Reviewed, UniProtKB/Swiss-Prot P33121 (ACSL1_HUMAN)

Names and origin

Protein names

Recommended name:
    Long-chain-fatty-acid--CoA ligase 1
    EC=6.2.1.3
Alternative name(s):
    Long-chain acyl-CoA synthetase 1
      Short name=LACS 1
    Long-chain acyl-CoA synthetase 2
      Short name=LACS 2
    Palmitoyl-CoA ligase 1
    Palmitoyl-CoA ligase 2
    Acyl-CoA synthetase 1
      Short name=ACS1
    Long-chain fatty acid-CoA ligase 2

Gene names

Name:	ACSL1
Synonyms:	FACL1, FACL2, LACS, LACS1, LACS2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	698 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Activation of long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation. Preferentially uses palmitoleate, oleate and linoleate.
Catalytic activity	ATP + a long-chain carboxylic acid + CoA = AMP + diphosphate + an acyl-CoA.
Cofactor	Magnesium.
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.
Tissue specificity	Highly expressed in liver, heart, skeletal muscle, kidney and erythroid cells, and to a lesser extent in brain, lung, placenta and pancreas. Ref.6
Developmental stage	Expressed during the early stages of erythroid development while expression is very low in reticulocytes and young erythrocytes.
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	Alternative splicing
Domain	Signal-anchor Transmembrane
Ligand	ATP-binding Magnesium Nucleotide-binding
Molecular function	Ligase
PTM	Acetylation Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	digestion Traceable author statement. Source: ProtInc fatty acid metabolic process Inferred from electronic annotation. Source: UniProtKB-KW regulation of fatty acid oxidation Inferred from Experiment. Source: Reactome
Cellular component	cytosol Ref.6 Inferred from Experiment. Source: Reactome endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW microsome Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrial outer membrane Inferred from electronic annotation. Source: UniProtKB-SubCell 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 Ref.6 Inferred from Experiment. Source: Reactome magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P33121-1)

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: P33121-2)

The sequence of this isoform differs from the canonical sequence as follows:
     508-517: Missing.

