ID   MAGC2_HUMAN             Reviewed;         373 AA.
AC   Q9UBF1; Q5JZ00; Q96D45; Q9P1M6; Q9P1M7;
DT   26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   27-MAR-2024, entry version 167.
DE   RecName: Full=Melanoma-associated antigen C2;
DE   AltName: Full=Cancer/testis antigen 10;
DE            Short=CT10;
DE   AltName: Full=Hepatocellular carcinoma-associated antigen 587;
DE   AltName: Full=MAGE-C2 antigen;
DE   AltName: Full=MAGE-E1 antigen;
GN   Name=MAGEC2; Synonyms=HCA587, MAGEE1;
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 / MRNA], AND IDENTIFICATION AS A
RP   CANCER/TESTIS ANTIGEN.
RX   PubMed=10699956;
RX   DOI=10.1002/(sici)1097-0215(20000301)85:5<726::aid-ijc21>3.0.co;2-f;
RA   Gure A.O., Stockert E., Arden K.C., Boyer A.D., Viars C.S., Scanlan M.J.,
RA   Old L.J., Chen Y.-T.;
RT   "CT10: a new cancer-testis (CT) antigen homologous to CT7 and the MAGE
RT   family, identified by representational difference analysis.";
RL   Int. J. Cancer 85:726-732(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX   PubMed=10861452;
RX   DOI=10.1002/1097-0215(20000701)87:1<55::aid-ijc8>3.3.co;2-a;
RA   Lucas S., De Plaen E., Boon T.;
RT   "MAGE-B5, MAGE-B6, MAGE-C2, and MAGE-C3: four new members of the MAGE
RT   family with tumor-specific expression.";
RL   Int. J. Cancer 87:55-60(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY, AND
RP   IDENTIFICATION AS A CANCER/TESTIS ANTIGEN.
RC   TISSUE=Hepatoma;
RX   PubMed=12097419; DOI=10.4049/jimmunol.169.2.1102;
RA   Wang Y., Han K.-J., Pang X.-W., Vaughan H.A., Qu W., Dong X.-Y.,
RA   Peng J.-R., Zhao H.-T., Rui J.-A., Leng X.-S., Cebon J., Burgess A.W.,
RA   Chen W.-F.;
RT   "Large scale identification of human hepatocellular carcinoma-associated
RT   antigens by autoantibodies.";
RL   J. Immunol. 169:1102-1109(2002).
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., Lovell F.L.,
RA   Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA   Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA   Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA   Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA   Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA   Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA   Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA   Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA   Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA   Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA   Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA   Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA   Chinault C., 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., Delgado O.,
RA   Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA   Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA   Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA   Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA   Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA   Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA   Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA   Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA   Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA   Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA   Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA   Liu W., 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., Milne S.,
RA   Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA   Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA   Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA   Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA   Rhodes S., 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., Teague B.,
RA   Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA   d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA   Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA   Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA   Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA   Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA   Rosenthal A., 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., Nelson D.L.,
RA   Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA   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].
RC   TISSUE=Chronic myeloid leukemia cell, and Melanoma;
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   [6]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=12920247; DOI=10.1097/01.lab.0000080605.73839.96;
RA   Li B., Qian X.-P., Pang X.-W., Zou W.-Z., Wang Y.-P., Wu H.-Y., Chen W.-F.;
RT   "HCA587 antigen expression in normal tissues and cancers: correlation with
RT   tumor differentiation in hepatocellular carcinoma.";
RL   Lab. Invest. 83:1185-1192(2003).
RN   [7]
RP   INTERACTION WITH TRIM28.
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, INTERACTION WITH TRIM28 AND UBE2H, AND MUTAGENESIS OF
RP   152-LEU-LEU-153.
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   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [11]
RP   VARIANT [LARGE SCALE ANALYSIS] CYS-6.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
CC   -!- FUNCTION: Proposed to enhance ubiquitin ligase activity of RING-type
CC       zinc finger-containing E3 ubiquitin-protein ligases. In vitro enhances
CC       ubiquitin ligase activity of TRIM28 and stimulates p53/TP53
CC       ubiquitination in presence of Ubl-conjugating enzyme UBE2H leading to
CC       p53/TP53 degradation. Proposed to act through recruitment and/or
CC       stabilization of the Ubl-conjugating enzymes (E2) at the E3:substrate
CC       complex. {ECO:0000269|PubMed:20864041}.
CC   -!- SUBUNIT: Interacts with TRIM28 and UBE2H. {ECO:0000269|PubMed:17942928,
CC       ECO:0000269|PubMed:20864041}.
