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P33121 (ACSL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length698 AA.
Sequence statusComplete.
Protein existenceEvidence 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 processFatty acid metabolism
Lipid metabolism
   Cellular componentEndoplasmic reticulum
Membrane
Microsome
Mitochondrion
Mitochondrion outer membrane
Peroxisome
   Coding sequence diversityAlternative splicing
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   LigandATP-binding
Magnesium
Nucleotide-binding
   Molecular functionLigase
   PTMAcetylation
Nitration
Phosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processadiponectin-activated signaling pathway

Inferred from electronic annotation. Source: Ensembl

alpha-linolenic acid metabolic process

Traceable author statement. Source: Reactome

cellular lipid metabolic process

Traceable author statement. Source: Reactome

linoleic acid metabolic process

Traceable author statement. Source: Reactome

lipid biosynthetic process

Inferred from direct assay PubMed 21242590. Source: UniProtKB

long-chain fatty acid import

Inferred from direct assay PubMed 22022213. Source: UniProtKB

long-chain fatty acid metabolic process

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: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to nutrient

Inferred from electronic annotation. Source: Ensembl

response to oleic acid

Inferred from electronic annotation. Source: Ensembl

response to organic cyclic compound

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

triglyceride biosynthetic process

Traceable author statement. Source: Reactome

unsaturated fatty acid metabolic process

Traceable author statement. Source: Reactome

xenobiotic catabolic process

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentendoplasmic reticulum membrane

Traceable author statement. Source: Reactome

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

mitochondrial outer membrane

Traceable author statement. Source: Reactome

mitochondrion

Inferred from direct assay PubMed 22022213. Source: UniProtKB

peroxisomal membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 698698Long-chain-fatty-acid--CoA ligase 1
PRO_0000193104

Regions

Transmembrane25 – 4521Helical; Signal-anchor for type III membrane protein; Potential
Topological domain46 – 698653Cytoplasmic Potential

Amino acid modifications

Modified residue11N-acetylmethionine Ref.5
Modified residue91Nitrated tyrosine By similarity
Modified residue841Phosphotyrosine By similarity
Modified residue2071N6-acetyllysine By similarity
Modified residue3561N6-acetyllysine By similarity
Modified residue3861N6-acetyllysine By similarity
Modified residue6201Phosphoserine By similarity
Modified residue6321N6-acetyllysine By similarity

Natural variations

Alternative sequence508 – 51710Missing in isoform 2.
VSP_009604

Experimental info

Sequence conflict21 – 233YVR → CV in AAB00959. Ref.2
Sequence conflict37 – 382AA → SRR in AAB00959. Ref.2
Sequence conflict44 – 474YATR → RPRH in AAB00959. Ref.2
Sequence conflict55 – 562CD → WH in AAB00959. Ref.2
Sequence conflict2291A → S in AAB00959. Ref.2
Sequence conflict3851L → V in AAB00959. Ref.2
Sequence conflict400 – 4012EL → DV in AAB00959. Ref.2
Sequence conflict4771A → T in AAB00959. Ref.2
Sequence conflict492 – 4943VDV → GWQL in AAB00959. Ref.2
Sequence conflict5021A → S in AAB00959. Ref.2
Sequence conflict6951T → I in AAB00959. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 1993. Version 1.
Checksum: FD6669453589D362

FASTA69877,943
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 815DF2AA8EE8A6B4
Show »

FASTA68876,871

References

« Hide '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. expand/collapse author list , 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, IDENTIFICATION BY 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. expand/collapse author list , 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.
PIRJX0202.
RefSeqNP_001273637.1. NM_001286708.1.
NP_001273639.1. NM_001286710.1.
NP_001273640.1. NM_001286711.1.
NP_001273641.1. NM_001286712.1.
NP_001986.2. NM_001995.3.
XP_005262885.1. XM_005262828.1.
XP_005262886.1. XM_005262829.1.
XP_005262888.1. XM_005262831.1.
UniGeneHs.406678.

3D structure databases

ProteinModelPortalP33121.
SMRP33121. Positions 81-639.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108476. 6 interactions.
IntActP33121. 3 interactions.
STRING9606.ENSP00000281455.

Chemistry

DrugBankDB00131. Adenosine monophosphate.
DB00171. Adenosine triphosphate.

PTM databases

PhosphoSiteP33121.

Polymorphism databases

DMDM417241.

Proteomic databases

PaxDbP33121.
PRIDEP33121.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000281455; ENSP00000281455; ENSG00000151726. [P33121-1]
ENST00000504342; ENSP00000425006; ENSG00000151726. [P33121-1]
ENST00000515030; ENSP00000422607; ENSG00000151726. [P33121-1]
GeneID2180.
KEGGhsa:2180.
UCSCuc003iwt.1. human. [P33121-1]

Organism-specific databases

CTD2180.
GeneCardsGC04M185676.
HGNCHGNC:3569. ACSL1.
HPAHPA011316.
HPA011964.
MIM152425. gene.
neXtProtNX_P33121.
PharmGKBPA27966.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1022.
HOGENOMHOG000159459.
HOVERGENHBG050452.
InParanoidP33121.
KOK01897.
OMAAKCPIVE.
OrthoDBEOG71CFKN.
PhylomeDBP33121.
TreeFamTF313877.

Enzyme and pathway databases

BioCycMetaCyc:HS07766-MONOMER.
BRENDA6.2.1.3. 2681.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressP33121.
BgeeP33121.
CleanExHS_ACSL1.
GenevestigatorP33121.

Family and domain databases

InterProIPR020845. AMP-binding_CS.
IPR000873. AMP-dep_Synth/Lig.
[Graphical view]
PfamPF00501. AMP-binding. 1 hit.
[Graphical view]
PROSITEPS00455. AMP_BINDING. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSACSL1. human.
GeneWikiACSL1.
GenomeRNAi2180.
NextBio8801.
PROP33121.
SOURCESearch...

Entry information

Entry nameACSL1_HUMAN
AccessionPrimary (citable) accession number: P33121
Secondary accession number(s): D3DP57 expand/collapse secondary AC list , P41215, Q8N8V7, Q8TA99
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: October 1, 1993
Last modified: April 16, 2014
This is version 135 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM