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Protein

Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 4

Gene

HACD4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the third of the four reactions of the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process, allows the addition of two carbons to the chain of long- and very long-chain fatty acids/VLCFAs per cycle. This enzyme catalyzes the dehydration of the 3-hydroxyacyl-CoA intermediate into trans-2,3-enoyl-CoA, within each cycle of fatty acid elongation. Thereby, it participates in the production of VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators.1 Publication

Catalytic activityi

A very-long-chain (3R)-3-hydroxyacyl-CoA = a very-long-chain trans-2,3-dehydroacyl-CoA + H2O.1 Publication

Kineticsi

  1. KM=6.8 µM for 3-hydroxypalmitoyl-CoA (at 37 degrees Celsius)1 Publication

    Pathwayi: fatty acid biosynthesis

    This protein is involved in the pathway fatty acid biosynthesis, which is part of Lipid metabolism.1 Publication
    View all proteins of this organism that are known to be involved in the pathway fatty acid biosynthesis and in Lipid metabolism.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei156By similarity1
    Active sitei163By similarity1

    GO - Molecular functioni

    • 3-hydroxyacyl-CoA dehydratase activity Source: UniProtKB
    • 3-hydroxy-behenoyl-CoA dehydratase activity Source: UniProtKB-EC
    • 3-hydroxy-lignoceroyl-CoA dehydratase activity Source: UniProtKB-EC
    • enzyme binding Source: UniProtKB

    GO - Biological processi

    • fatty acid elongation Source: UniProtKB
    • sphingolipid biosynthetic process Source: GO_Central
    • very long-chain fatty acid biosynthetic process Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Lyase

    Keywords - Biological processi

    Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism

    Enzyme and pathway databases

    BioCyciZFISH:G66-33148-MONOMER.
    ReactomeiR-HSA-75876. Synthesis of very long-chain fatty acyl-CoAs.
    UniPathwayiUPA00094.

    Chemistry databases

    SwissLipidsiSLP:000000440.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 4Curated (EC:4.2.1.1341 Publication)
    Alternative name(s):
    3-hydroxyacyl-CoA dehydratase 41 Publication
    Short name:
    HACD41 Publication
    Protein-tyrosine phosphatase-like A domain-containing protein 2Imported
    Gene namesi
    Name:HACD41 PublicationImported
    Synonyms:PTPLAD2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 9

    Organism-specific databases

    HGNCiHGNC:20920. HACD4.

    Subcellular locationi

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini1 – 19CytoplasmicSequence analysisAdd BLAST19
    Transmembranei20 – 40HelicalSequence analysisAdd BLAST21
    Topological domaini41 – 56LumenalSequence analysisAdd BLAST16
    Transmembranei57 – 77HelicalSequence analysisAdd BLAST21
    Topological domaini78 – 112CytoplasmicSequence analysisAdd BLAST35
    Transmembranei113 – 133HelicalSequence analysisAdd BLAST21
    Topological domaini134 – 135LumenalSequence analysis2
    Transmembranei136 – 156HelicalSequence analysisAdd BLAST21
    Topological domaini157CytoplasmicSequence analysis1
    Transmembranei158 – 178HelicalSequence analysisAdd BLAST21
    Topological domaini179 – 189LumenalSequence analysisAdd BLAST11
    Transmembranei190 – 210HelicalSequence analysisAdd BLAST21
    Topological domaini211 – 232CytoplasmicSequence analysisAdd BLAST22

    GO - Cellular componenti

    • endoplasmic reticulum Source: UniProtKB
    • integral component of endoplasmic reticulum membrane Source: GO_Central
    Complete GO annotation...

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Organism-specific databases

    OpenTargetsiENSG00000188921.
    PharmGKBiPA142671114.

    Polymorphism and mutation databases

    BioMutaiPTPLAD2.
    DMDMi74747375.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00003137301 – 232Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 4Add BLAST232

    Proteomic databases

    PaxDbiQ5VWC8.
    PeptideAtlasiQ5VWC8.
    PRIDEiQ5VWC8.
    TopDownProteomicsiQ5VWC8.

    Expressioni

    Tissue specificityi

    Highly expressed in leukocytes, and low expression in heart, spleen, kidney, and placenta.1 Publication

    Gene expression databases

    BgeeiENSG00000188921.
    CleanExiHS_PTPLAD2.
    GenevisibleiQ5VWC8. HS.

    Organism-specific databases

    HPAiHPA058666.

    Interactioni

    Subunit structurei

    May interact with enzymes of the ELO family (including ELOVL1); with those enzymes that mediate condensation, the first of the four steps of the reaction cycle responsible for fatty acids elongation, may be part of a larger fatty acids elongase complex.1 Publication

    GO - Molecular functioni

    • enzyme binding Source: UniProtKB

    Protein-protein interaction databases

    STRINGi9606.ENSP00000419503.

