Reviewed, UniProtKB/Swiss-Prot Q99NB1 (ACS2L_MOUSE)

Names and origin

Protein names

Recommended name:
    Acetyl-coenzyme A synthetase 2-like, mitochondrial
    EC=6.2.1.1
Alternative name(s):
    Acetate--CoA ligase 2
    Acetyl-CoA synthetase 2
      Short name=AceCS2
    Acyl-CoA synthetase short-chain family member 1

Gene names

Name:	Acss1
Synonyms:	Acas2, Acas2l

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	682 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Important for maintaining normal body temperature during fasting and for energy homeostasis. Essential for energy expenditure under ketogenic conditions. Converts acetate to acetyl-CoA so that it can be used for oxidation through the tricarboxylic cycle to produce ATP and CO2. Ref.1 Ref.4 Ref.5
Catalytic activity	ATP + acetate + CoA = AMP + diphosphate + acetyl-CoA.
Enzyme regulation	Inhibited by acetylation at Lys-635 and activated by deacetylation. Ref.4
Subunit structure	Interacts with SIRT3. Ref.4
Subcellular location	Mitochondrion matrix Ref.1.
Tissue specificity	Highly expressed in heart, testis, kidney, skeletal muscle, lung and spleen. Detected at low levels in brain.
Induction	By fasting. Ref.4
Post-translational modification	Reversibly acetylated at Lys-635. The acetyl-CoA synthase activity is inhibited by acetylation and activated by deacetylation.
Disruption phenotype	No visible phenotype at birth, but exhibit significant growth retardation at the time of weaning. Attain normal size and weight when fed normally. Exhibit hypothermia and hypoglycemia when fed high-fat, low-carbohydrate diet, leading to 50% mortality. Display strongly reduced whole-body acetate oxidation when fasting. Fasting adults exhibit hypothermia, reduced capacity to sustain running and low ATP levels. Ref.5
Sequence similarities	Belongs to the ATP-dependent AMP-binding enzyme family.

