Full text data of RBM8A
RBM8A
(RBM8)
[Confidence: low (only semi-automatic identification from reviews)]
RNA-binding protein 8A (Binder of OVCA1-1; BOV-1; RNA-binding motif protein 8A; RNA-binding protein Y14; Ribonucleoprotein RBM8A)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
RNA-binding protein 8A (Binder of OVCA1-1; BOV-1; RNA-binding motif protein 8A; RNA-binding protein Y14; Ribonucleoprotein RBM8A)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9Y5S9
ID RBM8A_HUMAN Reviewed; 174 AA.
AC Q9Y5S9; B3KQI9; Q6FHD1; Q6IQ40; Q9GZX8; Q9NZI4;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1999, sequence version 1.
DT 22-JAN-2014, entry version 161.
DE RecName: Full=RNA-binding protein 8A;
DE AltName: Full=Binder of OVCA1-1;
DE Short=BOV-1;
DE AltName: Full=RNA-binding motif protein 8A;
DE AltName: Full=RNA-binding protein Y14;
DE AltName: Full=Ribonucleoprotein RBM8A;
GN Name=RBM8A; Synonyms=RBM8; ORFNames=HSPC114, MDS014;
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).
RC TISSUE=Skeletal muscle;
RX PubMed=11004516; DOI=10.1016/S0167-4781(00)00090-7;
RA Conklin D.C., Rixon M.W., Kuestner R.E., Maurer M.F., Whitmore T.E.,
RA Millar R.P.;
RT "Cloning and gene expression of a novel human ribonucleoprotein.";
RL Biochim. Biophys. Acta 1492:465-469(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND INTERACTION WITH MAGOH.
RX PubMed=10662555; DOI=10.1006/geno.1999.6064;
RA Zhao X.F., Nowak N.J., Shows T.B., Aplan P.D.;
RT "MAGOH interacts with a novel RNA-binding protein.";
RL Genomics 63:145-148(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND INTERACTION WITH
RP OVCA1.
RC TISSUE=Brain;
RX PubMed=11013075; DOI=10.1006/geno.2000.6315;
RA Salicioni A.M., Xi M., Vanderveer L.A., Balsara B., Testa J.R.,
RA Dunbrack R.L. Jr., Godwin A.K.;
RT "Identification and structural analysis of human RBM8A and RBM8B: two
RT highly conserved RNA-binding motif proteins that interact with OVCA1,
RT a candidate tumor suppressor.";
RL Genomics 69:54-62(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CHARACTERIZATION.
RX PubMed=11030346; DOI=10.1016/S1097-2765(00)00065-4;
RA Kataoka N., Yong J., Kim V.N., Velazquez F., Perkinson R.A., Wang F.,
RA Dreyfuss G.;
RT "Pre-mRNA splicing imprints mRNA in the nucleus with a novel RNA-
RT binding protein that persists in the cytoplasm.";
RL Mol. Cell 6:673-682(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11707068; DOI=10.1006/geno.2001.6650;
RA Faurholm B., Millar R.P., Katz A.A.;
RT "The genes encoding the type II gonadotropin-releasing hormone
RT receptor and the ribonucleoprotein RBM8A in humans overlap in two
RT genomic loci.";
RL Genomics 78:15-18(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Hematopoietic stem cell;
RA Huang C., Qian B., Tu Y., Gu W., Wang Y., Han Z., Chen Z.;
RT "Novel genes expressed in hematopoietic stem/progenitor cells from
RT myelodysplastic syndrome patients.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for
RT 300 previously undefined genes expressed in CD34+ hematopoietic
RT stem/progenitor cells.";
RL Genome Res. 10:1546-1560(2000).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Teratocarcinoma;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-
RT length human cDNAs encoding secretion or membrane proteins from oligo-
RT capped cDNA libraries.";
RL DNA Res. 12:117-126(2005).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
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 [13]
RP IDENTIFICATION IN A MRNA SPLICING-DEPENDENT EXON JUNCTION COMPLEX
RP (EJC) WITH DEK; RNPS1; SRRM1 AND ALYREF/THOC4.
RX PubMed=11118221; DOI=10.1093/emboj/19.24.6860;
RA Le Hir H., Izaurralde E., Maquat L.E., Moore M.J.;
RT "The spliceosome deposits multiple proteins 20-24 nucleotides upstream
RT of mRNA exon-exon junctions.";
RL EMBO J. 19:6860-6869(2000).
RN [14]
RP INTERACTION WITH IPO13.
RX PubMed=11447110; DOI=10.1093/emboj/20.14.3685;
RA Mingot J.-M., Kostka S., Kraft R., Hartmann E., Goerlich D.;
RT "Importin 13: a novel mediator of nuclear import and export.";
RL EMBO J. 20:3685-3694(2001).
RN [15]
RP INTERACTION WITH ALYREF/THOC4 AND THE EXON JUNCTION COMPLEX.
RX PubMed=11707413; DOI=10.1093/emboj/20.22.6424;
RA Kataoka N., Diem M.D., Kim V.N., Yong J., Dreyfuss G.;
RT "Magoh, a human homolog of Drosophila mago nashi protein, is a
RT component of the splicing-dependent exon-exon junction complex.";
RL EMBO J. 20:6424-6433(2001).
RN [16]
RP IDENTIFICATION IN A MRNP COMPLEX WITH UPF3A AND UPF3B.
RX PubMed=11546873; DOI=10.1126/science.1062829;
RA Kim V.N., Kataoka N., Dreyfuss G.;
RT "Role of the nonsense-mediated decay factor hUpf3 in the splicing-
RT dependent exon-exon junction complex.";
RL Science 293:1832-1836(2001).
RN [17]
RP IDENTIFICATION IN A POST-SPLICING COMPLEX WITH NXF1; UPF1; UPF2;
RP UPF3A; UPF3B AND RNPS1.
RX PubMed=11546874; DOI=10.1126/science.1062786;
RA Lykke-Andersen J., Shu M.-D., Steitz J.A.;
RT "Communication of the position of exon-exon junctions to the mRNA
RT surveillance machinery by the protein RNPS1.";
RL Science 293:1836-1839(2001).
RN [18]
RP FUNCTION IN TRANSLATION, ASSOCIATION WITH POLYSOMES, AND RNA-BINDING.
RX PubMed=12121612; DOI=10.1016/S0960-9822(02)00902-8;
RA Dostie J., Dreyfuss G.;
RT "Translation is required to remove Y14 from mRNAs in the cytoplasm.";
RL Curr. Biol. 12:1060-1067(2002).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE
RP SPLICEOSOMAL C COMPLEX.
RX PubMed=11991638; DOI=10.1017/S1355838202021088;
RA Jurica M.S., Licklider L.J., Gygi S.P., Grigorieff N., Moore M.J.;
RT "Purification and characterization of native spliceosomes suitable for
RT three-dimensional structural analysis.";
RL RNA 8:426-439(2002).
RN [20]
RP INTERACTION WITH BAT1; RNPS1; SRRM1 AND ALYREF/THOC4.
RX PubMed=12944400; DOI=10.1074/jbc.M306856200;
RA McCracken S., Longman D., Johnstone I.L., Caceres J.F., Blencowe B.J.;
RT "An evolutionarily conserved role for SRm160 in 3'-end processing that
RT functions independently of exon junction complex formation.";
RL J. Biol. Chem. 278:44153-44160(2003).
RN [21]
RP FUNCTION IN NONSENSE-MEDIATED MRNA DECAY, AND INTERACTION WITH RENT3B.
RX PubMed=12718880; DOI=10.1016/S1097-2765(03)00142-4;
RA Gehring N.H., Neu-Yilik G., Schell T., Hentze M.W., Kulozik A.E.;
RT "Y14 and hUpf3b form an NMD-activating complex.";
RL Mol. Cell 11:939-949(2003).
RN [22]
RP FUNCTION, AND INTERACTION WITH MAGOH.
RX PubMed=12730685; DOI=10.1038/nsb926;
RA Fribourg S., Gatfield D., Izaurralde E., Conti E.;
RT "A novel mode of RBD-protein recognition in the Y14-Mago complex.";
RL Nat. Struct. Biol. 10:433-439(2003).
RN [23]
RP INTERACTION WITH WIBG.
RX PubMed=14968132; DOI=10.1038/sj.embor.7400091;
RA Bono F., Ebert J., Unterholzner L., Guettler T., Izaurralde E.,
RA Conti E.;
RT "Molecular insights into the interaction of PYM with the Mago-Y14 core
RT of the exon junction complex.";
RL EMBO Rep. 5:304-310(2004).
RN [24]
RP IDENTIFICATION IN A MRNA SPLICING-DEPENDENT EXON JUNCTION COMPLEX
RP (EJC) WITH RNPS1 AND SRRM1.
RX PubMed=14625303; DOI=10.1074/jbc.M307692200;
RA Kataoka N., Dreyfuss G.;
RT "A simple whole cell lysate system for in vitro splicing reveals a
RT stepwise assembly of the exon-exon junction complex.";
RL J. Biol. Chem. 279:7009-7013(2004).
RN [25]
RP FUNCTION, AND MUTAGENESIS OF 82-GLU-GLU-83; 106-LEU--ARG-108; LEU-118
RP AND 149-CYS-PHE-150.
RX PubMed=16209946; DOI=10.1016/j.molcel.2005.08.012;
RA Gehring N.H., Kunz J.B., Neu-Yilik G., Breit S., Viegas M.H.,
RA Hentze M.W., Kulozik A.E.;
RT "Exon-junction complex components specify distinct routes of nonsense-
RT mediated mRNA decay with differential cofactor requirements.";
RL Mol. Cell 20:65-75(2005).
RN [26]
RP IDENTIFICATION IN THE CORE EXON JUNCTION COMPLEX.
RX PubMed=16170325; DOI=10.1038/nsmb990;
RA Ballut L., Marchadier B., Baguet A., Tomasetto C., Seraphin B.,
RA Le Hir H.;
RT "The exon junction core complex is locked onto RNA by inhibition of
RT eIF4AIII ATPase activity.";
RL Nat. Struct. Mol. Biol. 12:861-869(2005).
RN [27]
RP IDENTIFICATION IN THE CORE EXON JUNCTION COMPLEX, IDENTIFICATION IN A
RP MRNA SPLICING-DEPENDENT EXON JUNCTION COMPLEX, AND MASS SPECTROMETRY.
