VMP1 (vacuole membrane protein 1)

Written2011-11Alejandro Ropolo, Andrea Lo Ré, María Inés Vaccaro
Molecular Pathophysiology Lab, School of Pharmacie, Biochemistry, University of Buenos Aires, Argentina

(Note : for Links provided by Atlas : click)

1. Identity

General Information
transmembrane protein 49
Alias_symbol (synonym)EPG3
Other aliasDKFZp566I133
HGNC (Hugo) VMP1
LocusID (NCBI) 81671
Atlas_Id 50079
Location 17q23.1  [Link to chromosome band 17q23]
Location_base_pair Starts at 59707465 and ends at 59842255 bp from pter ( according to hg19-Feb_2009)  [Mapping VMP1.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)
AKAP8 (19p13.12) / VMP1 (17q23.1)BCAS3 (17q23.2) / VMP1 (17q23.1)BRIP1 (17q23.2) / VMP1 (17q23.1)
CACNG4 (17q24.2) / VMP1 (17q23.1)CFAP97 (4q35.1) / VMP1 (17q23.1)CHMP5 (9p13.3) / VMP1 (17q23.1)
CKAP5 (11p11.2) / VMP1 (17q23.1)CLTC (17q23.1) / VMP1 (17q23.1)DCAF7 (17q23.3) / VMP1 (17q23.1)
EARS2 (16p12.2) / VMP1 (17q23.1)INTS2 (17q23.2) / VMP1 (17q23.1)MED13 (17q23.2) / VMP1 (17q23.1)
MGAT5B (17q25.2) / VMP1 (17q23.1)MICAL2 (11p15.3) / VMP1 (17q23.1)PALLD (4q32.3) / VMP1 (17q23.1)
PPM1E (17q22) / VMP1 (17q23.1)RBM39 (20q11.22) / VMP1 (17q23.1)RPS6KB1 (17q23.1) / VMP1 (17q23.1)
TRIM37 (17q22) / VMP1 (17q23.1)TUBD1 (17q23.1) / VMP1 (17q23.1)VARS (6p21.33) / VMP1 (17q23.1)
VMP1 (17q23.1) / CDC42EP4 (17q25.1)VMP1 (17q23.1) / CFAP97 (4q35.1)VMP1 (17q23.1) / CLTC (17q23.1)
VMP1 (17q23.1) / MARCH10 (17q23.2)VMP1 (17q23.1) / PDK2 (17q21.33)VMP1 (17q23.1) / PEX6 (6p21.1)
VMP1 (17q23.1) / PSMA6 (14q13.2)VMP1 (17q23.1) / PTRH2 (17q23.1)VMP1 (17q23.1) / RNFT1 (17q23.1)


  Genomic organization of the VMP1/TMEM49 gene.
Description 12 exons, spans approximately 133 kb of genomic DNA in the centromere-to-telomere orientation. The translation initiation codon is located to exon 2, and the stop codon to exon 12.
Transcription mRNA of 2,17 kb.

3. Protein

  Schematic representation of VMP1 protein and localization of transmembrane domains.
Description The pancreatitis-associated protein vacuole membrane protein 1 (VMP1) is a transmembrane protein of 406 amino-acid length containing 6 putative transmembrane domains and with no known homologues in yeast.
Expression VMP1 was characterized because is not constitutively expressed in pancreatic acinar cells and it is highly activated early during experimental acute pancreatitis in acinar cells.
Localisation Autophagosomal membrane.
Function VMP1 is an autophagy-related membrane protein. VMP1 expression triggers autophagy, even under nutrient-replete conditions. VMP1 is required for autophagosome development through interaction with Beclin1. Recently, it has been demonstrated that participate in a novel selective form of autophagy, called zymophagy, mediated by VMP1-USP9x-p62 pathway during acute pancreatitis.

