Full text data of UPF3B
UPF3B
(RENT3B, UPF3X)
[Confidence: low (only semi-automatic identification from reviews)]
Regulator of nonsense transcripts 3B (Nonsense mRNA reducing factor 3B; Up-frameshift suppressor 3 homolog B; hUpf3B; Up-frameshift suppressor 3 homolog on chromosome X; hUpf3p-X)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Regulator of nonsense transcripts 3B (Nonsense mRNA reducing factor 3B; Up-frameshift suppressor 3 homolog B; hUpf3B; Up-frameshift suppressor 3 homolog on chromosome X; hUpf3p-X)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9BZI7
ID REN3B_HUMAN Reviewed; 483 AA.
AC Q9BZI7; D3DWI3; D3DWI4; Q0VAK8; Q9H1J0;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUN-2001, sequence version 1.
DT 22-JAN-2014, entry version 111.
DE RecName: Full=Regulator of nonsense transcripts 3B;
DE AltName: Full=Nonsense mRNA reducing factor 3B;
DE AltName: Full=Up-frameshift suppressor 3 homolog B;
DE Short=hUpf3B;
DE AltName: Full=Up-frameshift suppressor 3 homolog on chromosome X;
DE Short=hUpf3p-X;
GN Name=UPF3B; Synonyms=RENT3B, UPF3X;
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 2), FUNCTION IN NONSENSE-MEDIATED
RP MRNA DECAY, INTERACTION WITH UPF1 AND UPF2, AND SUBCELLULAR LOCATION.
RX PubMed=11163187; DOI=10.1016/S0092-8674(00)00214-2;
RA Lykke-Andersen J., Shu M.-D., Steitz J.A.;
RT "Human Upf proteins target an mRNA for nonsense-mediated decay when
RT bound downstream of a termination codon.";
RL Cell 103:1121-1131(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH UPF2,
RP MUTAGENESIS OF 53-VAL--LEU-58 AND 117-TYR--PHE-119, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Cervix carcinoma;
RX PubMed=11113196; DOI=10.1128/MCB.21.1.209-223.2001;
RA Serin G., Gersappe A., Black J.D., Aronoff R., Maquat L.E.;
RT "Identification and characterization of human orthologues to
RT Saccharomyces cerevisiae Upf2 protein and Upf3 protein (Caenorhabditis
RT elegans SMG-4).";
RL Mol. Cell. Biol. 21:209-223(2001).
RN [3]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [5]
RP INTERACTION WITH RBM8A, IDENTIFICATION IN A POST-SPLICING MRNP
RP COMPLEX, ASSOCIATION WITH THE EJC COMPLEX, AND RNA-BINDING.
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 [6]
RP IDENTIFICATION IN A POST-SPLICING MRNP COMPLEX, AND ASSOCIATION WITH
RP THE EJC COMPLEX.
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 [7]
RP FUNCTION IN NONSENSE-MEDIATED MRNA DECAY, INTERACTION WITH RBM8A, AND
RP MUTAGENESIS OF ARG-430; ARG-432; 434-LYS--ARG-447; LYS-434; ASP-435;
RP ARG-436 AND LEU-441.
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 [8]
RP INTERACTION WITH EST1A.
RX PubMed=12554878; DOI=10.1261/rna.2137903;
RA Chiu S.-Y., Serin G., Ohara O., Maquat L.E.;
RT "Characterization of human Smg5/7a: a protein with similarities to
RT Caenorhabditis elegans SMG5 and SMG7 that functions in the
RT dephosphorylation of Upf1.";
RL RNA 9:77-87(2003).
RN [9]
RP FUNCTION IN NONSENSE-MEDIATED MRNA DECAY, ASSOCIATION WITH THE EJC
RP COMPLEX, AND IDENTIFICATION IN A COMPLEX WITH UPF2 AND RNPS1.
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 [10]
RP FUNCTION IN NONSENSE-MEDIATED MRNA DECAY, FUNCTION IN TRANSLATION
RP STIMULATION, ASSOCIATION WITH THE EJC COMPLEX, AND MUTAGENESIS OF
RP ARG-432.
RX PubMed=16601204; DOI=10.1261/rna.12506;
RA Kunz J.B., Neu-Yilik G., Hentze M.W., Kulozik A.E., Gehring N.H.;
RT "Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA decay and
RT translation.";
RL RNA 12:1015-1022(2006).
RN [11]
RP FUNCTION, AND RECONSTITUTION OF THE EJC CORE-UPF COMPLEX.
RX PubMed=18066079; DOI=10.1038/nsmb1330;
RA Chamieh H., Ballut L., Bonneau F., Le Hir H.;
RT "NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex
RT and stimulate its RNA helicase activity.";
RL Nat. Struct. Mol. Biol. 15:85-93(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-169, 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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-169, 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-198, AND MASS
RP 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 [15]
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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-169 AND SER-310, AND
RP 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 [17]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 50-140 IN COMPLEX WITH UPF2,
RP RNA-BINDING, AND MUTAGENESIS OF LYS-52 AND ARG-56.
RX PubMed=15004547; DOI=10.1038/nsmb741;
RA Kadlec J., Izaurralde E., Cusack S.;
RT "The structural basis for the interaction between nonsense-mediated
RT mRNA decay factors UPF2 and UPF3.";
RL Nat. Struct. Mol. Biol. 11:330-337(2004).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) OF 424-483 IN COMPLEX WITH
RP EIF4A3; MAGOH; RBM8A AND CASC3, AND MUTAGENESIS OF ARG-436; TYR-442;
RP ARG-447; ARG-449 AND ARG-451.
RX PubMed=20479275; DOI=10.1073/pnas.1000993107;
RA Buchwald G., Ebert J., Basquin C., Sauliere J., Jayachandran U.,
RA Bono F., Le Hir H., Conti E.;
RT "Insights into the recruitment of the NMD machinery from the crystal
RT structure of a core EJC-UPF3b complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:10050-10055(2010).
RN [19]
RP VARIANT MRXS14 ASP-160.
