SIR1_RAT
ID SIR1_RAT Reviewed; 555 AA.
AC A0A0G2JZ79;
DT 08-JUN-2016, integrated into UniProtKB/Swiss-Prot.
DT 08-JUN-2016, sequence version 2.
DT 03-AUG-2022, entry version 50.
DE RecName: Full=NAD-dependent protein deacetylase sirtuin-1 {ECO:0000250|UniProtKB:Q923E4};
DE EC=2.3.1.286 {ECO:0000250|UniProtKB:Q96EB6};
DE AltName: Full=NAD-dependent protein deacylase sirtuin-1;
DE EC=2.3.1.- {ECO:0000250|UniProtKB:Q923E4};
GN Name=Sirt1 {ECO:0000312|RGD:1308542};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
CC -!- FUNCTION: NAD-dependent protein deacetylase that links transcriptional
CC regulation directly to intracellular energetics and participates in the
CC coordination of several separated cellular functions such as cell
CC cycle, response to DNA damage, metabolism, apoptosis and autophagy. Can
CC modulate chromatin function through deacetylation of histones and can
CC promote alterations in the methylation of histones and DNA, leading to
CC transcriptional repression. Deacetylates a broad range of transcription
CC factors and coregulators, thereby regulating target gene expression
CC positively and negatively. Serves as a sensor of the cytosolic ratio of
CC NAD(+)/NADH which is altered by glucose deprivation and metabolic
CC changes associated with caloric restriction. Is essential in skeletal
CC muscle cell differentiation and in response to low nutrients mediates
CC the inhibitory effect on skeletal myoblast differentiation which also
CC involves 5'-AMP-activated protein kinase (AMPK) and nicotinamide
CC phosphoribosyltransferase (NAMPT). Component of the eNoSC (energy-
CC dependent nucleolar silencing) complex, a complex that mediates
CC silencing of rDNA in response to intracellular energy status and acts
CC by recruiting histone-modifying enzymes. The eNoSC complex is able to
CC sense the energy status of cell: upon glucose starvation, elevation of
CC NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3
CC deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by
CC SUV39H1 and the formation of silent chromatin in the rDNA locus.
CC Deacetylates 'Lys-266' of SUV39H1, leading to its activation. Inhibits
CC skeletal muscle differentiation by deacetylating PCAF and MYOD1.
CC Deacetylates H2A and 'Lys-26' of H1-4. Deacetylates 'Lys-16' of histone
CC H4 (in vitro). Involved in NR0B2/SHP corepression function through
CC chromatin remodeling: Recruited to LRH1 target gene promoters by
CC NR0B2/SHP thereby stimulating histone H3 and H4 deacetylation leading
CC to transcriptional repression. Proposed to contribute to genomic
CC integrity via positive regulation of telomere length; however, reports
CC on localization to pericentromeric heterochromatin are conflicting.
CC Proposed to play a role in constitutive heterochromatin (CH) formation
CC and/or maintenance through regulation of the available pool of nuclear
CC SUV39H1. Upon oxidative/metabolic stress decreases SUV39H1 degradation
CC by inhibiting SUV39H1 polyubiquitination by MDM2. This increase in
CC SUV39H1 levels enhances SUV39H1 turnover in CH, which in turn seems to
CC accelerate renewal of the heterochromatin which correlates with greater
CC genomic integrity during stress response. Deacetylates 'Lys-382' of
CC p53/TP53 and impairs its ability to induce transcription-dependent
CC proapoptotic program and modulate cell senescence. Deacetylates TAF1B
CC and thereby represses rDNA transcription by the RNA polymerase I.
