleavage activity is significant only when no
CC reducing agent is present in buffers.
CC -!- DISRUPTION PHENOTYPE: Disruption leads to an increased sensitivity to
CC acid and fails to maintain intrabacterial pH in acid in vitro and in
CC activated macrophages. Growth is also severely attenuated in mice.
CC {ECO:0000269|PubMed:18641659}.
CC -!- MISCELLANEOUS: Disulfide bond increases the proteolytic activity by
CC stabilizing the protease in the conformation in which the active site
CC residues are properly positioned for substrate binding and catalysis.
CC -!- SIMILARITY: Belongs to the peptidase S1C family. {ECO:0000305}.
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DR EMBL; AL123456; CCP46494.1; -; Genomic_DNA.
DR PIR; H70789; H70789.
DR RefSeq; NP_218188.1; NC_000962.3.
DR RefSeq; WP_003900734.1; NZ_NVQJ01000028.1.
DR PDB; 3K6Y; X-ray; 1.30 A; A=161-397.
DR PDB; 3K6Z; X-ray; 1.75 A; A/B=179-397.
DR PDB; 3LT3; X-ray; 2.10 A; A/B=181-397.
DR PDBsum; 3K6Y; -.
DR PDBsum; 3K6Z; -.
DR PDBsum; 3LT3; -.
DR AlphaFoldDB; P9WHR9; -.
DR SMR; P9WHR9; -.
DR STRING; 83332.Rv3671c; -.
DR MEROPS; S01.513; -.
DR PaxDb; P9WHR9; -.
DR DNASU; 885176; -.
DR GeneID; 885176; -.
DR KEGG; mtu:Rv3671c; -.
DR PATRIC; fig|83332.111.peg.4082; -.
DR TubercuList; Rv3671c; -.
DR eggNOG; COG0265; Bacteria.
DR OMA; YRQGFVV; -.
DR PhylomeDB; P9WHR9; -.
DR PRO; PR:P9WHR9; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; HDA:MTBBASE.
DR GO; GO:0005887; C:integral component of plasma membrane; HDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; IDA:MTBBASE.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0042783; P:evasion of host immune response; IMP:MTBBASE.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0010447; P:response to acidic pH; IMP:UniProtKB.
DR GO; GO:0009403; P:toxin biosynthetic process; IEA:InterPro.
DR Gene3D; 2.40.10.10; -; 2.
DR InterPro; IPR003825; Colicin-V_CvpA.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001940; Peptidase_S1C.
DR Pfam; PF02674; Colicin_V; 1.
DR PRINTS; PR00834; PROTEASES2C.
DR SUPFAM; SSF50494; SSF50494; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Autocatalytic cleavage; Disulfide bond; Hydrolase; Membrane;
KW Protease; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..397
FT /note="Serine protease Rv3671c"
FT /id="PRO_0000414589"
FT TRANSMEM 9..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 32..52
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 62..82
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 102..122
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 193..384
FT /note="Peptidase S1"
FT /evidence="ECO:0000305"
FT ACT_SITE 235
FT /note="Proton acceptor"
FT /evidence="ECO:0000255"
FT ACT_SITE 264
FT /evidence="ECO:0000255"
FT ACT_SITE 343
FT /evidence="ECO:0000255"
FT SITE 160..161
FT /note="Cleavage; by autolysis"
FT DISULFID 214..395
FT MUTAGEN 214
FT /note="C->A: Significant decrease of protease activity."
FT /evidence="ECO:0000269|PubMed:20947023"
FT MUTAGEN 343
FT /note="S->A: Abolishes complementation of the Rv3671c
FT mutant. It does not exhibit autocleavage activity."
FT /evidence="ECO:0000269|PubMed:18641659,
FT ECO:0000269|PubMed:20947023"
FT MUTAGEN 395
FT /note="C->A: Significant decrease of protease activity."
FT /evidence="ECO:0000269|PubMed:20947023"
FT HELIX 189..193
FT /evidence="ECO:0007829|PDB:3K6Y"
FT HELIX 195..200
FT /evidence="ECO:0007829|PDB:3K6Y"
FT HELIX 201..203
FT /evidence="ECO:0007829|PDB:3K6Y"
FT STRAND 204..211
FT /evidence="ECO:0007829|PDB:3K6Y"
FT HELIX 212..214
FT /evidence="ECO:0007829|PDB:3K6Y"
FT STRAND 216..226
FT /evidence="ECO:0007829|PDB:3K6Y"
FT STRAND 229..232
FT /evidence="ECO:0007829|PDB:3K6Y"
FT HELIX 234..236
FT /evidence="ECO:0007829|PDB:3K6Y"
FT TURN 237..239
FT /evidence="ECO:0007829|PDB:3K6Y"
FT STRAND 241..247
FT /evidence="ECO:0007829|PDB:3K6Y"
FT STRAND 250..253
FT /evidence="ECO:0007829|PDB:3K6Y"
FT STRAND 255..260
FT /evidence="ECO:0007829|PDB:3K6Y"
FT TURN 261..264
FT /evidence="ECO:0007829|PDB:3K6Y"
FT STRAND 265..269
FT /evidence="ECO:0007829|PDB:3K6Y"
FT STRAND 290..295
FT /evidence="ECO:0007829|PDB:3K6Y"
FT HELIX 297..299
FT /evidence="ECO:0007829|PDB:3K6Y"
FT STRAND 303..317
FT /evidence="ECO:0007829|PDB:3K6Y"
FT STRAND 327..336
FT /evidence="ECO:0007829|PDB:3K6Y"
FT HELIX 340..342
FT /evidence="ECO:0007829|PDB:3K6Z"
FT STRAND 346..348
FT /evidence="ECO:0007829|PDB:3K6Y"
FT STRAND 354..361
FT /evidence="ECO:0007829|PDB:3K6Y"
FT STRAND 363..365
FT /evidence="ECO:0007829|PDB:3K6Y"
FT STRAND 368..373
FT /evidence="ECO:0007829|PDB:3K6Y"
FT HELIX 374..378
FT /evidence="ECO:0007829|PDB:3K6Y"
FT HELIX 379..383
FT /evidence="ECO:0007829|PDB:3K6Y"
SQ SEQUENCE 397 AA; 40721 MW; 2759E1941B9C7F1C CRC64;
MTPSQWLDIA VLAVAFIAAI SGWRAGALGS MLSFGGVLLG ATAGVLLAPH IVSQISAPRA
KLFAALFLIL ALVVVGEVAG VVLGRAVRGA IRNRPIRLID SVIGVGVQLV VVLTAAWLLA
MPLTQSKEQP ELAAAVKGSR VLARVNEAAP TWLKTVPKRL SALLNTSGLP AVLEPFSRTP
VIPVASPDPA LVNNPVVAAT EPSVVKIRSL APRCQKVLEG TGFVISPDRV MTNAHVVAGS
NNVTVYAGDK PFEATVVSYD PSVDVAILAV PHLPPPPLVF AAEPAKTGAD VVVLGYPGGG
NFTATPARIR EAIRLSGPDI YGDPEPVTRD VYTIRADVEQ GDSGGPLIDL NGQVLGVVFG
AAIDDAETGF VLTAGEVAGQ LAKIGATQPV GTGACVS