RX PubMed=17704778; DOI=10.1038/ng2100;
RA Tarpey P.S., Raymond F.L., Nguyen L.S., Rodriguez J., Hackett A.,
RA Vandeleur L., Smith R., Shoubridge C., Edkins S., Stevens C.,
RA O'Meara S., Tofts C., Barthorpe S., Buck G., Cole J., Halliday K.,
RA Hills K., Jones D., Mironenko T., Perry J., Varian J., West S.,
RA Widaa S., Teague J., Dicks E., Butler A., Menzies A., Richardson D.,
RA Jenkinson A., Shepherd R., Raine K., Moon J., Luo Y., Parnau J.,
RA Bhat S.S., Gardner A., Corbett M., Brooks D., Thomas P.,
RA Parkinson-Lawrence E., Porteous M.E., Warner J.P., Sanderson T.,
RA Pearson P., Simensen R.J., Skinner C., Hoganson G., Superneau D.,
RA Wooster R., Bobrow M., Turner G., Stevenson R.E., Schwartz C.E.,
RA Futreal P.A., Srivastava A.K., Stratton M.R., Gecz J.;
RT "Mutations in UPF3B, a member of the nonsense-mediated mRNA decay
RT complex, cause syndromic and nonsyndromic mental retardation.";
RL Nat. Genet. 39:1127-1133(2007).
CC -!- FUNCTION: Involved in nonsense-mediated decay (NMD) of mRNAs
CC containing premature stop codons by associating with the nuclear
CC exon junction complex (EJC) and serving as link between the EJC
CC core and NMD machinery. Recruits UPF2 at the cytoplasmic side of
CC the nuclear envelope and the subsequent formation of an UPF1-UPF2-
CC UPF3 surveillance complex (including UPF1 bound to release factors
CC at the stalled ribosome) is believed to activate NMD. In
CC cooperation with UPF2 stimulates both ATPase and RNA helicase
CC activities of UPF1. Binds spliced mRNA upstream of exon-exon
CC junctions. In vitro, stimulates translation; the function is
CC independent of association with UPF2 and components of the EJC
CC core.
CC -!- SUBUNIT: Found in a post-splicing messenger ribonucleoprotein
CC (mRNP) complex. Associates with the exon junction complex (EJC);
CC the EJC core components EIF4A3 and the MAGOH-RBM8A dimer form a
CC composite binding site for UPF3B which overlaps with the EJC
CC binding site for WIBG. Interacts with EST1A, UPF2 and RBM8A.
CC -!- INTERACTION:
CC P38919:EIF4A3; NbExp=7; IntAct=EBI-372780, EBI-299104;
CC Q9Y5S9:RBM8A; NbExp=9; IntAct=EBI-372780, EBI-447231;
CC Q92900:UPF1; NbExp=8; IntAct=EBI-372780, EBI-373471;
CC Q9HAU5:UPF2; NbExp=6; IntAct=EBI-372780, EBI-372073;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Shuttling between
CC the nucleus and the cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BZI7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BZI7-2; Sequence=VSP_012963;
CC -!- TISSUE SPECIFICITY: Expressed in testis, uterus, prostate, heart,
CC muscle, brain, spinal cord and placenta.
CC -!- DISEASE: Mental retardation, X-linked, syndromic, 14 (MRXS14)
CC [MIM:300676]: A disorder characterized by significantly below
CC average general intellectual functioning associated with
CC impairments in adaptive behavior and manifested during the
CC developmental period. MRXS14 patients manifest mental retardation
CC associated with other variable signs such as autistic features,
CC slender build, poor musculature, long, thin face, high-arched
CC palate, high nasal bridge, and pectus deformities. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- SIMILARITY: Belongs to the RENT3 family.
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DR EMBL; AY013251; AAG48511.1; -; mRNA.
DR EMBL; AF318576; AAG60691.1; -; mRNA.
DR EMBL; CH471161; EAW89842.1; -; Genomic_DNA.
DR EMBL; CH471161; EAW89844.1; -; Genomic_DNA.
DR EMBL; CH471161; EAW89845.1; -; Genomic_DNA.
DR EMBL; CH471161; EAW89846.1; -; Genomic_DNA.
DR EMBL; BC121017; AAI21018.1; -; mRNA.
DR RefSeq; NP_075386.1; NM_023010.3.
DR RefSeq; NP_542199.1; NM_080632.2.
DR UniGene; Hs.103832; -.
DR PDB; 1UW4; X-ray; 1.95 A; A/C=50-140.
DR PDB; 2XB2; X-ray; 3.40 A; G/U=424-483.
DR PDBsum; 1UW4; -.
DR PDBsum; 2XB2; -.
DR ProteinModelPortal; Q9BZI7; -.
DR SMR; Q9BZI7; 50-140.
DR DIP; DIP-31143N; -.
DR IntAct; Q9BZI7; 19.
DR MINT; MINT-265168; -.
DR STRING; 9606.ENSP00000276201; -.
DR PhosphoSite; Q9BZI7; -.
DR DMDM; 60390643; -.
DR PaxDb; Q9BZI7; -.
DR PRIDE; Q9BZI7; -.
DR Ensembl; ENST00000276201; ENSP00000276201; ENSG00000125351.
DR Ensembl; ENST00000345865; ENSP00000245418; ENSG00000125351.
DR GeneID; 65109; -.
DR KEGG; hsa:65109; -.
DR UCSC; uc004erz.2; human.
DR CTD; 65109; -.
DR GeneCards; GC0XM118967; -.
DR HGNC; HGNC:20439; UPF3B.
DR HPA; HPA001800; -.
DR HPA; HPA001882; -.
DR MIM; 300298; gene.
DR MIM; 300676; phenotype.
DR neXtProt; NX_Q9BZI7; -.
DR Orphanet; 323; FG syndrome.
DR Orphanet; 776; X-linked intellectual deficit with marfanoid habitus.
DR Orphanet; 777; X-linked non-syndromic intellectual deficit.
DR PharmGKB; PA128394708; -.
DR eggNOG; NOG251520; -.
DR HOGENOM; HOG000230909; -.
DR HOVERGEN; HBG059714; -.
DR InParanoid; Q9BZI7; -.
DR KO; K14328; -.
DR OMA; YFEFFAN; -.
