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MIER1 (mesoderm induction early response 1 homolog (Xenopus laevis))

Identity

Other namesER1
Er1
KIAA1610
MGC150641
MGC131940
MGC150640
MI-ER1
hMI-ER1
RP5-944N15.1
DKFZp781G0451
HGNC (Hugo) MIER1
LocusID (NCBI) 57708
Location 1p31.3
Location_base_pair Starts at 67390578 and ends at 67454302 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Note MIER1 was identified by differential display as an immediate-early gene activated during fibroblast growth factor (FGF) induction of mesoderm differentiation in Xenopus laevis.

DNA/RNA

 
  A. Schematic illustrating the exon-intron organization of the human MIER1 gene. Exons are shown as red bars/vertical lines and introns as horizontal lines; exon numbers are indicated below each schematic. The light red bar indicates the facultative intron 16 and the position of the alpha and beta carboxy-terminal coding regions are indicated. Note that the beta coding region is located within the facultative intron. The three alternate starts of translation, ML-, MF- and MAE- are indicated as are the three polyadenylation signals (PAS): i, ii and iii. B. Schematic illustrating the variant 5' and 3' ends of human MIER1 transcripts. Alternate 5' ends are generated from differential promoter usage (P1 or P2) or alternate inclusion of exon 3A. This leads to three alternate starts of translation, indicated as ML-, MF- and MAE-, and produces three distinct amino termini. The four variant 3' ends, a, bi, bii and biii, produced by alternative splicing or alternate PAS usage, result in transcripts readily distinguished by size (1.7 kb, 2.5 kb, 3.4 kb and 4.8 kb, respectively) on a Northern blot. It should be noted that three of the variant 3' ends, bi, bii and biii encode the same protein sequence and differ only in their untranslated region. * indicates beta encoding transcript that contains the alpha exon in its 3'UTR. The locations of the alpha and beta carboxy-terminal coding regions and PAS i, ii and iii are indicated. The combination of three possible 5' ends with four possible 3' ends gives rise to 12 distinct transcripts, but only 6 distinct protein isoforms. In most adult tissues, the most abundant transcript is 4.8 kb. Additional transcripts have been reported in Ensembl.
Description 63 kb gene; 2 promoters controlling 2 distinct transcriptional start sites; 17 exons; intron 16 is facultative; 3 polyadenylation sites.

Protein

 
  Schematic illustrating the common internal domains of the MIER1 isoforms and the variant amino- (N-) and carboxy- (C-) termini. Transcription from the P1 promoter produces proteins that either begin with M-L- or with the sequence encoded by exon 3A (MFMFNWFTDCLWTLFLSNYQ). Transcription from the P2 promoter produces a protein that begins with M-A-E-. The variant N-termini of the MIER1 isoforms are followed by common internal sequence containing several distinct domains: acidic, which function in transcriptional activation (Paterno et al., 1997); ELM2, responsible for recruitment of HDAC1 (Ding et al., 2003); SANT, which interacts with Sp1 (Ding et al., 2004) and PSPPP, which is required for MIER1 activity in the Xenopus embryo (Teplitsky et al., 2003). The two alternate C-termini, alpha and beta, result from removal or inclusion and read-through of intron 16, respectively. The alpha C-terminus contains a classic LXXLL motif for interaction with nuclear receptors; the beta C-terminus contains a nuclear localization signal (NLS).
Description The six human MIER1 isoforms: M-3A-alpha (457 aa), M-3A-beta (536 aa), ML-alpha (432 aa), ML-beta (511 aa), MAE-alpha (433 aa), and MAE-beta (512 aa), range in predicted molecular size from 47.5 kDa-59 kDa; however all isoforms migrate slower than predicted on SDS-PAGE, with calculated molecular sizes ranging 78 kDa-90 kDa.
Expression MIER1beta protein is expressed ubiquitously, while MIER1alpha protein is expressed mainly in a subset of endocrine organs and endocrine responsive tissues, including the pancreatic islets, adrenal glands, testis, ovary, hypothalamus, pituitary, parafollicular cells of the thyroid and mammary ductal epithelium.
Localisation MIER1beta is nuclear in all adult cell types but is retained in the cytoplasm of the pre-gastrula Xenopus embryo. MIER1alpha is cytoplasmic in most cell types, but localized in the nucleus in normal mammary ductal epithelium. During progression to invasive breast carcinoma, its subcellular localization shifts from nuclear to exclusively cytoplasmic.
Function MIER1alpha and beta function in transcriptional repression by at least two distinct mechanisms: recruitment and regulation of chromatin modifying enzymes, including HDAC1, HDAC2, CBP and G9a; interaction with transcription factors, such as Sp1 and ERalpha, to repress transcription of their respective target genes. MIER1alpha inhibits estrogen-stimulated anchorage-independent growth of breast carcinoma cells.
Homology The MIER1 gene family contains two other members, MIER2 and MIER3. The MIER1 gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, frog, zebrafish, fruit fly, and C. elegans.