Ontologies

Keywords
Cellular component	Mitochondrion
Domain	Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Acetylation
Gene Ontology (GO)
Biological process	acetyl-CoA biosynthetic process Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	mitochondrial matrix Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	AMP binding Inferred from electronic annotation. Source: InterPro ATP binding Inferred from electronic annotation. Source: UniProtKB-KW acetate-CoA ligase activity Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 38	38	Mitochondrion Potential
	Chain	39 – 682	644	Acetyl-coenzyme A synthetase 2-like, mitochondrial		PRO_0000000597
Amino acid modifications
	Modified residue	389	1	N6-acetyllysine By similarity
	Modified residue	635	1	N6-acetyllysine Ref.4
Experimental info
	Sequence conflict	332	1	W → C in AAH30930. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q99NB1-1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 1B21981D29F9C8E7	FASTA	682	74,623
	10 20 30 40 50 60 MAARSLGSGV GRLLRGLQGR SGQSGWSLSV SRSTATRLPG CVPAAAQPGS YPALSAQAAQ 70 80 90 100 110 120 EPAAFWGPLA RDTLVWDTPY HTVWDCDFRT GKIGWFLGGQ LNVSVNCLDQ HVQKSPETIA 130 140 150 160 170 180 LIWERDEPGT EVRITYRELL ETTCRLANTL KRHGVHRGDR VAIYMPVSPL AVAAMLACAR 190 200 210 220 230 240 IGAIHTVVFA GFSAESLAGR INDAKCKAVI TFNQGLRGGR VVELKKIVDE AVKSCPTVQH 250 260 270 280 290 300 VLVAHRTDTK VPMGSLDIPL EQEMAKEAPV CTPESMSSED MLFMLYTSGS TGTPKGLVHT 310 320 330 340 350 360 QAGYLLYAAM THKLVFDYQP GDVFGCVADI GWITGHSYVV YGPLCNGATT VLFESTPVYP 370 380 390 400 410 420 DAGRYWETVQ RLKINQFYGA PTAVRLLLKY GDAWVKKYDR SSLRTLGSVG EPINHEAWEW 430 440 450 460 470 480 LHKVVGDGRC TLVDTWWQTE TGGICIAPRP SEDGAEILPG MAMRPFFGIV PVLMDEKGNV 490 500 510 520 530 540 LEGGDVSGAL CISQAWPGMA RTIYGDHQRF VDAYFRAYPG YYFTGDGAHR TEGGYYQITG 550 560 570 580 590 600 RMDDVINISG HRLGTAEIED AMADHPAVPE TAVIGYPHDI KGEAAFAFIV LKDNISDENM 610 620 630 640 650 660 VVNELKLSVA TKIAKYAVPD QILVVKRLPK TRSGKVMRRL LRKIITSRGQ DLGDTTTLED 670 680 PSVITEILSA FQKYEEQRAA TN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Acetyl-CoA synthetase 2, a mitochondrial matrix enzyme involved in the oxidation of acetate." Fujino T., Kondo J., Ishikawa M., Morikawa K., Yamamoto T.T. J. Biol. Chem. 276:11420-11426(2001) [PubMed: 11150295] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: NOD. Tissue: Thymus.
[3]	"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] OF 262-682. Tissue: Salivary gland.
[4]	"Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases." Hallows W.C., Lee S., Denu J.M. Proc. Natl. Acad. Sci. U.S.A. 103:10230-10235(2006) [PubMed: 16790548] [Abstract] Cited for: FUNCTION, INTERACTION WITH SIRT3, ENZYME REGULATION, MASS SPECTROMETRY, ACETYLATION AT LYS-635.
[5]	"Fasting-induced hypothermia and reduced energy production in mice lacking acetyl-CoA synthetase 2." Sakakibara I., Fujino T., Ishii M., Tanaka T., Shimosawa T., Miura S., Zhang W., Tokutake Y., Yamamoto J., Awano M., Iwasaki S., Motoike T., Okamura M., Inagaki T., Kita K., Ezaki O., Naito M., Kuwaki T. , Chohnan S., Yamamoto T.T., Hammer R.E., Kodama T., Yanagisawa M., Sakai J. Cell Metab. 9:191-202(2009) [PubMed: 19187775] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB046742 mRNA. Translation: BAB21612.1. AK088244 mRNA. Translation: BAC40232.1. BC030930 mRNA. Translation: AAH30930.1. Different initiation.
IPI	IPI00469942.
RefSeq	NP_542142.1.
UniGene	Mm.7044
3D structure databases
SMR	Q99NB1. Positions 46-670.
ModBase	Search...
Protein-protein interaction databases
STRING	Q99NB1.
PTM databases
PhosphoSite	Q99NB1.
Proteomic databases
PRIDE	Q99NB1.
Genome annotation databases
Ensembl	ENSMUST00000028944; ENSMUSP00000028944; ENSMUSG00000027452; Mus musculus. [Genome view]
GeneID	68738.
KEGG	mmu:68738.
UCSC	uc008muf.1. mouse.
Organism-specific databases
CTD	68738.
MGI	MGI:1915988. Acss1.
Phylogenomic databases
HOVERGEN	Q99NB1.
InParanoid	Q99NB1.
OMA	VNCLDQH.
OrthoDB	EOG94XN25.
PhylomeDB	Q99NB1.
Enzyme and pathway databases
BRENDA	6.2.1.1. 244.
Pathway_Interaction_DB	hdac_classiii_pathway. Signaling events mediated by HDAC Class III.
Gene expression databases
ArrayExpress	Q99NB1.
Bgee	Q99NB1.
CleanEx	MM_ACSS1.
Genevestigator	Q99NB1.
GermOnline	ENSMUSG00000027452. Mus musculus.
Family and domain databases
InterPro	IPR011904. Ac_CoA_lig_AcsA. IPR020845. AMP-binding_CS. IPR000873. AMP-dep_Synth/Lig. [Graphical view]
Pfam	PF00501. AMP-binding. 1 hit. [Graphical view]
TIGRFAMs	TIGR02188. Ac_CoA_lig_AcsA. 1 hit.
PROSITE	PS00455. AMP_BINDING. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	327818.
SOURCE	Search...

Entry information

Entry name

ACS2L_MOUSE

Accession

Primary (citable) accession number: Q99NB1
Secondary accession number(s): Q8K0M6

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 23, 2003
Last sequence update:	June 1, 2001
Last modified:	February 9, 2010
This is version 68 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)