MAGL2_HUMAN
ID MAGL2_HUMAN Reviewed; 1249 AA.
AC Q9UJ55; H0YDD5;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 16-SEP-2015, sequence version 2.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=MAGE-like protein 2;
DE AltName: Full=Necdin-like protein 1;
DE AltName: Full=Protein nM15;
GN Name=MAGEL2; Synonyms=NDNL1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 635-1249, AND TISSUE SPECIFICITY.
RX PubMed=10915770; DOI=10.1093/hmg/9.12.1813;
RA Lee S., Kozlov S., Hernandez L., Chamberlain S.J., Brannan C.I.,
RA Stewart C.L., Wevrick R.;
RT "Expression and imprinting of MAGEL2 suggest a role in Prader-Willi
RT syndrome and the homologous murine imprinting phenotype.";
RL Hum. Mol. Genet. 9:1813-1819(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 638-1249.
RC TISSUE=Brain, and Placenta;
RX PubMed=10556298; DOI=10.1093/hmg/8.13.2497;
RA Boccaccio I., Glatt-Deeley H., Watrin F., Roeckel N., Lalande M.,
RA Muscatelli F.;
RT "The human MAGEL2 gene and its mouse homologue are paternally expressed and
RT mapped to the Prader-Willi region.";
RL Hum. Mol. Genet. 8:2497-2505(1999).
RN [4]
RP FUNCTION, AND INTERACTION WITH TRIM27.
RX PubMed=20864041; DOI=10.1016/j.molcel.2010.08.029;
RA Doyle J.M., Gao J., Wang J., Yang M., Potts P.R.;
RT "MAGE-RING protein complexes comprise a family of E3 ubiquitin ligases.";
RL Mol. Cell 39:963-974(2010).
RN [5]
RP FUNCTION, INTERACTION WITH TRIM27 AND VPS35, AND SUBCELLULAR LOCATION.
RX PubMed=23452853; DOI=10.1016/j.cell.2013.01.051;
RA Hao Y.H., Doyle J.M., Ramanathan S., Gomez T.S., Jia D., Xu M., Chen Z.J.,
RA Billadeau D.D., Rosen M.K., Potts P.R.;
RT "Regulation of WASH-dependent actin polymerization and protein trafficking
RT by ubiquitination.";
RL Cell 152:1051-1064(2013).
RN [6]
RP INVOLVEMENT IN SHFYNG.
RX PubMed=24076603; DOI=10.1038/ng.2776;
RA Schaaf C.P., Gonzalez-Garay M.L., Xia F., Potocki L., Gripp K.W., Zhang B.,
RA Peters B.A., McElwain M.A., Drmanac R., Beaudet A.L., Caskey C.T., Yang Y.;
RT "Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism.";
RL Nat. Genet. 45:1405-1408(2013).
CC -!- FUNCTION: Probably enhances ubiquitin ligase activity of RING-type zinc
CC finger-containing E3 ubiquitin-protein ligases, possibly through
CC recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at
CC the E3:substrate complex. Acts as a regulator of retrograde transport
CC via its interaction with VPS35. Recruited to retromer-containing
CC endosomes and promotes the formation of 'Lys-63'-linked polyubiquitin
CC chains at 'Lys-220' of WASHC1 together with TRIM27, leading to promote
CC endosomal F-actin assembly (PubMed:23452853). Regulates the circadian
CC clock by repressing the transcriptional activator activity of the
CC CLOCK-ARNTL/BMAL1 heterodimer. Significantly promotes the cytoplasmic
CC accumulation of CLOCK (By similarity). {ECO:0000250|UniProtKB:Q9QZ04,
CC ECO:0000269|PubMed:20864041, ECO:0000269|PubMed:23452853}.
CC -!- SUBUNIT: Interacts with TRIM27. Interacts with VPS35; leading to
CC recruitment at retromer-containing endosomes. Interacts with
CC ARNTL/BMAL1 and PER2 (By similarity). {ECO:0000250|UniProtKB:Q9QZ04,
CC ECO:0000269|PubMed:20864041, ECO:0000269|PubMed:23452853}.
CC -!- INTERACTION:
CC Q9UJ55; P63010: AP2B1; NbExp=2; IntAct=EBI-5668174, EBI-432924;
CC Q9UJ55; Q14192: FHL2; NbExp=3; IntAct=EBI-5668174, EBI-701903;
CC Q9UJ55; Q9UMX1: SUFU; NbExp=3; IntAct=EBI-5668174, EBI-740595;
CC Q9UJ55; Q93009: USP7; NbExp=2; IntAct=EBI-5668174, EBI-302474;
CC -!- SUBCELLULAR LOCATION: Early endosome {ECO:0000269|PubMed:23452853}.