CC Deacetylates MYC, promotes the association of MYC with MAX and
CC decreases MYC stability leading to compromised transformational
CC capability. Deacetylates FOXO3 in response to oxidative stress thereby
CC increasing its ability to induce cell cycle arrest and resistance to
CC oxidative stress but inhibiting FOXO3-mediated induction of apoptosis
CC transcriptional activity; also leading to FOXO3 ubiquitination and
CC protesomal degradation. Appears to have a similar effect on MLLT7/FOXO4
CC in regulation of transcriptional activity and apoptosis. Deacetylates
CC DNMT1; thereby impairs DNMT1 methyltransferase-independent
CC transcription repressor activity, modulates DNMT1 cell cycle regulatory
CC function and DNMT1-mediated gene silencing. Deacetylates RELA/NF-kappa-
CC B p65 thereby inhibiting its transactivating potential and augments
CC apoptosis in response to TNF-alpha. Deacetylates HIF1A, KAT5/TIP60, RB1
CC and HIC1. Deacetylates FOXO1 resulting in its nuclear retention and
CC enhancement of its transcriptional activity leading to increased
CC gluconeogenesis in liver. Inhibits E2F1 transcriptional activity and
CC apoptotic function, possibly by deacetylation. Involved in HES1- and
CC HEY2-mediated transcriptional repression. In cooperation with MYCN
CC seems to be involved in transcriptional repression of DUSP6/MAPK3
CC leading to MYCN stabilization by phosphorylation at 'Ser-62'.
CC Deacetylates MEF2D. Required for antagonist-mediated transcription
CC suppression of AR-dependent genes which may be linked to local
CC deacetylation of histone H3. Represses HNF1A-mediated transcription.
CC Required for the repression of ESRRG by CREBZF. Deacetylates NR1H3 AND
CC NR1H2 and deacetylation of NR1H3 at 'Lys-434' positively regulates
CC transcription of NR1H3:RXR target genes, promotes NR1H3 proteosomal
CC degradation and results in cholesterol efflux; a promoter clearing
CC mechanism after reach round of transcription is proposed. Involved in
CC lipid metabolism: deacetylates LPIN1, thereby inhibiting diacylglycerol
CC synthesis. Implicated in regulation of adipogenesis and fat
CC mobilization in white adipocytes by repression of PPARG which probably
CC involves association with NCOR1 and SMRT/NCOR2. Deacetylates p300/EP300
CC and PRMT1. Deacetylates ACSS2 leading to its activation, and HMGCS1
CC deacetylation. Involved in liver and muscle metabolism. Through
CC deacetylation and activation of PPARGC1A is required to activate fatty
CC acid oxidation in skeletal muscle under low-glucose conditions and is
CC involved in glucose homeostasis. Involved in regulation of PPARA and
CC fatty acid beta-oxidation in liver. Involved in positive regulation of
CC insulin secretion in pancreatic beta cells in response to glucose; the
CC function seems to imply transcriptional repression of UCP2. Proposed to
CC deacetylate IRS2 thereby facilitating its insulin-induced tyrosine
CC phosphorylation. Deacetylates SREBF1 isoform SREBP-1C thereby
CC decreasing its stability and transactivation in lipogenic gene
CC expression. Involved in DNA damage response by repressing genes which
CC are involved in DNA repair, such as XPC and TP73, deacetylating
CC XRCC6/Ku70, and facilitating recruitment of additional factors to sites
CC of damaged DNA, such as SIRT1-deacetylated NBN can recruit ATM to
CC initiate DNA repair and SIRT1-deacetylated XPA interacts with RPA2.
CC Also involved in DNA repair of DNA double-strand breaks by homologous
CC recombination and specifically single-strand annealing independently of
CC XRCC6/Ku70 and NBN. Promotes DNA double-strand breaks by mediating
CC deacetylation of SIRT6. Transcriptional suppression of XPC probably
CC involves an E2F4:RBL2 suppressor complex and protein kinase B (AKT)
CC signaling. Transcriptional suppression of TP73 probably involves E2F4
CC and PCAF. Deacetylates WRN thereby regulating its helicase and
CC exonuclease activities and regulates WRN nuclear translocation in
CC response to DNA damage. Deacetylates APEX1 at 'Lys-6' and 'Lys-7' and
CC stimulates cellular AP endonuclease activity by promoting the
CC association of APEX1 to XRCC1. Catalyzes deacetylation of ERCC4/XPF,
CC thereby impairing interaction with ERCC1 and nucleotide excision repair
CC (NER). Increases p53/TP53-mediated transcription-independent apoptosis
CC by blocking nuclear translocation of cytoplasmic p53/TP53 and probably
CC redirecting it to mitochondria. Deacetylates XRCC6/Ku70 at 'Lys-539'
CC and 'Lys-542' causing it to sequester BAX away from mitochondria
CC thereby inhibiting stress-induced apoptosis. Is involved in autophagy,
CC presumably by deacetylating ATG5, ATG7 and MAP1LC3B/ATG8. Deacetylates
CC AKT1 which leads to enhanced binding of AKT1 and PDK1 to PIP3 and
CC promotes their activation. Proposed to play role in regulation of
CC STK11/LBK1-dependent AMPK signaling pathways implicated in cellular
CC senescence which seems to involve the regulation of the acetylation
CC status of STK11/LBK1. Can deacetylate STK11/LBK1 and thereby increase
CC its activity, cytoplasmic localization and association with STRAD;
CC however, the relevance of such activity in normal cells is unclear. In
CC endothelial cells is shown to inhibit STK11/LBK1 activity and to
CC promote its degradation. Deacetylates SMAD7 at 'Lys-64' and 'Lys-70'
CC thereby promoting its degradation. Deacetylates CIITA and augments its
CC MHC class II transactivation and contributes to its stability.
