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MIEN1 (migration and invasion enhancer 1)

Written2012-12Elad Katz
Division of Pathology, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK

(Note : for Links provided by Atlas : click)

Identity

Alias_namesC17orf37
chromosome 17 open reading frame 37
Alias_symbol (synonym)MGC14832
ORB3
XTP4
C35
Rdx12
Other aliasRDX12
HGNC (Hugo) MIEN1
LocusID (NCBI) 84299
Atlas_Id 52476
Location 17q12  [Link to chromosome band 17q12]
Location_base_pair Starts at 37885409 and ends at 37886788 bp from pter ( according to hg19-Feb_2009)  [Mapping MIEN1.png]
Fusion genes
(updated 2016)
HNRNPDL (4q21.22) / MIEN1 (17q12)ITGA3 (17q21.33) / MIEN1 (17q12)MIEN1 (17q12) / HNRNPDL (4q21.22)
PC (11q13.2) / MIEN1 (17q12)PIP4K2C (12q13.3) / MIEN1 (17q12)SRP68 (17q25.1) / MIEN1 (17q12)

DNA/RNA

Description MIEN1 DNA contains 4 coding exons over 1,63 kb on the minus strand between ERBB2 and GRB7 on human chromosome 17q12. It is also neighbouring mRNA4728.
Transcription Transcript (NC_000017.100) length: 1006 bps. Transcription was reported in a variety of cell lines and organs, mainly using gene expression arrays (EMBL-EBI).
Pseudogene None identified.

Protein

Description MIEN1 is a small (12 kDa) membrane bound protein found in a variety of human tumours (Evans et al., 2006). Its main function is to induce cell invasion and it may be involved in metastasis (Dasgupta et al., 2011; Dasgupta and Vishwanatha, 2007; Katz et al., 2010).
Expression MIEN1 is almost exclusively expressed in human tumours, with the notable exception of Leydig cells in testes (Evans et al., 2006).
Localisation MIEN1 protein is membrane bound and its stability depends on its localization (our unpublished observations). MIEN1 contains a CVIL amino acid sequence in the C-terminal, which fits the prenylation motif CaaX (Evans et al., 2006). Based on several physical properties, such as size, flexibility, membrane buried preference, and presence of leucine as the X residue, MIEN1 is predicted to be geranylgeranylated in vivo by GGTI enzyme, resulting in the addition of 20-carbon isoprenoid moiety.
 
  With permission by Hsu et al. (Hsu et al., 2012).
Function The MIEN1 sequence EATYLELASAVKEQYPGIEI conforms to a prototypical immuno-receptor tyrosine-based activation motif (ITAM). ITAMs, such as this of C35 rely on Syk protein kinase for their signaling capacities (Katz et al., 2010). The most commonly reported consequence of MIEN1 over-expression is the induction of cell motility and invasion (Dasgupta et al., 2011; Katz et al., 2010). High levels of MIEN1 expression lead to epithelial to mesenchymal transition in breast cell lines (Katz et al., 2011a). However, intermediate levels lead to a cancer phenomenon rarely observed in experimental models, collective invasion (Katz et al., 2011b).
Homology MIEN1 is very highly conserved among six higher eukaryotic species (identities >77%) but does not seem to have orthologues in microbial organisms (Evans et al., 2006). MIEN1 contains an ITAM motif which is prevalent in immune receptors as well as oncogenic viruses.

Mutations

Note A single SNP, rs3809717, was described with no bearing on breast cancer risk (attributed originally to the ERBB2 gene, (Einarsdóttir et al., 2006)).

Implicated in

Note
  
Entity Carcinomas
Note Several carcinomas (breast, ovarian, and gastro-intestinal cancers) show high expression of the ERBB2 amplicon containing the MIEN1 gene.
  
  
Entity Breast cancer
Disease Over-expression of ERBB2 amplicon is seen in ~20% of breast cancers and it confers worse biological behavior and clinical aggressiveness in breast cancer. Breast cancers can have up to 25 to 50 copies of the ERBB2 amplicon. MIEN1 is one of the core ERBB2 genes which are always over-expressed with ERBB2/HER2 (Kauraniemi et al., 2003).
Prognosis The prognosis of MIEN1 over-expressing breast cancer is indistinguishable from those of ERBB2 over-expressing breast cancers, due to the common amplification (Katz et al., 2010).
  
  
Entity Prostate cancer
Disease MIEN1 is highly overexpressed in prostate cancer, where it modulates the Akt activity as a membrane bound adapter protein (Dasgupta et al., 2009). MIEN1 is post-translationaly modified by addition of prenyl groups that translocates the protein to the inner face of the plasma membrane. Ectopic expression of MIEN1 activates Akt and cascades downstream signaling through NF-κB pathway upregulating expression of several migratory and invasive genes (Dasgupta et al., 2011). MIEN1 may act as a scaffolding protein blocking PTEN binding to Akt; however, the exact mechanism is not known.
Prognosis Unkown.
  

