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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)


Alias (NCBI)C17orf37
HGNC Alias symbMGC14832
HGNC Previous nameC17orf37
HGNC Previous namechromosome 17 open reading frame 37
LocusID (NCBI) 84299
Atlas_Id 52476
Location 17q12  [Link to chromosome band 17q12]
Location_base_pair Starts at 39728511 and ends at 39730532 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping MIEN1.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
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)SLFN11 (17q12)::MIEN1 (17q12)
SRP68 (17q25.1)::MIEN1 (17q12)


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.


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Localisation MIEN1 protein is membrane bound and its stability depends on its localization (our unpublished observations).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.


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

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.


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


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 ]

External links


HGNC (Hugo)MIEN1   28230
Entrez_Gene (NCBI)MIEN1    migration and invasion enhancer 1
AliasesC17orf37; C35; ORB3; RDX12; 
GeneCards (Weizmann)MIEN1
Ensembl hg19 (Hinxton)ENSG00000141741 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000141741 [Gene_View]  ENSG00000141741 [Sequence]  chr17:39728511-39730532 [Contig_View]  MIEN1 [Vega]
ICGC DataPortalENSG00000141741
TCGA cBioPortalMIEN1
Genatlas (Paris)MIEN1
SOURCE (Princeton)MIEN1
Genetics Home Reference (NIH)MIEN1
Genomic and cartography
GoldenPath hg38 (UCSC)MIEN1  -     chr17:39728511-39730532 -  17q12   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)MIEN1  -     17q12   [Description]    (hg19-Feb_2009)
GoldenPathMIEN1 - 17q12 [CytoView hg19]  MIEN1 - 17q12 [CytoView hg38]
Genome Data Viewer NCBIMIEN1 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AA010615 AF490253 AJ308025 AJ308026 AL554581
RefSeq transcript (Entrez)NM_001330206 NM_032339
Consensus coding sequences : CCDS (NCBI)MIEN1
Gene ExpressionMIEN1 [ NCBI-GEO ]   MIEN1 [ EBI - ARRAY_EXPRESS ]   MIEN1 [ SEEK ]   MIEN1 [ MEM ]
Gene Expression Viewer (FireBrowse)MIEN1 [ Firebrowse - Broad ]
GenevisibleExpression of MIEN1 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)84299
GTEX Portal (Tissue expression)MIEN1
Human Protein AtlasENSG00000141741-MIEN1 [pathology]   [cell]   [tissue]
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
Domains : Interpro (EBI)Selenoprotein_Rdx-typ    Thioredoxin-like_sf   
Domain families : Pfam (Sanger)Rdx (PF10262)   
Domain families : Pfam (NCBI)pfam10262   
Conserved Domain (NCBI)MIEN1
PDB Europe2LJK   
Structural Biology KnowledgeBase2LJK   
SCOP (Structural Classification of Proteins)2LJK   
CATH (Classification of proteins structures)2LJK   
AlphaFold pdb e-kbQ9BRT3   
Human Protein Atlas [tissue]ENSG00000141741-MIEN1 [tissue]
Protein Interaction databases
IntAct (EBI)Q9BRT3
Ontologies - Pathways
Ontology : AmiGOprotein binding  nucleoplasm  cytosol  cytosol  plasma membrane  apoptotic process  response to selenium ion  positive regulation of cell migration  intrinsic component of the cytoplasmic side of the plasma membrane  centriolar satellite  negative regulation of apoptotic process  negative regulation of apoptotic process  positive regulation of filopodium assembly  positive regulation of filopodium assembly  
Ontology : EGO-EBIprotein binding  nucleoplasm  cytosol  cytosol  plasma membrane  apoptotic process  response to selenium ion  positive regulation of cell migration  intrinsic component of the cytoplasmic side of the plasma membrane  centriolar satellite  negative regulation of apoptotic process  negative regulation of apoptotic process  positive regulation of filopodium assembly  positive regulation of filopodium assembly  
NDEx NetworkMIEN1
Atlas of Cancer Signalling NetworkMIEN1
Wikipedia pathwaysMIEN1
Orthology - Evolution
GeneTree (enSembl)ENSG00000141741
Phylogenetic Trees/Animal Genes : TreeFamMIEN1
Homologs : HomoloGeneMIEN1
Homology/Alignments : Family Browser (UCSC)MIEN1
Gene fusions - Rearrangements
Fusion : MitelmanITGA3::MIEN1 [17q21.33/17q12]  
Fusion : MitelmanSRP68::MIEN1 [17q25.1/17q12]  
Fusion : QuiverMIEN1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerMIEN1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MIEN1
Exome Variant ServerMIEN1
GNOMAD BrowserENSG00000141741
Varsome BrowserMIEN1
ACMGMIEN1 variants
Genomic Variants (DGV)MIEN1 [DGVbeta]
DECIPHERMIEN1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisMIEN1 
ICGC Data PortalMIEN1 
TCGA Data PortalMIEN1 
Broad Tumor PortalMIEN1
OASIS PortalMIEN1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICMIEN1  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DMIEN1
Mutations and Diseases : HGMDMIEN1
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)MIEN1
DoCM (Curated mutations)MIEN1
CIViC (Clinical Interpretations of Variants in Cancer)MIEN1
NCG (London)MIEN1
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry MIEN1
NextProtQ9BRT3 [Medical]
Target ValidationMIEN1
Huge Navigator MIEN1 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDMIEN1
Pharm GKB GenePA134947080
Clinical trialMIEN1
DataMed IndexMIEN1
PubMed37 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:22:10 CEST 2021

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