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P16638

- ACLY_RAT

UniProt

P16638 - ACLY_RAT

Protein

ATP-citrate synthase

Gene

Acly

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 138 (01 Oct 2014)
      Sequence version 1 (01 Aug 1990)
      Previous versions | rss
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    Functioni

    ATP citrate-lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. Has a central role in de novo lipid synthesis. In nervous tissue it may be involved in the biosynthesis of acetylcholine.

    Catalytic activityi

    ADP + phosphate + acetyl-CoA + oxaloacetate = ATP + citrate + CoA.

    Cofactori

    Magnesium.By similarity

    Enzyme regulationi

    Major regulation of ATP citrate-lyase activity is probably not by phosphorylation/dephosphorylation but by altering the amount of enzyme.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei58 – 581ATPBy similarity
    Binding sitei118 – 1181ATPBy similarity
    Metal bindingi201 – 2011MagnesiumBy similarity
    Metal bindingi203 – 2031MagnesiumBy similarity
    Binding sitei346 – 3461Citrate; via amide nitrogenBy similarity
    Binding sitei348 – 3481CitrateBy similarity
    Binding sitei379 – 3791CitrateBy similarity
    Metal bindingi717 – 7171MagnesiumBy similarity
    Active sitei759 – 7591Tele-phosphohistidine intermediate

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi66 – 672ATPBy similarity
    Nucleotide bindingi109 – 1113ATPBy similarity
    Nucleotide bindingi700 – 72021ATPBy similarityAdd
    BLAST
    Nucleotide bindingi751 – 77727ATPBy similarityAdd
    BLAST

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. ATP citrate synthase activity Source: RGD
    3. cofactor binding Source: InterPro
    4. metal ion binding Source: UniProtKB-KW
    5. succinate-CoA ligase (ADP-forming) activity Source: InterPro

    GO - Biological processi

    1. acetyl-CoA biosynthetic process Source: RGD
    2. acetyl-CoA metabolic process Source: RGD
    3. cellular carbohydrate metabolic process Source: InterPro
    4. citrate metabolic process Source: RGD
    5. fatty acid biosynthetic process Source: RGD
    6. lipid biosynthetic process Source: UniProtKB
    7. lipid metabolic process Source: RGD

    Keywords - Molecular functioni

    Transferase

    Keywords - Biological processi

    Lipid biosynthesis, Lipid metabolism

    Keywords - Ligandi

    ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    ATP-citrate synthase (EC:2.3.3.8)
    Alternative name(s):
    ATP-citrate (pro-S-)-lyase
    Citrate cleavage enzyme
    Gene namesi
    Name:Acly
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi2018. Acly.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 11001100ATP-citrate synthasePRO_0000102783Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei131 – 1311PhosphotyrosineBy similarity
    Modified residuei446 – 4461Phosphothreonine1 Publication
    Modified residuei450 – 4501Phosphoserine1 Publication
    Modified residuei454 – 4541Phosphoserine; by PKA and PKB/AKT1 or PKB/AKT21 Publication
    Modified residuei480 – 4801PhosphoserineBy similarity
    Modified residuei539 – 5391N6-acetyllysine; alternateBy similarity
    Cross-linki539 – 539Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
    Modified residuei545 – 5451N6-acetyllysine; alternateBy similarity
    Cross-linki545 – 545Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
    Modified residuei553 – 5531N6-acetyllysine; alternateBy similarity
    Cross-linki553 – 553Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
    Modified residuei638 – 6381PhosphothreonineBy similarity
    Modified residuei662 – 6621PhosphoserineBy similarity
    Modified residuei681 – 6811PhosphotyrosineBy similarity
    Modified residuei838 – 8381PhosphoserineBy similarity
    Modified residuei947 – 9471N6-acetyllysineBy similarity
    Modified residuei967 – 9671N6-acetyllysineBy similarity
    Modified residuei977 – 9771N6-acetyllysineBy similarity
    Modified residuei1076 – 10761N6-acetyllysineBy similarity
    Modified residuei1099 – 10991PhosphoserineBy similarity

