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Protein

O-acetyl-ADP-ribose deacetylase MACROD1

Gene

MACROD1

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

Functioni

Removes ADP-ribose from glutamate residues in proteins bearing a single ADP-ribose moiety. Inactive towards proteins bearing poly-ADP-ribose. Deacetylates O-acetyl-ADP ribose, a signaling molecule generated by the deacetylation of acetylated lysine residues in histones and other proteins. Plays a role in estrogen signaling. Binds to androgen receptor (AR) and amplifies the transactivation function of AR in response to androgen. May play an important role in carcinogenesis and/or progression of hormone-dependent cancers by feed-forward mechanism that activates ESR1 transactivation. Could be an ESR1 coactivator, providing a positive feedback regulatory loop for ESR1 signal transduction. Could be involved in invasive growth by down-regulating CDH1 in endometrial cancer cells. Enhances ESR1-mediated transcription activity.6 Publications

Enzyme regulationi

Subject to competitive inhibition by the product ADP-ribose.1 Publication

Kineticsi

  1. KM=373 µM for O-acetyl-ADP-ribose1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei306 – 3061SubstrateBy similarity

    GO - Molecular functioni

    • deacetylase activity Source: UniProtKB
    • hydrolase activity, acting on glycosyl bonds Source: UniProtKB

    GO - Biological processi

    • cellular response to DNA damage stimulus Source: UniProtKB
    • protein de-ADP-ribosylation Source: UniProtKB
    • purine nucleoside metabolic process Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    DNA damage

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    O-acetyl-ADP-ribose deacetylase MACROD1 (EC:3.2.2.-, EC:3.5.1.-)
    Alternative name(s):
    MACRO domain-containing protein 1
    Protein LRP16
    [Protein ADP-ribosylglutamate] hydrolase
    Gene namesi
    Name:MACROD1
    Synonyms:LRP16
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:29598. MACROD1.

    Subcellular locationi

    GO - Cellular componenti

    • mitochondrion Source: Ensembl
    • nucleus Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    A chromosomal aberration involving MACROD1 is found in acute leukemia. Translocation t(11;21)(q13;q22) that forms a RUNX1-MACROD1 fusion protein.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi160 – 1601D → A: Reduced enzyme activity. 1 Publication
    Mutagenesisi167 – 1671D → A: Reduced enzyme activity. 1 Publication
    Mutagenesisi171 – 1711N → A: Reduced enzyme activity. No significant effect on affinity for substrate. 1 Publication
    Mutagenesisi174 – 1741N → A: Slightly reduced ADP-ribosyl hydrolase activity; when associated with A-184. Reduces O-acetyl-ADP-ribose deacetylase activity by 93%; when associated with A-184. No significant effect on affinity for substrate. 2 Publications
    Mutagenesisi184 – 1841D → A: Slightly reduced ADP-ribosyl hydrolase activity; when associated with A-174. Reduces O-acetyl-ADP-ribose deacetylase activity by 93%; when associated with A-174. No significant effect on affinity for substrate. 2 Publications
    Mutagenesisi188 – 1881H → A: Reduced enzyme activity. 1 Publication
    Mutagenesisi268 – 2681S → A: No significant effect on enzyme activity. 1 Publication
    Mutagenesisi270 – 2701G → E: Loss of enzyme activity. 2 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei100 – 1001Breakpoint for translocation to form RUNX1-MACROD11 Publication

    Organism-specific databases

    PharmGKBiPA162394816.

    Polymorphism and mutation databases

    BioMutaiMACROD1.
    DMDMi32129719.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 325325O-acetyl-ADP-ribose deacetylase MACROD1PRO_0000084485Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei96 – 961N6-succinyllysineBy similarity
    Modified residuei103 – 1031N6-succinyllysineBy similarity
    Modified residuei129 – 1291N6-succinyllysineBy similarity
    Modified residuei163 – 1631N6-acetyllysineBy similarity

    Keywords - PTMi

    Acetylation

    Proteomic databases

    EPDiQ9BQ69.
    MaxQBiQ9BQ69.
    PaxDbiQ9BQ69.
    PeptideAtlasiQ9BQ69.
    PRIDEiQ9BQ69.