CC Cytoplasm {ECO:0000250|UniProtKB:Q9QZ04}. Nucleus
CC {ECO:0000250|UniProtKB:Q9QZ04}. Note=Recruited to retromer-containing
CC endosomes via interaction with VPS35. Colocalizes with CLOCK and
CC ARNTL/BMLA1 in the cytoplasm, and with PER2 in the cytoplasm and
CC nucleus (By similarity). {ECO:0000250|UniProtKB:Q9QZ04,
CC ECO:0000269|PubMed:23452853}.
CC -!- TISSUE SPECIFICITY: Expressed in placenta, fetal and adult brain. Not
CC detected in heart and small intestine, very low levels in fibroblasts.
CC Not expressed in brain of a Prader-Willi patient.
CC {ECO:0000269|PubMed:10915770}.
CC -!- DISEASE: Schaaf-Yang syndrome (SHFYNG) [MIM:615547]: A disease
CC characterized by clinical features of Prader-Willi syndrome, including
CC neonatal hypotonia with poor suck, feeding problems in infancy,
CC obesity, developmental delay, short stature, and hypogonadism.
CC Additionally, patients manifest autism spectrum disorder. Some patients
CC have dysmorphic facial features. {ECO:0000269|PubMed:24076603}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry. All mutations occurred on the paternal allele.
CC -!- MISCELLANEOUS: Imprinted, expressed from the paternal chromosome only.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG28577.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAB62393.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AC124309; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF200625; AAG28577.1; ALT_FRAME; Genomic_DNA.
DR EMBL; AJ243531; CAB62393.1; ALT_FRAME; mRNA.
DR CCDS; CCDS73700.1; -.
DR RefSeq; NP_061939.3; NM_019066.4.
DR AlphaFoldDB; Q9UJ55; -.
DR CORUM; Q9UJ55; -.
DR IntAct; Q9UJ55; 5.
DR STRING; 9606.ENSP00000433433; -.
DR iPTMnet; Q9UJ55; -.
DR PhosphoSitePlus; Q9UJ55; -.
DR BioMuta; MAGEL2; -.
DR DMDM; 17380152; -.
DR EPD; Q9UJ55; -.
DR MassIVE; Q9UJ55; -.
DR MaxQB; Q9UJ55; -.
DR PaxDb; Q9UJ55; -.
DR PeptideAtlas; Q9UJ55; -.
DR PRIDE; Q9UJ55; -.
DR Antibodypedia; 58530; 102 antibodies from 13 providers.
DR DNASU; 54551; -.
DR Ensembl; ENST00000650528.1; ENSP00000497810.1; ENSG00000254585.5.
DR Ensembl; ENST00000672700.1; ENSP00000499864.1; ENSG00000288188.1.
DR Ensembl; ENST00000673192.1; ENSP00000500572.1; ENSG00000288188.1.
DR GeneID; 54551; -.
DR KEGG; hsa:54551; -.
DR MANE-Select; ENST00000650528.1; ENSP00000497810.1; NM_019066.5; NP_061939.3.
DR UCSC; uc001ywj.5; human.
DR CTD; 54551; -.
DR DisGeNET; 54551; -.
DR GeneCards; MAGEL2; -.
DR GeneReviews; MAGEL2; -.
DR HGNC; HGNC:6814; MAGEL2.
DR HPA; ENSG00000254585; Group enriched (brain, pituitary gland).
DR MalaCards; MAGEL2; -.
DR MIM; 605283; gene.
DR MIM; 615547; phenotype.
DR neXtProt; NX_Q9UJ55; -.
DR OpenTargets; ENSG00000254585; -.
DR Orphanet; 398069; MAGEL2-related Prader-Willi-like syndrome.
DR Orphanet; 177910; Prader-Willi syndrome due to imprinting mutation.
DR Orphanet; 98754; Prader-Willi syndrome due to maternal uniparental disomy of chromosome 15.
DR Orphanet; 177901; Prader-Willi syndrome due to paternal deletion of 15q11q13 type 1.
DR Orphanet; 177904; Prader-Willi syndrome due to paternal deletion of 15q11q13 type 2.
DR VEuPathDB; HostDB:ENSG00000254585; -.
DR eggNOG; KOG4562; Eukaryota.
DR GeneTree; ENSGT00940000163006; -.
DR InParanoid; Q9UJ55; -.
DR OMA; TQVTWQA; -.
DR OrthoDB; 1195799at2759; -.
DR TreeFam; TF328505; -.
DR PathwayCommons; Q9UJ55; -.
DR SignaLink; Q9UJ55; -.
DR SIGNOR; Q9UJ55; -.
DR BioGRID-ORCS; 54551; 11 hits in 310 CRISPR screens.
DR GenomeRNAi; 54551; -.
DR Pharos; Q9UJ55; Tbio.
DR PRO; PR:Q9UJ55; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q9UJ55; protein.
