Gene

KWMTBOMO04972

Pre Gene Modal

BGIBMGA007984

Annotation

PREDICTED:_NAD-dependent_protein_deacylase-like_[Papilio_xuthus]

Location

Bomo_Chr9(-):3809984-3811659      View in EpiBrowser

Full name

NAD-dependent protein deacylase       + More
NAD-dependent protein deacylase sirtuin-5, mitochondrial      

Alternative Name

Regulatory protein SIR2 homolog 5
SIR2-like protein 5

Location in the cell

Mitochondrial   Reliability : 2.148

CDS

ATGTGCCTTAGTTTATTGAAAACACTAAATCAGAGAGTCATTCCTTGTTATATTAATAAAGTCATGAGTTCAAGACAATCTAGTGATTTCTCAAAGTTCAGAGTTGCTTTAAAATCGGCAAAAGAAATAGTTATCTTATCTGGAGCCGGCATTAGTGCAGAATCTGGAATACCTACTTTTCGTGGTGCTGGAGGGCTTTGGAGGAAATATCAAGCTTCGGCCTTAGCAACACCAGGAGCTTTTAGAGAAAGTCCAAGCTTAGTATGGGAATTTTACCACTACAGAAGAGAGGTGGCAGCAAAGGCGAAGCCTAATGCGGGACATTTTGCTATTGCTAAATTCGAAGATAACCATGGATCCCAAAAAAAAATTACAGTAATTACTCAGAATGTGGATGGTTTACATGCAAGAGCAGGAACGAAAAGATTGATAGAGCTTCATGGAAATTTATACAAAACTCGATGTACAAAATGTAAGGAAGTATTGGTGAATAATGACAGCCCTATATGTGAGGCACTTGCAAATAGAGGAGCCCCAGATTCTAATATGGTGGGTTCTGATATTCCTGTGAAATTATTACCACACTGTAAAAAGGCTCATTGTGGAGCCTTGCTAAGACCCCACATTGTGTGGTTCGGTGAAAGTTTAGAACATGATATTTTAGAAGCAGCTGAACATGCAATGTCCACCTGTGATGTATGCCTAGTTGTTGGTACATCATCAGTGGTATATCCTGCGGCAATGTTTGCTCCGCAAGCAGCTTTGAGGGGTGCAATTGTAGCAGAATTTAATATAGAACCAACACCGGCCACACCTGATTTCCATTTTTACTTCGAAGGACCTTGTGGTACAACACTGCCACAAGCACTGGCTGATTAG

Protein

MCLSLLKTLNQRVIPCYINKVMSSRQSSDFSKFRVALKSAKEIVILSGAGISAESGIPTFRGAGGLWRKYQASALATPGAFRESPSLVWEFYHYRREVAAKAKPNAGHFAIAKFEDNHGSQKKITVITQNVDGLHARAGTKRLIELHGNLYKTRCTKCKEVLVNNDSPICEALANRGAPDSNMVGSDIPVKLLPHCKKAHCGALLRPHIVWFGESLEHDILEAAEHAMSTCDVCLVVGTSSVVYPAAMFAPQAALRGAIVAEFNIEPTPATPDFHFYFEGPCGTTLPQALAD

Description

NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo.
NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins. Activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting: acts by mediating desuccinylation and deglutarylation of CPS1, thereby increasing CPS1 activity in response to elevated NAD levels during fasting. Activates SOD1 by mediating its desuccinylation, leading to reduced reactive oxygen species. Modulates ketogenesis through the desuccinylation and activation of HMGCS2. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) and a number of other proteins in vitro such as Uox.
NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins. Activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting: acts by mediating desuccinylation and deglutarylation of CPS1, thereby increasing CPS1 activity in response to elevated NAD levels during fasting. Activates SOD1 by mediating its desuccinylation, leading to reduced reactive oxygen species. Activates SHMT2 by mediating its desuccinylation. Modulates ketogenesis through the desuccinylation and activation of HMGCS2. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) and a number of other proteins in vitro such as UOX.
NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins (PubMed:21908771, PubMed:22076378, PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting: acts by mediating desuccinylation and deglutarylation of CPS1, thereby increasing CPS1 activity in response to elevated NAD levels during fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating its desuccinylation, leading to reduced reactive oxygen species (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation (PubMed:29180469). Modulates ketogenesis through the desuccinylation and activation of HMGCS2 (By similarity). Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) and a number of other proteins in vitro such as UOX.

