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Protein

Phospholipase C

Gene

plc

Organism
Clostridium perfringens (strain ATCC 13124 / DSM 756 / JCM 1290 / NCIMB 6125 / NCTC 8237 / Type A)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Bacterial hemolysins are exotoxins that attack blood cell membranes and cause cell rupture. Constitutes an essential virulence factor in gas gangrene. Binds to eukaryotic membranes where it hydrolyzes both phosphatidylcholine and sphingomyelin. The diacylglycerol produced can activate both the arachidonic acid pathway, leading to modulation of the inflammatory response cascade and thrombosis, and protein kinase C, leading to activation of eukaryotic phospholipases and further membrane damage. Acts on human and mouse erythrocytes, but not on rabbit or horse erythrocytes.

Catalytic activityi

A phosphatidylcholine + H2O = 1,2-diacyl-sn-glycerol + phosphocholine.

Cofactori

Protein has several cofactor binding sites:
  • Ca2+Note: Binds 3 Ca2+ ions per subunit.
  • Zn2+Note: Binds 3 Zn2+ ions per subunit.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi29 – 291Zinc 1
Metal bindingi39 – 391Zinc 1
Metal bindingi84 – 841Zinc 3
Metal bindingi96 – 961Zinc 3
Metal bindingi154 – 1541Zinc 3
Metal bindingi158 – 1581Zinc 1
Metal bindingi158 – 1581Zinc 3
Metal bindingi164 – 1641Zinc 2Curated
Metal bindingi176 – 1761Zinc 2Curated
Metal bindingi180 – 1801Zinc 2Curated
Metal bindingi297 – 2971Calcium 1
Metal bindingi299 – 2991Calcium 1; via carbonyl oxygen
Metal bindingi300 – 3001Calcium 3
Metal bindingi301 – 3011Calcium 3
Metal bindingi321 – 3211Calcium 2
Metal bindingi322 – 3221Calcium 2
Metal bindingi324 – 3241Calcium 2; via carbonyl oxygen
Metal bindingi325 – 3251Calcium 3
Metal bindingi326 – 3261Calcium 2
Metal bindingi326 – 3261Calcium 3
Metal bindingi364 – 3641Calcium 1
Metal bindingi365 – 3651Calcium 1; via carbonyl oxygen

GO - Molecular functioni

GO - Biological processi

  • hemolysis in other organism Source: CACAO
  • pathogenesis Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Toxin

Keywords - Biological processi

Cytolysis, Hemolysis, Virulence

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciCPER195103:GHAW-45-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Phospholipase C (EC:3.1.4.3)
Short name:
PLC
Alternative name(s):
Alpha-toxin
Hemolysin
Lecithinase
Phosphatidylcholine cholinephosphohydrolase
Gene namesi
Name:plc
Synonyms:cpa
Ordered Locus Names:CPF_0042
OrganismiClostridium perfringens (strain ATCC 13124 / DSM 756 / JCM 1290 / NCIMB 6125 / NCTC 8237 / Type A)
Taxonomic identifieri195103 [NCBI]
Taxonomic lineageiBacteriaFirmicutesClostridiaClostridialesClostridiaceaeClostridium
Proteomesi
  • UP000001823 Componenti: Chromosome

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Biotechnological usei

Vaccination of mice with a fragment (residues 275-398) protects them against a subsequent challenge with purified alpha-toxin.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi278 – 398121Missing : Loss of sphingomyelinase, hemolytic activity and lethality. 1 PublicationAdd
BLAST
Mutagenesisi297 – 2971D → Y: Binds less Ca(2+), small decrease in PLC, sphingomyelinase and myotoxicity, increased hemolytic and cytotoxic activities. 2 Publications
Mutagenesisi303 – 3031Y → F or N: Increased dependence of PLC on Ca(2+). Dramatically decreases hemolytic, cytotoxic and myotoxic activities. 1 Publication
Mutagenesisi321 – 3211D → S: Reduces affinity for Ca(2+), decreases toxin activity. 1 Publication
Mutagenesisi333 – 3331D → G: Decreases toxin activity in vivo and against aggregated substrates in vitro. May destabilize interactions between the N and C-terminal domains. 1 Publication
Mutagenesisi335 – 3351Y → F: Dramatically decreases hemolytic and cytotoxic activities. 1 Publication
Mutagenesisi358 – 3581K → E: Decreases toxin activity in vivo and against aggregated substrates in vitro. 1 Publication
Mutagenesisi359 – 3591Y → F or L: Dramatically decreases hemolytic and cytotoxic activities. 2 Publications
Mutagenesisi362 – 3621F → I: Dramatically decreases sphingomyelinase, cytotoxicity and hemolytic and myotoxic activities. 1 Publication
Mutagenesisi364 – 3641D → N: Increased dependence of PLC on Ca(2+). Dramatically decreases hemolytic, cytotoxic and myotoxic activities. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 28282 PublicationsAdd
BLAST
Chaini29 – 398370Phospholipase CPRO_0000259456Add
BLAST

Interactioni

Protein-protein interaction databases

STRINGi195103.CPF_0042.

