UniProt functional annotation for Q8IE47



	UniProt functional annotation for Q8IE47

UniProt code: Q8IE47.

Organism: Plasmodium falciparum (isolate 3D7).

Taxonomy: Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida; Plasmodiidae; Plasmodium; Plasmodium (Laverania).

Function: NAD-dependent protein deacylase. Catalyzes the NAD-dependent hydrolysis of medium and long chain fatty acyl groups from lysine residues. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Regulates the expression of the surface antigen-coding var genes central to the malaria pathogenesis. Cooperates with Sir2B to mediate silencing and mutual exclusive expression of only 1 of the 60 subtelomeric var genes at a time, coding for functionally different but epitopically variant versions of the erythrocyte membrane protein 1 (PfEMP1) molecule, to evade the detection by host immune surveillance. Can ADP-ribosylate both histones and itself. May also have a role in telomeric end protection. {ECO:0000269|PubMed:15820676, ECO:0000269|PubMed:17827348, ECO:0000269|PubMed:18221799, ECO:0000269|PubMed:18397290, ECO:0000269|PubMed:18525026, ECO:0000269|PubMed:18729382, ECO:0000269|PubMed:19402747, ECO:0000269|PubMed:20601220}.

Catalytic activity: Reaction=H2O + N(6)-acyl-L-lysyl-[protein] + NAD(+) = L-lysyl-[protein] + nicotinamide + O-acyl-ADP-D-ribose; Xref=Rhea:RHEA:54172, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13709, ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969, ChEBI:CHEBI:57540, ChEBI:CHEBI:137967, ChEBI:CHEBI:138087;

Activity regulation: Inhibited by nicotinamide. Inhibited by surfactin, which is a competitive inhibitor of NAD and an uncompetitive inhibitor of acetylated peptide. {ECO:0000269|PubMed:17827348, ECO:0000269|PubMed:18221799, ECO:0000269|PubMed:18397290}.

Biophysicochemical properties: Kinetic parameters: KM=12.2 uM for NAD(+) {ECO:0000269|PubMed:18221799, ECO:0000269|PubMed:18729382}; KM=39 uM for a synthetic histone H3K9 acetyllysine peptide {ECO:0000269|PubMed:18221799, ECO:0000269|PubMed:18729382}; KM=8 uM for a synthetic H3K9 butyryllysine peptide {ECO:0000269|PubMed:18221799, ECO:0000269|PubMed:18729382}; KM=1.2 uM for a synthetic H3K9 octanoyllysine peptide {ECO:0000269|PubMed:18221799, ECO:0000269|PubMed:18729382}; KM=1 uM for a synthetic H3K9 myristoyllysine peptide {ECO:0000269|PubMed:18221799, ECO:0000269|PubMed:18729382}; KM=372 uM for a synthetic histone H3K9K14 acetyllysine peptide {ECO:0000269|PubMed:18221799, ECO:0000269|PubMed:18729382}; KM=176 uM for a synthetic H4K5K8K12K16 acetyllysine peptide {ECO:0000269|PubMed:18221799, ECO:0000269|PubMed:18729382}; KM=85 uM for a synthetic p300 peptide acetylated at 'Lys-1020' and 'Lys-1024' {ECO:0000269|PubMed:18221799, ECO:0000269|PubMed:18729382};

Subunit: Homotrimer. Dissociates into monomers on binding NAD. {ECO:0000269|PubMed:18221799, ECO:0000269|PubMed:20601220, ECO:0000269|PubMed:21992006, ECO:0000269|Ref.11}.

Subcellular location: Nucleus, nucleolus. Chromosome, telomere. Note=Spreads out from the telomere over a distance of at least 20-40 kb and is an important component of the heterochromatin complex around Rep20, a region that lies adjacent to the regulatory 5'-UTR element of telomeric var genes. May relocate to the cytoplasm during the multiple rounds of DNA synthesis and nuclear mitosis in trophozoite stage.

Developmental stage: Present in trophozoite- and schizont-stage parasites, whereas not detected in the ring stage parasites. {ECO:0000269|PubMed:18397290}.

Miscellaneous: The reported ADP-ribosyltransferase activity of sirtuins is likely to be some inefficient side reaction of the deacetylase activity and may not be physiologically relevant. {ECO:0000250}.

Similarity: Belongs to the sirtuin family. Class III subfamily. {ECO:0000255|HAMAP-Rule:MF_03160}.

