SIR2_DANRE
ID SIR2_DANRE Reviewed; 379 AA.
AC Q7ZVK3;
DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=NAD-dependent protein deacetylase sirtuin-2;
DE EC=2.3.1.286 {ECO:0000305|PubMed:24940000};
DE AltName: Full=NAD-dependent protein defatty-acylase sirtuin-2 {ECO:0000305};
DE EC=2.3.1.- {ECO:0000250|UniProtKB:Q8IXJ6};
DE AltName: Full=Regulatory protein SIR2 homolog 2;
DE AltName: Full=SIR2-like protein 2;
GN Name=sirt2; ORFNames=zgc:77003;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=AB;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION IN REGULATION OF VEGFA EXPRESSION AND ANGIOGENESIS, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=24940000; DOI=10.7554/elife.02349;
RA Shi Y., Xu X., Zhang Q., Fu G., Mo Z., Wang G.S., Kishi S., Yang X.L.;
RT "tRNA synthetase counteracts c-Myc to develop functional vasculature.";
RL Elife 3:E02349-E02349(2014).
CC -!- FUNCTION: NAD-dependent protein deacetylase, which deacetylates
CC internal lysines on histone and alpha-tubulin as well as many other
CC proteins such as key transcription factors (By similarity).
CC Participates in the modulation of multiple and diverse biological
CC processes such as cell cycle control, genomic integrity, microtubule
CC dynamics, cell differentiation, metabolic networks, and autophagy.
CC Plays a major role in the control of cell cycle progression and genomic
CC stability. Deacetylates histone H4 at 'Lys-16' (H4K16ac) at the VEGFA
CC promoter (PubMed:24940000). Thereby contributes to regulate expression
CC of vegfa, a key regulator of angiogenesis (PubMed:24940000). In
CC addition to protein deacetylase activity, also has activity toward
CC long-chain fatty acyl groups and mediates protein-lysine
CC demyristoylation and depalmitoylation of target proteins (By
CC similarity). {ECO:0000250|UniProtKB:Q8IXJ6,
CC ECO:0000269|PubMed:24940000}.
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:0000305|PubMed:24940000};
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:Q8IXJ6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70568;
CC Evidence={ECO:0000250|UniProtKB:Q8IXJ6};
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:Q8IXJ6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70564;
CC Evidence={ECO:0000250|UniProtKB:Q8IXJ6};
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 -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8IXJ6}. Nucleus
CC {ECO:0000250|UniProtKB:Q8IXJ6}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown causes aberrant angiogenesis
CC with excessive intersegmental vessel branching, due to excessive
CC expression of vegfa. {ECO:0000269|PubMed:24940000}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class I subfamily.
CC {ECO:0000305}.
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DR EMBL; BC045510; AAH45510.1; -; mRNA.
DR RefSeq; NP_955890.1; NM_199596.1.
DR AlphaFoldDB; Q7ZVK3; -.
DR SMR; Q7ZVK3; -.
DR STRING; 7955.ENSDARP00000003412; -.
DR PaxDb; Q7ZVK3; -.
DR GeneID; 322309; -.
DR KEGG; dre:322309; -.
DR CTD; 22933; -.
DR ZFIN; ZDB-GENE-030131-1028; sirt2.
DR eggNOG; KOG2682; Eukaryota.
DR InParanoid; Q7ZVK3; -.
DR OrthoDB; 973532at2759; -.
DR PhylomeDB; Q7ZVK3; -.
DR Reactome; R-DRE-2995383; Initiation of Nuclear Envelope (NE) Reformation.
DR PRO; PR:Q7ZVK3; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005814; C:centriole; ISS:UniProtKB.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005694; C:chromosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0097386; C:glial cell projection; ISS:UniProtKB.
DR GO; GO:0000792; C:heterochromatin; ISS:UniProtKB.
DR GO; GO:0044224; C:juxtaparanode region of axon; ISS:UniProtKB.
