Overview
| Uniprot ID | O60488 |
| Protein Name | Long-chain-fatty-acid--CoA ligase 4 |
| Gene Name | ACSL4 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 117 |
PNGKVFKKLILGNYK |
| 213 |
ELLESKLKTALLDIS |
| 397 |
QEMNYIQKTLFKIGY |
| 500 |
ICCEIKLKDWQEGGY |
| 621 |
SFVVPNQKRLTLLAQ |
| 661 |
REAANAMKLERFEIP |
| 670 |
ERFEIPIKVRLSPEP |
| 702 |
ELRNHYLKDIERMYG |
| 89 |
LFDHAVSKFGKKDSL |
Function
Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:21242590, PubMed:22633490, PubMed:24269233, PubMed:31061331, PubMed:38720107). Preferentially activates arachidonate and eicosapentaenoate as substrates (PubMed:21242590). Preferentially activates 8,9-EET > 14,15-EET > 5,6-EET > 11,12-EET (PubMed:21242590). Modulates glucose-stimulated insulin secretion by regulating the levels of unesterified EETs (By similarity). Modulates prostaglandin E2 secretion (PubMed:21242590). Acts as an activator of ferroptosis by activating polyunsaturated fatty acids, especially arachidonate and adrenate, to their active form, generating the primary lipid-peroxidation substrates that contribute to ferroptosis (PubMed:27842070, PubMed:35027735, PubMed:38720107)
Protein Sequence
10
MKLKLNVLTI
20
ILLPVHLLIT
30
IYSALIFIPW
40
YFLTNAKKKN
50
AMAKRIKAKP
60
TSDKPGSPYR
70
SVTHFDSLAV
80
IDIPGADTLD
90
KLFDHAVSKF
100
GKKDSLGTRE
110
ILSEENEMQP
120
NGKVFKKLIL
130
GNYKWMNYLE
140
VNRRVNNFGS
150
GLTALGLKPK
160
NTIAIFCETR
170
AEWMIAAQTC
180
FKYNFPLVTL
190
YATLGKEAVV
200
HGLNESEASY
210
LITSVELLES
220
KLKTALLDIS
230
CVKHIIYVDN
240
KAINKAEYPE
250
GFEIHSMQSV
260
EELGSNPENL
270
GIPPSRPTPS
280
DMAIVMYTSG
290
STGRPKGVMM
300
HHSNLIAGMT
310
GQCERIPGLG
320
PKDTYIGYLP
330
LAHVLELTAE
340
ISCFTYGCRI
350
GYSSPLTLSD
360
QSSKIKKGSK
370
GDCTVLKPTL
380
MAAVPEIMDR
390
IYKNVMSKVQ
400
EMNYIQKTLF
410
KIGYDYKLEQ
420
IKKGYDAPLC
430
NLLLFKKVKA
440
LLGGNVRMML
450
SGGAPLSPQT
460
HRFMNVCFCC
470
PIGQGYGLTE
480
SCGAGTVTEV
490
TDYTTGRVGA
500
PLICCEIKLK
510
DWQEGGYTIN
520
DKPNPRGEIV
530
IGGQNISMGY
540
FKNEEKTAED
550
YSVDENGQRW
560
FCTGDIGEFH
570
PDGCLQIIDR
580
KKDLVKLQAG
590
EYVSLGKVEA
600
ALKNCPLIDN
610
ICAFAKSDQS
620
YVISFVVPNQ
630
KRLTLLAQQK
640
GVEGTWVDIC
650
NNPAMEAEIL
660
KEIREAANAM
670
KLERFEIPIK
680
VRLSPEPWTP
690
ETGLVTDAFK
700
LKRKELRNHY
710
LKDIERMYGG
K
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005789 |
endoplasmic reticulum membrane |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005783 |
endoplasmic reticulum |
| Cellular Component |
GO:0070062 |
extracellular exosome |
| Cellular Component |
GO:0005811 |
lipid droplet |
| Cellular Component |
GO:0016020 |
membrane |
| Cellular Component |
GO:0044233 |
mitochondria-associated endoplasmic reticulum membrane contact site |
| Cellular Component |
GO:0005741 |
mitochondrial outer membrane |
| Cellular Component |
GO:0005739 |
mitochondrion |
| Cellular Component |
GO:0005886 |
plasma membrane |
| Molecular Function |
GO:0047676 |
arachidonate-CoA ligase activity |
| Molecular Function |
GO:0005524 |
ATP binding |
| Molecular Function |
GO:0004467 |
long-chain fatty acid-CoA ligase activity |
| Molecular Function |
GO:0090433 |
palmitoyl-CoA ligase activity |
| Molecular Function |
GO:0031957 |
very long-chain fatty acid-CoA ligase activity |
| Biological Process |
GO:0006633 |
fatty acid biosynthetic process |
| Biological Process |
GO:0006631 |
fatty acid metabolic process |
| Biological Process |
GO:0008610 |
lipid biosynthetic process |
| Biological Process |
GO:0006629 |
lipid metabolic process |
| Biological Process |
GO:0001676 |
long-chain fatty acid metabolic process |
| Biological Process |
GO:0035338 |
long-chain fatty-acyl-CoA biosynthetic process |
| Biological Process |
GO:0035336 |
long-chain fatty-acyl-CoA metabolic process |
| Biological Process |
GO:0032307 |
negative regulation of prostaglandin secretion |
| Biological Process |
GO:0030182 |
neuron differentiation |
| Biological Process |
GO:0030307 |
positive regulation of cell growth |
| Biological Process |
GO:0160020 |
positive regulation of ferroptosis |
| Biological Process |
GO:0032024 |
positive regulation of insulin secretion |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.