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P22791

- HMCS2_RAT

UniProt

P22791 - HMCS2_RAT

Protein

Hydroxymethylglutaryl-CoA synthase, mitochondrial

Gene

Hmgcs2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 121 (01 Oct 2014)
      Sequence version 1 (01 Aug 1991)
      Previous versions | rss
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    Functioni

    This enzyme condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is the substrate for HMG-CoA reductase.

    Catalytic activityi

    Acetyl-CoA + H2O + acetoacetyl-CoA = (S)-3-hydroxy-3-methylglutaryl-CoA + CoA.PROSITE-ProRule annotation

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei80 – 801SubstrateBy similarity
    Active sitei132 – 1321Proton donor/acceptorPROSITE-ProRule annotation
    Active sitei166 – 1661Acyl-thioester intermediatePROSITE-ProRule annotation
    Binding sitei204 – 2041SubstrateBy similarity
    Binding sitei258 – 2581SubstrateBy similarity
    Active sitei301 – 3011Proton donor/acceptorPROSITE-ProRule annotation
    Binding sitei380 – 3801SubstrateBy similarity

    GO - Molecular functioni

    1. hydroxymethylglutaryl-CoA synthase activity Source: RGD

    GO - Biological processi

    1. adipose tissue development Source: RGD
    2. brain development Source: RGD
    3. cellular response to amino acid stimulus Source: RGD
    4. cellular response to fatty acid Source: RGD
    5. cellular response to glucocorticoid stimulus Source: RGD
    6. cellular response to hormone stimulus Source: RGD
    7. cellular response to insulin stimulus Source: RGD
    8. cellular response to lipopolysaccharide Source: RGD
    9. cellular response to organic cyclic compound Source: RGD
    10. cholesterol biosynthetic process Source: UniProtKB-KW
    11. isoprenoid biosynthetic process Source: InterPro
    12. ketone body biosynthetic process Source: RGD
    13. kidney development Source: RGD
    14. liver development Source: RGD
    15. lung development Source: RGD
    16. midgut development Source: RGD
    17. multicellular organismal response to stress Source: RGD
    18. response to bacterium Source: RGD
    19. response to cAMP Source: RGD
    20. response to drug Source: RGD
    21. response to ethanol Source: RGD
    22. response to fatty acid Source: RGD
    23. response to glucagon Source: RGD
    24. response to glucocorticoid Source: RGD
    25. response to growth hormone Source: RGD
    26. response to insulin Source: RGD
    27. response to linoleic acid Source: RGD
    28. response to metal ion Source: RGD
    29. response to monosaccharide Source: RGD
    30. response to nutrient Source: RGD
    31. response to organic cyclic compound Source: RGD
    32. response to peptide hormone Source: RGD
    33. response to prostaglandin F Source: RGD
    34. response to starvation Source: RGD
    35. response to temperature stimulus Source: RGD
    36. response to testosterone Source: RGD
    37. response to triglyceride Source: RGD

    Keywords - Molecular functioni

    Transferase

    Keywords - Biological processi

    Cholesterol biosynthesis, Cholesterol metabolism, Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis, Steroid metabolism, Sterol biosynthesis, Sterol metabolism

    Enzyme and pathway databases

    BRENDAi2.3.3.10. 5301.
    UniPathwayiUPA00058; UER00102.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Hydroxymethylglutaryl-CoA synthase, mitochondrial (EC:2.3.3.10)
    Short name:
    HMG-CoA synthase
    Alternative name(s):
    3-hydroxy-3-methylglutaryl coenzyme A synthase
    Gene namesi
    Name:Hmgcs2
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi2804. Hmgcs2.

