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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: -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.

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.

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

Keywordsi

Molecular functionHydrolase, Toxin
Biological processCytolysis, Hemolysis, Virulence
LigandCalcium, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciCPER195103:G1G5R-44-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

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

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG41064S2 Bacteria
ENOG4112CMR LUCA
KOiK16619
OMAiDHFWDPD
OrthoDBiPOG091H10JI

Family and domain databases

Gene3Di1.10.575.10, 1 hit
InterProiView protein in InterPro
IPR001024 PLAT/LH2_dom
IPR036392 PLAT/LH2_dom_sf
IPR008947 PLipase_C/P1_nuclease_dom_sf
IPR029002 PLPC/GPLD1
IPR001531 Zn_PLipaseC
PfamiView protein in Pfam
PF01477 PLAT, 1 hit
PF00882 Zn_dep_PLPC, 1 hit
PRINTSiPR00479 PRPHPHLPASEC
ProDomiView protein in ProDom or Entries sharing at least one domain
PD003946 PLipaseC_Zn-bd_prok, 1 hit
SMARTiView protein in SMART
SM00770 Zn_dep_PLPC, 1 hit
SUPFAMiSSF48537 SSF48537, 1 hit
SSF49723 SSF49723, 1 hit
PROSITEiView protein in PROSITE
PS50095 PLAT, 1 hit
PS00384 PROKAR_ZN_DEPEND_PLPC_1, 1 hit
PS51346 PROKAR_ZN_DEPEND_PLPC_2, 1 hit

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
GeneIDi29569865
KEGGicpf:CPF_0042

Similar proteinsi

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 historyiIntegrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: September 5, 2006
Last modified: March 28, 2018
This is version 84 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing
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Main funding by: National Institutes of Health