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Protein

Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 2

Gene

HACD2

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 to 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=121.7 µM for 3-hydroxypalmitoyl-CoA (at 37 degrees Celsius)1 Publication

    Pathway:ifatty 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)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei176 – 1761By similarity
    Active sitei183 – 1831By similarity

    GO - Molecular functioni

    • 3-hydroxyacyl-CoA dehydratase activity Source: UniProtKB
    • enzyme binding Source: UniProtKB

    GO - Biological processi

    • cellular lipid metabolic process Source: Reactome
    • fatty acid elongation Source: UniProtKB
    • long-chain fatty-acyl-CoA biosynthetic process Source: Reactome
    • small molecule metabolic process Source: Reactome
    • sphingolipid biosynthetic process Source: UniProtKB
    • triglyceride biosynthetic process Source: Reactome
    • 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

    ReactomeiREACT_380. Synthesis of very long-chain fatty acyl-CoAs.
    UniPathwayiUPA00094.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 2Curated (EC:4.2.1.1341 Publication)
    Alternative name(s):
    3-hydroxyacyl-CoA dehydratase 21 Publication
    Short name:
    HACD21 Publication
    Protein-tyrosine phosphatase-like member BImported
    Gene namesi
    Name:HACD21 PublicationImported
    Synonyms:PTPLBCurated
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 3

    Organism-specific databases

    HGNCiHGNC:9640. HACD2.

    Subcellular locationi

    Topology

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini2 – 4140CytoplasmicSequence AnalysisAdd
    BLAST
    Transmembranei42 – 6019HelicalSequence AnalysisAdd
    BLAST
    Topological domaini61 – 7919LumenalSequence AnalysisAdd
    BLAST
    Transmembranei80 – 9718HelicalSequence AnalysisAdd
    BLAST
    Topological domaini98 – 10710CytoplasmicSequence Analysis
    Transmembranei108 – 12518HelicalSequence AnalysisAdd
    BLAST
    Topological domaini126 – 1305LumenalSequence Analysis
    Transmembranei131 – 14616HelicalSequence AnalysisAdd
    BLAST
    Topological domaini147 – 16923CytoplasmicSequence AnalysisAdd
    BLAST
    Transmembranei170 – 18718HelicalSequence AnalysisAdd
    BLAST
    Topological domaini188 – 21730LumenalSequence AnalysisAdd
    BLAST
    Transmembranei218 – 23518HelicalSequence AnalysisAdd
    BLAST
    Topological domaini236 – 25419CytoplasmicSequence AnalysisAdd
    BLAST

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi101 – 1011P → R: Does not restore any protein tyrosine phosphatase activity. 1 Publication

    Organism-specific databases

    PharmGKBiPA33983.

    Polymorphism and mutation databases

    BioMutaiPTPLB.
    DMDMi74738322.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 254253Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 2PRO_0000349319Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanine1 Publication
    Glycosylationi209 – 2091N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Acetylation, Glycoprotein

    Proteomic databases

    MaxQBiQ6Y1H2.
    PaxDbiQ6Y1H2.
    PRIDEiQ6Y1H2.

    PTM databases

    PhosphoSiteiQ6Y1H2.

    Expressioni

    Tissue specificityi

    Highly expressed in testis, spleen, prostate, colon and heart, followed by moderate expression in thymus, ovary, small intestine, peripheral blood leukocytes, liver, skeletal muscle and pancreas. Weakly detected in kidney, placenta, brain and lung.1 Publication

    Gene expression databases

    BgeeiQ6Y1H2.
    CleanExiHS_PTPLB.
    ExpressionAtlasiQ6Y1H2. baseline and differential.
    GenevisibleiQ6Y1H2. HS.

    Organism-specific databases

    HPAiCAB019282.

    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 BCAP31 (PubMed:15024066).2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    BCAP31P515724EBI-530257,EBI-77683
    TECRQ9NZ013EBI-530257,EBI-2877718

    Protein-protein interaction databases

    BioGridi128393. 11 interactions.
    IntActiQ6Y1H2. 2 interactions.
    STRINGi9606.ENSP00000373153.

    Structurei

    3D structure databases

    ProteinModelPortaliQ6Y1H2.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi12 – 187Poly-Gly

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG5198.
    GeneTreeiENSGT00530000062962.
    HOGENOMiHOG000190538.
    HOVERGENiHBG057518.
    InParanoidiQ6Y1H2.
    KOiK10703.
    OMAiYHGLYYS.
    OrthoDBiEOG7X6M18.
    PhylomeDBiQ6Y1H2.
    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.