    Subcellular locationi

    GO - Cellular componenti

    1. mitochondrial matrix Source: RGD
    2. mitochondrion Source: RGD

    Keywords - Cellular componenti

    Mitochondrion

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 3737MitochondrionCuratedAdd
    BLAST
    Chaini38 – 508471Hydroxymethylglutaryl-CoA synthase, mitochondrialPRO_0000013486Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei52 – 521N6-succinyllysineBy similarity
    Modified residuei83 – 831N6-acetyllysine; alternateBy similarity
    Modified residuei83 – 831N6-succinyllysine; alternateBy similarity
    Modified residuei118 – 1181N6-acetyllysine; alternateBy similarity
    Modified residuei118 – 1181N6-succinyllysine; alternateBy similarity
    Modified residuei221 – 2211N6-succinyllysineBy similarity
    Modified residuei243 – 2431N6-acetyllysineBy similarity
    Modified residuei256 – 2561N6-acetyllysine; alternateBy similarity
    Modified residuei256 – 2561N6-succinyllysine; alternateBy similarity
    Modified residuei306 – 3061N6-acetyllysineBy similarity
    Modified residuei310 – 3101N6-acetyllysine; alternateBy similarity
    Modified residuei310 – 3101N6-succinyllysine; alternateBy similarity
    Modified residuei327 – 3271N6-acetyllysine; alternateBy similarity
    Modified residuei327 – 3271N6-succinyllysine; alternateBy similarity
    Modified residuei333 – 3331N6-succinyllysineBy similarity
    Modified residuei342 – 3421N6-acetyllysine; alternateBy similarity
    Modified residuei342 – 3421N6-succinyllysine; alternateBy similarity
    Modified residuei350 – 3501N6-acetyllysine; alternateBy similarity
    Modified residuei350 – 3501N6-succinyllysine; alternateBy similarity
    Modified residuei354 – 3541N6-acetyllysine; alternateBy similarity
    Modified residuei354 – 3541N6-succinyllysine; alternateBy similarity
    Modified residuei358 – 3581N6-acetyllysine; alternateBy similarity
    Modified residuei358 – 3581N6-succinyllysine; alternateBy similarity
    Modified residuei427 – 4271N6-acetyllysineBy similarity
    Modified residuei437 – 4371N6-acetyllysineBy similarity
    Modified residuei447 – 4471N6-acetyllysine; alternateBy similarity
    Modified residuei447 – 4471N6-succinyllysine; alternateBy similarity
    Modified residuei473 – 4731N6-acetyllysine; alternateBy similarity
    Modified residuei473 – 4731N6-succinyllysine; alternateBy similarity

    Keywords - PTMi

    Acetylation

    Proteomic databases

    PaxDbiP22791.
    PRIDEiP22791.

    PTM databases

    PhosphoSiteiP22791.

    Expressioni

    Tissue specificityi

    Liver and kidney.

    Gene expression databases

    GenevestigatoriP22791.

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Protein-protein interaction databases

    STRINGi10116.ENSRNOP00000026122.

    Structurei

    3D structure databases

    ProteinModelPortaliP22791.
    SMRiP22791. Positions 53-507.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the HMG-CoA synthase family.Curated

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiCOG3425.
    HOGENOMiHOG000012351.
    HOVERGENiHBG051912.
    InParanoidiP22791.
    PhylomeDBiP22791.

    Family and domain databases

    Gene3Di3.40.47.10. 1 hit.
    InterProiIPR000590. HMG_CoA_synt_AS.
    IPR013746. HMG_CoA_synt_C_dom.
    IPR013528. HMG_CoA_synth_N.
    IPR010122. HMG_CoA_synthase_euk.
    IPR016039. Thiolase-like.
    IPR016038. Thiolase-like_subgr.
    [Graphical view]
    PfamiPF08540. HMG_CoA_synt_C. 1 hit.
    PF01154. HMG_CoA_synt_N. 1 hit.
    [Graphical view]
    SUPFAMiSSF53901. SSF53901. 3 hits.
    TIGRFAMsiTIGR01833. HMG-CoA-S_euk. 1 hit.
    PROSITEiPS01226. HMG_COA_SYNTHASE. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    P22791-1 [UniParc]FASTAAdd to Basket