CC Deacetylates MECOM/EVI1. Deacetylates PML at 'Lys-487' and this
CC deacetylation promotes PML control of PER2 nuclear localization. During
CC the neurogenic transition, represses selective NOTCH1-target genes
CC through histone deacetylation in a BCL6-dependent manner and leading to
CC neuronal differentiation. Regulates the circadian expression of several
CC core clock genes, including ARNTL/BMAL1, RORC, PER2 and CRY1 and plays
CC a critical role in maintaining a controlled rhythmicity in histone
CC acetylation, thereby contributing to circadian chromatin remodeling.
CC Deacetylates ARNTL/BMAL1 and histones at the circadian gene promoters
CC in order to facilitate repression by inhibitory components of the
CC circadian oscillator. Deacetylates PER2, facilitating its
CC ubiquitination and degradation by the proteosome. Protects
CC cardiomyocytes against palmitate-induced apoptosis. Deacetylates XBP1
CC isoform 2; deacetylation decreases protein stability of XBP1 isoform 2
CC and inhibits its transcriptional activity. Deacetylates PCK1 and
CC directs its activity toward phosphoenolpyruvate production promoting
CC gluconeogenesis. Involved in the CCAR2-mediated regulation of PCK1 and
CC NR1D1. Deacetylates CTNB1 at 'Lys-49'. In POMC (pro-opiomelanocortin)
CC neurons, required for leptin-induced activation of PI3K signaling. In
CC addition to protein deacetylase activity, also acts as protein-lysine
CC deacylase by mediating protein depropionylation and decrotonylation.
CC Mediates depropionylation of Osterix (SP7). Catalyzes decrotonylation
CC of histones; it however does not represent a major histone
CC decrotonylase. Deacetylates SOX9; promoting SOX9 nuclear localization
CC and transactivation activity. Involved in the regulation of centrosome
CC duplication. Deacetylates CENATAC in G1 phase, allowing for SASS6
CC accumulation on the centrosome and subsequent procentriole assembly (By
CC similarity). Deacetylates NDC80/HEC1 (By similarity).
CC {ECO:0000250|UniProtKB:Q923E4, ECO:0000250|UniProtKB:Q96EB6}.
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:0000250|UniProtKB:Q96EB6,
CC ECO:0000255|PROSITE-ProRule:PRU00236};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-propanoyl-L-lysyl-[protein] + NAD(+) = 3''-O-
CC propanoyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
CC Xref=Rhea:RHEA:23500, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13758,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:138019, ChEBI:CHEBI:145015;
CC Evidence={ECO:0000250|UniProtKB:Q923E4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23501;
CC Evidence={ECO:0000250|UniProtKB:Q923E4};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-(2E)-butenoyl-L-lysyl-[protein] + NAD(+) = 2''-O-
CC (2E)-but-2-enoyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
CC Xref=Rhea:RHEA:69332, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13707,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:137954, ChEBI:CHEBI:183235;
CC Evidence={ECO:0000250|UniProtKB:Q96EB6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69333;
CC Evidence={ECO:0000250|UniProtKB:Q96EB6};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q8IXJ6};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q8IXJ6};
CC -!- ACTIVITY REGULATION: Inhibited by nicotinamide. Activated by
CC resveratrol (3,5,4'-trihydroxy-trans-stilbene), butein (3,4,2',4'-
CC tetrahydroxychalcone), piceatannol (3,5,3',4'-tetrahydroxy-trans-
CC stilbene), Isoliquiritigenin (4,2',4'-trihydroxychalcone), fisetin
CC (3,7,3',4'-tetrahydroxyflavone) and quercetin (3,5,7,3',4'-
CC pentahydroxyflavone). MAPK8/JNK1 and RPS19BP1/AROS act as positive
CC regulators of deacetylation activity. Negatively regulated by CCAR2.