RX PubMed=16314458; DOI=10.1261/rna.2155905;
RA Tange T.O., Shibuya T., Jurica M.S., Moore M.J.;
RT "Biochemical analysis of the EJC reveals two new factors and a stable
RT tetrameric protein core.";
RL RNA 11:1869-1883(2005).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [29]
RP INTERACTION WITH WIBG.
RX PubMed=18026120; DOI=10.1038/nsmb1321;
RA Diem M.D., Chan C.C., Younis I., Dreyfuss G.;
RT "PYM binds the cytoplasmic exon-junction complex and ribosomes to
RT enhance translation of spliced mRNAs.";
RL Nat. Struct. Mol. Biol. 14:1173-1179(2007).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42 AND SER-56, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [31]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [32]
RP FUNCTION IN MRNA TRANSLATION.
RX PubMed=19409878; DOI=10.1016/j.bbrc.2009.04.123;
RA Lee H.C., Choe J., Chi S.G., Kim Y.K.;
RT "Exon junction complex enhances translation of spliced mRNAs at
RT multiple steps.";
RL Biochem. Biophys. Res. Commun. 384:334-340(2009).
RN [33]
RP INTERACTION WITH WIBG.
RX PubMed=19410547; DOI=10.1016/j.cell.2009.02.042;
RA Gehring N.H., Lamprinaki S., Kulozik A.E., Hentze M.W.;
RT "Disassembly of exon junction complexes by PYM.";
RL Cell 137:536-548(2009).
RN [34]
RP SUBCELLULAR LOCATION.
RX PubMed=19324961; DOI=10.1261/rna.1387009;
RA Schmidt U., Im K.-B., Benzing C., Janjetovic S., Rippe K., Lichter P.,
RA Wachsmuth M.;
RT "Assembly and mobility of exon-exon junction complexes in living
RT cells.";
RL RNA 15:862-876(2009).
RN [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [36]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-24 AND SER-42, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [37]
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.,
RA Buerckstuemmer T., 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 [38]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-24; SER-42 AND SER-56, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [39]
RP FUNCTION.
RX PubMed=22203037; DOI=10.1128/MCB.06130-11;
RA Michelle L., Cloutier A., Toutant J., Shkreta L., Thibault P.,
RA Durand M., Garneau D., Gendron D., Lapointe E., Couture S., Le Hir H.,
RA Klinck R., Elela S.A., Prinos P., Chabot B.;
RT "Proteins associated with the exon junction complex also control the
RT alternative splicing of apoptotic regulators.";
RL Mol. Cell. Biol. 32:954-967(2012).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 50-155 IN COMPLEX WITH MAGOH.
RX PubMed=12781131; DOI=10.1016/S0960-9822(03)00328-2;
RA Lau C.K., Diem M.D., Dreyfuss G., Van Duyne G.D.;
RT "Structure of the Y14-Magoh core of the exon junction complex.";
RL Curr. Biol. 13:933-941(2003).
RN [41]
RP X-RAY CRYSTALLOGRAPHY (2.21 ANGSTROMS) OF 66-154 IN THE EJC COMPLEX
RP WITH CASC3; EIF4A3; MAGOH AND AMP-PNP.
RX PubMed=16923391; DOI=10.1016/j.cell.2006.08.006;
RA Bono F., Ebert J., Lorentzen E., Conti E.;
RT "The crystal structure of the exon junction complex reveals how it
RT maintains a stable grip on mRNA.";
RL Cell 126:713-725(2006).
RN [42]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 64-154 IN THE EJC COMPLEX
RP WITH CASC3; EIF4A3; MAGOH AND ADP-NP.
RX PubMed=16931718; DOI=10.1126/science.1131981;
RA Andersen C.B., Ballut L., Johansen J.S., Chamieh H., Nielsen K.H.,
RA Oliveira C.L., Pedersen J.S., Seraphin B., Le Hir H., Andersen G.R.;
RT "Structure of the exon junction core complex with a trapped DEAD-box
RT ATPase bound to RNA.";
RL Science 313:1968-1972(2006).
RN [43]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 51-174 IN THE EJC COMPLEX
RP WITH CASC3; EIF4A3; MAGOH AND TRANSITION STATE ANALOG ADP-ALF3.
RX PubMed=19033377; DOI=10.1261/rna.1283109;
RA Nielsen K.H., Chamieh H., Andersen C.B., Fredslund F., Hamborg K.,
RA Le Hir H., Andersen G.R.;
RT "Mechanism of ATP turnover inhibition in the EJC.";
RL RNA 15:67-75(2009).
CC -!- FUNCTION: Core component of the splicing-dependent multiprotein
CC exon junction complex (EJC) deposited at splice junctions on
CC mRNAs. The EJC is a dynamic structure consisting of core proteins
CC and several peripheral nuclear and cytoplasmic associated factors
CC that join the complex only transiently either during EJC assembly
CC or during subsequent mRNA metabolism. The EJC marks the position
CC of the exon-exon junction in the mature mRNA for the gene
CC expression machinery and the core components remain bound to
CC spliced mRNAs throughout all stages of mRNA metabolism thereby
CC influencing downstream processes including nuclear mRNA export,
CC subcellular mRNA localization, translation efficiency and
CC nonsense-mediated mRNA decay (NMD). The MAGOH-RBM8A heterodimer
CC inhibits the ATPase activity of EIF4A3, thereby trapping the ATP-
CC bound EJC core onto spliced mRNA in a stable conformation. The
CC MAGOH-RBM8A heterodimer interacts with the EJC key regulator
CC WIBG/PYM leading to EJC disassembly in the cytoplasm and
CC translation enhancement of EJC-bearing spliced mRNAs by recruiting
CC them to the ribosomal 48S preinitiation complex. Its removal from
CC cytoplasmic mRNAs requires translation initiation from EJC-bearing
CC spliced mRNAs. Associates preferentially with mRNAs produced by
CC splicing. Does not interact with pre-mRNAs, introns, or mRNAs
CC produced from intronless cDNAs. Associates with both nuclear mRNAs
CC and newly exported cytoplasmic mRNAs. The MAGOH-RBM8A heterodimer
CC is a component of the nonsense mediated decay (NMD) pathway.
CC Involved in the splicing modulation of BCL2L1/Bcl-X (and probably
CC other apoptotic genes); specifically inhibits formation of
CC proapoptotic isoforms such as Bcl-X(S); the function is different
CC from the established EJC assembly.
CC -!- SUBUNIT: Heterodimer with RBM8A. Part of the mRNA splicing-
CC dependent exon junction complex (EJC) complex; the core complex
CC contains CASC3, EIF4A3, MAGOH and RBM8A. Interacts with WIBG/PYM;
CC the interaction is direct and dissociates the EJC from spliced
CC mRNAs. Found in a post-splicing complex with NXF1, RBM8A, UPF1,
CC UPF2, UPF3A, UPF3B and RNPS1. Interacts with BAT1, MAGOH, OVCA1,
CC UPF3B, RNPS1, SRRM1 and ALYREF/THOC4. Interacts with IPO13; the
CC interaction mediates the nuclear import of the MAGOH-RBM8A
CC heterodimer. Identified in the spliceosome C complex. Associates
CC with polysomes.
CC -!- INTERACTION:
CC P38919:EIF4A3; NbExp=21; IntAct=EBI-447231, EBI-299104;
CC P61326:MAGOH; NbExp=22; IntAct=EBI-447231, EBI-299134;
CC Q96SB4:SRPK1; NbExp=2; IntAct=EBI-447231, EBI-539478;
CC P78362:SRPK2; NbExp=2; IntAct=EBI-447231, EBI-593303;
CC Q9H1J1:UPF3A; NbExp=4; IntAct=EBI-447231, EBI-521530;
CC Q9BZI7:UPF3B; NbExp=9; IntAct=EBI-447231, EBI-372780;
CC -!- SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Cytoplasm.
CC Note=Nucleocytoplasmic shuttling protein. Travels to the cytoplasm
CC as part of the exon junction complex (EJC) bound to mRNA.
CC Colocalizes with the core EJC, ALYREF/THOC4, NXF1 and UAP56 in the
CC nucleus and nuclear speckles.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=BOV-1a;
CC IsoId=Q9Y5S9-1; Sequence=Displayed;
CC Name=2; Synonyms=BOV-1b;
CC IsoId=Q9Y5S9-2; Sequence=VSP_005810;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- SIMILARITY: Belongs to the RBM8A family.
CC -!- SIMILARITY: Contains 1 RRM (RNA recognition motif) domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG14951.1; Type=Erroneous initiation;
CC Sequence=AAG16782.1; Type=Erroneous initiation;
CC Sequence=AAG16782.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA. A chimeric cDNA originating from chromosomes 1 and 5;
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DR EMBL; AF127761; AAD21089.1; -; mRNA.
DR EMBL; AF198620; AAF37551.1; -; mRNA.
DR EMBL; AF231511; AAG16781.1; -; mRNA.
DR EMBL; AF231512; AAG16782.1; ALT_INIT; mRNA.
DR EMBL; AF299118; AAG27091.1; -; mRNA.
DR EMBL; AF403012; AAL26999.1; -; Genomic_DNA.
DR EMBL; AF182415; AAG14951.1; ALT_INIT; mRNA.
DR EMBL; AF161463; AAF29078.1; -; mRNA.
DR EMBL; CR541823; CAG46622.1; -; mRNA.
DR EMBL; CR541805; CAG46604.1; -; mRNA.
DR EMBL; AK075009; BAG52051.1; -; mRNA.
DR EMBL; AL160282; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471244; EAW71419.1; -; Genomic_DNA.
DR EMBL; BC017088; AAH17088.1; -; mRNA.
DR RefSeq; NP_005096.1; NM_005105.4.
DR RefSeq; XP_005273042.1; XM_005272985.1.
DR RefSeq; XP_005277513.1; XM_005277456.1.
DR UniGene; Hs.591455; -.
DR PDB; 1P27; X-ray; 2.00 A; B/D=50-155.
DR PDB; 2HYI; X-ray; 2.30 A; B/H=64-154.
DR PDB; 2J0Q; X-ray; 3.20 A; D/G=66-174.
DR PDB; 2J0S; X-ray; 2.21 A; D=66-154.
DR PDB; 2XB2; X-ray; 3.40 A; D/Z=66-155.
DR PDB; 3EX7; X-ray; 2.30 A; B/G=51-174.
DR PDBsum; 1P27; -.
DR PDBsum; 2HYI; -.
DR PDBsum; 2J0Q; -.
DR PDBsum; 2J0S; -.
DR PDBsum; 2XB2; -.
DR PDBsum; 3EX7; -.
