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MAGA6_HUMAN
ID   MAGA6_HUMAN             Reviewed;         314 AA.
AC   P43360; A8IF93; Q6NW44;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   03-AUG-2022, entry version 172.
DE   RecName: Full=Melanoma-associated antigen 6 {ECO:0000305};
DE   AltName: Full=Cancer/testis antigen 1.6;
DE            Short=CT1.6;
DE   AltName: Full=MAGE-6 antigen {ECO:0000303|PubMed:7927540};
DE   AltName: Full=MAGE3B antigen;
GN   Name=MAGEA6 {ECO:0000303|PubMed:31267705, ECO:0000312|HGNC:HGNC:6804};
GN   Synonyms=MAGE6 {ECO:0000303|PubMed:7927540};
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 [GENOMIC DNA].
RX   PubMed=7927540; DOI=10.1007/bf01246677;
RA   De Plaen E., Arden K., Traversari C., Gaforio J.J., Szikora J.-P.,
RA   De Smet C., Brasseur F., van der Bruggen P., Lethe B.G., Lurquin C.,
RA   Brasseur R., Chomez P., de Backer O., Cavenee W., Boon T.;
RT   "Structure, chromosomal localization, and expression of 12 genes of the
RT   MAGE family.";
RL   Immunogenetics 40:360-369(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Skin;
RX   PubMed=8037761; DOI=10.1006/bbrc.1994.1963;
RA   Ding M., Beck R.J., Keller C.J., Fenton R.G.;
RT   "Cloning and analysis of MAGE-1-related genes.";
RL   Biochem. Biophys. Res. Commun. 202:549-555(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=7642112; DOI=10.1016/0378-1119(94)00680-q;
RA   Imai Y., Shichijo S., Yamada A., Katayama T., Yano H., Itoh K.;
RT   "Sequence analysis of the MAGE gene family encoding human tumor-rejection
RT   antigens.";
RL   Gene 160:287-290(1995).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Testis;
RA   Mastutik G., Putra S.T., Soetjipto S., Kusumobroto H.O., Hardjowijoto S.,
RA   Lunardi J.H., Puspaningsih N.N.T.;
RT   "The isolation and characterization of melanoma antigen 6 (MAGE-6).";
RL   Submitted (SEP-2007) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Esophageal carcinoma;
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., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-152.
RC   TISSUE=Brain, and Testis;
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   [7]
RP   FUNCTION.
RX   PubMed=17942928; DOI=10.1158/0008-5472.can-07-1478;
RA   Yang B., O'Herrin S.M., Wu J., Reagan-Shaw S., Ma Y., Bhat K.M.,
RA   Gravekamp C., Setaluri V., Peters N., Hoffmann F.M., Peng H., Ivanov A.V.,
RA   Simpson A.J., Longley B.J.;
RT   "MAGE-A, mMage-b, and MAGE-C proteins form complexes with KAP1 and suppress
RT   p53-dependent apoptosis in MAGE-positive cell lines.";
RL   Cancer Res. 67:9954-9962(2007).
RN   [8]
RP   FUNCTION, AND INTERACTION WITH TRIM28.
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   [9]
RP   FUNCTION, AND UBIQUITINATION.
RX   PubMed=31267705; DOI=10.15252/embr.201847352;
RA   Ravichandran R., Kodali K., Peng J., Potts P.R.;
RT   "Regulation of MAGE-A3/6 by the CRL4-DCAF12 ubiquitin ligase and nutrient
RT   availability.";
RL   EMBO Rep. 20:e47352-e47352(2019).
RN   [10]
RP   VARIANT ILE-152.
RX   PubMed=20598277; DOI=10.1016/j.ajhg.2010.06.008;
RA   Sun Y., Almomani R., Aten E., Celli J., van der Heijden J., Venselaar H.,
RA   Robertson S.P., Baroncini A., Franco B., Basel-Vanagaite L., Horii E.,
RA   Drut R., Ariyurek Y., den Dunnen J.T., Breuning M.H.;
RT   "Terminal osseous dysplasia is caused by a single recurrent mutation in the
RT   FLNA gene.";
RL   Am. J. Hum. Genet. 87:146-153(2010).
