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MACROD1 (MACRO domain containing 1)

Written2010-05Weidong Han, Xiaoyin Ma, Yukun Duan, Zhiqiang Wu
Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing 100853, China

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)LRP16
Other alias
HGNC (Hugo) MACROD1
LocusID (NCBI) 28992
Atlas_Id 50947
Location 11q13.1  [Link to chromosome band 11q13]
Location_base_pair Starts at 63998558 and ends at 64166113 bp from pter ( according to hg19-Feb_2009)  [Mapping MACROD1.png]
Local_order Next to OTUB1 and FLRT1.
 
Fusion genes
(updated 2016)
MACROD1 (11q13.1) / MACROD1 (11q13.1)MACROD1 (11q13.1) / NRXN2 (11q13.1)MACROD1 (11q13.1) / RUNX1 (21q22.12)
RUNX1 (21q22.12) / MACROD1 (11q13.1)
Note MACROD1/LRP16 is a member of macro domain protein family, which contains only a stand-alone macro domain functional module at its C-terminus. Through its macro domain module LRP16 binds poly (A), mono (ADP-ribose) or poly (ADP-ribose). LRP16 is an estrogen and androgen-responsive gene. Both estrogen receptor alpha (ERalpha) and androgen receptor (AR) can bind to LRP16 promoter to enhance its transcription. LRP16 also acts as a co-activator of ERalpha, AR, and possible other nuclear receptors, and nuclear factor-kappaB (NF-kappaB) to activate their transcriptional activities. Keratin 18 can associate with LRP16, by which LRP16 was sequestrated in the cytoplasm. In addition, LRP16 can recruit to chromatin when cells were exposed to ironing radiation (IR) by sensing poly (ADP-ribose) synthesized by PARP1, indicating that LRP16 is involved in IR-induced DNA-damage response.

DNA/RNA

Note MACROD1/LRP16, encoding a 35 kD protein, was originally isolated from human lymphocytes. The proximal region (nt-676 to -24) of the human LRP16 promoter contains a 1/2 estrogen response element (ERE)/Sp1 site and multiple GC-rich elements that confer estrogenic responsiveness and are sufficient for estrogenic action. In the presence of estrogen, ERalpha and Sp1 complex recruits to the LRP16 gene promoter to enhance LRP16 transcription.
Description Genomic structure of LRP16: spans 167 kb; 11 exons; ORF: 975 bp.
Transcription LRP16 mRNA (NM_014067.3) has a size of 1256 bp.
Exons: 11; transcript length: 1256 bp; translation length: 325 residues.
Pseudogene No pseudogenes reported.

Protein

Note MACROD1/LRP16 contains a single macro domain (Appr-1"-pase_ like). It contains an ADP-ribose-binding pocket through which it can bind mono (ADP-ribose). Moreover, LRP16 also can bind poly (ADP-ribose) and hydrolyze ADP-ribose-1" phosphate to yield ADP-ribose. Therefore, it is reasonable to propose that LRP16 may play an important role in the ADP-ribosylation of proteins, an important post-translational modification which occurs in DNA repair, transcription, chromatin biology, and long-term memory formation.
Description 325 amino acids; 35.505 kDa; containing a single macro domain (from amino acid 141 to 322).
Expression LRP16 is expressed ubiquitously in nearly all types of tissues and is up-regulated in hormone-dependent cancer cells such as MCF-7 breast cancer cells, Ishikawa endometrial cancer cells, and BG-1 ovarian cancer cells upon estrogenic stimulation. Conversely, estrogen reduces LRP16 expression in estrogen-resistant SKOV-3 ovarian cancer cells. Androgen also up-regulates LRP16 expression in androgen-sensitive prostate cancer cells. In addition, LRP16 is frequently over-expressed in several tumor tissues by comparison with their corresponding normal tissues.
Localisation Nuclear, cytoplasm and mitochondrion.
Function 1. LRP16 can recruit to DNA-damaged sites through sensing radiation-induced activation of poly-ADP-ribose polymerase-1 (PARP1).
2. LRP16 can interact with both ERalpha and AR to enhance their transcriptional activities.
3. Cytokeratin 18 (K18) can interact with LRP16 through its C-terminal region and sequester LRP16 in the cytoplasm, by which the LRP16 co-activation of ERalpha is inactivated.
4. LRP16 can bind to p65, a component of NF-kappaB, and participates into the NF-kappaB enhanceosome to enhance TNFalpha-induced NF-kappaB activity (our unpublished data).
Homology - Bos taurus: MACROD1;
- Pan troglodytes: MACROD1;
- Canis lupus familiaris: MACROD1;
- Rattus norvegicus: Macrod1;
- Mus musculus: Macrod1;
- Danio rerio: zgc: 92353;
- Magnaporthe grisea: MGG_09394;
- Neurospora crassa: NCU07925.1.

