Q86V21 (AACS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Acetoacetyl-CoA synthetase
EC=6.2.1.16

Alternative name(s):
Acyl-CoA synthetase family member 1
Protein sur-5 homolog

Gene names

Name:	AACS
Synonyms:	ACSF1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	672 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Activates acetoacetate to acetoacetyl-CoA. May be involved in utilizing ketone body for the fatty acid-synthesis during adipose tissue development By similarity.
Catalytic activity	ATP + acetoacetate + CoA = AMP + diphosphate + acetoacetyl-CoA.
Subcellular location	Cytoplasm › cytosol By similarity.
Tissue specificity	Highly expressed in kidney, heart and brain, but low in liver. Ref.1
Sequence similarities	Belongs to the ATP-dependent AMP-binding enzyme family.
Sequence caution	The sequence AAH41000.1 differs from that shown. Reason: Frameshift at position 201. The sequence BAB14793.1 differs from that shown. Reason: Frameshift at position 519.

Ontologies

Keywords
Biological process	Fatty acid metabolism Lipid metabolism
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adipose tissue development Inferred from electronic annotation. Source: Compara cellular response to cholesterol Inferred from electronic annotation. Source: Compara cellular response to glucose stimulus Inferred from electronic annotation. Source: Compara cellular response to testosterone stimulus Inferred from electronic annotation. Source: Compara fatty acid metabolic process Inferred from electronic annotation. Source: UniProtKB-KW liver development Inferred from electronic annotation. Source: Compara positive regulation of insulin secretion Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to ethanol Inferred from electronic annotation. Source: Compara response to nutrient Inferred from electronic annotation. Source: Compara response to oleic acid Inferred from electronic annotation. Source: Compara response to purine-containing compound Inferred from electronic annotation. Source: Compara response to starvation Inferred from electronic annotation. Source: Compara white fat cell differentiation Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW acetoacetate-CoA ligase activity Inferred from electronic annotation. Source: EC butyrate-CoA ligase activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q86V21-1)

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: Q86V21-2)

The sequence of this isoform differs from the canonical sequence as follows:
     561-672: ESFEEVEDSL...YRDIPELQGF → YAQRQESGSC...RDPGSVPGHP

Note: No experimental confirmation available.