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

    Q6Y1H2-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MAAVAATAAA KGNGGGGGRA GAGDASGTRK KKGPGPLATA YLVIYNVVMT
    60 70 80 90 100
    AGWLVIAVGL VRAYLAKGSY HSLYYSIEKP LKFFQTGALL EILHCAIGIV
    110 120 130 140 150
    PSSVVLTSFQ VMSRVFLIWA VTHSVKEVQS EDSVLLFVIA WTITEIIRYS
    160 170 180 190 200
    FYTFSLLNHL PYLIKWARYT LFIVLYPMGV SGELLTIYAA LPFVRQAGLY
    210 220 230 240 250
    SISLPNKYNF SFDYYAFLIL IMISYIPIFP QLYFHMIHQR RKILSHTEEH

    KKFE
    Length:254
    Mass (Da):28,368
    Last modified:July 5, 2004 - v1
    Checksum:i6B301176C696899E
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY191814 mRNA. Translation: AAP20101.1.
    AK289983 mRNA. Translation: BAF82672.1.
    AC020631 Genomic DNA. No translation available.
    AC023165 Genomic DNA. No translation available.
    AC025571 Genomic DNA. No translation available.
    AC084039 Genomic DNA. No translation available.
    BC049369 mRNA. Translation: AAH49369.1.
    BC060839 mRNA. Translation: AAH60839.1.
    CCDSiCCDS46895.1.
    RefSeqiNP_940684.1. NM_198402.3.
    UniGeneiHs.705480.

    Genome annotation databases

    EnsembliENST00000383657; ENSP00000373153; ENSG00000206527.
    GeneIDi201562.
    KEGGihsa:201562.
    UCSCiuc003egj.2. human.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY191814 mRNA. Translation: AAP20101.1.
    AK289983 mRNA. Translation: BAF82672.1.
    AC020631 Genomic DNA. No translation available.
    AC023165 Genomic DNA. No translation available.
    AC025571 Genomic DNA. No translation available.
    AC084039 Genomic DNA. No translation available.
    BC049369 mRNA. Translation: AAH49369.1.
    BC060839 mRNA. Translation: AAH60839.1.
    CCDSiCCDS46895.1.
    RefSeqiNP_940684.1. NM_198402.3.
    UniGeneiHs.705480.

    3D structure databases

    ProteinModelPortaliQ6Y1H2.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi128393. 11 interactions.
    IntActiQ6Y1H2. 2 interactions.
    STRINGi9606.ENSP00000373153.

    PTM databases

    PhosphoSiteiQ6Y1H2.

    Polymorphism and mutation databases

    BioMutaiPTPLB.
    DMDMi74738322.

    Proteomic databases

    MaxQBiQ6Y1H2.
    PaxDbiQ6Y1H2.
    PRIDEiQ6Y1H2.

    Protocols and materials databases

    DNASUi201562.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000383657; ENSP00000373153; ENSG00000206527.
    GeneIDi201562.
    KEGGihsa:201562.
    UCSCiuc003egj.2. human.

    Organism-specific databases

    CTDi201562.
    GeneCardsiGC03M123209.
    HGNCiHGNC:9640. HACD2.
    HPAiCAB019282.
    MIMi615939. gene.
    neXtProtiNX_Q6Y1H2.
    PharmGKBiPA33983.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG5198.
    GeneTreeiENSGT00530000062962.
    HOGENOMiHOG000190538.
    HOVERGENiHBG057518.
    InParanoidiQ6Y1H2.
    KOiK10703.
    OMAiYHGLYYS.
    OrthoDBiEOG7X6M18.
    PhylomeDBiQ6Y1H2.
    TreeFamiTF313326.

    Enzyme and pathway databases

    UniPathwayiUPA00094.
    ReactomeiREACT_380. Synthesis of very long-chain fatty acyl-CoAs.

    Miscellaneous databases

    GenomeRNAii201562.
    NextBioi90164.
    PROiQ6Y1H2.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ6Y1H2.
    CleanExiHS_PTPLB.
    ExpressionAtlasiQ6Y1H2. baseline and differential.
    GenevisibleiQ6Y1H2. HS.

    Family and domain databases

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

    Publicationsi

    « Hide 'large scale' publications
    1. "The yeast split-ubiquitin membrane protein two-hybrid screen identifies BAP31 as a regulator of the turnover of endoplasmic reticulum-associated protein tyrosine phosphatase-like B."
      Wang B., Pelletier J., Massaad M.J., Herscovics A., Shore G.C.
      Mol. Cell. Biol. 24:2767-2778(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH BCAP31, MUTAGENESIS OF PRO-101, CAUTION.
    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].
    3. "The DNA sequence, annotation and analysis of human chromosome 3."
      Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J.
      , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
      Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "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 Testis.
    5. "Characterization of four mammalian 3-hydroxyacyl-CoA dehydratases involved in very long-chain fatty acid synthesis."
      Ikeda M., Kanao Y., Yamanaka M., Sakuraba H., Mizutani Y., Igarashi Y., Kihara A.
      FEBS Lett. 582:2435-2440(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, PATHWAY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT.
    6. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
      Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
      Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
    7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    9. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
      Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
      J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.

    Entry informationi

    Entry nameiHACD2_HUMAN
    AccessioniPrimary (citable) accession number: Q6Y1H2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 2, 2008
    Last sequence update: July 5, 2004
    Last modified: July 22, 2015
    This is version 103 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

    Miscellaneous

    Turns over rapidly through degradation by the proteasome system.1 Publication

    Caution

    Shares some similarity with tyrosine phosphatase proteins but it has probably no phosphatase activity.1 Publication

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 3
      Human chromosome 3: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    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 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.