NAD-dependent protein lipoamidase sirtuin-4, mitochondrial (EC 2.3.1.-) (NAD-dependent ADP-ribosyltransferase sirtuin-4) (EC 2.4.2.-) (NAD-dependent protein biotinylase sirtuin-4) (EC 2.3.1.-) (NAD-dependent protein deacetylase sirtuin-4) (EC 2.3.1.286) (Regulatory protein SIR2 homolog 4) (SIR2-like protein 4)
1_MKMSF 6_ ALTFR 11_ SAKGR 16_ WIANP 21_ SQPCS 26_ KASIG 31_ LFVPA 36_ SPPLD 41_ PEKVK 46_ ELQRF 51_ ITLSK 56_ RLLVM 61_ TGAGI 66_ STESG 71_ IPDYR 76_ SEKVG 81_ LYART 86_ DRRPI 91_ QHGDF 96_ VRSAP 101_ IRQRY 106_ WARNF 111_ VGWPQ 116_ FSSHQ 121_ PNPAH 126_ WALST 131_ WEKLG 136_ KLYWL 141_ VTQNV 146_ DALHT 151_ KAGSR 156_ RLTEL 161_ HGCMD 166_ RVLCL 171_ DCGEQ 176_ TPRGV 181_ LQERF 186_ QVLNP 191_ TWSAE 196_ AHGLA 201_ PDGDV 206_ FLSEE 211_ QVRSF 216_ QVPTC 221_ VQCGG 226_ HLKPD 231_ VVFFG 236_ DTVNP 241_ DKVDF 246_ VHKRV 251_ KEADS 256_ LLVVG 261_ SSLQV 266_ YSGYR 271_ FILTA 276_ WEKKL 281_ PIAIL 286_ NIGPT 291_ RSDDL 296_ ACLKL 301_ NSRCG 306_ELLPL
1: Acts as a NAD-dependent protein lipoamidase, biotinylase, deacetylase and ADP-ribosyl transferase (PubMed:16959573, PubMed:17715127, PubMed:24052263, PubMed:25525879). Catalyzes more efficiently removal of lipoyl- and biotinyl- than acetyl-lysine modifications (PubMed:24052263, PubMed:25525879). 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 (PubMed:16959573, PubMed:17715127). 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 (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 (By similarity). Does not seem to deacetylate PC (PubMed:23438705). Controls fatty acid oxidation by inhibiting PPARA transcriptional activation (PubMed:24043310). Impairs SIRT1-PPARA interaction probably through the regulation of NAD(+) levels (PubMed:24043310). Down-regulates insulin secretion (PubMed:17715127)