Reviewed, UniProtKB/Swiss-Prot P16638 (ACLY_RAT)

Names 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

Name:

Acly

Organism

Rattus norvegicus (Rat)

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.
Sequence processing	The displayed sequence is not processed.
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	Cytoplasm.
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.
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

Keywords
Biological process	Lipid synthesis
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Transferase
PTM	Acetylation Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	acetyl-CoA biosynthetic process Ref.1 Non-traceable author statement. Source: RGD cellular carbohydrate metabolic process Inferred from electronic annotation. Source: InterPro lipid biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATP citrate synthase activity Ref.1 Inferred from direct assay. Source: RGD magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW succinate-CoA ligase (ADP-forming) activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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
Amino acid modifications
	Modified residue	86	1	N6-acetyllysine By similarity
	Modified residue	131	1	Phosphotyrosine By similarity
	Modified residue	446	1	Phosphothreonine
	Modified residue	450	1	Phosphoserine
	Modified residue	454	1	Phosphoserine; by PKA Ref.5
	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	681	1	Phosphotyrosine By similarity
	Modified residue	947	1	N6-acetyllysine By similarity
	Modified residue	961	1	N6-acetyllysine By similarity
	Modified residue	967	1	N6-acetyllysine By similarity
	Modified residue	977	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

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 1, 1990. Version 1. Checksum: 2C6BE4BC1F53BDD2	FASTA	1,100	120,636
	10 20 30 40 50 60 MSAKAISEQT GKELLYKYIC TTSAIQNRFK YARVTPDTDW AHLLQDHPWL LSQSLVVKPD 70 80 90 100 110 120 QLIKRRGKLG LVGVNLSLDG VKSWLKPRLG HEATVGKAKG FLKNFLIEPF VPHSQAEEFY 130 140 150 160 170 180 VCIYATREGD YVLFHHEGGV DVGDVDTKAQ KLLVGVDEKL NAEDIKRHLL VHAPEDKKEI 190 200 210 220 230 240 LASFISGLFN FYEDLYFTYL EINPLVVTKD GVYILDLAAK VDATADYICK VKWGDIEFPP 250 260 270 280 290 300 PFGREAYPEE AYIADLDAKS GASLKLTLLN PKGRIWTMVA GGGASVVYSD TICDLGGVNE 310 320 330 340 350 360 LANYGEYSGA PSEQQTYDYA KTILSLMTRE KHPDGKILII GGSIANFTNV AATFKGIVRA 370 380 390 400 410 420 IRDYQGSLKE HEVTIFVRRG GPNYQEGLRV MGEVGKTTGI PIHVFGTETH MTAIVGMAWA 430 440 450 460 470 480 PAIPNQPPTA AHTANFLLNA SGSTSTPAPS RTASFSESRA DEVAPAKKAK PAMPQDSVPS 490 500 510 520 530 540 PRSLQGKSAT LFSRHTKAIV WGMQTRAVQG MLDFDYVCSR DEPSVAAMVY PFTGDHKQKF 550 560 570 580 590 600 YWGHKEILIP VFKNMADAMK KHPEVDVLIN FASLRSAYDS TMETMNYAQI RTIAIIAEGI 610 620 630 640 650 660 PEALTRKLIK KADQKGVTII GPATVGGIKP GCFKIGNTGG MLDNILASKL YRPGSVAYVS 670 680 690 700 710 720 RSGGMSNELN NIISRTTDGV YEGVAIGGDR YPGSTFMDHV LRYQDTPGVK MIVVLGEIGG 730 740 750 760 770 780 TEEYKICRGI KEGRLTKPVV CWCIGTCATM FSSEVQFGHA GACANQASET AVAKNQALKE 790 800 810 820 830 840 AGVFVPRSFD ELGEIIQSVY EDLVAKGAIV PAQEVPPPTV PMDYSWAREL GLIRKPASFM 850 860 870 880 890 900 TSICDERGQE LIYAGMPITE VFKEEMGIGG VLGLLWFQRR LPKYSCQFIE MCLMVTADHG 910 920 930 940 950 960 PAVSGAHNTI ICARAGKDLV SSLTSGLLTI GDRFGGALDA AAKMFSKAFD SGIIPMEFVN 970 980 990 1000 1010 1020 KMKKEGKLIM GIGHRVKSIN NPDMRVQILK DFVKQHFPAT PLLDYALEVE KITTSKKPNL 1030 1040 1050 1060 1070 1080 ILNVDGFIGV AFVDMLRNCG SFTREEADEY VDIGALNGVF VLGRSMGFIG HYLDQKRLKQ 1090 1100 GLYRHPWDDI SYVLPEHMSM
	Isoform 2. Checksum: CC7A9B9F0C18E62E	FASTA	1,091	119,704
	10 20 30 40 50 60 MSAKAISEQT GKELLYKYIC TTSAIQNRFK YARVTPDTDW AHLLQDHPWL LSQSLVVKPD 70 80 90 100 110 120 QLIKRRGKLG LVGVNLSLDG VKSWLKPRLG HEATVGKAKG FLKNFLIEPF VPHSQAEEFY 130 140 150 160 170 180 VCIYATREGD YVLFHHEGGV DVGDVDTKAQ KLLVGVDEKL NAEDIKRHLL VHAPEDKKEI 190 200 210 220 230 240 LASFISGLFN FYEDLYFTYL EINPLVVTKD GVYILDLAAK VDATADYICK VKWGDIEFPP 250 260 270 280 290 300 PFGREAYPEE AYIADLDAKS GASLKLTLLN PKGRIWTMVA GGGASVVYSD TICDLGGVNE 310 320 330 340 350 360 LANYGEYSGA PSEQQTYDYA KTILSLMTRE KHPDGKILII GGSIANFTNV AATFKGIVRA 370 380 390 400 410 420 IRDYQGSLKE HEVTIFVRRG GPNYQEGLRV MGEVGKTTGI PIHVFGTETH MTAIVGMALG 430 440 450 460 470 480 HRPIPNQPPT AAHTANFLLN ASGSTSTPAP SRTASFSESR ADEVAPAKKA KPAMPQGKSA 490 500 510 520 530 540 TLFSRHTKAI VWGMQTRAVQ GMLDFDYVCS RDEPSVAAMV YPFTGDHKQK FYWGHKEILI 550 560 570 580 590 600 PVFKNMADAM KKHPEVDVLI NFASLRSAYD STMETMNYAQ IRTIAIIAEG IPEALTRKLI 610 620 630 640 650 660 KKADQKGVTI IGPATVGGIK PGCFKIGNTG GMLDNILASK LYRPGSVAYV SRSGGMSNEL 670 680 690 700 710 720 NNIISRTTDG VYEGVAIGGD RYPGSTFMDH VLRYQDTPGV KMIVVLGEIG GTEEYKICRG 730 740 750 760 770 780 IKEGRLTKPV VCWCIGTCAT MFSSEVQFGH AGACANQASE TAVAKNQALK EAGVFVPRSF 790 800 810 820 830 840 DELGEIIQSV YEDLVAKGAI VPAQEVPPPT VPMDYSWARE LGLIRKPASF MTSICDERGQ 850 860 870 880 890 900 ELIYAGMPIT EVFKEEMGIG GVLGLLWFQR RLPKYSCQFI EMCLMVTADH GPAVSGAHNT 910 920 930 940 950 960 IICARAGKDL VSSLTSGLLT IGDRFGGALD AAAKMFSKAF DSGIIPMEFV NKMKKEGKLI 970 980 990 1000 1010 1020 MGIGHRVKSI NNPDMRVQIL KDFVKQHFPA TPLLDYALEV EKITTSKKPN LILNVDGFIG 1030 1040 1050 1060 1070 1080 VAFVDMLRNC GSFTREEADE YVDIGALNGV FVLGRSMGFI GHYLDQKRLK QGLYRHPWDD 1090 ISYVLPEHMS M

