Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

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

Gene

HACD3

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. May be involved in Rac1-signaling pathways leading to the modulation of gene expression. Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization (PubMed:25687571).3 Publications

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=49.5 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 sitei286By similarity1
    Active sitei293By 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
    • GTPase activator activity Source: ProtInc

    GO - Biological processi

    • activation of JUN kinase activity Source: ProtInc
    • fatty acid elongation Source: UniProtKB
    • I-kappaB kinase/NF-kappaB signaling Source: ProtInc
    • positive regulation by virus of viral protein levels in host cell Source: AgBase
    • positive regulation of viral genome replication Source: AgBase
    • Rac protein signal transduction Source: UniProtKB
    • Rho protein signal transduction Source: Ensembl
    • small GTPase mediated signal transduction Source: ProtInc
    • 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:ENSG00000074696-MONOMER.
    ReactomeiR-HSA-75876. Synthesis of very long-chain fatty acyl-CoAs.
    UniPathwayiUPA00094.

    Chemistry databases

    SwissLipidsiSLP:000000439.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 3Curated (EC:4.2.1.1341 Publication)
    Alternative name(s):
    3-hydroxyacyl-CoA dehydratase 31 Publication
    Short name:
    HACD31 Publication
    Butyrate-induced protein 11 Publication
    Short name:
    B-ind11 Publication
    Short name:
    hB-ind11 Publication
    Protein-tyrosine phosphatase-like A domain-containing protein 1Imported
    Gene namesi
    Name:HACD31 PublicationImported
    Synonyms:BIND11 Publication, PTPLAD1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 15

    Organism-specific databases

    HGNCiHGNC:24175. HACD3.

    Subcellular locationi

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini1 – 149CytoplasmicSequence analysisAdd BLAST149
    Transmembranei150 – 170HelicalSequence analysisAdd BLAST21
    Topological domaini171 – 185LumenalSequence analysisAdd BLAST15
    Transmembranei186 – 207HelicalSequence analysisAdd BLAST22
    Topological domaini208 – 217CytoplasmicSequence analysis10
    Transmembranei218 – 235HelicalSequence analysisAdd BLAST18
    Topological domaini236 – 241LumenalSequence analysis6
    Transmembranei242 – 256HelicalSequence analysisAdd BLAST15
    Topological domaini257 – 279CytoplasmicSequence analysisAdd BLAST23
    Transmembranei280 – 298HelicalSequence analysisAdd BLAST19
    Topological domaini299 – 322LumenalSequence analysisAdd BLAST24
    Transmembranei323 – 343HelicalSequence analysisAdd BLAST21
    Topological domaini344 – 362CytoplasmicSequence analysisAdd BLAST19

    GO - Cellular componenti

    • cytoplasm Source: HPA
    • endoplasmic reticulum Source: UniProtKB
    • focal adhesion Source: UniProtKB
    • integral component of endoplasmic reticulum membrane Source: GO_Central
    • mitochondrion Source: HPA
    • nuclear membrane Source: HPA
    Complete GO annotation...

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Organism-specific databases

    OpenTargetsiENSG00000074696.
    PharmGKBiPA142671113.

    Polymorphism and mutation databases

    BioMutaiPTPLAD1.
    DMDMi166199462.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00003137241 – 362Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 3Add BLAST362

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei1N-acetylmethionineCombined sources1
    Modified residuei7PhosphothreonineCombined sources1
    Modified residuei114PhosphoserineCombined sources1
    Modified residuei135PhosphoserineCombined sources1

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    EPDiQ9P035.
    MaxQBiQ9P035.
    PaxDbiQ9P035.
    PeptideAtlasiQ9P035.
    PRIDEiQ9P035.
    TopDownProteomicsiQ9P035-1. [Q9P035-1]

    PTM databases

    iPTMnetiQ9P035.
    PhosphoSitePlusiQ9P035.
    SwissPalmiQ9P035.

    Expressioni

    Tissue specificityi

    Highly expressed in testis, kidney, brain, liver and weakly in skeletal muscle, spleen and heart. No expression detected in leukocytes.2 Publications

    Inductioni

    By AKAP12 and histone deacetylase inhibitors such as sodium butyrate.1 Publication

    Gene expression databases

    BgeeiENSG00000074696.
    CleanExiHS_PTPLAD1.
    ExpressionAtlasiQ9P035. baseline and differential.
    GenevisibleiQ9P035. HS.

    Organism-specific databases

    HPAiHPA014837.
    HPA060347.

    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 (PubMed:18554506). Interacts with RAC1 (PubMed:10747961). Associates with internalized insulin receptor/INSR complexes on Golgi/endosomal membranes; HACD3/PTPLAD1 together with ATIC and PRKAA2/AMPK2 is proposed to be part of a signaling network regulating INSR autophosphorylation and endocytosis (PubMed:25687571).3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Q034632EBI-359013,EBI-8803426From a different organism.
    Q99IB82EBI-359013,EBI-6927873From a different organism.
    Q9WMX23EBI-359013,EBI-6863748From a different organism.