Catalytic Activity

H2O + N(6)-glutaryl-L-lysyl-[protein] + NAD(+) = 2''-O-glutaryl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide
H2O + N(6)-malonyl-L-lysyl-[protein] + NAD(+) = 2''-O-malonyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide
H2O + N(6)-succinyl-L-lysyl-[protein] + NAD(+) = 2''-O-succinyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide

Cofactor

Zn(2+)

Biophysicochemical Properties

6.1 uM for a synthetic histone H3K9 malonyllysine peptide
5.8 uM for a synthetic histone H3K9 succinyllysine peptide
8.7 uM for a synthetic GLUD1 peptide malonylated at 'Lys-503'
14 uM for a synthetic GLUD1 peptide succinylated at 'Lys-503'
150 uM for a synthetic ACSS1 peptide malonylated at 'Lys-628'
450 uM for a synthetic ACSS1 peptide succinylated at 'Lys-628'

Subunit

Monomer. Homodimer. Interacts with CPS1.
Monomer. Homodimer. Interacts with CPS1. Interacts with PCCA (By similarity).
Interacts with CPS1 (By similarity). Interacts with PCCA (PubMed:23438705). Monomer (PubMed:17355872). Homodimer (PubMed:17355872). Forms homodimers upon suramin binding (PubMed:17355872).

Miscellaneous

The mechanism of demalonylation and desuccinylation involves the presence of a 1',2'-cyclic intermediate, suggesting that sirtuins use the ADP-ribose-peptidylamidate mechanism to remove acyl groups from substrate lysine residues.
This protein may be expected to contain an N-terminal transit peptide but none has been predicted.

Similarity

Belongs to the sirtuin family. Class III subfamily.

Keywords

Complete proteome   Cytoplasm   Hydrolase   Metal-binding   Mitochondrion   NAD   Nucleus   Reference proteome   Transit peptide   Zinc   Alternative splicing   3D-structure   Polymorphism  

Feature

chain  NAD-dependent protein deacylase sirtuin-5, mitochondrial
splice variant  In isoform 2.
sequence variant  In dbSNP:rs9464003.

Uniprot

H9JEN7   A0A2A4IU40   A0A2A4J757   A0A194PE30   A0A2W1BLQ1   A0A194QKF9   + More
A0A212F1S9   A0A2H1W3C4   A0A3S2TCY5   A0A0L7LGG5   A0A2W1B9B8   A0A2A4J4P9   A0A2P8YXP3   T1JM32   A0A0L8FJ96   A0A1S3I9P2   A0A1S3I3K6   A0A384C9F6   A0A3Q7W2D8   G1L0W8   A0A0A9VU74   R7TYG4   A0A347ZJG9   A0A347ZJH0   A0A2K5Z885   U6CSQ7   M3XNN7   G9KNZ1   L8I353   A0A1S3ARI7   A0A2U3ZJM8   A0A2Y9HU99   A0A2Y9KHV5   A0A2A4J8L1   A0A3Q7S747   A0A232EQW5   E2RDZ6   A0A0D9R5A6   A0A2K6EL10   G1SSN2   A0A3B3DLW2   A0A2K5D7U6   A0A1S3WWN1   L5KVZ6   G7MQR7   A0A1B6F0Z9   A0A2H1V7W5   A0A1U7TB08   I3MLJ1   T1FM78   V3ZQA2   A0A2K6KGU3   A0A2J8WN49   Q5R6G3   A0A2K5U3X0   Q3ZBQ0   A0A2A4IVN0   G7P4G1   F7EZ75   U3FQC2   A0A2K6PGP2   A0A341CYS1   A0A2K6SXL1   A0A024R012   Q9NXA8   A0A2Y9P5P3   A0A1B6MII4   A0A2K5IXA9   H2MC35   H2XWF2   A0A340WH59   A0A3Q7QM78   A0A2R9AH39   K7AYD4   A0A1W5BBZ1   A0A2I3G514   A0A3P9K193   A0A1U7QFA6   B0FWP7   G3H0G1   A0A093PXQ6   A0A2R5LA13   D7PD35   H0Z6V4   A0A0N7ZCB6   Q6DHI5   K7CAU0   A0A093FW32   A0A1B6J2U7   F6S899   A7XXV9   R9PXP3   E1BRE2   A0A2C9JNR9   A0A224YUG4   A0A131YYA3   A0A2K5SEN1   W5PVL7   E9GD30  

EC Number

3.5.1.-

Pubmed

19121390    26354079    28756777    22118469    26227816    29403074    + More
24813606    20010809    25401762    23254933    23236062    22751099    28648823    16341006    21993624    29451363    23258410    22002653    25319552    17431167    25243066    25362486    11181995    10381378    14702039    17974005    14574404    15489334    16079181    18680753    21269460    21143562    21908771    23028781    24140062    23438705    23806337    24703693    24275569    29180469    17355872    22076378    22767592    22849721    23185430    17554307    12481130    15114417    22722832    16136131    26319212    19389481    30723633    21804562    20725513    20360741    23594743    19892987    15592404    15562597    28797301    26830274    20809919    21292972   

