P33121 (ACSL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Long-chain-fatty-acid--CoA ligase 1
EC=6.2.1.3

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

Gene names

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

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	698 AA.
Sequence status	Complete.
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 fatty 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.7
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.
Sequence caution	The sequence BAC04704.1 differs from that shown. Reason: Erroneous initiation.

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 Transmembrane helix
Ligand	ATP-binding Magnesium Nucleotide-binding
Molecular function	Ligase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	adiponectin-mediated signaling pathway Inferred from electronic annotation. Source: Compara alpha-linolenic acid metabolic process Traceable author statement. Source: Reactome linoleic acid metabolic process Traceable author statement. Source: Reactome long-chain fatty acid import Inferred from direct assay PubMed 22022213. Source: UniProtKB long-chain fatty-acyl-CoA biosynthetic process Traceable author statement. Source: Reactome positive regulation of protein serine/threonine kinase activity Inferred from electronic annotation. Source: Compara regulation of fatty acid oxidation Traceable author statement. Source: Reactome response to drug 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 organic cyclic compound Inferred from electronic annotation. Source: Compara triglyceride biosynthetic process Traceable author statement. Source: Reactome xenobiotic catabolic process Inferred from electronic annotation. Source: Compara
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial outer membrane Traceable author statement. Source: Reactome peroxisomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW long-chain fatty acid-CoA ligase activity Inferred from direct assay PubMed 21242590PubMed 22022213. Source: UniProtKB
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	Helical; 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.5
	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 [UniParc]. 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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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 (SEP-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] (ISOFORM 1). Tissue: Testis.
[5]	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.
[6]	"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] OF 395-698 (ISOFORM 2).
[7]	"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] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[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	D10040 mRNA. Translation: BAA00931.1. L09229 mRNA. Translation: AAB00959.1. CH471056 Genomic DNA. Translation: EAX04662.1. CH471056 Genomic DNA. Translation: EAX04663.1. CH471056 Genomic DNA. Translation: EAX04665.1. 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. NM_001995.2.
UniGene	Hs.406678.
3D structure databases
ProteinModelPortal	P33121.
ModBase	Search...
Protein-protein interaction databases
IntAct	P33121. 3 interactions.
STRING	9606.ENSP00000281455.
PTM databases
PhosphoSite	P33121.
Polymorphism databases
DMDM	417241.
Proteomic databases
PaxDb	P33121.
PRIDE	P33121.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000281455; ENSP00000281455; ENSG00000151726. ENST00000504342; ENSP00000425006; ENSG00000151726. ENST00000515030; ENSP00000422607; ENSG00000151726.
GeneID	2180.
KEGG	hsa:2180.
UCSC	uc003iwt.1. human.
Organism-specific databases
CTD	2180.
GeneCards	GC04M185676.
HGNC	HGNC:3569. ACSL1.
HPA	HPA011316. HPA011964.
MIM	152425. gene.
neXtProt	NX_P33121.
PharmGKB	PA27966.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1022.
HOGENOM	HOG000159459.
HOVERGEN	HBG050452.
InParanoid	P33121.
KO	K01897.
OMA	SMKAMED.
PhylomeDB	P33121.
Enzyme and pathway databases
BioCyc	MetaCyc:HS07766-MONOMER.
BRENDA	6.2.1.3. 2681.
Reactome	REACT_111217. Metabolism. REACT_11163. Activated AMPK stimulates fatty-acid oxidation in muscle.
Gene expression databases
ArrayExpress	P33121.
Bgee	P33121.
CleanEx	HS_ACSL1.
Genevestigator	P33121.
GermOnline	ENSG00000151726. 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
ChiTaRS	ACSL1. human.
DrugBank	DB00131. Adenosine monophosphate. DB00171. Adenosine triphosphate.
GenomeRNAi	2180.
NextBio	8801.
SOURCE	Search...

Entry information

Entry name

ACSL1_HUMAN

Accession

Primary (citable) accession number: P33121
Secondary accession number(s): D3DP57 , P41215, Q8N8V7, Q8TA99

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	October 1, 1993
Last modified:	April 3, 2013
This is version 125 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.