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Conserved domains on  [gi|1007354799|ref|NP_001307992|]
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NAD-dependent protein deacylase sirtuin-6 isoform 8 [Homo sapiens]

Protein Classification

SIR2 family protein( domain architecture ID 1222)

SIR2 family protein similar to NAD-dependent deacetylase that catalyzes NAD+-dependent protein/histone deacetylation, where the acetyl group from the lysine epsilon-amino group is transferred to the ADP-ribose moiety of NAD+, producing nicotinamide and the novel metabolite O-acetyl-ADP-ribose

PubMed:  7498786

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
SIR2 super family cl00195
SIR2 superfamily of proteins includes silent information regulator 2 (Sir2) enzymes which ...
 45-144 1.36e-33

SIR2 superfamily of proteins includes silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation, where the acetyl group from the lysine epsilon-amino group is transferred to the ADP-ribose moiety of NAD+, producing nicotinamide and the novel metabolite O-acetyl-ADP-ribose. Sir2 proteins, also known as sirtuins, are found in all eukaryotes and many archaea and prokaryotes and have been shown to regulate gene silencing, DNA repair, metabolic enzymes, and life span. The most-studied function, gene silencing, involves the inactivation of chromosome domains containing key regulatory genes by packaging them into a specialized chromatin structure that is inaccessible to DNA-binding proteins. The oligomerization state of Sir2 appears to be organism-dependent, sometimes occurring as a monomer and sometimes as a multimer. Also included in this superfamily is a group of uncharacterized Sir2-like proteins which lack certain key catalytic residues and conserved zinc binding cysteines.


The actual alignment was detected with superfamily member cd01410:

Pssm-ID: 444738  Cd Length: 206  Bit Score: 118.17  E-value: 1.36e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007354799  45 SSVVFHTGAGISTASGIPDFR----------------------------------------------------------- 65
Cdd:cd01410     1 KHLVVFTGAGISTSAGIPDFRgpngvwtllpedkgrrrfswrfrraeptlthmalveleragllkfvisqnvdglhlrsg 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007354799  66 ---DKLAELHGNMFVEECAKCKTQYVRDTVVGTMGLKATGRLCTvakarglrACRGELRDTILDWEDSLPDR-DLALADE 141
Cdd:cd01410    81 lprEKLSELHGNMFIEVCKSCGPEYVRDDVVETRGDKETGRRCH--------ACGGILKDTIVDFGERLPPEnWMGAAAA 152


                  ...
gi 1007354799 142 ASR 144
Cdd:cd01410   153 ACR 155
 
Name Accession Description Interval E-value
SIRT7 cd01410
SIRT7: Eukaryotic and prokaryotic group (class4) which includes human sirtuin SIRT6, SIRT7, ...
 45-144 1.36e-33

SIRT7: Eukaryotic and prokaryotic group (class4) which includes human sirtuin SIRT6, SIRT7, and several bacterial homologs; and are members of the SIR2 family of proteins, silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation. Sir2 proteins have been shown to regulate gene silencing, DNA repair, metabolic enzymes, and life span.


Pssm-ID: 238701  Cd Length: 206  Bit Score: 118.17  E-value: 1.36e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007354799  45 SSVVFHTGAGISTASGIPDFR----------------------------------------------------------- 65
Cdd:cd01410     1 KHLVVFTGAGISTSAGIPDFRgpngvwtllpedkgrrrfswrfrraeptlthmalveleragllkfvisqnvdglhlrsg 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007354799  66 ---DKLAELHGNMFVEECAKCKTQYVRDTVVGTMGLKATGRLCTvakarglrACRGELRDTILDWEDSLPDR-DLALADE 141
Cdd:cd01410    81 lprEKLSELHGNMFIEVCKSCGPEYVRDDVVETRGDKETGRRCH--------ACGGILKDTIVDFGERLPPEnWMGAAAA 152


                  ...
gi 1007354799 142 ASR 144
Cdd:cd01410   153 ACR 155
PRK00481 PRK00481
NAD-dependent deacetylase; Provisional
 36-67 7.58e-10

NAD-dependent deacetylase; Provisional


Pssm-ID: 234777  Cd Length: 242  Bit Score: 56.34  E-value: 7.58e-10
                          10        20        30
                  ....*....|....*....|....*....|..
gi 1007354799  36 ELARLVWQSSSVVFHTGAGISTASGIPDFRDK 67
Cdd:PRK00481    5 ELAEILDKAKRIVVLTGAGISAESGIPDFRSA 36
SIR2 COG0846
NAD-dependent protein deacetylase, SIR2 family [Posttranslational modification, protein ...
 33-67 9.62e-10

