ID MAGD1_HUMAN Reviewed; 778 AA. AC Q9Y5V3; Q5VSH6; Q8IZ84; Q8WY92; Q9H352; Q9HBT4; Q9UF36; DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 26-APR-2005, sequence version 3. DT 07-JAN-2015, entry version 140. DE RecName: Full=Melanoma-associated antigen D1; DE AltName: Full=MAGE tumor antigen CCF; DE AltName: Full=MAGE-D1 antigen; DE AltName: Full=Neurotrophin receptor-interacting MAGE homolog; GN Name=MAGED1; Synonyms=NRAGE; ORFNames=PP2250, PRO2292; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=10985348; DOI=10.1016/S0896-6273(00)00036-2; RA Salehi A.H., Roux P.P., Kubu C.J., Zeindler C., Bhakar A., RA Tannis L.-L., Verdi J.M., Barker P.A.; RT "NRAGE, a novel MAGE protein, interacts with the p75 neurotrophin RT receptor and facilitates nerve growth factor dependent apoptosis."; RL Neuron 27:279-288(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=15094062; DOI=10.1016/S0014-5793(04)00353-9; RA Wen C.-J., Xue B., Qin W.-X., Yu M., Zhang M.-Y., Zhao D.-H., Gao X., RA Gu J.-R., Li C.-J.; RT "hNRAGE, a human neurotrophin receptor interacting MAGE homologue, RT regulates p53 transcriptional activity and inhibits cell RT proliferation."; RL FEBS Lett. 564:171-176(2004). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Chen Y.; RT "Identification and characterization of a new member of the MAGE gene RT family."; RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S., RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., RA Williams G., Williams L., Williamson A., Williamson H., Wilming L., RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Blood, and Skin; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 202-778 (ISOFORM 1). RC TISSUE=Bone marrow; RX PubMed=10409427; DOI=10.1006/geno.1999.5870; RA Pold M., Zhou J., Chen G.L., Hall J.M., Vescio R.A., Berenson J.R.; RT "Identification of a new, unorthodox member of the MAGE gene family."; RL Genomics 59:161-167(1999). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 304-778. RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 396-778. RC TISSUE=Fetal liver; RX PubMed=11280991; RA Zhang C.G., Xing G.C., Wei H.D., Yu Y.T., He F.C.; RT "A new melanoma antigen-encoding gene subfamily in human chromosome RT X."; RL Yi Chuan Xue Bao 28:197-203(2001). RN [9] RP IDENTIFICATION OF THE TRANSLATIONAL INITIATION CODON. RX PubMed=11087672; DOI=10.1006/geno.2000.6356; RA Kubu C.J., Goldhawk D.G., Barker P.A., Verdi J.M.; RT "Identification of the translational initiation codon in human RT MAGED1."; RL Genomics 70:150-152(2000). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-92, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer RT cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [11] RP FUNCTION, AND INTERACTION WITH TRIM28 AND PJA1. 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 RT ligases."; RL Mol. Cell 39:963-974(2010). CC -!- FUNCTION: Involved in the apoptotic response after nerve growth CC factor (NGF) binding in neuronal cells. Inhibits cell cycle CC progression, and facilitates NGFR-mediated apoptosis. May act as a CC regulator of the function of DLX family members. May enhance CC ubiquitin ligase activity of RING-type zinc finger-containing E3 CC ubiquitin-protein ligases. Proposed to act through recruitment CC and/or stabilization of the Ubl-conjugating enzyme (E2) at the CC E3:substrate complex. Plays a role in the circadian rythm CC regulation. May act as RORA co-regulator, modulating the CC expression of core clock genes such as ARNTL/BMAL1 and NFIL3, CC induced, or NR1D1, repressed. {ECO:0000269|PubMed:20864041}. CC -!