UniProt functional annotation for Q04IN8



	UniProt functional annotation for Q04IN8

UniProt code: Q04IN8.

Organism: Streptococcus pneumoniae serotype 2 (strain D39 / NCTC 7466).

Taxonomy: Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae; Streptococcus.

Function: A cholesterol-dependent toxin that causes cytolysis by forming pores in cholesterol-containing host membranes. After binding to target membranes, the protein undergoes a major conformation change, leading to its insertion in the host membrane and formation of an oligomeric pore complex. Cholesterol is required for binding to host membranes, membrane insertion and pore formation; cholesterol binding is mediated by a Thr-Leu pair in the C-terminus. Can be reversibly inactivated by oxidation. {ECO:0000269|PubMed:15851031, ECO:0000269|PubMed:20145114, ECO:0000269|PubMed:26333773, ECO:0000269|PubMed:28323617, ECO:0000269|PubMed:9445384}.

Activity regulation: Erythrocytes hemolysis is inhibited by cholesterol. {ECO:0000269|PubMed:26333773}.

Subunit: Elongated monomers align along their lengths, indicating intersubunit contacts and suggesting the prepore structure (PubMed:15851031, PubMed:26333773, PubMed:26403197, PubMed:27796097, PubMed:28323617). Modeling based on cryo-EM shows a homooligomeric pore complex containing 38-44 subunits; when inserted in the host membrane (Probable). The size of isolated pores is detergent-dependent; in amphipol A8-35 homogenous rings form with 42 subunits (PubMed:28323617). {ECO:0000269|PubMed:15851031, ECO:0000269|PubMed:26333773, ECO:0000269|PubMed:26403197, ECO:0000269|PubMed:27796097, ECO:0000269|PubMed:28323617, ECO:0000305|PubMed:15851031}.

Subcellular location: Secreted {ECO:0000250|UniProtKB:P0C2J9}. Host cell membrane {ECO:0000269|PubMed:28323617, ECO:0000305|PubMed:15851031}; Multi-pass membrane protein {ECO:0000269|PubMed:28323617}. Note=Secreted as soluble protein by the accessory Sec system (By similarity). It then inserts into the host cell membrane and forms pores formed by transmembrane beta-strands (PubMed:15851031, PubMed:28323617). {ECO:0000250|UniProtKB:P0C2J9, ECO:0000269|PubMed:15851031, ECO:0000269|PubMed:28323617}.

Domain: A highly conserved undecapeptide in the C-terminus has residues important for membrane binding and cell lysis (PubMed:9445384). Mature protein has 3 discontinuous domains; D1, D2, D3 followed by C-terminal D4 (PubMed:15851031, PubMed:26333773, PubMed:26403197, PubMed:27796097, PubMed:28323617). The domains rearrange substantially upon membrane insertion, in particular alpha-helices in D3 refold to form the transmembrane beta-strands (PubMed:15851031, PubMed:28323617). The relative position of domain D4 changes, allowing it to interact with host membranes (PubMed:26333773, PubMed:27796097, PubMed:28323617). {ECO:0000269|PubMed:15851031, ECO:0000269|PubMed:26333773, ECO:0000269|PubMed:26403197, ECO:0000269|PubMed:27796097, ECO:0000269|PubMed:28323617, ECO:0000269|PubMed:9445384}.

Similarity: Belongs to the cholesterol-dependent cytolysin family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Streptococcus pneumoniae serotype 2 (strain D39 / NCTC 7466).
Taxonomy:		Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae; Streptococcus.



Function:		A cholesterol-dependent toxin that causes cytolysis by forming pores in cholesterol-containing host membranes. After binding to target membranes, the protein undergoes a major conformation change, leading to its insertion in the host membrane and formation of an oligomeric pore complex. Cholesterol is required for binding to host membranes, membrane insertion and pore formation; cholesterol binding is mediated by a Thr-Leu pair in the C-terminus. Can be reversibly inactivated by oxidation. {ECO:0000269\|PubMed:15851031, ECO:0000269\|PubMed:20145114, ECO:0000269\|PubMed:26333773, ECO:0000269\|PubMed:28323617, ECO:0000269\|PubMed:9445384}.


Activity regulation:		Erythrocytes hemolysis is inhibited by cholesterol. {ECO:0000269\|PubMed:26333773}.
Subunit:		Elongated monomers align along their lengths, indicating intersubunit contacts and suggesting the prepore structure (PubMed:15851031, PubMed:26333773, PubMed:26403197, PubMed:27796097, PubMed:28323617). Modeling based on cryo-EM shows a homooligomeric pore complex containing 38-44 subunits; when inserted in the host membrane (Probable). The size of isolated pores is detergent-dependent; in amphipol A8-35 homogenous rings form with 42 subunits (PubMed:28323617). {ECO:0000269\|PubMed:15851031, ECO:0000269\|PubMed:26333773, ECO:0000269\|PubMed:26403197, ECO:0000269\|PubMed:27796097, ECO:0000269\|PubMed:28323617, ECO:0000305\|PubMed:15851031}.
Subcellular location:		Secreted {ECO:0000250\|UniProtKB:P0C2J9}. Host cell membrane {ECO:0000269\|PubMed:28323617, ECO:0000305\|PubMed:15851031}; Multi-pass membrane protein {ECO:0000269\|PubMed:28323617}. Note=Secreted as soluble protein by the accessory Sec system (By similarity). It then inserts into the host cell membrane and forms pores formed by transmembrane beta-strands (PubMed:15851031, PubMed:28323617). {ECO:0000250\|UniProtKB:P0C2J9, ECO:0000269\|PubMed:15851031, ECO:0000269\|PubMed:28323617}.
Domain:		A highly conserved undecapeptide in the C-terminus has residues important for membrane binding and cell lysis (PubMed:9445384). Mature protein has 3 discontinuous domains; D1, D2, D3 followed by C-terminal D4 (PubMed:15851031, PubMed:26333773, PubMed:26403197, PubMed:27796097, PubMed:28323617). The domains rearrange substantially upon membrane insertion, in particular alpha-helices in D3 refold to form the transmembrane beta-strands (PubMed:15851031, PubMed:28323617). The relative position of domain D4 changes, allowing it to interact with host membranes (PubMed:26333773, PubMed:27796097, PubMed:28323617). {ECO:0000269\|PubMed:15851031, ECO:0000269\|PubMed:26333773, ECO:0000269\|PubMed:26403197, ECO:0000269\|PubMed:27796097, ECO:0000269\|PubMed:28323617, ECO:0000269\|PubMed:9445384}.
Similarity:		Belongs to the cholesterol-dependent cytolysin family. {ECO:0000305}.