EMBL

BABH01023649    NWSH01006780    PCG63241.1    NWSH01002634    PCG67791.1    KQ459606    + More
KPI91283.1    KZ149974    PZC75979.1    KQ461198    KPJ06017.1    AGBW02010825    OWR47681.1    ODYU01006040    SOQ47533.1    RSAL01000337    RVE42433.1    JTDY01001216    KOB74505.1    KZ150212    PZC72172.1    NWSH01003389    PCG66393.1    PYGN01000298    PSN49016.1    JH431841    KQ430417    KOF64184.1    ACTA01040630    ACTA01048630    GBHO01044838    GBHO01044836    GBHO01044834    GBHO01040378    GBRD01007573    JAF98765.1    JAF98767.1    JAF98769.1    JAG03226.1    JAG58248.1    AMQN01010365    KB307653    ELT98667.1    FX985737    BBA84475.1    FX985738    BBA84476.1    HAAF01001889    CCP73715.1    AEYP01034983    AEYP01034984    JP018022    AES06620.1    JH882311    ELR49979.1    PCG63243.1    PCG67790.1    NNAY01002706    OXU20738.1    AQIB01159368    AAGW02052169    KB030554    ELK14968.1    JU333683    JV046590    CM001256    AFE77438.1    AFI36661.1    EHH17963.1    GECZ01029545    GECZ01025879    GECZ01013838    JAS40224.1    JAS43890.1    JAS55931.1    ODYU01000891    SOQ36334.1    AGTP01056265    AMQM01000782    KB096742    ESO02068.1    KB203049    ESO86512.1    NDHI03003384    PNJ71195.1    CR858318    CR860527    AQIA01052732    GQ166651    BC103176    PCG63242.1    CM001279    EHH52724.1    GAMT01006912    GAMS01004998    GAMR01003110    GAMQ01001890    GAMP01008095    JAB04949.1    JAB18138.1    JAB30822.1    JAB39961.1    JAB44660.1    CH471087    EAW55334.1    AF083110    AK000355    AK294162    AK302467    AM393414    AL441883    BC000126    GEBQ01004275    JAT35702.1    EAAA01001018    AJFE02080843    AJFE02080844    AACZ04065916    GABC01004479    GABD01002959    GABE01004668    NBAG03000244    JAA06859.1    JAA30141.1    JAA40071.1    PNI62788.1    ADFV01015635    ADFV01015636    ADFV01015637    ADFV01015638    ADFV01015639    ADFV01015640    ADFV01015641    EU357901    DQIR01075620    DQIR01075621    DQIR01082689    DQIR01099517    DQIR01103593    DQIR01135437    DQIR01135438    ABY65335.1    HDA31096.1    JH000091    EGV92882.1    KL671098    KFW81166.1    GGLE01002192    MBY06318.1    GU255947    ADI24340.1    ABQF01024072    GDRN01069784    JAI63992.1    BX511260    BC075987    GABF01000825    JAA21320.1    KL214871    KFV62135.1    GECU01014219    JAS93487.1    EU100953    ABU89799.1    AADN04000074    KX400578    APT36903.1    AADN02027504    GFPF01006767    MAA17913.1    GEDV01005025    JAP83532.1    AMGL01059584    AMGL01059585    GL732539   

Proteomes

UP000005204    UP000218220    UP000053268    UP000053240    UP000007151    UP000283053    + More
UP000037510    UP000245037    UP000053454    UP000085678    UP000261680    UP000291021    UP000286642    UP000008912    UP000014760    UP000233140    UP000000715    UP000079721    UP000245340    UP000248481    UP000248482    UP000286640    UP000215335    UP000002254    UP000029965    UP000233160    UP000001811    UP000261560    UP000233020    UP000010552    UP000189704    UP000005215    UP000015101    UP000030746    UP000233180    UP000001595    UP000233100    UP000009136    UP000009130    UP000006718    UP000008225    UP000233200    UP000252040    UP000233220    UP000005640    UP000248483    UP000233080    UP000001038    UP000008144    UP000265300    UP000286641    UP000240080    UP000002277    UP000001073    UP000265180    UP000189706    UP000001075    UP000053258    UP000007754    UP000000437    UP000053875    UP000002281    UP000000539    UP000076420    UP000233040    UP000002356    UP000000305   