CC   -!- INTERACTION:
CC       Q9UBF1; Q53GS7: GLE1; NbExp=3; IntAct=EBI-5651487, EBI-1955541;
CC       Q9UBF1; Q7Z4N8: P4HA3; NbExp=4; IntAct=EBI-5651487, EBI-10181968;
CC       Q9UBF1; Q5JS98: PBX3; NbExp=3; IntAct=EBI-5651487, EBI-10244393;
CC       Q9UBF1; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-5651487, EBI-5235340;
CC       Q9UBF1; Q16384: SSX1; NbExp=3; IntAct=EBI-5651487, EBI-10237585;
CC       Q9UBF1; Q16385: SSX2B; NbExp=3; IntAct=EBI-5651487, EBI-2210673;
CC       Q9UBF1; P04637: TP53; NbExp=3; IntAct=EBI-5651487, EBI-366083;
CC       Q9UBF1; Q13263: TRIM28; NbExp=14; IntAct=EBI-5651487, EBI-78139;
CC       Q9UBF1; Q86WV8: TSC1; NbExp=3; IntAct=EBI-5651487, EBI-12806590;
CC       Q9UBF1; P62256: UBE2H; NbExp=3; IntAct=EBI-5651487, EBI-2129909;
CC       Q9UBF1; P54577: YARS1; NbExp=3; IntAct=EBI-5651487, EBI-1048893;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12920247}. Nucleus
CC       {ECO:0000269|PubMed:12920247}. Note=Nuclear in germ cells. Cytoplasmic
CC       in well-differentiated hepatocellular carcinoma, nuclear in
CC       moderately- and poorly-differentiated hepatocellular carcinoma.
CC   -!- TISSUE SPECIFICITY: Not expressed in normal tissues, except in germ
CC       cells in the seminiferous tubules and in Purkinje cells of the
CC       cerebellum. Expressed in various tumors, including melanoma, lymphoma,
CC       as well as pancreatic cancer, mammary gland cancer, non-small cell lung
CC       cancer and liver cancer. In hepatocellular carcinoma, there is an
CC       inverse correlation between tumor differentiation and protein
CC       expression, i.e. the lower the differentiation, the higher percentage
CC       of expression. {ECO:0000269|PubMed:12097419,
CC       ECO:0000269|PubMed:12920247}.
CC   -!- DEVELOPMENTAL STAGE: Strongly expressed in spermatogonia and primary
CC       spermatocytes. At later stages of maturation, expression gradually
CC       decreases and becomes undetectable in mature spermatids.
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DR   EMBL; AF116194; AAF34816.1; -; mRNA.
DR   EMBL; AF116195; AAF34817.1; -; Genomic_DNA.
DR   EMBL; AF196482; AAF07210.1; -; mRNA.
DR   EMBL; AF196483; AAF07211.1; -; Genomic_DNA.
DR   EMBL; AF151378; AAF36533.1; -; mRNA.
DR   EMBL; AF239802; AAK15073.1; -; Genomic_DNA.
DR   EMBL; AL031073; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC005891; AAH05891.1; -; mRNA.
DR   EMBL; BC013318; AAH13318.1; -; mRNA.
DR   CCDS; CCDS14678.1; -.
DR   RefSeq; NP_057333.1; NM_016249.3.
DR   AlphaFoldDB; Q9UBF1; -.
DR   SMR; Q9UBF1; -.
DR   BioGRID; 119540; 30.
DR   IntAct; Q9UBF1; 14.
DR   MINT; Q9UBF1; -.
DR   STRING; 9606.ENSP00000354660; -.
DR   iPTMnet; Q9UBF1; -.
DR   PhosphoSitePlus; Q9UBF1; -.
DR   BioMuta; MAGEC2; -.
DR   DMDM; 17380150; -.
DR   jPOST; Q9UBF1; -.
DR   MassIVE; Q9UBF1; -.
DR   MaxQB; Q9UBF1; -.
DR   PaxDb; 9606-ENSP00000354660; -.
DR   PeptideAtlas; Q9UBF1; -.
DR   ProteomicsDB; 83954; -.
DR   Pumba; Q9UBF1; -.
DR   Antibodypedia; 30560; 201 antibodies from 24 providers.
DR   DNASU; 51438; -.
DR   Ensembl; ENST00000247452.4; ENSP00000354660.2; ENSG00000046774.10.
DR   GeneID; 51438; -.
DR   KEGG; hsa:51438; -.
DR   MANE-Select; ENST00000247452.4; ENSP00000354660.2; NM_016249.4; NP_057333.1.
DR   UCSC; uc004fbu.3; human.
DR   AGR; HGNC:13574; -.
DR   CTD; 51438; -.
DR   DisGeNET; 51438; -.
DR   GeneCards; MAGEC2; -.
DR   HGNC; HGNC:13574; MAGEC2.
