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Protein

Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 1

Gene

HACD1

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

Functioni

Isoform 1: 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
Isoform 2: In tooth development, may play a role in the recruitment and the differentiation of cells that contribute to cementum formation. May also bind hydroxyapatite and regulate its crystal nucleation to form cementum.1 Publication

Catalytic activityi

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

Kineticsi

  1. KM=33.6 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 sitei210By similarity1
    Active sitei217By 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
    • 3R-hydroxyacyl-CoA dehydratase activity Source: Reactome
    • enzyme binding Source: UniProtKB
    • hydroxyapatite binding Source: UniProtKB

    GO - Biological processi

    • cellular macromolecular complex assembly Source: UniProtKB
    • cementum mineralization Source: UniProtKB
    • fatty acid biosynthetic process Source: UniProtKB-UniPathway
    • fatty acid elongation Source: UniProtKB
    • long-chain fatty-acyl-CoA biosynthetic process Source: Reactome
    • multicellular organism development Source: UniProtKB-KW
    • positive regulation of cell-substrate adhesion Source: UniProtKB
    • sphingolipid biosynthetic process Source: UniProtKB
    • very long-chain fatty acid biosynthetic process Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Developmental protein, Lyase

    Keywords - Biological processi

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

    Enzyme and pathway databases

    ReactomeiR-HSA-75876. Synthesis of very long-chain fatty acyl-CoAs.
    UniPathwayiUPA00094.

    Chemistry databases

    SwissLipidsiSLP:000000435.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 1Curated (EC:4.2.1.1342 Publications)
    Alternative name(s):
    3-hydroxyacyl-CoA dehydratase 11 Publication
    Short name:
    HACD11 Publication
    Cementum-attachment protein1 Publication
    Short name:
    CAP1 Publication
    Protein-tyrosine phosphatase-like member AImported
    Gene namesi
    Name:HACD11 PublicationImported
    Synonyms:PTPLA
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 10

    Organism-specific databases

    HGNCiHGNC:9639. HACD1.

    Subcellular locationi

    Isoform 1 :

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini1 – 75CytoplasmicSequence analysisAdd BLAST75
    Transmembranei76 – 95HelicalSequence analysisAdd BLAST20
    Topological domaini96 – 114LumenalSequence analysisAdd BLAST19
    Transmembranei115 – 131HelicalSequence analysisAdd BLAST17
    Topological domaini132 – 141CytoplasmicSequence analysis10
    Transmembranei142 – 159HelicalSequence analysisAdd BLAST18
    Topological domaini160 – 165LumenalSequence analysis6
    Transmembranei166 – 180HelicalSequence analysisAdd BLAST15
    Topological domaini181 – 203CytoplasmicSequence analysisAdd BLAST23
    Transmembranei204 – 221HelicalSequence analysisAdd BLAST18
    Topological domaini222 – 251LumenalSequence analysisAdd BLAST30
    Transmembranei252 – 269HelicalSequence analysisAdd BLAST18
    Topological domaini270 – 288CytoplasmicSequence analysisAdd BLAST19

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Myopathy, congenital, with fiber-type disproportion (CFTD)1 Publication
    The gene represented in this entry may be involved in disease pathogenesis. A loss-of-function mutation that segregates with the disease was found in four members of a consanguineous family and not identified in unaffected controls. The mutation affects the expression of the mRNA and the produced protein is catalytically inactive.1 Publication
    Disease descriptionA genetically heterogeneous disorder in which there is relative hypotrophy of type 1 muscle fibers compared to type 2 fibers on skeletal muscle biopsy. However, these findings are not specific and can be found in many different myopathic and neuropathic conditions.
    See also OMIM:255310

    Organism-specific databases

    DisGeNETi9200.
    MIMi255310. phenotype.
    OpenTargetsiENSG00000165996.
    Orphaneti2020. Congenital fiber-type disproportion myopathy.
    PharmGKBiPA33982.

    Polymorphism and mutation databases

    BioMutaiPTPLA.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00003493151 – 288Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 1Add BLAST288

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei22PhosphoserineCombined sources1
    Glycosylationi243N-linked (GlcNAc...)Sequence analysis1

    Post-translational modificationi

    N-glycosylated.1 Publication

    Keywords - PTMi

    Glycoprotein, Phosphoprotein

    Proteomic databases

    EPDiB0YJ81.
    MaxQBiB0YJ81.
    PaxDbiB0YJ81.
    PRIDEiB0YJ81.

    PTM databases

    iPTMnetiB0YJ81.
    PhosphoSitePlusiB0YJ81.

    Expressioni

    Tissue specificityi

    Isoform 1 is highly expressed in the myocardium, and to a lesser extent in skeletal and smooth muscular tissues including those from stomach, jejunum, and bladder. Also detected in gingival fibroblasts, periodontal ligament cells, osteoblasts and cementoblasts (PubMed:11054553, PubMed:22067203). Isoform 2 is specifically expressed by cementoblasts but also detected in periodontal ligament cells, heart, liver and kidney (at protein level) (PubMed:22067203).2 Publications

    Developmental stagei

    Isoform 1 is expressed in fetal heart.1 Publication

    Gene expression databases

    BgeeiENSG00000165996.
    CleanExiHS_PTPLA.
    ExpressionAtlasiB0YJ81. baseline and differential.
    GenevisibleiB0YJ81. HS.

    Interactioni

    Subunit structurei

    Isoform 1: 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). Isoform 2: Homooligomer. Self-assembles into spheres which then aggregates to form strings and a meshwork that may support hydroxyapatite crystal nucleation (PubMed:25263524).2 Publications

    GO - Molecular functioni

    • enzyme binding Source: UniProtKB

    Protein-protein interaction databases

    BioGridi114634. 4 interactors.
    IntActiB0YJ81. 1 interactor.
    STRINGi9606.ENSP00000355308.

    Structurei

    3D structure databases

    ProteinModelPortaliB0YJ81.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG3187. Eukaryota.
    COG5198. LUCA.
    GeneTreeiENSGT00530000062962.
    HOGENOMiHOG000190538.
    HOVERGENiHBG057518.
    InParanoidiB0YJ81.
    KOiK10703.
    OMAiGTHRGLY.
    OrthoDBiEOG091G0Q7P.
    PhylomeDBiB0YJ81.
    TreeFamiTF313326.

    Family and domain databases

    InterProiIPR007482. Tyr_Pase-like_PTPLA.
    [Graphical view]
    PANTHERiPTHR11035. PTHR11035. 1 hit.
    PfamiPF04387. PTPLA. 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: B0YJ81-1) [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
    MGRLTEAAAA GSGSRAAGWA GSPPTLLPLS PTSPRCAATM ASSDEDGTNG
    60 70 80 90 100
    GASEAGEDRE APGERRRLGV LATAWLTFYD IAMTAGWLVL AIAMVRFYME
    110 120 130 140 150
    KGTHRGLYKS IQKTLKFFQT FALLEIVHCL IGIVPTSVIV TGVQVSSRIF
    160 170 180 190 200
    MVWLITHSIK PIQNEESVVL FLVAWTVTEI TRYSFYTFSL LDHLPYFIKW
    210 220 230 240 250
    ARYNFFIILY PVGVAGELLT IYAALPHVKK TGMFSIRLPN KYNVSFDYYY
    260 270 280
    FLLITMASYI PLFPQLYFHM LRQRRKVLHG EVIVEKDD
    Length:288
    Mass (Da):32,388
    Last modified:April 8, 2008 - v1
    Checksum:i1CB64F23C3907F6E
    GO
    Isoform 2 (identifier: B0YJ81-2) [UniParc]FASTAAdd to basket
    Also known as: CAP, cementum-attachment protein, PTPLA-CAP1 Publication

    The sequence of this isoform differs from the canonical sequence as follows:
         126-140: IVHCLIGIVPTSVIV → VSFPSCCFSIAVIFM
         141-288: Missing.

    Note: Catalytically inactive since it lacks the active site but may have an alternative function.1 Publication
    Show »
    Length:140
    Mass (Da):14,920
    Checksum:i21870B3D77BD5ECE
    GO

    Sequence cautioni

    The sequence AAG10713 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
    The sequence ACA06059 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti80D → N in AAF21976 (PubMed:10644438).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_04636664E → K.3 PublicationsCorresponds to variant rs7895850dbSNPEnsembl.1
    Natural variantiVAR_04636764E → Q.1 PublicationCorresponds to variant rs7895850dbSNPEnsembl.1
    Natural variantiVAR_04636870V → F.2 PublicationsCorresponds to variant rs11254692dbSNPEnsembl.1
    Natural variantiVAR_046369227H → Y.2 PublicationsCorresponds to variant rs1053926dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_035363126 – 140IVHCL…TSVIV → VSFPSCCFSIAVIFM in isoform 2. 1 PublicationAdd BLAST15
    Alternative sequenceiVSP_035364141 – 288Missing in isoform 2. 1 PublicationAdd BLAST148

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF266852
    , AF266848, AF266849, AF266850, AF266851 Genomic DNA. Translation: AAG10713.1. Different initiation.
    AF114494 mRNA. Translation: AAF21976.1.
    AY455942 mRNA. Translation: AAR22554.1.
    EF445016 Genomic DNA. Translation: ACA06059.1. Different initiation.
    EF445016 Genomic DNA. Translation: ACA06060.1.
    EF445016 Genomic DNA. Translation: ACA06061.1.
    AC069542 Genomic DNA. No translation available.
    BC010353 mRNA. Translation: AAH10353.1.
    CR608689 mRNA. No translation available.
    CCDSiCCDS7121.1. [B0YJ81-1]
    RefSeqiNP_055056.3. NM_014241.3. [B0YJ81-1]
    UniGeneiHs.114062.

    Genome annotation databases

    EnsembliENST00000361271; ENSP00000355308; ENSG00000165996. [B0YJ81-1]
    GeneIDi9200.
    KEGGihsa:9200.
    UCSCiuc001ipg.4. human. [B0YJ81-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF266852
    , AF266848, AF266849, AF266850, AF266851 Genomic DNA. Translation: AAG10713.1. Different initiation.
    AF114494 mRNA. Translation: AAF21976.1.
    AY455942 mRNA. Translation: AAR22554.1.
    EF445016 Genomic DNA. Translation: ACA06059.1. Different initiation.
    EF445016 Genomic DNA. Translation: ACA06060.1.
    EF445016 Genomic DNA. Translation: ACA06061.1.
    AC069542 Genomic DNA. No translation available.
    BC010353 mRNA. Translation: AAH10353.1.
    CR608689 mRNA. No translation available.
    CCDSiCCDS7121.1. [B0YJ81-1]
    RefSeqiNP_055056.3. NM_014241.3. [B0YJ81-1]
    UniGeneiHs.114062.

    3D structure databases

    ProteinModelPortaliB0YJ81.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi114634. 4 interactors.
    IntActiB0YJ81. 1 interactor.
    STRINGi9606.ENSP00000355308.

    Chemistry databases

    SwissLipidsiSLP:000000435.

    PTM databases

    iPTMnetiB0YJ81.
    PhosphoSitePlusiB0YJ81.

    Polymorphism and mutation databases

    BioMutaiPTPLA.

    Proteomic databases

    EPDiB0YJ81.
    MaxQBiB0YJ81.
    PaxDbiB0YJ81.
    PRIDEiB0YJ81.

    Protocols and materials databases

    DNASUi9200.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000361271; ENSP00000355308; ENSG00000165996. [B0YJ81-1]
    GeneIDi9200.
    KEGGihsa:9200.
    UCSCiuc001ipg.4. human. [B0YJ81-1]

    Organism-specific databases

    CTDi9200.
    DisGeNETi9200.
    GeneCardsiHACD1.
    H-InvDBHIX0008683.
    HGNCiHGNC:9639. HACD1.
    MIMi255310. phenotype.
    610467. gene.
    neXtProtiNX_B0YJ81.
    OpenTargetsiENSG00000165996.
    Orphaneti2020. Congenital fiber-type disproportion myopathy.
    PharmGKBiPA33982.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG3187. Eukaryota.
    COG5198. LUCA.
    GeneTreeiENSGT00530000062962.
    HOGENOMiHOG000190538.
    HOVERGENiHBG057518.
    InParanoidiB0YJ81.
    KOiK10703.
    OMAiGTHRGLY.
    OrthoDBiEOG091G0Q7P.
    PhylomeDBiB0YJ81.
    TreeFamiTF313326.

    Enzyme and pathway databases

    UniPathwayiUPA00094.
    ReactomeiR-HSA-75876. Synthesis of very long-chain fatty acyl-CoAs.

    Miscellaneous databases

    GenomeRNAii9200.
    PROiB0YJ81.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000165996.
    CleanExiHS_PTPLA.
    ExpressionAtlasiB0YJ81. baseline and differential.
    GenevisibleiB0YJ81. 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 nameiHACD1_HUMAN
    AccessioniPrimary (citable) accession number: B0YJ81
    Secondary accession number(s): B0YJ80
    , Q6JIC5, Q96FW7, Q9HB93, Q9UHX2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 2, 2008
    Last sequence update: April 8, 2008
    Last modified: November 30, 2016
    This is version 78 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

    Isoform 1 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 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. 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.