P16638 (ACLY_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified
April 3, 2013.
Version 127.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: ATP-citrate synthase EC=2.3.3.8 Alternative name(s): ATP-citrate (pro-S-)-lyase Citrate cleavage enzyme | ||
| Gene names |
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| Organism | Rattus norvegicus (Rat) [Reference proteome] | ||
| Taxonomic identifier | 10116 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus![]() |
Protein attributes
| Sequence length | 1100 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | 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 activity | ADP + phosphate + acetyl-CoA + oxaloacetate = ATP + citrate + CoA. |
| Enzyme regulation | Major regulation of ATP citrate-lyase activity is probably not by phosphorylation/dephosphorylation but by altering the amount of enzyme. |
| Subunit structure | Homotetramer. |
| Subcellular location | |
| Tissue specificity | Expreesed in the brain, kidney, mammary gland, lung and liver. Ref.3 |
| Post-translational modification | 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. Ref.4 Ref.5 The N-terminus is blocked. ISGylated By similarity. |
| Sequence similarities | In the N-terminal section; belongs to the succinate/malate CoA ligase beta subunit family. In the C-terminal section; belongs to the succinate/malate CoA ligase alpha subunit family. |
Ontologies
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: P16638-1) 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. | ||||||
| Isoform 2 (identifier: P16638-2) The sequence of this isoform differs from the canonical sequence as follows: 419-422: WAPA → LGHRP 475-484: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1100 | 1100 | ATP-citrate synthase | PRO_0000102783 | |||||
Regions | |||||||||
| Nucleotide binding | 700 – 720 | 21 | ATP By similarity | ||||||
| Nucleotide binding | 751 – 777 | 27 | ATP By similarity | ||||||
| Region | 778 – 788 | 11 | CoA-binding Potential | ||||||
Sites | |||||||||
| Active site | 759 | 1 | Tele-phosphohistidine intermediate | ||||||
| Metal binding | 717 | 1 | Magnesium By similarity | ||||||
| Binding site | 346 | 1 | Citrate; via amide nitrogen By similarity | ||||||
| Binding site | 348 | 1 | Citrate By similarity | ||||||
| Binding site | 379 | 1 | Citrate By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 131 | 1 | Phosphotyrosine By similarity | ||||||
| Modified residue | 446 | 1 | Phosphothreonine | ||||||
| Modified residue | 450 | 1 | Phosphoserine | ||||||
| Modified residue | 454 | 1 | Phosphoserine; by PKA and PKB/AKT1 or PKB/AKT2 Ref.5 Ref.6 | ||||||
| Modified residue | 480 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 545 | 1 | N6-acetyllysine By similarity | ||||||
| Modified residue | 553 | 1 | N6-acetyllysine By similarity | ||||||
| Modified residue | 638 | 1 | Phosphothreonine By similarity | ||||||
| Modified residue | 662 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 681 | 1 | Phosphotyrosine By similarity | ||||||
| Modified residue | 838 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 947 | 1 | N6-acetyllysine By similarity | ||||||
| Modified residue | 967 | 1 | N6-acetyllysine By similarity | ||||||
| Modified residue | 1076 | 1 | N6-acetyllysine By similarity | ||||||
| Modified residue | 1099 | 1 | Phosphoserine By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 419 – 422 | 4 | WAPA → LGHRP in isoform 2. | VSP_026273 | |||||
| Alternative sequence | 475 – 484 | 10 | Missing in isoform 2. | VSP_026274 | |||||
Experimental info | |||||||||
| Sequence conflict | 116 | 1 | A → V in AAI00619. Ref.2 | ||||||
| Sequence conflict | 367 | 1 | S → P in AAI00619. Ref.2 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [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. |
| [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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-454, MASS SPECTROMETRY. Strain: Fischer. Tissue: Liver. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | J05210 mRNA. Translation: AAA74463.1. BC100618 mRNA. Translation: AAI00619.1. AH011205 Genomic DNA. Translation: AAL34316.1. |
| IPI | IPI00214665. IPI00214801. |
| PIR | A35007. |
| RefSeq | NP_001104565.1. NM_001111095.1. NP_058683.2. NM_016987.2. |
| UniGene | Rn.29771. |
3D structure databases | |
| ProteinModelPortal | P16638. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | P16638. 1 interaction. |
PTM databases | |
| PhosphoSite | P16638. |
Proteomic databases | |
| PaxDb | P16638. |
| PRIDE | P16638. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| GeneID | 24159. |
| KEGG | rno:24159. |
Organism-specific databases | |
| CTD | 47. |
| RGD | 2018. Acly. |
Phylogenomic databases | |
| eggNOG | COG0372. |
| HOGENOM | HOG000151479. |
| HOVERGEN | HBG003318. |
| InParanoid | P16638. |
| KO | K01648. |
Gene expression databases | |
| ArrayExpress | P16638. |
| Genevestigator | P16638. |
| GermOnline | ENSRNOG00000016924. Rattus norvegicus. |
Family and domain databases | |
| Gene3D | 1.10.230.10. 1 hit. 3.30.470.20. 1 hit. 3.40.50.261. 2 hits. 3.40.50.720. 1 hit. |
| InterPro | 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] |
| Pfam | PF08442. ATP-grasp_2. 1 hit. PF00285. Citrate_synt. 1 hit. PF02629. CoA_binding. 1 hit. PF00549. Ligase_CoA. 1 hit. [Graphical view] |
| PIRSF | PIRSF036511. ATP_citrt_syn. 1 hit. |
| SUPFAM | SSF48256. Citrate_synthase_core. 1 hit. SSF52210. CoA_ligase. 1 hit. |
| PROSITE | PS01216. SUCCINYL_COA_LIG_1. 1 hit. PS00399. SUCCINYL_COA_LIG_2. 1 hit. PS01217. SUCCINYL_COA_LIG_3. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| BindingDB | P16638. |
| ChEMBL | CHEMBL2745. |
| NextBio | 602453. |
Entry information
| Entry name | ACLY_RAT | ||||||||
| Accession | Primary (citable) accession number: P16638 Secondary accession number(s): Q497C7, Q8VIQ1 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
Relevant documents
| SIMILARITY comments Index of protein domains and families |

Clusters with