CC   -!- FUNCTION: Activator of ubiquitin ligase activity of RING-type zinc
CC       finger-containing E3 ubiquitin-protein ligases that acts as a as
CC       repressor of autophagy (PubMed:31267705, PubMed:17942928,
CC       PubMed:20864041). May enhance ubiquitin ligase activity of TRIM28 and
CC       stimulate p53/TP53 ubiquitination by TRIM28. Proposed to act through
CC       recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at
CC       the E3:substrate complex (PubMed:17942928, PubMed:20864041). May play a
CC       role in tumor transformation or aspects of tumor progression
CC       (PubMed:17942928, PubMed:20864041). In vitro promotes cell viability in
CC       melanoma cell lines (PubMed:17942928). {ECO:0000269|PubMed:17942928,
CC       ECO:0000269|PubMed:20864041, ECO:0000269|PubMed:31267705}.
CC   -!- SUBUNIT: Interacts with TRIM28. {ECO:0000269|PubMed:20864041}.
CC   -!- INTERACTION:
CC       P43360; O00154: ACOT7; NbExp=3; IntAct=EBI-1045155, EBI-948905;
CC       P43360; O00154-4: ACOT7; NbExp=3; IntAct=EBI-1045155, EBI-12007918;
CC       P43360; Q08043: ACTN3; NbExp=3; IntAct=EBI-1045155, EBI-2880652;
CC       P43360; Q99996-2: AKAP9; NbExp=3; IntAct=EBI-1045155, EBI-9641546;
CC       P43360; Q6NSI1: ANKRD26P1; NbExp=3; IntAct=EBI-1045155, EBI-10250923;
CC       P43360; P06727: APOA4; NbExp=3; IntAct=EBI-1045155, EBI-1222447;
CC       P43360; P53367: ARFIP1; NbExp=3; IntAct=EBI-1045155, EBI-2808808;
CC       P43360; O75348: ATP6V1G1; NbExp=3; IntAct=EBI-1045155, EBI-711802;
CC       P43360; Q8N5M1: ATPAF2; NbExp=9; IntAct=EBI-1045155, EBI-1166928;
CC       P43360; Q9BQE9: BCL7B; NbExp=6; IntAct=EBI-1045155, EBI-2560588;
CC       P43360; O15155: BET1; NbExp=3; IntAct=EBI-1045155, EBI-749204;
CC       P43360; Q13515: BFSP2; NbExp=3; IntAct=EBI-1045155, EBI-10229433;
CC       P43360; Q53S33: BOLA3; NbExp=3; IntAct=EBI-1045155, EBI-12086950;
CC       P43360; Q8TAB5: C1orf216; NbExp=3; IntAct=EBI-1045155, EBI-747505;
CC       P43360; O94983-5: CAMTA2; NbExp=3; IntAct=EBI-1045155, EBI-10176008;
CC       P43360; O43439-4: CBFA2T2; NbExp=3; IntAct=EBI-1045155, EBI-11954144;
CC       P43360; Q8IYE0: CCDC146; NbExp=3; IntAct=EBI-1045155, EBI-10749669;
CC       P43360; Q8IYE0-2: CCDC146; NbExp=3; IntAct=EBI-1045155, EBI-10247802;
CC       P43360; Q8N715: CCDC185; NbExp=3; IntAct=EBI-1045155, EBI-740814;
CC       P43360; Q8N4L8: CCDC24; NbExp=3; IntAct=EBI-1045155, EBI-1104933;
CC       P43360; Q16619: CTF1; NbExp=3; IntAct=EBI-1045155, EBI-10238077;
CC       P43360; Q16619-2: CTF1; NbExp=3; IntAct=EBI-1045155, EBI-12276476;
CC       P43360; Q14203-5: DCTN1; NbExp=3; IntAct=EBI-1045155, EBI-25840379;
CC       P43360; O95886: DLGAP3; NbExp=3; IntAct=EBI-1045155, EBI-1752541;
CC       P43360; Q9Y2H0-1: DLGAP4; NbExp=3; IntAct=EBI-1045155, EBI-12000556;
CC       P43360; Q9H147: DNTTIP1; NbExp=3; IntAct=EBI-1045155, EBI-2795449;
