MAGEL2

MAGE family member L2 (MAGEL2) is a protein that in human is encoded by the MAGEL2 gene. This protein is a ubuquitin ligase enhancer which is necessary for endsomal protein recycling.^[5] This protein is a part of MUST complex (which consists of MAGEL2-USP7-TRIM27 complex).^[6][7]

MAGEL2
Identifiers
Aliases	MAGEL2, NDNL1, PWLS, nM15, SHFYNG, MAGE family member L2
External IDs	OMIM: 605283; MGI: 1351648; HomoloGene: 8460; GeneCards: MAGEL2; OMA:MAGEL2 - orthologs
Gene location (Human) Chr. Chromosome 15 (human)[1] Band 15q11.2 Start 23,643,549 bp[1] End 23,647,867 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7 C|7 34.37 cM Start 62,026,758 bp[2] End 62,031,388 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gonad testicle Hypothalamus Brodmann area 23 middle temporal gyrus tibia pituitary gland anterior pituitary islet of Langerhans nucleus accumbens Top expressed in arcuate nucleus median eminence ventromedial nucleus suprachiasmatic nucleus dorsomedial hypothalamic nucleus paraventricular nucleus of hypothalamus supraoptic nucleus nucleus of stria terminalis labioscrotal swelling tongue More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding ubiquitin-protein transferase activity Cellular component cytoplasm retromer complex endosome early endosome nucleus cytosol Biological process protein K63-linked ubiquitination retrograde transport, endosome to Golgi negative regulation of transcription, DNA-templated regulation of transcription, DNA-templated regulation of circadian rhythm transcription, DNA-templated positive regulation of actin nucleation rhythmic process Arp2/3 complex-mediated actin nucleation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 54551 27385 Ensembl ENSG00000254585 ENSMUSG00000056972 UniProt Q9UJ55 Q9QZ04 RefSeq (mRNA) NM_019066 NM_013779 RefSeq (protein) NP_061939 NP_038807 Location (UCSC) Chr 15: 23.64 – 23.65 Mb Chr 7: 62.03 – 62.03 Mb PubMed search [3] [4]
Wikidata
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Gene

The MAGEL2 gene is located on the long(q) arm of chromosome 15 on position 11.2, from base pair 23,643,549 to base pair 23,647,867.^[8] This gene is expressed from the paternal chromosome 15.^[9]

Function

This protein is known to regulate AMPA receptors in hypothalamus.^[10] Also it can regualte secretion of hormones such as: oxytocin, arginine vasopressin, somatostatin, TSH, somatotropin, LH.^[11] Loss of that protein showed decreased neuoronal activity in hypothalamus and hippocampus of mice via AMPA receptor trafficking defects, consequently neuronal activity gets disrupted and synaptic excitation/inhibition balance is lost.^[12][13]

MAGEL2 is required for balance of serotonin, dopamine and noradrenaline concentrations, in Magel2-null mice concetrations of that neurotransmitters had been decreased.^[14][15]

As mentioned above MAGEL2 participates in MUST complex, which promotes endosomal F-actin polymerization.^[16]

Clinical significance

Prader-Willi syndrome

Prader-Willi syndrome (PWS) is a rare genetic disorder that is caused by maternal UPD(15) or deletions/epimutations on paternal chromosome 15.^[17] PWS can cause variety of symptoms from hypotoniain infancy to behavioural problems in early childhood. Some symptoms can be found in infants aside from hypotonia, are a poor eye coordination, almond-shaped eyes, thin upper lip, also, due to hypotonia, problems with sucking reflex. Their cries are weak and they have difficulty of waking up.^[18]

Deletion of MAGEL2 (and other genes that are located on the same region) contributes to symptoms in PWS.^[19]

Schaaf-Yang syndrome

Schaaf-Yang syndrome (SYS) is a rare genetic disorder that is caused by a mutation in a paternally expressed gene MAGEL2.^[20] The signs of this disease are: hypotonia, developmental delay and contractures of joints, also another signs of that disease are unique facial features, small hands, problems with eye and short stature.^[21]

As mentioned above, SYS is caused by LoF variants of the paternal copy of MAGEL2.^[22]