| Tag |
Content |
| WERAM ID |
WERAM-Mum-0098 |
| Ensembl Protein ID |
ENSMUSP00000107697.1 |
| Uniprot Accession |
Q8R216; SIR4_MOUSE; D3Z1D9
|
| Genbank Protein ID |
NP_001161163.1; NP_598521.1
|
| Protein Name |
NAD-dependent protein lipoamidase sirtuin-4, mitochondrial |
| Genbank Nucleotide ID |
NM_001167691.1; NM_133760.1
|
| Gene Name |
SIRT4;Sir2l4 |
| Ensembl Information |
|
| Details |
| Type |
Family |
Domain |
Substrates |
AA |
References (PMIDs) |
| HDAC |
SIR2 |
Deacetylase sirtuin-type |
|
K |
23673559
|
|
| Status |
Reviewed |
| Classification |
| Type |
Family |
E-value |
Score |
Start |
End |
| HDAC |
SIR2 |
3.00e-77 |
260.9 |
43 |
312 |
|
| Organism |
Mus musculus |
| NCBI Taxa ID |
10090 |
Functional Description
(View)Functional Description
Acts as NAD-dependent protein lipoamidase, ADP-ribosyl transferase and deacetylase (PubMed:19220062). Catalyzes more efficiently removal of lipoyl- and biotinyl- than acetyl-lysine modifications. Inhibits the pyruvate dehydrogenase complex (PDH) activity via the enzymatic hydrolysis of the lipoamide cofactor from the E2 component, DLAT, in a phosphorylation-independent manner (PubMed:25525879). Catalyzes the transfer of ADP-ribosyl groups onto target proteins, including mitochondrial GLUD1, inhibiting GLUD1 enzyme activity. Acts as a negative regulator of mitochondrial glutamine metabolism by mediating mono ADP-ribosylation of GLUD1: expressed in response to DNA damage and negatively regulates anaplerosis by inhibiting GLUD1, leading to block metabolism of glutamine into tricarboxylic acid cycle and promoting cell cycle arrest (PubMed:16959573). In response to mTORC1 signal, SIRT4 expression is repressed, promoting anaplerosis and cell proliferation (PubMed:23663782). Acts as a tumor suppressor (PubMed:23562301, PubMed:23663782). Also acts as a NAD-dependent protein deacetylase: mediates deacetylation of 'Lys-471' of MLYCD, inhibiting its activity, thereby acting as a regulator of lipid homeostasis (PubMed:23746352). Controls fatty acid oxidation by inhibiting PPARA transcriptional activation. Impairs SIRT1:PPARA interaction probably through the regulation of NAD(+) levels (PubMed:24043310, PubMed:20685656). Down-regulates insulin secretion (By similarity). |
Acts as NAD-dependent protein lipoamidase, ADP-ribosyl transferase and deacetylase (PubMed:19220062). Catalyzes more efficiently removal of lipoyl- and biotinyl- than acetyl-lysine modifications. Inhibits the pyruvate dehydrogenase complex (PDH) activity via the enzymatic hydrolysis of the lipoamide cofactor from the E2 component, DLAT, in a phosphorylation-independent manner (PubMed:25525879). Catalyzes the transfer of ADP-ribosyl groups onto target proteins, including mitochondrial GLUD1, inhibiting GLUD1 enzyme activity. Acts as a negative regulator of mitochondrial glutamine metabolism by mediating mono ADP-ribosylation of GLUD1: expressed in response to DNA damage and negatively regulates anaplerosis by inhibiting GLUD1, leading to block metabolism of glutamine into tricarboxylic acid cycle and promoting cell cycle arrest (PubMed:16959573). In response to mTORC1 signal, SIRT4 expression is repressed, promoting anaplerosis and cell proliferation (PubMed:23663782). Acts as a tumor suppressor (PubMed:23562301, PubMed:23663782). Also acts as a NAD-dependent protein deacetylase: mediates deacetylation of 'Lys-471' of MLYCD, inhibiting its activity, thereby acting as a regulator of lipid homeostasis (PubMed:23746352). Controls fatty acid oxidation by inhibiting PPARA transcriptional activation. Impairs SIRT1:PPARA interaction probably through the regulation of NAD(+) levels (PubMed:24043310, PubMed:20685656). Down-regulates insulin secretion (By similarity).
