SMASE_MYCTU
ID SMASE_MYCTU Reviewed; 490 AA.
AC P9WKQ1; L0T574; P64743; Q10549;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 42.
DE RecName: Full=Sphingomyelinase {ECO:0000303|PubMed:26036301};
DE Short=SMase {ECO:0000303|PubMed:26036301};
DE EC=3.1.4.12 {ECO:0000269|PubMed:26036301};
DE Flags: Precursor;
GN Name=spmT {ECO:0000303|PubMed:26036301}; OrderedLocusNames=Rv0888;
GN ORFNames=MTCY31.16;
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 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 [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, DOMAIN, INDUCTION, 3D-STRUCTURE MODELING, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF HIS-353 AND HIS-481.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=26036301; DOI=10.1111/mmi.13073;
RA Speer A., Sun J., Danilchanka O., Meikle V., Rowland J.L., Walter K.,
RA Buck B.R., Pavlenok M., Hoelscher C., Ehrt S., Niederweis M.;
RT "Surface hydrolysis of sphingomyelin by the outer membrane protein Rv0888
RT supports replication of Mycobacterium tuberculosis in macrophages.";
RL Mol. Microbiol. 97:881-897(2015).
CC -!- FUNCTION: Catalyzes the cleavage of sphingomyelin, a major lipid in
CC eukaryotic cells, into ceramide and phosphocholine, which are then
CC utilized by M.tuberculosis as carbon, nitrogen and phosphorus sources,
CC respectively. Thus, enables M.tuberculosis to utilize sphingomyelin as
CC a source of several essential nutrients for intracellular growth during
CC infection. Furthermore, lyses erythrocytes and constitutes the main
CC hemolytic factor of M.tuberculosis. {ECO:0000269|PubMed:26036301}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a sphingomyelin + H2O = an N-acylsphing-4-enine + H(+) +
CC phosphocholine; Xref=Rhea:RHEA:19253, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17636, ChEBI:CHEBI:52639,
CC ChEBI:CHEBI:295975; EC=3.1.4.12;
CC Evidence={ECO:0000269|PubMed:26036301};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=671 uM for sphingomyelin {ECO:0000269|PubMed:26036301};
CC Note=kcat is 1797 sec(-1). {ECO:0000269|PubMed:26036301};
CC pH dependence:
CC Is most active at neutral pH. {ECO:0000269|PubMed:26036301};
CC -!- SUBCELLULAR LOCATION: Cell outer membrane
CC {ECO:0000269|PubMed:26036301}; Multi-pass membrane protein
CC {ECO:0000305|PubMed:26036301}.
CC -!- INDUCTION: Rv0888 protein levels are increased by 5-fold after contact
CC with erythrocytes for 24 hours, and by 100-fold in the presence of
CC sphingomyelin as the sole carbon source. {ECO:0000269|PubMed:26036301}.
CC -!- DOMAIN: Consists of a surface-exposed C-terminal sphingomyelinase
CC domain and a putative outer membrane-spanning N-terminal channel domain
CC able to mediate glucose and phosphocholine uptake across the outer
CC membrane. {ECO:0000305|PubMed:26036301}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene do not grow on
CC sphingomyelin as a sole carbon source anymore and replicate poorly in
CC macrophages indicating that M.tuberculosis utilizes sphingomyelin
CC during infection. Moreover, deletion of this gene reduces lysis of
CC erythrocytes by twofold compared with wild-type.
CC {ECO:0000269|PubMed:26036301}.
CC -!- SIMILARITY: Belongs to the SpmT family. {ECO:0000305}.
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DR EMBL; AL123456; CCP43636.1; -; Genomic_DNA.
DR PIR; E70781; E70781.
DR RefSeq; NP_215403.1; NC_000962.3.
DR RefSeq; WP_003901038.1; NZ_NVQJ01000001.1.
DR AlphaFoldDB; P9WKQ1; -.
DR SMR; P9WKQ1; -.
DR STRING; 83332.Rv0888; -.
DR TCDB; 1.B.79.1.1; the porin-sphingomyelinase fusion protein, spmt (spmt) family.
DR PaxDb; P9WKQ1; -.
DR DNASU; 885210; -.
DR GeneID; 45424852; -.
