Melanoma-associated antigen B17 (MAGEB17) is a protein which in humans is encoded by the MAGEB17 gene located on the X chromosome (Xp22.2). The protein has a molecular mass of approximately 37.4 kDa and an isoelectric point of approximately 9.25. MAGEB17 is classified as a cancer-testis antigen, with expression in normal adult tissues primarily restricted to germ cells and re-expression observed in a subset of human tumors.
Gene MAGEB17 is a protein-coding gene on chromosome X (Xp22.2), on the plus strand, spanning 3,984 bp across two exons.NCBI Gene entry 645864. https://www.ncbi.nlm.nih.gov/gene/645864 MAGEB17 is a member of the MAGEB gene family, in which the entire CDS is located within the last exon. MAGEB17 is classified as a cancer-testis antigen, with expression in normal adult tissues restricted to germ cells.Chomez P, et al. An overview of the MAGE gene family with the identification of all human members of the family. Cancer Res. 2001;61(14):5544–5551. PMID: 11454705.
Transcripts MAGEB17 produces a canonical transcript (NM_001277307.2) of 1,434 nt.NCBI Gene entry 645864. https://www.ncbi.nlm.nih.gov/gene/645864 One splice variant exists (XM_047442355.1, 1,566 nt), differing from the canonical transcript in the 5' UTR.
Protein
The MAGEB17 gene produces two isoforms, both 336 amino acids in length. The canonical protein, Melanoma-associated antigen B17 (NP_001264236.1), has a predicted molecular mass of ~37.4 kDa and a theoretical isoelectric point of ~9.25, indicating a basic protein at physiological pH.UniProt Consortium. UniProtKB entry A8MXT2 (MAGEB17_HUMAN). https://www.uniprot.org/uniprotkb/A8MXT2/entry Melanoma-associated antigen B17 isoform X1 (XP_047298311.1) is also 336 aa, differing from the canonical transcript in the 5' UTR. Gene Ontology annotations associate MAGEB17 with the negative regulation of transcription by RNA polymerase II and with activity in the nucleus.QuickGO — GO annotations for UniProtKB:A8MXT2. European Bioinformatics Institute. https://www.ebi.ac.uk/QuickGO/annotations?geneProductId=A8MXT2
Structure The protein contains two conserved domains: an N-terminal MAGE domain (MAGE_N, residues 5–93) and a MAGE homology domain (MHD, residues 116–283).NCBI Gene entry 645864. https://www.ncbi.nlm.nih.gov/gene/645864 The MHD serves as a structural scaffold, a feature conserved across the MAGE protein family.Chomez P, et al. An overview of the MAGE gene family with the identification of all human members of the family. Cancer Res. 2001;61(14):5544–5551. PMID: 11454705. Multiple sequence alignments indicate that a C-terminal core region flanks the MHD and is highly conserved across mammalian orthologs.Clustal Omega multiple sequence alignment of 20 MAGEB17 orthologs. https://www.ebi.ac.uk/jdispatcher/msa/clustalo
Gene level regulation
Expression MAGEB17 is non-ubiquitously expressed, with expression in normal adult tissues restricted to germ cells.Human Protein Atlas — MAGEB17 single-cell RNA expression. https://www.proteinatlas.org/ENSG00000182798-MAGEB17 Testis is the predominant site of expression, with all other normal adult tissues at near-zero levels.Human Protein Atlas — MAGEB17 tissue RNA expression (PRJEB4337). https://www.proteinatlas.org/ENSG00000182798-MAGEB17 Expression is transiently detected in fetal heart tissue at 18 weeks gestational age.Szabo L, et al. Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development. Genome Biol. 2015;16(1):126. PMID: 26076956. No substantial expression has been detected in any brain region in either fetal or adult tissue.BrainSpan Atlas of the Developing Human Brain — MAGEB17. https://www.brainspan.org In cancer, MAGEB17 is reactivated across a subset of tumor types including colon, rectal, and liver adenocarcinomas, and testicular germ cell tumors.Human Protein Atlas — MAGEB17 cancer RNA expression (TCGA). https://www.proteinatlas.org/ENSG00000182798-MAGEB17
Promoter The MAGEB17 promoter contains binding sites for transcription factors associated with cancer-testis antigen reactivation and germ cell biology, including STAT3, SRY, Nanog, and CREM.UCSC Genome Browser — Zoonomia 241-way placental mammal conservation, GRCh38 chrX:16,167,481–16,171,464. https://genome.ucsc.edu Promoter sequence conservation is largely restricted to primates, consistent with the primate-specific distribution of the MAGE gene family.UCSC Genome Browser — Zoonomia 241-way placental mammal conservation, GRCh38 chrX:16,167,481–16,171,464. https://genome.ucsc.edu
Protein level regulation MAGEB17 contains several experimentally confirmed and predicted regulatory modifications. Threonine 131 (T131), located at the MHD boundary, has been experimentally identified as a phosphorylation site and is conserved across mammalian orthologs.PhosphoSitePlus entry for MAGEB17. https://www.phosphosite.org/proteinAction.action?id=19104250 Two predicted SUMOylation sites exist at K88 and K292.GPS-SUMO 2.0 analysis of NP_001264236.1. A predicted SPOP degron motif is present at residues 39–43. A predicted MAPK docking motif at residues 152–160 suggests potential regulation by mitogen-activated protein kinase signaling.