NAD-dependent protein deacetylase, SIR2 family [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 440607  Cd Length: 243  Bit Score: 55.94  E-value: 9.62e-10
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1007354799  33 KVWELARLVWQSSSVVFHTGAGISTASGIPDFRDK 67
Cdd:COG0846     3 KIERLAELLREAKRIVVLTGAGISAESGIPDFRGP 37
SIR2 pfam02146
Sir2 family; This region is characteriztic of Silent information regulator 2 (Sir2) proteins, ...
 52-67 7.68e-05

Sir2 family; This region is characteriztic of Silent information regulator 2 (Sir2) proteins, or sirtuins. These are protein deacetylases that depend on nicotine adenine dinucleotide (NAD). They are found in many subcellular locations, including the nucleus, cytoplasm and mitochondria. Eukaryotic forms play in important role in the regulation of transcriptional repression. Moreover, they are involved in microtubule organization and DNA damage repair processes.i


Pssm-ID: 426621  Cd Length: 179  Bit Score: 41.47  E-value: 7.68e-05
                          10
                  ....*....|....*.
gi 1007354799  52 GAGISTASGIPDFRDK 67
Cdd:pfam02146   1 GAGISTESGIPDFRSD 16
 
Name Accession Description Interval E-value
SIRT7 cd01410
SIRT7: Eukaryotic and prokaryotic group (class4) which includes human sirtuin SIRT6, SIRT7, ...
 45-144 1.36e-33

SIRT7: Eukaryotic and prokaryotic group (class4) which includes human sirtuin SIRT6, SIRT7, and several bacterial homologs; and are members of the SIR2 family of proteins, silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation. Sir2 proteins have been shown to regulate gene silencing, DNA repair, metabolic enzymes, and life span.


Pssm-ID: 238701  Cd Length: 206  Bit Score: 118.17  E-value: 1.36e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007354799  45 SSVVFHTGAGISTASGIPDFR----------------------------------------------------------- 65
Cdd:cd01410     1 KHLVVFTGAGISTSAGIPDFRgpngvwtllpedkgrrrfswrfrraeptlthmalveleragllkfvisqnvdglhlrsg 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007354799  66 ---DKLAELHGNMFVEECAKCKTQYVRDTVVGTMGLKATGRLCTvakarglrACRGELRDTILDWEDSLPDR-DLALADE 141
Cdd:cd01410    81 lprEKLSELHGNMFIEVCKSCGPEYVRDDVVETRGDKETGRRCH--------ACGGILKDTIVDFGERLPPEnWMGAAAA 152


                  ...
gi 1007354799 142 ASR 144
Cdd:cd01410   153 ACR 155
SIR2-fam cd01407
SIR2 family of proteins includes silent information regulator 2 (Sir2) enzymes which catalyze ...
 47-145 6.30e-20

SIR2 family of proteins includes silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation, where the acetyl group from the lysine epsilon-amino group is transferred to the ADP-ribose moiety of NAD+, producing nicotinamide and the novel metabolite O-acetyl-ADP-ribose. Sir2 proteins, also known as sirtuins, are found in all eukaryotes and many archaea and prokaryotes and have been shown to regulate gene silencing, DNA repair, metabolic enzymes, and life span. The most-studied function, gene silencing, involves the inactivation of chromosome domains containing key regulatory genes by packaging them into a specialized chromatin structure that is inaccessible to DNA-binding proteins. The oligomerization state of Sir2 appears to be organism-dependent, sometimes occurring as a monomer and sometimes as a multimer.


Pssm-ID: 238698  Cd Length: 218  Bit Score: 83.00  E-value: 6.30e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007354799  47 VVFHTGAGISTASGIPDFRD------------------------------------------------------------ 66
Cdd:cd01407     3 IVVLTGAGISTESGIPDFRSpgglwarldpeelafspeafrrdpelfwgfyrerryplnaqpnpahralaelerkgklkr 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007354799  67 ----------------KLAELHGNMFVEECAKCKTQYVRDTVVgTMGLKATGRLCTvakarglrACRGELRDTILDWEDS 130
Cdd:cd01407    83 vitqnvdglhqragspKVIELHGSLFRVRCTKCGKEYPRDELQ-ADIDREEVPRCP--------KCGGLLRPDVVFFGES 153

                         170
                  ....*....|....*
gi 1007354799 131 LPDRDLALADEASRS 145
Cdd:cd01407   154 LPEELDEAAEALAKA 168
SIR2 cd00296
SIR2 superfamily of proteins includes silent information regulator 2 (Sir2) enzymes which ...
 47-142 1.58e-14

SIR2 superfamily of proteins includes silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation, where the acetyl group from the lysine epsilon-amino group is transferred to the ADP-ribose moiety of NAD+, producing nicotinamide and the novel metabolite O-acetyl-ADP-ribose. Sir2 proteins, also known as sirtuins, are found in all eukaryotes and many archaea and prokaryotes and have been shown to regulate gene silencing, DNA repair, metabolic enzymes, and life span. The most-studied function, gene silencing, involves the inactivation of chromosome domains containing key regulatory genes by packaging them into a specialized chromatin structure that is inaccessible to DNA-binding proteins. The oligomerization state of Sir2 appears to be organism-dependent, sometimes occurring as a monomer and sometimes as a multimer. Also included in this superfamily is a group of uncharacterized Sir2-like proteins which lack certain key catalytic residues and conserved zinc binding cysteines.


