O60488 (ACSL4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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.
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.7 Defects in ACSL4 are involved in Alport syndrome with mental retardation midface hypoplasia and elliptocytosis (ATS-MR) [MIM:300194]. A X-linked contiguous gene deletion syndrome characterized by glomerulonephritis, deafness, mental retardation, midface hypoplasia and elliptocytosis.
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 Deafness Disease mutation Elliptocytosis Hereditary hemolytic anemia Mental retardation
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	ATP-binding Magnesium Nucleotide-binding
Molecular function	Ligase
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	fatty acid metabolic process Inferred from electronic annotation. Source: UniProtKB-KW learning or memory Traceable author statement. Source: ProtInc long-chain fatty-acyl-CoA biosynthetic process Traceable author statement. Source: Reactome triglyceride biosynthetic process Traceable author statement. Source: Reactome
Cellular component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome 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
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW long-chain fatty acid-CoA ligase activity Inferred from direct assay. Source: MGI
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	Helical; Signal-anchor for type III membrane protein; Potential
	Topological domain	29 – 711	683	Cytoplasmic Potential
Amino acid modifications
	Modified residue	89	1	N6-acetyllysine Ref.5
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.8		VAR_036376
	Natural variant	570	1	R → S in MRX63. Ref.7		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 [UniParc]. 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]	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. , 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].
[4]	"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.
[5]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-89, MASS SPECTROMETRY.
[6]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]	"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.
[8]	"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
EMBL GenBank DDBJ	AF030555 mRNA. Translation: AAC17493.1. Y12777 mRNA. Translation: CAA73314.1. Y13058 mRNA. Translation: CAA73501.1. CH471120 Genomic DNA. Translation: EAX02671.1. CH471120 Genomic DNA. Translation: EAX02673.1. BC034959 mRNA. Translation: AAH34959.1.
IPI	IPI00029737. IPI00219897.
RefSeq	NP_004449.1. NM_004458.2. NP_075266.1. NM_022977.2.
UniGene	Hs.268785.
3D structure databases
ProteinModelPortal	O60488.
SMR	O60488. Positions 71-699.
ModBase	Search...
Protein-protein interaction databases
IntAct	O60488. 3 interactions.
MINT	MINT-3000036.
STRING	O60488.
PTM databases
PhosphoSite	O60488.
Proteomic databases
PRIDE	O60488.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000340800; ENSP00000339787; ENSG00000068366. ENST00000372078; ENSP00000361149; ENSG00000068366. ENST00000469796; ENSP00000419171; ENSG00000068366.
GeneID	2182.
KEGG	hsa:2182.
UCSC	uc004eoi.2. human.
Organism-specific databases
CTD	2182.
GeneCards	GC0XM108872.
HGNC	HGNC:3571. ACSL4.
HPA	HPA005552.
MIM	300157. gene. 300194. phenotype. 300387. phenotype.
neXtProt	NX_O60488.
Orphanet	86818. Alport syndrome - intellectual deficit - midface hypoplasia - elliptocytosis. 777. X-linked nonsyndromic intellectual deficit.
PharmGKB	PA27968.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG15833.
HOGENOM	HBG721674.
HOVERGEN	HBG106947.
InParanoid	O60488.
OMA	AKSDQSY.
PhylomeDB	O60488.
Enzyme and pathway databases
BRENDA	6.2.1.3. 2681.
Reactome	REACT_22258. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	O60488.
Bgee	O60488.
CleanEx	HS_ACSL4.
Genevestigator	O60488.
GermOnline	ENSG00000068366. Homo sapiens.
Family and domain databases
InterPro	IPR020845. AMP-binding_CS. IPR000873. AMP-dep_Synth/Lig. [Graphical view]
KO	K01897.
Pfam	PF00501. AMP-binding. 1 hit. [Graphical view]
PROSITE	PS00455. AMP_BINDING. 1 hit. [Graphical view]
ProtoNet	Search...
Other
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): D3DUY2, O60848, O60849

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	April 27, 2001
Last modified:	January 25, 2012
This is version 122 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.