CC       P43360; Q96FG2: ELMOD3; NbExp=3; IntAct=EBI-1045155, EBI-10285740;
CC       P43360; O00471: EXOC5; NbExp=6; IntAct=EBI-1045155, EBI-949824;
CC       P43360; Q32MH5: FAM214A; NbExp=3; IntAct=EBI-1045155, EBI-2866142;
CC       P43360; Q5SYB0: FRMPD1; NbExp=3; IntAct=EBI-1045155, EBI-10245120;
CC       P43360; Q8TAE8: GADD45GIP1; NbExp=3; IntAct=EBI-1045155, EBI-372506;
CC       P43360; P23434: GCSH; NbExp=3; IntAct=EBI-1045155, EBI-715444;
CC       P43360; Q9NXC2: GFOD1; NbExp=6; IntAct=EBI-1045155, EBI-8799578;
CC       P43360; Q96CS2: HAUS1; NbExp=3; IntAct=EBI-1045155, EBI-2514791;
CC       P43360; P52272: HNRNPM; NbExp=3; IntAct=EBI-1045155, EBI-486809;
CC       P43360; Q8NA54: IQUB; NbExp=3; IntAct=EBI-1045155, EBI-10220600;
CC       P43360; Q86VH2: KIF27; NbExp=3; IntAct=EBI-1045155, EBI-7950718;
CC       P43360; Q2WGJ6: KLHL38; NbExp=6; IntAct=EBI-1045155, EBI-6426443;
CC       P43360; Q8N3X6: LCORL; NbExp=3; IntAct=EBI-1045155, EBI-7138654;
CC       P43360; Q8N3X6-3: LCORL; NbExp=3; IntAct=EBI-1045155, EBI-12111580;
CC       P43360; Q96GY3: LIN37; NbExp=6; IntAct=EBI-1045155, EBI-748884;
CC       P43360; Q52LA3: LIN52; NbExp=3; IntAct=EBI-1045155, EBI-1389456;
CC       P43360; Q9Y333: LSM2; NbExp=6; IntAct=EBI-1045155, EBI-347416;
CC       P43360; Q96EZ8: MCRS1; NbExp=3; IntAct=EBI-1045155, EBI-348259;
CC       P43360; A0A0S2Z545: MED21; NbExp=3; IntAct=EBI-1045155, EBI-16431233;
CC       P43360; Q8IVT4: MGC50722; NbExp=3; IntAct=EBI-1045155, EBI-14086479;
CC       P43360; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-1045155, EBI-10172526;
CC       P43360; Q8TD10: MIPOL1; NbExp=6; IntAct=EBI-1045155, EBI-2548751;
CC       P43360; Q6PF18: MORN3; NbExp=6; IntAct=EBI-1045155, EBI-9675802;
CC       P43360; A6NI15: MSGN1; NbExp=3; IntAct=EBI-1045155, EBI-11991020;
CC       P43360; O43639: NCK2; NbExp=6; IntAct=EBI-1045155, EBI-713635;
CC       P43360; Q8IVI9-3: NOSTRIN; NbExp=3; IntAct=EBI-1045155, EBI-12280006;
CC       P43360; Q9H0N5: PCBD2; NbExp=3; IntAct=EBI-1045155, EBI-634289;
CC       P43360; Q08499: PDE4D; NbExp=3; IntAct=EBI-1045155, EBI-1642831;
CC       P43360; A6NK89: RASSF10; NbExp=3; IntAct=EBI-1045155, EBI-6912267;
CC       P43360; Q9H2L5: RASSF4; NbExp=6; IntAct=EBI-1045155, EBI-2933362;
CC       P43360; Q9P2K3: RCOR3; NbExp=3; IntAct=EBI-1045155, EBI-743428;
CC       P43360; Q9P2K3-2: RCOR3; NbExp=3; IntAct=EBI-1045155, EBI-1504830;
CC       P43360; Q96EN9: REX1BD; NbExp=3; IntAct=EBI-1045155, EBI-745810;
CC       P43360; P61513: RPL37A; NbExp=6; IntAct=EBI-1045155, EBI-356793;
CC       P43360; Q9BVN2: RUSC1; NbExp=3; IntAct=EBI-1045155, EBI-6257312;
CC       P43360; Q9HCY8: S100A14; NbExp=3; IntAct=EBI-1045155, EBI-751842;
CC       P43360; P06702: S100A9; NbExp=3; IntAct=EBI-1045155, EBI-1055001;