PRIDE

H9JEN7    Q3ZBQ0    Q9NXA8    G3H0G1    E1BRE2   

Pfam

PF02146   SIR2

Interpro

IPR027546   Sirtuin_class_III        + More
IPR003000   Sirtuin       
IPR026591   Sirtuin_cat_small_dom_sf       
IPR026590   Ssirtuin_cat_dom       
IPR029035   DHS-like_NAD/FAD-binding_dom       

SUPFAM

SSF52467   SSF52467       

Gene 3D

3.30.1600.10    

CDD

cd01412  SIRT5_Af1_CobB

ProteinModelPortal

H9JEN7   A0A2A4IU40   A0A2A4J757   A0A194PE30   A0A2W1BLQ1   A0A194QKF9   + More
A0A212F1S9   A0A2H1W3C4   A0A3S2TCY5   A0A0L7LGG5   A0A2W1B9B8   A0A2A4J4P9   A0A2P8YXP3   T1JM32   A0A0L8FJ96   A0A1S3I9P2   A0A1S3I3K6   A0A384C9F6   A0A3Q7W2D8   G1L0W8   A0A0A9VU74   R7TYG4   A0A347ZJG9   A0A347ZJH0   A0A2K5Z885   U6CSQ7   M3XNN7   G9KNZ1   L8I353   A0A1S3ARI7   A0A2U3ZJM8   A0A2Y9HU99   A0A2Y9KHV5   A0A2A4J8L1   A0A3Q7S747   A0A232EQW5   E2RDZ6   A0A0D9R5A6   A0A2K6EL10   G1SSN2   A0A3B3DLW2   A0A2K5D7U6   A0A1S3WWN1   L5KVZ6   G7MQR7   A0A1B6F0Z9   A0A2H1V7W5   A0A1U7TB08   I3MLJ1   T1FM78   V3ZQA2   A0A2K6KGU3   A0A2J8WN49   Q5R6G3   A0A2K5U3X0   Q3ZBQ0   A0A2A4IVN0   G7P4G1   F7EZ75   U3FQC2   A0A2K6PGP2   A0A341CYS1   A0A2K6SXL1   A0A024R012   Q9NXA8   A0A2Y9P5P3   A0A1B6MII4   A0A2K5IXA9   H2MC35   H2XWF2   A0A340WH59   A0A3Q7QM78   A0A2R9AH39   K7AYD4   A0A1W5BBZ1   A0A2I3G514   A0A3P9K193   A0A1U7QFA6   B0FWP7   G3H0G1   A0A093PXQ6   A0A2R5LA13   D7PD35   H0Z6V4   A0A0N7ZCB6   Q6DHI5   K7CAU0   A0A093FW32   A0A1B6J2U7   F6S899   A7XXV9   R9PXP3   E1BRE2   A0A2C9JNR9   A0A224YUG4   A0A131YYA3   A0A2K5SEN1   W5PVL7   E9GD30  

PDB

5XHS     E-value=4.66739e-95,     Score=886

KEGG

101741654    K11415 NAD-dependent deacetylase sirtuin 5 [EC:3.5.1.-] | (RefSeq) NAD-dependent protein deacylase-l

GO

GO:0005739   GO:0034979   GO:0036055   GO:0036054   GO:0008270   GO:0070403   GO:0005829   GO:0005634   GO:0010566   GO:0005743   GO:0005758   GO:2000378   GO:0061697   GO:0005759   GO:0036048   GO:0036046   GO:0000035   GO:0006476   GO:0036047   GO:0036049   GO:0031667   GO:0010667   GO:0003950   GO:0061698   GO:0007005   GO:0006342   GO:0006471   GO:1901363  

Subcellular location

Mitochondrion  
Cytoplasm   Mainly mitochondrial. Also present extramitochondrially, with a fraction present in the cytosol and very small amounts also detected in the nucleus.   With evidence from 1 publications.
Cytosol   Mainly mitochondrial. Also present extramitochondrially, with a fraction present in the cytosol and very small amounts also detected in the nucleus.   With evidence from 1 publications.
Nucleus   Mainly mitochondrial. Also present extramitochondrially, with a fraction present in the cytosol and very small amounts also detected in the nucleus.   With evidence from 1 publications.
Mitochondrion matrix  
Mitochondrion intermembrane space  

Length:

292

Number of predicted TMHs:

0

Exp number of AAs in TMHs:

0.20787

Exp number, first 60 AAs:

0.05784

Total prob of N-in:

0.01851

outside

1  -  292

 

 

Pi

35.389269

Theta

46.457822

Tajima's D

-1.157083

CLR

0

CSRT

0.115194240287986

Interpretation

Uncertain