Structurei

Secondary structure

1
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni33 – 353Combined sources
Helixi38 – 5316Combined sources
Helixi60 – 7112Combined sources
Helixi73 – 819Combined sources
Helixi82 – 843Combined sources
Helixi94 – 963Combined sources
Helixi102 – 1076Combined sources
Beta strandi108 – 1125Combined sources
Turni113 – 1153Combined sources
Helixi122 – 13817Combined sources
Helixi142 – 15918Combined sources
Turni163 – 1675Combined sources
Turni170 – 1723Combined sources
Helixi175 – 18612Combined sources
Helixi187 – 1904Combined sources
Helixi202 – 2098Combined sources
Helixi213 – 23422Combined sources
Beta strandi237 – 2404Combined sources
Helixi242 – 27332Combined sources
Turni277 – 2804Combined sources
Beta strandi285 – 2928Combined sources
Beta strandi302 – 3109Combined sources
Beta strandi315 – 3195Combined sources
Beta strandi332 – 3387Combined sources
Helixi346 – 3483Combined sources
Beta strandi349 – 3579Combined sources
Beta strandi359 – 3624Combined sources
Beta strandi368 – 3758Combined sources
Beta strandi378 – 3847Combined sources
Beta strandi394 – 3985Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1QM6X-ray2.50A/B29-398[»]
1QMDX-ray2.20A/B29-398[»]
2WXTX-ray2.00A29-398[»]
2WXUX-ray1.80A29-398[»]
2WY6X-ray3.20A/B/C29-398[»]
ProteinModelPortaliQ0TV31.
SMRiQ0TV31. Positions 29-398.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ0TV31.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini29 – 278250Zn-dependent PLCPROSITE-ProRule annotationAdd
BLAST
Domaini284 – 398115PLATPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni275 – 2839Linker

Domaini

The protein is composed of 2 domains; the N-terminal domain contains the phospholipase C active site (PLC), in a cleft which is also occupied by the 3 zinc ions. The C-terminal domain is a putative phospholipid-recognition domain, which shows structural homology with phospholipid-binding C2-like domains from a range of eukaryotic proteins. The ability to bind membrane phospholipids in a Ca2+ dependent manner and toxicity is conferred by this C-terminal domain, which also contributes to the sphingomyelinase activity.

Sequence similaritiesi

Belongs to the bacterial zinc-metallophospholipase C family.PROSITE-ProRule annotation
Contains 1 PLAT domain.PROSITE-ProRule annotation
Contains 1 Zn-dependent PLC domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG41064S2. Bacteria.
ENOG4112CMR. LUCA.
KOiK16619.
OMAiDHFWDPD.
OrthoDBiPOG091H10JI.

