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O60488 (ACSL4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | 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 4

EC=6.2.1.3
Alternative name(s):
Long-chain acyl-CoA synthetase 4
Short name=LACS 4
Gene names
Name:ACSL4
Synonyms:ACS4, FACL4, LACS4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length711 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 arachidonate and eicosapentaenoate as substrates.

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.

Involvement in disease

Mental retardation, X-linked 63 (MRX63) [MIM:300387]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

Alport syndrome with mental retardation, midface hypoplasia and elliptocytosis (ATS-MR) [MIM:300194]: A X-linked contiguous gene deletion syndrome characterized by glomerulonephritis, sensorineural hearing loss, mental retardation, midface hypoplasia and elliptocytosis.
Note: The gene represented in this entry may be involved in disease pathogenesis.

Sequence similarities

Belongs to the ATP-dependent AMP-binding enzyme family.

Ontologies

Keywords
   Biological processFatty acid metabolism
Lipid metabolism
   Cellular componentEndoplasmic reticulum
Membrane
Microsome
Mitochondrion
Mitochondrion outer membrane
Peroxisome
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseAlport syndrome
Deafness
Disease mutation
Elliptocytosis
Hereditary hemolytic anemia
Mental retardation
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   LigandATP-binding
Magnesium
Nucleotide-binding
   Molecular functionLigase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular lipid metabolic process

Traceable author statement. Source: Reactome

dendritic spine development

Inferred from electronic annotation. Source: Ensembl

embryonic process involved in female pregnancy

Inferred from electronic annotation. Source: Ensembl

fatty acid transport

Inferred from electronic annotation. Source: Ensembl

lipid biosynthetic process

Inferred from direct assay PubMed 21242590. Source: UniProtKB

lipid metabolic process

Inferred from direct assay Ref.1. Source: UniProtKB

long-chain fatty acid metabolic process

Inferred from direct assay PubMed 10669417PubMed 21242590. Source: GOC

long-chain fatty-acyl-CoA biosynthetic process

Traceable author statement. Source: Reactome

negative regulation of prostaglandin secretion

Inferred from direct assay PubMed 21242590. Source: UniProtKB

positive regulation of cell growth

Inferred from direct assay PubMed 17934335. Source: UniProtKB

response to interleukin-15

Inferred from electronic annotation. Source: Ensembl

response to nutrient

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

triglyceride biosynthetic process

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Inferred from direct assay Ref.8. Source: UniProtKB

endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 20458337PubMed 23376485. Source: UniProt

integral component of 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

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

peroxisomal membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

arachidonate-CoA ligase activity

Inferred from direct assay Ref.1PubMed 21242590. Source: UniProtKB

long-chain fatty acid-CoA ligase activity

Inferred from direct assay PubMed 10669417. Source: MGI

very long-chain fatty acid-CoA ligase activity

Inferred from mutant phenotype Ref.8. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Long (identifier: O60488-1)

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 Short (identifier: O60488-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 711711Long-chain-fatty-acid--CoA ligase 4
PRO_0000193109

Regions

Transmembrane8 – 2821Helical; Signal-anchor for type III membrane protein; Potential
Topological domain29 – 711683Cytoplasmic Potential

Natural variations

Alternative sequence1 – 4141Missing in isoform Short.
VSP_000238
Natural variant1331R → C in a colorectal cancer sample; somatic mutation. Ref.9
VAR_036376
Natural variant5701R → S in MRX63. Ref.8
VAR_013180

Experimental info

Sequence conflict1811Y → C in CAA73314. Ref.2

Sequences

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

Last modified April 27, 2001. Version 2.
Checksum: 6483CD17FE78FE73

FASTA71179,188
        10         20         30         40         50         60 
MKLKLNVLTI ILLPVHLLIT IYSALIFIPW YFLTNAKKKN AMAKRIKAKP TSDKPGSPYR 

        70         80         90        100        110        120 
SVTHFDSLAV IDIPGADTLD KLFDHAVSKF GKKDSLGTRE ILSEENEMQP NGKVFKKLIL 

       130        140        150        160        170        180 
GNYKWMNYLE VNRRVNNFGS GLTALGLKPK NTIAIFCETR AEWMIAAQTC FKYNFPLVTL 

       190        200        210        220        230        240 
YATLGKEAVV HGLNESEASY LITSVELLES KLKTALLDIS CVKHIIYVDN KAINKAEYPE 

       250        260        270        280        290        300 
GFEIHSMQSV EELGSNPENL GIPPSRPTPS DMAIVMYTSG STGRPKGVMM HHSNLIAGMT 

       310        320        330        340        350        360 
GQCERIPGLG PKDTYIGYLP LAHVLELTAE ISCFTYGCRI GYSSPLTLSD QSSKIKKGSK 

       370        380        390        400        410        420 
GDCTVLKPTL MAAVPEIMDR IYKNVMSKVQ EMNYIQKTLF KIGYDYKLEQ IKKGYDAPLC 

       430        440        450        460        470        480 
NLLLFKKVKA LLGGNVRMML SGGAPLSPQT HRFMNVCFCC PIGQGYGLTE SCGAGTVTEV 