DR ProteinModelPortal; Q9Y5S9; -.
DR SMR; Q9Y5S9; 12-155.
DR DIP; DIP-33070N; -.
DR IntAct; Q9Y5S9; 36.
DR MINT; MINT-265248; -.
DR STRING; 9606.ENSP00000333001; -.
DR TCDB; 3.A.18.1.1; the nuclear mrna exporter (mrna-e) family.
DR PhosphoSite; Q9Y5S9; -.
DR DMDM; 10720244; -.
DR PaxDb; Q9Y5S9; -.
DR PRIDE; Q9Y5S9; -.
DR DNASU; 9939; -.
DR Ensembl; ENST00000330165; ENSP00000333001; ENSG00000131795.
DR Ensembl; ENST00000369307; ENSP00000358313; ENSG00000131795.
DR Ensembl; ENST00000578414; ENSP00000462894; ENSG00000265241.
DR Ensembl; ENST00000583313; ENSP00000463058; ENSG00000265241.
DR GeneID; 9939; -.
DR KEGG; hsa:9939; -.
DR UCSC; uc001ent.2; human.
DR CTD; 9939; -.
DR GeneCards; GC01P145507; -.
DR HGNC; HGNC:9905; RBM8A.
DR HPA; CAB012803; -.
DR HPA; HPA018403; -.
DR MIM; 605313; gene.
DR neXtProt; NX_Q9Y5S9; -.
DR Orphanet; 3320; Thrombocytopenia - absent radius.
DR PharmGKB; PA34270; -.
DR eggNOG; COG0724; -.
DR HOGENOM; HOG000183826; -.
DR HOVERGEN; HBG055173; -.
DR InParanoid; Q9Y5S9; -.
DR KO; K12876; -.
DR OMA; WILFVTS; -.
DR OrthoDB; EOG7C5MB6; -.
DR PhylomeDB; Q9Y5S9; -.
DR Reactome; REACT_1675; mRNA Processing.
DR Reactome; REACT_1788; Transcription.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR Reactome; REACT_78; Post-Elongation Processing of the Transcript.
DR ChiTaRS; RBM8A; human.
DR EvolutionaryTrace; Q9Y5S9; -.
DR GeneWiki; RBM8A; -.
DR NextBio; 37498; -.
DR PMAP-CutDB; Q9Y5S9; -.
DR PRO; PR:Q9Y5S9; -.
DR Bgee; Q9Y5S9; -.
DR CleanEx; HS_RBM8A; -.
DR Genevestigator; Q9Y5S9; -.
DR GO; GO:0071013; C:catalytic step 2 spliceosome; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0035145; C:exon-exon junction complex; IDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0003729; F:mRNA binding; NAS:UniProtKB.
DR GO; GO:0000166; F:nucleotide binding; IEA:InterPro.
DR GO; GO:0031124; P:mRNA 3'-end processing; TAS:Reactome.
DR GO; GO:0006406; P:mRNA export from nucleus; TAS:Reactome.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IC:UniProtKB.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IMP:UniProtKB.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IMP:UniProtKB.
DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
DR GO; GO:0006369; P:termination of RNA polymerase II transcription; TAS:Reactome.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait.
DR InterPro; IPR008111; RNA-bd_8.
DR InterPro; IPR000504; RRM_dom.
DR Pfam; PF00076; RRM_1; 1.
DR PRINTS; PR01738; RNABINDINGM8.
DR SMART; SM00360; RRM; 1.
DR PROSITE; PS50102; RRM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; mRNA processing; mRNA splicing; mRNA transport;
KW Nonsense-mediated mRNA decay; Nucleus; Phosphoprotein;
KW Reference proteome; RNA-binding; Spliceosome; Translation regulation;
KW Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 174 RNA-binding protein 8A.
FT /FTId=PRO_0000081763.
FT DOMAIN 73 151 RRM.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 24 24 Phosphoserine.
FT MOD_RES 42 42 Phosphoserine.
FT MOD_RES 56 56 Phosphoserine.
FT VAR_SEQ 44 44 Missing (in isoform 2).
FT /FTId=VSP_005810.
FT MUTAGEN 82 83 EE->RR: Impaired nonsense-mediated decay
FT activity.
FT MUTAGEN 106 108 LDR->RDE: Complete loss of nonsense-
FT mediated decay activity.
FT MUTAGEN 118 118 L->R: Complete loss of nonsense-mediated
FT decay activity.
FT MUTAGEN 149 150 CF->KA: Complete loss of nonsense-
FT mediated decay activity.
FT CONFLICT 130 130 A -> V (in Ref. 8; CAG46622).
FT STRAND 72 78
FT HELIX 86 93
FT HELIX 94 96
FT STRAND 99 106
FT TURN 108 110
FT STRAND 111 122
FT HELIX 124 134
FT STRAND 138 143
FT STRAND 145 153
SQ SEQUENCE 174 AA; 19889 MW; 70BBD03CDDFEECFE CRC64;
MADVLDLHEA GGEDFAMDED GDESIHKLKE KAKKRKGRGF GSEEGSRARM REDYDSVEQD
GDEPGPQRSV EGWILFVTGV HEEATEEDIH DKFAEYGEIK NIHLNLDRRT GYLKGYTLVE
YETYKEAQAA MEGLNGQDLM GQPISVDWCF VRGPPKGKRR GGRRRSRSPD RRRR
//
ID RBM8A_HUMAN Reviewed; 174 AA.
AC Q9Y5S9; B3KQI9; Q6FHD1; Q6IQ40; Q9GZX8; Q9NZI4;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1999, sequence version 1.
DT 22-JAN-2014, entry version 161.
DE RecName: Full=RNA-binding protein 8A;
DE AltName: Full=Binder of OVCA1-1;
DE Short=BOV-1;
DE AltName: Full=RNA-binding motif protein 8A;
DE AltName: Full=RNA-binding protein Y14;
DE AltName: Full=Ribonucleoprotein RBM8A;
GN Name=RBM8A; Synonyms=RBM8; ORFNames=HSPC114, MDS014;
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).
RC TISSUE=Skeletal muscle;
RX PubMed=11004516; DOI=10.1016/S0167-4781(00)00090-7;
RA Conklin D.C., Rixon M.W., Kuestner R.E., Maurer M.F., Whitmore T.E.,
RA Millar R.P.;
RT "Cloning and gene expression of a novel human ribonucleoprotein.";
RL Biochim. Biophys. Acta 1492:465-469(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND INTERACTION WITH MAGOH.
RX PubMed=10662555; DOI=10.1006/geno.1999.6064;
RA Zhao X.F., Nowak N.J., Shows T.B., Aplan P.D.;
RT "MAGOH interacts with a novel RNA-binding protein.";
RL Genomics 63:145-148(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND INTERACTION WITH
RP OVCA1.
RC TISSUE=Brain;
RX PubMed=11013075; DOI=10.1006/geno.2000.6315;
RA Salicioni A.M., Xi M., Vanderveer L.A., Balsara B., Testa J.R.,
RA Dunbrack R.L. Jr., Godwin A.K.;
RT "Identification and structural analysis of human RBM8A and RBM8B: two
RT highly conserved RNA-binding motif proteins that interact with OVCA1,
RT a candidate tumor suppressor.";
RL Genomics 69:54-62(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CHARACTERIZATION.
RX PubMed=11030346; DOI=10.1016/S1097-2765(00)00065-4;
RA Kataoka N., Yong J., Kim V.N., Velazquez F., Perkinson R.A., Wang F.,
RA Dreyfuss G.;
RT "Pre-mRNA splicing imprints mRNA in the nucleus with a novel RNA-
RT binding protein that persists in the cytoplasm.";
RL Mol. Cell 6:673-682(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11707068; DOI=10.1006/geno.2001.6650;
RA Faurholm B., Millar R.P., Katz A.A.;
RT "The genes encoding the type II gonadotropin-releasing hormone
RT receptor and the ribonucleoprotein RBM8A in humans overlap in two
RT genomic loci.";
RL Genomics 78:15-18(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Hematopoietic stem cell;
RA Huang C., Qian B., Tu Y., Gu W., Wang Y., Han Z., Chen Z.;
RT "Novel genes expressed in hematopoietic stem/progenitor cells from
RT myelodysplastic syndrome patients.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for
RT 300 previously undefined genes expressed in CD34+ hematopoietic
RT stem/progenitor cells.";
RL Genome Res. 10:1546-1560(2000).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Teratocarcinoma;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-
RT length human cDNAs encoding secretion or membrane proteins from oligo-
RT capped cDNA libraries.";
RL DNA Res. 12:117-126(2005).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
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 [13]
RP IDENTIFICATION IN A MRNA SPLICING-DEPENDENT EXON JUNCTION COMPLEX
RP (EJC) WITH DEK; RNPS1; SRRM1 AND ALYREF/THOC4.
RX PubMed=11118221; DOI=10.1093/emboj/19.24.6860;
RA Le Hir H., Izaurralde E., Maquat L.E., Moore M.J.;
RT "The spliceosome deposits multiple proteins 20-24 nucleotides upstream
RT of mRNA exon-exon junctions.";
RL EMBO J. 19:6860-6869(2000).
RN [14]
RP INTERACTION WITH IPO13.
RX PubMed=11447110; DOI=10.1093/emboj/20.14.3685;
RA Mingot J.-M., Kostka S., Kraft R., Hartmann E., Goerlich D.;
RT "Importin 13: a novel mediator of nuclear import and export.";
RL EMBO J. 20:3685-3694(2001).
RN [15]
RP INTERACTION WITH ALYREF/THOC4 AND THE EXON JUNCTION COMPLEX.
RX PubMed=11707413; DOI=10.1093/emboj/20.22.6424;
RA Kataoka N., Diem M.D., Kim V.N., Yong J., Dreyfuss G.;
RT "Magoh, a human homolog of Drosophila mago nashi protein, is a
RT component of the splicing-dependent exon-exon junction complex.";
RL EMBO J. 20:6424-6433(2001).
RN [16]
RP IDENTIFICATION IN A MRNP COMPLEX WITH UPF3A AND UPF3B.
RX PubMed=11546873; DOI=10.1126/science.1062829;
RA Kim V.N., Kataoka N., Dreyfuss G.;
RT "Role of the nonsense-mediated decay factor hUpf3 in the splicing-
RT dependent exon-exon junction complex.";
RL Science 293:1832-1836(2001).
RN [17]
RP IDENTIFICATION IN A POST-SPLICING COMPLEX WITH NXF1; UPF1; UPF2;
RP UPF3A; UPF3B AND RNPS1.
