SIR6_MACFA
ID SIR6_MACFA Reviewed; 355 AA.
AC A0A2K5TU92;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 02-JUN-2021, sequence version 2.
DT 03-AUG-2022, entry version 25.
DE RecName: Full=NAD-dependent protein deacylase sirtuin-6 {ECO:0000305};
DE EC=2.3.1.- {ECO:0000250|UniProtKB:Q8N6T7};
DE AltName: Full=NAD-dependent protein deacetylase sirtuin-6 {ECO:0000305};
DE EC=2.3.1.286 {ECO:0000269|PubMed:30135584};
DE AltName: Full=Protein mono-ADP-ribosyltransferase sirtuin-6 {ECO:0000305};
DE EC=2.4.2.- {ECO:0000250|UniProtKB:Q8N6T7};
GN Name=SIRT6 {ECO:0000303|PubMed:30135584};
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Warren W., Wilson R.K.;
RL Submitted (MAR-2013) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=30135584; DOI=10.1038/s41586-018-0437-z;
RA Zhang W., Wan H., Feng G., Qu J., Wang J., Jing Y., Ren R., Liu Z.,
RA Zhang L., Chen Z., Wang S., Zhao Y., Wang Z., Yuan Y., Zhou Q., Li W.,
RA Liu G.H., Hu B.;
RT "SIRT6 deficiency results in developmental retardation in cynomolgus
RT monkeys.";
RL Nature 560:661-665(2018).
CC -!- FUNCTION: NAD-dependent protein deacetylase, deacylase and mono-ADP-
CC ribosyltransferase that plays an essential role in DNA damage repair,
CC telomere maintenance, metabolic homeostasis, inflammation,
CC tumorigenesis and aging (PubMed:30135584). Displays protein-lysine
CC deacetylase or defatty-acylase (demyristoylase and depalmitoylase)
CC activity, depending on the context (By similarity). Acts as a key
CC histone deacetylase by catalyzing deacetylation of histone H3 at 'Lys-
CC 9', 'Lys-18' and 'Lys-56' (H3K9ac, H3K18ac and H3K56ac, respectively),
CC suppressing target gene expression of several transcription factors,
CC including NF-kappa-B (PubMed:30135584). Acts as an inhibitor of
CC transcription elongation by mediating deacetylation of H3K9ac and
CC H3K56ac, preventing release of NELFE from chromatin and causing
CC transcriptional pausing (By similarity). Involved in DNA repair by
CC promoting double-strand break (DSB) repair: acts as a DSB sensor by
CC recognizing and binding DSB sites, leading to (1) recruitment of DNA
CC repair proteins, such as SMARCA5/SNF2H, and (2) deacetylation of
CC histone H3K9ac and H3K56ac (By similarity). SIRT6 participation to DSB
CC repair is probably involved in extension of life span (By similarity).
CC Also promotes DNA repair by deacetylating non-histone proteins, such as
CC DDB2 and p53/TP53 (By similarity). Specifically deacetylates H3K18ac at
CC pericentric heterochromatin, thereby maintaining pericentric
CC heterochromatin silencing at centromeres and protecting against genomic
CC instability and cellular senescence (By similarity). Involved in
CC telomere maintenance by catalyzing deacetylation of histone H3 in
CC telomeric chromatin, regulating telomere position effect and telomere
CC movement in response to DNA damage (By similarity). Required for
CC embryonic stem cell differentiation by mediating histone deacetylation
CC of H3K9ac (By similarity). Plays a major role in metabolism by
CC regulating processes such as glycolysis, gluconeogenesis, insulin
CC secretion and lipid metabolism (By similarity). Inhibits glycolysis via
CC histone deacetylase activity and by acting as a corepressor of the
CC transcription factor HIF1A, thereby controlling the expression of
CC multiple glycolytic genes (By similarity). Has tumor suppressor
CC activity by repressing glycolysis, thereby inhibiting the Warburg
CC effect (By similarity). Also regulates glycolysis and tumorigenesis by
CC mediating deacetylation and nuclear export of non-histone proteins,
CC such as isoform M2 of PKM (PKM2) (By similarity). Acts as a negative
CC regulator of gluconeogenesis by mediating deacetylation of non-histone
CC proteins, such as FOXO1 and KAT2A/GCN5 (By similarity). Promotes beta-
CC oxidation of fatty acids during fasting by catalyzing deacetylation of
CC NCOA2, inducing coactivation of PPARA (By similarity). Acts as a
CC regulator of lipid catabolism in brown adipocytes, both by catalyzing
CC deacetylation of histones and non-histone proteins, such as FOXO1 (By
CC similarity). Also acts as a regulator of circadian rhythms, both by
CC regulating expression of clock-controlled genes involved in lipid and
CC carbohydrate metabolism, and by catalyzing deacetylation of PER2 (By
CC similarity). The defatty-acylase activity is specifically involved in
CC regulation of protein secretion (By similarity). Has high activity
CC toward long-chain fatty acyl groups and mediates protein-lysine
CC demyristoylation and depalmitoylation of target proteins, such as RRAS2
CC and TNF, thereby regulating their secretion (By similarity). Also acts
CC as a mono-ADP-ribosyltransferase by mediating mono-ADP-ribosylation of
CC PARP1, TRIM28/KAP1 or SMARCC2/BAF170 (By similarity). Mono-ADP-
CC ribosyltransferase activity is involved in DNA repair, cellular
CC senescence, repression of LINE-1 retrotransposon elements and
CC regulation of transcription (By similarity).
