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O60488

- ACSL4_HUMAN

UniProt

O60488 - ACSL4_HUMAN

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Protein

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

Gene
ACSL4, ACS4, FACL4, LACS4
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - 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

Magnesium By similarity.

GO - Molecular functioni

  1. arachidonate-CoA ligase activity Source: UniProtKB
  2. ATP binding Source: UniProtKB-KW
  3. long-chain fatty acid-CoA ligase activity Source: Ensembl
  4. very long-chain fatty acid-CoA ligase activity Source: UniProtKB

GO - Biological processi

  1. cellular lipid metabolic process Source: Reactome
  2. dendritic spine development Source: Ensembl
  3. embryonic process involved in female pregnancy Source: Ensembl
  4. fatty acid transport Source: Ensembl
  5. lipid biosynthetic process Source: UniProtKB
  6. lipid metabolic process Source: UniProtKB
  7. long-chain fatty acid metabolic process Source: GOC
  8. long-chain fatty-acyl-CoA biosynthetic process Source: Reactome
  9. negative regulation of prostaglandin secretion Source: UniProtKB
  10. positive regulation of cell growth Source: UniProtKB
  11. response to interleukin-15 Source: Ensembl
  12. response to nutrient Source: Ensembl
  13. small molecule metabolic process Source: Reactome
  14. triglyceride biosynthetic process Source: Reactome
  15. triglyceride metabolic process Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Fatty acid metabolism, Lipid metabolism

Keywords - Ligandi

ATP-binding, Magnesium, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS00935-MONOMER.
BRENDAi6.2.1.3. 2681.
ReactomeiREACT_380. Synthesis of very long-chain fatty acyl-CoAs.

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
ProteomesiUP000005640: Chromosome X

Organism-specific databases

HGNCiHGNC:3571. ACSL4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei8 – 2821Helical; Signal-anchor for type III membrane protein; Reviewed predictionAdd
BLAST
Topological domaini29 – 711683Cytoplasmic Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. endoplasmic reticulum membrane Source: Reactome
  3. extracellular vesicular exosome Source: UniProt
  4. integral component of membrane Source: UniProtKB-KW
  5. lipid particle Source: UniProtKB
  6. mitochondrial membrane Source: Ensembl
  7. mitochondrial outer membrane Source: UniProtKB-SubCell
  8. neuronal cell body Source: Ensembl
  9. peroxisomal membrane Source: UniProtKB-SubCell
  10. peroxisome Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

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.1 Publication
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti570 – 5701R → S in MRX63. 1 Publication
VAR_013180
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.

Keywords - Diseasei

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

Organism-specific databases

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 711711Long-chain-fatty-acid--CoA ligase 4PRO_0000193109Add
BLAST

Proteomic databases

MaxQBiO60488.
PaxDbiO60488.
PRIDEiO60488.

PTM databases

PhosphoSiteiO60488.

Expressioni

Gene expression databases

ArrayExpressiO60488.
BgeeiO60488.
CleanExiHS_ACSL4.
GenevestigatoriO60488.

Organism-specific databases

HPAiHPA000286.
HPA005552.

Interactioni

Protein-protein interaction databases

BioGridi108478. 11 interactions.
IntActiO60488. 7 interactions.
MINTiMINT-3000036.
STRINGi9606.ENSP00000339787.

Structurei

3D structure databases

ProteinModelPortaliO60488.
SMRiO60488. Positions 122-598.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1022.
HOGENOMiHOG000159459.
HOVERGENiHBG106947.
InParanoidiO60488.
KOiK01897.
OMAiNAMKLER.
OrthoDBiEOG7P2XRD.
PhylomeDBiO60488.
TreeFamiTF314012.

Family and domain databases

InterProiIPR020845. AMP-binding_CS.
IPR000873. AMP-dep_Synth/Lig.
[Graphical view]
PfamiPF00501. AMP-binding. 1 hit.
[Graphical view]
PROSITEiPS00455. AMP_BINDING. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

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

MKLKLNVLTI ILLPVHLLIT IYSALIFIPW YFLTNAKKKN AMAKRIKAKP    50
TSDKPGSPYR SVTHFDSLAV IDIPGADTLD KLFDHAVSKF GKKDSLGTRE 100
ILSEENEMQP NGKVFKKLIL GNYKWMNYLE VNRRVNNFGS GLTALGLKPK 150
NTIAIFCETR AEWMIAAQTC FKYNFPLVTL YATLGKEAVV HGLNESEASY 200
LITSVELLES KLKTALLDIS CVKHIIYVDN KAINKAEYPE GFEIHSMQSV 250
EELGSNPENL GIPPSRPTPS DMAIVMYTSG STGRPKGVMM HHSNLIAGMT 300
GQCERIPGLG PKDTYIGYLP LAHVLELTAE ISCFTYGCRI GYSSPLTLSD 350
QSSKIKKGSK GDCTVLKPTL MAAVPEIMDR IYKNVMSKVQ EMNYIQKTLF 400
KIGYDYKLEQ IKKGYDAPLC NLLLFKKVKA LLGGNVRMML SGGAPLSPQT 450
HRFMNVCFCC PIGQGYGLTE SCGAGTVTEV TDYTTGRVGA PLICCEIKLK 500
DWQEGGYTIN DKPNPRGEIV IGGQNISMGY FKNEEKTAED YSVDENGQRW 550
FCTGDIGEFH PDGCLQIIDR KKDLVKLQAG EYVSLGKVEA ALKNCPLIDN 600
ICAFAKSDQS YVISFVVPNQ KRLTLLAQQK GVEGTWVDIC NNPAMEAEIL 650
KEIREAANAM KLERFEIPIK VRLSPEPWTP ETGLVTDAFK LKRKELRNHY 700
LKDIERMYGG K 711
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

