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PRXL2C (Peroxiredoxin like 2C)

Written2018-11Jean Loup Huret
jean-loup.huret@atlasgeneticsoncology.org

Abstract Review on PRXL2C, with data on DNA, on the protein encoded, and where the gene is implicated.

Keywords PRXL2C; oxidation; reduction; Mutation; Overexpression; Cancer; Gastric cancer; Attention-deficit/hyperactivity disorder

(Note : for Links provided by Atlas : click)

Identity

Other aliasC9orf21
AAED1 (AhpC/TSA antioxidant enzyme domain containing 1)
HGNC (Hugo) AAED1
Atlas_Id 60014
Location 9q22.33  [Link to chromosome band 9q22]
Location_base_pair Starts at 96641251 and ends at 96655317 bp from pter ( according to hg19-Feb_2009)
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)

DNA/RNA

 
  Figure 1 PRXL2C gene
Description Six exons, four splice forms, one of which codes for a protein:
Transcription Coding transcript: 2863bp

Protein

Description A selenoprotein is a protein containing selenocysteines (Sec), with an atom of selenium SHE taking the place of the sulfur SH of the cysteine. Decoding of UGA into a selenocysteine (Sec) is alternative to the stop signal in the canonical genetic code. The human selenoproteins (SelU family) are composed of three Cys-containing members, one of which being PRXL2C (Ensembl ENSG00000158122) (Castellano et al., 2004). PRXL2C amino acids 68-71 are: CYIC, a CXXC motif.
According to InterPro http://www.ebi.ac.uk/interpro/protein/Q7RTV5 , PRXL2C signature matches with thioredoxin-like superfamily in amino acids 35-135 (or 21-90) (with a thioredoxin CXXC motif at aa 68-71 (CYIC); the two cysteines can forms a disulfide bond), and also matches with peroxiredoxin-like 2A/B/C in aa 86-196 (or 40-150). Peroxiredoxins and thioredoxins are involved in oxidation-reduction process (antioxidants). Peroxiredoxins form a family of thiol oxidoreductases and play a role in peroxides detoxification (see Figure2). A peroxidatic cysteine reduces the peroxide to water. Thioredoxin system reduce peroxiredoxins restoring to them their catalytically active form (West et al., 2018).
 
  Figure 2 Peroxides detoxification by Peroxiredoxins motifs -C-X-X-C-
Expression PRXL2C is widely expressed (The Human Protein Atlas).
Function Aaed1 was found to be one of the few primitive endoderm transition markers in preimplantation mouse embryos (Gerovska and Arauzo-Bravo, 2016).

Mutations

Somatic According to Cosmic
Glioma astrocytoma grade IV amino acid (aa) mutation: p.V91A from CDS mutation c.272T>C
Papillary thyroid carcinomas aa mutation p.I81S (c.242T>G)
Thyroid carcinomas NOS aa mutations: p.V95L (c.283G>T); p.G183V (c.548G>T)
Lung small cell carcinoma aa mutation: p.E136K (c.406G>A) (Rudin et al. 2012)
Lung adenocarcinoma aa mutations: p.H145N (c.433C>A) (Imielinski et al. 2012); p.S152L (c.455C>T)
Skin melanoma aa mutations: p.M131I (c.393G>A); p.S148L (c.443C>T); p.W159* (c.476G>A)
Colon adenocarcinoma aa mutations: p.E76D (c.228G>T); p.L110Q (c.329T>A) (Giannakis et al. 2016); p.S143I (c.428G>T) (Giannakis et al. 2016); p.Q208H (c.624G>T) (Wood et al. 2007); p.P221H (c.662C>A)
Duodenum adenoma aa mutations: p.K201N (c.603A>C) (Yachida et al. 2016); p.T218A (c.652A>G) (Yachida et al. 2016)
Prostate adenocarcinoma aa mutation: p.H214R (c.641A>G)

Implicated in

  
Entity Gastric cancer
Note (AhpC/TSA antioxidant enzyme domain containing 1), which is upregulated in gastric cancer cells. Silencing of PRXL2C inhibited cancer cell proliferation in vitro in gastric cancer cell lines. Possibly though MAPK signaling, PRXL2C upregulates HIF1A (hypoxia inducible factor 1 subunit alpha), a transcriptional activator of many genes, including glycolytic enzymes and glucose transporters in aerobic glycolysis (Zhang et al., 2018).
  
