Reviewed, UniProtKB/Swiss-Prot O60488 (ACSL4_HUMAN)

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

Name:	ACSL4
Synonyms:	ACS4, FACL4, LACS4

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

Keywords
Biological process	Fatty acid metabolism Lipid metabolism
Cellular component	Endoplasmic reticulum Membrane Microsome Mitochondrion Mitochondrion outer membrane Peroxisome
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Alport syndrome Disease mutation Elliptocytosis Hereditary hemolytic anemia Mental retardation
Domain	Signal-anchor Transmembrane
Ligand	ATP-binding Magnesium Nucleotide-binding
Molecular function	Ligase
Gene Ontology (GO)
Biological process	fatty acid metabolic process Inferred from electronic annotation. Source: UniProtKB-KW learning or memory Ref.2 Traceable author statement. Source: ProtInc
Cellular component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW microsome Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrial outer membrane Inferred from electronic annotation. Source: UniProtKB-SubCell peroxisomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from direct assay. Source: HPA
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW long-chain-fatty-acid-CoA ligase activity Ref.2 Traceable author statement. Source: ProtInc magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW
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 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

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified April 27, 2001. Version 2. Checksum: 6483CD17FE78FE73	FASTA	711	79,188
	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
	Isoform Short. Checksum: 676E2E8124D399F2	FASTA	670	74,436
	10 20 30 40 50 60 MAKRIKAKPT SDKPGSPYRS VTHFDSLAVI DIPGADTLDK LFDHAVSKFG KKDSLGTREI 70 80 90 100 110 120 LSEENEMQPN GKVFKKLILG NYKWMNYLEV NRRVNNFGSG LTALGLKPKN TIAIFCETRA 130 140 150 160 170 180 EWMIAAQTCF KYNFPLVTLY ATLGKEAVVH GLNESEASYL ITSVELLESK LKTALLDISC 190 200 210 220 230 240 VKHIIYVDNK AINKAEYPEG FEIHSMQSVE ELGSNPENLG IPPSRPTPSD MAIVMYTSGS 250 260 270 280 290 300 TGRPKGVMMH HSNLIAGMTG QCERIPGLGP KDTYIGYLPL AHVLELTAEI SCFTYGCRIG 310 320 330 340 350 360 YSSPLTLSDQ SSKIKKGSKG DCTVLKPTLM AAVPEIMDRI YKNVMSKVQE MNYIQKTLFK 370 380 390 400 410 420 IGYDYKLEQI KKGYDAPLCN LLLFKKVKAL LGGNVRMMLS GGAPLSPQTH RFMNVCFCCP 430 440 450 460 470 480 IGQGYGLTES CGAGTVTEVT DYTTGRVGAP LICCEIKLKD WQEGGYTIND KPNPRGEIVI 490 500 510 520 530 540 GGQNISMGYF KNEEKTAEDY SVDENGQRWF CTGDIGEFHP DGCLQIIDRK KDLVKLQAGE 550 560 570 580 590 600 YVSLGKVEAA LKNCPLIDNI CAFAKSDQSY VISFVVPNQK RLTLLAQQKG VEGTWVDICN 610 620 630 640 650 660 NPAMEAEILK EIREAANAMK LERFEIPIKV RLSPEPWTPE TGLVTDAFKL KRKELRNHYL 670 KDIERMYGGK

References

	« Hide 'large scale' referencesShow '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. , 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: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] CYS-133.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	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

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	April 27, 2001
Last modified:	June 16, 2009
This is version 95 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)