WERAM Information

Tag Content
WERAM ID WERAM-Hos-0046
Ensembl Protein ID ENSP00000202967.4
Uniprot Accession Q9Y6E7; SIR4_HUMAN; O43346; Q32M33
Genbank Protein ID NP_036372.1; XP_006719371.1; XP_006719372.1
Protein Name NAD-dependent protein lipoamidase sirtuin-4, mitochondrial
Genbank Nucleotide ID NM_012240.2; XM_006719308.2; XM_006719309.2
Gene Name SIRT4;SIR2L4
Ensembl Information
Ensembl Gene ID Ensembl Transcript ID Ensembl Protein ID
ENSG00000089163.4 ENST00000202967.4 ENSP00000202967.4
Details
Type Family Domain Substrates AA References (PMIDs)
HDAC SIR2 Deacetylase sirtuin-type K 19698979
Status Reviewed
Classification
Type Family E-value Score Start End
HDAC SIR2 2.70e-75 255.4 46 311
Organism Homo sapiens
NCBI Taxa ID 9606
Functional Description
(View)		 Acts as NAD-dependent protein lipoamidase, ADP-ribosyl transferase and deacetylase. 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, PubMed:17715127). In response to mTORC1 signal, SIRT4 expression is repressed, promoting anaplerosis and cell proliferation. 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 (By similarity). Controls fatty acid oxidation by inhibiting PPARA transcriptional activation. Impairs SIRT1:PPARA interaction probably through the regulation of NAD(+) levels (PubMed:24043310). Down-regulates insulin secretion.
Domain Profile
  HDAC SIR2
           SIR2.txt   2 klakllkkskkivvltGAGiStsaGIPDFRs.seGlysklkkeelpspeaifdldffrkdpkv..fyalakelyp.lgsakPtktHyflael 89 
                        +l+++++ sk+++v+tGAGiSt++GIPD+Rs + Gly++++++      +i++ df+r+ p +  ++a++   +p ++s++P+++H++l+++
  ENSP00000202967.4  46 ELQRFITLSKRLLVMTGAGISTESGIPDYRSeKVGLYARTDRR------PIQHGDFVRSAPIRqrYWARNFVGWPqFSSHQPNPAHWALSTW 131
                        78999**********************************9998......9**********99889*************************** PP
           SIR2.txt  90 ekkgkllrlytQNiDgLerkaglkedklvelHGslatasCtkCkkefpreeikeklkak..........................ekvpkCe 155
                        ek gkl +l+tQN+D L++kag++  +l+elHG++ ++ C++C++++pr +++e+++                            ++vp+C 
  ENSP00000202967.4 132 EKLGKLYWLVTQNVDALHTKAGSR--RLTELHGCMDRVLCLDCGEQTPRGVLQERFQVLnptwsaeahglapdgdvflseeqvrsFQVPTCV 221
                        ***********************9..******************************9999******************************** PP
           SIR2.txt 156 kCkgvlkpdivffgenlpeefleeveedlkeadlllvlGtSlkvepvaslvkkavkkkvpvllvnleevkadkladlkllgdcdevveel 245
                        +C+g+lkpd+vffg++++ ++++ v++++kead llv+G+Sl+v++ ++++++a++kk p++++n++++++d+la+lkl+++c+e++  +