Isoform 3 (identifier: Q86V21-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-402: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 672	672	Acetoacetyl-CoA synthetase		PRO_0000315784
Amino acid modifications
	Modified residue	524	1	Phosphotyrosine By similarity
Natural variations
	Alternative sequence	1 – 402	402	Missing in isoform 3.		VSP_030701
	Alternative sequence	561 – 672	112	ESFEE…ELQGF → YAQRQESGSCRQTDHRWKSR GARRCFLEPRDPGSVPGHP in isoform 2.		VSP_030702
	Natural variant	118	1	I → V. Ref.4 Corresponds to variant rs12831803 [ dbSNP | Ensembl ].		VAR_038303
	Natural variant	470	1	A → V. Corresponds to variant rs59883951 [ dbSNP | Ensembl ].		VAR_060997
Experimental info
	Sequence conflict	70	1	G → E in BAB14793. Ref.2
	Sequence conflict	119	1	A → V in BAB14040. Ref.2
	Sequence conflict	128	1	K → E in BAB14793. Ref.2
	Sequence conflict	137	1	E → G in BAB14040. Ref.2
	Sequence conflict	150	1	V → A in BAB14040. Ref.2
	Sequence conflict	391	1	K → E in AAH41000. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2003. Version 1. Checksum: 36006739EE4857D9	FASTA	672	75,144
	10 20 30 40 50 60 MSKEERPGRE EILECQVMWE PDSKKNTQMD RFRAAVGAAC GLALESYDDL YHWSVESYSD 70 80 90 100 110 120 FWAEFWKFSG IVFSRVYDEV VDTSKGIADV PEWFKGSRLN YAENLLRHKE NDRVALYIAR 130 140 150 160 170 180 EGKEEIVKVT FEELRQEVAL FAAAMRKMGV KKGDRVVGYL PNSEHAVEAM LAAASIGAIW 190 200 210 220 230 240 SSTSPDFGVN GVLDRFSQIQ PKLIFSVEAV VYNGKEHNHM EKLQQVVKGL PDLKKVVVIP 250 260 270 280 290 300 YVSSRENIDL SKIPNSVFLD DFLATGTSEQ APQLEFEQLP FSHPLFIMFS SGTTGAPKCM 310 320 330 340 350 360 VHSAGGTLIQ HLKEHLLHGN MTSSDILLCY TTVGWMMWNW MVSLLATGAA MVLYDGSPLV 370 380 390 400 410 420 PTPNVLWDLV DRIGITVLVT GAKWLSVLEE KAMKPVETHS LQMLHTILST GSPLKAQSYE 430 440 450 460 470 480 YVYRCIKSSI LLGSISGGTD IISCFMGHNF SLPVYKGEIQ ARNLGMAVEA WNEEGKAVWG 490 500 510 520 530 540 ESGELVCTKP IPCQPTHFWN DENGNKYRKA YFSKFPGIWA HGDYCRINPK TGGIVMLGRS 550 560 570 580 590 600 DGTLNPNGVR FGSSEIYNIV ESFEEVEDSL CVPQYNKYRE ERVILFLKMA SGHAFQPDLV 610 620 630 640 650 660 KRIRDAIRMG LSARHVPSLI LETKGIPYTL NGKKVEVAVK QIIAGKAVEQ GGAFSNPETL 670 DLYRDIPELQ GF
	Isoform 2 [UniParc]. Checksum: 1C454CA0635CB5C5	FASTA	599	67,035
	10 20 30 40 50 60 MSKEERPGRE EILECQVMWE PDSKKNTQMD RFRAAVGAAC GLALESYDDL YHWSVESYSD 70 80 90 100 110 120 FWAEFWKFSG IVFSRVYDEV VDTSKGIADV PEWFKGSRLN YAENLLRHKE NDRVALYIAR 130 140 150 160 170 180 EGKEEIVKVT FEELRQEVAL FAAAMRKMGV KKGDRVVGYL PNSEHAVEAM LAAASIGAIW 190 200 210 220 230 240 SSTSPDFGVN GVLDRFSQIQ PKLIFSVEAV VYNGKEHNHM EKLQQVVKGL PDLKKVVVIP 250 260 270 280 290 300 YVSSRENIDL SKIPNSVFLD DFLATGTSEQ APQLEFEQLP FSHPLFIMFS SGTTGAPKCM 310 320 330 340 350 360 VHSAGGTLIQ HLKEHLLHGN MTSSDILLCY TTVGWMMWNW MVSLLATGAA MVLYDGSPLV 370 380 390 400 410 420 PTPNVLWDLV DRIGITVLVT GAKWLSVLEE KAMKPVETHS LQMLHTILST GSPLKAQSYE 430 440 450 460 470 480 YVYRCIKSSI LLGSISGGTD IISCFMGHNF SLPVYKGEIQ ARNLGMAVEA WNEEGKAVWG 490 500 510 520 530 540 ESGELVCTKP IPCQPTHFWN DENGNKYRKA YFSKFPGIWA HGDYCRINPK TGGIVMLGRS 550 560 570 580 590 DGTLNPNGVR FGSSEIYNIV YAQRQESGSC RQTDHRWKSR GARRCFLEPR DPGSVPGHP
	Isoform 3 [UniParc]. Checksum: 930E1C6E82B5061D	FASTA	270	30,061
