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Protein

Long-chain-fatty-acid--CoA ligase 5

Gene

ACSL5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Acyl-CoA synthetases (ACSL) activate long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation. ACSL5 may activate fatty acids from exogenous sources for the synthesis of triacylglycerol destined for intracellular storage (By similarity). Utilizes a wide range of saturated fatty acids with a preference for C16-C18 unsaturated fatty acids (By similarity). It was suggested that it may also stimulate fatty acid oxidation (By similarity). At the villus tip of the crypt-villus axis of the small intestine may sensitize epithelial cells to apoptosis specifically triggered by the death ligand TRAIL. May have a role in the survival of glioma cells.By similarity3 Publications

Catalytic activityi

ATP + a long-chain fatty acid + CoA = AMP + diphosphate + an acyl-CoA.

Cofactori

Mg2+By similarity

Kineticsi

  1. KM=0.11 µM for palmitic acid (isoform 1 at pH 7.5)1 Publication
  2. KM=0.38 µM for palmitic acid (isoform 1 at pH 9.5)1 Publication
  3. KM=0.04 µM for palmitic acid (isoform 3 at pH 7.5)1 Publication
  4. KM=0.15 µM for palmitic acid (isoform 3 at pH 8.5)1 Publication

    pH dependencei

    Optimum pH is 9.5 (isoform 1), 7.5-8.5 (isoform 3).1 Publication

    GO - Molecular functioni

    GO - Biological processi

    • long-chain fatty acid metabolic process Source: UniProtKB
    • long-chain fatty-acyl-CoA biosynthetic process Source: Reactome
    • regulation of extrinsic apoptotic signaling pathway Source: UniProtKB

    Keywordsi

    Molecular functionLigase
    Biological processFatty acid metabolism, Lipid metabolism
    LigandATP-binding, Magnesium, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS01349-MONOMER
    ReactomeiR-HSA-75876 Synthesis of very long-chain fatty acyl-CoAs
    SABIO-RKiQ9ULC5

    Chemistry databases

    SwissLipidsiSLP:000000202
    SLP:000000517 [Q9ULC5-3]
    SLP:000000518 [Q9ULC5-1]

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Long-chain-fatty-acid--CoA ligase 5 (EC:6.2.1.3)
    Alternative name(s):
    Long-chain acyl-CoA synthetase 5
    Short name:
    LACS 5
    Gene namesi
    Name:ACSL5
    Synonyms:ACS5, FACL5
    ORF Names:UNQ633/PRO1250
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 10

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000197142.10
    HGNCiHGNC:16526 ACSL5
    MIMi605677 gene
    neXtProtiNX_Q9ULC5

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Transmembranei12 – 32Helical; Signal-anchor for type III membrane proteinSequence analysisAdd BLAST21
    Topological domaini33 – 683CytoplasmicSequence analysisAdd BLAST651

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Mitochondrion, Mitochondrion outer membrane

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi51703
    OpenTargetsiENSG00000197142
    PharmGKBiPA27969

    Polymorphism and mutation databases

    BioMutaiACSL5
    DMDMi13431659

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001931121 – 683Long-chain-fatty-acid--CoA ligase 5Add BLAST683

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei361N6-acetyllysineBy similarity1
    Isoform 2 (identifier: Q9ULC5-3)
    Modified residuei32PhosphoserineCombined sources1

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    EPDiQ9ULC5
    PaxDbiQ9ULC5
    PeptideAtlasiQ9ULC5
    PRIDEiQ9ULC5
    ProteomicsDBi84979
    84980 [Q9ULC5-3]
    84981 [Q9ULC5-4]

    PTM databases

    iPTMnetiQ9ULC5
    PhosphoSitePlusiQ9ULC5
    SwissPalmiQ9ULC5

    Expressioni

    Gene expression databases

    BgeeiENSG00000197142
    CleanExiHS_ACSL5
    GenevisibleiQ9ULC5 HS

    Organism-specific databases

    HPAiCAB035986
    CAB062546
    HPA007162

    Interactioni

    Protein-protein interaction databases

    BioGridi119687, 4 interactors
    IntActiQ9ULC5, 14 interactors
    MINTiQ9ULC5
    STRINGi9606.ENSP00000348429

    Structurei

    3D structure databases

    ProteinModelPortaliQ9ULC5
    SMRiQ9ULC5
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG1256 Eukaryota
    COG1022 LUCA
    GeneTreeiENSGT00690000101725
    HOGENOMiHOG000159459
    HOVERGENiHBG050452
    InParanoidiQ9ULC5
    KOiK01897
    OMAiLGCQIFE
    OrthoDBiEOG091G03G9
    PhylomeDBiQ9ULC5
    TreeFamiTF313877

    Family and domain databases

    InterProiView protein in InterPro
    IPR020845 AMP-binding_CS
    IPR000873 AMP-dep_Synth/Lig
    PfamiView protein in Pfam
    PF00501 AMP-binding, 1 hit
    PROSITEiView protein in PROSITE
    PS00455 AMP_BINDING, 1 hit

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q9ULC5-1) [UniParc]FASTAAdd to basket
    Also known as: ACSL5b, ACSL5-fl

