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P28330

- ACADL_HUMAN

UniProt

P28330 - ACADL_HUMAN

Protein

Long-chain specific acyl-CoA dehydrogenase, mitochondrial

Gene

ACADL

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 146 (01 Oct 2014)
      Sequence version 2 (10 Feb 2009)
      Previous versions | rss
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    Functioni

    Catalytic activityi

    Long-chain-acyl-CoA + electron-transfer flavoprotein = long-chain-2,3-dehydroacyl-CoA + reduced electron-transfer flavoprotein.

    Cofactori

    FAD.

    Pathwayi

    GO - Molecular functioni

    1. acyl-CoA dehydrogenase activity Source: Reactome
    2. fatty-acyl-CoA binding Source: Ensembl
    3. flavin adenine dinucleotide binding Source: Ensembl
    4. long-chain-acyl-CoA dehydrogenase activity Source: BHF-UCL
    5. palmitoyl-CoA oxidase activity Source: BHF-UCL

    GO - Biological processi

    1. carnitine catabolic process Source: BHF-UCL
    2. carnitine metabolic process, CoA-linked Source: BHF-UCL
    3. cellular lipid catabolic process Source: BHF-UCL
    4. cellular lipid metabolic process Source: Reactome
    5. fatty acid beta-oxidation Source: Reactome
    6. fatty acid beta-oxidation using acyl-CoA dehydrogenase Source: BHF-UCL
    7. long-chain fatty acid catabolic process Source: Ensembl
    8. negative regulation of fatty acid biosynthetic process Source: BHF-UCL
    9. negative regulation of fatty acid oxidation Source: BHF-UCL
    10. oxidation-reduction process Source: BHF-UCL
    11. protein homotetramerization Source: Ensembl
    12. regulation of cholesterol metabolic process Source: BHF-UCL
    13. small molecule metabolic process Source: Reactome
    14. temperature homeostasis Source: BHF-UCL

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Fatty acid metabolism, Lipid metabolism

    Keywords - Ligandi

    FAD, Flavoprotein

    Enzyme and pathway databases

    BioCyciMetaCyc:HS03876-MONOMER.
    ReactomeiREACT_160. mitochondrial fatty acid beta-oxidation of unsaturated fatty acids.
    REACT_2108. Beta oxidation of myristoyl-CoA to lauroyl-CoA.
    REACT_735. Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA.
    SABIO-RKP28330.
    UniPathwayiUPA00660.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Long-chain specific acyl-CoA dehydrogenase, mitochondrial (EC:1.3.8.8)
    Short name:
    LCAD
    Gene namesi
    Name:ACADL
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:88. ACADL.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: HPA
    2. mitochondrial matrix Source: Reactome
    3. mitochondrial membrane Source: Ensembl
    4. mitochondrion Source: HPA

    Keywords - Cellular componenti

    Mitochondrion

    Pathology & Biotechi

    Involvement in diseasei

    Acyl-CoA dehydrogenase very long-chain deficiency (ACADVLD) [MIM:201475]: An inborn error of mitochondrial fatty acid beta-oxidation which leads to impaired long-chain fatty acid beta-oxidation. It is clinically heterogeneous, with three major phenotypes: a severe childhood form characterized by early onset, high mortality and high incidence of cardiomyopathy; a milder childhood form with later onset, characterized by hypoketotic hypoglycemia, low mortality and rare cardiomyopathy; an adult form, with isolated skeletal muscle involvement, rhabdomyolysis and myoglobinuria, usually triggered by exercise or fasting.
    Note: The disease is caused by mutations affecting the gene represented in this entry.

    Organism-specific databases

    MIMi201475. phenotype.
    Orphaneti99900. Long chain acyl-CoA dehydrogenase deficiency.
    PharmGKBiPA24424.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 3030MitochondrionAdd
    BLAST
    Chaini31 – 430400Long-chain specific acyl-CoA dehydrogenase, mitochondrialPRO_0000000509Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei42 – 421N6-acetyllysineBy similarity
    Modified residuei66 – 661N6-acetyllysine; alternateBy similarity
    Modified residuei66 – 661N6-succinyllysine; alternateBy similarity
    Modified residuei81 – 811N6-acetyllysine; alternateBy similarity
    Modified residuei81 – 811N6-succinyllysine; alternateBy similarity
    Modified residuei92 – 921N6-acetyllysineBy similarity
    Modified residuei95 – 951N6-acetyllysineBy similarity
    Modified residuei165 – 1651N6-succinyllysineBy similarity
    Modified residuei240 – 2401N6-succinyllysineBy similarity
    Modified residuei254 – 2541N6-acetyllysine; alternateBy similarity
    Modified residuei254 – 2541N6-succinyllysine; alternateBy similarity
    Modified residuei279 – 2791N6-acetyllysine; alternateBy similarity
    Modified residuei279 – 2791N6-succinyllysine; alternateBy similarity
    Modified residuei318 – 3181N6-acetyllysineBy similarity
    Modified residuei322 – 3221N6-acetyllysine; alternateBy similarity
    Modified residuei322 – 3221N6-succinyllysine; alternateBy similarity
    Modified residuei358 – 3581N6-acetyllysineBy similarity