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti133 – 1331R → C in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_036376
Natural varianti570 – 5701R → S in MRX63. 1 Publication
VAR_013180

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4141Missing in isoform Short. VSP_000238Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti181 – 1811Y → C in CAA73314. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_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]
UniGeneiHs.268785.

Genome annotation databases

EnsembliENST00000340800; ENSP00000339787; ENSG00000068366. [O60488-1]
ENST00000348502; ENSP00000262835; ENSG00000068366. [O60488-2]
ENST00000469796; ENSP00000419171; ENSG00000068366. [O60488-1]
ENST00000469857; ENSP00000423077; ENSG00000068366.
GeneIDi2182.
KEGGihsa:2182.
UCSCiuc004eoi.2. human. [O60488-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS14548.1. [O60488-1 ]
CCDS14549.1. [O60488-2 ]
RefSeqi NP_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 ]
UniGenei Hs.268785.

3D structure databases

ProteinModelPortali O60488.
SMRi O60488. Positions 122-598.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 108478. 11 interactions.
IntActi O60488. 7 interactions.
MINTi MINT-3000036.
STRINGi 9606.ENSP00000339787.

Chemistry

DrugBanki DB00159. Icosapent.
DB00197. Troglitazone.

PTM databases

PhosphoSitei O60488.

Proteomic databases

MaxQBi O60488.
PaxDbi O60488.
PRIDEi O60488.

Protocols and materials databases

DNASUi 2182.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000340800 ; ENSP00000339787 ; ENSG00000068366 . [O60488-1 ]
ENST00000348502 ; ENSP00000262835 ; ENSG00000068366 . [O60488-2 ]
ENST00000469796 ; ENSP00000419171 ; ENSG00000068366 . [O60488-1 ]
ENST00000469857 ; ENSP00000423077 ; ENSG00000068366 .
GeneIDi 2182.
KEGGi hsa:2182.
UCSCi uc004eoi.2. human. [O60488-1 ]

Organism-specific databases

CTDi 2182.
GeneCardsi GC0XM108872.
HGNCi HGNC:3571. ACSL4.
HPAi HPA000286.
HPA005552.
MIMi 300157. gene.
300194. phenotype.
300387. phenotype.
neXtProti NX_O60488.
Orphaneti 86818. Alport syndrome - intellectual disability - midface hypoplasia - elliptocytosis.
777. X-linked non-syndromic intellectual disability.
PharmGKBi PA27968.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG1022.
HOGENOMi HOG000159459.
HOVERGENi HBG106947.
InParanoidi O60488.
KOi K01897.
OMAi NAMKLER.
OrthoDBi EOG7P2XRD.
PhylomeDBi O60488.
TreeFami TF314012.

Enzyme and pathway databases

BioCyci MetaCyc:HS00935-MONOMER.
BRENDAi 6.2.1.3. 2681.
Reactomei REACT_380. Synthesis of very long-chain fatty acyl-CoAs.

Miscellaneous databases

ChiTaRSi ACSL4. human.
GeneWikii ACSL4.
GenomeRNAii 2182.
NextBioi 8811.
PROi O60488.
SOURCEi Search...

Gene expression databases

ArrayExpressi O60488.
Bgeei O60488.
CleanExi HS_ACSL4.
Genevestigatori O60488.

Family and domain databases

InterProi IPR020845. AMP-binding_CS.
IPR000873. AMP-dep_Synth/Lig.
[Graphical view ]
Pfami PF00501. AMP-binding. 1 hit.
[Graphical view ]
PROSITEi PS00455. AMP_BINDING. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  8. Cited for: VARIANT MRX63 SER-570.
  9. Cited for: VARIANT [LARGE SCALE ANALYSIS] CYS-133.

Entry informationi

Entry nameiACSL4_HUMAN
AccessioniPrimary (citable) accession number: O60488
Secondary accession number(s): D3DUY2
, O60848, O60849, Q5JWV8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: April 27, 2001
Last modified: September 3, 2014
This is version 147 of the entry and version 2 of the sequence. [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. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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