DR OrthoDB; EOG7M6D9K; -.
DR PhylomeDB; Q9BZI7; -.
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; UPF3B; human.
DR EvolutionaryTrace; Q9BZI7; -.
DR GeneWiki; UPF3B; -.
DR GenomeRNAi; 65109; -.
DR NextBio; 67302; -.
DR PRO; PR:Q9BZI7; -.
DR ArrayExpress; Q9BZI7; -.
DR Bgee; Q9BZI7; -.
DR CleanEx; HS_UPF3B; -.
DR Genevestigator; Q9BZI7; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0035145; C:exon-exon junction complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0003729; F:mRNA binding; IDA:UniProtKB.
DR GO; GO:0005487; F:nucleocytoplasmic transporter activity; 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; TAS:Reactome.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IDA:UniProtKB.
DR GO; GO:0045727; P:positive regulation of translation; IDA:UniProtKB.
DR GO; GO:0006369; P:termination of RNA polymerase II transcription; TAS:Reactome.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR005120; Nonsense_mediated_decay_UPF3.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait.
DR Pfam; PF03467; Smg4_UPF3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Cytoplasm;
KW Disease mutation; Mental retardation; mRNA transport;
KW Nonsense-mediated mRNA decay; Nucleus; Phosphoprotein;
KW Reference proteome; RNA-binding; Transport.
FT CHAIN 1 483 Regulator of nonsense transcripts 3B.
FT /FTId=PRO_0000215297.
FT REGION 30 255 Necessary for interaction with UPF2.
FT REGION 52 57 Binds to UPF2.
FT REGION 94 483 Sufficient for association with EJC core.
FT REGION 430 447 Necessary for interaction with RBM8A and
FT for activating NMD.
FT MOD_RES 169 169 Phosphothreonine.
FT MOD_RES 198 198 Phosphothreonine.
FT MOD_RES 310 310 Phosphoserine.
FT VAR_SEQ 270 282 Missing (in isoform 2).
FT /FTId=VSP_012963.
FT VARIANT 160 160 Y -> D (in MRXS14).
FT /FTId=VAR_037666.
FT MUTAGEN 52 52 K->E: Abolishes interaction with UPF2.
FT MUTAGEN 53 58 VVIRRL->AVARRA: Abolishes interaction
FT with UPF2.
FT MUTAGEN 56 56 R->E: Does not abolish interaction with
FT UPF2.
FT MUTAGEN 117 119 YVF->DVD: Abolishes interaction with
FT UPF2.
FT MUTAGEN 430 430 R->A: Reduces NMD.
FT MUTAGEN 432 432 R->A: Reduces NMD.
FT MUTAGEN 434 447 Missing: Abolishes NMD.
FT MUTAGEN 434 434 K->A: Reduces NMD.
FT MUTAGEN 435 435 D->A: Reduces NMD.
FT MUTAGEN 436 436 R->A: Impairs association with EJC.
FT MUTAGEN 436 436 R->A: Reduces NMD.
FT MUTAGEN 441 441 L->F: Reduces NMD.
FT MUTAGEN 442 442 Y->A: Impairs association with EJC.
FT MUTAGEN 447 447 R->E: Abolishes NMD; when associated with
FT E-449 and E-451.
FT MUTAGEN 449 449 R->E: Abolishes NMD; when associated with
FT E-447 and E-451.
FT MUTAGEN 451 451 R->E: Abolishes NMD; when associated with
FT E-447 and E-449.
FT CONFLICT 358 358 R -> H (in Ref. 4; AAI21018).
FT STRAND 52 58
FT HELIX 64 71
FT STRAND 77 85
FT STRAND 95 104
FT HELIX 105 114
FT STRAND 118 120
FT STRAND 126 128
FT STRAND 130 133
FT TURN 433 435
SQ SEQUENCE 483 AA; 57762 MW; F5A8A395783D1A69 CRC64;
MKEEKEHRPK EKRVTLLTPA GATGSGGGTS GDSSKGEDKQ DRNKEKKEAL SKVVIRRLPP
TLTKEQLQEH LQPMPEHDYF EFFSNDTSLY PHMYARAYIN FKNQEDIILF RDRFDGYVFL
DNKGQEYPAI VEFAPFQKAA KKKTKKRDTK VGTIDDDPEY RKFLESYATD NEKMTSTPET
LLEEIEAKNR ELIAKKTTPL LSFLKNKQRM REEKREERRR REIERKRQRE EERRKWKEEE
KRKRKDIEKL KKIDRIPERD KLKDEPKIKV HRFLLQAVNQ KNLLKKPEKG DEKELDKREK
AKKLDKENLS DERASGQSCT LPKRSDSELK DEKPKRPEDE SGRDYRERER EYERDQERIL
RERERLKRQE EERRRQKERY EKEKTFKRKE EEMKKEKDTL RDKGKKAEST ESIGSSEKTE
KKEEVVKRDR IRNKDRPAMQ LYQPGARSRN RLCPPDDSTK SGDSAAERKQ ESGISHRKEG
GEE
//
ID REN3B_HUMAN Reviewed; 483 AA.
AC Q9BZI7; D3DWI3; D3DWI4; Q0VAK8; Q9H1J0;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUN-2001, sequence version 1.
DT 22-JAN-2014, entry version 111.
DE RecName: Full=Regulator of nonsense transcripts 3B;
DE AltName: Full=Nonsense mRNA reducing factor 3B;
DE AltName: Full=Up-frameshift suppressor 3 homolog B;
DE Short=hUpf3B;
DE AltName: Full=Up-frameshift suppressor 3 homolog on chromosome X;
DE Short=hUpf3p-X;
GN Name=UPF3B; Synonyms=RENT3B, UPF3X;
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 2), FUNCTION IN NONSENSE-MEDIATED
RP MRNA DECAY, INTERACTION WITH UPF1 AND UPF2, AND SUBCELLULAR LOCATION.