CC {ECO:0000250|UniProtKB:Q96EB6}.
CC -!- SUBUNIT: Interacts with XBP1 isoform 2 (By similarity). Found in a
CC complex with PCAF and MYOD1. Interacts with FOXO1; the interaction
CC deacetylates FOXO1, resulting in its nuclear retention and promotion of
CC its transcriptional activity Component of the eNoSC complex, composed
CC of SIRT1, SUV39H1 and RRP8. Interacts with HES1, HEY2 and PML.
CC Interacts with RPS19BP1/AROS. Interacts with CCAR2 (via N-terminus);
CC the interaction disrupts the interaction between SIRT1 and p53/TP53.
CC Interacts with SETD7; the interaction induces the dissociation of SIRT1
CC from p53/TP53 and increases p53/TP53 activity. Interacts with MYCN,
CC NR1I2, CREBZF, TSC2, TLE1, FOS, JUN, NR0B2, PPARG, NCOR, IRS1, IRS2 and
CC NMNAT1. Interacts with HNF1A; the interaction occurs under nutrient
CC restriction. Interacts with SUZ12; the interaction mediates the
CC association with the PRC4 histone methylation complex which is specific
CC as an association with PCR2 and PCR3 complex variants is not found.
CC Interacts with HIV-1 tat. Interacts with BCL6; leads to a epigenetic
CC repression of specific target genes. Interacts with CLOCK, ARNTL/BMAL1
CC and PER2 (By similarity). Interacts with PPARA; the interaction seems
CC to be modulated by NAD(+) levels. Interacts with NR1H3 and this
CC interaction is inhibited in the presence of CCAR2. Interacts with
CC CHEK2. Interacts with p53/TP53. Exhibits a preferential interaction
CC with sumoylated CCAR2 over its unmodified form (By similarity).
CC Interacts with PACS2 (By similarity). Interacts with SIRT7 (By
CC similarity). Interacts with PUS7 (By similarity).
CC {ECO:0000250|UniProtKB:Q923E4, ECO:0000250|UniProtKB:Q96EB6}.
CC -!- SUBCELLULAR LOCATION: Nucleus, PML body {ECO:0000250|UniProtKB:Q96EB6}.
CC Cytoplasm {ECO:0000250|UniProtKB:Q96EB6}. Nucleus
CC {ECO:0000250|UniProtKB:Q96EB6}. Note=Recruited to the nuclear bodies
CC via its interaction with PML. Colocalized with APEX1 in the nucleus.
CC May be found in nucleolus, nuclear euchromatin, heterochromatin and
CC inner membrane (By similarity). Shuttles between nucleus and cytoplasm
CC (By similarity). Colocalizes in the nucleus with XBP1 isoform 2 (By
CC similarity). {ECO:0000250|UniProtKB:Q923E4,
CC ECO:0000250|UniProtKB:Q96EB6}.
CC -!- PTM: Methylated on multiple lysine residues; methylation is enhanced
CC after DNA damage and is dispensable for deacetylase activity toward
CC p53/TP53. {ECO:0000250|UniProtKB:Q96EB6}.
CC -!- PTM: Phosphorylated. Phosphorylated by STK4/MST1, resulting in
CC inhibition of SIRT1-mediated p53/TP53 deacetylation. Phosphorylation by
CC MAPK8/JNK1 at Thr-338 leads to increased nuclear localization and
CC enzymatic activity. Phosphorylation at Thr-338 by DYRK1A and DYRK3
CC activates deacetylase activity and promotes cell survival.
CC Phosphorylated by CaMK2, leading to increased p53/TP53 and NF-kappa-B
CC p65/RELA deacetylation activity (By similarity).
CC {ECO:0000250|UniProtKB:Q923E4, ECO:0000250|UniProtKB:Q96EB6}.
CC -!- PTM: S-nitrosylated by GAPDH, leading to inhibit the NAD-dependent
CC protein deacetylase activity. {ECO:0000250|UniProtKB:Q923E4}.