CC       P43360; Q9H788: SH2D4A; NbExp=6; IntAct=EBI-1045155, EBI-747035;
CC       P43360; Q96GM5: SMARCD1; NbExp=3; IntAct=EBI-1045155, EBI-358489;
CC       P43360; Q5SQN1: SNAP47; NbExp=3; IntAct=EBI-1045155, EBI-10244848;
CC       P43360; O95219: SNX4; NbExp=3; IntAct=EBI-1045155, EBI-724909;
CC       P43360; Q96FJ0: STAMBPL1; NbExp=6; IntAct=EBI-1045155, EBI-745021;
CC       P43360; Q13190: STX5; NbExp=3; IntAct=EBI-1045155, EBI-714206;
CC       P43360; Q12899: TRIM26; NbExp=4; IntAct=EBI-1045155, EBI-2341136;
CC       P43360; Q13263: TRIM28; NbExp=2; IntAct=EBI-1045155, EBI-78139;
CC       P43360; Q8N831: TSPYL6; NbExp=3; IntAct=EBI-1045155, EBI-12023322;
CC       P43360; O75386: TULP3; NbExp=7; IntAct=EBI-1045155, EBI-5357290;
CC       P43360; O14530: TXNDC9; NbExp=4; IntAct=EBI-1045155, EBI-707554;
CC       P43360; Q13426: XRCC4; NbExp=3; IntAct=EBI-1045155, EBI-717592;
CC       P43360; P36508: ZNF76; NbExp=3; IntAct=EBI-1045155, EBI-7254550;
CC       P43360; Q6ZRV7; NbExp=3; IntAct=EBI-1045155, EBI-17900348;
CC       P43360; Q9BS57; NbExp=3; IntAct=EBI-1045155, EBI-12418810;
CC   -!- TISSUE SPECIFICITY: Expressed in many tumors of several types, such as
CC       melanoma, head and neck squamous cell carcinoma, lung carcinoma and
CC       breast carcinoma, but not in normal tissues except for testes.
CC   -!- PTM: Ubiquitinated by the DCX(DCAF12) complex specifically recognizes
CC       the diglutamate (Glu-Glu) at the C-terminus, leading to its
CC       degradation. {ECO:0000269|PubMed:31267705}.
CC   -!- CAUTION: In vitro experiments measuring cell viability in melanoma cell
CC       lines used siRNA specific for MAGEA3 and MAGEA6.
CC       {ECO:0000269|PubMed:17942928}.
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DR   EMBL; U10691; AAA68875.1; -; Genomic_DNA.
DR   EMBL; U10339; AAA19006.1; -; mRNA.
DR   EMBL; D32076; BAA06842.1; -; mRNA.
DR   EMBL; EU161101; ABW06860.1; -; mRNA.
DR   EMBL; BX640600; CAE45706.1; -; mRNA.
DR   EMBL; BC041599; AAH41599.1; -; mRNA.
DR   EMBL; BC067731; AAH67731.1; -; mRNA.
DR   CCDS; CCDS76050.1; -.
DR   PIR; JC2360; JC2360.
DR   RefSeq; NP_005354.1; NM_005363.3.
DR   RefSeq; NP_787064.1; NM_175868.2.
DR   AlphaFoldDB; P43360; -.
DR   SMR; P43360; -.
DR   BioGRID; 110279; 88.
DR   IntAct; P43360; 80.
DR   MINT; P43360; -.
DR   STRING; 9606.ENSP00000480637; -.
DR   iPTMnet; P43360; -.
DR   PhosphoSitePlus; P43360; -.
DR   BioMuta; MAGEA6; -.
DR   DMDM; 1170860; -.
DR   jPOST; P43360; -.
DR   MassIVE; P43360; -.
DR   MaxQB; P43360; -.
DR   PaxDb; P43360; -.
DR   PeptideAtlas; P43360; -.
DR   PRIDE; P43360; -.
DR   ProteomicsDB; 55622; -.
DR   Antibodypedia; 30735; 177 antibodies from 29 providers.
DR   DNASU; 4105; -.
DR   Ensembl; ENST00000329342.10; ENSP00000329199.5; ENSG00000197172.11.
DR   Ensembl; ENST00000616035.4; ENSP00000480637.1; ENSG00000197172.11.
DR   GeneID; 4105; -.