    GO - Molecular functioni

    • enzyme binding Source: UniProtKB

    Protein-protein interaction databases

    BioGridi119570. 38 interactors.
    IntActiQ9P035. 35 interactors.
    MINTiMINT-1135933.
    STRINGi9606.ENSP00000261875.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9P035.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini5 – 94CSPROSITE-ProRule annotationAdd BLAST90

    Coiled coil

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Coiled coili111 – 136Sequence analysisAdd BLAST26

    Compositional bias

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Compositional biasi350 – 353Poly-Arg4
    Compositional biasi357 – 360Poly-Lys4

    Sequence similaritiesi

    Contains 1 CS domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Coiled coil, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG3187. Eukaryota.
    COG5198. LUCA.
    GeneTreeiENSGT00530000062962.
    HOGENOMiHOG000008043.
    HOVERGENiHBG108301.
    InParanoidiQ9P035.
    KOiK10703.
    PhylomeDBiQ9P035.
    TreeFamiTF313326.

    Family and domain databases

    Gene3Di2.60.40.790. 1 hit.
    InterProiIPR007052. CS_dom.
    IPR008978. HSP20-like_chaperone.
    IPR007482. Tyr_Pase-like_PTPLA.
    [Graphical view]
    PANTHERiPTHR11035. PTHR11035. 1 hit.
    PfamiPF04387. PTPLA. 1 hit.
    [Graphical view]
    SUPFAMiSSF49764. SSF49764. 1 hit.
    PROSITEiPS51203. CS. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q9P035-1) [UniParc]FASTAAdd to basket

    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
    MENQVLTPHV YWAQRHRELY LRVELSDVQN PAISITENVL HFKAQGHGAK
    60 70 80 90 100
    GDNVYEFHLE FLDLVKPEPV YKLTQRQVNI TVQKKVSQWW ERLTKQEKRP
    110 120 130 140 150
    LFLAPDFDRW LDESDAEMEL RAKEEERLNK LRLESEGSPE TLTNLRKGYL
    160 170 180 190 200
    FMYNLVQFLG FSWIFVNLTV RFCILGKESF YDTFHTVADM MYFCQMLAVV
    210 220 230 240 250
    ETINAAIGVT TSPVLPSLIQ LLGRNFILFI IFGTMEEMQN KAVVFFVFYL
    260 270 280 290 300
    WSAIEIFRYS FYMLTCIDMD WKVLTWLRYT LWIPLYPLGC LAEAVSVIQS
    310 320 330 340 350
    IPIFNETGRF SFTLPYPVKI KVRFSFFLQI YLIMIFLGLY INFRHLYKQR
    360
    RRRYGQKKKK IH
    Length:362
    Mass (Da):43,160
    Last modified:January 15, 2008 - v2
    Checksum:i1B3591E88DD85D16
    GO
    Isoform 2 (identifier: Q9P035-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         69-123: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:307
    Mass (Da):36,431
    Checksum:iB14E762EB96B17F8
    GO

    Sequence cautioni

    The sequence AAF29085 differs from that shown. Reason: Frameshift at position 356.Curated
    The sequence BAC11249 differs from that shown. Reason: Frameshift at position 359.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti60E → K in BAB55101 (PubMed:14702039).Curated1
    Sequence conflicti245F → I in BAC11277 (PubMed:14702039).Curated1
    Sequence conflicti282W → G in AAH35508 (PubMed:15489334).Curated1
    Sequence conflicti292A → V in AAF29085 (PubMed:11042152).Curated1
    Sequence conflicti352 – 362RRYGQKKKKIH → LKMRAGAVAHACDPSALGG in CAB69070 (PubMed:10747961).CuratedAdd BLAST11
    Sequence conflicti361I → K in AAH35508 (PubMed:15489334).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_03771256E → K.Corresponds to variant rs11632737dbSNPEnsembl.1
    Natural variantiVAR_037713269M → L.Corresponds to variant rs2279854dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_05607069 – 123Missing in isoform 2. 1 PublicationAdd BLAST55

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AJ271091 mRNA. Translation: CAB69070.1.
    AF161470 mRNA. Translation: AAF29085.1. Frameshift.
    AK027421 mRNA. Translation: BAB55101.1.
    AK074857 mRNA. Translation: BAC11249.1. Frameshift.
    AK074898 mRNA. Translation: BAC11277.1.
    AK299234 mRNA. Translation: BAG61266.1.
    AC011846 Genomic DNA. No translation available.
    AC027220 Genomic DNA. No translation available.
    BC019873 mRNA. Translation: AAH19873.1.
    BC035508 mRNA. Translation: AAH35508.1.
    BC047685 mRNA. Translation: AAH47685.1.
    BC058912 mRNA. Translation: AAH58912.1.
    DQ251107 Genomic DNA. Translation: ABB83547.1.
    CCDSiCCDS45282.1. [Q9P035-1]
    RefSeqiNP_057479.2. NM_016395.2. [Q9P035-1]
    UniGeneiHs.512973.

