A0A2S3R7M0 · MARTX_VIBVL

  • Protein
    Multifunctional-autoprocessing repeats-in-toxin
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Multifunctional-autoprocessing repeats-in-toxin

Precursor of a multifunctional toxin that causes destruction of the actin cytoskeleton by covalent cross-linking of actin and inactivation of Rho GTPases when translocated into the host cytoplasm. Upon translocation into the host cell, undergoes autoprocessing in cis mediated by the peptidase C80 domain (also named CPD domain): the protease activity is activated upon binding inositol hexakisphosphate (InsP6) present at the host cell membrane and delivers the Cysteine protease domain-containing toxin F3 chain to the host cytosol. The Cysteine protease domain-containing toxin F3 chain will then further cleave and release effector toxin chains that cause disassembly of the actin cytoskeleton and enhance V.vulnificus colonization of the small intestine, possibly by facilitating evasion of phagocytic cells.

Cysteine protease domain-containing toxin F3

Following autocatalytic cleavage in cis, this chain mediates processing in trans to release other individual toxin chains to the host cytosol. Released effector toxin chains cause disassembly of the actin cytoskeleton and enhance V.vulnificus colonization of the small intestine, possibly by facilitating evasion of phagocytic cells.

Actin cross-linking toxin F1

Actin-directed toxin that catalyzes the covalent cross-linking of host cytoplasmic monomeric actin. Mediates the cross-link between 'Lys-50' of one monomer and 'Glu-270' of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding. The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin-dependent and independent manners. Acts as an acid--amino-acid ligase that transfers the gamma-phosphoryl group of ATP to the 'Glu-270' actin residue, resulting in the formation of an activated acyl phosphate intermediate. This intermediate is further hydrolyzed and the energy of hydrolysis is utilized for the formation of the amide bond between actin subunits.

N-epsilon-fatty acyltransferase F2

N-epsilon-fatty acyltransferase that mediates lysine-palmitoylation of host Rho GTPase proteins, with a strong preference for host Rac1. After delivery to the host cytosol, localizes to the host cell membrane where it palmitoylates host Rho GTPase proteins, resulting in loss of all active GTP-bound Rho and subsequent actin depolymerization. Prenylation of host Rac1 at the C-terminus is required for lysine-palmitoylation.

ABH effector region toxin F5

Indirectly activates the small GTPase CDC42.

Catalytic activity

Cofactor

Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

Note: Binds 2 Mg2+ ions per subunit. Mg2+ is required for actin cross-linking activity. Can also use Mn2+ ions instead of Mg2+.

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site4117-41191D-myo-inositol hexakisphosphate (UniProtKB | ChEBI)
Binding site4144-41451D-myo-inositol hexakisphosphate (UniProtKB | ChEBI)
Binding site41751D-myo-inositol hexakisphosphate (UniProtKB | ChEBI)
Active site4181For cysteine protease activity
Binding site42261D-myo-inositol hexakisphosphate (UniProtKB | ChEBI)
Active site4230Nucleophile; for cysteine protease activity
Binding site4259-42611D-myo-inositol hexakisphosphate (UniProtKB | ChEBI)
Binding site4272-42731D-myo-inositol hexakisphosphate (UniProtKB | ChEBI)
Binding site42851D-myo-inositol hexakisphosphate (UniProtKB | ChEBI)
Binding site42901D-myo-inositol hexakisphosphate (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentextracellular region
Cellular Componenthost cell cytosol
Cellular Componenthost cell plasma membrane
Cellular Componentmembrane
Molecular Functionacyltransferase activity
Molecular Functioncysteine-type peptidase activity
Molecular Functionligase activity
Molecular Functionlipid binding
Molecular Functionmetal ion binding
Molecular Functiontoxin activity
Biological Processproteolysis

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

Gene names

    • ORF names
      CRN52_02910

Organism names

  • Taxonomic identifier
  • Strain
    • CECT4608
  • Taxonomic lineage
    Bacteria > Pseudomonadota > Gammaproteobacteria > Vibrionales > Vibrionaceae > Vibrio

Accessions

  • Primary accession
    A0A2S3R7M0

Proteomes

Subcellular Location

Multifunctional-autoprocessing repeats-in-toxin

Secreted
Note: Secreted via the type I secretion system.