DR   KEGG; hsa:4105; -.
DR   MANE-Select; ENST00000329342.10; ENSP00000329199.5; NM_005363.5; NP_005354.1.
DR   UCSC; uc033fan.1; human.
DR   CTD; 4105; -.
DR   DisGeNET; 4105; -.
DR   GeneCards; MAGEA6; -.
DR   HGNC; HGNC:6804; MAGEA6.
DR   HPA; ENSG00000197172; Tissue enriched (testis).
DR   MIM; 300176; gene.
DR   neXtProt; NX_P43360; -.
DR   OpenTargets; ENSG00000197172; -.
DR   PharmGKB; PA30550; -.
DR   VEuPathDB; HostDB:ENSG00000197172; -.
DR   eggNOG; KOG4562; Eukaryota.
DR   GeneTree; ENSGT00940000164672; -.
DR   HOGENOM; CLU_039582_1_2_1; -.
DR   InParanoid; P43360; -.
DR   OMA; GRARAYM; -.
DR   OrthoDB; 1195799at2759; -.
DR   PhylomeDB; P43360; -.
DR   TreeFam; TF328505; -.
DR   PathwayCommons; P43360; -.
DR   SignaLink; P43360; -.
DR   BioGRID-ORCS; 4105; 10 hits in 613 CRISPR screens.
DR   GenomeRNAi; 4105; -.
DR   Pharos; P43360; Tbio.
DR   PRO; PR:P43360; -.
DR   Proteomes; UP000005640; Chromosome X.
DR   RNAct; P43360; protein.
DR   Bgee; ENSG00000197172; Expressed in right testis and 29 other tissues.
DR   ExpressionAtlas; P43360; baseline and differential.
DR   Genevisible; P43360; HS.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0042826; F:histone deacetylase binding; IBA:GO_Central.
DR   GO; GO:0010507; P:negative regulation of autophagy; IDA:UniProtKB.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   Gene3D; 1.10.10.1200; -; 1.
DR   Gene3D; 1.10.10.1210; -; 1.
DR   InterPro; IPR037445; MAGE.
DR   InterPro; IPR021072; MAGE_N.
DR   InterPro; IPR041898; MAGE_WH1.
DR   InterPro; IPR041899; MAGE_WH2.
DR   InterPro; IPR030097; MAGEA3/MAGEA6.
DR   InterPro; IPR002190; MHD_dom.
DR   PANTHER; PTHR11736; PTHR11736; 1.
DR   PANTHER; PTHR11736:SF60; PTHR11736:SF60; 1.
DR   Pfam; PF01454; MAGE; 1.
DR   Pfam; PF12440; MAGE_N; 1.
DR   SMART; SM01373; MAGE; 1.
DR   SMART; SM01392; MAGE_N; 1.
DR   PROSITE; PS50838; MAGE; 1.
PE   1: Evidence at protein level;
KW   Reference proteome; Tumor antigen; Ubl conjugation;
KW   Ubl conjugation pathway.
FT   CHAIN           1..314
FT                   /note="Melanoma-associated antigen 6"
FT                   /id="PRO_0000156706"
FT   DOMAIN          109..308
FT                   /note="MAGE"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00127"
FT   REGION          1..99
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        34..48
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        62..96
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VARIANT         152
FT                   /note="S -> I (in dbSNP:rs7056365)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:20598277"
FT                   /id="VAR_053493"
SQ   SEQUENCE   314 AA;  34891 MW;  29B83C7FA6E50263 CRC64;
     MPLEQRSQHC KPEEGLEARG EALGLVGAQA PATEEQEAAS SSSTLVEVTL GEVPAAESPD
     PPQSPQGASS LPTTMNYPLW SQSYEDSSNQ EEEGPSTFPD LESEFQAALS RKVAKLVHFL
     LLKYRAREPV TKAEMLGSVV GNWQYFFPVI FSKASDSLQL VFGIELMEVD PIGHVYIFAT
     CLGLSYDGLL GDNQIMPKTG FLIIILAIIA KEGDCAPEEK IWEELSVLEV FEGREDSIFG
     DPKKLLTQYF VQENYLEYRQ VPGSDPACYE FLWGPRALIE TSYVKVLHHM VKISGGPRIS
     YPLLHEWALR EGEE
 
 
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