    Post-translational modificationi

    Acetylation at Lys-318 and Lys-322 in proximity of the cofactor-binding sites strongly reduces catalytic activity. These sites are deacetylated by SIRT3 By similarity.By similarity

    Keywords - PTMi

    Acetylation

    Proteomic databases

    MaxQBiP28330.
    PaxDbiP28330.
    PRIDEiP28330.

    PTM databases

    PhosphoSiteiP28330.

    Expressioni

    Gene expression databases

    ArrayExpressiP28330.
    BgeeiP28330.
    CleanExiHS_ACADL.
    GenevestigatoriP28330.

    Organism-specific databases

    HPAiHPA010611.
    HPA011990.

    Interactioni

    Subunit structurei

    Homotetramer.

    Protein-protein interaction databases

    BioGridi106551. 2 interactions.
    STRINGi9606.ENSP00000233710.

    Structurei

    3D structure databases

    ProteinModelPortaliP28330.
    SMRiP28330. Positions 51-426.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the acyl-CoA dehydrogenase family.Curated

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiCOG1960.
    HOGENOMiHOG000131659.
    HOVERGENiHBG104903.
    InParanoidiP28330.
    KOiK00255.
    OMAiYMWEYPV.
    OrthoDBiEOG77126W.
    PhylomeDBiP28330.
    TreeFamiTF105054.

    Family and domain databases

    Gene3Di1.10.540.10. 1 hit.
    2.40.110.10. 1 hit.
    InterProiIPR006089. Acyl-CoA_DH_CS.
    IPR006091. Acyl-CoA_Oxase/DH_cen-dom.
    IPR009075. AcylCo_DH/oxidase_C.
    IPR013786. AcylCoA_DH/ox_N.
    IPR009100. AcylCoA_DH/oxidase_NM_dom.
    [Graphical view]
    PfamiPF00441. Acyl-CoA_dh_1. 1 hit.
    PF02770. Acyl-CoA_dh_M. 1 hit.
    PF02771. Acyl-CoA_dh_N. 1 hit.
    [Graphical view]
    SUPFAMiSSF47203. SSF47203. 1 hit.
    SSF56645. SSF56645. 1 hit.
    PROSITEiPS00072. ACYL_COA_DH_1. 1 hit.
    PS00073. ACYL_COA_DH_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P28330-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAARLLRGSL RVLGGHRAPR QLPAARCSHS GGEERLETPS AKKLTDIGIR    50
    RIFSPEHDIF RKSVRKFFQE EVIPHHSEWE KAGEVSREVW EKAGKQGLLG 100
    VNIAEHLGGI GGDLYSAAIV WEEQAYSNCS GPGFSIHSGI VMSYITNHGS 150
    EEQIKHFIPQ MTAGKCIGAI AMTEPGAGSD LQGIKTNAKK DGSDWILNGS 200
    KVFISNGSLS DVVIVVAVTN HEAPSPAHGI SLFLVENGMK GFIKGRKLHK 250
    MGLKAQDTAE LFFEDIRLPA SALLGEENKG FYYIMKELPQ ERLLIADVAI 300
    SASEFMFEET RNYVKQRKAF GKTVAHLQTV QHKLAELKTH ICVTRAFVDN 350
    CLQLHEAKRL DSATACMAKY WASELQNSVA YDCVQLHGGW GYMWEYPIAK 400
    AYVDARVQPI YGGTNEIMKE LIAREIVFDK 430
    Length:430
    Mass (Da):47,656
    Last modified:February 10, 2009 - v2
    Checksum:i72F9803685406DF9
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti303 – 3031S → T.1 Publication
    Corresponds to variant rs1801204 [ dbSNP | Ensembl ].
    VAR_000328
    Natural varianti333 – 3331K → Q.2 Publications
    Corresponds to variant rs2286963 [ dbSNP | Ensembl ].
    VAR_000329

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M74096 mRNA. Translation: AAA51565.1.
    AK313498 mRNA. Translation: BAG36280.1.
    AC006994 Genomic DNA. Translation: AAY14881.1.
    CH471063 Genomic DNA. Translation: EAW70481.1.
    BC039063 mRNA. Translation: AAH39063.1.
    BC064549 mRNA. Translation: AAH64549.1.
    CCDSiCCDS2389.1.
    PIRiA40559.
    RefSeqiNP_001599.1. NM_001608.3.
    UniGeneiHs.471277.

