MAGL2_MOUSE
ID MAGL2_MOUSE Reviewed; 1284 AA.
AC Q9QZ04; F8WIA8;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 16-SEP-2015, sequence version 2.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=MAGE-like protein 2;
DE AltName: Full=Protein nS7;
GN Name=Magel2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 706-1284.
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 780-1284.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP 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 [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=17728320; DOI=10.1093/hmg/ddm225;
RA Bischof J.M., Stewart C.L., Wevrick R.;
RT "Inactivation of the mouse Magel2 gene results in growth abnormalities
RT similar to Prader-Willi syndrome.";
RL Hum. Mol. Genet. 16:2713-2719(2007).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ARNTL AND PER2.
RX PubMed=22208286; DOI=10.1186/1740-3391-9-12;
RA Devos J., Weselake S.V., Wevrick R.;
RT "Magel2, a Prader-Willi syndrome candidate gene, modulates the activities
RT of circadian rhythm proteins in cultured cells.";
RL J. Circadian. Rhythms. 9:12-12(2011).
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 (By similarity). 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 (PubMed:22208286). {ECO:0000250|UniProtKB:Q9UJ55,
CC ECO:0000269|PubMed:22208286}.
CC -!- SUBUNIT: Interacts with TRIM27. Interacts with VPS35; leading to
CC recruitment at retromer-containing endosomes (By similarity). Interacts
CC with ARNTL/BMAL1 and PER2. {ECO:0000250|UniProtKB:Q9UJ55,
CC ECO:0000269|PubMed:22208286}.
CC -!- SUBCELLULAR LOCATION: Early endosome. Cytoplasm
CC {ECO:0000269|PubMed:22208286}. Nucleus {ECO:0000269|PubMed:22208286}.
CC Note=Recruited to retromer-containing endosomes via interaction with
CC VPS35. Colocalizes with CLOCK and ARNTL/BMLA1 in the cytoplasm, and
CC with PER2 in the cytoplasm and nucleus. {ECO:0000250|UniProtKB:Q9UJ55,
CC ECO:0000269|PubMed:22208286}.
CC -!- TISSUE SPECIFICITY: Expressed predominantly in late development stages
CC and adult brain. {ECO:0000269|PubMed:10915770}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice show reduced embryonic viability,
CC neonatal growth retardation, excessive weight gain after weaning, and
CC increased adiposity with altered metabolism, including increased
CC fasting insulin and elevated cholesterol, in adulthood. Mutant mice
CC also show abnormalities in the circadian pattern of feeding behavior.
CC Deficient mice show features similar to those of Prader-Willi syndrome
CC in humans. {ECO:0000269|PubMed:17728320}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH54763.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAB62395.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AC156555; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AJ243608; CAB62395.1; ALT_INIT; mRNA.
DR EMBL; BC054763; AAH54763.1; ALT_INIT; mRNA.
DR CCDS; CCDS52264.1; -.
DR RefSeq; NP_038807.4; NM_013779.2.
DR AlphaFoldDB; Q9QZ04; -.
DR SMR; Q9QZ04; -.
DR STRING; 10090.ENSMUSP00000079265; -.
DR PhosphoSitePlus; Q9QZ04; -.
DR MaxQB; Q9QZ04; -.
DR PaxDb; Q9QZ04; -.
DR PRIDE; Q9QZ04; -.
DR ProteomicsDB; 252720; -.
DR Antibodypedia; 58530; 102 antibodies from 13 providers.
DR Ensembl; ENSMUST00000080403; ENSMUSP00000079265; ENSMUSG00000056972.
DR GeneID; 27385; -.
DR KEGG; mmu:27385; -.
DR UCSC; uc009hfh.2; mouse.
DR CTD; 54551; -.
DR MGI; MGI:1351648; Magel2.
DR VEuPathDB; HostDB:ENSMUSG00000056972; -.
DR eggNOG; KOG4562; Eukaryota.
DR GeneTree; ENSGT00940000163006; -.
DR InParanoid; Q9QZ04; -.
DR OMA; TQVTWQA; -.
DR OrthoDB; 1195799at2759; -.
DR TreeFam; TF328505; -.
DR BioGRID-ORCS; 27385; 5 hits in 71 CRISPR screens.
DR PRO; PR:Q9QZ04; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9QZ04; protein.