CC -!- PTM: Acetylated at various Lys residues. Deacetylated via an
CC autocatalytic mechanism. Autodeacetylation at Lys-46 promotes its
CC protein deacetylase activity. {ECO:0000250|UniProtKB:Q923E4}.
CC -!- MISCELLANEOUS: Red wine, which contains resveratrol, may participate in
CC activation of sirtuin proteins, and may therefore contribute to an
CC extended lifespan as has been observed in yeast.
CC {ECO:0000250|UniProtKB:Q96EB6}.
CC -!- MISCELLANEOUS: Calf histone H1 is used as substrate in the in vitro
CC deacetylation assay. As, in vivo, interaction occurs between SIRT1 with
CC H1-4, deacetylation has been validated only for H1-4.
CC {ECO:0000250|UniProtKB:Q96EB6}.
CC -!- MISCELLANEOUS: The reported ADP-ribosyltransferase activity of sirtuins
CC is likely to be an inefficient side reaction of the deacetylase
CC activity and may not be physiologically relevant.
CC {ECO:0000250|UniProtKB:Q96EB6}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class I subfamily.
CC {ECO:0000305}.
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DR EMBL; AABR07044925; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; A0A0G2JZ79; -.
DR SMR; A0A0G2JZ79; -.
DR IntAct; A0A0G2JZ79; 1.
DR MINT; A0A0G2JZ79; -.
DR STRING; 10116.ENSRNOP00000000427; -.
DR PaxDb; A0A0G2JZ79; -.
DR RGD; 1308542; Sirt1.
DR eggNOG; KOG2684; Eukaryota.
DR Reactome; R-RNO-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-RNO-427359; SIRT1 negatively regulates rRNA expression.
DR Reactome; R-RNO-9617629; Regulation of FOXO transcriptional activity by acetylation.
DR PRO; PR:A0A0G2JZ79; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0000785; C:chromatin; ISO:RGD.
DR GO; GO:0005677; C:chromatin silencing complex; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0061773; C:eNoSc complex; ISO:RGD.
DR GO; GO:0000791; C:euchromatin; ISO:RGD.
DR GO; GO:0030426; C:growth cone; IDA:RGD.
DR GO; GO:0000792; C:heterochromatin; ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0005635; C:nuclear envelope; ISO:RGD.
DR GO; GO:0005637; C:nuclear inner membrane; ISO:RGD.
DR GO; GO:0005730; C:nucleolus; ISO:RGD.
DR GO; GO:0005654; C:nucleoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0016605; C:PML body; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0033553; C:rDNA heterochromatin; ISO:RGD.
DR GO; GO:0043425; F:bHLH transcription factor binding; ISO:RGD.
DR GO; GO:0019213; F:deacetylase activity; ISO:RGD.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0042393; F:histone binding; ISO:RGD.
DR GO; GO:0004407; F:histone deacetylase activity; ISO:RGD.
DR GO; GO:0043398; F:HLH domain binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:1990254; F:keratin filament binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; ISO:RGD.
DR GO; GO:0070403; F:NAD+ binding; IBA:GO_Central.
DR GO; GO:0017136; F:NAD-dependent histone deacetylase activity; IDA:RGD.
DR GO; GO:0046969; F:NAD-dependent histone deacetylase activity (H3-K9 specific); ISO:RGD.
DR GO; GO:0160012; F:NAD-dependent histone decrotonylase activity; ISS:UniProtKB.
DR GO; GO:0034979; F:NAD-dependent protein deacetylase activity; ISO:RGD.
DR GO; GO:0016922; F:nuclear receptor binding; ISO:RGD.
DR GO; GO:0002039; F:p53 binding; ISO:RGD.
DR GO; GO:1990841; F:promoter-specific chromatin binding; ISO:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:RGD.
DR GO; GO:0019904; F:protein domain specific binding; ISO:RGD.
DR GO; GO:0043422; F:protein kinase B binding; IDA:RGD.
DR GO; GO:0033558; F:protein lysine deacetylase activity; ISO:RGD.
DR GO; GO:0106231; F:protein-propionyllysine depropionylase activity; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0003713; F:transcription coactivator activity; ISO:RGD.
DR GO; GO:0003714; F:transcription corepressor activity; ISO:RGD.
DR GO; GO:0001525; P:angiogenesis; ISO:RGD.