    PTM databases

    iPTMnetiQ9BQ69.
    PhosphoSiteiQ9BQ69.

    Expressioni

    Inductioni

    Overexpressed by estrogens in breast cancer MCF-7 cells, probably via an activation of nuclear receptors for steroids (ESR1 but not ESR2). Significantly increased by estrogens in ESR1-positive Ishikawa endometrial cancer cells. Up-regulated in 17-beta-estradiol-responsive BG-1 ovarian cancer cells but down-regulated in estrogen-resistant SKOV3 ovarian cancer cells. Induced by androgen.4 Publications

    Gene expression databases

    BgeeiQ9BQ69.
    CleanExiHS_MACROD1.
    GenevisibleiQ9BQ69. HS.

    Organism-specific databases

    HPAiHPA041031.

    Interactioni

    Subunit structurei

    Interacts with ESR1; Interacts in a manner that is estrogen independent but is enhanced by estrogen. Interacts (via macro domain) with AR.2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ESR1P033724EBI-5324932,EBI-78473

    Protein-protein interaction databases

    BioGridi118813. 14 interactions.
    IntActiQ9BQ69. 2 interactions.
    STRINGi9606.ENSP00000255681.

    Structurei

    Secondary structure

    1
    325
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi94 – 10310Combined sources
    Helixi107 – 1104Combined sources
    Helixi111 – 1133Combined sources
    Helixi122 – 1243Combined sources
    Helixi128 – 1325Combined sources
    Helixi148 – 1514Combined sources
    Beta strandi154 – 1596Combined sources
    Helixi161 – 1633Combined sources
    Beta strandi164 – 1729Combined sources
    Helixi182 – 19110Combined sources
    Helixi193 – 2008Combined sources
    Beta strandi210 – 2145Combined sources
    Beta strandi218 – 22710Combined sources
    Helixi237 – 25620Combined sources
    Beta strandi261 – 2644Combined sources
    Helixi276 – 29419Combined sources
    Helixi295 – 2973Combined sources
    Beta strandi299 – 3057Combined sources
    Helixi308 – 32114Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2X47X-ray1.70A91-325[»]
    ProteinModelPortaliQ9BQ69.
    SMRiQ9BQ69. Positions 91-325.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9BQ69.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini141 – 322182MacroPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni159 – 1613Substrate bindingBy similarity
    Regioni172 – 1743Substrate bindingBy similarity
    Regioni179 – 1846Substrate bindingBy similarity
    Regioni267 – 2737Substrate bindingCurated

    Sequence similaritiesi

    Contains 1 Macro domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiKOG2633. Eukaryota.
    COG2110. LUCA.
    GeneTreeiENSGT00520000055566.
    HOGENOMiHOG000086960.
    HOVERGENiHBG052356.
    InParanoidiQ9BQ69.
    OMAiKITCGYR.
    OrthoDBiEOG7D2FFN.
    PhylomeDBiQ9BQ69.
    TreeFamiTF341440.

    Family and domain databases

    InterProiIPR002589. Macro_dom.
    [Graphical view]
    PfamiPF01661. Macro. 1 hit.
    [Graphical view]
    SMARTiSM00506. A1pp. 1 hit.
    [Graphical view]
    PROSITEiPS51154. MACRO. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9BQ69-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MSLQSRLSGR LAQLRAAGQL LVPPRPRPGH LAGATRTRSS TCGPPAFLGV
    60 70 80 90 100
    FGRRARTSAG VGAWGAAAVG RTAGVRTWAP LAMAAKVDLS TSTDWKEAKS
    110 120 130 140 150
    FLKGLSDKQR EEHYFCKDFV RLKKIPTWKE MAKGVAVKVE EPRYKKDKQL
    160 170 180 190 200
    NEKISLLRSD ITKLEVDAIV NAANSSLLGG GGVDGCIHRA AGPLLTDECR
    210 220 230 240 250
    TLQSCKTGKA KITGGYRLPA KYVIHTVGPI AYGEPSASQA AELRSCYLSS
    260 270 280 290 300
    LDLLLEHRLR SVAFPCISTG VFGYPCEAAA EIVLATLREW LEQHKDKVDR
    310 320
    LIICVFLEKD EDIYRSRLPH YFPVA
    Length:325
    Mass (Da):35,505
    Last modified:June 16, 2003 - v2
    Checksum:i82294BFC904FA4D0
    GO