Pssm-ID: 238184 [Multi-domain]  Cd Length: 222  Bit Score: 68.91  E-value: 1.58e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007354799  47 VVFHTGAGISTASGIPDFRD------------------------------------------------------------ 66
Cdd:cd00296     3 VVVFTGAGISTESGIPDFRGlgtglwtrldpeelafspeafrrdpelfwlfykerrytpldakpnpahralaelerkgkl 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1007354799  67 --------------------KLAELHGNMFVEECAKCKTQYVRDTVVGTMglkatgrlctvaKARGLRACRGELRDTILD 126
Cdd:cd00296    83 kriitqnvdglheragsrrnRVIELHGSLDRVRCTSCGKEYPRDEVLERE------------KPPRCPKCGGLLRPDVVD 150

                         170
                  ....*....|....*.
gi 1007354799 127 WEDSLPDRDLALADEA 142
Cdd:cd00296   151 FGEALPKEWFDRALEA 166
PRK00481 PRK00481
NAD-dependent deacetylase; Provisional
 36-67 7.58e-10

NAD-dependent deacetylase; Provisional


Pssm-ID: 234777  Cd Length: 242  Bit Score: 56.34  E-value: 7.58e-10
                          10        20        30
                  ....*....|....*....|....*....|..
gi 1007354799  36 ELARLVWQSSSVVFHTGAGISTASGIPDFRDK 67
Cdd:PRK00481    5 ELAEILDKAKRIVVLTGAGISAESGIPDFRSA 36
SIR2 COG0846
NAD-dependent protein deacetylase, SIR2 family [Posttranslational modification, protein ...
 33-67 9.62e-10

NAD-dependent protein deacetylase, SIR2 family [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 440607  Cd Length: 243  Bit Score: 55.94  E-value: 9.62e-10
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1007354799  33 KVWELARLVWQSSSVVFHTGAGISTASGIPDFRDK 67
Cdd:COG0846     3 KIERLAELLREAKRIVVLTGAGISAESGIPDFRGP 37
SIR2H cd01411
SIR2H: Uncharacterized prokaryotic Sir2 homologs from several gram positive bacterial species ...
 43-67 1.36e-06

SIR2H: Uncharacterized prokaryotic Sir2 homologs from several gram positive bacterial species and Fusobacteria; and are members of the SIR2 family of proteins, silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation. Sir2 proteins have been shown to regulate gene silencing, DNA repair, metabolic enzymes, and life span.


Pssm-ID: 238702  Cd Length: 225  Bit Score: 46.98  E-value: 1.36e-06
                          10        20
                  ....*....|....*....|....*
gi 1007354799  43 QSSSVVFHTGAGISTASGIPDFRDK 67
Cdd:cd01411     7 NAKRIVFFTGAGVSTASGIPDYRSK 31
SIRT4 cd01409
SIRT4: Eukaryotic and prokaryotic group (class2) which includes human sirtuin SIRT4 and ...
 37-67 2.09e-06

SIRT4: Eukaryotic and prokaryotic group (class2) which includes human sirtuin SIRT4 and several bacterial homologs; and are members of the SIR2 family of proteins, silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation. Sir2 proteins have been shown to regulate gene silencing, DNA repair, metabolic enzymes, and life span.


Pssm-ID: 238700  Cd Length: 260  Bit Score: 46.52  E-value: 2.09e-06
                          10        20        30
                  ....*....|....*....|....*....|.
gi 1007354799  37 LARLVWQSSSVVFHTGAGISTASGIPDFRDK 67
Cdd:cd01409     1 LQDFVARSRRLLVLTGAGISTESGIPDYRSE 31
SIR2_Af2 cd01413
SIR2_Af2: Archaeal and prokaryotic group which includes Archaeoglobus fulgidus Sir2-Af2, ...
 47-65 1.27e-05

SIR2_Af2: Archaeal and prokaryotic group which includes Archaeoglobus fulgidus Sir2-Af2, Sulfolobus solfataricus ssSir2, and several bacterial homologs; and are members of the SIR2 family of proteins, silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation. Sir2 proteins have been shown to regulate gene silencing, DNA repair, metabolic enzymes, and life span. The Sir2 homolog from the archaea Sulfolobus solftaricus deacetylates the non-specific DNA protein Alba to mediate transcription repression.