Subcellular localization MAGEB17 localizes primarily to the nucleus, consistent with two predicted nuclear localization signals at residues 7–12 and 126–145.Human Protein Atlas — MAGEB17 subcellular localization. https://www.proteinatlas.org/ENSG00000182798-MAGEB17 A cytoplasmic pool has also been observed, potentially reflecting pre-import localization prior to nuclear transport.
Homology and evolution
Paralogs
MAGEB17 is a member of the MAGE protein family, which comprises over 50 paralogs in humans.Chomez P, et al. An overview of the MAGE gene family with the identification of all human members of the family. Cancer Res. 2001;61(14):5544–5551. PMID: 11454705. MAGEB4 shares greater sequence identity with MAGEB17 than MAGEB1, suggesting a closer evolutionary relationship within the MAGE-B subfamily.Clustal Omega multiple sequence alignment of MAGEB17, MAGEB1, and MAGEB4. https://www.ebi.ac.uk/jdispatcher/msa/clustalo
Orthologs
MAGEB17 orthologs are found exclusively in mammals, consistent with the mammal-specific expansion of the MAGE protein family.Chomez P, et al. An overview of the MAGE gene family with the identification of all human members of the family. Cancer Res. 2001;61(14):5544–5551. PMID: 11454705. Sequence identity decreases with increasing evolutionary distance from humans.NCBI BLAST; EMBOSS Needle pairwise alignment. https://www.ebi.ac.uk/jdispatcher/psa/emboss_needle
Rate of divergence
MAGEB17 diverges more rapidly than both Cytochrome c and Complement factor I, suggesting relatively weak purifying selection on the protein sequence compared to these broadly expressed proteins.TimeTree — The Timescale of Life. https://timetree.org
Distant homologs The most distant detectable homolog is the Drosophila melanogaster MAGE protein, sharing 16.9% sequence identity with human MAGEB17, with conservation restricted to the MAGE homology domain.EMBOSS Needle pairwise alignment. https://www.ebi.ac.uk/jdispatcher/psa/emboss_needle
Interacting proteins
STRING analysis identifies several predicted functional partners for MAGEB17, primarily on the basis of co-expression and text mining.STRING v12 — MAGEB17 functional protein association network. https://string-db.org No experimentally validated protein-protein interactions have been identified for MAGEB17 in BioGRID. A single genetic interaction with LDLR is recorded, though this is considered a likely artifact given the high-throughput nature of the screen.BioGRID v5 — MAGEB17 interactions. https://thebiogrid.org
Clinical significance MAGEB17 is classified as a cancer-testis antigen, with expression silenced in normal somatic tissues via DNA methylation and reactivated in a subset of tumors.Chomez P, et al. An overview of the MAGE gene family with the identification of all human members of the family. Cancer Res. 2001;61(14):5544–5551. PMID: 11454705. RNA expression data indicate enrichment in colon, rectal, and liver adenocarcinomas, and testicular germ cell tumors.Human Protein Atlas — MAGEB17 cancer RNA expression (TCGA). https://www.proteinatlas.org/ENSG00000182798-MAGEB17 A stop-gain variant (V297*) has been identified, resulting in a truncated protein.UniProt Consortium. UniProtKB entry A8MXT2 (MAGEB17_HUMAN). https://www.uniprot.org/uniprotkb/A8MXT2/entry By virtue of its tumor-specific expression, MAGEB17 represents a potential target for cancer immunotherapy.Chomez P, et al. An overview of the MAGE gene family with the identification of all human members of the family. Cancer Res. 2001;61(14):5544–5551. PMID: 11454705.
Because of its tumor-associated expression pattern, MAGEB17 has been proposed as a potential target for cancer immunotherapy.
References
Suggested reading Chomez P, et al. An Overview of the MAGE Gene Family with the Identification of All Human Members of the Family. Cancer Res. 2001.