    Sequence cautioni

    The sequence AAH03188.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
    The sequence AAH03188.1 differs from that shown. Reason: Erroneous initiation. Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF202922 mRNA. Translation: AAF15294.2.
    BC000270 mRNA. Translation: AAH00270.2.
    BC003188 mRNA. Translation: AAH03188.1. Different initiation.
    BC007297 mRNA. Translation: AAH07297.1.
    BC008316 mRNA. Translation: AAH08316.1.
    CCDSiCCDS8056.1.
    RefSeqiNP_054786.2. NM_014067.3.
    UniGeneiHs.602898.

    Genome annotation databases

    EnsembliENST00000255681; ENSP00000255681; ENSG00000133315.
    GeneIDi28992.
    KEGGihsa:28992.
    UCSCiuc001nyh.4. human.

    Keywords - Coding sequence diversityi

    Chromosomal rearrangement

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF202922 mRNA. Translation: AAF15294.2.
    BC000270 mRNA. Translation: AAH00270.2.
    BC003188 mRNA. Translation: AAH03188.1. Different initiation.
    BC007297 mRNA. Translation: AAH07297.1.
    BC008316 mRNA. Translation: AAH08316.1.
    CCDSiCCDS8056.1.
    RefSeqiNP_054786.2. NM_014067.3.
    UniGeneiHs.602898.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2X47X-ray1.70A91-325[»]
    ProteinModelPortaliQ9BQ69.
    SMRiQ9BQ69. Positions 91-325.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi118813. 14 interactions.
    IntActiQ9BQ69. 2 interactions.
    STRINGi9606.ENSP00000255681.

    PTM databases

    iPTMnetiQ9BQ69.
    PhosphoSiteiQ9BQ69.

    Polymorphism and mutation databases

    BioMutaiMACROD1.
    DMDMi32129719.

    Proteomic databases

    EPDiQ9BQ69.
    MaxQBiQ9BQ69.
    PaxDbiQ9BQ69.
    PeptideAtlasiQ9BQ69.
    PRIDEiQ9BQ69.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000255681; ENSP00000255681; ENSG00000133315.
    GeneIDi28992.
    KEGGihsa:28992.
    UCSCiuc001nyh.4. human.

    Organism-specific databases

    CTDi28992.
    GeneCardsiMACROD1.
    HGNCiHGNC:29598. MACROD1.
    HPAiHPA041031.
    MIMi610400. gene.
    neXtProtiNX_Q9BQ69.
    PharmGKBiPA162394816.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG2633. Eukaryota.
    COG2110. LUCA.
    GeneTreeiENSGT00520000055566.
    HOGENOMiHOG000086960.
    HOVERGENiHBG052356.
    InParanoidiQ9BQ69.
    OMAiKITCGYR.
    OrthoDBiEOG7D2FFN.
    PhylomeDBiQ9BQ69.
    TreeFamiTF341440.

    Miscellaneous databases

    ChiTaRSiMACROD1. human.
    EvolutionaryTraceiQ9BQ69.
    GenomeRNAii28992.
    NextBioi51921.
    PROiQ9BQ69.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ9BQ69.
    CleanExiHS_MACROD1.
    GenevisibleiQ9BQ69. HS.