Implicated in

Note
  
Entity Prostate cancer
Note Androgen up-regulates LRP16 expression in both mRNA and protein levels in androgen-sensitive prostate cancer cells such as LNCaP cells, but not in prostate cancer cells without overexpression of LRP16, which significantly stimulates cell growth in the presence of androgen. Reversely, inhibition of the endogenous LRP16 in androgen-sensitive prostate cancer cells markedly diminishes androgen-stimulated cell growth. LRP16 is not only a target of AR in androgen-sensitive prostate cancer cells, but also a coactivator of AR. By the AR-LRP16 feedback pathway, LRP16 may play an important role in the progression of androgen-sensitive prostate cancers.
  
  
Entity Estrogen-dependent breast cancer and endometrial cancer
Note LRP16 is not only a target gene of ERalpha, but also an ERalpha coactivator. LRP16 overexpression significantly promotes MCF-7 cell proliferation. Reversely, knockdown of LRP16 in MCF-7 cells markedly impaired estrogen-stimulated ERalpha activity and cell growth. LRP16 overexpression was observed in more than 30% primary breast cancers.
LRP16 represses E-cadherin (a molecule associated with cell adhesion and tumor metastasis) expression through antagonizing the binding of ERalpha to the E-cadherin promoter. Inhibition of LRP16 expression in both estrogen-responsive MCF-7 breast cancer and Ishikawa endometrial cancer cells significantly attenuates their invasive capacity.
Collectively, LRP16 may be involved in the progression of estrogen-dependent cancers.
  
  
Entity Gastric carcinoma
Note The expression level of LRP16 in primary gastric carcinoma tissues was significantly higher than that in normal mucosa tissues. In addition, overexpression of LRP16 was positively linked with tumor size, depth of invasion, lymph node metastasis, distant metastasis and TNM stage. Higher expression of LRP16 predicts a poor prognosis of gastric carcinoma patients.
  
  
Entity Colorectal carcinoma
Note The higher expression level of LRP16 was found to be positively associated with the poor differentiation of primary human colorectal carcinomas. In addition, higher expression of LRP16 in primary human colorectal carcinomas was also linked to poor prognosis of patients.
Prognosis LRP16 overexpression predicts a poor prognosis in several tumors.
  
  
Entity t(11;21)(q13;q22) in myelodysplastic syndrome
Hybrid/Mutated Gene A kind of chromosome rearrangement t(11;21)(q13;q22), involved in RUNX1 (also known as AML1) and LRP16, was found in a patient with monocytic leukemia evolving from myelodysplastic syndrome (MDS). The fusion junction of hybrid gene RUNX1-LRP16 has two types, involving either exon 5 or exon 6 of RUNX1 and exon 2 of LRP16. The reciprocal LRP16-RUNX1 chimera is a fusion between exon 1 of LRP16 and exon 7 of RUNX1.
Abnormal Protein Both RUNX1 (exon 5)-LRP16 and RUNX1 (exon 6)-LRP16 retain the RUNT domain (RD) of RUNX1 and the macro domain of LRP16, whereas reciprocal LRP16-RUNX1 retains the transactivation domain (TA) of RUNX1. The formation of fusion protein RUNX1-LRP16 may lead to the inhibition of myeloid differentiation and contributes to leukemia genesis.
  

