Reviewed,
UniProtKB/Swiss-Prot O60488 (ACSL4_HUMAN)
Last modified
June 16, 2009.
Version 95.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | 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 names |
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| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 711 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| 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 arachidonate and eicosapentaenoate as substrates. |
| Catalytic activity | ATP + a long-chain carboxylic 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 | Defects in ACSL4 are the cause of mental retardation X-linked type 63 (MRX63) [MIM:300387]. Mental retardation is a mental disorder characterized by significantly sub-average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Non-syndromic mental retardation patients do not manifest other clinical signs. Ref.5 Defects in ACSL4 may be a cause of AMME complex [MIM:300194]; also known as Alport syndrome with mental retardation, midface hypoplasia and elliptocytosis. The AMME complex is a contiguous gene deletion syndrome. |
| Sequence similarities | Belongs to the ATP-dependent AMP-binding enzyme family. |
Ontologies
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 key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 711 | 711 | Long-chain-fatty-acid--CoA ligase 4 | PRO_0000193109 | |||||
Regions | |||||||||
| Transmembrane | 8 – 28 | 21 | Signal-anchor for type III membrane protein Potential | ||||||
| Topological domain | 29 – 711 | 683 | Cytoplasmic Potential | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 41 | 41 | Missing in isoform Short. | VSP_000238 | |||||
| Natural variant | 133 | 1 | R → C in a colorectal cancer sample; somatic mutation. Ref.6 | VAR_036376 | |||||
| Natural variant | 570 | 1 | R → S in MRX63. Ref.5 | VAR_013180 | |||||
Experimental info | |||||||||
| Sequence conflict | 181 | 1 | Y → C in CAA73314. Ref.2 | ||||||
Sequences
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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: 9598324] [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: 9480748] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT). Tissue: Placenta and Retina. |
| [3] | "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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT). Tissue: Testis. |
| [4] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [5] | "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: 11889465] [Abstract] Cited for: VARIANT MRX63 SER-570. |
| [6] | "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. Velculescu V.E.Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] CYS-133. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| AF030555 mRNA. Translation: AAC17493.1. Y12777 mRNA. Translation: CAA73314.1. Y13058 mRNA. Translation: CAA73501.1. BC034959 mRNA. Translation: AAH34959.1. | |
| IPI | IPI00029737. IPI00219897. |
| RefSeq | NP_004449.1. NP_075266.1. |
| UniGene | Hs.268785 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1LCI based on UniProtKB P08659. |
| ModBase | Search... |
PTM databases | |
| PhosphoSite | O60488. |
Proteomic databases | |
| PRIDE | O60488. |
Genome annotation databases | |
| Ensembl | ENSG00000068366. Homo sapiens. [Contig view] |
| GeneID | 2182. |
| KEGG | hsa:2182. |
Organism-specific databases | |
| GeneCards | GC0XM108771. |
| H-InvDB | HIX0028331. |
| HGNC | HGNC:3571. ACSL4. |
| HPA | HPA005552. |
| MIM | 300157. gene. 300194. phenotype. 300387. phenotype. |
| Orphanet | 86818. Alport syndrome - intellectual deficit - midface hypoplasia - elliptocytosis. 777. Intellectual deficit, X-linked, nonspecific. |
| PharmGKB | PA27968. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | O60488. |
| HOVERGEN | O60488. |
| OMA | O60488. AKSDQSY. |
Enzyme and pathway databases | |
| BRENDA | 6.2.1.3. 247. |
Gene expression databases | |
| ArrayExpress | O60488. |
| Bgee | O60488. |
| CleanEx | HS_ACSL4. |
| GermOnline | ENSG00000068366. Homo sapiens. |
Family and domain databases | |
| InterPro | 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 Resources | |
| DrugBank | DB00159. Icosapent. DB00197. Troglitazone. |
| NextBio | 8811. |
| SOURCE | Search... |
Entry information
| Entry name | ACSL4_HUMAN | ||||||||
| Accession | Primary (citable) accession number: O60488 Secondary accession number(s): O60848, O60849 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome X Human chromosome X: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


