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Protein

Long-chain-fatty-acid--CoA ligase 4

Gene

ACSL4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Activation of long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation. Preferentially uses arachidonate and eicosapentaenoate as substrates.

Catalytic activityi

ATP + a long-chain fatty acid + CoA = AMP + diphosphate + an acyl-CoA.

Cofactori

Mg2+By similarity

GO - Molecular functioni

  • arachidonate-CoA ligase activity Source: UniProtKB
  • ATP binding Source: UniProtKB-KW
  • decanoate-CoA ligase activity Source: UniProtKB-EC
  • long-chain fatty acid-CoA ligase activity Source: UniProtKB
  • very long-chain fatty acid-CoA ligase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionLigase
Biological processFatty acid metabolism, Lipid metabolism
LigandATP-binding, Magnesium, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS00935-MONOMER
BRENDAi6.2.1.15 2681
6.2.1.3 2681
ReactomeiR-HSA-75876 Synthesis of very long-chain fatty acyl-CoAs

Chemistry databases

SwissLipidsiSLP:000000201
SLP:000000515 [O60488-1]
SLP:000000516 [O60488-2]

Names & Taxonomyi

Protein namesi
Recommended name:
Long-chain-fatty-acid--CoA ligase 4 (EC:6.2.1.3)
Alternative name(s):
Long-chain acyl-CoA synthetase 4
Short name:
LACS 4
Gene namesi
Name:ACSL4
Synonyms:ACS4, FACL4, LACS4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000068366.19
HGNCiHGNC:3571 ACSL4
MIMi300157 gene
neXtProtiNX_O60488

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei8 – 28Helical; Signal-anchor for type III membrane proteinSequence analysisAdd BLAST21
Topological domaini29 – 711CytoplasmicSequence analysisAdd BLAST683

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome, Mitochondrion, Mitochondrion outer membrane, Peroxisome

Pathology & Biotechi

Involvement in diseasei

Mental retardation, X-linked 63 (MRX63)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations.
See also OMIM:300387
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_013180570R → S in MRX63. 1 PublicationCorresponds to variant dbSNP:rs122458138EnsemblClinVar.1
Alport syndrome with mental retardation, midface hypoplasia and elliptocytosis (ATS-MR)1 Publication
The gene represented in this entry may be involved in disease pathogenesis.
Disease descriptionA X-linked contiguous gene deletion syndrome characterized by glomerulonephritis, sensorineural hearing loss, mental retardation, midface hypoplasia and elliptocytosis.
See also OMIM:300194

Keywords - Diseasei

Alport syndrome, Deafness, Disease mutation, Elliptocytosis, Hereditary hemolytic anemia, Mental retardation

Organism-specific databases

DisGeNETi2182
MalaCardsiACSL4
MIMi300194 phenotype
300387 phenotype
OpenTargetsiENSG00000068366
Orphaneti86818 Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome
777 X-linked non-syndromic intellectual disability
PharmGKBiPA27968

Chemistry databases

DrugBankiDB00159 Icosapent
DB00412 Rosiglitazone
DB00197 Troglitazone

Polymorphism and mutation databases

BioMutaiACSL4

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001931091 – 711Long-chain-fatty-acid--CoA ligase 4Add BLAST711

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei447PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO60488
MaxQBiO60488
PaxDbiO60488
PeptideAtlasiO60488
PRIDEiO60488
ProteomicsDBi49426
49427 [O60488-2]

PTM databases

iPTMnetiO60488
PhosphoSitePlusiO60488
SwissPalmiO60488

Expressioni

Gene expression databases

BgeeiENSG00000068366 Expressed in 215 organ(s), highest expression level in adrenal tissue
CleanExiHS_ACSL4
ExpressionAtlasiO60488 baseline and differential
GenevisibleiO60488 HS

Organism-specific databases

HPAiHPA000286
HPA005552

Interactioni

Protein-protein interaction databases

BioGridi108478, 45 interactors
IntActiO60488, 25 interactors
MINTiO60488
STRINGi9606.ENSP00000339787

Structurei

3D structure databases

ProteinModelPortaliO60488
SMRiO60488
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1256 Eukaryota
COG1022 LUCA
GeneTreeiENSGT00930000150966
HOGENOMiHOG000159459
HOVERGENiHBG106947
InParanoidiO60488
KOiK01897
OMAiNHYLNDI
OrthoDBiEOG091G02F4
PhylomeDBiO60488
TreeFamiTF314012

Family and domain databases

InterProiView protein in InterPro
IPR020845 AMP-binding_CS
IPR000873 AMP-dep_Synth/Lig
PfamiView protein in Pfam
PF00501 AMP-binding, 1 hit
PROSITEiView protein in PROSITE
PS00455 AMP_BINDING, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All