DR Bgee; ENSMUSG00000056972; Expressed in arcuate nucleus of hypothalamus and 118 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0030904; C:retromer complex; ISO:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0034314; P:Arp2/3 complex-mediated actin nucleation; ISS: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; IDA:UniProtKB.
DR GO; GO:0051127; P:positive regulation of actin nucleation; IGI:MGI.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; ISS: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 Biological rhythms; Cytoplasm; Endosome; Nucleus; Reference proteome;
KW Repressor; Transcription; Transcription regulation;
KW Ubl conjugation pathway.
FT CHAIN 1..1284
FT /note="MAGE-like protein 2"
FT /id="PRO_0000156739"
FT DOMAIN 1052..1251
FT /note="MAGE"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00127"
FT REGION 1..51
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 114..208
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 406..431
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 673..717
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 747..792
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 839..860
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 913..964
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 985..1051
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1261..1284
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 35..49
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 136..207
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 674..717
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 774..792
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 839..854
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 933..952
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 987..1043
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1284 AA; 137987 MW; 26C56CC0AEC03D68 CRC64;
MSQLSTNLGD SSPPESPVPA VHSRPTVLMR APPASSRAPP VPWDPPPVDL QAPMAAWQAP
QPAWEAPEGQ LPAPVAQLAQ PPGLGAPMVQ APPLGGGMAK PPTPGVLMVH QPPPGAPMAQ
SSTPGVLMLH PSVTGAPLAH PPPPGTPMTH PPGTSMAHPP PPPPPPPPPP PPGTPMTHPP
PPGTPMGHHP PPGNPMTHPP PGNPMVHPLT HGAPMVHGGP HGTPMPHVPI TGTPIAQQPT
PGVLMAQQLT PGVLMVQPPA PGAPMVQPPP QAALMTQPAP SITPMAKPPG PGVVMIHPPG
ARGPIIQTPV SGAPMAQTVL PPGQPLATWA PQGQPLILQI QSQVIRAPPQ VPSVPQAPQV
QLATPPGWQA TTPNWQVTPQ GWPATPLTWQ ATQVTWQAPT IAWQATQPGR QGHSTIRTGH
TPIRPGPAPL LRQIPPMIRQ IQPVMRQAPP LIRQVPIRPA PHGIASQPQL WQVLPPPPPL
RQAPQARLLL PRVPGTGQVS TVPPVAQIHL VPQSGPQVPQ TVLPAQLSIP IPVPQAAAQS
APRTVHCPPI IWQAPKGQAP VPQELPVPQE LPVPQELPVP QEVPVPQEIP VPQEIPVPQE
LPVPQELPVP QELPVPQELP VPQELPVPQE LPVPQELPVP QELPVPLEFQ EVQQAQAVGW
RAPKVPPHFW QPVSAQEAQE QATQIAHVEQ QQPFQGAPAS SKALQTQLPT HQAQASGLQA
ELPSVQLQPS WQGPLPMLQA QPGASATLAN FPRGSTRSRM APSGEPGPSS LEPRGPPRER
RAPARDKKGP PKERMFIGAT FCAPRGASAS RAYVPTAWKN LPATSETFPA TSRVFPSTSH
FQPASSNAFR GPSAASESPK SLPFALQDPY ACVEALPAVP WVPYPDGNAS SACKSVPAIL
MVAAAAPQAS ATAAEASKSS EPPRRPGKAT RKKKHLEPKE DNCGHRLSSR DWRGPRTWGN
PSHSDWEIQR AMQLLGDRES LYTPQGLNDW GCPNTSRMPR SLEGPSTSRD QEFCGDSGGS
QTWMASEVPS VSRGSSAAQE DPDRESQPLS PLDERANALV QFLLVKDQAK VPVQLSEMVN
VVIREYKDDS LDIINRANTK LECTFGCQLK EVDTKTHTYI IVNKMAYPQC NLLASYLERP
KFSLLMVVLS LIFMKGYCIR ENLLFSFLFQ LGLDVQETSG LFRITKKLIT SVFVRHRYLE
YRQIPFTEPA EYELLWGPRA FLETNRVHIL RFLAALYENQ PQIWSCQYLD SLAELEYKDA
NAAAEESHDS DDDAHDPTSS PHPH