    Genome annotation databases

    EnsembliENST00000261875; ENSP00000261875; ENSG00000074696. [Q9P035-1]
    ENST00000442729; ENSP00000392491; ENSG00000074696. [Q9P035-2]
    GeneIDi51495.
    KEGGihsa:51495.
    UCSCiuc002apc.4. human. [Q9P035-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AJ271091 mRNA. Translation: CAB69070.1.
    AF161470 mRNA. Translation: AAF29085.1. Frameshift.
    AK027421 mRNA. Translation: BAB55101.1.
    AK074857 mRNA. Translation: BAC11249.1. Frameshift.
    AK074898 mRNA. Translation: BAC11277.1.
    AK299234 mRNA. Translation: BAG61266.1.
    AC011846 Genomic DNA. No translation available.
    AC027220 Genomic DNA. No translation available.
    BC019873 mRNA. Translation: AAH19873.1.
    BC035508 mRNA. Translation: AAH35508.1.
    BC047685 mRNA. Translation: AAH47685.1.
    BC058912 mRNA. Translation: AAH58912.1.
    DQ251107 Genomic DNA. Translation: ABB83547.1.
    CCDSiCCDS45282.1. [Q9P035-1]
    RefSeqiNP_057479.2. NM_016395.2. [Q9P035-1]
    UniGeneiHs.512973.

    3D structure databases

    ProteinModelPortaliQ9P035.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi119570. 38 interactors.
    IntActiQ9P035. 35 interactors.
    MINTiMINT-1135933.
    STRINGi9606.ENSP00000261875.

    Chemistry databases

    SwissLipidsiSLP:000000439.

    PTM databases

    iPTMnetiQ9P035.
    PhosphoSitePlusiQ9P035.
    SwissPalmiQ9P035.

    Polymorphism and mutation databases

    BioMutaiPTPLAD1.
    DMDMi166199462.

    Proteomic databases

    EPDiQ9P035.
    MaxQBiQ9P035.
    PaxDbiQ9P035.
    PeptideAtlasiQ9P035.
    PRIDEiQ9P035.
    TopDownProteomicsiQ9P035-1. [Q9P035-1]

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000261875; ENSP00000261875; ENSG00000074696. [Q9P035-1]
    ENST00000442729; ENSP00000392491; ENSG00000074696. [Q9P035-2]
    GeneIDi51495.
    KEGGihsa:51495.
    UCSCiuc002apc.4. human. [Q9P035-1]

    Organism-specific databases

    CTDi51495.
    GeneCardsiHACD3.
    H-InvDBHIX0012353.
    HGNCiHGNC:24175. HACD3.
    HPAiHPA014837.
    HPA060347.
    MIMi615940. gene.
    neXtProtiNX_Q9P035.
    OpenTargetsiENSG00000074696.
    PharmGKBiPA142671113.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG3187. Eukaryota.
    COG5198. LUCA.
    GeneTreeiENSGT00530000062962.
    HOGENOMiHOG000008043.
    HOVERGENiHBG108301.
    InParanoidiQ9P035.
    KOiK10703.
    PhylomeDBiQ9P035.
    TreeFamiTF313326.

    Enzyme and pathway databases

    UniPathwayiUPA00094.
    BioCyciZFISH:ENSG00000074696-MONOMER.
    ReactomeiR-HSA-75876. Synthesis of very long-chain fatty acyl-CoAs.

    Miscellaneous databases

    ChiTaRSiPTPLAD1. human.
    GeneWikiiPTPLAD1.
    GenomeRNAii51495.
    PROiQ9P035.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000074696.
    CleanExiHS_PTPLAD1.
    ExpressionAtlasiQ9P035. baseline and differential.
    GenevisibleiQ9P035. HS.

    Family and domain databases

    Gene3Di2.60.40.790. 1 hit.
    InterProiIPR007052. CS_dom.
    IPR008978. HSP20-like_chaperone.
    IPR007482. Tyr_Pase-like_PTPLA.
    [Graphical view]
    PANTHERiPTHR11035. PTHR11035. 1 hit.
    PfamiPF04387. PTPLA. 1 hit.
    [Graphical view]
    SUPFAMiSSF49764. SSF49764. 1 hit.
    PROSITEiPS51203. CS. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiHACD3_HUMAN
    AccessioniPrimary (citable) accession number: Q9P035
    Secondary accession number(s): A0PJA1
    , B4DRF4, Q280Z3, Q6PD63, Q8IUI5, Q8NC86, Q8NCB1, Q96T12, Q9NQA7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 15, 2008
    Last sequence update: January 15, 2008
    Last modified: November 30, 2016
    This is version 122 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

    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 15
      Human chromosome 15: 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.