DR Bgee; ENSG00000254585; Expressed in adrenal tissue and 96 other tissues.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IMP:UniProtKB.
DR GO; GO:0034314; P:Arp2/3 complex-mediated actin nucleation; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0051127; P:positive regulation of actin nucleation; IEA:Ensembl.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; IMP:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; IDA:UniProtKB.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR Gene3D; 1.10.10.1200; -; 1.
DR Gene3D; 1.10.10.1210; -; 1.
DR InterPro; IPR037445; MAGE.
DR InterPro; IPR041898; MAGE_WH1.
DR InterPro; IPR041899; MAGE_WH2.
DR InterPro; IPR002190; MHD_dom.
DR PANTHER; PTHR11736; PTHR11736; 1.
DR Pfam; PF01454; MAGE; 1.
DR SMART; SM01373; MAGE; 1.
DR PROSITE; PS50838; MAGE; 1.
PE 1: Evidence at protein level;
KW Autism spectrum disorder; Biological rhythms; Cytoplasm; Endosome;
KW Intellectual disability; Nucleus; Obesity; Reference proteome; Repressor;
KW Transcription; Transcription regulation; Transport;
KW Ubl conjugation pathway.
FT CHAIN 1..1249
FT /note="MAGE-like protein 2"
FT /id="PRO_0000156738"
FT DOMAIN 1020..1219
FT /note="MAGE"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00127"
FT REGION 1..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 134..233
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 300..327
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 349..378
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 410..433
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 515..569
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 647..679
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 714..746
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 862..910
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 930..957
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1226..1249
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 136..232
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 307..325
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 539..569
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 649..679
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 726..746
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 862..876
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 889..903
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1249 AA; 132822 MW; 17AA2FB3F8477D82 CRC64;
MSQLSKNLGD SSPPAEAPKP PVYSRPTVLM RAPPASSRAP PVPWDPPPID LQASLAAWQA
PQPAWEAPQG QLPAPVVPMT QPPALGGPIV PAPPLGGPMG KPPTPGVLMV HPPPPGAPMA
QPPTPGVLMV HPSAPGAPMA HPPPPGTPMS HPPPPGTPMA HPPPPGTPMA HPPPPGTPMV
HPPPPGTPMA HPPPPGTPMA HPPPPGTPMA HPPPPGTPMA HPPPPGTPMA QPPAPGVLMA
QPLTPGVLMV QPAAPGAPMV QPPPAAMMTQ PQPSGAPMAK PPGPGVLMIH PPGARAPMTQ
PPASGAPMAQ PAAPPAQPMA PPAQPMASWA PQAQPLILQI QSQVIRAPPQ VPQGPQAPPA
QLATPPGWQA TSPGWQATQQ GWQATPLTWQ TTQVTWQAPA VTWQVPPPMR QGPPPIRPGP
PPIRPGPPPV RQAPPLIRQA PPVIRQAPPV IRQAPPVIRQ APAVIRQAPP VIRQAPPVIR
QAPPVIRQAP PLIRQAPPPI RPAPQVLATQ PPLWQALPPP PPLRQAPQAR LPAPQVQAAP
QVPTAPPATQ VPAAPPAGPQ VPQPVLPAPL SAPLSAPQAV HCPSIIWQAP KGQPPVPHEI
PTSMEFQEVQ QTQALAWQAQ KAPTHIWQPL PAQEAQRQAP PLVQLEQPFQ GAPPSQKAVQ
IQLPPQQAQA SGPQAEVPTL PLQPSWQAPP AVLQAQPGPP VAAANFPLGS AKSLMTPSGE
CRASSIDRRG SSKERRTSSK ERRAPSKDRM IFAATFCAPK AVSAARAHLP AAWKNLPATP
ETFAPSSSVF PATSQFQPAS LNAFKGPSAA SETPKSLPYA LQDPFACVEA LPAVPWVPQP
NMNASKASQA VPTFLMATAA APQATATTQE ASKTSVEPPR RSGKATRKKK HLEAQEDSRG
HTLAFHDWQG PRPWENLNLS DWEVQSPIQV SGDWEHPNTP RGLSGWEGPS TSRILSGWEG
PSASWALSAW EGPSTSRALG LSESPGSSLP VVVSEVASVS PGSSATQDNS KVEAQPLSPL
DERANALVQF LLVKDQAKVP VQRSEMVKVI LREYKDECLD IINRANNKLE CAFGYQLKEI
DTKNHAYIII NKLGYHTGNL VASYLDRPKF GLLMVVLSLI FMKGNCVRED LIFNFLFKLG
LDVRETNGLF GNTKKLITEV FVRQKYLEYR RIPYTEPAEY EFLWGPRAFL ETSKMLVLRF
LAKLHKKDPQ SWPFHYLEAL AECEWEDTDE DEPDTGDSAH GPTSRPPPR