4. Implicated in

Entity Pancreatic cancer
Disease Pancreatic ductal adenocarcinoma is one of the most aggressive human malignancies with a 2-3% 5-year survival rate. This is due to both the aggressive nature of the disease and the lack of specific symptoms and early-detection tools. It is relatively refractory to traditional cytotoxic agents and radiotherapy. Gemcitabine, the standard chemotherapy agent for the treatment of pancreatic cancer, induces autophagy of cancer cells and that this process mediates the cell death-promoting activity of this compound. Early induction of autophagy by gemcitabine leads to cancer cell death and this cellular process is mediated by the activation of VMP1 expression. In PANC-1 and MIAPaCa-2 cells the inhibition of autophagy significantly reduced the percentage of dead cells in response to gemcitabine. In addition, gemcitabine promoted early VMP1 expression, and downregulation of VMP1 expression significantly reduced cell death.
Entity Acute pancreatitis
Disease VMP1 was characterized because is not constitutively expressed in pancreatic acinar cells and it is highly activated early during experimental acute pancreatitis in acinar cells. VMP1 is an autophagy-related membrane protein involved in the initial steps of the mammalian cell autophagic process. VMP1 is a transmembrane protein that co-localizes with LC3, a marker of the autophagosomes, in pancreas tissue undergoing pancreatitis-induced autophagy. VMP1 interacts with with Beclin1, a mammalian autophagy initiator, to start autophagosome formation. We developed the ElaI-VMP1 mouse in which acinar cell-specific constitutive expression of a VMP1-EGFP chimera induces the formation of autophagosomes. Upon CCK-R hyperstimulation, wild type mice developed acute pancreatitis with high amylase and lipase serum levels. On the contrary, enzymatic levels in cerulein-treated ElaI-VMP1 mice were significantly lower compared to wild type mice. Consistently, ElaI-VMP1 mouse pancreata showed remarkably less macroscopic evidence of acute pancreatitis compared to wild type animals, which showed marked edema and hemorrhage. Histological analyses displayed a high degree of necrosis as well as infiltration in wild type pancreata with acute pancreatitis. In contrast, neither necrosis nor significant inflammation was seen in cerulein-treated ElaI-VMP1 mice. ElaIVMP1 mice showed secretory granules with normal ultrastructural characteristics CCK-R hyperstimulation in wild type animals induced a markedly altered distribution pattern of the secretory granules. Acinar cells lose their polarity, which results in the relocation of zymogen granules to the basolateral membrane. These alterations in vesicular traffic are known to occur in acinar cells during acute pancreatitis and upon hyperstimulation of their CCK-R with cerulein. ElaI-VMP1 mice subjected to CCK-R hyperstimulation revealed that acinar cells preserve their structure and polarity with negligible or no alteration in vesicular transport. Surprisingly, in pancreata from cerulein-treated ElaI-VMP1 mice, we observed autophagosomes containing zymogen granules displaying a distinct localization to the apical area of the acinar cell. VMP1, the ubiquitin-protease USP9x, and the ubiquitin-binding protein p62 mediate this process. Moreover, VMP1 interacts with USP9x, indicating that there is a close cooperation between the autophagy pathway and the ubiquitin recognition machinery required for selective autophagosome formation. We have coined the term "zymophagy" to refer to this process. Zymophagy is activated by experimental pancreatitis and by acute pancreatitis in humans. Furthermore, zymophagy has pathophysiological relevance by controlling pancreatitis-induced intracellular zymogen activation and helping to prevent cell death. This new selective autophagy is activated in pancreatic acinar cells during pancreatitis-induced vesicular transport alteration to sequester and degrade potentially deleterious activated zymogen granules.
Confocal microscopy of AR42J cell transfected with pEGFP-VMP1.
Entity Diabetes
Disease Experimental diabetes activates VMP1 expression and autophagy in pancreas beta cells as a direct response to streptozotocin (STZ). VMP1 mRNA expression is activated after STZ treatment by islet beta cells. Electron microscopy shows chromatin aggregation and autophagy morphology that was confirmed by LC3 expression and LC3-VMP1 co-localization. Apoptotic cell death and the reduction of beta cell pool are evident after 24h treatment, while VMP1 is still expressed in the remaining cells. VMP1-Beclin1 colocalization in pancreas tissue from STZ-treated rats suggests that VMP1-Beclin1 interaction is involved in the autophagic process activation during experimental diabetes. Pancreas beta cells trigger VMP1 expression and autophagy during the early cellular events in response to experimental diabetes.

