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MOAP1 (Modulator Of Apoptosis 1)

Written2014-01Gamze Ayaz, Mesut Muyan
Department of Biological Sciences, Middle East Technical University, Ankara, Turkey

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)MAP-1
PNMA4
Other alias
HGNC (Hugo) MOAP1
LocusID (NCBI) 64112
Atlas_Id 46494
Location 14q32.12  [Link to chromosome band 14q32]
Location_base_pair Starts at 93648541 and ends at 93651249 bp from pter ( according to hg19-Feb_2009)  [Mapping MOAP1.png]
Fusion genes
(updated 2016)
MOAP1 (14q32.12) / ZAK (2q31.1)P3H4 (17q21.2) / MOAP1 (14q32.12)

DNA/RNA

 
  The MOAP1 gene is located in the reverse strand. Exons are shown as boxes and introns as lines. The filled box in the exon 3 is the coding sequence of MOAP1. Numbers below represent the size of exon or intron in base pair.
Description Human MOAP1 gene contains three exons and the encoding sequence of 1056 bases is in the exon 3.
Transcription MOAP1 is a 351 amino-acid long protein.
Pseudogene No reported pseudogenes.

Protein

Note MOAP1 is a short-lived protein with a half-life of 25 minutes. It is degraded by the ubiquitin-proteosome system (Fu et al., 2007).
Description MOAP-1 is a 351 amino-acid long protein with a molecular mass of 39.5 kDa. Isoelectric point (pI) of MOAP-1 is 4.939 at pH 7.0. MOAP-1 contains a BH3 (Bcl-2 homology 3) like domain required for homodimerization and interaction with Bcl-2 associated X (Bax) protein. Under normal condition, MOAP1 is held as an inactive conformation through intramolecular interactions. Interaction between RASSF1A (ras-association domain family 1, isoform A) and MOAP1 reduces the inhibitory intramolecular interaction of MOAP1 and allows MOAP1 through the BH3 like domain to bind Bax (Baksh et al., 2005).
Expression MOAP1 is expressed in the adipose, adrenal, blood, brain, breast, colon and heart. MOAP1 is expressed in higher level in the heart and brain.
Localisation MOAP-1 protein localizes in the cytoplasm (Law, 2012) and also seen in the mitochondria (Tan et al., 2005).
Function MOAP1 is a BH3-like protein that acts as a pro-apoptotic molecule (Tan et al., 2001). When overexpressed, MOAP1 induces caspase-dependent apoptosis in mammalian cells (Tan et al., 2005). Studies showed that TNFα stimulation recruits RASSF1A and MOAP1 to death receptors complexes. This recruitment leads to the association of RASSF1A with MOAP1 and to the induction of a conformational change in MOAP1. This results in the opening of the BH3 domain to allow MOAP1 to interact with Bax. Bax is subsequently inserted into the mitochondrial membrane leading to apoptosis (Baksh et al., 2005; Foley et al., 2008).
Homology Also highly conserved in rat (Rattus norvegicus) and mouse (Mus musculus), human MOAP1 protein shares 99% amino acids identity with that of chimpanzee (Pan troglodytes) (Law et al., 2012).

Mutations

Note Gene mutations have not been described yet.

Implicated in

Note
  
Entity Breast cancer
Disease Microarray analysis of 176 primary, treatment-naive breast cancer and of 10 normal breast tissue samples suggests that the MOAP1 gene expression is significantly down-regulated in breast cancer. It appears that there is a positive correlation between the downregulation of MOAP1 expression and the aggressiveness of breast cancer (Law, 2012).
  

To be noted

miRNA: It is reported that miR-1228 prevents cellular apoptosis by binding to the 3'UTR of MOAP1 mRNA, thereby decreasing MOAP-1 protein levels (Yan and Zhao, 2012).