    Family and domain databases

    InterProiIPR002589. Macro_dom.
    [Graphical view]
    PfamiPF01661. Macro. 1 hit.
    [Graphical view]
    SMARTiSM00506. A1pp. 1 hit.
    [Graphical view]
    PROSITEiPS51154. MACRO. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "The application of RACE technique to clone the full-length cDNA of a novel leukemia associated gene LRP16."
      Han W.-D., Yu L., Lou F.D., Wang Q.S., Zhao Y., Shi Z.J., Jin H.J.
      Zhongguo Shi Yan Xue Ye Xue Za Zhi 9:18-21(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Lymphocyte.
    2. "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 Eye.
    3. "Up-regulation of LRP16 mRNA by 17beta-estradiol through activation of estrogen receptor alpha (ERalpha), but not ERbeta, and promotion of human breast cancer MCF-7 cell proliferation: a preliminary report."
      Han W.-D., Mu Y.-M., Lu X.-C., Xu Z.-M., Li X.-J., Yu L., Song H.-J., Li M., Lu J.-M., Zhao Y.-L., Pan C.-Y.
      Endocr. Relat. Cancer 10:217-224(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION.
    4. "Induction of the LRP16 gene by estrogen promotes the invasive growth of Ishikawa human endometrial cancer cells through the downregulation of E-cadherin."
      Meng Y.G., Han W.-D., Zhao Y.-L., Huang K., Si Y.-L., Wu Z.-Q., Mu Y.-M.
      Cell Res. 17:869-880(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION, FUNCTION.
    5. "Estrogenically regulated LRP16 interacts with estrogen receptor alpha and enhances the receptor's transcriptional activity."
      Han W.-D., Zhao Y.-L., Meng Y.G., Zang L., Wu Z.-Q., Li Q., Si Y.-L., Huang K., Ba J.-M., Morinaga H., Nomura M., Mu Y.-M.
      Endocr. Relat. Cancer 14:741-753(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ESR1, FUNCTION.
    6. "LRP16 is fused to RUNX1 in monocytic leukemia cell line with t(11;21)(q13;q22)."
      Imagama S., Abe A., Suzuki M., Hayakawa F., Katsumi A., Emi N., Kiyoi H., Naoe T.
      Eur. J. Haematol. 79:25-31(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHROMOSOMAL TRANSLOCATION WITH RUNX1.
    7. "The single-macro domain protein LRP16 is an essential cofactor of androgen receptor."
      Yang J., Zhao Y.-L., Wu Z.-Q., Si Y.-L., Meng Y.G., Fu X.B., Mu Y.-M., Han W.-D.
      Endocr. Relat. Cancer 16:139-153(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH ANDROGENE RECEPTOR, INDUCTION BY ANDROGEN.
    8. "Differential induction of LRP16 by liganded and unliganded estrogen receptor alpha in SKOV3 ovarian carcinoma cells."
      Tian L., Wu Z., Zhao Y., Meng Y., Si Y., Fu X., Mu Y., Han W.
      J. Endocrinol. 202:167-177(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION, FUNCTION.
    9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    10. "A family of macrodomain proteins reverses cellular mono-ADP-ribosylation."
      Jankevicius G., Hassler M., Golia B., Rybin V., Zacharias M., Timinszky G., Ladurner A.G.
      Nat. Struct. Mol. Biol. 20:508-514(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ASN-174; ASP-184 AND GLY-270.
    11. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    12. Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 91-325, FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ASP-160; ASP-167; ASN-171; ASN-174; ASP-184; HIS-188; SER-268 AND GLY-270, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.

    Entry informationi

    Entry nameiMACD1_HUMAN
    AccessioniPrimary (citable) accession number: Q9BQ69
    Secondary accession number(s): Q9UH96
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 16, 2003
    Last sequence update: June 16, 2003
    Last modified: March 16, 2016
    This is version 121 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

    Miscellaneous

    Overexpression may promote MCF-7 cells proliferation. There is an approximate one-third increase of the invasive capacity of MACROD1-overexpressing cells. The expression of CDH1 is repressed by MACROD1. Further analyzes demonstrats that MACROD1 inhibits CDH1 transactivation in a dose dependent manner. Inhibition is abolished by estrogen deprivation, indicating that the down-regulation of CDH1 transcription by MACROD1 requires ESR1 mediation. Binding of ESR1 to the CDH1 promoter is antagonized by MACROD1, suggesting that MACROD1 could interfere with ESR1-mediated transcription. Knockdown of MACROD1 leads to impaired AR function and greatly attenuates the coactivation of AR by other AR coactivators such as UXT and NCOA1. This interference also markedly inhibits the androgen-stimulated proliferation of androgen-sensitive LNCaP prostate cancer cells. MACROD1 knockdown does not significantly affect the growth rate of AR-negative PC-3 prostate cancer cells.

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. 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.