5. Bibliography

Cloning and expression of the rat vacuole membrane protein 1 (VMP1), a new gene activated in pancreas with acute pancreatitis, which promotes vacuole formation.
Dusetti NJ, Jiang Y, Vaccaro MI, Tomasini R, Azizi Samir A, Calvo EL, Ropolo A, Fiedler F, Mallo GV, Dagorn JC, Iovanna JL.
Biochem Biophys Res Commun. 2002 Jan 18;290(2):641-9.
PMID 11785947
Zymophagy, a novel selective autophagy pathway mediated by VMP1-USP9x-p62, prevents pancreatic cell death.
Grasso D, Ropolo A, Lo Re A, Boggio V, Molejon MI, Iovanna JL, Gonzalez CD, Urrutia R, Vaccaro MI.
J Biol Chem. 2011 Mar 11;286(10):8308-24. Epub 2010 Dec 20.
PMID 21173155
Autophagy and VMP1 expression are early cellular events in experimental diabetes.
Grasso D, Sacchetti ML, Bruno L, Lo Re A, Iovanna JL, Gonzalez CD, Vaccaro MI.
Pancreatology. 2009;9(1-2):81-8. Epub 2008 May 5.
PMID 19077458
Expression of vacuole membrane protein 1 (VMP1) in spontaneous chronic pancreatitis in the WBN/Kob rat.
Jiang PH, Motoo Y, Vaccaro MI, Iovanna JL, Okada G, Sawabu N.
Pancreas. 2004 Oct;29(3):225-30.
PMID 15367889
Gemcitabine induces the VMP1-mediated autophagy pathway to promote apoptotic death in human pancreatic cancer cells.
Pardo R, Lo Re A, Archange C, Ropolo A, Papademetrio DL, Gonzalez CD, Alvarez EM, Iovanna JL, Vaccaro MI.
Pancreatology. 2010;10(1):19-26. Epub 2010 Mar 19.
PMID 20299819
The pancreatitis-induced vacuole membrane protein 1 triggers autophagy in mammalian cells.
Ropolo A, Grasso D, Pardo R, Sacchetti ML, Archange C, Lo Re A, Seux M, Nowak J, Gonzalez CD, Iovanna JL, Vaccaro MI.
J Biol Chem. 2007 Dec 21;282(51):37124-33. Epub 2007 Oct 16.
PMID 17940279
A novel mammalian trans-membrane protein reveals an alternative initiation pathway for autophagy.
Vaccaro MI, Ropolo A, Grasso D, Iovanna JL.
Autophagy. 2008 Apr;4(3):388-90. Epub 2008 Jan 30.
PMID 18253086
Autophagy and pancreas disease.
Vaccaro MI.
Pancreatology. 2008;8(4-5):425-9. Epub 2008 Aug 20. (REVIEW)
PMID 18714176