  ENSP00000202967.4 222 QCGGHLKPDVVFFGDTVNPDKVDFVHKRVKEADSLLVVGSSLQVYSGYRFILTAWEKKLPIAILNIGPTRSDDLACLKLNSRCGELLPLI 311
                        ************************************************************************************998766 PP
Protein Sequence
(Fasta)		MKMSFALTFR SAKGRWIANP SQPCSKASIG LFVPASPPLD PEKVKELQRF ITLSKRLLVM 60
TGAGISTESG IPDYRSEKVG LYARTDRRPI QHGDFVRSAP IRQRYWARNF VGWPQFSSHQ 120
PNPAHWALST WEKLGKLYWL VTQNVDALHT KAGSRRLTEL HGCMDRVLCL DCGEQTPRGV 180
LQERFQVLNP TWSAEAHGLA PDGDVFLSEE QVRSFQVPTC VQCGGHLKPD VVFFGDTVNP 240
DKVDFVHKRV KEADSLLVVG SSLQVYSGYR FILTAWEKKL PIAILNIGPT RSDDLACLKL 300
NSRCGELLPL IDPC 314
Nucleotide Sequence
(Fasta)		GCAAATGCAA TCAGACGGTC CCACTGTGGG GTGTGAAGTG TCCGTAGAGC TGTGAGAGAA 60
TGAAGATGAG CTTTGCGTTG ACTTTCAGGT CAGCAAAAGG CCGTTGGATC GCAAACCCCA 120
GCCAGCCGTG CTCGAAAGCC TCCATTGGGT TATTTGTGCC AGCAAGTCCT CCTCTGGACC 180
CTGAGAAGGT CAAAGAGTTA CAGCGCTTCA TCACCCTTTC CAAGAGACTC CTTGTGATGA 240
CTGGGGCAGG AATCTCCACC GAATCGGGGA TACCAGACTA CAGGTCAGAA AAAGTGGGGC 300
TTTATGCCCG CACTGACCGC AGGCCCATCC AGCATGGTGA TTTTGTCCGG AGTGCCCCAA 360
TCCGCCAGCG GTACTGGGCG AGAAACTTCG TAGGCTGGCC TCAATTCTCC TCCCACCAGC 420
CTAACCCTGC ACACTGGGCT TTGAGCACCT GGGAGAAACT CGGAAAGCTG TACTGGTTGG 480
TGACCCAAAA TGTGGATGCT TTGCACACCA AGGCGGGGAG TCGGCGCCTG ACAGAGCTCC 540
ACGGATGCAT GGACAGGGTC CTGTGCTTGG ATTGTGGGGA ACAGACTCCC CGGGGGGTGC 600
TGCAAGAGCG TTTCCAAGTC CTGAACCCCA CCTGGAGTGC TGAGGCCCAT GGCCTGGCTC 660
CTGATGGTGA CGTCTTTCTC TCAGAGGAGC AAGTCCGGAG CTTTCAGGTC CCAACCTGCG 720
TTCAATGTGG AGGCCATCTG AAACCAGATG TCGTTTTCTT CGGGGACACA GTGAACCCTG 780
ACAAGGTTGA TTTTGTGCAC AAGCGTGTAA AAGAAGCCGA CTCCCTCTTG GTGGTGGGAT 840
CATCCTTGCA GGTATACTCT GGTTACAGGT TTATCCTCAC TGCCTGGGAG AAGAAGCTCC 900
CGATTGCAAT ACTGAACATT GGGCCCACAC GGTCGGATGA CTTGGCGTGT CTGAAACTGA 960
ATTCTCGTTG TGGAGAGTTG CTGCCTTTGA TAGACCCATG CTGACCACAG CCTGATATTC 1020
CAGAACCTGG AACAGGGACT TTCACTTGAA TCTTGCTGCT AAATGTAAAT GCCTTCTCAA 1080
ATGACAGATT CCAGTTCCCA TTCAACAGAG TAGGGTGCAC TGACAAAGTA TAGAAGGTTC 1140
TAGGTATCTT AATGTGTGGA TATTCTTAAT TAAAACTCAT TTTTTTTAAA TAAAAAATTG 1200
TTCAGCTTTA TATGAAA 1218
Sequence Source Ensembl
Keyword

KW-0181--Complete proteome
KW-0903--Direct protein sequencing
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:0006974--P:cellular response to DNA damage stimulus
GO:0071456--P:cellular response to hypoxia
GO:0006342--P:chromatin silencing
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
WERAM ID Ensembl Protein ID Species Identity E-value Score
WERAM-Pat-0044 ENSPTRP00000009383.4 Pan troglodytes 100 0.0 647
