Reviewed, UniProtKB/Swiss-Prot O95573 (ACSL3_HUMAN)

Names and origin

Protein names

Recommended name:
    Long-chain-fatty-acid--CoA ligase 3
    EC=6.2.1.3
Alternative name(s):
    Long-chain acyl-CoA synthetase 3
      Short name=LACS 3

Gene names

Name:	ACSL3
Synonyms:	ACS3, FACL3, LACS3

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	720 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Acyl-CoA synthetases (ACSL) activates long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation. ACSL3 mediates hepatic lipogenesis By similarity. Preferentially uses myristate, laurate, arachidonate and eicosapentaenoate as substrates By similarity. Has mainly an anabolic role in energy metabolism. Required for the incorporation of fatty acids into phosphatidylcholine, the major phospholipid located on the surface of VLDL (very low density lipoproteins).
Catalytic activity	ATP + a long-chain carboxylic acid + CoA = AMP + diphosphate + an acyl-CoA.
Cofactor	Magnesium By similarity.
Subcellular location	Mitochondrion outer membrane; Single-pass type III membrane protein By similarity. Peroxisome membrane; Single-pass type III membrane protein By similarity. Microsome membrane; Single-pass type III membrane protein By similarity. Endoplasmic reticulum membrane; Single-pass type III membrane protein By similarity.
Sequence similarities	Belongs to the ATP-dependent AMP-binding enzyme family.

Ontologies

Keywords
Biological process	Fatty acid metabolism Lipid metabolism
Cellular component	Endoplasmic reticulum Membrane Microsome Mitochondrion Mitochondrion outer membrane Peroxisome
Coding sequence diversity	Polymorphism
Domain	Signal-anchor Transmembrane
Ligand	ATP-binding Magnesium Nucleotide-binding
Molecular function	Ligase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	fatty acid metabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell microsome Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial outer membrane Inferred from electronic annotation. Source: UniProtKB-KW peroxisome Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW fatty-acyl-CoA synthase activity Traceable author statement. Source: ProtInc long-chain-fatty-acid-CoA ligase activity Inferred from electronic annotation. Source: EC magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NDRG1	Q92597	1	EBI-1190822,EBI-716486