6. Citation

7. External links

HGNC (Hugo)VMP1   29559
Entrez_Gene (NCBI)VMP1  81671  vacuole membrane protein 1
AliasesEPG3; TANGO5; TMEM49
GeneCards (Weizmann)VMP1
Ensembl hg19 (Hinxton)ENSG00000062716 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000062716 [Gene_View] &nbspENSG00000062716 [Sequence]  chr17:59707465-59842255 [Contig_View]  VMP1 [Vega]
ICGC DataPortalENSG00000062716
TCGA cBioPortalVMP1
AceView (NCBI)VMP1
Genatlas (Paris)VMP1
SOURCE (Princeton)VMP1
Genetics Home Reference (NIH)VMP1
Genomic and cartography
GoldenPath hg38 (UCSC)VMP1  -     chr17:59707465-59842255 +  17q23.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)VMP1  -     17q23.1   [Description]    (hg19-Feb_2009)
EnsemblVMP1 - 17q23.1 [CytoView hg19]  VMP1 - 17q23.1 [CytoView hg38]
Mapping of homologs : NCBIVMP1 [Mapview hg19]  VMP1 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AB047551 AF161410 AF214006 AK024969 AK025987
RefSeq transcript (Entrez)NM_001329394 NM_001329395 NM_001329396 NM_001329397 NM_001329398 NM_001329399 NM_001329400 NM_001329401 NM_001329402 NM_030938
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)VMP1
Cluster EST : UnigeneHs.743288 [ NCBI ]
CGAP (NCI)Hs.743288
Alternative Splicing GalleryENSG00000062716
Gene ExpressionVMP1 [ NCBI-GEO ]   VMP1 [ EBI - ARRAY_EXPRESS ]   VMP1 [ SEEK ]   VMP1 [ MEM ]
Gene Expression Viewer (FireBrowse)VMP1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets] &nbsp [Normal Tissue Atlas] &nbsp[carcinoma Classsification] &nbsp[NCI60]
GenevestigatorExpression in : [tissues] &nbsp[cell-lines] &nbsp[cancer] &nbsp[perturbations] &nbsp
BioGPS (Tissue expression)81671
GTEX Portal (Tissue expression)VMP1
Human Protein AtlasENSG00000062716-VMP1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ96GC9   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ96GC9  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ96GC9
Splice isoforms : SwissVarQ96GC9
Domains : Interpro (EBI)SNARE_assoc   
Domain families : Pfam (Sanger)SNARE_assoc (PF09335)   
Domain families : Pfam (NCBI)pfam09335   
Conserved Domain (NCBI)VMP1
DMDM Disease mutations81671
Blocks (Seattle)VMP1
Human Protein Atlas [tissue]ENSG00000062716-VMP1 [tissue]
Peptide AtlasQ96GC9
IPIIPI01015255   IPI01015169   IPI01013905   IPI00792839   IPI01014766   IPI00742911   
Protein Interaction databases
IntAct (EBI)Q96GC9
Ontologies - Pathways
Ontology : AmiGOautophagosome assembly  phagophore assembly site  autophagosome membrane  protein binding  nucleolus  endoplasmic reticulum  endoplasmic reticulum  plasma membrane  autophagy  Golgi organization  embryo implantation  integral component of membrane  endoplasmic reticulum-Golgi intermediate compartment membrane  cell junction assembly  cell-cell adhesion  
Ontology : EGO-EBIautophagosome assembly  phagophore assembly site  autophagosome membrane  protein binding  nucleolus  endoplasmic reticulum  endoplasmic reticulum  plasma membrane  autophagy  Golgi organization  embryo implantation  integral component of membrane  endoplasmic reticulum-Golgi intermediate compartment membrane  cell junction assembly  cell-cell adhesion  
NDEx NetworkVMP1
Atlas of Cancer Signalling NetworkVMP1
Wikipedia pathwaysVMP1
Orthology - Evolution
GeneTree (enSembl)ENSG00000062716
Phylogenetic Trees/Animal Genes : TreeFamVMP1
Homologs : HomoloGeneVMP1
Homology/Alignments : Family Browser (UCSC)VMP1
Gene fusions - Rearrangements
Fusion : Mitelman-/17q23.1 [VMP1/t(17;17)(q22;q23)] &nbsp
Fusion : MitelmanAKAP8/VMP1 [19p13.12/17q23.1] &nbsp[t(17;19)(q23;p13)]  
Fusion : MitelmanBCAS3/VMP1 [17q23.2/17q23.1] &nbsp[t(17;17)(q23;q23)]  
Fusion : MitelmanBRIP1/VMP1 [17q23.2/17q23.1] &nbsp[t(17;17)(q23;q23)]  
Fusion : MitelmanCACNG4/VMP1 [17q24.2/17q23.1] &nbsp[t(17;17)(q23;q24)]  
Fusion : MitelmanCHMP5/VMP1 [9p13.3/17q23.1] &nbsp[t(9;17)(p13;q23)]  