DR GO; GO:0072687; C:meiotic spindle; ISS:UniProtKB.
DR GO; GO:0030496; C:midbody; ISS:UniProtKB.
DR GO; GO:0072686; C:mitotic spindle; ISS:UniProtKB.
DR GO; GO:0043209; C:myelin sheath; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0033010; C:paranodal junction; ISS:UniProtKB.
DR GO; GO:0033270; C:paranode region of axon; ISS:UniProtKB.
DR GO; GO:0043204; C:perikaryon; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0043220; C:Schmidt-Lanterman incisure; ISS:UniProtKB.
DR GO; GO:0005819; C:spindle; ISS:UniProtKB.
DR GO; GO:0004407; F:histone deacetylase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070403; F:NAD+ binding; IBA:GO_Central.
DR GO; GO:0017136; F:NAD-dependent histone deacetylase activity; IBA:GO_Central.
DR GO; GO:0046970; F:NAD-dependent histone deacetylase activity (H4-K16 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:0042903; F:tubulin deacetylase activity; ISS:UniProtKB.
DR GO; GO:0061433; P:cellular response to caloric restriction; ISS:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; ISS:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0060271; P:cilium assembly; IMP:ZFIN.
DR GO; GO:0030097; P:hemopoiesis; IMP:ZFIN.
DR GO; GO:0070933; P:histone H4 deacetylation; ISS:UniProtKB.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:ZFIN.
DR GO; GO:0010507; P:negative regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0070446; P:negative regulation of oligodendrocyte progenitor proliferation; ISS:UniProtKB.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; ISS:UniProtKB.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0061428; P:negative regulation of transcription from RNA polymerase II promoter in response to hypoxia; ISS:UniProtKB.
DR GO; GO:0043388; P:positive regulation of DNA binding; ISS:UniProtKB.
DR GO; GO:1900119; P:positive regulation of execution phase of apoptosis; ISS:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:2000777; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process involved in cellular response to hypoxia; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0006476; P:protein deacetylation; ISS:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0090042; P:tubulin deacetylation; ISS:UniProtKB.
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; IPR017328; Sirtuin_class_I.
DR InterPro; IPR026590; Ssirtuin_cat_dom.
DR Pfam; PF02146; SIR2; 1.
DR PIRSF; PIRSF037938; SIR2_euk; 1.
DR SUPFAM; SSF52467; SSF52467; 1.
DR PROSITE; PS50305; SIRTUIN; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Metal-binding; NAD; Nucleus; Reference proteome; Transferase;
KW Zinc.
FT CHAIN 1..379
FT /note="NAD-dependent protein deacetylase sirtuin-2"
FT /id="PRO_0000110262"
FT DOMAIN 63..337
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 349..379
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..15
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 16..32
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 185
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 83..87
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 93..95
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 165..168
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 193
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 198
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 219
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 222
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 260..261
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 284..286
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 321
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
SQ SEQUENCE 379 AA; 42315 MW; 1FD8A103DA2EC325 CRC64;
MSEEVSKRVE EEADTPGLEG QSDDSSDEGD ASGDTEMDFL RSLFSRTLGL SPGDKVLDEL
TLDSVARYIL SGKCKNIICM VGAGISTSAG IPDFRSPGTG LYANLQKYNL PYPEAIFQID
YFKKHPEPFF ALARELYPGQ FKPTVYHYFI KMLKDKGLLR RCYSQNIDTL ERVAGLEGED
LIEAHGTFHT SHCVSFLCRK EYSMDWMKNQ IFSEEIPKCD SCGSLVKPDI VFFGESLPSR
FFTSMKADFP QCDLLIIMGT SLQVQPFASL VSRVSNRCPR LLINMEKTGQ SEFGMGLFSF
GGGMDFDSDK AYRDVAHLST CDDGCMTLAE LLGWKKELEE MVKREHALID SKDAKKTDKE
ASQSSKSAVA EAEKTDKTE