Annotations taken from UniProtKB at the EBI.


Organism:		Plasmodium falciparum (isolate 3D7).
Taxonomy:		Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida; Plasmodiidae; Plasmodium; Plasmodium (Laverania).



Function:		NAD-dependent protein deacylase. Catalyzes the NAD-dependent hydrolysis of medium and long chain fatty acyl groups from lysine residues. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Regulates the expression of the surface antigen-coding var genes central to the malaria pathogenesis. Cooperates with Sir2B to mediate silencing and mutual exclusive expression of only 1 of the 60 subtelomeric var genes at a time, coding for functionally different but epitopically variant versions of the erythrocyte membrane protein 1 (PfEMP1) molecule, to evade the detection by host immune surveillance. Can ADP-ribosylate both histones and itself. May also have a role in telomeric end protection. {ECO:0000269\|PubMed:15820676, ECO:0000269\|PubMed:17827348, ECO:0000269\|PubMed:18221799, ECO:0000269\|PubMed:18397290, ECO:0000269\|PubMed:18525026, ECO:0000269\|PubMed:18729382, ECO:0000269\|PubMed:19402747, ECO:0000269\|PubMed:20601220}.


Catalytic activity:		Reaction=H2O + N(6)-acyl-L-lysyl-[protein] + NAD(+) = L-lysyl-[protein] + nicotinamide + O-acyl-ADP-D-ribose; Xref=Rhea:RHEA:54172, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13709, ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969, ChEBI:CHEBI:57540, ChEBI:CHEBI:137967, ChEBI:CHEBI:138087;
Activity regulation:		Inhibited by nicotinamide. Inhibited by surfactin, which is a competitive inhibitor of NAD and an uncompetitive inhibitor of acetylated peptide. {ECO:0000269\|PubMed:17827348, ECO:0000269\|PubMed:18221799, ECO:0000269\|PubMed:18397290}.
Biophysicochemical properties:		Kinetic parameters: KM=12.2 uM for NAD(+) {ECO:0000269\|PubMed:18221799, ECO:0000269\|PubMed:18729382}; KM=39 uM for a synthetic histone H3K9 acetyllysine peptide {ECO:0000269\|PubMed:18221799, ECO:0000269\|PubMed:18729382}; KM=8 uM for a synthetic H3K9 butyryllysine peptide {ECO:0000269\|PubMed:18221799, ECO:0000269\|PubMed:18729382}; KM=1.2 uM for a synthetic H3K9 octanoyllysine peptide {ECO:0000269\|PubMed:18221799, ECO:0000269\|PubMed:18729382}; KM=1 uM for a synthetic H3K9 myristoyllysine peptide {ECO:0000269\|PubMed:18221799, ECO:0000269\|PubMed:18729382}; KM=372 uM for a synthetic histone H3K9K14 acetyllysine peptide {ECO:0000269\|PubMed:18221799, ECO:0000269\|PubMed:18729382}; KM=176 uM for a synthetic H4K5K8K12K16 acetyllysine peptide {ECO:0000269\|PubMed:18221799, ECO:0000269\|PubMed:18729382}; KM=85 uM for a synthetic p300 peptide acetylated at 'Lys-1020' and 'Lys-1024' {ECO:0000269\|PubMed:18221799, ECO:0000269\|PubMed:18729382};
Subunit:		Homotrimer. Dissociates into monomers on binding NAD. {ECO:0000269\|PubMed:18221799, ECO:0000269\|PubMed:20601220, ECO:0000269\|PubMed:21992006, ECO:0000269\|Ref.11}.
Subcellular location:		Nucleus, nucleolus. Chromosome, telomere. Note=Spreads out from the telomere over a distance of at least 20-40 kb and is an important component of the heterochromatin complex around Rep20, a region that lies adjacent to the regulatory 5'-UTR element of telomeric var genes. May relocate to the cytoplasm during the multiple rounds of DNA synthesis and nuclear mitosis in trophozoite stage.
Developmental stage:		Present in trophozoite- and schizont-stage parasites, whereas not detected in the ring stage parasites. {ECO:0000269\|PubMed:18397290}.
Miscellaneous:		The reported ADP-ribosyltransferase activity of sirtuins is likely to be some inefficient side reaction of the deacetylase activity and may not be physiologically relevant. {ECO:0000250}.
Similarity:		Belongs to the sirtuin family. Class III subfamily. {ECO:0000255\|HAMAP-Rule:MF_03160}.