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FLASH GENE
Symbol SIRT4 contributors: mct - updated : 05-05-2009
HGNC name sirtuin (silent mating type information regulation 2 homolog) 4 (S. cerevisiae)
HGNC id 14932
Location 12q24.31      Physical location : 120.740.123 - 120.751.044
Synonym name
  • sirtuin 4
  • SIR2-like protein 4
  • Synonym symbol(s) SIR2L4, MGC130046, MGC130047, MGC57437
    EC.number 3.5.1.-
    DNA
    TYPE functioning gene
    STRUCTURE 10.92 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    LOC387890 12 similar to hypothetical protein C130069F04 PRKAB1 12q24.1-q24.3 protein kinase, AMP-activated, beta 1 non-catalytic subunit CIT 12q24.2 citron (rho-interacting, serine/threonine kinase 21) LOC92558 12q24.31 hypothetical protein LOC92558 RAB35 12q24.31 RAB35, member RAS oncogene family GCN1L1 12q24.3 GCN1 general control of amino-acid synthesis 1-like 1 (yeast) RPLP0 12q24.2 ribosomal protein, large, P0 PXN 12q24 paxillin FLJ23042 12q24.31 hypothetical protein FLJ23042 LOC283458 12q24.31 nucleoside diphosphate kinase B-like pseudogene SIRT4 12q sirtuin (silent mating type information regulation 2 homolog) 4 (S. cerevisiae) PLA2G1B 12q23-q24.32 phospholipase A2, group IB (pancreas) MSI1 12q24.1-q24.31 musashi homolog 1 (Drosophila) COX6A1 12q24.2 cytochrome c oxidase subunit VIa polypeptide 1 HSPC132 12q24.31 hypothetical protein HSPC132 LOC387891 12 LOC387891 SFRS9 12q24.31 splicing factor, arginine/serine-rich 9 DNCL1 12q24.23 dynein, cytoplasmic, light polypeptide 1 MGC4767 12q24.31 hypothetical protein MGC4767 RNF10 12q24.2-q24.3 ring finger protein 10 POP5 12q24.31 RNase MRP/RNase P protein-like LOC390362 12 similar to 60S ribosomal protein L11 CABP1 12q24.2-q24.3 calcium binding protein 1 (calbrain) KIAA0152 12q24.31 calcium binding protein 1 (calbrain) ACADS 12q24.31-q24.32 acyl-Coenzyme A dehydrogenase, C-2 to C-3 short chain LOC387892 12 LOC387892 MGC5139 12q24.31 hypothetical protein MGC5139 SPPL3 12q24.31 SPPL3 protein LOC390363 12 similar to 60S ribosomal protein L12 FLJ38690 12q24.31 hypothetical protein FLJ38690 TCF1 12q24.2 transcription factor 1, hepatic; LF-B1, hepatic nuclear factor (HNF1), albumin proximal factor FLJ12448 12q hypothetical protein FLJ12448 OASL 12q24.2 2'-5'-oligoadenylate synthetase-like
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 1213 35.06 314 - 2006 16959573
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly Homo sapiens
    Digestiveliver   highly Homo sapiens
    Endocrinepancreasislet of Langerhans    Homo sapiens
    Nervousbrain   highly Homo sapiens
    Urinarykidney   highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal moderately Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...) Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text tissues
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a deacetylase sirtuin-type core domain
  • mono polymer complex
    HOMOLOGY
    interspecies homolog to yeast Sir2
    homolog to E.coli CobB
    ortholog to rattus Sirt4 predicted
    ortholog to murine Sirt4
    homolog to Drosophila sirt4
    Homologene
    FAMILY
  • sirtuin family
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    text
  • matrix protein and becomes cleaved at amino acid 28 after import into mitochondria
  • mainly localized in the mitochondria
  • basic FUNCTION
  • lacks deacetylase activities but efficiently works as an ADP-ribosyltransferase
  • playing a role in the regulation of insulin secretion
  • required to maintain cell survival after genotoxic stress in a NAD+-dependent manner
  • with SIRT3, modulate mitochondrial function in response to its [NADH]/[NAD+] ratio by regulating the activity of key metabolic enzymes
  • play a central role in epigenetic gene silencing, DNA repair and recombination, cell-cycle, microtubule organization, and in the regulation of aging
  • by participating in the stress response to genomic insults, sirtuins are thought to protect against cancer, but they are also emerging as direct participants in the growth of some cancers
  • implicated in the regulation of insulin secretion by modulation of glutamate dehydrogenase
  • playing a role in regulating hepatic fat metabolism
  • is potentially a negative regulator of fat oxidation and overall mitochondrial oxidative metabolism
  • negative regulator of oxidative metabolism, which is in stark contrast to the functions of SIRT1 and SIRT3, which enhance the oxidative capacity of tissues
  • CELLULAR PROCESS nucleotide, transcription, regulation
    protein, post translation
    PHYSIOLOGICAL PROCESS
    text chromatin silencing, protein ADP-ribosylation
    PATHWAY
    metabolism
    signaling
    a component
  • chromatin silencing complex
  • INTERACTION
    DNA binding
    RNA
    small molecule metal binding, cofactor,
  • Zn2+
  • NAD
  • protein
  • downregulating GLUD1
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
             
    loss of SIRT4 in insulinoma cells activates GLUD1, thereby upregulating amino acid-stimulated insulin secretion
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabetetype 2 
    its inhibition increases fat oxidative capacity in liver and mitochondrial function in muscle, which might provide therapeutic benefits for diseases associated with ectopic lipid storage such as type 2 diabetes
    ANIMAL & CELL MODELS