RX PubMed=11163187; DOI=10.1016/S0092-8674(00)00214-2;
RA Lykke-Andersen J., Shu M.-D., Steitz J.A.;
RT "Human Upf proteins target an mRNA for nonsense-mediated decay when
RT bound downstream of a termination codon.";
RL Cell 103:1121-1131(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH UPF2,
RP MUTAGENESIS OF 53-VAL--LEU-58 AND 117-TYR--PHE-119, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Cervix carcinoma;
RX PubMed=11113196; DOI=10.1128/MCB.21.1.209-223.2001;
RA Serin G., Gersappe A., Black J.D., Aronoff R., Maquat L.E.;
RT "Identification and characterization of human orthologues to
RT Saccharomyces cerevisiae Upf2 protein and Upf3 protein (Caenorhabditis
RT elegans SMG-4).";
RL Mol. Cell. Biol. 21:209-223(2001).
RN [3]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [5]
RP INTERACTION WITH RBM8A, IDENTIFICATION IN A POST-SPLICING MRNP
RP COMPLEX, ASSOCIATION WITH THE EJC COMPLEX, AND RNA-BINDING.
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 [6]
RP IDENTIFICATION IN A POST-SPLICING MRNP COMPLEX, AND ASSOCIATION WITH
RP THE EJC COMPLEX.
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 [7]
RP FUNCTION IN NONSENSE-MEDIATED MRNA DECAY, INTERACTION WITH RBM8A, AND
RP MUTAGENESIS OF ARG-430; ARG-432; 434-LYS--ARG-447; LYS-434; ASP-435;
RP ARG-436 AND LEU-441.
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 [8]
RP INTERACTION WITH EST1A.
RX PubMed=12554878; DOI=10.1261/rna.2137903;
RA Chiu S.-Y., Serin G., Ohara O., Maquat L.E.;
RT "Characterization of human Smg5/7a: a protein with similarities to
RT Caenorhabditis elegans SMG5 and SMG7 that functions in the
RT dephosphorylation of Upf1.";
RL RNA 9:77-87(2003).
RN [9]
RP FUNCTION IN NONSENSE-MEDIATED MRNA DECAY, ASSOCIATION WITH THE EJC
RP COMPLEX, AND IDENTIFICATION IN A COMPLEX WITH UPF2 AND RNPS1.
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 [10]
RP FUNCTION IN NONSENSE-MEDIATED MRNA DECAY, FUNCTION IN TRANSLATION
RP STIMULATION, ASSOCIATION WITH THE EJC COMPLEX, AND MUTAGENESIS OF
RP ARG-432.
RX PubMed=16601204; DOI=10.1261/rna.12506;
RA Kunz J.B., Neu-Yilik G., Hentze M.W., Kulozik A.E., Gehring N.H.;
RT "Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA decay and
RT translation.";
RL RNA 12:1015-1022(2006).
RN [11]
RP FUNCTION, AND RECONSTITUTION OF THE EJC CORE-UPF COMPLEX.
RX PubMed=18066079; DOI=10.1038/nsmb1330;
RA Chamieh H., Ballut L., Bonneau F., Le Hir H.;
RT "NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex
RT and stimulate its RNA helicase activity.";
RL Nat. Struct. Mol. Biol. 15:85-93(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-169, 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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-169, 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-198, AND MASS
RP 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 [15]
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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-169 AND SER-310, AND
RP 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 [17]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 50-140 IN COMPLEX WITH UPF2,
RP RNA-BINDING, AND MUTAGENESIS OF LYS-52 AND ARG-56.
RX PubMed=15004547; DOI=10.1038/nsmb741;
RA Kadlec J., Izaurralde E., Cusack S.;
RT "The structural basis for the interaction between nonsense-mediated
RT mRNA decay factors UPF2 and UPF3.";
RL Nat. Struct. Mol. Biol. 11:330-337(2004).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) OF 424-483 IN COMPLEX WITH
RP EIF4A3; MAGOH; RBM8A AND CASC3, AND MUTAGENESIS OF ARG-436; TYR-442;
RP ARG-447; ARG-449 AND ARG-451.
RX PubMed=20479275; DOI=10.1073/pnas.1000993107;
RA Buchwald G., Ebert J., Basquin C., Sauliere J., Jayachandran U.,
RA Bono F., Le Hir H., Conti E.;
RT "Insights into the recruitment of the NMD machinery from the crystal
RT structure of a core EJC-UPF3b complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:10050-10055(2010).
RN [19]
RP VARIANT MRXS14 ASP-160.
RX PubMed=17704778; DOI=10.1038/ng2100;
RA Tarpey P.S., Raymond F.L., Nguyen L.S., Rodriguez J., Hackett A.,
RA Vandeleur L., Smith R., Shoubridge C., Edkins S., Stevens C.,
RA O'Meara S., Tofts C., Barthorpe S., Buck G., Cole J., Halliday K.,
RA Hills K., Jones D., Mironenko T., Perry J., Varian J., West S.,
RA Widaa S., Teague J., Dicks E., Butler A., Menzies A., Richardson D.,
RA Jenkinson A., Shepherd R., Raine K., Moon J., Luo Y., Parnau J.,
RA Bhat S.S., Gardner A., Corbett M., Brooks D., Thomas P.,
RA Parkinson-Lawrence E., Porteous M.E., Warner J.P., Sanderson T.,
RA Pearson P., Simensen R.J., Skinner C., Hoganson G., Superneau D.,
RA Wooster R., Bobrow M., Turner G., Stevenson R.E., Schwartz C.E.,
RA Futreal P.A., Srivastava A.K., Stratton M.R., Gecz J.;
RT "Mutations in UPF3B, a member of the nonsense-mediated mRNA decay
RT complex, cause syndromic and nonsyndromic mental retardation.";
RL Nat. Genet. 39:1127-1133(2007).
CC -!- FUNCTION: Involved in nonsense-mediated decay (NMD) of mRNAs
CC containing premature stop codons by associating with the nuclear
CC exon junction complex (EJC) and serving as link between the EJC
CC core and NMD machinery. Recruits UPF2 at the cytoplasmic side of
CC the nuclear envelope and the subsequent formation of an UPF1-UPF2-
CC UPF3 surveillance complex (including UPF1 bound to release factors
CC at the stalled ribosome) is believed to activate NMD. In
CC cooperation with UPF2 stimulates both ATPase and RNA helicase
CC activities of UPF1. Binds spliced mRNA upstream of exon-exon
CC junctions. In vitro, stimulates translation; the function is
CC independent of association with UPF2 and components of the EJC
CC core.
