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P16638

- ACLY_RAT

UniProt

P16638 - ACLY_RAT

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Protein

ATP-citrate synthase

Gene

Acly

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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

Phosphorylation results in a 6-fold increase in V(max) and the conversion of citrate dependence from sigmoidal to hyperbolic. Fructose 6-phosphate (F6P) is also a potent activator.By similarity

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
Complete GO annotation...

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-KW
Complete GO annotation...

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

        10         20         30         40         50
MSAKAISEQT GKELLYKYIC TTSAIQNRFK YARVTPDTDW AHLLQDHPWL
60 70 80 90 100
LSQSLVVKPD QLIKRRGKLG LVGVNLSLDG VKSWLKPRLG HEATVGKAKG
110 120 130 140 150
FLKNFLIEPF VPHSQAEEFY VCIYATREGD YVLFHHEGGV DVGDVDTKAQ
160 170 180 190 200
KLLVGVDEKL NAEDIKRHLL VHAPEDKKEI LASFISGLFN FYEDLYFTYL
210 220 230 240 250
EINPLVVTKD GVYILDLAAK VDATADYICK VKWGDIEFPP PFGREAYPEE
260 270 280 290 300
AYIADLDAKS GASLKLTLLN PKGRIWTMVA GGGASVVYSD TICDLGGVNE
310 320 330 340 350
LANYGEYSGA PSEQQTYDYA KTILSLMTRE KHPDGKILII GGSIANFTNV
360 370 380 390 400
AATFKGIVRA IRDYQGSLKE HEVTIFVRRG GPNYQEGLRV MGEVGKTTGI
410 420 430 440 450
PIHVFGTETH MTAIVGMAWA PAIPNQPPTA AHTANFLLNA SGSTSTPAPS
460 470 480 490 500
RTASFSESRA DEVAPAKKAK PAMPQDSVPS PRSLQGKSAT LFSRHTKAIV
510 520 530 540 550
WGMQTRAVQG MLDFDYVCSR DEPSVAAMVY PFTGDHKQKF YWGHKEILIP
560 570 580 590 600
VFKNMADAMK KHPEVDVLIN FASLRSAYDS TMETMNYAQI RTIAIIAEGI
610 620 630 640 650
PEALTRKLIK KADQKGVTII GPATVGGIKP GCFKIGNTGG MLDNILASKL
660 670 680 690 700
YRPGSVAYVS RSGGMSNELN NIISRTTDGV YEGVAIGGDR YPGSTFMDHV
710 720 730 740 750
LRYQDTPGVK MIVVLGEIGG TEEYKICRGI KEGRLTKPVV CWCIGTCATM
760 770 780 790 800
FSSEVQFGHA GACANQASET AVAKNQALKE AGVFVPRSFD ELGEIIQSVY
810 820 830 840 850
EDLVAKGAIV PAQEVPPPTV PMDYSWAREL GLIRKPASFM TSICDERGQE
860 870 880 890 900
LIYAGMPITE VFKEEMGIGG VLGLLWFQRR LPKYSCQFIE MCLMVTADHG
910 920 930 940 950
PAVSGAHNTI ICARAGKDLV SSLTSGLLTI GDRFGGALDA AAKMFSKAFD
960 970 980 990 1000
SGIIPMEFVN KMKKEGKLIM GIGHRVKSIN NPDMRVQILK DFVKQHFPAT
1010 1020 1030 1040 1050
PLLDYALEVE KITTSKKPNL ILNVDGFIGV AFVDMLRNCG SFTREEADEY
1060 1070 1080 1090 1100
VDIGALNGVF VLGRSMGFIG HYLDQKRLKQ GLYRHPWDDI SYVLPEHMSM
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

« Hide 'large scale' publications
  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 29, 2014
This is version 139 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