Bibliography

Poly(ADP-ribosyl)ation directs recruitment and activation of an ATP-dependent chromatin remodeler.
Gottschalk AJ, Timinszky G, Kong SE, Jin J, Cai Y, Swanson SK, Washburn MP, Florens L, Ladurner AG, Conaway JW, Conaway RC.
Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13770-4. Epub 2009 Aug 6.
PMID 19666485
 
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 WD, Mu YM, Lu XC, Xu ZM, Li XJ, Yu L, Song HJ, Li M, Lu JM, Zhao YL, Pan CY.
Endocr Relat Cancer. 2003 Jun;10(2):217-24.
PMID 12790785
 
GC-rich promoter elements maximally confers estrogen-induced transactivation of LRP16 gene through ERalpha/Sp1 interaction in MCF-7 cells.
Han WD, Si YL, Zhao YL, Li Q, Wu ZQ, Hao HJ, Song HJ.
J Steroid Biochem Mol Biol. 2008 Mar;109(1-2):47-56. Epub 2007 Dec 8.
PMID 18206366
 
Estrogenically regulated LRP16 interacts with estrogen receptor alpha and enhances the receptor's transcriptional activity.
Han WD, Zhao YL, Meng YG, Zang L, Wu ZQ, Li Q, Si YL, Huang K, Ba JM, Morinaga H, Nomura M, Mu YM.
Endocr Relat Cancer. 2007 Sep;14(3):741-53.
PMID 17914104
 
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. 2007 Jul;79(1):25-31. Epub 2007 May 28.
PMID 17532767
 
Clinicopathological significance of LRP16 protein in 336 gastric carcinoma patients.
Li YZ, Zhao P, Han WD.
World J Gastroenterol. 2009 Oct 14;15(38):4833-7.
PMID 19824120
 
[Expression and clinical significance of LRP16 gene in human breast cancer]
Liao DX, Han WD, Zhao YL, Pu YD, Mu YM, Luo CH, Li XH.
Ai Zheng. 2006 Jul;25(7):866-70.
PMID 16831279
 
Keratin 18 attenuates estrogen receptor alpha-mediated signaling by sequestering LRP16 in cytoplasm.
Meng Y, Wu Z, Yin X, Zhao Y, Chen M, Si Y, Yang J, Fu X, Han W.
BMC Cell Biol. 2009 Dec 26;10:96.
PMID 20035625
 
Induction of the LRP16 gene by estrogen promotes the invasive growth of Ishikawa human endometrial cancer cells through the downregulation of E-cadherin.
Meng YG, Han WD, Zhao YL, Huang K, Si YL, Wu ZQ, Mu YM.
Cell Res. 2007 Oct;17(10):869-80.
PMID 17893710
 
Differential activities of cellular and viral macro domain proteins in binding of ADP-ribose metabolites.
Neuvonen M, Ahola T.
J Mol Biol. 2009 Jan 9;385(1):212-25. Epub 2008 Nov 1.
PMID 18983849
 
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. 2009 Jul;202(1):167-77. Epub 2009 Apr 29.
PMID 19403568
 
A macrodomain-containing histone rearranges chromatin upon sensing PARP1 activation.
Timinszky G, Till S, Hassa PO, Hothorn M, Kustatscher G, Nijmeijer B, Colombelli J, Altmeyer M, Stelzer EH, Scheffzek K, Hottiger MO, Ladurner AG.
Nat Struct Mol Biol. 2009 Sep;16(9):923-9. Epub 2009 Aug 13.
PMID 19680243
 
