UniProt functional annotation for Q9Y5S9



	UniProt functional annotation for Q9Y5S9

UniProt code: Q9Y5S9.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Required for pre-mRNA splicing as component of the spliceosome (PubMed:28502770, PubMed:29301961). Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). The MAGOH-RBM8A heterodimer inhibits the ATPase activity of EIF4A3, thereby trapping the ATP-bound EJC core onto spliced mRNA in a stable conformation. The MAGOH-RBM8A heterodimer interacts with the EJC key regulator PYM1 leading to EJC disassembly in the cytoplasm and translation enhancement of EJC-bearing spliced mRNAs by recruiting them to the ribosomal 48S preinitiation complex. Its removal from cytoplasmic mRNAs requires translation initiation from EJC-bearing spliced mRNAs. Associates preferentially with mRNAs produced by splicing. Does not interact with pre-mRNAs, introns, or mRNAs produced from intronless cDNAs. Associates with both nuclear mRNAs and newly exported cytoplasmic mRNAs. The MAGOH-RBM8A heterodimer is a component of the nonsense mediated decay (NMD) pathway. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl- X(S); the function is different from the established EJC assembly. {ECO:0000269|PubMed:12121612, ECO:0000269|PubMed:12718880, ECO:0000269|PubMed:12730685, ECO:0000269|PubMed:16209946, ECO:0000269|PubMed:19409878, ECO:0000269|PubMed:22203037, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961}.

Subunit: Heterodimer with either MAGOH or MAGOHB (PubMed:10662555, PubMed:12730685, PubMed:23917022, PubMed:12781131). Part of the mRNA splicing-dependent exon junction complex (EJC) complex; the core complex contains CASC3, EIF4A3, MAGOH or MAGOHB, and RBM8A (PubMed:11707413, PubMed:16170325, PubMed:16314458, PubMed:23917022, PubMed:16923391, PubMed:16931718, PubMed:19033377, PubMed:20479275). Interacts with PYM1; the interaction is direct and dissociates the EJC from spliced mRNAs (PubMed:14968132, PubMed:18026120, PubMed:19410547). Part of a complex that contains the EJC core components CASC3, EIF4A3, MAGOH and RBM8A plus proteins involved in nonsense-mediated mRNA decay, such as UPF1, UPF2, UPF3A and UPF3B (PubMed:11546873, PubMed:12718880, PubMed:20479275). Found in a post-splicing complex with NXF1, MAGOH, UPF1, UPF2, UPF3A, UPF3B and RNPS1 (PubMed:11546874). Interacts with DDX39B, MAGOH, DPH1, UPF3B, RNPS1, SRRM1 and ALYREF/THOC4 (PubMed:11013075, PubMed:11118221, PubMed:11707413, PubMed:12944400). Interacts with IPO13; the interaction mediates the nuclear import of the MAGOH-RBM8A heterodimer (PubMed:11447110). Identified in the spliceosome C complex (PubMed:11991638, PubMed:28502770, PubMed:29301961). Associates with polysomes (PubMed:12121612). {ECO:0000269|PubMed:10662555, ECO:0000269|PubMed:11013075, ECO:0000269|PubMed:11118221, ECO:0000269|PubMed:11447110, ECO:0000269|PubMed:11546873, ECO:0000269|PubMed:11546874, ECO:0000269|PubMed:11707413, ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:12121612, ECO:0000269|PubMed:12718880, ECO:0000269|PubMed:12730685, ECO:0000269|PubMed:12781131, ECO:0000269|PubMed:12944400, ECO:0000269|PubMed:14625303, ECO:0000269|PubMed:14968132, ECO:0000269|PubMed:16170325, ECO:0000269|PubMed:16314458, ECO:0000269|PubMed:16923391, ECO:0000269|PubMed:16931718, ECO:0000269|PubMed:18026120, ECO:0000269|PubMed:19033377, ECO:0000269|PubMed:19410547, ECO:0000269|PubMed:20479275, ECO:0000269|PubMed:23917022, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961}.

Subcellular location: Nucleus {ECO:0000269|PubMed:11030346, ECO:0000269|PubMed:19324961, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961}. Nucleus speckle {ECO:0000269|PubMed:11030346, ECO:0000269|PubMed:19324961}. Cytoplasm {ECO:0000269|PubMed:11030346, ECO:0000269|PubMed:19324961}. Note=Nucleocytoplasmic shuttling protein (PubMed:11030346). Travels to the cytoplasm as part of the exon junction complex (EJC) bound to mRNA. Colocalizes with the core EJC, ALYREF/THOC4, NXF1 and UAP56 in the nucleus and nuclear speckles (PubMed:19324961). {ECO:0000269|PubMed:11030346, ECO:0000269|PubMed:19324961}.

Tissue specificity: Ubiquitous.

Disease: Thrombocytopenia-absent radius syndrome (TAR) [MIM:274000]: An autosomal recessive disorder characterized by bilateral absence of the radii with the presence of both thumbs, thrombocytopenia, low numbers of megakaryocytes, and bleeding episodes in the first year of life. Thrombocytopenic episodes decrease with age. Skeletal anomalies range from absence of radii to virtual absence of upper limbs, with or without lower limb defects such as malformations of the hip and knee. {ECO:0000269|PubMed:22366785}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the RBM8A family. {ECO:0000305}.