Implicated in

Entity Breast cancer
Note Initial studies showed that total MIER1 mRNA levels were increased in breast carcinoma cell lines and tumour samples (Paterno et al., 1998); in a more recent study, no consistent difference in MIER1alpha protein expression levels between normal breast and tumour samples was detected (McCarthy et al., 2008). Immunohistochemical analysis of patient biopsies revealed that MIER1alpha protein is expressed primarily in ductal epithelial cells in normal breast tissue, with little or no expression in the surrounding stroma; in breast carcinoma samples, its expression is restricted to tumour cells. While there is no difference in expression levels, the subcellular localization of MIER1alpha changes dramatically during tumour progression: MIER1alpha is nuclear in 75% of normal breast samples and in 77% of hyperplasia, but in breast carcinoma, only 51% of ductal carcinoma in situ, 25% of invasive lobular carcinoma and 4% of invasive ductal carcinoma contained nuclear MIER1alpha (McCarthy et al., 2008). This shift from nuclear to cytoplasmic localization of MIER1alpha during breast cancer progression suggests that loss of nuclear MIER1alpha contributes to the development of invasive breast carcinoma. MIER1alpha inhibits ERalpha transcriptional activity and overexpression of MIER1alpha in breast carcinoma cells inhibits estrogen-stimulated anchorage-independent growth (McCarthy et al., 2008).
  