DR GeneID; 885210; -.
DR KEGG; mtu:Rv0888; -.
DR TubercuList; Rv0888; -.
DR eggNOG; COG3021; Bacteria.
DR OMA; YNLHANT; -.
DR SABIO-RK; P9WKQ1; -.
DR PHI-base; PHI:6473; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0009279; C:cell outer membrane; IDA:UniProtKB.
DR GO; GO:0046930; C:pore complex; IEA:UniProtKB-KW.
DR GO; GO:0061751; F:neutral sphingomyelin phosphodiesterase activity; IDA:UniProtKB.
DR GO; GO:0015288; F:porin activity; IEA:UniProtKB-KW.
DR GO; GO:0022857; F:transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0071396; P:cellular response to lipid; IDA:UniProtKB.
DR GO; GO:0044179; P:hemolysis in another organism; IMP:UniProtKB.
DR GO; GO:0006811; P:ion transport; IEA:UniProtKB-KW.
DR GO; GO:0071702; P:organic substance transport; IDA:UniProtKB.
DR GO; GO:0006685; P:sphingomyelin catabolic process; IDA:UniProtKB.
DR Gene3D; 3.60.10.10; -; 1.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR SUPFAM; SSF56219; SSF56219; 1.
PE 1: Evidence at protein level;
KW Cell outer membrane; Cytolysis; Hemolysis; Hydrolase; Ion transport;
KW Lipid degradation; Lipid metabolism; Membrane; Porin; Reference proteome;
KW Signal; Transmembrane; Transmembrane beta strand; Transport.
FT SIGNAL 1..31
FT /evidence="ECO:0000255, ECO:0000305|PubMed:26036301"
FT CHAIN 32..490
FT /note="Sphingomyelinase"
FT /id="PRO_0000103731"
FT TOPO_DOM 32..136
FT /note="Periplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 137..145
FT /note="Beta stranded"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:26036301"
FT TOPO_DOM 146..161
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 162..168
FT /note="Beta stranded"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:26036301"
FT TOPO_DOM 169..171
FT /note="Periplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 172..182
FT /note="Beta stranded"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:26036301"
FT TOPO_DOM 183..187
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 188..196
FT /note="Beta stranded"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:26036301"
FT TOPO_DOM 197..204
FT /note="Periplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 205..213
FT /note="Beta stranded"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:26036301"
FT TOPO_DOM 214..490
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:26036301"
FT REGION 30..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 30..47
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 353
FT /note="H->N: Loss of catalytic activity but still able to
FT mediate uptake of glucose and phosphocholine; when
FT associated with N-481."
FT /evidence="ECO:0000269|PubMed:26036301"
FT MUTAGEN 481
FT /note="H->N: Loss of catalytic activity but still able to
FT mediate uptake of glucose and phosphocholine; when
FT associated with N-353."
FT /evidence="ECO:0000269|PubMed:26036301"
SQ SEQUENCE 490 AA; 52034 MW; 8A6DEA5E95A3D26E CRC64;
MDYAKRIGQV GALAVVLGVG AAVTTHAIGS AAPTDPSSSS TDSPVDACSP LGGSASSLAA
IPGASVPQVG VRQVDPGSIP DDLLNALIDF LAAVRNGLVP IIENRTPVAN PQQVSVPEGG
TVGPVRFDAC DPDGNRMTFA VRERGAPGGP QHGIVTVDQR TASFIYTADP GFVGTDTFSV
NVSDDTSLHV HGLAGYLGPF HGHDDVATVT VFVGNTPTDT ISGDFSMLTY NIAGLPFPLS
SAILPRFFYT KEIGKRLNAY YVANVQEDFA YHQFLIKKSK MPSQTPPEPP TLLWPIGVPF
SDGLNTLSEF KVQRLDRQTW YECTSDNCLT LKGFTYSQMR LPGGDTVDVY NLHTNTGGGP
TTNANLAQVA NYIQQNSAGR AVIVTGDFNA RYSDDQSALL QFAQVNGLTD AWVQVEHGPT
TPPFAPTCMV GNECELLDKI FYRSGQGVTL QAVSYGNEAP KFFNSKGEPL SDHSPAVVGF
HYVADNVAVR