    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

            10         20         30         40         50
    MLFIFNFLFS PLPTPALICI LTFGAAIFLW LITRPQPVLP LLDLNNQSVG
    60 70 80 90 100
    IEGGARKGVS QKNNDLTSCC FSDAKTMYEV FQRGLAVSDN GPCLGYRKPN
    110 120 130 140 150
    QPYRWLSYKQ VSDRAEYLGS CLLHKGYKSS PDQFVGIFAQ NRPEWIISEL
    160 170 180 190 200
    ACYTYSMVAV PLYDTLGPEA IVHIVNKADI AMVICDTPQK ALVLIGNVEK
    210 220 230 240 250
    GFTPSLKVII LMDPFDDDLK QRGEKSGIEI LSLYDAENLG KEHFRKPVPP
    260 270 280 290 300
    SPEDLSVICF TSGTTGDPKG AMITHQNIVS NAAAFLKCVE HAYEPTPDDV
    310 320 330 340 350
    AISYLPLAHM FERIVQAVVY SCGARVGFFQ GDIRLLADDM KTLKPTLFPA
    360 370 380 390 400
    VPRLLNRIYD KVQNEAKTPL KKFLLKLAVS SKFKELQKGI IRHDSFWDKL
    410 420 430 440 450
    IFAKIQDSLG GRVRVIVTGA APMSTSVMTF FRAAMGCQVY EAYGQTECTG
    460 470 480 490 500
    GCTFTLPGDW TSGHVGVPLA CNYVKLEDVA DMNYFTVNNE GEVCIKGTNV
    510 520 530 540 550
    FKGYLKDPEK TQEALDSDGW LHTGDIGRWL PNGTLKIIDR KKNIFKLAQG
    560 570 580 590 600
    EYIAPEKIEN IYNRSQPVLQ IFVHGESLRS SLVGVVVPDT DVLPSFAAKL
    610 620 630 640 650
    GVKGSFEELC QNQVVREAIL EDLQKIGKES GLKTFEQVKA IFLHPEPFSI
    660 670 680
    ENGLLTPTLK AKRGELSKYF RTQIDSLYEH IQD
    Note: Localize in mitochondrion and endoplasmic reticulum.
    Length:683
    Mass (Da):75,991
    Last modified:May 1, 2000 - v1
    Checksum:i781AFE1A7A78C286
    GO
    Isoform 2 (identifier: Q9ULC5-3) [UniParc]FASTAAdd to basket
    Also known as: ACSL5a

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MDALKPPCLWRNHERGKKDRDSCGRKNSEPGSPHSLEALRDAAPSQGLNFLLLFTKM

    Show »
    Length:739
    Mass (Da):82,263
    Checksum:iC3A1ABCA53717BCE
    GO
    Isoform 3 (identifier: Q9ULC5-4) [UniParc]FASTAAdd to basket
    Also known as: ACSL5delta20

    The sequence of this isoform differs from the canonical sequence as follows:
         614-637: Missing.

    Note: Localize in mitochondrion and endoplasmic reticulum.
    Show »
    Length:659
    Mass (Da):73,278
    Checksum:i8FA678B997F35EF7
    GO

    Sequence cautioni

    The sequence BAA85979 differs from that shown. Reason: Erroneous initiation.Curated
    The sequence BAA86054 differs from that shown. Reason: Erroneous gene model prediction.Curated

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_022117182M → V. Corresponds to variant dbSNP:rs3736946Ensembl.1
    Natural variantiVAR_036377388K → R in a colorectal cancer sample; somatic mutation. 1 Publication1
    Natural variantiVAR_036378466G → D in a colorectal cancer sample; somatic mutation. 1 Publication1
    Natural variantiVAR_048240486T → A. Corresponds to variant dbSNP:rs12254915Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0379471M → MDALKPPCLWRNHERGKKDR DSCGRKNSEPGSPHSLEALR DAAPSQGLNFLLLFTKM in isoform 2. 3 Publications1
    Alternative sequenceiVSP_038233614 – 637Missing in isoform 3. 1 PublicationAdd BLAST24

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AM262166 mRNA Translation: CAK18174.1
    AY358520 mRNA Translation: AAQ88884.1
    AK000339 mRNA No translation available.
    AK222782 mRNA No translation available.
    AL157786 Genomic DNA No translation available.
    CH471066 Genomic DNA Translation: EAW49532.1
    CH471066 Genomic DNA Translation: EAW49535.1
    CH471066 Genomic DNA Translation: EAW49536.1
    CH471066 Genomic DNA Translation: EAW49539.1
    BC007985 mRNA Translation: AAH07985.2
    AB033899 mRNA Translation: BAA85979.1 Different initiation.
    AB033920 Genomic DNA Translation: BAA86054.1 Sequence problems.
    CCDSiCCDS7572.1 [Q9ULC5-3]
    CCDS7573.1 [Q9ULC5-1]
    RefSeqiNP_057318.2, NM_016234.3 [Q9ULC5-3]
    NP_976313.1, NM_203379.1 [Q9ULC5-1]
    NP_976314.1, NM_203380.1 [Q9ULC5-1]
    UniGeneiHs.11638

    Genome annotation databases

    EnsembliENST00000354273; ENSP00000346223; ENSG00000197142 [Q9ULC5-1]
    ENST00000354655; ENSP00000346680; ENSG00000197142 [Q9ULC5-1]
    ENST00000356116; ENSP00000348429; ENSG00000197142 [Q9ULC5-3]
    ENST00000393081; ENSP00000376796; ENSG00000197142 [Q9ULC5-1]
    ENST00000433418; ENSP00000403647; ENSG00000197142 [Q9ULC5-4]
    GeneIDi51703
    KEGGihsa:51703
    UCSCiuc001kzs.4 human [Q9ULC5-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiACSL5_HUMAN
    AccessioniPrimary (citable) accession number: Q9ULC5
    Secondary accession number(s): A6GV77
    , D3DRB3, Q6UX44, Q9UIU4
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
    Last sequence update: May 1, 2000
    Last modified: July 18, 2018
    This is version 166 of the entry and version 1 of the sequence. See 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 10
      Human chromosome 10: 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

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