Bibliography

Prenylated c17orf37 induces filopodia formation to promote cell migration and metastasis.
Dasgupta S, Cushman I, Kpetemey M, Casey PJ, Vishwanatha JK.
J Biol Chem. 2011 Jul 22;286(29):25935-46. doi: 10.1074/jbc.M111.254599. Epub 2011 May 31.
PMID 21628459
 
Comprehensive analysis of the ATM, CHEK2 and ERBB2 genes in relation to breast tumour characteristics and survival: a population-based case-control and follow-up study.
Einarsdottir K, Rosenberg LU, Humphreys K, Bonnard C, Palmgren J, Li Y, Li Y, Chia KS, Liu ET, Hall P, Liu J, Wedren S.
Breast Cancer Res. 2006;8(6):R67.
PMID 17132159
 
C35 (C17orf37) is a novel tumor biomarker abundantly expressed in breast cancer.
Evans EE, Henn AD, Jonason A, Paris MJ, Schiffhauer LM, Borrello MA, Smith ES, Sahasrabudhe DM, Zauderer M.
Mol Cancer Ther. 2006 Nov;5(11):2919-30.
PMID 17121940
 
Solution structure of the oncogenic MIEN1 protein reveals a thioredoxin-like fold with a redox-active motif.
Hsu CH, Shen TL, Chang CF, Chang YY, Huang LY.
PLoS One. 2012;7(12):e52292. doi: 10.1371/journal.pone.0052292. Epub 2012 Dec 20.
PMID 23284973
 
An in vitro model that recapitulates the epithelial to mesenchymal transition (EMT) in human breast cancer.
Katz E, Dubois-Marshall S, Sims AH, Gautier P, Caldwell H, Meehan RR, Harrison DJ.
PLoS One. 2011a Feb 15;6(2):e17083. doi: 10.1371/journal.pone.0017083.
PMID 21347235
 
An analytical approach differentiates between individual and collective cancer invasion.
Katz E, Verleyen W, Blackmore CG, Edward M, Smith VA, Harrison DJ.
Anal Cell Pathol (Amst). 2011b;34(1-2):35-48. doi: 10.3233/ACP-2011-0003.
PMID 21483102
 
Amplification of a 280-kilobase core region at the ERBB2 locus leads to activation of two hypothetical proteins in breast cancer.
Kauraniemi P, Kuukasjarvi T, Sauter G, Kallioniemi A.
Am J Pathol. 2003 Nov;163(5):1979-84.
PMID 14578197
 

Citation

This paper should be referenced as such :
Katz, E
MIEN1 (migration, invasion enhancer 1)
Atlas Genet Cytogenet Oncol Haematol. 2013;17(6):411-413.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/MIEN1ID52476ch17q12.html