Sequence caution: Sequence=AAG14951.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAG16782.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAG16782.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA. A chimeric cDNA originating from chromosomes 1 and 5.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Required for pre-mRNA splicing as component of the spliceosome (PubMed:28502770, PubMed:29301961). Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). The MAGOH-RBM8A heterodimer inhibits the ATPase activity of EIF4A3, thereby trapping the ATP-bound EJC core onto spliced mRNA in a stable conformation. The MAGOH-RBM8A heterodimer interacts with the EJC key regulator PYM1 leading to EJC disassembly in the cytoplasm and translation enhancement of EJC-bearing spliced mRNAs by recruiting them to the ribosomal 48S preinitiation complex. Its removal from cytoplasmic mRNAs requires translation initiation from EJC-bearing spliced mRNAs. Associates preferentially with mRNAs produced by splicing. Does not interact with pre-mRNAs, introns, or mRNAs produced from intronless cDNAs. Associates with both nuclear mRNAs and newly exported cytoplasmic mRNAs. The MAGOH-RBM8A heterodimer is a component of the nonsense mediated decay (NMD) pathway. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl- X(S); the function is different from the established EJC assembly. {ECO:0000269\|PubMed:12121612, ECO:0000269\|PubMed:12718880, ECO:0000269\|PubMed:12730685, ECO:0000269\|PubMed:16209946, ECO:0000269\|PubMed:19409878, ECO:0000269\|PubMed:22203037, ECO:0000269\|PubMed:28502770, ECO:0000269\|PubMed:29301961}.


Subunit:		Heterodimer with either MAGOH or MAGOHB (PubMed:10662555, PubMed:12730685, PubMed:23917022, PubMed:12781131). Part of the mRNA splicing-dependent exon junction complex (EJC) complex; the core complex contains CASC3, EIF4A3, MAGOH or MAGOHB, and RBM8A (PubMed:11707413, PubMed:16170325, PubMed:16314458, PubMed:23917022, PubMed:16923391, PubMed:16931718, PubMed:19033377, PubMed:20479275). Interacts with PYM1; the interaction is direct and dissociates the EJC from spliced mRNAs (PubMed:14968132, PubMed:18026120, PubMed:19410547). Part of a complex that contains the EJC core components CASC3, EIF4A3, MAGOH and RBM8A plus proteins involved in nonsense-mediated mRNA decay, such as UPF1, UPF2, UPF3A and UPF3B (PubMed:11546873, PubMed:12718880, PubMed:20479275). Found in a post-splicing complex with NXF1, MAGOH, UPF1, UPF2, UPF3A, UPF3B and RNPS1 (PubMed:11546874). Interacts with DDX39B, MAGOH, DPH1, UPF3B, RNPS1, SRRM1 and ALYREF/THOC4 (PubMed:11013075, PubMed:11118221, PubMed:11707413, PubMed:12944400). Interacts with IPO13; the interaction mediates the nuclear import of the MAGOH-RBM8A heterodimer (PubMed:11447110). Identified in the spliceosome C complex (PubMed:11991638, PubMed:28502770, PubMed:29301961). Associates with polysomes (PubMed:12121612). {ECO:0000269\|PubMed:10662555, ECO:0000269\|PubMed:11013075, ECO:0000269\|PubMed:11118221, ECO:0000269\|PubMed:11447110, ECO:0000269\|PubMed:11546873, ECO:0000269\|PubMed:11546874, ECO:0000269\|PubMed:11707413, ECO:0000269\|PubMed:11991638, ECO:0000269\|PubMed:12121612, ECO:0000269\|PubMed:12718880, ECO:0000269\|PubMed:12730685, ECO:0000269\|PubMed:12781131, ECO:0000269\|PubMed:12944400, ECO:0000269\|PubMed:14625303, ECO:0000269\|PubMed:14968132, ECO:0000269\|PubMed:16170325, ECO:0000269\|PubMed:16314458, ECO:0000269\|PubMed:16923391, ECO:0000269\|PubMed:16931718, ECO:0000269\|PubMed:18026120, ECO:0000269\|PubMed:19033377, ECO:0000269\|PubMed:19410547, ECO:0000269\|PubMed:20479275, ECO:0000269\|PubMed:23917022, ECO:0000269\|PubMed:28502770, ECO:0000269\|PubMed:29301961}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:11030346, ECO:0000269\|PubMed:19324961, ECO:0000269\|PubMed:28502770, ECO:0000269\|PubMed:29301961}. Nucleus speckle {ECO:0000269\|PubMed:11030346, ECO:0000269\|PubMed:19324961}. Cytoplasm {ECO:0000269\|PubMed:11030346, ECO:0000269\|PubMed:19324961}. Note=Nucleocytoplasmic shuttling protein (PubMed:11030346). Travels to the cytoplasm as part of the exon junction complex (EJC) bound to mRNA. Colocalizes with the core EJC, ALYREF/THOC4, NXF1 and UAP56 in the nucleus and nuclear speckles (PubMed:19324961). {ECO:0000269\|PubMed:11030346, ECO:0000269\|PubMed:19324961}.
Tissue specificity:		Ubiquitous.
Disease:		Thrombocytopenia-absent radius syndrome (TAR) [MIM:274000]: An autosomal recessive disorder characterized by bilateral absence of the radii with the presence of both thumbs, thrombocytopenia, low numbers of megakaryocytes, and bleeding episodes in the first year of life. Thrombocytopenic episodes decrease with age. Skeletal anomalies range from absence of radii to virtual absence of upper limbs, with or without lower limb defects such as malformations of the hip and knee. {ECO:0000269\|PubMed:22366785}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the RBM8A family. {ECO:0000305}.
Sequence caution:		Sequence=AAG14951.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAG16782.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAG16782.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA. A chimeric cDNA originating from chromosomes 1 and 5.; Evidence={ECO:0000305};