External links

Nomenclature
HGNC (Hugo)MIER1   29657
Cards
AtlasMIER1ID50389ch1p31
Entrez_Gene (NCBI)MIER1  57708  mesoderm induction early response 1, transcriptional regulator
GeneCards (Weizmann)MIER1
Ensembl (Hinxton)ENSG00000198160 [Gene_View]  chr1:67390578-67454302 [Contig_View]  MIER1 [Vega]
ICGC DataPortalENSG00000198160
cBioPortalMIER1
AceView (NCBI)MIER1
Genatlas (Paris)MIER1
WikiGenes57708
SOURCE (Princeton)NM_001077700 NM_001077701 NM_001077702 NM_001077703 NM_001077704 NM_001146110 NM_001146111 NM_001146112 NM_001146113 NM_001278215 NM_020948
Genomic and cartography
GoldenPath (UCSC)MIER1  -  1p31.3   chr1:67390578-67454302 +  1p31.2   [Description]    (hg19-Feb_2009)
EnsemblMIER1 - 1p31.2 [CytoView]
Mapping of homologs : NCBIMIER1 [Mapview]
Gene and transcription
Genbank (Entrez)AB046830 AF515446 AF515447 AF515448 AK302061
RefSeq transcript (Entrez)NM_001077700 NM_001077701 NM_001077702 NM_001077703 NM_001077704 NM_001146110 NM_001146111 NM_001146112 NM_001146113 NM_001278215 NM_020948
RefSeq genomic (Entrez)AC_000133 NC_000001 NC_018912 NG_029847 NT_032977 NW_001838579 NW_004929290
Consensus coding sequences : CCDS (NCBI)MIER1
Cluster EST : UnigeneHs.605432 [ NCBI ]
CGAP (NCI)Hs.605432
Alternative Splicing : Fast-db (Paris)GSHG0000609
Alternative Splicing GalleryENSG00000198160
Gene ExpressionMIER1 [ NCBI-GEO ]     MIER1 [ SEEK ]   MIER1 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ8N108 (Uniprot)
NextProtQ8N108  [Medical]
With graphics : InterProQ8N108
Splice isoforms : SwissVarQ8N108 (Swissvar)
Domaine pattern : Prosite (Expaxy)ELM2 (PS51156)    SANT (PS51293)   
Domains : Interpro (EBI)ELM2_dom [organisation]   Homeodomain-like [organisation]   SANT/Myb [organisation]   SANT_dom [organisation]  
Related proteins : CluSTrQ8N108
Domain families : Pfam (Sanger)ELM2 (PF01448)   
Domain families : Pfam (NCBI)pfam01448   
Domain families : Smart (EMBL)SANT (SM00717)  
DMDM Disease mutations57708
Blocks (Seattle)Q8N108
Human Protein AtlasENSG00000198160 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ8N108
HPRD11362
IPIIPI00477825   IPI00478280   IPI00479032   IPI00655845   IPI00646985   IPI00656089   IPI00655630   IPI00656079   IPI00433492   IPI00925194   IPI00927624   IPI00640919   IPI00655783   
Protein Interaction databases
DIP (DOE-UCLA)Q8N108
IntAct (EBI)Q8N108
FunCoupENSG00000198160
BioGRIDMIER1
InParanoidQ8N108
Interologous Interaction database Q8N108
IntegromeDBMIER1
STRING (EMBL)MIER1
Ontologies - Pathways
Ontology : AmiGODNA binding  chromatin binding  signal transducer activity  protein binding  nucleus  nucleolus  cytoplasm  transcription, DNA-templated  signal transduction  transcriptional repressor complex  positive regulation of chromatin silencing  positive regulation of I-kappaB kinase/NF-kappaB signaling  
Ontology : EGO-EBIDNA binding  chromatin binding  signal transducer activity  protein binding  nucleus  nucleolus  cytoplasm  transcription, DNA-templated  signal transduction  transcriptional repressor complex  positive regulation of chromatin silencing  positive regulation of I-kappaB kinase/NF-kappaB signaling  
Protein Interaction DatabaseMIER1
Wikipedia pathwaysMIER1
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)MIER1
snp3D : Map Gene to Disease57708
SNP (GeneSNP Utah)MIER1
SNP : HGBaseMIER1
Genetic variants : HAPMAPMIER1
Exome VariantMIER1
1000_GenomesMIER1 
ICGC programENSG00000198160 
Somatic Mutations in Cancer : COSMICMIER1 
CONAN: Copy Number AnalysisMIER1 
Mutations and Diseases : HGMDMIER1
Genomic VariantsMIER1  MIER1 [DGVbeta]
dbVarMIER1
ClinVarMIER1
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM
MedgenMIER1
GENETestsMIER1
Disease Genetic AssociationMIER1
Huge Navigator MIER1 [HugePedia]  MIER1 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneMIER1
Homology/Alignments : Family Browser (UCSC)MIER1
Phylogenetic Trees/Animal Genes : TreeFamMIER1
Chemical/Protein Interactions : CTD57708
Chemical/Pharm GKB GenePA142671456
Clinical trialMIER1
Cancer Resource (Charite)ENSG00000198160
Other databases
Probes
Litterature
PubMed27 Pubmed reference(s) in Entrez
CoreMineMIER1
iHOPMIER1
OncoSearchMIER1

Bibliography

cDNA cloning of a novel, developmentally regulated immediate early gene activated by fibroblast growth factor and encoding a nuclear protein.
Paterno GD, Li Y, Luchman HA, Ryan PJ, Gillespie LL.
J Biol Chem. 1997 Oct 10;272(41):25591-5.
PMID 9325278
 
Molecular cloning of human er1 cDNA and its differential expression in breast tumours and tumour-derived cell lines.
Paterno GD, Mercer FC, Chayter JJ, Yang X, Robb JD, Gillespie LL.
Gene. 1998 Nov 5;222(1):77-82.
PMID 9813250
 
Differential nuclear localization of ER1 protein during embryonic development in Xenopus laevis.
Luchman HA, Paterno GD, Kao KR, Gillespie LL.
Mech Dev. 1999 Jan;80(1):111-4.
PMID 10096069
 
Nuclear localization signals in the Xenopus FGF embryonic early response 1 protein.
Post JN, Gillespie LL, Paterno GD.
FEBS Lett. 2001 Jul 27;502(1-2):41-5.
PMID 11478945
 
Genomic organization of the human mi-er1 gene and characterization of alternatively spliced isoforms: regulated use of a facultative intron determines subcellular localization.
Paterno GD, Ding Z, Lew YY, Nash GW, Mercer FC, Gillespie LL.
Gene. 2002 Jul 24;295(1):79-88.
PMID 12242014
 