    Post-translational modificationi

    Phosphorylated on two serines and one threonine. Phosphorylation on Thr-446 and Ser-450 depends on the phosphorylation state of Ser-454. Phosphorylation on Ser-454 is decreased by prior phosphorylation on the other 2 residues.2 Publications
    The N-terminus is blocked.
    ISGylated.By similarity
    Acetylated at Lys-539, Lys-545 and Lys-553 by KAT2B/PCAF. Acetylation is promoted by glucose and stabilizes the protein, probably by preventing ubiquitination at the same sites. Acetylation promotes de novo lipid synthesis. Deacetylated by SIRT2 By similarity.By similarity
    Ubiquitinated at Lys-539, Lys-545 and Lys-553 by UBR4, leading to its degradation. Ubiquitination is probably inhibited by acetylation at same site By similarity.By similarity

    Keywords - PTMi

    Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiP16638.
    PRIDEiP16638.

    PTM databases

    PhosphoSiteiP16638.

    Expressioni

    Tissue specificityi

    Expreesed in the brain, kidney, mammary gland, lung and liver.1 Publication

    Gene expression databases

    GenevestigatoriP16638.

    Interactioni

    Subunit structurei

    Homotetramer.

    Protein-protein interaction databases

    BioGridi246351. 2 interactions.
    IntActiP16638. 1 interaction.
    MINTiMINT-4568685.

    Structurei

    3D structure databases

    ProteinModelPortaliP16638.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini4 – 265262ATP-graspAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni778 – 78811CoA-bindingSequence AnalysisAdd
    BLAST

    Sequence similaritiesi

    In the N-terminal section; belongs to the succinate/malate CoA ligase beta subunit family.Curated
    In the C-terminal section; belongs to the succinate/malate CoA ligase alpha subunit family.Curated
    Contains 1 ATP-grasp domain.Curated

    Phylogenomic databases

    eggNOGiCOG0372.
    HOGENOMiHOG000151479.
    HOVERGENiHBG003318.
    InParanoidiP16638.
    KOiK01648.
    PhylomeDBiP16638.