RX PubMed=11546874; DOI=10.1126/science.1062786;
RA Lykke-Andersen J., Shu M.-D., Steitz J.A.;
RT "Communication of the position of exon-exon junctions to the mRNA
RT surveillance machinery by the protein RNPS1.";
RL Science 293:1836-1839(2001).
RN [18]
RP FUNCTION IN TRANSLATION, ASSOCIATION WITH POLYSOMES, AND RNA-BINDING.
RX PubMed=12121612; DOI=10.1016/S0960-9822(02)00902-8;
RA Dostie J., Dreyfuss G.;
RT "Translation is required to remove Y14 from mRNAs in the cytoplasm.";
RL Curr. Biol. 12:1060-1067(2002).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE
RP SPLICEOSOMAL C COMPLEX.
RX PubMed=11991638; DOI=10.1017/S1355838202021088;
RA Jurica M.S., Licklider L.J., Gygi S.P., Grigorieff N., Moore M.J.;
RT "Purification and characterization of native spliceosomes suitable for
RT three-dimensional structural analysis.";
RL RNA 8:426-439(2002).
RN [20]
RP INTERACTION WITH BAT1; RNPS1; SRRM1 AND ALYREF/THOC4.
RX PubMed=12944400; DOI=10.1074/jbc.M306856200;
RA McCracken S., Longman D., Johnstone I.L., Caceres J.F., Blencowe B.J.;
RT "An evolutionarily conserved role for SRm160 in 3'-end processing that
RT functions independently of exon junction complex formation.";
RL J. Biol. Chem. 278:44153-44160(2003).
RN [21]
RP FUNCTION IN NONSENSE-MEDIATED MRNA DECAY, AND INTERACTION WITH RENT3B.
RX PubMed=12718880; DOI=10.1016/S1097-2765(03)00142-4;
RA Gehring N.H., Neu-Yilik G., Schell T., Hentze M.W., Kulozik A.E.;
RT "Y14 and hUpf3b form an NMD-activating complex.";
RL Mol. Cell 11:939-949(2003).
RN [22]
RP FUNCTION, AND INTERACTION WITH MAGOH.
RX PubMed=12730685; DOI=10.1038/nsb926;
RA Fribourg S., Gatfield D., Izaurralde E., Conti E.;
RT "A novel mode of RBD-protein recognition in the Y14-Mago complex.";
RL Nat. Struct. Biol. 10:433-439(2003).
RN [23]
RP INTERACTION WITH WIBG.
RX PubMed=14968132; DOI=10.1038/sj.embor.7400091;
RA Bono F., Ebert J., Unterholzner L., Guettler T., Izaurralde E.,
RA Conti E.;
RT "Molecular insights into the interaction of PYM with the Mago-Y14 core
RT of the exon junction complex.";
RL EMBO Rep. 5:304-310(2004).
RN [24]
RP IDENTIFICATION IN A MRNA SPLICING-DEPENDENT EXON JUNCTION COMPLEX
RP (EJC) WITH RNPS1 AND SRRM1.
RX PubMed=14625303; DOI=10.1074/jbc.M307692200;
RA Kataoka N., Dreyfuss G.;
RT "A simple whole cell lysate system for in vitro splicing reveals a
RT stepwise assembly of the exon-exon junction complex.";
RL J. Biol. Chem. 279:7009-7013(2004).
RN [25]
RP FUNCTION, AND MUTAGENESIS OF 82-GLU-GLU-83; 106-LEU--ARG-108; LEU-118
RP AND 149-CYS-PHE-150.
RX PubMed=16209946; DOI=10.1016/j.molcel.2005.08.012;
RA Gehring N.H., Kunz J.B., Neu-Yilik G., Breit S., Viegas M.H.,
RA Hentze M.W., Kulozik A.E.;
RT "Exon-junction complex components specify distinct routes of nonsense-
RT mediated mRNA decay with differential cofactor requirements.";
RL Mol. Cell 20:65-75(2005).
RN [26]
RP IDENTIFICATION IN THE CORE EXON JUNCTION COMPLEX.
RX PubMed=16170325; DOI=10.1038/nsmb990;
RA Ballut L., Marchadier B., Baguet A., Tomasetto C., Seraphin B.,
RA Le Hir H.;
RT "The exon junction core complex is locked onto RNA by inhibition of
RT eIF4AIII ATPase activity.";
RL Nat. Struct. Mol. Biol. 12:861-869(2005).
RN [27]
RP IDENTIFICATION IN THE CORE EXON JUNCTION COMPLEX, IDENTIFICATION IN A
RP MRNA SPLICING-DEPENDENT EXON JUNCTION COMPLEX, AND MASS SPECTROMETRY.
RX PubMed=16314458; DOI=10.1261/rna.2155905;
RA Tange T.O., Shibuya T., Jurica M.S., Moore M.J.;
RT "Biochemical analysis of the EJC reveals two new factors and a stable
RT tetrameric protein core.";
RL RNA 11:1869-1883(2005).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [29]
RP INTERACTION WITH WIBG.
RX PubMed=18026120; DOI=10.1038/nsmb1321;
RA Diem M.D., Chan C.C., Younis I., Dreyfuss G.;
RT "PYM binds the cytoplasmic exon-junction complex and ribosomes to
RT enhance translation of spliced mRNAs.";
RL Nat. Struct. Mol. Biol. 14:1173-1179(2007).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42 AND SER-56, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [31]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [32]
RP FUNCTION IN MRNA TRANSLATION.
RX PubMed=19409878; DOI=10.1016/j.bbrc.2009.04.123;
RA Lee H.C., Choe J., Chi S.G., Kim Y.K.;
RT "Exon junction complex enhances translation of spliced mRNAs at
RT multiple steps.";
RL Biochem. Biophys. Res. Commun. 384:334-340(2009).
RN [33]
RP INTERACTION WITH WIBG.
RX PubMed=19410547; DOI=10.1016/j.cell.2009.02.042;
RA Gehring N.H., Lamprinaki S., Kulozik A.E., Hentze M.W.;
RT "Disassembly of exon junction complexes by PYM.";
RL Cell 137:536-548(2009).
RN [34]
RP SUBCELLULAR LOCATION.
RX PubMed=19324961; DOI=10.1261/rna.1387009;
RA Schmidt U., Im K.-B., Benzing C., Janjetovic S., Rippe K., Lichter P.,
RA Wachsmuth M.;
RT "Assembly and mobility of exon-exon junction complexes in living
RT cells.";
RL RNA 15:862-876(2009).
RN [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [36]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-24 AND SER-42, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [37]
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.,
RA Buerckstuemmer T., 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 [38]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-24; SER-42 AND SER-56, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [39]
RP FUNCTION.
RX PubMed=22203037; DOI=10.1128/MCB.06130-11;
RA Michelle L., Cloutier A., Toutant J., Shkreta L., Thibault P.,
RA Durand M., Garneau D., Gendron D., Lapointe E., Couture S., Le Hir H.,
RA Klinck R., Elela S.A., Prinos P., Chabot B.;
RT "Proteins associated with the exon junction complex also control the
RT alternative splicing of apoptotic regulators.";
RL Mol. Cell. Biol. 32:954-967(2012).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 50-155 IN COMPLEX WITH MAGOH.
RX PubMed=12781131; DOI=10.1016/S0960-9822(03)00328-2;
RA Lau C.K., Diem M.D., Dreyfuss G., Van Duyne G.D.;
RT "Structure of the Y14-Magoh core of the exon junction complex.";
RL Curr. Biol. 13:933-941(2003).
RN [41]
RP X-RAY CRYSTALLOGRAPHY (2.21 ANGSTROMS) OF 66-154 IN THE EJC COMPLEX
RP WITH CASC3; EIF4A3; MAGOH AND AMP-PNP.
RX PubMed=16923391; DOI=10.1016/j.cell.2006.08.006;
RA Bono F., Ebert J., Lorentzen E., Conti E.;
RT "The crystal structure of the exon junction complex reveals how it
RT maintains a stable grip on mRNA.";
RL Cell 126:713-725(2006).
RN [42]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 64-154 IN THE EJC COMPLEX
RP WITH CASC3; EIF4A3; MAGOH AND ADP-NP.
RX PubMed=16931718; DOI=10.1126/science.1131981;
RA Andersen C.B., Ballut L., Johansen J.S., Chamieh H., Nielsen K.H.,
RA Oliveira C.L., Pedersen J.S., Seraphin B., Le Hir H., Andersen G.R.;
RT "Structure of the exon junction core complex with a trapped DEAD-box
RT ATPase bound to RNA.";
RL Science 313:1968-1972(2006).
RN [43]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 51-174 IN THE EJC COMPLEX
RP WITH CASC3; EIF4A3; MAGOH AND TRANSITION STATE ANALOG ADP-ALF3.
RX PubMed=19033377; DOI=10.1261/rna.1283109;
RA Nielsen K.H., Chamieh H., Andersen C.B., Fredslund F., Hamborg K.,
RA Le Hir H., Andersen G.R.;
RT "Mechanism of ATP turnover inhibition in the EJC.";
RL RNA 15:67-75(2009).
CC -!- FUNCTION: Core component of the splicing-dependent multiprotein
CC exon junction complex (EJC) deposited at splice junctions on
CC mRNAs. The EJC is a dynamic structure consisting of core proteins
CC and several peripheral nuclear and cytoplasmic associated factors
CC that join the complex only transiently either during EJC assembly
CC or during subsequent mRNA metabolism. The EJC marks the position
CC of the exon-exon junction in the mature mRNA for the gene
CC expression machinery and the core components remain bound to
CC spliced mRNAs throughout all stages of mRNA metabolism thereby
CC influencing downstream processes including nuclear mRNA export,
CC subcellular mRNA localization, translation efficiency and
CC nonsense-mediated mRNA decay (NMD). The MAGOH-RBM8A heterodimer
CC inhibits the ATPase activity of EIF4A3, thereby trapping the ATP-
CC bound EJC core onto spliced mRNA in a stable conformation. The
CC MAGOH-RBM8A heterodimer interacts with the EJC key regulator
CC WIBG/PYM leading to EJC disassembly in the cytoplasm and
CC translation enhancement of EJC-bearing spliced mRNAs by recruiting
CC them to the ribosomal 48S preinitiation complex. Its removal from
CC cytoplasmic mRNAs requires translation initiation from EJC-bearing
CC spliced mRNAs. Associates preferentially with mRNAs produced by
CC splicing. Does not interact with pre-mRNAs, introns, or mRNAs
CC produced from intronless cDNAs. Associates with both nuclear mRNAs
CC and newly exported cytoplasmic mRNAs. The MAGOH-RBM8A heterodimer
CC is a component of the nonsense mediated decay (NMD) pathway.