DR   HPA; ENSG00000046774; Tissue enriched (testis).
DR   MIM; 300468; gene.
DR   neXtProt; NX_Q9UBF1; -.
DR   OpenTargets; ENSG00000046774; -.
DR   PharmGKB; PA134954317; -.
DR   VEuPathDB; HostDB:ENSG00000046774; -.
DR   eggNOG; KOG4562; Eukaryota.
DR   GeneTree; ENSGT00940000164535; -.
DR   HOGENOM; CLU_039582_1_1_1; -.
DR   InParanoid; Q9UBF1; -.
DR   OMA; QGHYLEY; -.
DR   OrthoDB; 4734198at2759; -.
DR   PhylomeDB; Q9UBF1; -.
DR   TreeFam; TF328505; -.
DR   PathwayCommons; Q9UBF1; -.
DR   SignaLink; Q9UBF1; -.
DR   SIGNOR; Q9UBF1; -.
DR   BioGRID-ORCS; 51438; 12 hits in 778 CRISPR screens.
DR   GeneWiki; MAGEC2; -.
DR   GenomeRNAi; 51438; -.
DR   Pharos; Q9UBF1; Tbio.
DR   PRO; PR:Q9UBF1; -.
DR   Proteomes; UP000005640; Chromosome X.
DR   RNAct; Q9UBF1; Protein.
DR   Bgee; ENSG00000046774; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 30 other cell types or tissues.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; IDA:UniProtKB.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0051443; P:positive regulation of ubiquitin-protein transferase activity; IMP:UniProtKB.
DR   GO; GO:0030163; P:protein catabolic process; IMP:UniProtKB.
DR   Gene3D; 1.10.10.1200; MAGE homology domain, winged helix WH1 motif; 1.
DR   Gene3D; 1.10.10.1210; MAGE homology domain, winged helix WH2 motif; 1.
DR   InterPro; IPR037445; MAGE.
DR   InterPro; IPR041898; MAGE_WH1.
DR   InterPro; IPR041899; MAGE_WH2.
DR   InterPro; IPR002190; MHD_dom.
DR   PANTHER; PTHR11736:SF161; MELANOMA-ASSOCIATED ANTIGEN C2; 1.
DR   PANTHER; PTHR11736; MELANOMA-ASSOCIATED ANTIGEN MAGE ANTIGEN; 1.
DR   Pfam; PF01454; MAGE; 1.
DR   SMART; SM01373; MAGE; 1.
DR   PROSITE; PS50838; MAGE; 1.
DR   Genevisible; Q9UBF1; HS.
PE   1: Evidence at protein level;
KW   Cytoplasm; Nucleus; Reference proteome; Tumor antigen;
KW   Ubl conjugation pathway.
FT   CHAIN           1..373
FT                   /note="Melanoma-associated antigen C2"
FT                   /id="PRO_0000156721"
FT   DOMAIN          141..336
FT                   /note="MAGE"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00127"
FT   REGION          1..102
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          135..373
FT                   /note="Interaction with TRIM28"
FT   COMPBIAS        41..63
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VARIANT         6
FT                   /note="G -> C (in a breast cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036583"
FT   MUTAGEN         152..153
FT                   /note="LL->AA: Decreases interaction with TRIM28, abolishes
FT                   in vitro ubiquitination of TP53."
FT                   /evidence="ECO:0000269|PubMed:20864041"
FT   CONFLICT        12
FT                   /note="V -> A (in Ref. 5; AAH13318)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        189
FT                   /note="M -> T (in Ref. 1; AAF34816)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        334
FT                   /note="K -> E (in Ref. 1; AAF34816/AAF34817)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   373 AA;  41163 MW;  D55867D7972BF49F CRC64;
     MPPVPGVPFR NVDNDSPTSV ELEDWVDAQH PTDEEEEEAS SASSTLYLVF SPSSFSTSSS
     LILGGPEEEE VPSGVIPNLT ESIPSSPPQG PPQGPSQSPL SSCCSSFSWS SFSEESSSQK
     GEDTGTCQGL PDSESSFTYT LDEKVAELVE FLLLKYEAEE PVTEAEMLMI VIKYKDYFPV
     ILKRAREFME LLFGLALIEV GPDHFCVFAN TVGLTDEGSD DEGMPENSLL IIILSVIFIK
     GNCASEEVIW EVLNAVGVYA GREHFVYGEP RELLTKVWVQ GHYLEYREVP HSSPPYYEFL
     WGPRAHSESI KKKVLEFLAK LNNTVPSSFP SWYKDALKDV EERVQATIDT ADDATVMASE
     SLSVMSSNVS FSE
//