WERAM-Gog-0207 ENSGGOP00000025620.1 Gorilla gorilla 99 0.0 644
WERAM-Poa-0046 ENSPPYP00000005727.2 Pongo abelii 98 0.0 639
WERAM-Paa-0081 ENSPANP00000005490.1 Papio anubis 97 5e-179 624
WERAM-Chs-0026 ENSCSAP00000015768.1 Chlorocebus sabaeus 97 8e-179 623
WERAM-Caj-0096 ENSCJAP00000015889.2 Callithrix jacchus 94 3e-174 608
WERAM-Otg-0098 ENSOGAP00000008496.1 Otolemur garnettii 90 8e-168 586
WERAM-Eqc-0095 ENSECAP00000011260.1 Equus caballus 89 1e-166 582
WERAM-Sus-0071 ENSSSCP00000010568.2 Sus scrofa 89 5e-166 580
WERAM-Ova-0127 ENSOARP00000012850.1 Ovis aries 90 7e-166 580
WERAM-Tas-0026 ENSTSYP00000002962.1 Tarsius syrichta 91 3e-165 578
WERAM-Bot-0183 ENSBTAP00000028210.3 Bos taurus 90 9e-165 576
WERAM-Orc-0113 ENSOCUP00000009744.3 Oryctolagus cuniculus 88 3e-164 575
WERAM-Fec-0171 ENSFCAP00000020847.1 Felis catus 88 4e-162 567
WERAM-Ict-0083 ENSSTOP00000008774.2 Ictidomys tridecemlineatus 88 9e-162 566
WERAM-Mup-0031 ENSMPUP00000003126.1 Mustela putorius furo 87 1e-161 566
WERAM-Loa-0028 ENSLAFP00000001879.2 Loxodonta africana 86 4e-161 564
WERAM-Aim-0062 ENSAMEP00000005483.1 Ailuropoda melanoleuca 86 4e-161 564
WERAM-Ocp-0148 ENSOPRP00000015399.1 Ochotona princeps 85 1e-158 556
WERAM-Mum-0098 ENSMUSP00000107697.1 Mus musculus 87 2e-158 555
WERAM-Ptv-0014 ENSPVAP00000002101.1 Pteropus vampyrus 85 4e-158 554
WERAM-Cap-0138 ENSCPOP00000011117.2 Cavia porcellus 84 7e-158 553
WERAM-Caf-0113 ENSCAFP00000015057.3 Canis familiaris 85 3e-157 551
WERAM-Chh-0046 ENSCHOP00000005172.1 Choloepus hoffmanni 84 1e-156 549
WERAM-Ran-0010 ENSRNOP00000001523.4 Rattus norvegicus 86 8e-156 546
WERAM-Nol-0169 ENSNLEP00000018942.2 Nomascus leucogenys 98 2e-148 522
WERAM-Ect-0086 ENSETEP00000009903.1 Echinops telfairi 82 3e-145 511
WERAM-Soa-0051 ENSSARP00000004940.1 Sorex araneus 80 2e-143 505
WERAM-Sah-0071 ENSSHAP00000008646.1 Sarcophilus harrisii 83 2e-142 502
WERAM-Tut-0072 ENSTTRP00000005343.1 Tursiops truncatus 89 9e-142 499
WERAM-Tub-0044 ENSTBEP00000005291.1 Tupaia belangeri 80 4e-141 498
WERAM-Pes-0110 ENSPSIP00000013404.1 Pelodiscus sinensis 77 1e-130 463
WERAM-Dan-0155 ENSDNOP00000033669.1 Dasypus novemcinctus 79 2e-130 462
WERAM-Meg-0094 ENSMGAP00000009092.2 Meleagris gallopavo 74 9e-127 450
WERAM-Tag-0120 ENSTGUP00000009802.1 Taeniopygia guttata 75 1e-126 449
WERAM-Fia-0095 ENSFALP00000007922.1 Ficedula albicollis 74 2e-126 448
WERAM-Anp-0117 ENSAPLP00000013436.1 Anas platyrhynchos 76 4e-126 448
WERAM-Gaga-0078 ENSGALP00000011706.4 Gallus gallus 75 1e-125 446