    Family and domain databases

    Gene3Di1.10.230.10. 1 hit.
    3.30.470.20. 1 hit.
    3.40.50.261. 2 hits.
    3.40.50.720. 1 hit.
    InterProiIPR014608. ATP-citrate_synthase.
    IPR013650. ATP-grasp_succ-CoA_synth-type.
    IPR013816. ATP_grasp_subdomain_2.
    IPR017440. Cit_synth/succinyl-CoA_lig_AS.
    IPR016143. Citrate_synth-like_sm_a-sub.
    IPR002020. Citrate_synthase-like.
    IPR016141. Citrate_synthase-like_core.
    IPR003781. CoA-bd.
    IPR005810. CoA_lig_alpha.
    IPR005811. CoA_ligase.
    IPR016040. NAD(P)-bd_dom.
    IPR017866. Succ-CoA_synthase_bsu_CS.
    IPR016102. Succinyl-CoA_synth-like.
    [Graphical view]
    PfamiPF08442. ATP-grasp_2. 1 hit.
    PF00285. Citrate_synt. 1 hit.
    PF02629. CoA_binding. 1 hit.
    PF00549. Ligase_CoA. 1 hit.
    [Graphical view]
    PIRSFiPIRSF036511. ATP_citrt_syn. 1 hit.
    SUPFAMiSSF48256. SSF48256. 2 hits.
    SSF52210. SSF52210. 1 hit.
    PROSITEiPS01216. SUCCINYL_COA_LIG_1. 1 hit.
    PS00399. SUCCINYL_COA_LIG_2. 1 hit.
    PS01217. SUCCINYL_COA_LIG_3. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P16638-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MSAKAISEQT GKELLYKYIC TTSAIQNRFK YARVTPDTDW AHLLQDHPWL     50
    LSQSLVVKPD QLIKRRGKLG LVGVNLSLDG VKSWLKPRLG HEATVGKAKG 100
    FLKNFLIEPF VPHSQAEEFY VCIYATREGD YVLFHHEGGV DVGDVDTKAQ 150
    KLLVGVDEKL NAEDIKRHLL VHAPEDKKEI LASFISGLFN FYEDLYFTYL 200
    EINPLVVTKD GVYILDLAAK VDATADYICK VKWGDIEFPP PFGREAYPEE 250
    AYIADLDAKS GASLKLTLLN PKGRIWTMVA GGGASVVYSD TICDLGGVNE 300
    LANYGEYSGA PSEQQTYDYA KTILSLMTRE KHPDGKILII GGSIANFTNV 350
    AATFKGIVRA IRDYQGSLKE HEVTIFVRRG GPNYQEGLRV MGEVGKTTGI 400
    PIHVFGTETH MTAIVGMAWA PAIPNQPPTA AHTANFLLNA SGSTSTPAPS 450
    RTASFSESRA DEVAPAKKAK PAMPQDSVPS PRSLQGKSAT LFSRHTKAIV 500
    WGMQTRAVQG MLDFDYVCSR DEPSVAAMVY PFTGDHKQKF YWGHKEILIP 550
    VFKNMADAMK KHPEVDVLIN FASLRSAYDS TMETMNYAQI RTIAIIAEGI 600
    PEALTRKLIK KADQKGVTII GPATVGGIKP GCFKIGNTGG MLDNILASKL 650
    YRPGSVAYVS RSGGMSNELN NIISRTTDGV YEGVAIGGDR YPGSTFMDHV 700
    LRYQDTPGVK MIVVLGEIGG TEEYKICRGI KEGRLTKPVV CWCIGTCATM 750
    FSSEVQFGHA GACANQASET AVAKNQALKE AGVFVPRSFD ELGEIIQSVY 800
    EDLVAKGAIV PAQEVPPPTV PMDYSWAREL GLIRKPASFM TSICDERGQE 850
    LIYAGMPITE VFKEEMGIGG VLGLLWFQRR LPKYSCQFIE MCLMVTADHG 900
    PAVSGAHNTI ICARAGKDLV SSLTSGLLTI GDRFGGALDA AAKMFSKAFD 950
    SGIIPMEFVN KMKKEGKLIM GIGHRVKSIN NPDMRVQILK DFVKQHFPAT 1000
    PLLDYALEVE KITTSKKPNL ILNVDGFIGV AFVDMLRNCG SFTREEADEY 1050
    VDIGALNGVF VLGRSMGFIG HYLDQKRLKQ GLYRHPWDDI SYVLPEHMSM 1100
    Length:1,100
    Mass (Da):120,636
    Last modified:August 1, 1990 - v1
    Checksum:i2C6BE4BC1F53BDD2
    GO
    Isoform 2 (identifier: P16638-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         419-422: WAPA → LGHRP
         475-484: Missing.

    Show »
    Length:1,091
    Mass (Da):119,704
    Checksum:iCC7A9B9F0C18E62E
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti116 – 1161A → V in AAI00619. (PubMed:15489334)Curated
    Sequence conflicti367 – 3671S → P in AAI00619. (PubMed:15489334)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei419 – 4224WAPA → LGHRP in isoform 2. 1 PublicationVSP_026273
    Alternative sequencei475 – 48410Missing in isoform 2. 1 PublicationVSP_026274

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J05210 mRNA. Translation: AAA74463.1.
    BC100618 mRNA. Translation: AAI00619.1.
    AH011205 Genomic DNA. Translation: AAL34316.1.
    PIRiA35007.
    RefSeqiNP_001104565.1. NM_001111095.1.
    NP_058683.2. NM_016987.2.
    UniGeneiRn.29771.

    Genome annotation databases

    GeneIDi24159.
    KEGGirno:24159.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J05210 mRNA. Translation: AAA74463.1 .
    BC100618 mRNA. Translation: AAI00619.1 .
    AH011205 Genomic DNA. Translation: AAL34316.1 .
    PIRi A35007.
    RefSeqi NP_001104565.1. NM_001111095.1.
    NP_058683.2. NM_016987.2.
    UniGenei Rn.29771.

    3D structure databases

    ProteinModelPortali P16638.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 246351. 2 interactions.
    IntActi P16638. 1 interaction.
    MINTi MINT-4568685.