|
| Domain Profile |
HDAC SIR2
SIR2.txt 2 klakllkkskkivvltGAGiStsaGIPDFRs.seGlysklkkeelpspeaifdldffrkdpkv..fyalakelyp.lgsakPtktHyfl 86
+l+++++ skk++v+tGAGiSt++GIPD+Rs + Gly++++++ +i+++df+r+ p + ++a++ +p ++s++P+++H++l
ENSMUSP00000107697.1 43 ELQRFISLSKKLLVMTGAGISTESGIPDYRSeKVGLYARTDRR------PIQHIDFVRSAPVRqrYWARNFVGWPqFSSHQPNPAHWAL 125
7899***********************************9998......9***********9999************************ PP
SIR2.txt 87 aelekkgkllrlytQNiDgLerkaglkedklvelHGslatasCtkCkkefpreeikeklkak..........................e 149
+++e+ gkl++l+tQN+D L++kag++ +l+elHG+++++ C++C++++ r++++e+++a +
ENSMUSP00000107697.1 126 SNWERLGKLHWLVTQNVDALHSKAGSQ--RLTELHGCMHRVLCLNCGEQTARRVLQERFQALnpswsaeaqgvapdgdvflteeqvrsF 212
**************************9..*******************************99*************************** PP
SIR2.txt 150 kvpkCekCkgvlkpdivffgenlpeefleeveedlkeadlllvlGtSlkvepvaslvkkavkkkvpvllvnleevkadkladlkllgdc 238
+vp C++C+g lkpd+vffg++++ ++++ v++++kead llv+G+Sl+v++ ++++++a ++k p++++n++++++d+la+lkl+++c
ENSMUSP00000107697.1 213 QVPCCDRCGGPLKPDVVFFGDTVNPDKVDFVHRRVKEADSLLVVGSSLQVYSGYRFILTAREQKLPIAILNIGPTRSDDLACLKLDSRC 301
***************************************************************************************** PP
SIR2.txt 239 devveellkll 249
+e++ + +
ENSMUSP00000107697.1 302 GELLPLIDPRR 312
**999887665 PP
|
Protein Sequence
(Fasta) | MSGLTFRPTK GRWITHLSRP RSCGPSGLFV PPSPPLDPEK IKELQRFISL SKKLLVMTGA 60
GISTESGIPD YRSEKVGLYA RTDRRPIQHI DFVRSAPVRQ RYWARNFVGW PQFSSHQPNP 120
AHWALSNWER LGKLHWLVTQ NVDALHSKAG SQRLTELHGC MHRVLCLNCG EQTARRVLQE 180
RFQALNPSWS AEAQGVAPDG DVFLTEEQVR SFQVPCCDRC GGPLKPDVVF FGDTVNPDKV 240
DFVHRRVKEA DSLLVVGSSL QVYSGYRFIL TAREQKLPIA ILNIGPTRSD DLACLKLDSR 300
CGELLPLIDP RRQHSDVQRL EMNFPLSSAA QDP 333Protein Fasta Sequence
>ENSMUSP00000107697.1|SIRT4;Sir2l4|Mus musculus
MSGLTFRPTKGRWITHLSRPRSCGPSGLFVPPSPPLDPEKIKELQRFISLSKKLLVMTGAGISTESGIPDYRSEKVGLYARTDRRPIQHIDFVRSAPVRQRYWARNFVGWPQFSSHQPNPAHWALSNWERLGKLHWLVTQNVDALHSKAGSQRLTELHGCMHRVLCLNCGEQTARRVLQERFQALNPSWSAEAQGVAPDGDVFLTEEQVRSFQVPCCDRCGGPLKPDVVFFGDTVNPDKVDFVHRRVKEADSLLVVGSSLQVYSGYRFILTAREQKLPIAILNIGPTRSDDLACLKLDSRCGELLPLIDPRRQHSDVQRLEMNFPLSSAAQDP |
Nucleotide Sequence
(Fasta) | GGACATGGGA AATATTAACC ACTTCTTTGG TGGCACAAGC CTCTAATCCG AGCACTTGGG 60
AGGTGGAGCC AGGAGGATCA CGGATTTGGA GTCAGACAAG GATATGTCAG ACCCTCTCTC 120
AGCAAACAAC ACAAGCCACA AACAAACAAA CACTACAAGA ACCTCAAAAG GCAATCATTG 180
CCCCAGGCGT CAGCAGCATA TCCGGAACCT TAACTGAGCT GAGCAGGAAA GACAGCGGGC 240
AATCCGTAGA GGAGCGCCCA AGAATCTTGG CGTGGGAGAC ACGTAGGATT CTGGGACTTG 300
TAGTTTTCTT CCAACTAGAT CGGCTTCGCG GACTACATTT CCCAAGATGC ACACGTAACA 360