External links

Nomenclature
HGNC (Hugo)MIEN1   28230
Cards
AtlasMIEN1ID52476ch17q12
Entrez_Gene (NCBI)MIEN1  84299  migration and invasion enhancer 1
AliasesC17orf37; C35; ORB3; RDX12; 
XTP4
GeneCards (Weizmann)MIEN1
Ensembl hg19 (Hinxton)ENSG00000141741 [Gene_View]  chr17:37885409-37886788 [Contig_View]  MIEN1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000141741 [Gene_View]  chr17:37885409-37886788 [Contig_View]  MIEN1 [Vega]
ICGC DataPortalENSG00000141741
TCGA cBioPortalMIEN1
AceView (NCBI)MIEN1
Genatlas (Paris)MIEN1
WikiGenes84299
SOURCE (Princeton)MIEN1
Genetics Home Reference (NIH)MIEN1
Genomic and cartography
GoldenPath hg19 (UCSC)MIEN1  -     chr17:37885409-37886788 -  17q12   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)MIEN1  -     17q12   [Description]    (hg38-Dec_2013)
EnsemblMIEN1 - 17q12 [CytoView hg19]  MIEN1 - 17q12 [CytoView hg38]
Mapping of homologs : NCBIMIEN1 [Mapview hg19]  MIEN1 [Mapview hg38]
OMIM611802   
Gene and transcription
Genbank (Entrez)AA010615 AF490253 AJ308025 AJ308026 AL554581
RefSeq transcript (Entrez)NM_032339
RefSeq genomic (Entrez)NC_000017 NC_018928 NG_007503 NT_010783 NW_004929407
Consensus coding sequences : CCDS (NCBI)MIEN1
Cluster EST : UnigeneHs.333526 [ NCBI ]
CGAP (NCI)Hs.333526
Alternative Splicing GalleryENSG00000141741
Gene ExpressionMIEN1 [ NCBI-GEO ]   MIEN1 [ EBI - ARRAY_EXPRESS ]   MIEN1 [ SEEK ]   MIEN1 [ MEM ]
Gene Expression Viewer (FireBrowse)MIEN1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)84299
GTEX Portal (Tissue expression)MIEN1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9BRT3   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9BRT3  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9BRT3
Splice isoforms : SwissVarQ9BRT3
PhosPhoSitePlusQ9BRT3
Domains : Interpro (EBI)Selenoprotein_Rdx-typ    Thioredoxin-like_fold   
Domain families : Pfam (Sanger)Rdx (PF10262)   
Domain families : Pfam (NCBI)pfam10262   
Conserved Domain (NCBI)MIEN1
DMDM Disease mutations84299
Blocks (Seattle)MIEN1
PDB (SRS)2LJK   
PDB (PDBSum)2LJK   
PDB (IMB)2LJK   
PDB (RSDB)2LJK   
Structural Biology KnowledgeBase2LJK   
SCOP (Structural Classification of Proteins)2LJK   
CATH (Classification of proteins structures)2LJK   
SuperfamilyQ9BRT3
Human Protein AtlasENSG00000141741
Peptide AtlasQ9BRT3
HPRD12681
IPIIPI00878073   IPI00979233   
Protein Interaction databases
DIP (DOE-UCLA)Q9BRT3
IntAct (EBI)Q9BRT3
FunCoupENSG00000141741
BioGRIDMIEN1
STRING (EMBL)MIEN1
ZODIACMIEN1
Ontologies - Pathways
QuickGOQ9BRT3
Ontology : AmiGOprotein binding  nucleoplasm  cytoplasm  cytosol  apoptotic process  positive regulation of cell migration  intrinsic component of the cytoplasmic side of the plasma membrane  negative regulation of apoptotic process  positive regulation of filopodium assembly  extracellular exosome  
Ontology : EGO-EBIprotein binding  nucleoplasm  cytoplasm  cytosol  apoptotic process  positive regulation of cell migration  intrinsic component of the cytoplasmic side of the plasma membrane  negative regulation of apoptotic process  positive regulation of filopodium assembly  extracellular exosome  
NDEx NetworkMIEN1
Atlas of Cancer Signalling NetworkMIEN1
Wikipedia pathwaysMIEN1
Orthology - Evolution
OrthoDB84299
GeneTree (enSembl)ENSG00000141741
Phylogenetic Trees/Animal Genes : TreeFamMIEN1
HOVERGENQ9BRT3
HOGENOMQ9BRT3
Homologs : HomoloGeneMIEN1
Homology/Alignments : Family Browser (UCSC)MIEN1
Gene fusions - Rearrangements
Fusion : MitelmanITGA3/MIEN1 [17q21.33/17q12]  [t(17;17)(q12;q21)]  
Fusion : MitelmanSRP68/MIEN1 [17q25.1/17q12]  [del(17)(q12q25)]  
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerMIEN1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MIEN1
dbVarMIEN1
ClinVarMIEN1
1000_GenomesMIEN1 
Exome Variant ServerMIEN1
ExAC (Exome Aggregation Consortium)MIEN1 (select the gene name)
Genetic variants : HAPMAP84299
Genomic Variants (DGV)MIEN1 [DGVbeta]
DECIPHER (Syndromes)17:37885409-37886788  ENSG00000141741
CONAN: Copy Number AnalysisMIEN1 
Mutations
ICGC Data PortalMIEN1 
TCGA Data PortalMIEN1 
Broad Tumor PortalMIEN1
OASIS PortalMIEN1 [ Somatic mutations - Copy number]
Mutations and Diseases : HGMDMIEN1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch MIEN1
DgiDB (Drug Gene Interaction Database)MIEN1
DoCM (Curated mutations)MIEN1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)MIEN1 (select a term)
intoGenMIEN1
NCG5 (London)MIEN1
Cancer3DMIEN1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM611802   
Orphanet
MedgenMIEN1
Genetic Testing Registry MIEN1
NextProtQ9BRT3 [Medical]
TSGene84299
GENETestsMIEN1
Huge Navigator MIEN1 [HugePedia]
snp3D : Map Gene to Disease84299
BioCentury BCIQMIEN1
ClinGenMIEN1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD84299
Chemical/Pharm GKB GenePA134947080
Clinical trialMIEN1
Miscellaneous
canSAR (ICR)MIEN1 (select the gene name)
Probes
Litterature
PubMed25 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineMIEN1
EVEXMIEN1
GoPubMedMIEN1
iHOPMIEN1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Apr 12 11:35:04 CEST 2017

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