    Chemistry

    BindingDBi P16638.
    ChEMBLi CHEMBL2745.

    PTM databases

    PhosphoSitei P16638.

    Proteomic databases

    PaxDbi P16638.
    PRIDEi P16638.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 24159.
    KEGGi rno:24159.

    Organism-specific databases

    CTDi 47.
    RGDi 2018. Acly.

    Phylogenomic databases

    eggNOGi COG0372.
    HOGENOMi HOG000151479.
    HOVERGENi HBG003318.
    InParanoidi P16638.
    KOi K01648.
    PhylomeDBi P16638.

    Miscellaneous databases

    NextBioi 602453.
    PROi P16638.

    Gene expression databases

    Genevestigatori P16638.

    Family and domain databases

    Gene3Di 1.10.230.10. 1 hit.
    3.30.470.20. 1 hit.
    3.40.50.261. 2 hits.
    3.40.50.720. 1 hit.
    InterProi IPR014608. ATP-citrate_synthase.
    IPR013650. ATP-grasp_succ-CoA_synth-type.
    IPR013816. ATP_grasp_subdomain_2.
    IPR017440. Cit_synth/succinyl-CoA_lig_AS.
    IPR016143. Citrate_synth-like_sm_a-sub.
    IPR002020. Citrate_synthase-like.
    IPR016141. Citrate_synthase-like_core.
    IPR003781. CoA-bd.
    IPR005810. CoA_lig_alpha.
    IPR005811. CoA_ligase.
    IPR016040. NAD(P)-bd_dom.
    IPR017866. Succ-CoA_synthase_bsu_CS.
    IPR016102. Succinyl-CoA_synth-like.
    [Graphical view ]
    Pfami PF08442. ATP-grasp_2. 1 hit.
    PF00285. Citrate_synt. 1 hit.
    PF02629. CoA_binding. 1 hit.
    PF00549. Ligase_CoA. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF036511. ATP_citrt_syn. 1 hit.
    SUPFAMi SSF48256. SSF48256. 2 hits.
    SSF52210. SSF52210. 1 hit.
    PROSITEi PS01216. SUCCINYL_COA_LIG_1. 1 hit.
    PS00399. SUCCINYL_COA_LIG_2. 1 hit.
    PS01217. SUCCINYL_COA_LIG_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Rat ATP citrate-lyase. Molecular cloning and sequence analysis of a full-length cDNA and mRNA abundance as a function of diet, organ, and age."
      Elshourbagy N.A., Near J.C., Kmetz P.J., Sathe G.M., Southan C., Strickler J.E., Gross M., Young J.F., Wells T.N.C., Groot P.H.E.
      J. Biol. Chem. 265:1430-1435(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
      Tissue: Liver.
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Tissue: Prostate.
    3. "Cloning and identification of exon-intron organization of the rat ATP-citrate lyase gene."
      Moon Y.-A., Kim K.-S., Park S.-W., Kim Y.-S.
      Biochim. Biophys. Acta 1307:280-284(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 250-1100, ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
    4. "Sequence of sites on ATP-citrate lyase and phosphatase inhibitor 2 phosphorylated by multifunctional protein kinase (a glycogen synthase kinase 3 like kinase)."
      Ramakrishna S., D'Angelo G., Benjamin W.B.
      Biochemistry 29:7617-7624(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 418-459, PHOSPHORYLATION AT THR-446 AND SER-450.
    5. "The identification of ATP-citrate lyase as a protein kinase B (Akt) substrate in primary adipocytes."
      Berwick D.C., Hers I., Heesom K.J., Moule S.K., Tavare J.M.
      J. Biol. Chem. 277:33895-33900(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-454.
    6. "Phosphoproteomic analysis of rat liver by high capacity IMAC and LC-MS/MS."
      Moser K., White F.M.
      J. Proteome Res. 5:98-104(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiACLY_RAT
    AccessioniPrimary (citable) accession number: P16638
    Secondary accession number(s): Q497C7, Q8VIQ1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1990
    Last sequence update: August 1, 1990
    Last modified: October 1, 2014
    This is version 138 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3