  
Entity Renal cancer
Note PRXL2C High expression is related with an unfavourable prognosis according to the Human Protein Atlas https://www.proteinatlas.org/ENSG00000158122-AAED1/pathology
  
  
Entity
Attention-deficit/hyperactivity disorder (ADHD)
Note A rare variant of PRXL2C (rs151326868) amino acid p.H200D (c.598C>G) was found to segregate with ADHD in one of the families with an apparent dominant inheritance that was studied (Corominas et al., 2018).
PRXL2C binds PICK1 (Protein Kinase C-Alpha-Binding Protein) and PICK1 binds SLC6A3 (solute carrier family 6 member 3, also known as DAT, the dopamine transporter 1), regulating SLC6A3 trafficking in presynaptic sites of dopaminergic neurons, and DRD3 (dopamine D3 receptor 3). PICK1 also has a role in glutamate receptor regulation (Corominas et al., 2018).
Disease ADHD is characterized by of lack of attention, impulsivity, hyperactivity and distractibility. It is a highly heritable (80%-90%) childhood behavioral disorder with a prevalence estimated at 5-7% in children, male predominance, and half of them have persisting symptoms in adulthood. In addition to genetic factors, environmental factors (adverse circumstances in maternal or children life) have been implicated in the etiology of ADHD.
  

Bibliography

Reconsidering the evolution of eukaryotic selenoproteins: a novel nonmammalian family with scattered phylogenetic distribution
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EMBO Rep 2004 Jan;5(1):71-7
PMID 14710190
 
Identification of ADHD risk genes in extended pedigrees by combining linkage analysis and whole-exome sequencing
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PMID 30116028
 
Does mouse embryo primordial germ cell activation start before implantation as suggested by single-cell transcriptomics dynamics? Mol Hum Reprod
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2016 Mar;22(3):208-25 doi: 10
PMID 26740066
 
Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma
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Cell Rep 2016 Apr 26;15(4):857-865
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Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing
Imielinski M, Berger AH, Hammerman PS, Hernandez B, Pugh TJ, Hodis E, Cho J, Suh J, Capelletti M, Sivachenko A, Sougnez C, Auclair D, Lawrence MS, Stojanov P, Cibulskis K, Choi K, de Waal L, Sharifnia T, Brooks A, Greulich H, Banerji S, Zander T, Seidel D, Leenders F, Ansén S, Ludwig C, Engel-Riedel W, Stoelben E, Wolf J, Goparju C, Thompson K, Winckler W, Kwiatkowski D, Johnson BE, Jänne PA, Miller VA, Pao W, Travis WD, Pass HI, Gabriel SB, Lander ES, Thomas RK, Garraway LA, Getz G, Meyerson M
Cell 2012 Sep 14;150(6):1107-20
PMID 22980975
 
Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer
Rudin CM, Durinck S, Stawiski EW, Poirier JT, Modrusan Z, Shames DS, Bergbower EA, Guan Y, Shin J, Guillory J, Rivers CS, Foo CK, Bhatt D, Stinson J, Gnad F, Haverty PM, Gentleman R, Chaudhuri S, Janakiraman V, Jaiswal BS, Parikh C, Yuan W, Zhang Z, Koeppen H, Wu TD, Stern HM, Yauch RL, Huffman KE, Paskulin DD, Illei PB, Varella-Garcia M, Gazdar AF, de Sauvage FJ, Bourgon R, Minna JD, Brock MV, Seshagiri S
Nat Genet 2012 Oct;44(10):1111-6
PMID 22941189
 
Piecing Together How Peroxiredoxins Maintain Genomic Stability
West JD, Roston TJ, David JB, Allan KM, Loberg MA
Antioxidants (Basel) 2018 Nov 28;7(12)
PMID 30486489
 
The genomic landscapes of human breast and colorectal cancers
Wood LD, Parsons DW, Jones S, Lin J, Sjöblom T, Leary RJ, Shen D, Boca SM, Barber T, Ptak J, Silliman N, Szabo S, Dezso Z, Ustyanksky V, Nikolskaya T, Nikolsky Y, Karchin R, Wilson PA, Kaminker JS, Zhang Z, Croshaw R, Willis J, Dawson D, Shipitsin M, Willson JK, Sukumar S, Polyak K, Park BH, Pethiyagoda CL, Pant PV, Ballinger DG, Sparks AB, Hartigan J, Smith DR, Suh E, Papadopoulos N, Buckhaults P, Markowitz SD, Parmigiani G, Kinzler KW, Velculescu VE, Vogelstein B
Science 2007 Nov 16;318(5853):1108-13
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Genomic Sequencing Identifies ELF3 as a Driver of Ampullary Carcinoma
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Citation

This paper should be referenced as such :
Huret JL
PRXL2C (Peroxiredoxin like 2C);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/PRXL2CID60014ch9q22.html