CC Involved in the splicing modulation of BCL2L1/Bcl-X (and probably
CC other apoptotic genes); specifically inhibits formation of
CC proapoptotic isoforms such as Bcl-X(S); the function is different
CC from the established EJC assembly.
CC -!- SUBUNIT: Heterodimer with RBM8A. Part of the mRNA splicing-
CC dependent exon junction complex (EJC) complex; the core complex
CC contains CASC3, EIF4A3, MAGOH and RBM8A. Interacts with WIBG/PYM;
CC the interaction is direct and dissociates the EJC from spliced
CC mRNAs. Found in a post-splicing complex with NXF1, RBM8A, UPF1,
CC UPF2, UPF3A, UPF3B and RNPS1. Interacts with BAT1, MAGOH, OVCA1,
CC UPF3B, RNPS1, SRRM1 and ALYREF/THOC4. Interacts with IPO13; the
CC interaction mediates the nuclear import of the MAGOH-RBM8A
CC heterodimer. Identified in the spliceosome C complex. Associates
CC with polysomes.
CC -!- INTERACTION:
CC P38919:EIF4A3; NbExp=21; IntAct=EBI-447231, EBI-299104;
CC P61326:MAGOH; NbExp=22; IntAct=EBI-447231, EBI-299134;
CC Q96SB4:SRPK1; NbExp=2; IntAct=EBI-447231, EBI-539478;
CC P78362:SRPK2; NbExp=2; IntAct=EBI-447231, EBI-593303;
CC Q9H1J1:UPF3A; NbExp=4; IntAct=EBI-447231, EBI-521530;
CC Q9BZI7:UPF3B; NbExp=9; IntAct=EBI-447231, EBI-372780;
CC -!- SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Cytoplasm.
CC Note=Nucleocytoplasmic shuttling protein. Travels to the cytoplasm
CC as part of the exon junction complex (EJC) bound to mRNA.
CC Colocalizes with the core EJC, ALYREF/THOC4, NXF1 and UAP56 in the
CC nucleus and nuclear speckles.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=BOV-1a;
CC IsoId=Q9Y5S9-1; Sequence=Displayed;
CC Name=2; Synonyms=BOV-1b;
CC IsoId=Q9Y5S9-2; Sequence=VSP_005810;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- SIMILARITY: Belongs to the RBM8A family.
CC -!- SIMILARITY: Contains 1 RRM (RNA recognition motif) domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG14951.1; Type=Erroneous initiation;
CC Sequence=AAG16782.1; Type=Erroneous initiation;
CC Sequence=AAG16782.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA. A chimeric cDNA originating from chromosomes 1 and 5;
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DR EMBL; AF127761; AAD21089.1; -; mRNA.
DR EMBL; AF198620; AAF37551.1; -; mRNA.
DR EMBL; AF231511; AAG16781.1; -; mRNA.
DR EMBL; AF231512; AAG16782.1; ALT_INIT; mRNA.
DR EMBL; AF299118; AAG27091.1; -; mRNA.
DR EMBL; AF403012; AAL26999.1; -; Genomic_DNA.
DR EMBL; AF182415; AAG14951.1; ALT_INIT; mRNA.
DR EMBL; AF161463; AAF29078.1; -; mRNA.
DR EMBL; CR541823; CAG46622.1; -; mRNA.
DR EMBL; CR541805; CAG46604.1; -; mRNA.
DR EMBL; AK075009; BAG52051.1; -; mRNA.
DR EMBL; AL160282; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471244; EAW71419.1; -; Genomic_DNA.
DR EMBL; BC017088; AAH17088.1; -; mRNA.
DR RefSeq; NP_005096.1; NM_005105.4.
DR RefSeq; XP_005273042.1; XM_005272985.1.
DR RefSeq; XP_005277513.1; XM_005277456.1.
DR UniGene; Hs.591455; -.
DR PDB; 1P27; X-ray; 2.00 A; B/D=50-155.
DR PDB; 2HYI; X-ray; 2.30 A; B/H=64-154.
DR PDB; 2J0Q; X-ray; 3.20 A; D/G=66-174.
DR PDB; 2J0S; X-ray; 2.21 A; D=66-154.
DR PDB; 2XB2; X-ray; 3.40 A; D/Z=66-155.
DR PDB; 3EX7; X-ray; 2.30 A; B/G=51-174.
DR PDBsum; 1P27; -.
DR PDBsum; 2HYI; -.
DR PDBsum; 2J0Q; -.
DR PDBsum; 2J0S; -.
DR PDBsum; 2XB2; -.
DR PDBsum; 3EX7; -.
DR ProteinModelPortal; Q9Y5S9; -.
DR SMR; Q9Y5S9; 12-155.
DR DIP; DIP-33070N; -.
DR IntAct; Q9Y5S9; 36.
DR MINT; MINT-265248; -.
DR STRING; 9606.ENSP00000333001; -.
DR TCDB; 3.A.18.1.1; the nuclear mrna exporter (mrna-e) family.
DR PhosphoSite; Q9Y5S9; -.
DR DMDM; 10720244; -.
DR PaxDb; Q9Y5S9; -.
DR PRIDE; Q9Y5S9; -.
DR DNASU; 9939; -.
DR Ensembl; ENST00000330165; ENSP00000333001; ENSG00000131795.
DR Ensembl; ENST00000369307; ENSP00000358313; ENSG00000131795.
DR Ensembl; ENST00000578414; ENSP00000462894; ENSG00000265241.
DR Ensembl; ENST00000583313; ENSP00000463058; ENSG00000265241.
DR GeneID; 9939; -.
DR KEGG; hsa:9939; -.
DR UCSC; uc001ent.2; human.
DR CTD; 9939; -.
DR GeneCards; GC01P145507; -.
DR HGNC; HGNC:9905; RBM8A.
DR HPA; CAB012803; -.
DR HPA; HPA018403; -.
DR MIM; 605313; gene.
DR neXtProt; NX_Q9Y5S9; -.
DR Orphanet; 3320; Thrombocytopenia - absent radius.
DR PharmGKB; PA34270; -.
DR eggNOG; COG0724; -.
DR HOGENOM; HOG000183826; -.
DR HOVERGEN; HBG055173; -.
DR InParanoid; Q9Y5S9; -.
DR KO; K12876; -.
DR OMA; WILFVTS; -.
DR OrthoDB; EOG7C5MB6; -.
DR PhylomeDB; Q9Y5S9; -.
DR Reactome; REACT_1675; mRNA Processing.
DR Reactome; REACT_1788; Transcription.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR Reactome; REACT_78; Post-Elongation Processing of the Transcript.
DR ChiTaRS; RBM8A; human.
DR EvolutionaryTrace; Q9Y5S9; -.
DR GeneWiki; RBM8A; -.
DR NextBio; 37498; -.
DR PMAP-CutDB; Q9Y5S9; -.
DR PRO; PR:Q9Y5S9; -.
DR Bgee; Q9Y5S9; -.
DR CleanEx; HS_RBM8A; -.
DR Genevestigator; Q9Y5S9; -.
DR GO; GO:0071013; C:catalytic step 2 spliceosome; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0035145; C:exon-exon junction complex; IDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0003729; F:mRNA binding; NAS:UniProtKB.
DR GO; GO:0000166; F:nucleotide binding; IEA:InterPro.
DR GO; GO:0031124; P:mRNA 3'-end processing; TAS:Reactome.
DR GO; GO:0006406; P:mRNA export from nucleus; TAS:Reactome.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IC:UniProtKB.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IMP:UniProtKB.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IMP:UniProtKB.
DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
DR GO; GO:0006369; P:termination of RNA polymerase II transcription; TAS:Reactome.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait.
DR InterPro; IPR008111; RNA-bd_8.
DR InterPro; IPR000504; RRM_dom.
DR Pfam; PF00076; RRM_1; 1.
DR PRINTS; PR01738; RNABINDINGM8.
DR SMART; SM00360; RRM; 1.
DR PROSITE; PS50102; RRM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; mRNA processing; mRNA splicing; mRNA transport;
KW Nonsense-mediated mRNA decay; Nucleus; Phosphoprotein;
KW Reference proteome; RNA-binding; Spliceosome; Translation regulation;
KW Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 174 RNA-binding protein 8A.
FT /FTId=PRO_0000081763.
FT DOMAIN 73 151 RRM.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 24 24 Phosphoserine.
FT MOD_RES 42 42 Phosphoserine.
FT MOD_RES 56 56 Phosphoserine.
FT VAR_SEQ 44 44 Missing (in isoform 2).
FT /FTId=VSP_005810.
FT MUTAGEN 82 83 EE->RR: Impaired nonsense-mediated decay
FT activity.
FT MUTAGEN 106 108 LDR->RDE: Complete loss of nonsense-
FT mediated decay activity.
FT MUTAGEN 118 118 L->R: Complete loss of nonsense-mediated
FT decay activity.
FT MUTAGEN 149 150 CF->KA: Complete loss of nonsense-
FT mediated decay activity.
FT CONFLICT 130 130 A -> V (in Ref. 8; CAG46622).
FT STRAND 72 78
FT HELIX 86 93
FT HELIX 94 96
FT STRAND 99 106
FT TURN 108 110
FT STRAND 111 122
FT HELIX 124 134
FT STRAND 138 143
FT STRAND 145 153
SQ SEQUENCE 174 AA; 19889 MW; 70BBD03CDDFEECFE CRC64;
MADVLDLHEA GGEDFAMDED GDESIHKLKE KAKKRKGRGF GSEEGSRARM REDYDSVEQD
GDEPGPQRSV EGWILFVTGV HEEATEEDIH DKFAEYGEIK NIHLNLDRRT GYLKGYTLVE
YETYKEAQAA MEGLNGQDLM GQPISVDWCF VRGPPKGKRR GGRRRSRSPD RRRR
//
MIM
605313
*RECORD*
*FIELD* NO
605313
*FIELD* TI
*605313 RNA-BINDING MOTIF PROTEIN 8A; RBM8A
;;RNA-BINDING MOTIF PROTEIN 8; RBM8;;
Y14
read more*FIELD* TX
DESCRIPTION
The RBM8A gene encodes Y14, 1 of the 4 components of the exon-junction
complex (EJC), which is involved in basic cellular functions such as
nuclear export and subcellular localization of specific transcripts,
translational enhancement, and nonsense-mediated RNA decay (NMD)
(summary by Albers et al., 2012).