CC -!- SUBUNIT: Found in a post-splicing messenger ribonucleoprotein
CC (mRNP) complex. Associates with the exon junction complex (EJC);
CC the EJC core components EIF4A3 and the MAGOH-RBM8A dimer form a
CC composite binding site for UPF3B which overlaps with the EJC
CC binding site for WIBG. Interacts with EST1A, UPF2 and RBM8A.
CC -!- INTERACTION:
CC P38919:EIF4A3; NbExp=7; IntAct=EBI-372780, EBI-299104;
CC Q9Y5S9:RBM8A; NbExp=9; IntAct=EBI-372780, EBI-447231;
CC Q92900:UPF1; NbExp=8; IntAct=EBI-372780, EBI-373471;
CC Q9HAU5:UPF2; NbExp=6; IntAct=EBI-372780, EBI-372073;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Shuttling between
CC the nucleus and the cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BZI7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BZI7-2; Sequence=VSP_012963;
CC -!- TISSUE SPECIFICITY: Expressed in testis, uterus, prostate, heart,
CC muscle, brain, spinal cord and placenta.
CC -!- DISEASE: Mental retardation, X-linked, syndromic, 14 (MRXS14)
CC [MIM:300676]: A disorder characterized by significantly below
CC average general intellectual functioning associated with
CC impairments in adaptive behavior and manifested during the
CC developmental period. MRXS14 patients manifest mental retardation
CC associated with other variable signs such as autistic features,
CC slender build, poor musculature, long, thin face, high-arched
CC palate, high nasal bridge, and pectus deformities. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- SIMILARITY: Belongs to the RENT3 family.
CC -----------------------------------------------------------------------
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DR EMBL; AY013251; AAG48511.1; -; mRNA.
DR EMBL; AF318576; AAG60691.1; -; mRNA.
DR EMBL; CH471161; EAW89842.1; -; Genomic_DNA.
DR EMBL; CH471161; EAW89844.1; -; Genomic_DNA.
DR EMBL; CH471161; EAW89845.1; -; Genomic_DNA.
DR EMBL; CH471161; EAW89846.1; -; Genomic_DNA.
DR EMBL; BC121017; AAI21018.1; -; mRNA.
DR RefSeq; NP_075386.1; NM_023010.3.
DR RefSeq; NP_542199.1; NM_080632.2.
DR UniGene; Hs.103832; -.
DR PDB; 1UW4; X-ray; 1.95 A; A/C=50-140.
DR PDB; 2XB2; X-ray; 3.40 A; G/U=424-483.
DR PDBsum; 1UW4; -.
DR PDBsum; 2XB2; -.
DR ProteinModelPortal; Q9BZI7; -.
DR SMR; Q9BZI7; 50-140.
DR DIP; DIP-31143N; -.
DR IntAct; Q9BZI7; 19.
DR MINT; MINT-265168; -.
DR STRING; 9606.ENSP00000276201; -.
DR PhosphoSite; Q9BZI7; -.
DR DMDM; 60390643; -.
DR PaxDb; Q9BZI7; -.
DR PRIDE; Q9BZI7; -.
DR Ensembl; ENST00000276201; ENSP00000276201; ENSG00000125351.
DR Ensembl; ENST00000345865; ENSP00000245418; ENSG00000125351.
DR GeneID; 65109; -.
DR KEGG; hsa:65109; -.
DR UCSC; uc004erz.2; human.
DR CTD; 65109; -.
DR GeneCards; GC0XM118967; -.
DR HGNC; HGNC:20439; UPF3B.
DR HPA; HPA001800; -.
DR HPA; HPA001882; -.
DR MIM; 300298; gene.
DR MIM; 300676; phenotype.
DR neXtProt; NX_Q9BZI7; -.
DR Orphanet; 323; FG syndrome.
DR Orphanet; 776; X-linked intellectual deficit with marfanoid habitus.
DR Orphanet; 777; X-linked non-syndromic intellectual deficit.
DR PharmGKB; PA128394708; -.
DR eggNOG; NOG251520; -.
DR HOGENOM; HOG000230909; -.
DR HOVERGEN; HBG059714; -.
DR InParanoid; Q9BZI7; -.
DR KO; K14328; -.
DR OMA; YFEFFAN; -.
DR OrthoDB; EOG7M6D9K; -.
DR PhylomeDB; Q9BZI7; -.
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; UPF3B; human.
DR EvolutionaryTrace; Q9BZI7; -.
DR GeneWiki; UPF3B; -.
DR GenomeRNAi; 65109; -.
DR NextBio; 67302; -.
DR PRO; PR:Q9BZI7; -.
DR ArrayExpress; Q9BZI7; -.
DR Bgee; Q9BZI7; -.
DR CleanEx; HS_UPF3B; -.
DR Genevestigator; Q9BZI7; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0035145; C:exon-exon junction complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0003729; F:mRNA binding; IDA:UniProtKB.
DR GO; GO:0005487; F:nucleocytoplasmic transporter activity; 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; TAS:Reactome.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IDA:UniProtKB.
DR GO; GO:0045727; P:positive regulation of translation; IDA:UniProtKB.
DR GO; GO:0006369; P:termination of RNA polymerase II transcription; TAS:Reactome.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR005120; Nonsense_mediated_decay_UPF3.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait.
DR Pfam; PF03467; Smg4_UPF3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Cytoplasm;
KW Disease mutation; Mental retardation; mRNA transport;
KW Nonsense-mediated mRNA decay; Nucleus; Phosphoprotein;
KW Reference proteome; RNA-binding; Transport.
FT CHAIN 1 483 Regulator of nonsense transcripts 3B.
FT /FTId=PRO_0000215297.
FT REGION 30 255 Necessary for interaction with UPF2.
FT REGION 52 57 Binds to UPF2.
FT REGION 94 483 Sufficient for association with EJC core.
FT REGION 430 447 Necessary for interaction with RBM8A and
FT for activating NMD.