References

	« Hide 'large scale' referencesShow '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: 2295639] [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: 15489334] [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: 8688462] [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: 2176822] [Abstract] Cited for: PROTEIN SEQUENCE OF 418-459, PHOSPHORYLATION.
[5]	"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: 16396499] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-454, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	J05210 mRNA. Translation: AAA74463.1. BC100618 mRNA. Translation: AAI00619.1. L47319 , L47300, L47301, L47302, L47303, L47304, L47305, L47306, L47307, L47308, L47309, L47310, L47311, L47312, L47313, L47314, L47315, L47316, L47317, L47318, L47320 Genomic DNA. Translation: AAL34316.1.
IPI	IPI00214665. IPI00214801.
PIR	A35007.
RefSeq	NP_001104565.1. NP_058683.2.
UniGene	Rn.29771
3D structure databases
HSSP	HSSP built from PDB template 1SCU based on UniProtKB P07459.
ModBase	Search...
Protein-protein interaction databases
STRING	P16638.
PTM databases
PhosphoSite	P16638.
Proteomic databases
PRIDE	P16638.
Genome annotation databases
Ensembl	ENSRNOT00000023447; ENSRNOP00000023447; ENSRNOG00000016924; Rattus norvegicus. [Genome view] ENSRNOT00000043172; ENSRNOP00000046597; ENSRNOG00000016924; Rattus norvegicus. [Genome view]
GeneID	24159.
KEGG	rno:24159.
UCSC	BC100618. rat. NM_016987. rat.
Organism-specific databases
CTD	24159.
RGD	2018. Acly.
Phylogenomic databases
HOVERGEN	P16638.
Enzyme and pathway databases
BRENDA	2.3.3.8. 248.
Gene expression databases
ArrayExpress	P16638.
Genevestigator	P16638.
GermOnline	ENSRNOG00000016924. Rattus norvegicus.
Family and domain databases
InterPro	IPR014608. ATP-citrate_synthase. IPR013816. ATP_grasp_subdomain_2. IPR017440. Cit_synth/succinyl-CoA_lig_AS. IPR016143. Citrate_synth-like_sm_a-sub. 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]
Gene3D	G3DSA:3.30.470.20. ATP_grasp_subdomain_2. 1 hit. G3DSA:1.10.230.10. Citrate_synthase_sm_a-sub. 1 hit. G3DSA:3.40.50.720. NAD(P)-bd. 1 hit. G3DSA:3.40.50.261. Succinyl-CoA_synth-like. 1 hit.
Pfam	PF02629. CoA_binding. 1 hit. PF00549. Ligase_CoA. 1 hit. [Graphical view]
PIRSF	PIRSF036511. ATP_citrt_syn. 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 Resources
NextBio	602453.

Entry information

Entry name

ACLY_RAT

Accession

Primary (citable) accession number: P16638
Secondary accession number(s): Q497C7, Q8VIQ1

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	August 1, 1990
Last modified:	October 13, 2009
This is version 100 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)