Human MI-ER1 alpha and beta function as transcriptional repressors by recruitment of histone deacetylase 1 to their conserved ELM2 domain.
Ding Z, Gillespie LL, Paterno GD.
Mol Cell Biol. 2003 Jan;23(1):250-8.
PMID 12482978
 
Proline365 is a critical residue for the activity of XMI-ER1 in Xenopus embryonic development.
Teplitsky Y, Paterno GD, Gillespie LL.
Biochem Biophys Res Commun. 2003 Sep 5;308(4):679-83.
PMID 12927772
 
Large-scale characterization of HeLa cell nuclear phosphoproteins.
Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villen J, Li J, Cohn MA, Cantley LC, Gygi SP.
Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12130-5. Epub 2004 Aug 9.
PMID 15302935
 
The SANT domain of human MI-ER1 interacts with Sp1 to interfere with GC box recognition and repress transcription from its own promoter.
Ding Z, Gillespie LL, Mercer FC, Paterno GD.
J Biol Chem. 2004 Jul 2;279(27):28009-16. Epub 2004 Apr 26.
PMID 15117948
 
Developmentally regulated cytoplasmic retention of the transcription factor XMI-ER1 requires sequence in the acidic activation domain.
Post JN, Luchman HA, Mercer FC, Paterno GD, Gillespie LL.
Int J Biochem Cell Biol. 2005 Feb;37(2):463-77.
PMID 15474990
 
Cloning and characterization of the mouse ortholog of mi-er1.
Thorne LB, Grant AL, Paterno GD, Gillespie LL.
DNA Seq. 2005 Jun;16(3):237-40.
PMID 16147882
 
Phosphoproteome analysis of the human mitotic spindle.
Nousiainen M, Sillje HH, Sauer G, Nigg EA, Korner R.
Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5391-6. Epub 2006 Mar 24.
PMID 16565220
 
The transcriptional cofactor MIER1-beta negatively regulates histone acetyltransferase activity of the CREB-binding protein.
Blackmore TM, Mercer CF, Paterno GD, Gillespie LL.
BMC Res Notes. 2008 Aug 22;1:68.
PMID 18721470
 
Changes in subcellular localisation of MI-ER1 alpha, a novel oestrogen receptor-alpha interacting protein, is associated with breast cancer progression.
McCarthy PL, Mercer FC, Savicky MW, Carter BA, Paterno GD, Gillespie LL.
Br J Cancer. 2008 Aug 19;99(4):639-46. Epub 2008 Jul 29.
PMID 18665173
 
Protein expression of the transcriptional regulator MI-ER1 alpha in adult mouse tissues.
Thorne LB, McCarthy PL, Paterno GD, Gillespie LL.
J Mol Histol. 2008 Feb;39(1):15-24. Epub 2007 Jul 11.
PMID 17622490
 
Atrophin recruits HDAC1/2 and G9a to modify histone H3K9 and to determine cell fates.
Wang L, Charroux B, Kerridge S, Tsai CC.
EMBO Rep. 2008 Jun;9(6):555-62. Epub 2008 May 2.
PMID 18451879
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written12-2009Laura L Gillespie, Gary D Paterno
Terry Fox Cancer Research Labs, Division of Biomedical Sciences, Faculty of Medicine, Memorial University, St John's, NL, Canada
Updated09-2011Laura L Gillespie, Gary D Paterno
Terry Fox Cancer Research Labs, Division of Biomedical Sciences, Faculty of Medicine, Memorial University, St John's, NL, Canada

Citation

This paper should be referenced as such :
Gillespie, LL ; Paterno, GD
MIER1 (mesoderm induction early response 1 homolog (Xenopus laevis))
Atlas Genet Cytogenet Oncol Haematol. 2012;16(2):127-130.
Free online version   Free pdf version   [Bibliographic record ]
History of this paper:
Gillespie, LL ; Paterno, GD. MIER1 (mesoderm induction early response 1 homolog (Xenopus laevis)). Atlas Genet Cytogenet Oncol Haematol. 2012;16(2):127-130.
http://documents.irevues.inist.fr/bitstream/2042/46943/1/09-2011-MIER1ID50389ch1p31.pdf
URL : http://AtlasGeneticsOncology.org/Genes/MIER1ID50389ch1p31.html

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