CC {ECO:0000250|UniProtKB:P59941, ECO:0000250|UniProtKB:Q8N6T7,
CC ECO:0000269|PubMed:30135584}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-acetyl-L-lysyl-[protein] + NAD(+) = 2''-O-acetyl-
CC ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
CC Xref=Rhea:RHEA:43636, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:61930, ChEBI:CHEBI:83767;
CC EC=2.3.1.286; Evidence={ECO:0000255|PROSITE-ProRule:PRU00236,
CC ECO:0000269|PubMed:30135584};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43637;
CC Evidence={ECO:0000269|PubMed:30135584};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-tetradecanoyl-L-lysyl-[protein] + NAD(+) = 2''-O-
CC tetradecanoyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
CC Xref=Rhea:RHEA:70567, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:15437,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:141129, ChEBI:CHEBI:189674;
CC Evidence={ECO:0000250|UniProtKB:Q8N6T7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70568;
CC Evidence={ECO:0000250|UniProtKB:Q8N6T7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-hexadecanoyl-L-lysyl-[protein] + NAD(+) = 2''-O-
CC hexadecanoyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
CC Xref=Rhea:RHEA:70563, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:14175,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:138936, ChEBI:CHEBI:189673;
CC Evidence={ECO:0000250|UniProtKB:Q8N6T7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70564;
CC Evidence={ECO:0000250|UniProtKB:Q8N6T7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl-[protein] + NAD(+) = H(+) + N(6)-(ADP-D-ribosyl)-L-
CC lysyl-[protein] + nicotinamide; Xref=Rhea:RHEA:58220, Rhea:RHEA-
CC COMP:9752, Rhea:RHEA-COMP:15088, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17154, ChEBI:CHEBI:29969, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:142515; Evidence={ECO:0000250|UniProtKB:P59941};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58221;
CC Evidence={ECO:0000250|UniProtKB:P59941};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-arginyl-[protein] + NAD(+) = H(+) + N(omega)-(ADP-D-
CC ribosyl)-L-arginyl-[protein] + nicotinamide; Xref=Rhea:RHEA:19149,
CC Rhea:RHEA-COMP:10532, Rhea:RHEA-COMP:15087, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17154, ChEBI:CHEBI:29965, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:142554; Evidence={ECO:0000250|UniProtKB:P59941};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19150;
CC Evidence={ECO:0000250|UniProtKB:P59941};
CC -!- ACTIVITY REGULATION: Compared to the defatty-acylase activity, the
CC protein deacetylase activity is weak in vitro, and requires activation.
CC The histone deacetylase activity is strongly activated upon binding to
CC nucleosomes and chromatin in vivo. Two molecules of SIRT6 associate
CC with the acidic patch of one nucleosome, while the C-terminal
CC disordered region of SIRT6 associates with nucleosomal DNA, leading to
CC efficient histone deacetylation. The protein-lysine deacetylase
CC activity is also activated by long-chain free fatty-acids.
CC {ECO:0000250|UniProtKB:Q8N6T7}.
CC -!- SUBUNIT: Homodimer; binds to nucleosomes and DNA ends as a homodimer
CC (By similarity). Interacts with RELA; interferes with RELA binding to
CC target DNA (By similarity). Interacts with SMARCA5; promoting
CC recruitment of SMARCA5/SNF2H to double-strand breaks (DSBs) sites (By
CC similarity). Interacts with the mTORC2 complex; preventing the ability
CC of SIRT6 to deacetylate FOXO1. Interacts with the CLOCK-BMAL1 complex;
CC recruited by the CLOCK-BMAL1 complex to regulate expression of clock-
CC controlled genes. Interacts with CSNK2A2; preventing CSNK2A2
CC localization to the nucleus (By similarity).
CC {ECO:0000250|UniProtKB:P59941, ECO:0000250|UniProtKB:Q8N6T7}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P59941}.
CC Chromosome {ECO:0000250|UniProtKB:Q8N6T7}. Chromosome, telomere
CC {ECO:0000250|UniProtKB:Q8N6T7}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P59941}. Note=Predominantly nuclear. Associated
CC with pericentric heterochromatin and telomeric heterochromatin regions.