CLONING
Mago nashi (MAGOH; 602603), meaning grandchildless, is the homolog of a
Drosophila protein required for normal germ plasm development in fly
embryos. By performing a yeast 2-hybrid screen on a fetal brain cDNA
library with MAGOH as the bait, Zhao et al. (2000) recovered a cDNA
encoding RBM8. The 173-amino acid RBM8 protein is more than 93%
identical to the mouse and zebrafish sequences, and the mouse
differences are all accounted for by an 11-amino acid N-terminal
insertion and another single-residue insertion in the mouse sequence.
Exchange partner and GST pull-down assays confirmed the MAGOH-RBM8
interaction and showed that RBM8 is expressed as a 26-kD protein,
slightly larger than the predicted mass of 23 kD. Northern blot analysis
detected a major RBM8 transcript of less than 1.0 kb in all tissues
tested, with weakest expression in pancreas and brain.
By searching an EST database for homologs of the gonadotropin-releasing
hormone receptor (GNRHR; 138850), followed by 5-prime RACE on a skeletal
muscle cDNA library, Conklin et al. (2000) identified a cDNA encoding
RBM8. Northern blot analysis detected a major 0.9-kb transcript in all
tissues tested. Sequence analysis of the 174-amino acid protein
predicted an RNA-binding domain, which is composed of 2 amphipathic
alpha helices packed against a 4-stranded beta sheet, and a C-terminal
arg-rich segment.
By performing a yeast 2-hybrid screen on a HeLa cell cDNA library to
identify potential cargoes for RAN-binding protein-5 (RANBP5; 602008),
Kataoka et al. (2000) isolated cDNAs encoding RBM8, which they called
Y14. RBM8 encodes a predicted 174-amino acid, predominantly nuclear
nucleocytoplasmic shuttling protein.
Salicioni et al. (2000) used a yeast 2-hybrid screen to identify cDNAs
from a human fetal brain cDNA library encoding proteins that interact
with OVCA1 (603527), a candidate tumor suppressor protein. They
identified cDNAs, which they initially referred to as BOV1, that
appeared to encode a new member of the conserved RNA-binding motif
protein family. One of the cDNAs isolated was identical to RBM8A;
another, designated RBM8B, was thought by Salicioni et al. (2000) to be
a novel functional gene, but was later determined to be a pseudogene.
Northern blot analysis revealed that BOV1 is ubiquitously expressed as 3
distinct mRNA species of 1, 3.2, and 5.8 kb.
GENE FUNCTION
Kataoka et al. (2000) found that RBM8 associates preferentially with
mRNAs produced by splicing and not with pre-mRNAs, introns, or mRNAs
produced from intronless cDNAs. RBM8 associates with both nuclear mRNAs
and newly exported cytoplasmic mRNAs. Splicing of a single intron is
sufficient for RBM8 association. RBM8-containing nuclear complexes are
different from general heterogeneous nuclear ribonucleoprotein (hnRNP)
complexes in that they contain hnRNP proteins and several unique
proteins, including the mRNA export factor TAP (NXF1; 602647). Thus,
RBM8 defines novel intermediates in the pathway of gene expression,
postsplicing nuclear preexport mRNPs, and newly exported cytoplasmic
mRNPs, whose composition is established by splicing. These findings
suggested that pre-mRNA splicing imprints mRNA with a unique set of
proteins that persists in the cytoplasm and thereby communicates the
history of the transcript.
Kim et al. (2001) analyzed the binding of RBM8A, which they called Y14,
to pre-mRNAs injected into nuclei of Xenopus oocytes. They found that
RBM8A stably bound mRNA sequences approximately -20 nucleotides upstream
of exon-exon junctions.
Oskar mRNA localization at the posterior pole of the Drosophila oocyte
is essential for germline and abdomen formation in the future embryo.
Y14/RBM8 and MAGOH (602603), human homologs of nuclear shuttling
proteins required for oskar mRNA localization, are core components of
the exon-exon junction complex (EJC). The EJC is deposited on mRNAs in a
splicing-dependent manner, 20 to 24 nucleotides upstream of exon-exon
junctions, independent of the RNA sequence. This indicates a possible
role of splicing in oskar mRNA localization, challenging the established
notion that the oskar 3-prime untranslated region is sufficient for this
process. Hachet and Ephrussi (2004) demonstrated that splicing at the
first exon-exon junction of oskar RNA is essential for oskar mRNA
localization at the posterior pole. They revisited the issue of
sufficiency of the oskar 3-prime untranslated region for posterior
localization and showed that the localization of unrelated transcripts
bearing the oskar 3-prime untranslated region is mediated by endogenous
oskar mRNA. Hachet and Ephrussi (2004) concluded that their results
revealed an important new function for splicing: regulation of messenger
ribonucleoprotein complex assembly and organization for mRNA cytoplasmic
localization.
Albers et al. (2012) showed that RBM8A is expressed in all hematopoietic
lineages, and that its encoded protein sequence is highly conserved
between species. Albers et al. (2012) suggested that, given the
important functions of the EJC, it is likely that a complete lack of Y14
in humans is not viable. Indeed, in Drosophila melanogaster, knockdown
of its ortholog tsu leads to major defects in abdomen formation (Hachet
and Ephrussi, 2001), and Albers et al. (2012) found that knockdown of
the orthologous rbm8a transcript in Danio rerio using antisense
morpholinos resulted in extreme malformations and death at 2 days
post-fertilization.
GENE STRUCTURE
Albers et al. (2012) determined that the RBM8A gene comprises 6 exons.
MAPPING
By PCR and radiation hybrid analysis, Zhao et al. (2000) mapped the
RBM8A gene to 1q12. Conklin et al. (2000) mapped the RBM8 gene to
14q21-q23 using radiation hybrid analysis, but it appears that the
sequence on chromosome 14 is a pseudogene.
MOLECULAR GENETICS
It had been shown that an inherited or de novo deletion on chromosome
1q21.1 (Klopocki et al., 2007) is found in the majority of individuals
with TAR syndrome (274000), but the apparent autosomal recessive nature
of that syndrome required the existence of an additional causative
allele. To identify the additional causative allele, Albers et al.
(2012) selected 5 individuals with TAR of European ancestry who had the
1q21.1 deletion and sequenced their exomes, but were unable to find
TAR-associated coding mutations in any gene. However, 4 of the cases
carried the minor allele of a low-frequency SNP in the 5-prime UTR of
the RBM8A gene (dbSNP rs139428292; 605313.0001), while the remaining
case carried a previously unknown SNP in the first intron of the same
gene (605313.0002). Genotyping by Sanger sequencing of another 48 cases
of European ancestry identified the 2 SNPs in 35 and 11 samples,
respectively. In the 25 trios where the deletion in the child was not a
de novo event, Albers et al. (2012) confirmed that the deletion and the
newly identified SNPs were inherited from different parents. The minor
allele frequency of the 5-prime UTR and intronic SNPs were 3.05% and
0.42%, respectively, in 7,504 healthy individuals of the Cambridge
BioResource, and the deletion was absent from 5,919 shared healthy
controls of the Wellcome Trust Case Control Consortium. There were 2 TAR
cases who did not carry the 1q21.1 deletion but were found to carry the
5-prime UTR SNP. Albers et al. (2012) identified a 4-bp frameshift
insertion at the start of the fourth exon (605313.0003) in the first
case and established that the noncoding SNP and insertion were on
different chromosomes; in the second case, they identified a nonsense
mutation in the last exon of RBM8A (605313.0004). Both mutations were
absent from 458 exome samples of the 1000 Genomes Project and 416
samples from the Cohorte Lausannoise. Albers et al. (2012) concluded
that in the vast majority of cases, compound inheritance of a rare null
allele (containing a deletion, frameshift mutation, or encoded premature
stop codon) and 1 of 2 low-frequency noncoding SNPs in RBM8A causes TAR
syndrome. Albers et al. (2012) showed that the 2 regulatory SNPs result
in diminished RBM8A transcription in vitro and that expression of Y14 is
reduced in platelets from individuals with TAR. Albers et al. (2012)
concluded that their data implicated Y14 insufficiency and, presumably,
an EJC defect as the cause of TAR syndrome.
Given the expression of Y14 in hematopoietic lineages and major defects
observed in Drosophila and zebrafish resulting from knockdown of the
respective Y14 orthologs, Albers et al. (2012) suggested that their
results are compatible with both a dose-effect phenomenon and a
lineage-dependent deficiency in Y14. The possibility of a dose-effect
phenomenon was supported by the observation that simple
haploinsufficiency is not sufficient to create an aberrant phenotype, as
evidenced by the seemingly healthy carriers of the 1q21.1 deletion.
Albers et al. (2012) did not observe an effect on platelet count for
either the 5-prime UTR or the intronic SNP in the 403 and 59 individuals
from the Cambridge BioResource who carried the minor allele for each
SNP, respectively. The authors suggested that compound inheritance of a
null allele together with the minor allele of 1 of the 2 regulatory SNPs
brings Y14 levels below a critical threshold in certain tissues. The
cell line-dependent effect shown in luciferase assays suggested a
combinatorial binding of transcription factors, including EVI1 (165215),
in the context of regulatory SNPs.
*FIELD* AV
.0001
THROMBOCYTOPENIA-ABSENT RADIUS SYNDROME
RBM8A, 5-PRIME UTR, G-A (dbSNP rs139428292)
In 41 of 55 patients with thrombocytopenia-absent radius syndrome (TAR;
274000), Albers et al. (2012) identified the presence of the minor
allele (A) of a G-to-A SNP, dbSNP rs139428292 (chr1:145507646, GRCh37),
in the 5-prime untranslated region (UTR) of the RBM8A gene. In 39 of
these patients this SNP was found in compound heterozygosity with a
200-kb deletion including the RBM8A gene and 10 other genes; in 2
patients the SNP occurred in compound heterozygosity with 1 of 2 null
mutations in the RBM8A gene. The minor allele frequency of the SNP dbSNP
rs139428292 was 3.05% in 7,504 healthy individuals of the Cambridge
BioResource. This SNP resulted in diminished RBM8A transcription in
vitro.