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    MQRLLAPARR VLQVKRVMQE SSLSPAHLLP AAQQRFSTIP PAPLAKTDTW    50
    PKDVGILALE VYFPAQYVDQ TDLEKFNNVE AGKYTVGLGQ TRMGFCSVQE 100
    DINSLCLTVV QRLMERTKLP WDAVGRLEVG TETIIDKSKA VKTVLMELFQ 150
    DSGNTDIEGI DTTNACYGGT ASLFNAANWM ESSYWDGRYA LVVCGDIAVY 200
    PSGNPRPTGG AGAVAMLIGP KAPLVLEQGL RGTHMENAYD FYKPNLASEY 250
    PLVDGKLSIQ CYLRALDRCY AAYRRKIQNQ WKQAGNNQPF TLDDVQYMIF 300
    HTPFCKMVQK SLARLMFNDF LSSSSDKQNN LYKGLEAFKG LKLEETYTNK 350
    DVDKALLKAS LDMFNKKTKA SLYLSTNNGN MYTSSLYGCL ASLLSHHSAQ 400
    ELAGSRIGAF SYGSGLAASF FSFRVSKDAS PGSPLEKLVS SVSDLPKRLD 450
    SRRRMSPEEF TEIMNQREQF YHKVNFSPPG DTSNLFPGTW YLERVDEMHR 500
    RKYARRPV 508
    Length:508
    Mass (Da):56,912
    Last modified:August 1, 1991 - v1
    Checksum:iEC37693A5541D47E
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M33648 mRNA. Translation: AAA41336.1.
    M63800 Genomic DNA. No translation available.
    PIRiA35865.
    UniGeneiRn.29594.

    Genome annotation databases

    UCSCiRGD:2804. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M33648 mRNA. Translation: AAA41336.1 .
    M63800 Genomic DNA. No translation available.
    PIRi A35865.
    UniGenei Rn.29594.

    3D structure databases

    ProteinModelPortali P22791.
    SMRi P22791. Positions 53-507.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10116.ENSRNOP00000026122.

    PTM databases

    PhosphoSitei P22791.

    Proteomic databases

    PaxDbi P22791.
    PRIDEi P22791.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    UCSCi RGD:2804. rat.

    Organism-specific databases

    RGDi 2804. Hmgcs2.

    Phylogenomic databases

    eggNOGi COG3425.
    HOGENOMi HOG000012351.
    HOVERGENi HBG051912.
    InParanoidi P22791.
    PhylomeDBi P22791.

    Enzyme and pathway databases

    UniPathwayi UPA00058 ; UER00102 .
    BRENDAi 2.3.3.10. 5301.

    Miscellaneous databases

    NextBioi 603355.
    PROi P22791.

    Gene expression databases

    Genevestigatori P22791.

    Family and domain databases

    Gene3Di 3.40.47.10. 1 hit.
    InterProi IPR000590. HMG_CoA_synt_AS.
    IPR013746. HMG_CoA_synt_C_dom.
    IPR013528. HMG_CoA_synth_N.
    IPR010122. HMG_CoA_synthase_euk.
    IPR016039. Thiolase-like.
    IPR016038. Thiolase-like_subgr.
    [Graphical view ]
    Pfami PF08540. HMG_CoA_synt_C. 1 hit.
    PF01154. HMG_CoA_synt_N. 1 hit.
    [Graphical view ]
    SUPFAMi SSF53901. SSF53901. 3 hits.
    TIGRFAMsi TIGR01833. HMG-CoA-S_euk. 1 hit.
    PROSITEi PS01226. HMG_COA_SYNTHASE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Rat mitochondrial and cytosolic 3-hydroxy-3-methylglutaryl-CoA synthases are encoded by two different genes."
      Ayte J., Gil-Gomez G., Haro D., Marrero P.F., Hegardt F.G.
      Proc. Natl. Acad. Sci. U.S.A. 87:3874-3878(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Sprague-Dawley.
      Tissue: Liver.
    2. "The rat mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme-A-synthase gene contains elements that mediate its multihormonal regulation and tissue specificity."
      Gil-Gomez G., Ayte J., Hegardt F.G.
      Eur. J. Biochem. 213:773-779(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-35.

    Entry informationi

    Entry nameiHMCS2_RAT
    AccessioniPrimary (citable) accession number: P22791
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1991
    Last sequence update: August 1, 1991
    Last modified: October 1, 2014
    This is version 121 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3