CC Localizes to DNA damage sites: directly recognizes and binds double-
CC strand breaks (DSBs) sites via a tunnel-like structure that has high
CC affinity for DSBs (By similarity). A fraction localizes to the
CC endoplasmic reticulum (By similarity). {ECO:0000250|UniProtKB:P59941,
CC ECO:0000250|UniProtKB:Q8N6T7}.
CC -!- DOMAIN: The C-terminal disordered region mediates non-specific DNA-
CC binding. {ECO:0000250|UniProtKB:Q8N6T7}.
CC -!- PTM: Acetylated at Lys-33. Deacetylation at Lys-33 by SIRT1 promotes
CC homomultimerization and binding to double-strand breaks (DSBs) sites.
CC {ECO:0000250|UniProtKB:Q8N6T7}.
CC -!- PTM: Phosphorylation at Ser-10 by MAPK8/JNK1 in response to oxidative
CC stress stimulates the mono-ADP-ribosyltransferase activity on PARP1,
CC leading to PARP1 recruitment to double-strand breaks (DSBs).
CC {ECO:0000250|UniProtKB:Q8N6T7}.
CC -!- PTM: Monoubiquitinated at Lys-170 by STUB1/CHIP, preventing its
CC degradation by the proteasome. {ECO:0000250|UniProtKB:Q8N6T7}.
CC -!- PTM: Sumoylated, leading to specifically decrease ability to
CC deacetylate histone H3 at 'Lys-56' (H3K56ac).
CC {ECO:0000250|UniProtKB:Q8N6T7}.
CC -!- DISRUPTION PHENOTYPE: Monkeys die soon after birth and exhibit severe
CC prenatal developmental retardation (PubMed:30135584). The molecular
CC developmental stage of the monkeys mimics that of wild-type fetuses at
CC 2-4 months of gestational age (PubMed:30135584). Neuronal
CC differentiation is strongly delayed, due to hyperacetylation of histone
CC H3 at 'Lys-56' (H3K56ac), leading to up-regulation of the long non-
CC coding RNA H19 (PubMed:30135584). {ECO:0000269|PubMed:30135584}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class IV subfamily.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR RefSeq; XP_005587603.1; XM_005587546.2.
DR STRING; 9541.XP_005587603.1; -.
DR Ensembl; ENSMFAT00000022292; ENSMFAP00000003631; ENSMFAG00000001546.
DR GeneID; 102141535; -.
DR KEGG; mcf:102141535; -.
DR CTD; 51548; -.
DR VEuPathDB; HostDB:ENSMFAG00000001546; -.
DR GeneTree; ENSGT00940000160088; -.
DR OrthoDB; 1503290at2759; -.
DR Proteomes; UP000233100; Chromosome 19.
DR Bgee; ENSMFAG00000001546; Expressed in colon and 13 other tissues.
DR GO; GO:0000785; C:chromatin; ISS:UniProtKB.
DR GO; GO:0099115; C:chromosome, subtelomeric region; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005721; C:pericentric heterochromatin; IEA:Ensembl.
DR GO; GO:0035861; C:site of double-strand break; IEA:Ensembl.
DR GO; GO:0031490; F:chromatin DNA binding; ISS:UniProtKB.
DR GO; GO:0003684; F:damaged DNA binding; ISS:UniProtKB.
DR GO; GO:0140612; F:DNA damage sensor activity; ISS:UniProtKB.
DR GO; GO:0106222; F:lncRNA binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070403; F:NAD+ binding; IEA:InterPro.
DR GO; GO:0106274; F:NAD+-protein-arginine ADP-ribosyltransferase activity; ISS:UniProtKB.
DR GO; GO:0097372; F:NAD-dependent histone deacetylase activity (H3-K18 specific); ISS:UniProtKB.
DR GO; GO:0140765; F:NAD-dependent histone deacetylase activity (H3-K56 specific); IDA:UniProtKB.
DR GO; GO:0046969; F:NAD-dependent histone deacetylase activity (H3-K9 specific); ISS:UniProtKB.
DR GO; GO:0034979; F:NAD-dependent protein deacetylase activity; ISS:UniProtKB.
DR GO; GO:0140773; F:NAD-dependent protein demyristoylase activity; ISS:UniProtKB.
DR GO; GO:0140774; F:NAD-dependent protein depalmitoylase activity; ISS:UniProtKB.
DR GO; GO:0031491; F:nucleosome binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:1904841; F:TORC2 complex binding; ISS:UniProtKB.
DR GO; GO:0055007; P:cardiac muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; IEA:Ensembl.
DR GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB.
DR GO; GO:0042181; P:ketone biosynthetic process; ISS:UniProtKB.