Note: May be due to a competing acceptor splice site. No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 698	698	Long-chain-fatty-acid--CoA ligase 1		PRO_0000193104
Regions
	Transmembrane	25 – 45	21	Signal-anchor for type III membrane protein Potential
	Topological domain	46 – 698	653	Cytoplasmic Potential
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine Ref.4
	Modified residue	84	1	Phosphotyrosine By similarity
	Modified residue	543	1	N6-acetyllysine By similarity
	Modified residue	632	1	N6-acetyllysine By similarity
Natural variations
	Alternative sequence	508 – 517	10	Missing in isoform 2.		VSP_009604
Experimental info
	Sequence conflict	21 – 23	3	YVR → CV in AAB00959. Ref.2
	Sequence conflict	37 – 38	2	AA → SRR in AAB00959. Ref.2
	Sequence conflict	44 – 47	4	YATR → RPRH in AAB00959. Ref.2
	Sequence conflict	55 – 56	2	CD → WH in AAB00959. Ref.2
	Sequence conflict	229	1	A → S in AAB00959. Ref.2
	Sequence conflict	385	1	L → V in AAB00959. Ref.2
	Sequence conflict	400 – 401	2	EL → DV in AAB00959. Ref.2
	Sequence conflict	477	1	A → T in AAB00959. Ref.2
	Sequence conflict	492 – 494	3	VDV → GWQL in AAB00959. Ref.2
	Sequence conflict	502	1	A → S in AAB00959. Ref.2
	Sequence conflict	695	1	T → I in AAB00959. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 1993. Version 1. Checksum: FD6669453589D362	FASTA	698	77,943
	10 20 30 40 50 60 MQAHELFRYF RMPELVDFRQ YVRTLPTNTL MGFGAFAALT TFWYATRPKP LKPPCDLSMQ 70 80 90 100 110 120 SVEVAGSGGA RRSALLDSDE PLVYFYDDVT TLYEGFQRGI QVSNNGPCLG SRKPDQPYEW 130 140 150 160 170 180 LSYKQVAELS ECIGSALIQK GFKTAPDQFI GIFAQNRPEW VIIEQGCFAY SMVIVPLYDT 190 200 210 220 230 240 LGNEAITYIV NKAELSLVFV DKPEKAKLLL EGVENKLIPG LKIIVVMDAY GSELVERGQR 250 260 270 280 290 300 CGVEVTSMKA MEDLGRANRR KPKPPAPEDL AVICFTSGTT GNPKGAMVTH RNIVSDCSAF 310 320 330 340 350 360 VKATENTVNP CPDDTLISFL PLAHMFERVV ECVMLCHGAK IGFFQGDIRL LMDDLKVLQP 370 380 390 400 410 420 TVFPVVPRLL NRMFDRIFGQ ANTTLKRWLL DFASKRKEAE LRSGIIRNNS LWDRLIFHKV 430 440 450 460 470 480 QSSLGGRVRL MVTGAAPVSA TVLTFLRAAL GCQFYEGYGQ TECTAGCCLT MPGDWTAGHV 490 500 510 520 530 540 GAPMPCNLIK LVDVEEMNYM AAEGEGEVCV KGPNVFQGYL KDPAKTAEAL DKDGWLHTGD 550 560 570 580 590 600 IGKWLPNGTL KIIDRKKHIF KLAQGEYIAP EKIENIYMRS EPVAQVFVHG ESLQAFLIAI 610 620 630 640 650 660 VVPDVETLCS WAQKRGFEGS FEELCRNKDV KKAILEDMVR LGKDSGLKPF EQVKGITLHP 670 680 690 ELFSIDNGLL TPTMKAKRPE LRNYFRSQID DLYSTIKV
	Isoform 2. Checksum: 815DF2AA8EE8A6B4	FASTA	688	76,871
	10 20 30 40 50 60 MQAHELFRYF RMPELVDFRQ YVRTLPTNTL MGFGAFAALT TFWYATRPKP LKPPCDLSMQ 70 80 90 100 110 120 SVEVAGSGGA RRSALLDSDE PLVYFYDDVT TLYEGFQRGI QVSNNGPCLG SRKPDQPYEW 130 140 150 160 170 180 LSYKQVAELS ECIGSALIQK GFKTAPDQFI GIFAQNRPEW VIIEQGCFAY SMVIVPLYDT 190 200 210 220 230 240 LGNEAITYIV NKAELSLVFV DKPEKAKLLL EGVENKLIPG LKIIVVMDAY GSELVERGQR 250 260 270 280 290 300 CGVEVTSMKA MEDLGRANRR KPKPPAPEDL AVICFTSGTT GNPKGAMVTH RNIVSDCSAF 310 320 330 340 350 360 VKATENTVNP CPDDTLISFL PLAHMFERVV ECVMLCHGAK IGFFQGDIRL LMDDLKVLQP 370 380 390 400 410 420 TVFPVVPRLL NRMFDRIFGQ ANTTLKRWLL DFASKRKEAE LRSGIIRNNS LWDRLIFHKV 430 440 450 460 470 480 QSSLGGRVRL MVTGAAPVSA TVLTFLRAAL GCQFYEGYGQ TECTAGCCLT MPGDWTAGHV 490 500 510 520 530 540 GAPMPCNLIK LVDVEEMNYM AAEGEGEGYL KDPAKTAEAL DKDGWLHTGD IGKWLPNGTL 550 560 570 580 590 600 KIIDRKKHIF KLAQGEYIAP EKIENIYMRS EPVAQVFVHG ESLQAFLIAI VVPDVETLCS 610 620 630 640 650 660 WAQKRGFEGS FEELCRNKDV KKAILEDMVR LGKDSGLKPF EQVKGITLHP ELFSIDNGLL 670 680 TPTMKAKRPE LRNYFRSQID DLYSTIKV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human long-chain acyl-CoA synthetase: structure and chromosomal location." Abe T., Fujino T., Fukuyama R., Minoshima S., Shimizu N., Toh H., Suzuki H., Yamamoto T. J. Biochem. 111:123-128(1992) [PubMed: 1607358] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver.
[2]	"Molecular cloning and sequencing of human palmitoyl-CoA ligase and its tissue specific expression." Ghosh B., Barbosa E., Singh I. Mol. Cell. Biochem. 151:77-81(1995) [PubMed: 8584017] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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] (ISOFORM 1). Tissue: Testis.
[4]	Bienvenut W.V. Submitted (JUN-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 1-8; 12-19; 341-349; 377-386; 562-572; 633-640 AND 655-675, ACETYLATION AT MET-1, MASS SPECTROMETRY. Tissue: B-cell lymphoma.
[5]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 395-698 (ISOFORM 2).
[6]	"Identification and molecular characterization of acyl-CoA synthetase in human red cells and erythroid precursor." Malhotra K.T., Malhotra K., Lubin B.H., Kuypers F.A. Biochem. J. 344:135-143(1999) [PubMed: 10548543] [Abstract] Cited for: TISSUE SPECIFICITY.
[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	D10040 mRNA. Translation: BAA00931.1. L09229 mRNA. Translation: AAB00959.1. BC026290 mRNA. Translation: AAH26290.1. BC050073 mRNA. Translation: AAH50073.1. AK096117 mRNA. Translation: BAC04704.1. Different initiation.
IPI	IPI00012728. IPI00401448.
PIR	JX0202.
RefSeq	NP_001986.2.
UniGene	Hs.406678
3D structure databases
HSSP	HSSP built from PDB template 1LCI based on UniProtKB P08659.
ModBase	Search...
PTM databases
PhosphoSite	P33121.
Proteomic databases
PRIDE	P33121.
Genome annotation databases
Ensembl	ENSG00000151726. Homo sapiens. [Contig view]
GeneID	2180.
KEGG	hsa:2180.
Organism-specific databases
GeneCards	GC04M185914.
H-InvDB	HIX0004675.
HGNC	HGNC:3569. ACSL1.
HPA	HPA011316. HPA011964.
MIM	152425. gene.
PharmGKB	PA27966.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P33121.
HOVERGEN	P33121.
OMA	P33121. HELFRYF.
Enzyme and pathway databases
BRENDA	6.2.1.3. 247.
Reactome	REACT_1505. Integration of energy metabolism.
Gene expression databases
ArrayExpress	P33121.
Bgee	P33121.
CleanEx	HS_ACSL1.
GermOnline	ENSG00000151726. Homo sapiens.
Family and domain databases
InterPro	IPR000873. AMP-dep_Synth/Lig. [Graphical view]
Pfam	PF00501. AMP-binding. 2 hits. [Graphical view]
PROSITE	PS00455. AMP_BINDING. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00131. Adenosine monophosphate. DB00171. Adenosine triphosphate.
NextBio	8801.
SOURCE	Search...

Entry information

Entry name

ACSL1_HUMAN

Accession

Primary (citable) accession number: P33121
Secondary accession number(s): P41215, Q8N8V7, Q8TA99

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	October 1, 1993
Last modified:	June 16, 2009
This is version 86 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)