WERAM-Ora-0041 ENSOANP00000006568.2 Ornithorhynchus anatinus 79 1e-125 446
WERAM-Lac-0179 ENSLACP00000020887.1 Latimeria chalumnae 67 1e-122 436
WERAM-Anc-0024 ENSACAP00000002561.3 Anolis carolinensis 69 9e-114 407
WERAM-Xet-0032 ENSXETP00000009271.1 Xenopus tropicalis 66 5e-112 401
WERAM-Tar-0187 ENSTRUP00000038866.1 Takifugu rubripes 66 8e-112 400
WERAM-Pof-0223 ENSPFOP00000018246.2 Poecilia formosa 68 9e-112 400
WERAM-Orn-0178 ENSONIP00000018093.1 Oreochromis niloticus 64 1e-111 400
WERAM-Orla-0208 ENSORLP00000024753.1 Oryzias latipes 68 1e-111 399
WERAM-Xim-0194 ENSXMAP00000015621.1 Xiphophorus maculatus 67 9e-111 397
WERAM-Dar-0026 ENSDARP00000027611.6 Danio rerio 65 1e-110 396
WERAM-Asm-0019 ENSAMXP00000002317.1 Astyanax mexicanus 64 8e-110 394
WERAM-Gaa-0017 ENSGACP00000001945.1 Gasterosteus aculeatus 62 2e-108 389
WERAM-Gam-0012 ENSGMOP00000001231.1 Gadus morhua 63 3e-108 388
WERAM-Pem-0012 ENSPMAP00000001780.1 Petromyzon marinus 61 4e-104 375
WERAM-Cii-0061 ENSCINP00000027422.2 Ciona intestinalis 51 4e-82 301
WERAM-Drm-0032 FBpp0070817 Drosophila melanogaster 47 6e-76 281
WERAM-Cae-0023 F46G10.7a Caenorhabditis elegans 50 4e-75 278
WERAM-Sei-0033 Si009965m Setaria italica 46 2e-70 263
WERAM-Ors-0107 OS12T0179800-01 Oryza sativa 43 6e-70 261
WERAM-Orm-0103 OMERI12G03020.1 Oryza meridionalis 43 7e-70 261
WERAM-Orp-0109 OPUNC12G04720.1 Oryza punctata 43 8e-70 261
WERAM-Lep-0113 LPERR12G04350.1 Leersia perrieri 46 1e-69 260
WERAM-Ori-0126 BGIOSGA036526-PA Oryza indica 43 1e-69 260
WERAM-Orbr-0122 OB12G14620.1 Oryza brachyantha 43 1e-69 260
WERAM-Orr-0119 ORUFI12G05460.1 Oryza rufipogon 43 2e-69 259
WERAM-Sob-0114 Sb08g004900.1 Sorghum bicolor 46 3e-69 259
WERAM-Orl-0007 KN538685.1_FGP039 Oryza longistaminata 46 7e-69 258
WERAM-Brd-0118 BRADI4G41127.1 Brachypodium distachyon 45 8e-69 257
WERAM-Tra-0230 Traes_5DL_84C49FB59.2 Triticum aestivum 45 3e-68 255
WERAM-Php-0025 PP1S15_90V6.1 Physcomitrella patens 45 4e-68 255
WERAM-Mua-0095 GSMUA_Achr6P25880_001 Musa acuminata 45 1e-66 250
WERAM-Amt-0023 ERN08785 Amborella trichopoda 44 2e-66 250
WERAM-Viv-0046 VIT_07s0031g02510.t01 Vitis vinifera 45 2e-66 249
WERAM-Thc-0008 EOX92647 Theobroma cacao 45 3e-66 249
WERAM-Aet-0050 EMT19694 Aegilops tauschii 42 2e-65 246
WERAM-Art-0118 AT5G09230.7 Arabidopsis thaliana 43 4e-64 242
WERAM-Prp-0069 EMJ12669 Prunus persica 44 5e-64 241
WERAM-Zem-0150 GRMZM5G807054_P01 Zea mays 42 6e-64 241
WERAM-Orni-0118 ONIVA12G04440.1 Oryza nivara 46 1e-63 240
WERAM-Orgl-0114 OGLUM12G05580.1 Oryza glumaepatula 46 1e-63 240
WERAM-Glm-0041 GLYMA04G38730.1 Glycine max 44 1e-63 240