Family and domain databases

Gene3Di1.10.575.10. 1 hit.
2.60.60.20. 1 hit.
InterProiIPR001024. PLAT/LH2_dom.
IPR008947. PLipase_C/P1_nuclease.
IPR029002. PLPC/GPLD1.
IPR001531. Zn_PLipaseC.
[Graphical view]
PfamiPF01477. PLAT. 1 hit.
PF00882. Zn_dep_PLPC. 1 hit.
[Graphical view]
PRINTSiPR00479. PRPHPHLPASEC.
ProDomiPD003946. PLipaseC_Zn-bd_prok. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00770. Zn_dep_PLPC. 1 hit.
[Graphical view]
SUPFAMiSSF48537. SSF48537. 1 hit.
SSF49723. SSF49723. 1 hit.
PROSITEiPS50095. PLAT. 1 hit.
PS00384. PROKAR_ZN_DEPEND_PLPC_1. 1 hit.
PS51346. PROKAR_ZN_DEPEND_PLPC_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q0TV31-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKRKICKALI CAALATSLWA GASTKVYAWD GKIDGTGTHA MIVTQGVSIL
60 70 80 90 100
ENDLSKNEPE SVRKNLEILK ENMHELQLGS TYPDYDKNAY DLYQDHFWDP
110 120 130 140 150
DTDNNFSKDN SWYLAYSIPD TGESQIRKFS ALARYEWQRG NYKQATFYLG
160 170 180 190 200
EAMHYFGDID TPYHPANVTA VDSAGHVKFE TFAEERKEQY KINTAGCKTN
210 220 230 240 250
EAFYTDILKN KDFNAWSKEY ARGFAKTGKS IYYSHASMSH SWDDWDYAAK
260 270 280 290 300
VTLANSQKGT AGYIYRFLHD VSEGNDPSVG KNVKELVAYI STSGEKDAGT
310 320 330 340 350
DDYMYFGIKT KDGKTQEWEM DNPGNDFMTG SKDTYTFKLK DENLKIDDIQ
360 370 380 390
NMWIRKRKYT AFSDAYKPEN IKIIANGKVV VDKDINEWIS GNSTYNIK
Length:398
Mass (Da):45,476
Last modified:September 5, 2006 - v1
Checksum:i4A36E7E2A7139724
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti17 – 171S → T (PubMed:2536356).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M24904 Genomic DNA. Translation: AAA23272.1.
X13608 Genomic DNA. Translation: CAA31943.1.
CP000246 Genomic DNA. Translation: ABG84486.1.
PIRiA30565.
RefSeqiWP_011590041.1. NC_008261.1.

Genome annotation databases

EnsemblBacteriaiABG84486; ABG84486; CPF_0042.
KEGGicpf:CPF_0042.
PATRICi19482373. VBICloPer106549_0034.

Cross-referencesi

Web resourcesi

Worthington enzyme manual

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M24904 Genomic DNA. Translation: AAA23272.1.
X13608 Genomic DNA. Translation: CAA31943.1.
CP000246 Genomic DNA. Translation: ABG84486.1.
PIRiA30565.
RefSeqiWP_011590041.1. NC_008261.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1QM6X-ray2.50A/B29-398[»]
1QMDX-ray2.20A/B29-398[»]
2WXTX-ray2.00A29-398[»]
2WXUX-ray1.80A29-398[»]
2WY6X-ray3.20A/B/C29-398[»]
ProteinModelPortaliQ0TV31.
SMRiQ0TV31. Positions 29-398.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi195103.CPF_0042.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiABG84486; ABG84486; CPF_0042.
KEGGicpf:CPF_0042.
PATRICi19482373. VBICloPer106549_0034.

Phylogenomic databases

eggNOGiENOG41064S2. Bacteria.
ENOG4112CMR. LUCA.
KOiK16619.
OMAiDHFWDPD.
OrthoDBiPOG091H10JI.

Enzyme and pathway databases

BioCyciCPER195103:GHAW-45-MONOMER.

Miscellaneous databases

EvolutionaryTraceiQ0TV31.

Family and domain databases

Gene3Di1.10.575.10. 1 hit.
2.60.60.20. 1 hit.
InterProiIPR001024. PLAT/LH2_dom.
IPR008947. PLipase_C/P1_nuclease.
IPR029002. PLPC/GPLD1.
IPR001531. Zn_PLipaseC.
[Graphical view]
PfamiPF01477. PLAT. 1 hit.
PF00882. Zn_dep_PLPC. 1 hit.
[Graphical view]
PRINTSiPR00479. PRPHPHLPASEC.
ProDomiPD003946. PLipaseC_Zn-bd_prok. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00770. Zn_dep_PLPC. 1 hit.
[Graphical view]
SUPFAMiSSF48537. SSF48537. 1 hit.
SSF49723. SSF49723. 1 hit.
PROSITEiPS50095. PLAT. 1 hit.
PS00384. PROKAR_ZN_DEPEND_PLPC_1. 1 hit.
PS51346. PROKAR_ZN_DEPEND_PLPC_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPHLC_CLOP1
AccessioniPrimary (citable) accession number: Q0TV31
Secondary accession number(s): P15310
, P94658, Q46246, Q46279, Q46280, Q46281, Q46282, Q57317, Q59303, Q59304, Q59305, Q59313, Q60121
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: September 5, 2006
Last modified: September 7, 2016
This is version 74 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

Two main forms of alpha-toxin can be purified from C.perfringens; a major form with a pI of 5.48, and a minor form with a pI of 5.6. Both are equally active. Variations seen in PLC activity between different strains may be due to transcriptional regulation.
Mutating residues 303 or 359 of the C.perfringens toxin to match those found in C.bifermentans (301 and 358 respectively) reduces toxicity considerably.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.