O95573 (ACSL3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [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	720 AA.
Sequence status	Complete.
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). Ref.4
Catalytic activity	ATP + a long-chain fatty 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 Transmembrane helix
Ligand	ATP-binding Magnesium Nucleotide-binding
Molecular function	Ligase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	brain development Inferred from electronic annotation. Source: Compara fatty acid biosynthetic process Inferred from electronic annotation. Source: Compara long-chain fatty acid import Inferred from direct assay PubMed 20219900. Source: UniProtKB long-chain fatty-acyl-CoA biosynthetic process Traceable author statement. Source: Reactome positive regulation of Golgi to plasma membrane protein transport Inferred from mutant phenotype PubMed 20605918. Source: UniProtKB positive regulation of phosphatidylcholine biosynthetic process Inferred from mutant phenotype Ref.4. Source: UniProtKB positive regulation of secretion Inferred from mutant phenotype Ref.4. Source: UniProtKB response to nutrient Inferred from electronic annotation. Source: Compara response to organic cyclic compound Inferred from electronic annotation. Source: Compara triglyceride biosynthetic process Traceable author statement. Source: Reactome very-low-density lipoprotein particle assembly Inferred from mutant phenotype Ref.4. Source: UniProtKB
Cellular_component	Golgi apparatus Inferred from direct assay PubMed 20605918. Source: UniProtKB endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW lipid particle Inferred from direct assay PubMed 14741744. Source: UniProtKB mitochondrial outer membrane Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from direct assay PubMed 14741744PubMed 20605918. Source: UniProtKB peroxisomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW long-chain fatty acid-CoA ligase activity Inferred from mutant phenotype PubMed 20219900. Source: UniProtKB
Complete GO annotation...

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	Helical; Signal-anchor for type III membrane protein; Potential
	Topological domain	42 – 720	679	Cytoplasmic Potential
Amino acid modifications
	Modified residue	683	1	Phosphoserine Ref.5
Natural variations
	Natural variant	551	1	F → S. Ref.1 Ref.2 Corresponds to variant rs1046032 [ dbSNP | Ensembl ].		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 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas.
[4]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION.
[5]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-683, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[6]	"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	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. NM_004457.3. NP_976251.1. NM_203372.1.
UniGene	Hs.655772.
3D structure databases
ProteinModelPortal	O95573.
ModBase	Search...
Protein-protein interaction databases
IntAct	O95573. 6 interactions.
STRING	9606.ENSP00000350012.
PTM databases
PhosphoSite	O95573.
Proteomic databases
PaxDb	O95573.
PeptideAtlas	O95573.
PRIDE	O95573.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000357430; ENSP00000350012; ENSG00000123983. ENST00000392066; ENSP00000375918; ENSG00000123983.
GeneID	2181.
KEGG	hsa:2181.
UCSC	uc002vni.3. human.
Organism-specific databases
CTD	2181.
GeneCards	GC02P223725.
HGNC	HGNC:3570. ACSL3.
HPA	HPA011315.
MIM	602371. gene.
neXtProt	NX_O95573.
PharmGKB	PA27967.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1022.
HOGENOM	HOG000159459.
HOVERGEN	HBG106947.
InParanoid	O95573.
KO	K01897.
OMA	NQIKAKP.
OrthoDB	EOG4Z8XVW.
PhylomeDB	O95573.
Enzyme and pathway databases
BRENDA	6.2.1.3. 2681.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	O95573.
Bgee	O95573.
CleanEx	HS_ACSL3.
Genevestigator	O95573.
GermOnline	ENSG00000123983. Homo sapiens.
Family and domain databases
InterPro	IPR020845. AMP-binding_CS. 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
DrugBank	DB00159. Icosapent.
GenomeRNAi	2181.
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:	April 3, 2013
This is version 117 of the entry and version 3 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.