N-epsilon-fatty acyltransferase F2

Host cell membrane
Note: Targeted to the host cell membrane via the membrane localization region (MLD).

Actin cross-linking toxin F1

Keywords

PTM/Processing

Features

Showing features for signal, chain.

TypeIDPosition(s)Description
Signal1-19
ChainPRO_000045565920-1958Actin cross-linking toxin F1
ChainPRO_000045565820-5206Multifunctional-autoprocessing repeats-in-toxin
ChainPRO_00004556602296-2901N-epsilon-fatty acyltransferase F2
ChainPRO_00004556612902-3400ABH effector region toxin F5
ChainPRO_00004556624091-5206Cysteine protease domain-containing toxin F3

Keywords

Structure

Family & Domains

Features

Showing features for repeat, compositional bias, region, domain.

TypeIDPosition(s)Description
Repeat101-118RtxA 1
Repeat121-138RtxA 2
Repeat141-157RtxA 3
Repeat161-184RtxA 4
Repeat187-204RtxA 5
Repeat207-224RtxA 6
Repeat255-272RtxA 7
Repeat275-291RtxA 8
Repeat584-601RtxA 9
Repeat604-620RtxA 10
Repeat624-641RtxA 11
Repeat644-658RtxA 12
Repeat741-753RtxA 13
Repeat759-771RtxA 14
Repeat782-798RtxA 15
Repeat801-816RtxA 16
Repeat820-835RtxA 17
Repeat841-855RtxA 18
Repeat858-875RtxA 19
Repeat877-891RtxA 20
Repeat896-910RtxA 21
Repeat915-932RtxA 22
Repeat934-950RtxA 23
Repeat972-984RtxA 24
Repeat991-1006RtxA 25
Repeat1031-1043RtxA 26
Repeat1067-1079RtxA 27
Repeat1087-1102RtxA 28
Repeat1110-1122RtxA 29
Repeat1125-1142RtxA 30
Repeat1145-1159RtxA 31
Repeat1163-1179RtxA 32
Repeat1184-1199RtxA 33
Repeat1201-1217RtxA 34
Repeat1220-1236RtxA 35
Repeat1242-1256RtxA 36
Repeat1258-1275RtxA 37
Repeat1296-1313RtxA 38
Repeat1315-1332RtxA 39
Compositional bias1606-1627Polar residues
Region1606-1682Disordered
Compositional bias1628-1645Basic and acidic residues
Compositional bias1647-1670Polar residues
Compositional bias1738-1752Polar residues
Region1738-1895Disordered
Compositional bias1774-1801Basic and acidic residues
Compositional bias1867-1886Polar residues
Region2377-2461Membrane localization region (MLD)
Region2537-2901Rho inactivation domain (RID)
Region2998-3113ABH effector region
Domain4111-4295Peptidase C80
Region4333-4362Disordered
Region4738-4779Disordered
Compositional bias4749-4779Polar residues

Keywords

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    5,206
  • Mass (Da)
    556,341
  • Last updated
    2018-07-18 v1
  • Checksum
    85BB805918FD1C5A

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias1606-1627Polar residues
Compositional bias1628-1645Basic and acidic residues
Compositional bias1647-1670Polar residues
Compositional bias1738-1752Polar residues
Compositional bias1774-1801Basic and acidic residues
Compositional bias1867-1886Polar residues
Compositional bias4749-4779Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
PDGH01000027
EMBL· GenBank· DDBJ
POB49698.1
EMBL· GenBank· DDBJ
Genomic DNA

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