.0002
THROMBOCYTOPENIA-ABSENT RADIUS SYNDROME
RBM8A, IVS1, G-C
In 12 of 55 patients with thrombocytopenia-absent radius syndrome (TAR;
274000), Albers et al. (2012) identified the presence of the minor
allele (C) of a SNP in the first intron of the RBM8A gene
(chr1:145507765, GRCh37). The SNP occurred in compound heterozygosity
with a 200-kb deletion including the RBM8A gene and 10 other genes. The
minor allele frequency of this intronic SNP was 0.42% in 7,504 healthy
individuals of the Cambridge BioResource. This SNP resulted in
diminished RBM8A transcription in vitro.
.0003
THROMBOCYTOPENIA-ABSENT RADIUS SYNDROME
RBM8A, 4-BP INS, EX4
In a patient with thrombocytopenia-absent radius syndrome (TAR; 274000),
Albers et al. (2012) found compound heterozygosity for a 4-bp insertion
(AGCG, chr1:145508476, GRCh37) in exon 4 of the RBM8A gene, resulting in
frameshift, and a SNP in the 5-prime UTR (605313.0001).
.0004
THROMBOCYTOPENIA-ABSENT RADIUS SYNDROME
RBM8A, C-T, EX6
In a patient with thrombocytopenia-absent radius syndrome (TAR; 274000),
Albers et al. (2012) found compound heterozygosity for a premature
termination mutation in the last exon of the RBM8A gene (C-T,
chr1:145509173, GRCh37) and a SNP in the 5-prime UTR (605313.0001).
*FIELD* RF
1. Albers, C. A.; Paul, D. S.; Schulze, H.; Freson, K.; Stephens,
J. C.; Smethurst, P. A.; Jolley, J. D.; Cvejic, A.; Kostadima, M.;
Bertone, P.; Breuning, M. H.; Debili, N.; and 19 others: Compound
inheritance of a low-frequency regulatory SNP and a rare null mutation
in exon-junction complex subunit RBM8A causes TAR syndrome. Nature
Genet. 44: 435-439, 2012.
2. Conklin, D. C.; Rixon, M. W.; Kuestner, R. E.; Maurer, M. F.; Whitmore,
T. E.; Millar, R. P.: Cloning and gene expression of a novel human
ribonucleoprotein. Biochim. Biophys. Acta 1492: 465-469, 2000.
3. Hachet, O.; Ephrussi, A.: Drosophila Y14 shuttles to the posterior
of the oocyte and is required for oskar mRNA transport. Curr. Biol. 11:
1666-1674, 2001.
4. Hachet, O.; Ephrussi, A.: Splicing of oskar RNA in the nucleus
is coupled to its cytoplasmic localization. Nature 428: 959-963,
2004.
5. Kataoka, N.; Yong, J.; Kim, V. N.; Velazquez, F.; Perkinson, R.
A.; Wang, F.; Dreyfuss, G.: Pre-mRNA splicing imprints mRNA in the
nucleus with a novel RNA-binding protein that persists in the cytoplasm. Molec.
Cell 6: 673-682, 2000.
6. Kim, V. N.; Yong, J.; Kataoka, N.; Abel, L.; Diem, M. D.; Dreyfuss,
G.: The Y14 protein communicates to the cytoplasm the position of
exon-exon junctions. EMBO J. 20: 2062-2068, 2001.
7. Klopocki, E.; Schulze, H.; Strauss, G.; Ott, C.-E.; Hall, J.; Trotier,
F.; Fleischhauer, S.; Greenhalgh, L.; Newbury-Ecob, R. A.; Neumann,
L. M.; Habenicht, R.; Konig, R.; Seemanova, E.; Megarbane, A.; Ropers,
H.-H.; Ullmann, R.; Horn, D.; Mundlos, S.: Complex inheritance pattern
resembling autosomal recessive inheritance involving a microdeletion
in thrombocytopenia-absent radius syndrome. Am. J. Hum. Genet. 80:
232-240, 2007.
8. Salicioni, A. M.; Xi. M.; Vanderveer, L. A.; Balsara, B.; Testa,
J. R.; Dunbrack, R. L., Jr.; Godwin, A. K.: Identification and structural
analysis of human RBM8A and RBM8B: two highly conserved RNA-binding
motif proteins that interact with OVCA1, a candidate tumor suppressor. Genomics 69:
54-62, 2000.
9. Zhao, X.-F.; Nowak, N. J.; Shows, T. B.; Aplan, P. D.: MAGOH interacts
with a novel RNA-binding protein. Genomics 63: 145-148, 2000.
*FIELD* CN
Ada Hamosh - updated: 4/18/2012
Ada Hamosh - updated: 4/27/2004
Patricia A. Hartz - updated: 1/16/2003
Carol A. Bocchini - updated: 12/21/2000
Paul J. Converse - updated: 11/9/2000
*FIELD* CD
Stylianos E. Antonarakis: 10/2/2000
*FIELD* ED
alopez: 04/19/2012
alopez: 4/18/2012
terry: 4/18/2012
wwang: 3/26/2007
alopez: 4/27/2004
terry: 4/27/2004
cwells: 1/17/2003
terry: 1/16/2003
mgross: 10/7/2002
carol: 12/14/2001
carol: 12/26/2000
carol: 12/21/2000
mgross: 11/9/2000
mgross: 10/2/2000
*RECORD*
*FIELD* NO
605313
*FIELD* TI
*605313 RNA-BINDING MOTIF PROTEIN 8A; RBM8A
;;RNA-BINDING MOTIF PROTEIN 8; RBM8;;
Y14
read more*FIELD* TX
DESCRIPTION
The RBM8A gene encodes Y14, 1 of the 4 components of the exon-junction
complex (EJC), which is involved in basic cellular functions such as
nuclear export and subcellular localization of specific transcripts,
translational enhancement, and nonsense-mediated RNA decay (NMD)
(summary by Albers et al., 2012).
CLONING
Mago nashi (MAGOH; 602603), meaning grandchildless, is the homolog of a
Drosophila protein required for normal germ plasm development in fly
embryos. By performing a yeast 2-hybrid screen on a fetal brain cDNA
library with MAGOH as the bait, Zhao et al. (2000) recovered a cDNA
encoding RBM8. The 173-amino acid RBM8 protein is more than 93%
identical to the mouse and zebrafish sequences, and the mouse
differences are all accounted for by an 11-amino acid N-terminal
insertion and another single-residue insertion in the mouse sequence.
Exchange partner and GST pull-down assays confirmed the MAGOH-RBM8
interaction and showed that RBM8 is expressed as a 26-kD protein,
slightly larger than the predicted mass of 23 kD. Northern blot analysis
detected a major RBM8 transcript of less than 1.0 kb in all tissues
tested, with weakest expression in pancreas and brain.
By searching an EST database for homologs of the gonadotropin-releasing
hormone receptor (GNRHR; 138850), followed by 5-prime RACE on a skeletal
muscle cDNA library, Conklin et al. (2000) identified a cDNA encoding
RBM8. Northern blot analysis detected a major 0.9-kb transcript in all
tissues tested. Sequence analysis of the 174-amino acid protein
predicted an RNA-binding domain, which is composed of 2 amphipathic
alpha helices packed against a 4-stranded beta sheet, and a C-terminal
arg-rich segment.
By performing a yeast 2-hybrid screen on a HeLa cell cDNA library to
identify potential cargoes for RAN-binding protein-5 (RANBP5; 602008),
Kataoka et al. (2000) isolated cDNAs encoding RBM8, which they called
Y14. RBM8 encodes a predicted 174-amino acid, predominantly nuclear
nucleocytoplasmic shuttling protein.
Salicioni et al. (2000) used a yeast 2-hybrid screen to identify cDNAs
from a human fetal brain cDNA library encoding proteins that interact
with OVCA1 (603527), a candidate tumor suppressor protein. They
identified cDNAs, which they initially referred to as BOV1, that
appeared to encode a new member of the conserved RNA-binding motif
protein family. One of the cDNAs isolated was identical to RBM8A;
another, designated RBM8B, was thought by Salicioni et al. (2000) to be
a novel functional gene, but was later determined to be a pseudogene.
Northern blot analysis revealed that BOV1 is ubiquitously expressed as 3
distinct mRNA species of 1, 3.2, and 5.8 kb.
GENE FUNCTION
Kataoka et al. (2000) found that RBM8 associates preferentially with
mRNAs produced by splicing and not with pre-mRNAs, introns, or mRNAs
produced from intronless cDNAs. RBM8 associates with both nuclear mRNAs
and newly exported cytoplasmic mRNAs. Splicing of a single intron is
sufficient for RBM8 association. RBM8-containing nuclear complexes are
different from general heterogeneous nuclear ribonucleoprotein (hnRNP)
complexes in that they contain hnRNP proteins and several unique
proteins, including the mRNA export factor TAP (NXF1; 602647). Thus,
RBM8 defines novel intermediates in the pathway of gene expression,
postsplicing nuclear preexport mRNPs, and newly exported cytoplasmic
mRNPs, whose composition is established by splicing. These findings
suggested that pre-mRNA splicing imprints mRNA with a unique set of
proteins that persists in the cytoplasm and thereby communicates the
history of the transcript.
Kim et al. (2001) analyzed the binding of RBM8A, which they called Y14,
to pre-mRNAs injected into nuclei of Xenopus oocytes. They found that
RBM8A stably bound mRNA sequences approximately -20 nucleotides upstream
of exon-exon junctions.
Oskar mRNA localization at the posterior pole of the Drosophila oocyte
is essential for germline and abdomen formation in the future embryo.
Y14/RBM8 and MAGOH (602603), human homologs of nuclear shuttling
proteins required for oskar mRNA localization, are core components of
the exon-exon junction complex (EJC). The EJC is deposited on mRNAs in a
splicing-dependent manner, 20 to 24 nucleotides upstream of exon-exon
junctions, independent of the RNA sequence. This indicates a possible
role of splicing in oskar mRNA localization, challenging the established
notion that the oskar 3-prime untranslated region is sufficient for this
process. Hachet and Ephrussi (2004) demonstrated that splicing at the
first exon-exon junction of oskar RNA is essential for oskar mRNA
localization at the posterior pole. They revisited the issue of
sufficiency of the oskar 3-prime untranslated region for posterior
localization and showed that the localization of unrelated transcripts
bearing the oskar 3-prime untranslated region is mediated by endogenous
oskar mRNA. Hachet and Ephrussi (2004) concluded that their results
revealed an important new function for splicing: regulation of messenger
ribonucleoprotein complex assembly and organization for mRNA cytoplasmic
localization.