       490        500        510        520        530        540 
TDYTTGRVGA PLICCEIKLK DWQEGGYTIN DKPNPRGEIV IGGQNISMGY FKNEEKTAED 

       550        560        570        580        590        600 
YSVDENGQRW FCTGDIGEFH PDGCLQIIDR KKDLVKLQAG EYVSLGKVEA ALKNCPLIDN 

       610        620        630        640        650        660 
ICAFAKSDQS YVISFVVPNQ KRLTLLAQQK GVEGTWVDIC NNPAMEAEIL KEIREAANAM 

       670        680        690        700        710 
KLERFEIPIK VRLSPEPWTP ETGLVTDAFK LKRKELRNHY LKDIERMYGG K 

« Hide

Isoform Short [UniParc].

Checksum: 676E2E8124D399F2
Show »

FASTA67074,436

References

« Hide 'large scale' references
[1]"Cloning, expression, and chromosomal localization of human long-chain fatty acid-CoA ligase 4 (FACL4)."
Cao Y., Traer E., Zimmerman G.A., McIntyre T.M., Prescott S.M.
Genomics 49:327-330(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
[2]"FACL4, a new gene encoding long-chain acyl-CoA synthetase 4, is deleted in a family with Alport syndrome, elliptocytosis, and mental retardation."
Piccini M., Vitelli F., Bruttini M., Pober B.R., Jonsson J.J., Villanova M., Zollo M., Borsani G., Ballabio A., Renieri A.
Genomics 47:350-358(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
Tissue: Placenta and Retina.
[3]"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] (ISOFORM SHORT).
Tissue: Stomach.
[4]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].
[5]"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 SHORT).
Tissue: Testis.
[6]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"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].
[8]"FACL4, encoding fatty acid-CoA ligase 4, is mutated in nonspecific X-linked mental retardation."
Meloni I., Muscettola M., Raynaud M., Longo I., Bruttini M., Moizard M.-P., Gomot M., Chelly J., des Portes V., Fryns J.-P., Ropers H.-H., Magi B., Bellan C., Volpi N., Yntema H.G., Lewis S.E., Schaffer J.E., Renieri A.
Nat. Genet. 30:436-440(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MRX63 SER-570.
[9]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] CYS-133.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS14548.1. [O60488-1]
CCDS14549.1. [O60488-2]
RefSeqNP_004449.1. NM_004458.2. [O60488-2]
NP_075266.1. NM_022977.2. [O60488-1]
XP_005262165.1. XM_005262108.1. [O60488-1]
XP_005262166.1. XM_005262109.1. [O60488-1]
XP_005262167.1. XM_005262110.1. [O60488-2]
XP_006724698.1. XM_006724635.1. [O60488-2]
UniGeneHs.268785.

3D structure databases

ProteinModelPortalO60488.
SMRO60488. Positions 122-598.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108478. 11 interactions.
IntActO60488. 7 interactions.
MINTMINT-3000036.
STRING9606.ENSP00000339787.

Chemistry

DrugBankDB00159. Icosapent.
DB00197. Troglitazone.

PTM databases

PhosphoSiteO60488.

Proteomic databases

MaxQBO60488.
PaxDbO60488.
PRIDEO60488.

Protocols and materials databases

DNASU2182.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000340800; ENSP00000339787; ENSG00000068366. [O60488-1]
ENST00000348502; ENSP00000262835; ENSG00000068366. [O60488-2]
ENST00000469796; ENSP00000419171; ENSG00000068366. [O60488-1]
ENST00000469857; ENSP00000423077; ENSG00000068366.
GeneID2182.
KEGGhsa:2182.
UCSCuc004eoi.2. human. [O60488-1]

Organism-specific databases

CTD2182.
GeneCardsGC0XM108872.
HGNCHGNC:3571. ACSL4.
HPAHPA000286.
HPA005552.
MIM300157. gene.
300194. phenotype.
300387. phenotype.
neXtProtNX_O60488.
Orphanet86818. Alport syndrome - intellectual disability - midface hypoplasia - elliptocytosis.
777. X-linked non-syndromic intellectual disability.
PharmGKBPA27968.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1022.
HOGENOMHOG000159459.
HOVERGENHBG106947.
InParanoidO60488.
KOK01897.
OMANAMKLER.
OrthoDBEOG7P2XRD.
PhylomeDBO60488.
TreeFamTF314012.

Enzyme and pathway databases

BioCycMetaCyc:HS00935-MONOMER.
BRENDA6.2.1.3. 2681.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressO60488.
BgeeO60488.
CleanExHS_ACSL4.
GenevestigatorO60488.

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

ChiTaRSACSL4. human.
GeneWikiACSL4.
GenomeRNAi2182.
NextBio8811.
PROO60488.
SOURCESearch...

Entry information

Entry nameACSL4_HUMAN
AccessionPrimary (citable) accession number: O60488
Secondary accession number(s): D3DUY2 expand/collapse secondary AC list , O60848, O60849, Q5JWV8
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: April 27, 2001
Last modified: July 9, 2014
This is version 146 of the entry and version 2 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

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