AGCGAGTCCC ACTGTTGGGT GAGAATTGTG GAAGAATAAG AATGAGCGGA TTGACTTTCA 420
GGCCGACAAA GGGCCGTTGG ATCACCCACC TCAGCCGGCC GCGTTCTTGT GGACCCTCGG 480
GGTTATTTGT GCCGCCCAGC CCTCCTTTGG ACCCTGAAAA GATCAAAGAG TTACAGCGCT 540
TCATTAGCCT TTCCAAGAAA CTCCTCGTGA TGACAGGCGC GGGGATCTCC ACCGAGTCCG 600
GCATCCCAGA CTACAGGTCA GAAAAGGTGG GACTTTACGC CCGCACTGAC CGGAGACCCA 660
TCCAGCACAT TGATTTCGTC CGCAGTGCTC CGGTCCGCCA GCGGTACTGG GCCCGAAACT 720
TTGTGGGCTG GCCTCAATTC TCCTCTCACC AACCCAACCC AGCACACTGG GCTCTGAGCA 780
ACTGGGAGAG ACTGGGGAAG CTGCACTGGT TGGTGACTCA GAACGTGGAC GCTTTGCACT 840
CCAAAGCAGG GAGTCAGCGG CTGACGGAGC TCCACGGATG CATGCACAGA GTCCTGTGCC 900
TGAACTGTGG GGAGCAGACT GCCCGCAGGG TGCTGCAGGA ACGCTTCCAA GCCCTGAACC 960
CCAGCTGGAG CGCCGAGGCG CAGGGCGTGG CTCCCGACGG CGACGTGTTC CTCACTGAGG 1020
AGCAGGTCCG GAGCTTTCAG GTCCCGTGCT GTGATCGATG CGGCGGCCCT CTGAAACCGG 1080
ACGTCGTTTT CTTTGGGGAC ACGGTGAACC CAGACAAGGT TGACTTTGTG CACCGGCGTG 1140
TGAAAGAGGC GGACTCCCTA CTGGTGGTGG GATCATCCCT GCAGGTGTAC TCTGGTTACA 1200
GGTTCATCCT CACCGCCCGC GAGCAAAAGC TCCCAATAGC CATTCTGAAT ATCGGCCCCA 1260
CCCGGTCTGA CGATTTGGCT TGCCTGAAGC TGGATTCCCG CTGTGGAGAG TTGCTGCCTT 1320
TAATAGACCC GCGGAGACAG CACTCTGATG TCCAAAGGCT GGAAATGAAC TTTCCTCTGA 1380
GTTCCGCTGC TCAAGATCCC TAAGGATCCC CCCACCCCCC AATGCCGCTC CAACTCTGAA 1440
TCCTAGAGGT GGCAAAGCCA CGTCTAGAGG CCAGGCACCC TCCTGTTTAC AGAAATGAGA 1500
GCTGCCCCCT AAGGAAAGAC TTTTCCAAAG AAATAGCTGC TCTTGATGGA GTAGCTGTGT 1560
CGCCTTCTGG TAACCGGAAG AAGGACCAGG CAGAAGTCAG TAAACCACAA CTGTCTATGA 1620
GGGGCAACGT GGAGATAGAT CTCACTCATT CAGGGCATTT ATAATTCATT CATAATTCCA 1680
AATGGATGTG TCTGACTGAA GCACTTTGAT ATTTCTGATG GCAGGAGCAA TAGCTAACAC 1740
GGCTTTTTTT TTTTTAATTA TTAGCCAAAT AATAAATTAT TTTTAATAGC ATAA
1795Nucleotide Fasta Sequence
>ENSMUSP00000107697.1|SIR2|Mus musculus
GGACATGGGAAATATTAACCACTTCTTTGGTGGCACAAGCCTCTAATCCGAGCACTTGGGAGGTGGAGCCAGGAGGATCACGGATTTGGAGTCAGACAAGGATATGTCAGACCCTCTCTCAGCAAACAACACAAGCCACAAACAAACAAACACTACAAGAACCTCAAAAGGCAATCATTGCCCCAGGCGTCAGCAGCATATCCGGAACCTTAACTGAGCTGAGCAGGAAAGACAGCGGGCAATCCGTAGAGGAGCGCCCAAGAATCTTGGCGTGGGAGACACGTAGGATTCTGGGACTTGTAGTTTTCTTCCAACTAGATCGGCTTCGCGGACTACATTTCCCAAGATGCACACGTAACAAGCGAGTCCCACTGTTGGGTGAGAATTGTGGAAGAATAAGAATGAGCGGATTGACTTTCAGGCCGACAAAGGGCCGTTGGATCACCCACCTCAGCCGGCCGCGTTCTTGTGGACCCTCGGGGTTATTTGTGCCGCCCAGCCCTCCTTTGGACCCTGAAAAGATCAAAGAGTTACAGCGCTTCATTAGCCTTTCCAAGAAACTCCTCGTGATGACAGGCGCGGGGATCTCCACCGAGTCCGGCATCCCAGACTACAGGTCAGAAAAGGTGGGACTTTACGCCCGCACTGACCGGAGACCCATCCAGCACATTGATTTCGTCCGCAGTGCTCCGGTCCGCCAGCGGTACTGGGCCCGAAACTTTGTGGGCTGGCCTCAATTCTCCTCTCACCAACCCAACCCAGCACACTGGGCTCTGAGCAACTGGGAGAGACTGGGGAAGCTGCACTGGTTGGTGACTCAGAACGTGGACGCTTTGCACTCCAAAGCAGGGAGTCAGCGGCTGACGGAGCTCCACGGATGCATGCACAGAGTCCTGTGCCTGAACTGTGGGGAGCAGACTGCCCGCAGGGTGCTGCAGGAACGCTTCCAAGCCCTGAACCCCAGCTGGAGCGCCGAGGCGCAGGGCGTGGCTCCCGACGGCGACGTGTTCCTCACTGAGGAGCAGGTCCGGAGCTTTCAGGTCCCGTGCTGTGATCGATGCGGCGGCCCTCTGAAACCGGACGTCGTTTTCTTTGGGGACACGGTGAACCCAGACAAGGTTGACTTTGTGCACCGGCGTGTGAAAGAGGCGGACTCCCTACTGGTGGTGGGATCATCCCTGCAGGTGTACTCTGGTTACAGGTTCATCCTCACCGCCCGCGAGCAAAAGCTCCCAATAGCCATTCTGAATATCGGCCCCACCCGGTCTGACGATTTGGCTTGCCTGAAGCTGGATTCCCGCTGTGGAGAGTTGCTGCCTTTAATAGACCCGCGGAGACAGCACTCTGATGTCCAAAGGCTGGAAATGAACTTTCCTCTGAGTTCCGCTGCTCAAGATCCCTAAGGATCCCCCCACCCCCCAATGCCGCTCCAACTCTGAATCCTAGAGGTGGCAAAGCCACGTCTAGAGGCCAGGCACCCTCCTGTTTACAGAAATGAGAGCTGCCCCCTAAGGAAAGACTTTTCCAAAGAAATAGCTGCTCTTGATGGAGTAGCTGTGTCGCCTTCTGGTAACCGGAAGAAGGACCAGGCAGAAGTCAGTAAACCACAACTGTCTATGAGGGGCAACGTGGAGATAGATCTCACTCATTCAGGGCATTTATAATTCATTCATAATTCCAAATGGATGTGTCTGACTGAAGCACTTTGATATTTCTGATGGCAGGAGCAATAGCTAACACGGCTTTTTTTTTTTTAATTATTAGCCAAATAATAAATTATTTTTAATAGCATAA
|
| Sequence Source |
Ensembl |
| Keyword |
KW-0181--Complete proteome
KW-0227--DNA damage
KW-0378--Hydrolase
KW-0479--Metal-binding
KW-0496--Mitochondrion
KW-0520--NAD
KW-1185--Reference proteome
KW-0808--Transferase
KW-0809--Transit peptide
KW-0043--Tumor suppressor
KW-0862--Zinc
--
|
| Interpro |
IPR029035--DHS-like_NAD/FAD-binding_dom
IPR003000--Sirtuin
IPR026591--Sirtuin_cat_small_dom
IPR026587--Sirtuin_class_II
IPR026590--Ssirtuin_cat_dom
|
| PROSITE |
PS50305--SIRTUIN
|
| Pfam |
PF02146--SIR2
|
| Gene Ontology |
GO:0005743--C:mitochondrial inner membrane
GO:0005759--C:mitochondrial matrix
GO:0005739--C:mitochondrion
GO:0047708--F:biotinidase activity
GO:0061690--F:lipoamidase activity
GO:0046872--F:metal ion binding
GO:0003950--F:NAD+ ADP-ribosyltransferase activity
GO:0070403--F:NAD+ binding
GO:0034979--F:NAD-dependent protein deacetylase activity
GO:0006974--P:cellular response to DNA damage stimulus
GO:0071456--P:cellular response to hypoxia
GO:0006541--P:glutamine metabolic process
GO:0010667--P:negative regulation of cardiac muscle cell apoptotic process
GO:0046322--P:negative regulation of fatty acid oxidation
GO:0046676--P:negative regulation of insulin secretion
GO:1903217--P:negative regulation of protein processing involved in protein targeting to mitochondrion
GO:0034983--P:peptidyl-lysine deacetylation
GO:0046889--P:positive regulation of lipid biosynthetic process
GO:0006471--P:protein ADP-ribosylation
GO:0000820--P:regulation of glutamine family amino acid metabolic process
GO:1904182--P:regulation of pyruvate dehydrogenase activity
GO:0072350--P:tricarboxylic acid metabolic process
|
| Orthology |
|
| Created Date |
25-Jun-2016 |
