HIP1_MYCTO
ID HIP1_MYCTO Reviewed; 520 AA.
AC P9WHR2; L0TBN5; P65823; Q10509;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 37.
DE RecName: Full=Serine protease Hip1 {ECO:0000250|UniProtKB:P9WHR3};
DE EC=3.4.21.- {ECO:0000250|UniProtKB:P9WHR3};
DE AltName: Full=Carboxylesterase A {ECO:0000303|PubMed:17428787};
DE Flags: Precursor;
GN Name=hip1 {ECO:0000250|UniProtKB:P9WHR3};
GN Synonyms=caeA {ECO:0000303|PubMed:17428787}; OrderedLocusNames=MT2282;
OS Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83331;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CDC 1551 / Oshkosh;
RX PubMed=12218036; DOI=10.1128/jb.184.19.5479-5490.2002;
RA Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O.,
RA Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K.,
RA Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L.,
RA Delcher A., Utterback T.R., Weidman J.F., Khouri H.M., Gill J., Mikula A.,
RA Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M.;
RT "Whole-genome comparison of Mycobacterium tuberculosis clinical and
RT laboratory strains.";
RL J. Bacteriol. 184:5479-5490(2002).
RN [2]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION,
RP DISRUPTION PHENOTYPE, MUTAGENESIS OF SER-228; ASP-463 AND HIS-490, ACTIVE
RP SITE, AND NOMENCLATURE.
RC STRAIN=CDC 1551 / Oshkosh;
RX PubMed=17428787; DOI=10.1074/jbc.m700035200;
RA Lun S., Bishai W.R.;
RT "Characterization of a novel cell wall-anchored protein with
RT carboxylesterase activity required for virulence in Mycobacterium
RT tuberculosis.";
RL J. Biol. Chem. 282:18348-18356(2007).
CC -!- FUNCTION: Serine protease that promotes tuberculosis (TB) pathogenesis
CC by promoting the processing and the extracellular release of the
CC M.tuberculosis (Mtb) heat-shock protein GroEL2 (By similarity). In
CC vitro, catalyzes the cleavage of ester bonds. Esterase activity
CC increases with increasing carbon chain length of the substrate
CC (PubMed:17428787). {ECO:0000250|UniProtKB:P9WHR3,
CC ECO:0000269|PubMed:17428787}.
CC -!- FUNCTION: Key immunomodulatory virulence factor, which promotes
CC survival in host macrophages and modulates host immune responses.
CC {ECO:0000250|UniProtKB:P9WHR3}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=738 uM for 4-methylumbelliferyl butyrate
CC {ECO:0000269|PubMed:17428787};
CC Vmax=128 umol/min/mg enzyme with 4-methylumbelliferyl butyrate as
CC substrate {ECO:0000269|PubMed:17428787};
CC pH dependence:
CC Optimum pH is 7. {ECO:0000269|PubMed:17428787};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:17428787}.
CC -!- SUBCELLULAR LOCATION: Cell envelope {ECO:0000269|PubMed:17428787}. Cell
CC membrane {ECO:0000255|PROSITE-ProRule:PRU00303}; Lipid-anchor
CC {ECO:0000255|PROSITE-ProRule:PRU00303}.
CC -!- DISRUPTION PHENOTYPE: Mouse aerosol infections with this mutant show
CC reduced colony-forming unit loads in lungs and spleens and reduced lung
CC pathology. High dose intravenous infection of mice with the mutant
CC results in a significantly delayed mortality compared with the wild-
CC type. {ECO:0000269|PubMed:17428787}.
CC -!- SIMILARITY: Belongs to the peptidase S33 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK46567.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AE000516; AAK46567.1; ALT_INIT; Genomic_DNA.
DR PIR; D70776; D70776.
DR RefSeq; WP_003411486.1; NZ_KK341227.1.
DR AlphaFoldDB; P9WHR2; -.
DR SMR; P9WHR2; -.
DR ESTHER; myctu-ym24; AlphaBeta_hydrolase.
DR MEROPS; S33.023; -.
DR EnsemblBacteria; AAK46567; AAK46567; MT2282.
DR GeneID; 45426201; -.
DR KEGG; mtc:MT2282; -.
DR PATRIC; fig|83331.31.peg.2456; -.
DR HOGENOM; CLU_013364_3_1_11; -.
DR Proteomes; UP000001020; Chromosome.
DR GO; GO:0031975; C:envelope; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR000073; AB_hydrolase_1.
DR Pfam; PF00561; Abhydrolase_1; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS51257; PROKAR_LIPOPROTEIN; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Hydrolase; Lipoprotein; Membrane; Palmitate; Signal;
KW Virulence.
FT SIGNAL 1..30
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT CHAIN 31..520
FT /note="Serine protease Hip1"
FT /id="PRO_0000428138"
FT DOMAIN 102..497
FT /note="AB hydrolase-1"
FT /evidence="ECO:0000255"
FT ACT_SITE 228
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:17428787"
FT ACT_SITE 463
FT /evidence="ECO:0000305|PubMed:17428787"
FT ACT_SITE 490
FT /note="Proton donor"
FT /evidence="ECO:0000305|PubMed:17428787"
FT LIPID 31
FT /note="N-palmitoyl cysteine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT LIPID 31
FT /note="S-diacylglycerol cysteine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00303"
FT MUTAGEN 228
FT /note="S->A: Completely abolishes esterase activity."
FT /evidence="ECO:0000269|PubMed:17428787"
FT MUTAGEN 463
FT /note="D->A: Completely abolishes esterase activity."
FT /evidence="ECO:0000269|PubMed:17428787"
FT MUTAGEN 490
FT /note="H->A: Completely abolishes esterase activity."
FT /evidence="ECO:0000269|PubMed:17428787"
SQ SEQUENCE 520 AA; 55924 MW; 8DC560534ABE9B0E CRC64;
MGMRLSRRDK IARMLLIWAA LAAVALVLVG CIRVVGGRAR MAEPKLGQPV EWTPCRSSNP
QVKIPGGALC GKLAVPVDYD RPDGDVAALA LIRFPATGDK IGSLVINPGG PGESGIEAAL
GVFQTLPKRV HERFDLVGFD PRGVASSRPA IWCNSDADND RLRAEPQVDY SREGVAHIEN
ETKQFVGRCV DKMGKNFLAH VGTVNVAKDL DAIRAALGDD KLTYLGYSYG TRIGSAYAEE
FPQRVRAMIL DGAVDPNADP IEAELRQAKG FQDAFNNYAA DCAKNAGCPL GADPAKAVEV
YHSLVDPLVD PDNPRISRPA RTKDPRGLSY SDAIVGTIMA LYSPNLWQHL TDGLSELVDN
RGDTLLALAD MYMRRDSHGR YNNSGDARVA INCVDQPPVT DRDKVIDEDR RAREIAPFMS
YGKFTGDAPL GTCAFWPVPP TSQPHAVSAP GLVPTVVVST THDPATPYKA GVDLANQLRG
SLLTFDGTQH TVVFQGDSCI DEYVTAYLIG GTTPPSGAKC