Pssm-ID: 238704  Cd Length: 222  Bit Score: 43.90  E-value: 1.27e-05
                          10
                  ....*....|....*....
gi 1007354799  47 VVFhTGAGISTASGIPDFR 65
Cdd:cd01413     8 VVL-TGAGISTESGIPDFR 25
SIRT1 cd01408
SIRT1: Eukaryotic group (class1) which includes human sirtuins SIRT1-3 and yeast Hst1-4; and ...
 46-65 2.42e-05

SIRT1: Eukaryotic group (class1) which includes human sirtuins SIRT1-3 and yeast Hst1-4; and are members of the SIR2 family of proteins, silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation. Sir2 proteins have been shown to regulate gene silencing, DNA repair, and life span. The most-studied function, gene silencing, involves the inactivation of chromosome domains containing key regulatory genes by packaging them into a specialized chromatin structure that is inaccessible to DNA-binding proteins. The nuclear SIRT1 has been shown to target the p53 tumor suppressor protein for deacetylation to suppress DNA damage, and the cytoplasmic SIRT2 homolog has been shown to target alpha-tubulin for deacetylation for the maintenance of cell integrity.


Pssm-ID: 238699  Cd Length: 235  Bit Score: 43.39  E-value: 2.42e-05
                          10        20
                  ....*....|....*....|
gi 1007354799  46 SVVFHTGAGISTASGIPDFR 65
Cdd:cd01408     2 KIVVLVGAGISTSAGIPDFR 21
SIR2 pfam02146
Sir2 family; This region is characteriztic of Silent information regulator 2 (Sir2) proteins, ...
 52-67 7.68e-05

Sir2 family; This region is characteriztic of Silent information regulator 2 (Sir2) proteins, or sirtuins. These are protein deacetylases that depend on nicotine adenine dinucleotide (NAD). They are found in many subcellular locations, including the nucleus, cytoplasm and mitochondria. Eukaryotic forms play in important role in the regulation of transcriptional repression. Moreover, they are involved in microtubule organization and DNA damage repair processes.i


Pssm-ID: 426621  Cd Length: 179  Bit Score: 41.47  E-value: 7.68e-05
                          10
                  ....*....|....*.
gi 1007354799  52 GAGISTASGIPDFRDK 67
Cdd:pfam02146   1 GAGISTESGIPDFRSD 16
PRK14138 PRK14138
NAD-dependent deacetylase; Provisional
 36-65 1.02e-04

NAD-dependent deacetylase; Provisional


Pssm-ID: 172627 [Multi-domain]  Cd Length: 244  Bit Score: 41.35  E-value: 1.02e-04
                          10        20        30
                  ....*....|....*....|....*....|
gi 1007354799  36 ELARLVWQSSSVVFHTGAGISTASGIPDFR 65
Cdd:PRK14138    3 EFLELLNESRLTVTLTGAGISTPSGIPDFR 32
PRK05333 PRK05333
NAD-dependent protein deacetylase;
51-66 3.87e-04

NAD-dependent protein deacetylase;


Pssm-ID: 235415  Cd Length: 285  Bit Score: 40.05  E-value: 3.87e-04
                          10
                  ....*....|....*.
gi 1007354799  51 TGAGISTASGIPDFRD 66
Cdd:PRK05333   26 TGAGISTDSGIPDYRD 41
PTZ00408 PTZ00408
NAD-dependent deacetylase; Provisional
 47-81 1.46e-03

NAD-dependent deacetylase; Provisional


Pssm-ID: 240405  Cd Length: 242  Bit Score: 38.27  E-value: 1.46e-03
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1007354799  47 VVFHTGAGISTASGIPDFRDKlAELHGNMFVEECA 81
Cdd:PTZ00408    7 ITILTGAGISAESGISTFRDG-NGLWENHRVEDVA 40
SIRT5_Af1_CobB cd01412
SIRT5_Af1_CobB: Eukaryotic, archaeal and prokaryotic group (class3) which includes human ...
 47-67 2.31e-03

SIRT5_Af1_CobB: Eukaryotic, archaeal and prokaryotic group (class3) which includes human sirtuin SIRT5, Archaeoglobus fulgidus Sir2-Af1, and E. coli CobB; and are members of the SIR2 family of proteins, silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation. Sir2 proteins have been shown to regulate gene silencing, DNA repair, metabolic enzymes, and life span. CobB is a bacterial sirtuin that deacetylates acetyl-CoA synthetase at an active site lysine to stimulate its enzymatic activity.


Pssm-ID: 238703  Cd Length: 224  Bit Score: 37.57  E-value: 2.31e-03
                          10        20
                  ....*....|....*....|.
gi 1007354799  47 VVFhTGAGISTASGIPDFRDK 67
Cdd:cd01412     4 VVL-TGAGISAESGIPTFRDA 23
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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