DR GO; GO:2000773; P:negative regulation of cellular senescence; IEA:Ensembl.
DR GO; GO:0045721; P:negative regulation of gluconeogenesis; ISS:UniProtKB.
DR GO; GO:0045820; P:negative regulation of glycolytic process; ISS:UniProtKB.
DR GO; GO:0042308; P:negative regulation of protein import into nucleus; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0034244; P:negative regulation of transcription elongation from RNA polymerase II promoter; ISS:UniProtKB.
DR GO; GO:0010529; P:negative regulation of transposition; ISS:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; IMP:UniProtKB.
DR GO; GO:0031508; P:pericentric heterochromatin assembly; ISS:UniProtKB.
DR GO; GO:1905555; P:positive regulation of blood vessel branching; IEA:Ensembl.
DR GO; GO:1902732; P:positive regulation of chondrocyte proliferation; IEA:Ensembl.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:UniProtKB.
DR GO; GO:2000781; P:positive regulation of double-strand break repair; ISS:UniProtKB.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0032024; P:positive regulation of insulin secretion; ISS:UniProtKB.
DR GO; GO:0046827; P:positive regulation of protein export from nucleus; ISS:UniProtKB.
DR GO; GO:0120187; P:positive regulation of protein localization to chromatin; ISS:UniProtKB.
DR GO; GO:2000738; P:positive regulation of stem cell differentiation; ISS:UniProtKB.
DR GO; GO:0032206; P:positive regulation of telomere maintenance; IEA:Ensembl.
DR GO; GO:1901485; P:positive regulation of transcription factor catabolic process; IEA:Ensembl.
DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; IEA:Ensembl.
DR GO; GO:0006476; P:protein deacetylation; IEA:Ensembl.
DR GO; GO:0051697; P:protein delipidation; ISS:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; ISS:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0010569; P:regulation of double-strand break repair via homologous recombination; ISS:UniProtKB.
DR GO; GO:0050994; P:regulation of lipid catabolic process; ISS:UniProtKB.
DR GO; GO:0019216; P:regulation of lipid metabolic process; ISS:UniProtKB.
DR GO; GO:0009411; P:response to UV; IEA:Ensembl.
DR GO; GO:0031509; P:subtelomeric heterochromatin assembly; IEA:Ensembl.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR003000; Sirtuin.
DR InterPro; IPR026590; Ssirtuin_cat_dom.
DR Pfam; PF02146; SIR2; 2.
DR SUPFAM; SSF52467; SSF52467; 1.
DR PROSITE; PS50305; SIRTUIN; 1.
PE 1: Evidence at protein level;
KW Acetylation; Acyltransferase; Chromatin regulator; Chromosome;
KW Developmental protein; DNA damage; DNA repair; DNA-binding;
KW Endoplasmic reticulum; Glycosyltransferase; Isopeptide bond; Metal-binding;
KW NAD; Nucleotidyltransferase; Nucleus; Phosphoprotein; Reference proteome;
KW RNA-binding; Telomere; Transferase; Tumor suppressor; Ubl conjugation;
KW Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT CHAIN 2..355
FT /note="NAD-dependent protein deacylase sirtuin-6"
FT /id="PRO_0000455608"
FT DOMAIN 35..274
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT REGION 284..355
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 133
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 53
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT BINDING 57
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT BINDING 64
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT BINDING 65
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT BINDING 71
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT BINDING 113
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT BINDING 133
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT BINDING 141
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7,
FT ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 144
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7,
FT ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 166
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7,
FT ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 177
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7,
FT ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 214
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT BINDING 216
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT BINDING 240
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT BINDING 242
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT BINDING 258
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT MOD_RES 33
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT MOD_RES 294
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT MOD_RES 303
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT MOD_RES 330
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
FT CROSSLNK 170
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q8N6T7"
SQ SEQUENCE 355 AA; 39078 MW; E13A25B77E9D9DE2 CRC64;
MSVNYAAGLS PYADKGKCGL PEIFDPPEEL ERKVWELARL VWQSSHVVFH TGAGISTASG
IPDFRGPHGV WTMEERGLAP KFDTTFESAR PTQTHMALVQ LERVGLLRFL VSQNVDGLHV
RSGFPRDKLA ELHGNMFVEE CAKCKTQYVR DTVVGTMGLK ATGRLCTVAK ARGLRACRGE
LRDTILDWED SLPDRDLALA DEASRNADLS ITLGTSLQIR PSGNLPLATK RRGGRLVIVN
LQPTKHDRHA DLRIHGYVDE VMTRLMKHLG LEIPAWDGPH VLERALPPLP RPPTPKLEPK
EESPTRINGS IPAGSCLEPC AQHNGSEPAS PKRERPTSPA PNRPPKRVKA EAVPS