FT MOD_RES 169 169 Phosphothreonine.
FT MOD_RES 198 198 Phosphothreonine.
FT MOD_RES 310 310 Phosphoserine.
FT VAR_SEQ 270 282 Missing (in isoform 2).
FT /FTId=VSP_012963.
FT VARIANT 160 160 Y -> D (in MRXS14).
FT /FTId=VAR_037666.
FT MUTAGEN 52 52 K->E: Abolishes interaction with UPF2.
FT MUTAGEN 53 58 VVIRRL->AVARRA: Abolishes interaction
FT with UPF2.
FT MUTAGEN 56 56 R->E: Does not abolish interaction with
FT UPF2.
FT MUTAGEN 117 119 YVF->DVD: Abolishes interaction with
FT UPF2.
FT MUTAGEN 430 430 R->A: Reduces NMD.
FT MUTAGEN 432 432 R->A: Reduces NMD.
FT MUTAGEN 434 447 Missing: Abolishes NMD.
FT MUTAGEN 434 434 K->A: Reduces NMD.
FT MUTAGEN 435 435 D->A: Reduces NMD.
FT MUTAGEN 436 436 R->A: Impairs association with EJC.
FT MUTAGEN 436 436 R->A: Reduces NMD.
FT MUTAGEN 441 441 L->F: Reduces NMD.
FT MUTAGEN 442 442 Y->A: Impairs association with EJC.
FT MUTAGEN 447 447 R->E: Abolishes NMD; when associated with
FT E-449 and E-451.
FT MUTAGEN 449 449 R->E: Abolishes NMD; when associated with
FT E-447 and E-451.
FT MUTAGEN 451 451 R->E: Abolishes NMD; when associated with
FT E-447 and E-449.
FT CONFLICT 358 358 R -> H (in Ref. 4; AAI21018).
FT STRAND 52 58
FT HELIX 64 71
FT STRAND 77 85
FT STRAND 95 104
FT HELIX 105 114
FT STRAND 118 120
FT STRAND 126 128
FT STRAND 130 133
FT TURN 433 435
SQ SEQUENCE 483 AA; 57762 MW; F5A8A395783D1A69 CRC64;
MKEEKEHRPK EKRVTLLTPA GATGSGGGTS GDSSKGEDKQ DRNKEKKEAL SKVVIRRLPP
TLTKEQLQEH LQPMPEHDYF EFFSNDTSLY PHMYARAYIN FKNQEDIILF RDRFDGYVFL
DNKGQEYPAI VEFAPFQKAA KKKTKKRDTK VGTIDDDPEY RKFLESYATD NEKMTSTPET
LLEEIEAKNR ELIAKKTTPL LSFLKNKQRM REEKREERRR REIERKRQRE EERRKWKEEE
KRKRKDIEKL KKIDRIPERD KLKDEPKIKV HRFLLQAVNQ KNLLKKPEKG DEKELDKREK
AKKLDKENLS DERASGQSCT LPKRSDSELK DEKPKRPEDE SGRDYRERER EYERDQERIL
RERERLKRQE EERRRQKERY EKEKTFKRKE EEMKKEKDTL RDKGKKAEST ESIGSSEKTE
KKEEVVKRDR IRNKDRPAMQ LYQPGARSRN RLCPPDDSTK SGDSAAERKQ ESGISHRKEG
GEE
//
MIM
300298
*RECORD*
*FIELD* NO
300298
*FIELD* TI
*300298 UPF3, YEAST, HOMOLOG OF, B; UPF3B
;;REGULATOR OF NONSENSE TRANSCRIPTS 3B; RENT3B;;
read moreUPF3X
*FIELD* TX
DESCRIPTION
Nonsense-mediated decay (NMD) is a mechanism for degrading transcripts
with premature termination codons arising from errors in transcription
or splicing, from mutated genes, or from genes that are physiologically
regulated by NMD. UPF3A (605530) and UPF3B are components of an
exon-junction complex that promotes NMD and regulates translation
efficiency (summary by Kunz et al., 2006).
CLONING
By searching sequence databases for homologs of the yeast Upf2 and Upf3
genes, followed by RT-PCR, Lykke-Andersen et al. (2000) isolated cDNAs
encoding 3 human proteins, which they named UPF2 (605529), UPF3A, and
UPF3B. The predicted UPF2, UPF3A, and UPF3B proteins contain 1,272, 476,
and 470 amino acids, respectively.
Using comparative genomics and RACE, Serin et al. (2001) isolated cDNAs
encoding UPF3A, which they called UPF3, and UPF3B, which they called
UPF3X. UPF3B encodes a 483-amino acid protein and a 470-amino acid
splice variant that lacks exon 8. Northern blot analysis revealed
expression of a 2.4-kb UPF3B transcript in HeLa cells. RT-PCR detected
variable UPF3B expression in all tissues examined, with highest
expression in testis and fetal brain. Epitope-tagged UPF3B was expressed
in the nucleus of transfected HeLa cells.
GENE FUNCTION
Using mutation and Western blot analyses, Serin et al. (2001) showed
that the central-to-C-terminal portion of UPF2 interacted with the
N-terminal nuclear export signal of UPF3B.
Lykke-Andersen et al. (2000) found that UPF2, UPF3A, and UPF3B were
complexed with UPF1 (RENT1; 601430) while in HeLa cell extracts. In
intact cells, UPF3A and UPF3B were found to be nucleocytoplasmic
shuttling proteins, while UPF2 was perinuclear, and UPF1 was
cytoplasmic. UPF3A and UPF3B associated selectively with spliced
beta-globin (141900) mRNA in vivo, and tethering of any UPF protein to
the 3-prime untranslated region of beta-globin mRNA elicited NMD. These
data suggested that assembly of a dynamic human UPF complex initiates in
the nucleus at mRNA exon-exon junctions and triggers NMD in the
cytoplasm when recognized downstream of a translation termination site.