Clinicopathological significance and prognostic value of LRP16 expression in colorectal carcinoma.
Xi HQ, Zhao P, Han WD.
World J Gastroenterol. 2010 Apr 7;16(13):1644-8.
PMID 20355243
 
The single-macro domain protein LRP16 is an essential cofactor of androgen receptor.
Yang J, Zhao YL, Wu ZQ, Si YL, Meng YG, Fu XB, Mu YM, Han WD.
Endocr Relat Cancer. 2009 Mar;16(1):139-53. Epub 2008 Nov 20.
PMID 19022849
 
Mechanism of transcriptional regulation of LRP16 gene expression by 17-beta estradiol in MCF-7 human breast cancer cells.
Zhao YL, Han WD, Li Q, Mu YM, Lu XC, Yu L, Song HJ, Li X, Lu JM, Pan CY.
J Mol Endocrinol. 2005 Feb;34(1):77-89.
PMID 15691879
 

Citation

This paper should be referenced as such :
Han, W ; Ma, X ; Duan, Y ; Wu, Z
MACROD1 (MACRO domain containing 1)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(2):195-197.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/MACROD1ID50947ch11q13.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ]
  t(11;21)(q13;q22) RUNX1/MACROD1
t(11;21)(q21;q22) RUNX1/LPXN


