ID:MACD1_HUMAN DESCRIPTION: RecName: Full=O-acetyl-ADP-ribose deacetylase MACROD1; EC=3.5.1.-; AltName: Full=MACRO domain-containing protein 1; AltName: Full=Protein LRP16; FUNCTION: 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. ENZYME REGULATION: Subject to competitive inhibition by the product ADP-ribose. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=373 uM for O-acetyl-ADP-ribose; SUBUNIT: Interacts with ESR1; Interacts in a manner that is estrogen independent but is enhanced by estrogen. Interacts (via macro domain) with AR. INTERACTION: P03372:ESR1; NbExp=4; IntAct=EBI-5324932, EBI-78473; INDUCTION: 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. DISEASE: Note=A chromosomal aberration involving MACROD1 is found in acute leukemia. Translocation t(11;21)(q13;q22) that forms a RUNX1-MACROD1 fusion protein. 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. SIMILARITY: Contains 1 Macro domain. SEQUENCE CAUTION: Sequence=AAH03188.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAH03188.1; Type=Erroneous initiation;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9BQ69
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0005515 protein binding GO:0016787 hydrolase activity GO:0016798 hydrolase activity, acting on glycosyl bonds GO:0019213 deacetylase activity
Biological Process: GO:0006974 cellular response to DNA damage stimulus GO:0042278 purine nucleoside metabolic process GO:0051725 protein de-ADP-ribosylation
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