DR GO; GO:0042595; P:behavioral response to starvation; ISO:RGD.
DR GO; GO:0001678; P:cellular glucose homeostasis; ISO:RGD.
DR GO; GO:1904646; P:cellular response to amyloid-beta; IMP:ARUK-UCL.
DR GO; GO:0071236; P:cellular response to antibiotic; IEP:RGD.
DR GO; GO:1904644; P:cellular response to curcumin; IEP:RGD.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:RGD.
DR GO; GO:0042149; P:cellular response to glucose starvation; ISO:RGD.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEP:RGD.
DR GO; GO:0071456; P:cellular response to hypoxia; ISO:RGD.
DR GO; GO:0071479; P:cellular response to ionizing radiation; ISO:RGD.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; ISO:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEP:RGD.
DR GO; GO:1904648; P:cellular response to rotenone; IEP:RGD.
DR GO; GO:0009267; P:cellular response to starvation; ISO:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; ISO:RGD.
DR GO; GO:0071303; P:cellular response to vitamin B3; IEP:RGD.
DR GO; GO:0035356; P:cellular triglyceride homeostasis; ISO:RGD.
DR GO; GO:0042632; P:cholesterol homeostasis; ISO:RGD.
DR GO; GO:0006325; P:chromatin organization; ISO:RGD.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISO:RGD.
DR GO; GO:0007623; P:circadian rhythm; ISO:RGD.
DR GO; GO:0000731; P:DNA synthesis involved in DNA repair; ISO:RGD.
DR GO; GO:0097009; P:energy homeostasis; ISO:RGD.
DR GO; GO:0055089; P:fatty acid homeostasis; ISO:RGD.
DR GO; GO:0031507; P:heterochromatin assembly; ISO:RGD.
DR GO; GO:0016575; P:histone deacetylation; ISO:RGD.
DR GO; GO:0070932; P:histone H3 deacetylation; IMP:RGD.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; ISO:RGD.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISO:RGD.
DR GO; GO:0033210; P:leptin-mediated signaling pathway; ISO:RGD.
DR GO; GO:0030225; P:macrophage differentiation; ISO:RGD.
DR GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
DR GO; GO:0060766; P:negative regulation of androgen receptor signaling pathway; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:2000480; P:negative regulation of cAMP-dependent protein kinase activity; ISO:RGD.
DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IMP:RGD.
DR GO; GO:0045786; P:negative regulation of cell cycle; ISO:RGD.
DR GO; GO:0060548; P:negative regulation of cell death; IMP:RGD.
DR GO; GO:0030308; P:negative regulation of cell growth; ISO:RGD.
DR GO; GO:2000655; P:negative regulation of cellular response to testosterone stimulus; ISO:RGD.
DR GO; GO:2000773; P:negative regulation of cellular senescence; ISO:RGD.
DR GO; GO:0043392; P:negative regulation of DNA binding; IMP:RGD.
DR GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; ISO:RGD.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; ISO:RGD.
DR GO; GO:2000270; P:negative regulation of fibroblast apoptotic process; IMP:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0060125; P:negative regulation of growth hormone secretion; IMP:RGD.
DR GO; GO:0051097; P:negative regulation of helicase activity; ISO:RGD.
DR GO; GO:0071441; P:negative regulation of histone H3-K14 acetylation; ISO:RGD.
DR GO; GO:1900113; P:negative regulation of histone H3-K9 trimethylation; ISO:RGD.
DR GO; GO:2000619; P:negative regulation of histone H4-K16 acetylation; ISO:RGD.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISO:RGD.
DR GO; GO:1902166; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:ARUK-UCL.
DR GO; GO:1901215; P:negative regulation of neuron death; ISO:RGD.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:RGD.
DR GO; GO:1902176; P:negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:2000757; P:negative regulation of peptidyl-lysine acetylation; ISO:RGD.
DR GO; GO:0042326; P:negative regulation of phosphorylation; ISO:RGD.
DR GO; GO:0031393; P:negative regulation of prostaglandin biosynthetic process; ISO:RGD.
DR GO; GO:1901984; P:negative regulation of protein acetylation; IMP:RGD.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; ISO:RGD.
DR GO; GO:1900181; P:negative regulation of protein localization to nucleus; IMP:RGD.