WERAM-Arl-0027 fgenesh1_pg.C_scaffold_6000741 Arabidopsis lyrata 44 2e-63 240
WERAM-Met-0074 AES72910 Medicago truncatula 45 4e-63 238
WERAM-Pot-0061 POPTR_0005s06930.1 Populus trichocarpa 44 8e-63 238
WERAM-Sot-0097 PGSC0003DMT400082473 Solanum tuberosum 44 2e-62 236
WERAM-Sem-0074 EFJ28669 Selaginella moellendorffii 42 4e-62 235
WERAM-Sol-0062 Solyc04g009430.2.1 Solanum lycopersicum 44 7e-62 234
WERAM-Brr-0142 Bra028643.1-P Brassica rapa 44 2e-61 233
WERAM-Bro-0024 Bo2g009270.1 Brassica oleracea 43 1e-60 230
WERAM-Chr-0008 EDP00705 Chlamydomonas reinhardtii 49 3e-60 229
WERAM-Ten-0147 ENSTNIP00000015282.1 Tetraodon nigroviridis 30 1e-27 121
WERAM-Ere-0059 ENSEEUP00000005136.1 Erinaceus europaeus 29 2e-26 117
WERAM-Dio-0050 ENSDORP00000004937.1 Dipodomys ordii 28 6e-24 108
WERAM-Cis-0081 ENSCSAVP00000017799.1 Ciona savignyi 30 1e-23 107
WERAM-Myl-0161 ENSMLUP00000013308.2 Myotis lucifugus 27 8e-23 105
WERAM-Scs-0014 EDN99996 Sclerotinia sclerotiorum 32 4e-22 102
WERAM-Mam-0069 ENSMMUP00000011380.2 Macaca mulatta 28 4e-22 102
WERAM-Fuo-0021 FOXG_06023P0 Fusarium oxysporum 33 7e-22 102
WERAM-Kll-0027 CAG98291 Kluyveromyces lactis 28 2e-21 100
WERAM-Mao-0040 MGG_17827T0 Magnaporthe oryzae 31 3e-21 99.8
WERAM-Trr-0018 EGR46788 Trichoderma reesei 30 5e-21 99.0
WERAM-Trv-0012 EHK19002 Trichoderma virens 29 7e-21 98.6
WERAM-Gag-0013 GGTG_03219T0 Gaeumannomyces graminis 31 7e-21 98.6
WERAM-Nec-0006 EFNCRP00000000764 Neurospora crassa 32 3e-20 96.3
WERAM-Org-0043 ORGLA04G0042700.1 Oryza glaberrima 30 5e-20 95.9
WERAM-Leo-0156 ENSLOCP00000018785.1 Lepisosteus oculatus 28 6e-20 95.5
WERAM-Asfu-0001 CADAFUAP00000229 Aspergillus fumigatus 30 3e-19 93.2
WERAM-Pyt-0039 EFQ86136 Pyrenophora teres 29 6e-19 92.0
WERAM-Asni-0009 CADANGAP00002892 Aspergillus niger 29 8e-19 91.7
WERAM-Mod-0192 ENSMODP00000026476.2 Monodelphis domestica 30 2e-18 90.9
WERAM-Kop-0007 CAY68156 Komagataella pastoris 28 2e-18 90.5
WERAM-Scj-0005 EEB06048 Schizosaccharomyces japonicus 26 2e-18 90.1
WERAM-Lab-0008 EDR12994 Laccaria bicolor 26 3e-18 90.1
WERAM-Osl-0012 ABO98065 Ostreococcus lucimarinus 29 3e-18 89.7
WERAM-Ast-0036 CADATEAP00009630 Aspergillus terreus 30 4e-18 89.7
WERAM-Crn-0031 AAW44797 Cryptococcus neoformans 30 5e-18 89.0
WERAM-Aso-0005 CADAORAP00000633 Aspergillus oryzae 28 5e-18 89.0
WERAM-Asf-0024 CADAFLAP00010064 Aspergillus flavus 28 5e-18 89.0
WERAM-Asc-0026 CADACLAP00005809 Aspergillus clavatus 31 8e-18 88.6
WERAM-Zyt-0001 Mycgr3P100618 Zymoseptoria tritici 29 2e-17 87.0
Created Date 25-Jun-2016