    Genome annotation databases

    EnsembliENST00000233710; ENSP00000233710; ENSG00000115361.
    GeneIDi33.
    KEGGihsa:33.
    UCSCiuc002vdz.4. human.

    Polymorphism databases

    DMDMi223590148.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M74096 mRNA. Translation: AAA51565.1 .
    AK313498 mRNA. Translation: BAG36280.1 .
    AC006994 Genomic DNA. Translation: AAY14881.1 .
    CH471063 Genomic DNA. Translation: EAW70481.1 .
    BC039063 mRNA. Translation: AAH39063.1 .
    BC064549 mRNA. Translation: AAH64549.1 .
    CCDSi CCDS2389.1.
    PIRi A40559.
    RefSeqi NP_001599.1. NM_001608.3.
    UniGenei Hs.471277.

    3D structure databases

    ProteinModelPortali P28330.
    SMRi P28330. Positions 51-426.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 106551. 2 interactions.
    STRINGi 9606.ENSP00000233710.

    PTM databases

    PhosphoSitei P28330.

    Polymorphism databases

    DMDMi 223590148.

    Proteomic databases

    MaxQBi P28330.
    PaxDbi P28330.
    PRIDEi P28330.

    Protocols and materials databases

    DNASUi 33.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000233710 ; ENSP00000233710 ; ENSG00000115361 .
    GeneIDi 33.
    KEGGi hsa:33.
    UCSCi uc002vdz.4. human.

    Organism-specific databases

    CTDi 33.
    GeneCardsi GC02M211052.
    HGNCi HGNC:88. ACADL.
    HPAi HPA010611.
    HPA011990.
    MIMi 201475. phenotype.
    609576. gene.
    neXtProti NX_P28330.
    Orphaneti 99900. Long chain acyl-CoA dehydrogenase deficiency.
    PharmGKBi PA24424.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG1960.
    HOGENOMi HOG000131659.
    HOVERGENi HBG104903.
    InParanoidi P28330.
    KOi K00255.
    OMAi YMWEYPV.
    OrthoDBi EOG77126W.
    PhylomeDBi P28330.
    TreeFami TF105054.

    Enzyme and pathway databases

    UniPathwayi UPA00660 .
    BioCyci MetaCyc:HS03876-MONOMER.
    Reactomei REACT_160. mitochondrial fatty acid beta-oxidation of unsaturated fatty acids.
    REACT_2108. Beta oxidation of myristoyl-CoA to lauroyl-CoA.
    REACT_735. Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA.
    SABIO-RK P28330.

    Miscellaneous databases

    GenomeRNAii 33.
    NextBioi 127.
    PROi P28330.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P28330.
    Bgeei P28330.
    CleanExi HS_ACADL.
    Genevestigatori P28330.

    Family and domain databases

    Gene3Di 1.10.540.10. 1 hit.
    2.40.110.10. 1 hit.
    InterProi IPR006089. Acyl-CoA_DH_CS.
    IPR006091. Acyl-CoA_Oxase/DH_cen-dom.
    IPR009075. AcylCo_DH/oxidase_C.
    IPR013786. AcylCoA_DH/ox_N.
    IPR009100. AcylCoA_DH/oxidase_NM_dom.
    [Graphical view ]
    Pfami PF00441. Acyl-CoA_dh_1. 1 hit.
    PF02770. Acyl-CoA_dh_M. 1 hit.
    PF02771. Acyl-CoA_dh_N. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47203. SSF47203. 1 hit.
    SSF56645. SSF56645. 1 hit.
    PROSITEi PS00072. ACYL_COA_DH_1. 1 hit.
    PS00073. ACYL_COA_DH_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning and nucleotide sequence of cDNAs encoding human long-chain acyl-CoA dehydrogenase and assignment of the location of its gene (ACADL) to chromosome 2."
      Indo Y., Yang-Feng T., Glassberg R., Tanaka K.
      Genomics 11:609-620(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-333.
      Tissue: Brain.
    3. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
      Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
      , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
      Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "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] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain and Colon.
    6. "The molecular basis of human long chain acyl-CoA dehydrogenase deficiency."
      Kelly D., Ogden M., Hale D., Hainline B., Strauss A.
      Am. J. Hum. Genet. 49:409-409(1991)
      Cited for: VARIANTS THR-303 AND GLN-333.

    Entry informationi

    Entry nameiACADL_HUMAN
    AccessioniPrimary (citable) accession number: P28330
    Secondary accession number(s): B2R8T3, Q8IUN8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 1992
    Last sequence update: February 10, 2009
    Last modified: October 1, 2014
    This is version 146 of the entry and version 2 of the sequence. [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

    Miscellaneous

    A number of straight-chain acyl-CoA dehydrogenases of different substrate specificities are present in mammalian tissues.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: 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. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3