	10 20 30 40 50 60 MLHTILSTGS PLKAQSYEYV YRCIKSSILL GSISGGTDII SCFMGHNFSL PVYKGEIQAR 70 80 90 100 110 120 NLGMAVEAWN EEGKAVWGES GELVCTKPIP CQPTHFWNDE NGNKYRKAYF SKFPGIWAHG 130 140 150 160 170 180 DYCRINPKTG GIVMLGRSDG TLNPNGVRFG SSEIYNIVES FEEVEDSLCV PQYNKYREER 190 200 210 220 230 240 VILFLKMASG HAFQPDLVKR IRDAIRMGLS ARHVPSLILE TKGIPYTLNG KKVEVAVKQI 250 260 270 IAGKAVEQGG AFSNPETLDL YRDIPELQGF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Expression of acetoacetyl-CoA synthetase, a novel cytosolic ketone body-utilizing enzyme, in human brain." Ohgami M., Takahashi N., Yamasaki M., Fukui T. Biochem. Pharmacol. 65:989-994(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Mammary gland and Retinoblastoma.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] (ISOFORMS 1; 2 AND 3), VARIANT VAL-118. Tissue: Brain, Kidney and Testis.
[5]	"Caenorhabditis elegans SUR-5, a novel but conserved protein, negatively regulates LET-60 Ras activity during vulval induction." Gu T., Orita S., Han M. Mol. Cell. Biol. 18:4556-4564(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 12-672 (ISOFORM 1).
[6]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 48-672 (ISOFORM 1). Tissue: Stomach.
[7]	"Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human genome." Watkins P.A., Maiguel D., Jia Z., Pevsner J. J. Lipid Res. 48:2736-2750(2007) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION.
[8]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB054121 mRNA. Translation: BAD22560.1. AK022451 mRNA. Translation: BAB14040.1. AK024036 mRNA. Translation: BAB14793.1. Frameshift. CH471054 Genomic DNA. Translation: EAW98474.1. BC004997 mRNA. Translation: AAH04997.1. BC040490 mRNA. Translation: AAH40490.2. BC040574 mRNA. Translation: AAH40574.1. BC041000 mRNA. Translation: AAH41000.1. Frameshift. BC051862 mRNA. Translation: AAH51862.1. AY091468 mRNA. Translation: AAM44124.1. AL833047 mRNA. Translation: CAH56309.1.
IPI	IPI00217272. IPI00646775. IPI00789348.
RefSeq	NP_076417.2. NM_023928.3.
UniGene	Hs.656073.
3D structure databases
ProteinModelPortal	Q86V21.
ModBase	Search...
PTM databases
PhosphoSite	Q86V21.
Polymorphism databases
DMDM	74750446.
Proteomic databases
PaxDb	Q86V21.
PRIDE	Q86V21.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000261686; ENSP00000261686; ENSG00000081760. ENST00000316519; ENSP00000324842; ENSG00000081760. ENST00000316543; ENSP00000324929; ENSG00000081760.
GeneID	65985.
KEGG	hsa:65985.
UCSC	uc001uhc.3. human. uc001uhd.3. human. uc009zyi.3. human.
Organism-specific databases
CTD	65985.
GeneCards	GC12P125549.
H-InvDB	HIX0022598.
HGNC	HGNC:21298. AACS.
HPA	HPA039811.
MIM	614364. gene.
neXtProt	NX_Q86V21.
PharmGKB	PA134940696.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0365.
HOVERGEN	HBG059947.
InParanoid	Q86V21.
KO	K01907.
OMA	GNMTSSD.
OrthoDB	EOG4HQDHT.
Enzyme and pathway databases
BRENDA	6.2.1.16. 2681.
Gene expression databases
ArrayExpress	Q86V21.
Bgee	Q86V21.
CleanEx	HS_AACS.
Genevestigator	Q86V21.
Family and domain databases
InterPro	IPR005914. Acac_CoA_synth. IPR024597. Acyl-CoA_synth_DUF3448. IPR020845. AMP-binding_CS. IPR000873. AMP-dep_Synth/Lig. [Graphical view]
Pfam	PF00501. AMP-binding. 1 hit. PF11930. DUF3448. 1 hit. [Graphical view]
TIGRFAMs	TIGR01217. ac_ac_CoA_syn. 1 hit.
PROSITE	PS00455. AMP_BINDING. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	AACS. human.
GenomeRNAi	65985.
NextBio	67451.
SOURCE	Search...

Entry information

Entry name

AACS_HUMAN

Accession

Primary (citable) accession number: Q86V21
Secondary accession number(s): Q49AB9 , Q49AC3, Q658Q8, Q8IWD2, Q8NEW5, Q9BSJ9, Q9H829, Q9HA19

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 15, 2008
Last sequence update:	June 1, 2003
Last modified:	May 1, 2013
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.