Isoform Long (identifier: O60488-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MKLKLNVLTI ILLPVHLLIT IYSALIFIPW YFLTNAKKKN AMAKRIKAKP
60 70 80 90 100
TSDKPGSPYR SVTHFDSLAV IDIPGADTLD KLFDHAVSKF GKKDSLGTRE
110 120 130 140 150
ILSEENEMQP NGKVFKKLIL GNYKWMNYLE VNRRVNNFGS GLTALGLKPK
160 170 180 190 200
NTIAIFCETR AEWMIAAQTC FKYNFPLVTL YATLGKEAVV HGLNESEASY
210 220 230 240 250
LITSVELLES KLKTALLDIS CVKHIIYVDN KAINKAEYPE GFEIHSMQSV
260 270 280 290 300
EELGSNPENL GIPPSRPTPS DMAIVMYTSG STGRPKGVMM HHSNLIAGMT
310 320 330 340 350
GQCERIPGLG PKDTYIGYLP LAHVLELTAE ISCFTYGCRI GYSSPLTLSD
360 370 380 390 400
QSSKIKKGSK GDCTVLKPTL MAAVPEIMDR IYKNVMSKVQ EMNYIQKTLF
410 420 430 440 450
KIGYDYKLEQ IKKGYDAPLC NLLLFKKVKA LLGGNVRMML SGGAPLSPQT
460 470 480 490 500
HRFMNVCFCC PIGQGYGLTE SCGAGTVTEV TDYTTGRVGA PLICCEIKLK
510 520 530 540 550
DWQEGGYTIN DKPNPRGEIV IGGQNISMGY FKNEEKTAED YSVDENGQRW
560 570 580 590 600
FCTGDIGEFH PDGCLQIIDR KKDLVKLQAG EYVSLGKVEA ALKNCPLIDN
610 620 630 640 650
ICAFAKSDQS YVISFVVPNQ KRLTLLAQQK GVEGTWVDIC NNPAMEAEIL
660 670 680 690 700
KEIREAANAM KLERFEIPIK VRLSPEPWTP ETGLVTDAFK LKRKELRNHY
710
LKDIERMYGG K
Length:711
Mass (Da):79,188
Last modified:April 27, 2001 - v2
Checksum:i6483CD17FE78FE73
GO
Isoform Short (identifier: O60488-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-41: Missing.

Show »
Length:670
Mass (Da):74,436
Checksum:i676E2E8124D399F2
GO

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RFW9D6RFW9_HUMAN
Long-chain-fatty-acid--CoA ligase 4
ACSL4
126Annotation score:
D6RD96D6RD96_HUMAN
Long-chain-fatty-acid--CoA ligase 4
ACSL4
145Annotation score:
D6RDA8D6RDA8_HUMAN
Long-chain-fatty-acid--CoA ligase 4
ACSL4
128Annotation score:
A0A0C4DGB7A0A0C4DGB7_HUMAN
Long-chain-fatty-acid--CoA ligase 4
ACSL4
54Annotation score:
D6RF95D6RF95_HUMAN
Long-chain-fatty-acid--CoA ligase 4
ACSL4
154Annotation score:
H0Y9A0H0Y9A0_HUMAN
Long-chain-fatty-acid--CoA ligase 4
ACSL4
156Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti181Y → C in CAA73314 (PubMed:9480748).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036376133R → C in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs753267653Ensembl.1
Natural variantiVAR_013180570R → S in MRX63. 1 PublicationCorresponds to variant dbSNP:rs122458138EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0002381 – 41Missing in isoform Short. 4 PublicationsAdd BLAST41

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF030555 mRNA Translation: AAC17493.1
Y12777 mRNA Translation: CAA73314.1
Y13058 mRNA Translation: CAA73501.1
AK292070 mRNA Translation: BAF84759.1
CH471120 Genomic DNA Translation: EAX02671.1
CH471120 Genomic DNA Translation: EAX02672.1
CH471120 Genomic DNA Translation: EAX02673.1
CH471120 Genomic DNA Translation: EAX02674.1
BC034959 mRNA Translation: AAH34959.1
CCDSiCCDS14548.1 [O60488-1]
CCDS14549.1 [O60488-2]
RefSeqiNP_001305438.1, NM_001318509.1 [O60488-1]
NP_001305439.1, NM_001318510.1 [O60488-2]
NP_004449.1, NM_004458.2 [O60488-2]
NP_075266.1, NM_022977.2 [O60488-1]
XP_005262166.1, XM_005262109.2 [O60488-1]
XP_006724698.1, XM_006724635.2 [O60488-2]
XP_011529190.1, XM_011530888.2 [O60488-1]
XP_011529191.1, XM_011530889.2 [O60488-1]
UniGeneiHs.268785

