SIR6_CASCN
ID SIR6_CASCN Reviewed; 355 AA.
AC A0A250YGJ5;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 22-NOV-2017, sequence version 1.
DT 03-AUG-2022, entry version 19.
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:31002797};
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:28087693};
OS Castor canadensis (American beaver).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Castorimorpha; Castoridae;
OC Castor.
OX NCBI_TaxID=51338;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=31002797; DOI=10.1016/j.cell.2019.03.043;
RA Tian X., Firsanov D., Zhang Z., Cheng Y., Luo L., Tombline G., Tan R.,
RA Simon M., Henderson S., Steffan J., Goldfarb A., Tam J., Zheng K.,
RA Cornwell A., Johnson A., Yang J.N., Mao Z., Manta B., Dang W., Zhang Z.,
RA Vijg J., Wolfe A., Moody K., Kennedy B.K., Bohmann D., Gladyshev V.N.,
RA Seluanov A., Gorbunova V.;
RT "SIRT6 is responsible for more efficient DNA double-strand break repair in
RT long-lived species.";
RL Cell 177:622-638(2019).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Ward;
RX PubMed=28087693; DOI=10.1534/g3.116.038208;
RA Lok S., Paton T.A., Wang Z., Kaur G., Walker S., Yuen R.K., Sung W.W.,
RA Whitney J., Buchanan J.A., Trost B., Singh N., Apresto B., Chen N.,
RA Coole M., Dawson T.J., Ho K.Y., Hu Z., Pullenayegum S., Samler K.,
RA Shipstone A., Tsoi F., Wang T., Pereira S.L., Rostami P., Ryan C.A.,
RA Tong A.H., Ng K., Sundaravadanam Y., Simpson J.T., Lim B.K., Engstrom M.D.,
RA Dutton C.J., Kerr K.C., Franke M., Rapley W., Wintle R.F., Scherer S.W.;
RT "De Novo Genome and Transcriptome Assembly of the Canadian Beaver (Castor
RT canadensis).";
RL G3 (Bethesda) 7:755-773(2017).
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 (By similarity). 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:31002797). 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
CC (PubMed:31002797). Also promotes DNA repair by deacetylating non-
CC histone proteins, such as DDB2 and p53/TP53 (By similarity).
CC Specifically deacetylates H3K18ac at pericentric heterochromatin,
CC thereby maintaining pericentric heterochromatin silencing at
CC centromeres and protecting against genomic instability and cellular
CC senescence (By similarity). Involved in telomere maintenance by
CC catalyzing deacetylation of histone H3 in telomeric chromatin,
CC regulating telomere position effect and telomere movement in response
CC to DNA damage (By similarity). Required for embryonic stem cell
CC differentiation by mediating histone deacetylation of H3K9ac (By
CC similarity). Plays a major role in metabolism by regulating processes
CC such as glycolysis, gluconeogenesis, insulin secretion and lipid
CC metabolism (By similarity). Inhibits glycolysis via histone deacetylase
CC activity and by acting as a corepressor of the transcription factor
CC HIF1A, thereby controlling the expression of multiple glycolytic genes
CC (By similarity). Has tumor suppressor activity by repressing
CC glycolysis, thereby inhibiting the Warburg effect (By similarity). Also
CC regulates glycolysis and tumorigenesis by mediating deacetylation and
CC nuclear export of non-histone proteins, such as isoform M2 of PKM
CC (PKM2) (By similarity). Acts as a negative regulator of gluconeogenesis
CC by mediating deacetylation of non-histone proteins, such as FOXO1 and
CC KAT2A/GCN5 (By similarity). Promotes beta-oxidation of fatty acids
CC during fasting by catalyzing deacetylation of NCOA2, inducing
CC coactivation of PPARA (By similarity). Acts as a regulator of lipid
CC catabolism in brown adipocytes, both by catalyzing deacetylation of
CC histones and non-histone proteins, such as FOXO1 (By similarity). Also
CC acts as a regulator of circadian rhythms, both by regulating expression
CC of clock-controlled genes involved in lipid and carbohydrate
CC metabolism, and by catalyzing deacetylation of PER2 (By similarity).
CC The defatty-acylase activity is specifically involved in regulation of
CC protein secretion (By similarity). Has high activity toward long-chain
CC fatty acyl groups and mediates protein-lysine demyristoylation and
CC depalmitoylation of target proteins, such as RRAS2 and TNF, thereby
CC regulating their secretion (By similarity). Also acts as a mono-ADP-
CC ribosyltransferase by mediating mono-ADP-ribosylation of PARP1,
CC 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:31002797}.
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:31002797};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43637;
CC Evidence={ECO:0000269|PubMed:31002797};
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 -!- MISCELLANEOUS: Compared to other rodents, beaver SIRT6 displays higher
CC histone deacetylase activity and ability to promote double-strand break
CC (DSB) repair, possibly leading to longer life span.
CC {ECO:0000269|PubMed:31002797}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class IV subfamily.
CC {ECO:0000305}.
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DR EMBL; MK482069; QBK17522.1; -; mRNA.
DR EMBL; GFFW01002122; JAV42666.1; -; Transcribed_RNA.
DR SMR; A0A250YGJ5; -.
DR Proteomes; UP000694852; Unplaced.
DR GO; GO:0000785; C:chromatin; ISS:UniProtKB.
DR GO; GO:0000781; C:chromosome, telomeric region; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
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: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); IMP: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); IMP: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:0003723; F:RNA binding; IEA:UniProtKB-KW.
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; IMP:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB.
DR GO; GO:0042181; P:ketone biosynthetic process; ISS:UniProtKB.
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; ISS: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:0031508; P:pericentric heterochromatin assembly; ISS:UniProtKB.
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; IMP: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: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 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; Hydrolase; Isopeptide bond;
KW Metal-binding; NAD; Nucleotidyltransferase; Nucleus; Phosphoprotein;
KW Reference proteome; RNA-binding; Telomere; Transferase; Tumor suppressor;
KW Ubl conjugation; 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_0000455607"
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; 39068 MW; AE6CB557825AC1EF CRC64;
MSVNYAAGLS PYADKGKCGL PEIFDPPEEL ERKVWELARL VRQSSNVVFH TGAGISTASG
IPDFRGPHGV WTMEERGLAP KFDTTFENAR PTQTHMALVQ LERVGLLHFV VSQNVDGLHV
RSGFPRDKLA ELHGNMFVEE CAKCKTQYVR DTVVGTMGLK TTGRLCTVAK ARGLRACRGE
LRDTILDWED ALPDRDLALA DEASRNADLS ITLGTSLQIR PSGNLPLATK RRGGKLVIVN
LQPTKHDRHA DLRIHGYVDD VMTQLMKHLG LEIPAWDGPR VLEKALPPLP RPPTPKLEPT
DKSLAQLNGS VPADSKPEPC TWHNGSQPAS PKREQPDSPA PRRPPKRVKA EVTPS