External links

Nomenclature
HGNC (Hugo)PRXL2C   16881
Cards
AtlasPRXL2CID60014ch9q22
Entrez_Gene (NCBI)PRXL2C  195827  peroxiredoxin like 2C
AliasesAAED1; C9orf21
GeneCards (Weizmann)PRXL2C
Ensembl hg19 (Hinxton)ENSG00000158122 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000158122 [Gene_View]  ENSG00000158122 [Sequence]  chr9:96641251-96655317 [Contig_View]  PRXL2C [Vega]
ICGC DataPortalENSG00000158122
TCGA cBioPortalPRXL2C
AceView (NCBI)PRXL2C
Genatlas (Paris)PRXL2C
WikiGenes195827
SOURCE (Princeton)PRXL2C
Genetics Home Reference (NIH)PRXL2C
Genomic and cartography
GoldenPath hg38 (UCSC)PRXL2C  -     chr9:96641251-96655317 -  9q22.33   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PRXL2C  -     9q22.33   [Description]    (hg19-Feb_2009)
GoldenPathPRXL2C - 9q22.33 [CytoView hg19]  PRXL2C - 9q22.33 [CytoView hg38]
ImmunoBaseENSG00000158122
Mapping of homologs : NCBIPRXL2C [Mapview hg19]  PRXL2C [Mapview hg38]
Gene and transcription
Genbank (Entrez)BC136501 BC136503 BF445089 BK000255 BM843088
RefSeq transcript (Entrez)NM_153698
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)PRXL2C
Cluster EST : UnigeneHs.44640 [ NCBI ]
CGAP (NCI)Hs.44640
Alternative Splicing GalleryENSG00000158122
Gene ExpressionPRXL2C [ NCBI-GEO ]   PRXL2C [ EBI - ARRAY_EXPRESS ]   PRXL2C [ SEEK ]   PRXL2C [ MEM ]
Gene Expression Viewer (FireBrowse)PRXL2C [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
GTEX Portal (Tissue expression)PRXL2C
Human Protein AtlasENSG00000158122-PRXL2C [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ7RTV5   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ7RTV5  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ7RTV5
Splice isoforms : SwissVarQ7RTV5
PhosPhoSitePlusQ7RTV5
Domains : Interpro (EBI)FAM213/AAED1    Thioredoxin-like_sf   
Domain families : Pfam (Sanger)AhpC-TSA_2 (PF13911)   
Domain families : Pfam (NCBI)pfam13911   
Conserved Domain (NCBI)PRXL2C
DMDM Disease mutations195827
Blocks (Seattle)PRXL2C
SuperfamilyQ7RTV5
Human Protein Atlas [tissue]ENSG00000158122-PRXL2C [tissue]
Peptide AtlasQ7RTV5
IPIIPI00146380   IPI00552550   IPI00552717   
Protein Interaction databases
DIP (DOE-UCLA)Q7RTV5
IntAct (EBI)Q7RTV5
FunCoupENSG00000158122
BioGRIDPRXL2C
STRING (EMBL)PRXL2C
ZODIACPRXL2C
Ontologies - Pathways
QuickGOQ7RTV5
Ontology : AmiGOantioxidant activity  positive regulation of glycolytic process  oxidation-reduction process  positive regulation of ERK1 and ERK2 cascade  cellular oxidant detoxification  
Ontology : EGO-EBIantioxidant activity  positive regulation of glycolytic process  oxidation-reduction process  positive regulation of ERK1 and ERK2 cascade  cellular oxidant detoxification  
NDEx NetworkPRXL2C
Atlas of Cancer Signalling NetworkPRXL2C
Wikipedia pathwaysPRXL2C
Orthology - Evolution
GeneTree (enSembl)ENSG00000158122
Phylogenetic Trees/Animal Genes : TreeFamPRXL2C
HOGENOMQ7RTV5
Homologs : HomoloGenePRXL2C
Homology/Alignments : Family Browser (UCSC)PRXL2C
Gene fusions - Rearrangements
Fusion : QuiverPRXL2C
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPRXL2C [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PRXL2C
dbVarPRXL2C
ClinVarPRXL2C
1000_GenomesPRXL2C 
Exome Variant ServerPRXL2C
ExAC (Exome Aggregation Consortium)ENSG00000158122
GNOMAD BrowserENSG00000158122
Varsome BrowserPRXL2C
Genetic variants : HAPMAP195827
Genomic Variants (DGV)PRXL2C [DGVbeta]
DECIPHERPRXL2C [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPRXL2C 
Mutations
ICGC Data PortalPRXL2C 
TCGA Data PortalPRXL2C 
Broad Tumor PortalPRXL2C
OASIS PortalPRXL2C [ Somatic mutations - Copy number]
Mutations and Diseases : HGMDPRXL2C
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 PRXL2C
DgiDB (Drug Gene Interaction Database)PRXL2C
DoCM (Curated mutations)PRXL2C (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PRXL2C (select a term)
intoGenPRXL2C
Cancer3DPRXL2C(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM
Orphanet
DisGeNETPRXL2C
MedgenPRXL2C
Genetic Testing Registry PRXL2C
NextProtQ7RTV5 [Medical]
GENETestsPRXL2C
Target ValidationPRXL2C
Huge Navigator PRXL2C [HugePedia]
snp3D : Map Gene to Disease
BioCentury BCIQPRXL2C
ClinGenPRXL2C
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD195827
Chemical/Pharm GKB GenePA38190
Clinical trialPRXL2C
Miscellaneous
canSAR (ICR)PRXL2C (select the gene name)
DataMed IndexPRXL2C
Probes
Litterature
PubMed10 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePRXL2C
EVEXPRXL2C
GoPubMedPRXL2C
iHOPPRXL2C
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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