External links

Nomenclature
HGNC (Hugo)MACROD1   29598
Cards
AtlasMACROD1ID50947ch11q13
Entrez_Gene (NCBI)MACROD1  28992  MACRO domain containing 1
AliasesLRP16
GeneCards (Weizmann)MACROD1
Ensembl hg19 (Hinxton)ENSG00000133315 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000133315 [Gene_View]  chr11:63998558-64166113 [Contig_View]  MACROD1 [Vega]
ICGC DataPortalENSG00000133315
TCGA cBioPortalMACROD1
AceView (NCBI)MACROD1
Genatlas (Paris)MACROD1
WikiGenes28992
SOURCE (Princeton)MACROD1
Genetics Home Reference (NIH)MACROD1
Genomic and cartography
GoldenPath hg38 (UCSC)MACROD1  -     chr11:63998558-64166113 -  11q13.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)MACROD1  -     11q13.1   [Description]    (hg19-Feb_2009)
EnsemblMACROD1 - 11q13.1 [CytoView hg19]  MACROD1 - 11q13.1 [CytoView hg38]
Mapping of homologs : NCBIMACROD1 [Mapview hg19]  MACROD1 [Mapview hg38]
OMIM610400   
Gene and transcription
Genbank (Entrez)AF086206 AF202922 BC000270 BC003188 BC007297
RefSeq transcript (Entrez)NM_014067
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)MACROD1
Cluster EST : UnigeneHs.602898 [ NCBI ]
CGAP (NCI)Hs.602898
Alternative Splicing GalleryENSG00000133315
Gene ExpressionMACROD1 [ NCBI-GEO ]   MACROD1 [ EBI - ARRAY_EXPRESS ]   MACROD1 [ SEEK ]   MACROD1 [ MEM ]
Gene Expression Viewer (FireBrowse)MACROD1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)28992
GTEX Portal (Tissue expression)MACROD1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9BQ69   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9BQ69  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9BQ69
Splice isoforms : SwissVarQ9BQ69
Catalytic activity : Enzyme3.2.2.- [ Enzyme-Expasy ]   3.2.2.-3.2.2.- [ IntEnz-EBI ]   3.2.2.- [ BRENDA ]   3.2.2.- [ KEGG ]   
PhosPhoSitePlusQ9BQ69
Domaine pattern : Prosite (Expaxy)MACRO (PS51154)   
Domains : Interpro (EBI)Macro_dom   
Domain families : Pfam (Sanger)Macro (PF01661)   
Domain families : Pfam (NCBI)pfam01661   
Domain families : Smart (EMBL)A1pp (SM00506)  
Conserved Domain (NCBI)MACROD1
DMDM Disease mutations28992
Blocks (Seattle)MACROD1
PDB (SRS)2X47   
PDB (PDBSum)2X47   
PDB (IMB)2X47   
PDB (RSDB)2X47   
Structural Biology KnowledgeBase2X47   
SCOP (Structural Classification of Proteins)2X47   
CATH (Classification of proteins structures)2X47   
SuperfamilyQ9BQ69
Human Protein AtlasENSG00000133315
Peptide AtlasQ9BQ69
HPRD17448
IPIIPI00155601   
Protein Interaction databases
DIP (DOE-UCLA)Q9BQ69
IntAct (EBI)Q9BQ69
FunCoupENSG00000133315
BioGRIDMACROD1
STRING (EMBL)MACROD1
ZODIACMACROD1
Ontologies - Pathways
QuickGOQ9BQ69
Ontology : AmiGOprotein binding  nucleus  nucleoplasm  mitochondrion  cellular response to DNA damage stimulus  hydrolase activity, acting on glycosyl bonds  deacetylase activity  purine nucleoside metabolic process  protein de-ADP-ribosylation  
Ontology : EGO-EBIprotein binding  nucleus  nucleoplasm  mitochondrion  cellular response to DNA damage stimulus  hydrolase activity, acting on glycosyl bonds  deacetylase activity  purine nucleoside metabolic process  protein de-ADP-ribosylation  
NDEx NetworkMACROD1
Atlas of Cancer Signalling NetworkMACROD1
Wikipedia pathwaysMACROD1
Orthology - Evolution
OrthoDB28992
GeneTree (enSembl)ENSG00000133315
Phylogenetic Trees/Animal Genes : TreeFamMACROD1
HOVERGENQ9BQ69
HOGENOMQ9BQ69
Homologs : HomoloGeneMACROD1
Homology/Alignments : Family Browser (UCSC)MACROD1
Gene fusions - Rearrangements
Fusion : MitelmanMACROD1/NRXN2 [11q13.1/11q13.1]  
Fusion : MitelmanRUNX1/MACROD1 [21q22.12/11q13.1]  [t(11;21)(q13;q22)]  
Fusion: TCGAMACROD1 11q13.1 NRXN2 11q13.1 BLCA
Fusion : TICdbRUNX1 [21q22.12]  -  MACROD1 [11q13.1]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerMACROD1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MACROD1
dbVarMACROD1
ClinVarMACROD1
1000_GenomesMACROD1 
Exome Variant ServerMACROD1
ExAC (Exome Aggregation Consortium)MACROD1 (select the gene name)
Genetic variants : HAPMAP28992
Genomic Variants (DGV)MACROD1 [DGVbeta]
DECIPHERMACROD1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisMACROD1 
Mutations
ICGC Data PortalMACROD1 
TCGA Data PortalMACROD1 
Broad Tumor PortalMACROD1
OASIS PortalMACROD1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICMACROD1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDMACROD1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch MACROD1
DgiDB (Drug Gene Interaction Database)MACROD1
DoCM (Curated mutations)MACROD1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)MACROD1 (select a term)
intoGenMACROD1
NCG5 (London)MACROD1
Cancer3DMACROD1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM610400   
Orphanet
MedgenMACROD1
Genetic Testing Registry MACROD1
NextProtQ9BQ69 [Medical]
TSGene28992
GENETestsMACROD1
Target ValidationMACROD1
Huge Navigator MACROD1 [HugePedia]
snp3D : Map Gene to Disease28992
BioCentury BCIQMACROD1
ClinGenMACROD1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD28992
Chemical/Pharm GKB GenePA162394816
Clinical trialMACROD1
Miscellaneous
canSAR (ICR)MACROD1 (select the gene name)
Probes
Litterature
PubMed24 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineMACROD1
EVEXMACROD1
GoPubMedMACROD1
iHOPMACROD1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Mon May 22 09:15:24 CEST 2017

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