Fusion : MitelmanCKAP5/VMP1 [11p11.2/17q23.1] &nbsp[t(11;17)(p11;q23)]  
Fusion : MitelmanCLTC/VMP1 [17q23.1/17q23.1] &nbsp[t(17;17)(q23;q23)]  
Fusion : MitelmanDCAF7/VMP1 [17q23.3/17q23.1] &nbsp[t(17;17)(q23;q23)]  
Fusion : MitelmanEARS2/VMP1 [16p12.2/17q23.1] &nbsp[t(16;17)(p12;q23)]  
Fusion : MitelmanINTS2/VMP1 [17q23.2/17q23.1] &nbsp[t(17;17)(q23;q23)]  
Fusion : MitelmanMED13/VMP1 [17q23.2/17q23.1] &nbsp[t(17;17)(q23;q23)]  
Fusion : MitelmanMGAT5B/VMP1 [17q25.2/17q23.1] &nbsp[t(17;17)(q23;q25)]  
Fusion : MitelmanPPM1E/VMP1 [17q22/17q23.1] &nbsp[t(17;17)(q22;q23)]  
Fusion : MitelmanRBM39/VMP1 [20q11.22/17q23.1] &nbsp[t(17;20)(q23;q11)]  
Fusion : MitelmanRPS6KB1/VMP1 [17q23.1/17q23.1] &nbsp[dup(17)(q23q23)]  [t(17;17)(q23;q23)]  
Fusion : MitelmanTRIM37/VMP1 [17q22/17q23.1] &nbsp[t(17;17)(q22;q23)]  
Fusion : MitelmanTUBD1/VMP1 [17q23.1/17q23.1] &nbsp[t(17;17)(q23;q23)]  
Fusion : MitelmanVARS/VMP1 [6p21.33/17q23.1] &nbsp[t(6;17)(p21;q23)]  
Fusion : MitelmanVMP1/CDC42EP4 [17q23.1/17q25.1] &nbsp[t(17;17)(q23;q25)]  
Fusion : MitelmanVMP1/CLTC [17q23.1/17q23.1] &nbsp[t(17;17)(q23;q23)]  
Fusion : MitelmanVMP1/MARCH10 [17q23.1/17q23.2] &nbsp[t(17;17)(q23;q23)]  
Fusion : MitelmanVMP1/PSMA6 [17q23.1/14q13.2] &nbsp[t(14;17)(q13;q23)]  
Fusion : MitelmanVMP1/PTRH2 [17q23.1/17q23.1] &nbsp[t(17;17)(q23;q23)]  
Fusion : MitelmanVMP1/RNFT1 [17q23.1/17q23.1] &nbsp[t(17;17)(q23;q23)]  
Fusion PortalAKAP8 19p13.12 VMP1 17q23.1 BRCA
Fusion PortalBCAS3 17q23.2 VMP1 17q23.1 BRCA
Fusion PortalCACNG4 17q24.2 VMP1 17q23.1 BRCA
Fusion PortalCHMP5 9p13.3 VMP1 17q23.1 BRCA
Fusion PortalCKAP5 11p11.2 VMP1 17q23.1 BRCA
Fusion PortalDCAF7 17q23.3 VMP1 17q23.1 BRCA
Fusion PortalEARS2 16p12.2 VMP1 17q23.1 LUAD
Fusion PortalMED13 17q23.2 VMP1 17q23.1 BRCA
Fusion PortalMGAT5B 17q25.2 VMP1 17q23.1 KIRC
Fusion PortalPPM1E 17q22 VMP1 17q23.1 BRCA
Fusion PortalRBM39 20q11.22 VMP1 17q23.1 BRCA
Fusion PortalRPS6KB1 17q23.1 VMP1 17q23.1 BLCA BRCA HNSC LUAD OV
Fusion PortalTUBD1 17q23.1 VMP1 17q23.1 LUAD
Fusion PortalVARS 6p21.33 VMP1 17q23.1 LUAD
Fusion PortalVMP1 17q23.1 CDC42EP4 17q25.1 BRCA
Fusion PortalVMP1 17q23.1 CLTC 17q23.1 BRCA
Fusion PortalVMP1 17q23.1 MARCH10 17q23.2 BRCA
Fusion PortalVMP1 17q23.1 PSMA6 14q13.2 BRCA
Fusion PortalVMP1 17q23.1 PTRH2 17q23.1 HNSC
Fusion PortalVMP1 17q23.1 RNFT1 17q23.1 BRCA
Fusion PortalVMP1 17q23.1 RP11-433C9.2 BRCA
Fusion Cancer (Beijing)CLTC [17q23.1]  -  VMP1 [17q23.1]  [FUSC003429]
Fusion Cancer (Beijing)RPS6KB1 [17q23.1]  -  VMP1 [17q23.1]  [FUSC001256]  [FUSC001256]
Fusion : QuiverVMP1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerVMP1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)VMP1
Exome Variant ServerVMP1
ExAC (Exome Aggregation Consortium)ENSG00000062716
GNOMAD BrowserENSG00000062716
Varsome BrowserVMP1
Genetic variants : HAPMAP81671
Genomic Variants (DGV)VMP1 [DGVbeta]
DECIPHERVMP1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisVMP1 
ICGC Data PortalVMP1 
TCGA Data PortalVMP1 
Broad Tumor PortalVMP1
OASIS PortalVMP1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICVMP1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDVMP1
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 VMP1
DgiDB (Drug Gene Interaction Database)VMP1
DoCM (Curated mutations)VMP1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)VMP1 (select a term)
NCG5 (London)VMP1
Cancer3DVMP1(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry VMP1
NextProtQ96GC9 [Medical]
Target ValidationVMP1
Huge Navigator VMP1 [HugePedia]
snp3D : Map Gene to Disease81671
BioCentury BCIQVMP1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD81671
Chemical/Pharm GKB GenePA142670765
Clinical trialVMP1
canSAR (ICR)VMP1 (select the gene name)
DataMed IndexVMP1
Other databaseThe Pancreapedia
PubMed41 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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