    Structurei

    3D structure databases

    ProteinModelPortaliQ5VWC8.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Compositional bias

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Compositional biasi228 – 231Poly-Lys4

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG3187. Eukaryota.
    COG5198. LUCA.
    GeneTreeiENSGT00530000062962.
    HOGENOMiHOG000008043.
    HOVERGENiHBG098372.
    InParanoidiQ5VWC8.
    KOiK10703.
    OMAiPYVLKMY.
    OrthoDBiEOG091G09PF.
    PhylomeDBiQ5VWC8.
    TreeFamiTF313326.

    Family and domain databases

    InterProiIPR007482. Tyr_Pase-like_PTPLA.
    [Graphical view]
    PANTHERiPTHR11035. PTHR11035. 1 hit.
    PfamiPF04387. PTPLA. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q5VWC8-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MGPLALPAWL QPRYRKNAYL FIYYLIQFCG HSWIFTNMTV RFFSFGKDSM
    60 70 80 90 100
    VDTFYAIGLV MRLCQSVSLL ELLHIYVGIE SNHLLPRFLQ LTERIIILFV
    110 120 130 140 150
    VITSQEEVQE KYVVCVLFVF WNLLDMVRYT YSMLSVIGIS YAVLTWLSQT
    160 170 180 190 200
    LWMPIYPLCV LAEAFAIYQS LPYFESFGTY STKLPFDLSI YFPYVLKIYL
    210 220 230
    MMLFIGMYFT YSHLYSERRD ILGIFPIKKK KM
    Length:232
    Mass (Da):27,520
    Last modified:December 7, 2004 - v1
    Checksum:i696D578BA5239DDD
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti133M → V in CAD97990 (PubMed:17974005).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_03771436T → A.Corresponds to variant rs2298260dbSNPEnsembl.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AL390882 Genomic DNA. Translation: CAH70162.1.
    CH471071 Genomic DNA. Translation: EAW58626.1.
    BC114215 mRNA. Translation: AAI14216.1.
    BX538052 mRNA. Translation: CAD97990.1.
    CCDSiCCDS43791.1.
    RefSeqiNP_001010915.2. NM_001010915.4.
    NP_001308812.1. NM_001321883.1.
    UniGeneiHs.716678.

    Genome annotation databases

    EnsembliENST00000495827; ENSP00000419503; ENSG00000188921.
    GeneIDi401494.
    KEGGihsa:401494.
    UCSCiuc010miq.3. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AL390882 Genomic DNA. Translation: CAH70162.1.
    CH471071 Genomic DNA. Translation: EAW58626.1.
    BC114215 mRNA. Translation: AAI14216.1.
    BX538052 mRNA. Translation: CAD97990.1.
    CCDSiCCDS43791.1.
    RefSeqiNP_001010915.2. NM_001010915.4.
    NP_001308812.1. NM_001321883.1.
    UniGeneiHs.716678.

    3D structure databases

    ProteinModelPortaliQ5VWC8.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi9606.ENSP00000419503.

    Chemistry databases

    SwissLipidsiSLP:000000440.

    Polymorphism and mutation databases

    BioMutaiPTPLAD2.
    DMDMi74747375.

    Proteomic databases

    PaxDbiQ5VWC8.
    PeptideAtlasiQ5VWC8.
    PRIDEiQ5VWC8.
    TopDownProteomicsiQ5VWC8.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000495827; ENSP00000419503; ENSG00000188921.
    GeneIDi401494.
    KEGGihsa:401494.
    UCSCiuc010miq.3. human.

    Organism-specific databases

    CTDi401494.
    GeneCardsiHACD4.
    H-InvDBHIX0025749.
    HGNCiHGNC:20920. HACD4.
    HPAiHPA058666.
    MIMi615941. gene.
    neXtProtiNX_Q5VWC8.
    OpenTargetsiENSG00000188921.
    PharmGKBiPA142671114.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG3187. Eukaryota.
    COG5198. LUCA.
    GeneTreeiENSGT00530000062962.
    HOGENOMiHOG000008043.
    HOVERGENiHBG098372.
    InParanoidiQ5VWC8.
    KOiK10703.
    OMAiPYVLKMY.
    OrthoDBiEOG091G09PF.
    PhylomeDBiQ5VWC8.
    TreeFamiTF313326.

    Enzyme and pathway databases

    UniPathwayiUPA00094.
    BioCyciZFISH:G66-33148-MONOMER.
    ReactomeiR-HSA-75876. Synthesis of very long-chain fatty acyl-CoAs.

    Miscellaneous databases

    GenomeRNAii401494.
    PROiQ5VWC8.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000188921.
    CleanExiHS_PTPLAD2.
    GenevisibleiQ5VWC8. HS.

    Family and domain databases

    InterProiIPR007482. Tyr_Pase-like_PTPLA.
    [Graphical view]
    PANTHERiPTHR11035. PTHR11035. 1 hit.
    PfamiPF04387. PTPLA. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiHACD4_HUMAN
    AccessioniPrimary (citable) accession number: Q5VWC8
    Secondary accession number(s): Q7Z385
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 15, 2008
    Last sequence update: December 7, 2004
    Last modified: November 2, 2016
    This is version 85 of the entry and version 1 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

    Caution

    Shares some similarity with tyrosine phosphatase proteins but it has probably no phosphatase activity.By similarity1 Publication

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 9
      Human chromosome 9: 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

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.