DR GO; GO:1903427; P:negative regulation of reactive oxygen species biosynthetic process; IMP:RGD.
DR GO; GO:0032007; P:negative regulation of TOR signaling; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:RGD.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IMP:RGD.
DR GO; GO:0001542; P:ovulation from ovarian follicle; ISO:RGD.
DR GO; GO:0018394; P:peptidyl-lysine acetylation; ISO:RGD.
DR GO; GO:0034983; P:peptidyl-lysine deacetylation; ISO:RGD.
DR GO; GO:0002821; P:positive regulation of adaptive immune response; ISO:RGD.
DR GO; GO:1904179; P:positive regulation of adipose tissue development; ISO:RGD.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:RGD.
DR GO; GO:2000481; P:positive regulation of cAMP-dependent protein kinase activity; ISO:RGD.
DR GO; GO:0061051; P:positive regulation of cell growth involved in cardiac muscle cell development; IMP:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:2000774; P:positive regulation of cellular senescence; ISO:RGD.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; ISO:RGD.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:0045739; P:positive regulation of DNA repair; ISO:RGD.
DR GO; GO:1902237; P:positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISO:RGD.
DR GO; GO:0045722; P:positive regulation of gluconeogenesis; IMP:RGD.
DR GO; GO:0010460; P:positive regulation of heart rate; IMP:RGD.
DR GO; GO:0031065; P:positive regulation of histone deacetylation; ISO:RGD.
DR GO; GO:0051574; P:positive regulation of histone H3-K9 methylation; ISO:RGD.
DR GO; GO:0031062; P:positive regulation of histone methylation; ISO:RGD.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; ISO:RGD.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:RGD.
DR GO; GO:0016239; P:positive regulation of macroautophagy; ISO:RGD.
DR GO; GO:2000111; P:positive regulation of macrophage apoptotic process; ISO:RGD.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; ISO:RGD.
DR GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; ISO:RGD.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:RGD.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISO:RGD.
DR GO; GO:0090312; P:positive regulation of protein deacetylation; IMP:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0014858; P:positive regulation of skeletal muscle cell proliferation; IMP:RGD.
DR GO; GO:0051152; P:positive regulation of smooth muscle cell differentiation; ISO:RGD.
DR GO; GO:2000614; P:positive regulation of thyroid-stimulating hormone secretion; IMP:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISO:RGD.
DR GO; GO:0006476; P:protein deacetylation; IDA:RGD.
DR GO; GO:0106230; P:protein depropionylation; ISS:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; ISO:RGD.
DR GO; GO:0016567; P:protein ubiquitination; ISO:RGD.
DR GO; GO:0000720; P:pyrimidine dimer repair by nucleotide-excision repair; ISO:RGD.
DR GO; GO:0000183; P:rDNA heterochromatin assembly; ISO:RGD.
DR GO; GO:0042981; P:regulation of apoptotic process; ISO:RGD.
DR GO; GO:0070857; P:regulation of bile acid biosynthetic process; ISO:RGD.
DR GO; GO:0090335; P:regulation of brown fat cell differentiation; ISO:RGD.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0010824; P:regulation of centrosome duplication; ISS:UniProtKB.
DR GO; GO:0032071; P:regulation of endodeoxyribonuclease activity; ISO:RGD.
DR GO; GO:0010906; P:regulation of glucose metabolic process; ISO:RGD.
DR GO; GO:0010883; P:regulation of lipid storage; ISO:RGD.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; ISO:RGD.
DR GO; GO:0035358; P:regulation of peroxisome proliferator activated receptor signaling pathway; ISO:RGD.
DR GO; GO:0071900; P:regulation of protein serine/threonine kinase activity; ISO:RGD.
DR GO; GO:0034391; P:regulation of smooth muscle cell apoptotic process; ISO:RGD.
DR GO; GO:0046015; P:regulation of transcription by glucose; ISO:RGD.
DR GO; GO:0045471; P:response to ethanol; IDA:RGD.
DR GO; GO:1902617; P:response to fluoride; IEP:RGD.
DR GO; GO:0042542; P:response to hydrogen peroxide; ISO:RGD.
DR GO; GO:0032868; P:response to insulin; ISO:RGD.
DR GO; GO:1904373; P:response to kainic acid; IEP:RGD.
DR GO; GO:0044321; P:response to leptin; ISO:RGD.