Albers et al. (2012) showed that RBM8A is expressed in all hematopoietic
lineages, and that its encoded protein sequence is highly conserved
between species. Albers et al. (2012) suggested that, given the
important functions of the EJC, it is likely that a complete lack of Y14
in humans is not viable. Indeed, in Drosophila melanogaster, knockdown
of its ortholog tsu leads to major defects in abdomen formation (Hachet
and Ephrussi, 2001), and Albers et al. (2012) found that knockdown of
the orthologous rbm8a transcript in Danio rerio using antisense
morpholinos resulted in extreme malformations and death at 2 days
post-fertilization.
GENE STRUCTURE
Albers et al. (2012) determined that the RBM8A gene comprises 6 exons.
MAPPING
By PCR and radiation hybrid analysis, Zhao et al. (2000) mapped the
RBM8A gene to 1q12. Conklin et al. (2000) mapped the RBM8 gene to
14q21-q23 using radiation hybrid analysis, but it appears that the
sequence on chromosome 14 is a pseudogene.
MOLECULAR GENETICS
It had been shown that an inherited or de novo deletion on chromosome
1q21.1 (Klopocki et al., 2007) is found in the majority of individuals
with TAR syndrome (274000), but the apparent autosomal recessive nature
of that syndrome required the existence of an additional causative
allele. To identify the additional causative allele, Albers et al.
(2012) selected 5 individuals with TAR of European ancestry who had the
1q21.1 deletion and sequenced their exomes, but were unable to find
TAR-associated coding mutations in any gene. However, 4 of the cases
carried the minor allele of a low-frequency SNP in the 5-prime UTR of
the RBM8A gene (dbSNP rs139428292; 605313.0001), while the remaining
case carried a previously unknown SNP in the first intron of the same
gene (605313.0002). Genotyping by Sanger sequencing of another 48 cases
of European ancestry identified the 2 SNPs in 35 and 11 samples,
respectively. In the 25 trios where the deletion in the child was not a
de novo event, Albers et al. (2012) confirmed that the deletion and the
newly identified SNPs were inherited from different parents. The minor
allele frequency of the 5-prime UTR and intronic SNPs were 3.05% and
0.42%, respectively, in 7,504 healthy individuals of the Cambridge
BioResource, and the deletion was absent from 5,919 shared healthy
controls of the Wellcome Trust Case Control Consortium. There were 2 TAR
cases who did not carry the 1q21.1 deletion but were found to carry the
5-prime UTR SNP. Albers et al. (2012) identified a 4-bp frameshift
insertion at the start of the fourth exon (605313.0003) in the first
case and established that the noncoding SNP and insertion were on
different chromosomes; in the second case, they identified a nonsense
mutation in the last exon of RBM8A (605313.0004). Both mutations were
absent from 458 exome samples of the 1000 Genomes Project and 416
samples from the Cohorte Lausannoise. Albers et al. (2012) concluded
that in the vast majority of cases, compound inheritance of a rare null
allele (containing a deletion, frameshift mutation, or encoded premature
stop codon) and 1 of 2 low-frequency noncoding SNPs in RBM8A causes TAR
syndrome. Albers et al. (2012) showed that the 2 regulatory SNPs result
in diminished RBM8A transcription in vitro and that expression of Y14 is
reduced in platelets from individuals with TAR. Albers et al. (2012)
concluded that their data implicated Y14 insufficiency and, presumably,
an EJC defect as the cause of TAR syndrome.
Given the expression of Y14 in hematopoietic lineages and major defects
observed in Drosophila and zebrafish resulting from knockdown of the
respective Y14 orthologs, Albers et al. (2012) suggested that their
results are compatible with both a dose-effect phenomenon and a
lineage-dependent deficiency in Y14. The possibility of a dose-effect
phenomenon was supported by the observation that simple
haploinsufficiency is not sufficient to create an aberrant phenotype, as
evidenced by the seemingly healthy carriers of the 1q21.1 deletion.
Albers et al. (2012) did not observe an effect on platelet count for
either the 5-prime UTR or the intronic SNP in the 403 and 59 individuals
from the Cambridge BioResource who carried the minor allele for each
SNP, respectively. The authors suggested that compound inheritance of a
null allele together with the minor allele of 1 of the 2 regulatory SNPs
brings Y14 levels below a critical threshold in certain tissues. The
cell line-dependent effect shown in luciferase assays suggested a
combinatorial binding of transcription factors, including EVI1 (165215),
in the context of regulatory SNPs.
*FIELD* AV
.0001
THROMBOCYTOPENIA-ABSENT RADIUS SYNDROME
RBM8A, 5-PRIME UTR, G-A (dbSNP rs139428292)
In 41 of 55 patients with thrombocytopenia-absent radius syndrome (TAR;
274000), Albers et al. (2012) identified the presence of the minor
allele (A) of a G-to-A SNP, dbSNP rs139428292 (chr1:145507646, GRCh37),
in the 5-prime untranslated region (UTR) of the RBM8A gene. In 39 of
these patients this SNP was found in compound heterozygosity with a
200-kb deletion including the RBM8A gene and 10 other genes; in 2
patients the SNP occurred in compound heterozygosity with 1 of 2 null
mutations in the RBM8A gene. The minor allele frequency of the SNP dbSNP
rs139428292 was 3.05% in 7,504 healthy individuals of the Cambridge
BioResource. This SNP resulted in diminished RBM8A transcription in
vitro.
.0002
THROMBOCYTOPENIA-ABSENT RADIUS SYNDROME
RBM8A, IVS1, G-C
In 12 of 55 patients with thrombocytopenia-absent radius syndrome (TAR;
274000), Albers et al. (2012) identified the presence of the minor
allele (C) of a SNP in the first intron of the RBM8A gene
(chr1:145507765, GRCh37). The SNP occurred in compound heterozygosity
with a 200-kb deletion including the RBM8A gene and 10 other genes. The
minor allele frequency of this intronic SNP was 0.42% in 7,504 healthy
individuals of the Cambridge BioResource. This SNP resulted in
diminished RBM8A transcription in vitro.
.0003
THROMBOCYTOPENIA-ABSENT RADIUS SYNDROME
RBM8A, 4-BP INS, EX4
In a patient with thrombocytopenia-absent radius syndrome (TAR; 274000),
Albers et al. (2012) found compound heterozygosity for a 4-bp insertion
(AGCG, chr1:145508476, GRCh37) in exon 4 of the RBM8A gene, resulting in
frameshift, and a SNP in the 5-prime UTR (605313.0001).
.0004
THROMBOCYTOPENIA-ABSENT RADIUS SYNDROME
RBM8A, C-T, EX6
In a patient with thrombocytopenia-absent radius syndrome (TAR; 274000),
Albers et al. (2012) found compound heterozygosity for a premature
termination mutation in the last exon of the RBM8A gene (C-T,
chr1:145509173, GRCh37) and a SNP in the 5-prime UTR (605313.0001).
*FIELD* RF
1. Albers, C. A.; Paul, D. S.; Schulze, H.; Freson, K.; Stephens,
J. C.; Smethurst, P. A.; Jolley, J. D.; Cvejic, A.; Kostadima, M.;
Bertone, P.; Breuning, M. H.; Debili, N.; and 19 others: Compound
inheritance of a low-frequency regulatory SNP and a rare null mutation
in exon-junction complex subunit RBM8A causes TAR syndrome. Nature
Genet. 44: 435-439, 2012.
2. Conklin, D. C.; Rixon, M. W.; Kuestner, R. E.; Maurer, M. F.; Whitmore,
T. E.; Millar, R. P.: Cloning and gene expression of a novel human
ribonucleoprotein. Biochim. Biophys. Acta 1492: 465-469, 2000.
3. Hachet, O.; Ephrussi, A.: Drosophila Y14 shuttles to the posterior
of the oocyte and is required for oskar mRNA transport. Curr. Biol. 11:
1666-1674, 2001.
4. Hachet, O.; Ephrussi, A.: Splicing of oskar RNA in the nucleus
is coupled to its cytoplasmic localization. Nature 428: 959-963,
2004.
5. Kataoka, N.; Yong, J.; Kim, V. N.; Velazquez, F.; Perkinson, R.
A.; Wang, F.; Dreyfuss, G.: Pre-mRNA splicing imprints mRNA in the
nucleus with a novel RNA-binding protein that persists in the cytoplasm. Molec.
Cell 6: 673-682, 2000.
6. Kim, V. N.; Yong, J.; Kataoka, N.; Abel, L.; Diem, M. D.; Dreyfuss,
G.: The Y14 protein communicates to the cytoplasm the position of
exon-exon junctions. EMBO J. 20: 2062-2068, 2001.
7. Klopocki, E.; Schulze, H.; Strauss, G.; Ott, C.-E.; Hall, J.; Trotier,
F.; Fleischhauer, S.; Greenhalgh, L.; Newbury-Ecob, R. A.; Neumann,
L. M.; Habenicht, R.; Konig, R.; Seemanova, E.; Megarbane, A.; Ropers,
H.-H.; Ullmann, R.; Horn, D.; Mundlos, S.: Complex inheritance pattern
resembling autosomal recessive inheritance involving a microdeletion
in thrombocytopenia-absent radius syndrome. Am. J. Hum. Genet. 80:
232-240, 2007.
8. Salicioni, A. M.; Xi. M.; Vanderveer, L. A.; Balsara, B.; Testa,
J. R.; Dunbrack, R. L., Jr.; Godwin, A. K.: Identification and structural
analysis of human RBM8A and RBM8B: two highly conserved RNA-binding
motif proteins that interact with OVCA1, a candidate tumor suppressor. Genomics 69:
54-62, 2000.
9. Zhao, X.-F.; Nowak, N. J.; Shows, T. B.; Aplan, P. D.: MAGOH interacts
with a novel RNA-binding protein. Genomics 63: 145-148, 2000.
*FIELD* CN
Ada Hamosh - updated: 4/18/2012
Ada Hamosh - updated: 4/27/2004
Patricia A. Hartz - updated: 1/16/2003
Carol A. Bocchini - updated: 12/21/2000
Paul J. Converse - updated: 11/9/2000
*FIELD* CD
Stylianos E. Antonarakis: 10/2/2000
*FIELD* ED
alopez: 04/19/2012
alopez: 4/18/2012
terry: 4/18/2012
wwang: 3/26/2007
alopez: 4/27/2004
terry: 4/27/2004
cwells: 1/17/2003
terry: 1/16/2003
mgross: 10/7/2002
carol: 12/14/2001
carol: 12/26/2000
carol: 12/21/2000
mgross: 11/9/2000
mgross: 10/2/2000