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 720	720	Long-chain-fatty-acid--CoA ligase 3		PRO_0000193107
Regions
	Transmembrane	21 – 41	21	Signal-anchor for type III membrane protein Potential
	Topological domain	42 – 720	679	Cytoplasmic Potential
Amino acid modifications
	Modified residue	593	1	Phosphoserine Ref.4
	Modified residue	683	1	Phosphoserine Ref.6
	Modified residue	688	1	Phosphothreonine Ref.6
Natural variations
	Natural variant	551	1	F → S: dbSNP rs1046032. Ref.1 Ref.2		VAR_026716
Experimental info
	Sequence conflict	246	1	E → D in BAA37142. Ref.1
	Sequence conflict	246	1	E → D in BAB72074. Ref.2
	Sequence conflict	246	1	E → D in BAB72139. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O95573-1 [UniParc]. Last modified October 3, 2006. Version 3. Checksum: AAC4B0B4543EC8DD	FASTA	720	80,420
	10 20 30 40 50 60 MNNHVSSKPS TMKLKHTINP ILLYFIHFLI SLYTILTYIP FYFFSESRQE KSNRIKAKPV 70 80 90 100 110 120 NSKPDSAYRS VNSLDGLASV LYPGCDTLDK VFTYAKNKFK NKRLLGTREV LNEEDEVQPN 130 140 150 160 170 180 GKIFKKVILG QYNWLSYEDV FVRAFNFGNG LQMLGQKPKT NIAIFCETRA EWMIAAQACF 190 200 210 220 230 240 MYNFQLVTLY ATLGGPAIVH ALNETEVTNI ITSKELLQTK LKDIVSLVPR LRHIITVDGK 250 260 270 280 290 300 PPTWSEFPKG IIVHTMAAVE ALGAKASMEN QPHSKPLPSD IAVIMYTSGS TGLPKGVMIS 310 320 330 340 350 360 HSNIIAGITG MAERIPELGE EDVYIGYLPL AHVLELSAEL VCLSHGCRIG YSSPQTLADQ 370 380 390 400 410 420 SSKIKKGSKG DTSMLKPTLM AAVPEIMDRI YKNVMNKVSE MSSFQRNLFI LAYNYKMEQI 430 440 450 460 470 480 SKGRNTPLCD SFVFRKVRSL LGGNIRLLLC GGAPLSATTQ RFMNICFCCP VGQGYGLTES 490 500 510 520 530 540 AGAGTISEVW DYNTGRVGAP LVCCEIKLKN WEEGGYFNTD KPHPRGEILI GGQSVTMGYY 550 560 570 580 590 600 KNEAKTKADF FEDENGQRWL CTGDIGEFEP DGCLKIIDRK KDLVKLQAGE YVSLGKVEAA 610 620 630 640 650 660 LKNLPLVDNI CAYANSYHSY VIGFVVPNQK ELTELARKKG LKGTWEELCN SCEMENEVLK 670 680 690 700 710 720 VLSEAAISAS LEKFEIPVKI RLSPEPWTPE TGLVTDAFKL KRKELKTHYQ ADIERMYGRK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human acyl-coenzyme A synthetase 3 cDNA and localization of its gene (ACS3) to chromosome band 2q34-q35." Minekura H., Fujino T., Kang M.-J., Fujita T., Endo Y., Yamamoto T.T. Genomics 42:180-181(1997) [PubMed: 9177793] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-551. Tissue: Placenta.
[2]	"Genomic organization and transcription units of the human acyl-CoA synthetase 3 gene." Minekura H., Kang M.-J., Inagaki Y., Suzuki H., Sato H., Fujino T., Yamamoto T.T. Gene 278:185-192(2001) [PubMed: 11707336] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT SER-551.
[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]. Tissue: Pancreas.
[4]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-593, MASS SPECTROMETRY. Tissue: Epithelium.
[5]	"Long chain acyl-CoA synthetase 3-mediated phosphatidylcholine synthesis is required for assembly of very low density lipoproteins in human hepatoma Huh7 cells." Yao H., Ye J. J. Biol. Chem. 283:849-854(2008) [PubMed: 18003621] [Abstract] Cited for: FUNCTION.
[6]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-683 AND THR-688, MASS SPECTROMETRY.
[7]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	D89053 mRNA. Translation: BAA37142.1. AB061712 mRNA. Translation: BAB72074.1. AB061436 Genomic DNA. Translation: BAB72139.1. BC041692 mRNA. Translation: AAH41692.1.
IPI	IPI00031397.
RefSeq	NP_004448.2. NP_976251.1.
UniGene	Hs.655772
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	O95573. 1 interaction.
STRING	O95573.
PTM databases
PhosphoSite	O95573.
Proteomic databases
PeptideAtlas	O95573.
PRIDE	O95573.
Genome annotation databases
Ensembl	ENST00000357430; ENSP00000350012; ENSG00000123983; Homo sapiens. [Genome view] ENST00000392066; ENSP00000375918; ENSG00000123983; Homo sapiens. [Genome view] ENST00000407441; ENSP00000385157; ENSG00000123983; Homo sapiens. [Genome view] ENST00000413316; ENSP00000416913; ENSG00000123983; Homo sapiens. [Genome view] ENST00000421680; ENSP00000404182; ENSG00000123983; Homo sapiens. [Genome view]
GeneID	2181.
KEGG	hsa:2181.
UCSC	uc002vni.1. human.
Organism-specific databases
CTD	2181.
GeneCards	GC02P223433.
HGNC	HGNC:3570. ACSL3.
HPA	HPA011315.
MIM	602371. gene.
PharmGKB	PA27967.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O95573.
HOVERGEN	O95573.
OMA	NKFKDKR.
Enzyme and pathway databases
BRENDA	6.2.1.3. 247.
Gene expression databases
ArrayExpress	O95573.
Bgee	O95573.
CleanEx	HS_ACSL3.
Genevestigator	O95573.
GermOnline	ENSG00000123983. Homo sapiens.
Family and domain databases
InterPro	IPR000873. AMP-dep_Synth/Lig. [Graphical view]
Pfam	PF00501. AMP-binding. 1 hit. [Graphical view]
PROSITE	PS00455. AMP_BINDING. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00159. Icosapent.
NextBio	8805.
SOURCE	Search...

Entry information

Entry name

ACSL3_HUMAN

Accession

Primary (citable) accession number: O95573
Secondary accession number(s): Q60I92, Q8IUM9

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	October 3, 2006
Last modified:	November 3, 2009
This is version 86 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.