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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)DescriptionActionsGraphical viewLength
Metal bindingi29Zinc 11
Metal bindingi39Zinc 11
Metal bindingi84Zinc 31
Metal bindingi96Zinc 31
Metal bindingi154Zinc 31
Metal bindingi158Zinc 11
Metal bindingi158Zinc 31
Metal bindingi164Zinc 2Curated1
Metal bindingi176Zinc 2Curated1
Metal bindingi180Zinc 2Curated1
Metal bindingi297Calcium 11
Metal bindingi299Calcium 1; via carbonyl oxygen1
Metal bindingi300Calcium 31
Metal bindingi301Calcium 31
Metal bindingi321Calcium 21
Metal bindingi322Calcium 21
Metal bindingi324Calcium 2; via carbonyl oxygen1
Metal bindingi325Calcium 31
Metal bindingi326Calcium 21
Metal bindingi326Calcium 31
Metal bindingi364Calcium 11
Metal bindingi365Calcium 1; via carbonyl oxygen1

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

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)DescriptionActionsGraphical viewLength
Mutagenesisi278 – 398Missing : Loss of sphingomyelinase, hemolytic activity and lethality. 1 PublicationAdd BLAST121
Mutagenesisi297D → Y: Binds less Ca(2+), small decrease in PLC, sphingomyelinase and myotoxicity, increased hemolytic and cytotoxic activities. 2 Publications1
Mutagenesisi303Y → F or N: Increased dependence of PLC on Ca(2+). Dramatically decreases hemolytic, cytotoxic and myotoxic activities. 1 Publication1
Mutagenesisi321D → S: Reduces affinity for Ca(2+), decreases toxin activity. 1 Publication1
Mutagenesisi333D → G: Decreases toxin activity in vivo and against aggregated substrates in vitro. May destabilize interactions between the N and C-terminal domains. 1 Publication1
Mutagenesisi335Y → F: Dramatically decreases hemolytic and cytotoxic activities. 1 Publication1
Mutagenesisi358K → E: Decreases toxin activity in vivo and against aggregated substrates in vitro. 1 Publication1
Mutagenesisi359Y → F or L: Dramatically decreases hemolytic and cytotoxic activities. 2 Publications1
Mutagenesisi362F → I: Dramatically decreases sphingomyelinase, cytotoxicity and hemolytic and myotoxic activities. 1 Publication1
Mutagenesisi364D → N: Increased dependence of PLC on Ca(2+). Dramatically decreases hemolytic, cytotoxic and myotoxic activities. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 282 PublicationsAdd BLAST28
ChainiPRO_000025945629 – 398Phospholipase CAdd BLAST370

Interactioni

Protein-protein interaction databases

STRINGi195103.CPF_0042.

Structurei

Secondary structure

1398
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni33 – 35Combined sources3
Helixi38 – 53Combined sources16
Helixi60 – 71Combined sources12
Helixi73 – 81Combined sources9
Helixi82 – 84Combined sources3
Helixi94 – 96Combined sources3
Helixi102 – 107Combined sources6
Beta strandi108 – 112Combined sources5
Turni113 – 115Combined sources3
Helixi122 – 138Combined sources17
Helixi142 – 159Combined sources18
Turni163 – 167Combined sources5
Turni170 – 172Combined sources3
Helixi175 – 186Combined sources12
Helixi187 – 190Combined sources4
Helixi202 – 209Combined sources8
Helixi213 – 234Combined sources22
Beta strandi237 – 240Combined sources4
Helixi242 – 273Combined sources32
Turni277 – 280Combined sources4
Beta strandi285 – 292Combined sources8
Beta strandi302 – 310Combined sources9
Beta strandi315 – 319Combined sources5
Beta strandi332 – 338Combined sources7
Helixi346 – 348Combined sources3
Beta strandi349 – 357Combined sources9
Beta strandi359 – 362Combined sources4
Beta strandi368 – 375Combined sources8
Beta strandi378 – 384Combined sources7
Beta strandi394 – 398Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ0TV31.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini29 – 278Zn-dependent PLCPROSITE-ProRule annotationAdd BLAST250
Domaini284 – 398PLATPROSITE-ProRule annotationAdd BLAST115

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni275 – 283Linker9

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)DescriptionActionsGraphical viewLength
Sequence conflicti17S → T (PubMed:2536356).Curated1

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
PDB 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.
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.

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: November 2, 2016
This is version 76 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.