Bibliography

The tumor suppressor RASSF1A and MAP-1 link death receptor signaling to Bax conformational change and cell death.
Baksh S, Tommasi S, Fenton S, Yu VC, Martins LM, Pfeifer GP, Latif F, Downward J, Neel BG.
Mol Cell. 2005 Jun 10;18(6):637-50.
PMID 15949439
 
Dynamics of RASSF1A/MOAP-1 association with death receptors.
Foley CJ, Freedman H, Choo SL, Onyskiw C, Fu NY, Yu VC, Tuszynski J, Pratt JC, Baksh S.
Mol Cell Biol. 2008 Jul;28(14):4520-35. doi: 10.1128/MCB.02011-07. Epub 2008 May 12.
PMID 18474619
 
Inhibition of ubiquitin-mediated degradation of MOAP-1 by apoptotic stimuli promotes Bax function in mitochondria.
Fu NY, Sukumaran SK, Yu VC.
Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10051-6. Epub 2007 May 29.
PMID 17535899
 
Modulator of Apoptosis 1: A Highly Regulated RASSF1A-Interacting BH3-Like Protein.
Law J, Yu VC, Baksh S.
Mol Biol Int. 2012;2012:536802. doi: 10.1155/2012/536802. Epub 2012 Jun 14.
PMID 22745908
 
MOAP1: A Candidate Tumor Suppressor Protein
Law J.
Master Thesis, University of Alberta, Canada, 2012 http://hdl.handle.net/10402/era.24828.
 
MAP-1 is a mitochondrial effector of Bax.
Tan KO, Fu NY, Sukumaran SK, Chan SL, Kang JH, Poon KL, Chen BS, Yu VC.
Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14623-8. Epub 2005 Sep 30.
PMID 16199525
 
MAP-1, a novel proapoptotic protein containing a BH3-like motif that associates with Bax through its Bcl-2 homology domains.
Tan KO, Tan KM, Chan SL, Yee KS, Bevort M, Ang KC, Yu VC.
J Biol Chem. 2001 Jan 26;276(4):2802-7. Epub 2000 Nov 1.
PMID 11060313
 
miR-1228 prevents cellular apoptosis through targeting of MOAP1 protein.
Yan B, Zhao JL.
Apoptosis. 2012 Jul;17(7):717-24. doi: 10.1007/s10495-012-0710-9.
PMID 22434376
 

Citation

This paper should be referenced as such :
G Ayaz, M Muyan
MOAP1 (Modulator Of Apoptosis 1)
Atlas Genet Cytogenet Oncol Haematol. 2014;18(9):650-651.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/MOAP1ID46494ch14q32.html