DR GO; GO:0010046; P:response to mycotoxin; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0006979; P:response to oxidative stress; ISO:RGD.
DR GO; GO:1904638; P:response to resveratrol; IEP:RGD.
DR GO; GO:0000012; P:single strand break repair; ISO:RGD.
DR GO; GO:0007283; P:spermatogenesis; ISO:RGD.
DR GO; GO:0090400; P:stress-induced premature senescence; ISO:RGD.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:RGD.
DR GO; GO:0006642; P:triglyceride mobilization; ISO:RGD.
DR GO; GO:0070914; P:UV-damage excision repair; ISO:RGD.
DR GO; GO:0042311; P:vasodilation; IMP:RGD.
DR GO; GO:0050872; P:white fat cell differentiation; ISO:RGD.
DR Gene3D; 3.30.1600.10; -; 1.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR003000; Sirtuin.
DR InterPro; IPR026591; Sirtuin_cat_small_dom_sf.
DR InterPro; IPR026590; Ssirtuin_cat_dom.
DR Pfam; PF02146; SIR2; 1.
DR SUPFAM; SSF52467; SSF52467; 1.
DR PROSITE; PS50305; SIRTUIN; 1.
PE 3: Inferred from homology;
KW Acetylation; Apoptosis; Biological rhythms; Cytoplasm;
KW Developmental protein; Differentiation; Metal-binding; Methylation;
KW Myogenesis; NAD; Nucleus; Phosphoprotein; Reference proteome;
KW S-nitrosylation; Transcription; Transcription regulation; Transferase;
KW Zinc.
FT CHAIN 1..555
FT /note="NAD-dependent protein deacetylase sirtuin-1"
FT /id="PRO_0000436411"
FT DOMAIN 52..306
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT REGION 64..67
FT /note="Required for interaction with the sumoylated form of
FT CCAR2"
FT /evidence="ECO:0000250|UniProtKB:Q96EB6"
FT REGION 335..354
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 469..529
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 39..46
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q923E4"
FT MOTIF 241..247
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:Q923E4"
FT COMPBIAS 340..354
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 469..493
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 494..508
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 171
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 69..88
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 153..156
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 179
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 182
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 203
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 206
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 248..250
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 273..275
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 290
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT MOD_RES 46
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q923E4"
FT MOD_RES 185
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q923E4"
FT MOD_RES 203
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:Q923E4"
FT MOD_RES 206
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:Q923E4"
FT MOD_RES 238
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q923E4"
FT MOD_RES 321
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q923E4"
FT MOD_RES 338
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q96EB6"
FT MOD_RES 343
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96EB6"
FT MOD_RES 352
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q96EB6"
FT MOD_RES 417
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q923E4"
FT MOD_RES 466
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q923E4"
FT MOD_RES 468
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96EB6"
FT MOD_RES 552
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96EB6"
SQ SEQUENCE 555 AA; 62059 MW; A408C8A746AB812F CRC64;
MIGTDPRTIL KDLLPETIPP PELDDMTLWQ IVINILSEPP KRKKRKDINT IEDAVKLLQE
CKKIIVLTGA GVSVSCGIPD FRSRDGIYAR LAVDFPDLPD PQAMFDIEYF RKDPRPFFKF
AKEIYPGQFQ PSLCHKFIAL SDKEGKLLRN YTQNIDTLEQ VAGIQRIIQC HGSFATASCL
ICKYKVDCEA VRGDIFNQVV PRCPRCPADE PLAIMKPEIV FFGENLPEQF HRAMKYDKDE
VDLLIVIGSS LKVRPVALIP SSIPHEVPQI LINREPLPHL HFDVELLGDC DVIINELCHR
LGGEYAKLCC NPVKLSEITE KPPRTQKELV HLSELPPTPL HISEDSSSPE RTVPQDSSVI
ATLVDQTIKN KVDDLEVSEP KSCVEEKSQE VQTYRNVESI NVENPDFKAV GSSTGDKNER
TSVAETVRKC WPNRLAKEQI SKRLDGNQYL FVPPNRYIFH GAEVYSDSED DALSSSSCGS
NSDSGTCQSP SLEEPLEDES EIEEFYNGLE DDADRPECAG GSGADGGDQE AVNEAIAMKQ
ELTDVNCTPD KSEHY