- SUBUNIT: Interacts with DLX5, DLX7 and MSX2 and forms CC homomultimers. Interacts with UNC5A. Interacts with TRIM28 and CC PJA1. Interacts with NGFR/p75NTR and RORA. CC {ECO:0000269|PubMed:20864041}. CC -!- INTERACTION: CC Q8NG27:PJA1; NbExp=4; IntAct=EBI-716006, EBI-714606; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Nucleus CC {ECO:0000250}. Note=Expression shifts from the cytoplasm to the CC plasma membrane upon stimulation with NGF. {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9Y5V3-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9Y5V3-2; Sequence=VSP_009286; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Expressed in bone marrow stromal cells from CC both multiple myeloma patients and healthy donors. Seems to be CC ubiquitously expressed. CC -!- SIMILARITY: Contains 1 MAGE domain. {ECO:0000255|PROSITE- CC ProRule:PRU00127}. CC -!- SEQUENCE CAUTION: CC Sequence=AAD31421.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=AAG35551.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF217963; AAG09704.1; -; mRNA. DR EMBL; AF258554; AAG23757.1; -; mRNA. DR EMBL; AF300328; AAQ14483.1; -; mRNA. DR EMBL; AL929410; CAH71560.1; -; Genomic_DNA. DR EMBL; AL929410; CAH71561.1; -; Genomic_DNA. DR EMBL; BC014070; AAH14070.1; -; mRNA. DR EMBL; BC032473; AAH32473.1; -; mRNA. DR EMBL; AF124440; AAD31421.1; ALT_INIT; mRNA. DR EMBL; AL133628; CAB63752.1; -; mRNA. DR EMBL; AF132205; AAG35551.1; ALT_INIT; mRNA. DR CCDS; CCDS14337.1; -. [Q9Y5V3-1] DR CCDS; CCDS35279.1; -. [Q9Y5V3-2] DR PIR; T43464; T43464. DR RefSeq; NP_001005332.1; NM_001005332.1. [Q9Y5V3-1] DR RefSeq; NP_001005333.1; NM_001005333.1. [Q9Y5V3-2] DR RefSeq; NP_008917.3; NM_006986.3. [Q9Y5V3-1] DR UniGene; Hs.5258; -. DR ProteinModelPortal; Q9Y5V3; -. DR SMR; Q9Y5V3; 465-672. DR BioGrid; 114879; 72. DR IntAct; Q9Y5V3; 27. DR MINT; MINT-209401; -. DR STRING; 9606.ENSP00000364847; -. DR PhosphoSite; Q9Y5V3; -. DR DMDM; 62906893; -. DR MaxQB; Q9Y5V3; -. DR PaxDb; Q9Y5V3; -. DR PRIDE; Q9Y5V3; -. DR Ensembl; ENST00000326587; ENSP00000325333; ENSG00000179222. [Q9Y5V3-1] DR Ensembl; ENST00000375695; ENSP00000364847; ENSG00000179222. [Q9Y5V3-2] DR Ensembl; ENST00000375722; ENSP00000364874; ENSG00000179222. [Q9Y5V3-1] DR Ensembl; ENST00000375772; ENSP00000364927; ENSG00000179222. [Q9Y5V3-1] DR GeneID; 9500; -. DR KEGG; hsa:9500; -. DR UCSC; uc004dpm.3; human. [Q9Y5V3-1] DR UCSC; uc004dpn.3; human. [Q9Y5V3-2] DR CTD; 9500; -. DR GeneCards; GC0XP051562; -. DR HGNC; HGNC:6813; MAGED1. DR HPA; CAB015165; -. DR HPA; HPA043645; -. DR MIM; 300224; gene. DR neXtProt; NX_Q9Y5V3; -. DR PharmGKB; PA30559; -. DR eggNOG; NOG310785; -. DR GeneTree; ENSGT00760000118824; -. DR HOVERGEN; HBG003714; -. DR InParanoid; Q9Y5V3; -. DR KO; K12464; -. DR OMA; WQNPVIW; -. DR OrthoDB; EOG75F4GM; -. DR PhylomeDB; Q9Y5V3; -. DR TreeFam; TF352132; -. DR Reactome; REACT_13638; NRAGE signals death through JNK. DR Reactome; REACT_22128; Role of DCC in regulating apoptosis. DR SignaLink; Q9Y5V3; -. DR ChiTaRS; MAGED1; human. DR GeneWiki; MAGED1; -. DR GenomeRNAi; 9500; -. DR NextBio; 35594; -. DR PRO; PR:Q9Y5V3; -. DR Proteomes; UP000005640; Chromosome X. DR Bgee; Q9Y5V3; -. DR CleanEx; HS_MAGED1; -. DR Genevestigator; Q9Y5V3; -. DR GO; GO:0000785; C:chromatin; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0043234; C:protein complex; IDA:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; IEA:Ensembl. DR GO; GO:0006915; P:apoptotic process; TAS:Reactome. DR GO; GO:0097190; P:apoptotic signaling pathway; TAS:Reactome. DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB. DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IDA:UniProtKB. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IEA:Ensembl. DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome. DR GO; GO:0043065; P:positive regulation of apoptotic process; TAS:Reactome. DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; IEA:Ensembl. DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:Ensembl. DR GO; GO:0042981; P:regulation of apoptotic process; TAS:UniProtKB. DR GO; GO:0042752; P:regulation of circadian rhythm; IEA:Ensembl. DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; IEA:Ensembl. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:UniProtKB. DR InterPro; IPR030083; MAGED1. DR InterPro; IPR002190; MHD_dom. DR PANTHER; PTHR11736; PTHR11736; 1. DR PANTHER; PTHR11736:SF28; PTHR11736:SF28; 1. DR Pfam; PF01454; MAGE; 1. DR PROSITE; PS50838; MAGE; 1. PE 1: Evidence at protein level; KW Alternative splicing; Biological rhythms; Cell membrane; KW Complete proteome; Cytoplasm; Membrane; Nucleus; Phosphoprotein; KW Polymorphism; Reference proteome; Repeat; Tumor antigen; KW Ubl conjugation pathway. FT CHAIN 1 778 Melanoma-associated antigen D1. FT /FTId=PRO_0000156723. FT REPEAT 296 301 1. FT REPEAT 302 307 2. FT REPEAT 308 313 3. FT REPEAT 332 337 4. FT REPEAT 338 343 5. FT REPEAT 344 349 6. FT REPEAT 350 355 7. FT REPEAT 356 361 8. FT REPEAT 362 367 9. FT REPEAT 368 373 10. FT REPEAT 374 379 11. FT REPEAT 380 385 12. FT REPEAT 386 391 13. FT REPEAT 392 397 14. FT REPEAT 398 403 15. FT REPEAT 404 409 16. FT REPEAT 410 415 17. FT REPEAT 416 421 18. FT REPEAT 422 427 19. FT REPEAT 428 432 20; approximate. FT REPEAT 433 438 21. FT REPEAT 439 444 22. FT DOMAIN 471 669 MAGE. {ECO:0000255|PROSITE- FT ProRule:PRU00127}. FT REGION 296 444 22 X 6 AA tandem repeats of W-[PQ]-X-P-X- FT X. FT COMPBIAS 279 452 Pro-rich. FT MOD_RES 92 92 Phosphotyrosine. FT {ECO:0000269|PubMed:15592455}. FT VAR_SEQ 15 15 Q -> QNPDACRAVCHPLPQPPASTLPLSAFPTLCDPPYSQ FT LRDPPAVLSCYCTPLGASPAP (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_009286. FT VARIANT 238 238 L -> M (in dbSNP:rs12689461). FT /FTId=VAR_060070. FT CONFLICT 119 119 P -> S (in Ref. 1; AAG09704). FT {ECO:0000305}. SQ SEQUENCE 778 AA; 86161 MW; D818690052D166CE CRC64; MAQKMDCGAG LLGFQAEASV EDSALLMQTL MEAIQISEAP PTNQATAAAS PQSSQPPTAN EMADIQVSAA AARPKSAFKV QNATTKGPNG VYDFSQAHNA KDVPNTQPKA AFKSQNATPK GPNAAYDFSQ AATTGELAAN KSEMAFKAQN ATTKVGPNAT YNFSQSLNAN DLANSRPKTP FKAWNDTTKA PTADTQTQNV NQAKMATSQA DIETDPGISE PDGATAQTSA DGSQAQNLES RTIIRGKRTR KINNLNVEEN SSGDQRRAPL AAGTWRSAPV PVTTQNPPGA PPNVLWQTPL AWQNPSGWQN QTARQTPPAR QSPPARQTPP AWQNPVAWQN PVIWPNPVIW QNPVIWPNPI VWPGPVVWPN PLAWQNPPGW QTPPGWQTPP GWQGPPDWQG PPDWPLPPDW PLPPDWPLPT DWPLPPDWIP ADWPIPPDWQ NLRPSPNLRP SPNSRASQNP GAAQPRDVAL LQERANKLVK YLMLKDYTKV PIKRSEMLRD IIREYTDVYP EIIERACFVL EKKFGIQLKE IDKEEHLYIL ISTPESLAGI LGTTKDTPKL GLLLVILGVI FMNGNRASEA VLWEALRKMG LRPGVRHPLL GDLRKLLTYE FVKQKYLDYR RVPNSNPPEY EFLWGLRSYH ETSKMKVLRF IAEVQKRDPR DWTAQFMEAA DEALDALDAA AAEAEARAEA RTRMGIGDEA VSGPWSWDDI EFELLTWDEE GDFGDPWSRI PFTFWARYHQ NARSRFPQTF AGPIIGPGGT ASANFAANFG AIGFFWVE //