External links

Nomenclature
HGNC (Hugo)MOAP1   16658
Cards
AtlasMOAP1ID46494ch14q32
Entrez_Gene (NCBI)MOAP1  64112  modulator of apoptosis 1
AliasesMAP-1; PNMA4
GeneCards (Weizmann)MOAP1
Ensembl hg19 (Hinxton)ENSG00000165943 [Gene_View]  chr14:93648541-93651249 [Contig_View]  MOAP1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000165943 [Gene_View]  chr14:93648541-93651249 [Contig_View]  MOAP1 [Vega]
ICGC DataPortalENSG00000165943
TCGA cBioPortalMOAP1
AceView (NCBI)MOAP1
Genatlas (Paris)MOAP1
WikiGenes64112
SOURCE (Princeton)MOAP1
Genetics Home Reference (NIH)MOAP1
Genomic and cartography
GoldenPath hg19 (UCSC)MOAP1  -     chr14:93648541-93651249 -  14q32.12   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)MOAP1  -     14q32.12   [Description]    (hg38-Dec_2013)
EnsemblMOAP1 - 14q32.12 [CytoView hg19]  MOAP1 - 14q32.12 [CytoView hg38]
Mapping of homologs : NCBIMOAP1 [Mapview hg19]  MOAP1 [Mapview hg38]
OMIM609485   
Gene and transcription
Genbank (Entrez)AF305550 AK024029 AK315522 AM392976 BC015044
RefSeq transcript (Entrez)NM_022151
RefSeq genomic (Entrez)NC_000014 NC_018925 NT_026437 NT_187601 NW_004929393
Consensus coding sequences : CCDS (NCBI)MOAP1
Cluster EST : UnigeneHs.24719 [ NCBI ]
CGAP (NCI)Hs.24719
Alternative Splicing GalleryENSG00000165943
Gene ExpressionMOAP1 [ NCBI-GEO ]   MOAP1 [ EBI - ARRAY_EXPRESS ]   MOAP1 [ SEEK ]   MOAP1 [ MEM ]
Gene Expression Viewer (FireBrowse)MOAP1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)64112
GTEX Portal (Tissue expression)MOAP1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ96BY2   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ96BY2  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ96BY2
Splice isoforms : SwissVarQ96BY2
PhosPhoSitePlusQ96BY2
Domains : Interpro (EBI)PNMA   
Domain families : Pfam (Sanger)PNMA (PF14893)   
Domain families : Pfam (NCBI)pfam14893   
Conserved Domain (NCBI)MOAP1
DMDM Disease mutations64112
Blocks (Seattle)MOAP1
SuperfamilyQ96BY2
Human Protein AtlasENSG00000165943
Peptide AtlasQ96BY2
HPRD17580
IPIIPI00100939   
Protein Interaction databases
DIP (DOE-UCLA)Q96BY2
IntAct (EBI)Q96BY2
FunCoupENSG00000165943
BioGRIDMOAP1
STRING (EMBL)MOAP1
ZODIACMOAP1
Ontologies - Pathways
QuickGOQ96BY2
Ontology : AmiGOprotein insertion into mitochondrial membrane involved in apoptotic signaling pathway  protein binding  cytoplasm  mitochondrion  mitochondrial outer membrane  cytosol  extrinsic apoptotic signaling pathway via death domain receptors  intrinsic apoptotic signaling pathway in response to DNA damage  ubiquitin protein ligase binding  positive regulation of apoptotic process  positive regulation of release of cytochrome c from mitochondria  apoptotic signaling pathway  extrinsic apoptotic signaling pathway in absence of ligand  
Ontology : EGO-EBIprotein insertion into mitochondrial membrane involved in apoptotic signaling pathway  protein binding  cytoplasm  mitochondrion  mitochondrial outer membrane  cytosol  extrinsic apoptotic signaling pathway via death domain receptors  intrinsic apoptotic signaling pathway in response to DNA damage  ubiquitin protein ligase binding  positive regulation of apoptotic process  positive regulation of release of cytochrome c from mitochondria  apoptotic signaling pathway  extrinsic apoptotic signaling pathway in absence of ligand  
NDEx NetworkMOAP1
Atlas of Cancer Signalling NetworkMOAP1
Wikipedia pathwaysMOAP1
Orthology - Evolution
OrthoDB64112
GeneTree (enSembl)ENSG00000165943
Phylogenetic Trees/Animal Genes : TreeFamMOAP1
HOVERGENQ96BY2
HOGENOMQ96BY2
Homologs : HomoloGeneMOAP1
Homology/Alignments : Family Browser (UCSC)MOAP1
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerMOAP1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MOAP1
dbVarMOAP1
ClinVarMOAP1
1000_GenomesMOAP1 
Exome Variant ServerMOAP1
ExAC (Exome Aggregation Consortium)MOAP1 (select the gene name)
Genetic variants : HAPMAP64112
Genomic Variants (DGV)MOAP1 [DGVbeta]
DECIPHER (Syndromes)14:93648541-93651249  ENSG00000165943
CONAN: Copy Number AnalysisMOAP1 
Mutations
ICGC Data PortalMOAP1 
TCGA Data PortalMOAP1 
Broad Tumor PortalMOAP1
OASIS PortalMOAP1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICMOAP1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDMOAP1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch MOAP1
DgiDB (Drug Gene Interaction Database)MOAP1
DoCM (Curated mutations)MOAP1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)MOAP1 (select a term)
intoGenMOAP1
NCG5 (London)MOAP1
Cancer3DMOAP1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM609485   
Orphanet
MedgenMOAP1
Genetic Testing Registry MOAP1
NextProtQ96BY2 [Medical]
TSGene64112
GENETestsMOAP1
Huge Navigator MOAP1 [HugePedia]
snp3D : Map Gene to Disease64112
BioCentury BCIQMOAP1
ClinGenMOAP1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD64112
Chemical/Pharm GKB GenePA134908381
Clinical trialMOAP1
Miscellaneous
canSAR (ICR)MOAP1 (select the gene name)
Probes
Litterature
PubMed26 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineMOAP1
EVEXMOAP1
GoPubMedMOAP1
iHOPMOAP1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Apr 12 11:35:38 CEST 2017

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