Genome annotation databases

EnsembliENST00000340800; ENSP00000339787; ENSG00000068366 [O60488-1]
ENST00000348502; ENSP00000262835; ENSG00000068366 [O60488-2]
ENST00000469796; ENSP00000419171; ENSG00000068366 [O60488-1]
GeneIDi2182
KEGGihsa:2182
UCSCiuc004eoi.3 human [O60488-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF030555 mRNA Translation: AAC17493.1
Y12777 mRNA Translation: CAA73314.1
Y13058 mRNA Translation: CAA73501.1
AK292070 mRNA Translation: BAF84759.1
CH471120 Genomic DNA Translation: EAX02671.1
CH471120 Genomic DNA Translation: EAX02672.1
CH471120 Genomic DNA Translation: EAX02673.1
CH471120 Genomic DNA Translation: EAX02674.1
BC034959 mRNA Translation: AAH34959.1
CCDSiCCDS14548.1 [O60488-1]
CCDS14549.1 [O60488-2]
RefSeqiNP_001305438.1, NM_001318509.1 [O60488-1]
NP_001305439.1, NM_001318510.1 [O60488-2]
NP_004449.1, NM_004458.2 [O60488-2]
NP_075266.1, NM_022977.2 [O60488-1]
XP_005262166.1, XM_005262109.2 [O60488-1]
XP_006724698.1, XM_006724635.2 [O60488-2]
XP_011529190.1, XM_011530888.2 [O60488-1]
XP_011529191.1, XM_011530889.2 [O60488-1]
UniGeneiHs.268785

3D structure databases

ProteinModelPortaliO60488
SMRiO60488
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108478, 45 interactors
IntActiO60488, 25 interactors
MINTiO60488
STRINGi9606.ENSP00000339787

Chemistry databases

DrugBankiDB00159 Icosapent
DB00412 Rosiglitazone
DB00197 Troglitazone
SwissLipidsiSLP:000000201
SLP:000000515 [O60488-1]
SLP:000000516 [O60488-2]

PTM databases

iPTMnetiO60488
PhosphoSitePlusiO60488
SwissPalmiO60488

Polymorphism and mutation databases

BioMutaiACSL4

Proteomic databases

EPDiO60488
MaxQBiO60488
PaxDbiO60488
PeptideAtlasiO60488
PRIDEiO60488
ProteomicsDBi49426
49427 [O60488-2]

Protocols and materials databases

DNASUi2182
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000340800; ENSP00000339787; ENSG00000068366 [O60488-1]
ENST00000348502; ENSP00000262835; ENSG00000068366 [O60488-2]
ENST00000469796; ENSP00000419171; ENSG00000068366 [O60488-1]
GeneIDi2182
KEGGihsa:2182
UCSCiuc004eoi.3 human [O60488-1]

Organism-specific databases

CTDi2182
DisGeNETi2182
EuPathDBiHostDB:ENSG00000068366.19
GeneCardsiACSL4
HGNCiHGNC:3571 ACSL4
HPAiHPA000286
HPA005552
MalaCardsiACSL4
MIMi300157 gene
300194 phenotype
300387 phenotype
neXtProtiNX_O60488
OpenTargetsiENSG00000068366
Orphaneti86818 Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome
777 X-linked non-syndromic intellectual disability
PharmGKBiPA27968
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1256 Eukaryota
COG1022 LUCA
GeneTreeiENSGT00930000150966
HOGENOMiHOG000159459
HOVERGENiHBG106947
InParanoidiO60488
KOiK01897
OMAiNHYLNDI
OrthoDBiEOG091G02F4
PhylomeDBiO60488
TreeFamiTF314012

Enzyme and pathway databases

BioCyciMetaCyc:HS00935-MONOMER
BRENDAi6.2.1.15 2681
6.2.1.3 2681
ReactomeiR-HSA-75876 Synthesis of very long-chain fatty acyl-CoAs

Miscellaneous databases

ChiTaRSiACSL4 human
GeneWikiiACSL4
GenomeRNAii2182
PROiPR:O60488
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000068366 Expressed in 215 organ(s), highest expression level in adrenal tissue
CleanExiHS_ACSL4
ExpressionAtlasiO60488 baseline and differential
GenevisibleiO60488 HS

Family and domain databases

InterProiView protein in InterPro
IPR020845 AMP-binding_CS
IPR000873 AMP-dep_Synth/Lig
PfamiView protein in Pfam
PF00501 AMP-binding, 1 hit
PROSITEiView protein in PROSITE
PS00455 AMP_BINDING, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiACSL4_HUMAN
AccessioniPrimary (citable) accession number: O60488
Secondary accession number(s): D3DUY2
, O60848, O60849, Q5JWV8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: April 27, 2001
Last modified: November 7, 2018
This is version 189 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
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