By immunoprecipitation and immunoblot analyses of nucleoplasmic
fractions, Kim et al. (2001) showed that UPF3A and UPF3B are associated
in an RNase-resistant manner with Y14 (RBM8A; 605313), as well as with
the mRNA export factors ALY (604171) and TAP (NXF1; 602647), in
mRNA-protein complexes. UPF3 proteins appeared to bind immediately
upstream of exon-exon junctions. Kim et al. (2001) concluded that UPF3
proteins facilitate the export of spliced mRNAs by recruiting mRNA
export proteins. They proposed that UPF3 functions in NMD and travels
with the mRNA to the cytoplasm, where a leading translating ribosome
displaces the UPF3-Y14 complexes from the mRNA.
Using a reporter gene assay to quantify mRNA stability against NMD, Kunz
et al. (2006) showed that UPF3B caused NMD, whereas both isoforms of
UPF3A, UPF3AL and UPF3AS, had only weak NMD activity. Mutation analysis
revealed that the C termini of UPF3A and UPF3B were largely responsible
for NMD activity. The elevated NMD activity of UPF3B was due to the
presence of arg419, which is lacking in UPF3A. Immunoprecipitation
analysis revealed that NMD activity also required interaction of UPF3AL,
UPF3AS, or UPF3B with Magoh (602603), but not with UPF2. All UPF3
isoforms that showed at least partial NMD activity coprecipitated with
Magoh and also with EIF4AIII (EIF4A3; 608546) and BTZ (CASCS; 606504).
UPF3AS, UPF3AL, and, more potently, UPF3B also stimulated translation of
a reporter mRNA, and this stimulation was independent of their
C-terminal domains or interaction with Magoh, EIF4AIII, or BTZ. Deletion
of the N-terminal RRM domain, including the UPF2-interacting site,
significantly decreased translational activity of UPF3B.
In lymphoblastoid cells from 3 individuals with X-linked mental
retardation (MRXS14; 300676) and mutations in the UPF3B gene (e.g.,
300298.0001) resulting in undetectable full-length UPF3B protein, Chan
et al. (2009) observed upregulation of UPF3AL protein, but not UPF3AL
mRNA. Using overexpression and knockdown studies with HeLa and mouse
LM-TK cells, Chan et al. (2009) found that UPF3AL and UPF3B competed for
binding to UPF2, with UPF3B showing higher binding affinity for UPF2. In
the absence of UPF3B, UPF2 bound and stabilized UPF3AL against
proteolytic degradation. Microarray analysis identified 44 transcripts,
most of which showed NMD-inducing features, that were significantly
upregulated in response to depletion of both UPF3A and UPF3B, but not in
response to depletion of UPF3A or UPF3B alone, suggesting redundancy of
function.
Using chromatin immunoprecipitation and luciferase expression studies,
Leoyklang et al. (2013) demonstrated that the transcriptional regulator
SATB2 (608148) binds to the UPF3B promoter and activates UPF3B gene
transcription. Leoyklang et al. (2013) chose to study this interaction
because patients with mutation in the SATB2 gene (see Glass syndrome;
612313) have overlapping features with patients carrying mutations in
the UPF3B gene.
GENE STRUCTURE
By analysis of a PAC clone, Serin et al. (2001) determined that the
UPF3B gene contains 11 exons and spans 18.9 kb.
MAPPING
Scott (2001) mapped the UPF3B gene to Xq25-q26 based on sequence
similarity between the UPF3B sequence (GenBank GENBANK AY013251), an X
chromosome clone (GenBank GENBANK AC002477), and a genomic contig
(GenBank GENBANK NT_025333).
MOLECULAR GENETICS
In affected members of 4 unrelated families with X-linked syndromic
mental retardation (MRXS14; 300676), Tarpey et al. (2007) identified
hemizygous mutations in the UPF3B gene (300298.0001-300298.0004). The
phenotype was variable, but commonly included mild to severe mental
retardation, autistic features, slender build, poor musculature, long
face, high-arched palate, and pectus deformities.
Tarpey et al. (2009) sequenced the coding exons of the X chromosome in
208 families with X-linked mental retardation. They identified 3
separate nonrecurring truncating mutations in UPF3B that segregated
absolutely with the phenotype. In addition to the X-linked mental
retardation, affected family members had elements of the Opitz-Kaveggia
(305450) and Lujan-Fryns (309520) syndromes.
By exome sequencing of a Chinese family with nonsyndromic X-linked
mental retardation, Xu et al. (2013) identified a hemizygous mutation in
the UPF3B gene (R430X; 300298.0003).
*FIELD* AV
.0001
MENTAL RETARDATION, X-LINKED, SYNDROMIC 14
UPF3B, 4-BP DEL, 674GAAA
In 2 brothers with X-linked syndromic mental retardation (MRXS14;
300676), Tarpey et al. (2007) identified a hemizygous 4-bp deletion
(674delGAAA) in exon 7 of the UPF3B gene, resulting in a frameshift and
premature termination of the protein. The family had originally been
reported by Graham et al. (1998) as having Opitz-Kaveggia syndrome
(305450). Clinical features included macrocephaly, long, thin face,
widow's peak, upslanting palpebral fissures, long fingers, broad thumbs,
and severe mental retardation associated with dysgenesis of the corpus
callosum. Further studies showed that nonsense-mediated decay of mutant
mRNA was only partially compromised.
.0002
MENTAL RETARDATION, X-LINKED, SYNDROMIC 14
UPF3B, 2-BP DEL, 867AG
In 2 Australian brothers with MRXS14 (300676), Tarpey et al. (2007)
identified a hemizygous 2-bp deletion (867delAG) in exon 9 of the UPF3B
gene, resulting in a frameshift and premature termination of the
protein. Although the patients had originally been diagnosed with
Lujan-Fryns syndrome (309520), review showed that unaffected family
members were also tall. The patients had severe mental retardation,
long, thin face with high-arched palate, narrow chest, and poorly
developed musculature. One patient exhibited psychotic behavior. Further
studies showed that nonsense-mediated decay of mutant mRNA was only
partially compromised.
.0003
MENTAL RETARDATION, X-LINKED, SYNDROMIC 14
UPF3B, ARG430TER
In affected members of a 4-generation family with MRXS14 (300676),
Tarpey et al. (2007) identified a hemizygous 1288C-T transition in exon
10 of the UPF3B gene, resulting in an arg430-to-ter (R430X)
substitution. The family had originally been diagnosed with Lujan-Fryns
syndrome (309520). Affected males had severe mental retardation, long,
thin face and body habitus, high-arched palate, and stereotypical
behaviors.
By exome sequencing of a Chinese family with nonsyndromic X-linked
mental retardation, Xu et al. (2013) identified a hemizygous R430X
mutation in the UPF3B gene. The mutation was validated by Sanger
sequencing and segregated with the disorder. X-chromosome inactivation
studies in 3 carrier mothers showed that only 18%, 17%, and 13% of
lymphocytes, respectively, expressed the mutant allele. PCR analysis of
patient cells showed decreased levels of mutant mRNA in the patients,
suggesting that it undergoes nonsense-mediated mRNA decay. Patient cells
showed higher expression of the GADD45B gene (604948), a component of
the classical nonsense-mediated decay pathway, compared to controls,
suggesting that the UPF3B mutation caused dysregulation of this pathway.
.0004
MENTAL RETARDATION, X-LINKED, SYNDROMIC 14
UPF3B, TYR160ASP
In affected members of a family with MRXS14 (300676), Tarpey et al.
(2007) identified a hemizygous 478T-G transversion in exon 5 of the
UPF3B gene, resulting in a tyr160-to-asp (Y160D) substitution. One of
the patients was diagnosed with 'high-functioning autism.' Other
affected family members had long facies and mental retardation.
*FIELD* RF
1. Chan, W.-K.; Bhalla, A. D.; Le Hir, H.; Nguyen, L. S.; Huang, L.;
Gecz, J.; Wilkinson, M. F.: A UPF3-mediated regulatory switch that
maintains RNA surveillance. Nature Struct. Molec. Biol. 16: 747-753,
2009.
2. Graham, J. M., Jr.; Tackels, D.; Dibbern, K.; Superneau, D.; Rogers,
C.; Corning, K.; Schwartz, C. E.: FG syndrome: report of three new
families with linkage to Xq12-q22.1. Am. J. Med. Genet. 80: 145-156,
1998.
3. Kim, V. N.; Kataoka, N.; Dreyfuss, G.: Role of the nonsense-mediated
decay factor hUpf3 in the splicing-dependent exon-exon junction complex. Science 293:
1832-1836, 2001.
4. Kunz, J. B.; Neu-Yilik, G.; Hentze, M. W.; Kulozik, A. E.; Gehring,
N. H.: Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA decay
and translation. RNA 12: 1015-1022, 2006.
5. Leoyklang, P.; Suphapeetiporn, K.; Srichomthong, C.; Tongkobpetch,
S.; Fietze, S.; Dorward, H.; Cullinane, A. R.; Gahl, W. A.; Huizing,
M.; Shotelersuk, V.: Disorders with similar clinical phenotypes reveal
underlying genetic interaction: SATB2 acts as an activator of the
UPF3B gene. Hum. Genet. 132: 1383-1393, 2013.
6. Lykke-Andersen, J.; Shu, M.-D.; Steitz, J. A.: Human Upf proteins
target an mRNA for nonsense-mediated decay when bound downstream of
a termination codon. Cell 103: 1121-1131, 2000.
7. Scott, A. F.: Personal Communication. Baltimore, Md. 2/9/2001.
8. Serin, G.; Gersappe, A.; Black, J. D.; Aronoff, R.; Maquat, L.
E.: Identification and characterization of human orthologues to Saccharomyces
cerevisiae Upf2 protein and Upf3 protein (Caenorhabditis elegans SMG-4). Molec.
Cell. Biol. 21: 209-223, 2001.
9. Tarpey, P. S.; Raymond, F. L.; Nguyen, L. S.; Rodriguez, J.; Hackett,
A.; Vandeleur, L.; Smith, R.; Shoubridge, C.; Edkins, S.; Stevens,
C.; O'Meara, S.; Tofts, C.; and 45 others: Mutations in UPF3B,
a member of the nonsense-mediated mRNA decay complex, cause syndromic
and nonsyndromic mental retardation. Nature Genet. 39: 1127-1133,
2007.
10. Tarpey, P. S.; Smith, R.; Pleasance, E.; Whibley, A.; Edkins,
S.; Hardy, C.; O'Meara, S.; Latimer, C.; Dicks, E.; Menzies, A.; Stephens,
P.; Blow, M.; and 67 others: A systematic, large-scale resequencing
screen of X-chromosome coding exons in mental retardation. Nature
Genet. 41: 535-543, 2009.
11. Xu, X.; Zhang, L.; Tong, P.; Xun, G.; Su, W.; Xiong, Z.; Zhu,
T.; Zheng, Y.; Luo, S.; Pan, Y.; Xia, K.; Hu, Z.: Exome sequencing
identifies UPF3B as the causative gene for a Chinese non-syndrome
mental retardation pedigree. Clin. Genet. 83: 560-564, 2013.
*FIELD* CN
Cassandra L. Kniffin - updated: 1/13/2014
Cassandra L. Kniffin - updated: 6/4/2013
Patricia A. Hartz - updated: 2/14/2011
Ada Hamosh - updated: 10/1/2009
Cassandra L. Kniffin - updated: 9/13/2007
Paul J. Converse - updated: 9/19/2001
*FIELD* CD
Stylianos E. Antonarakis: 2/9/2001
*FIELD* ED
carol: 01/14/2014
ckniffin: 1/13/2014
carol: 9/11/2013
alopez: 6/12/2013
ckniffin: 6/4/2013
mgross: 4/6/2011
terry: 2/14/2011
alopez: 10/7/2009
terry: 10/1/2009
alopez: 9/24/2007
ckniffin: 9/13/2007
mgross: 3/12/2003
mgross: 9/19/2001
mgross: 2/9/2001
*RECORD*
*FIELD* NO
300298
*FIELD* TI
*300298 UPF3, YEAST, HOMOLOG OF, B; UPF3B
;;REGULATOR OF NONSENSE TRANSCRIPTS 3B; RENT3B;;
read moreUPF3X
*FIELD* TX
DESCRIPTION
Nonsense-mediated decay (NMD) is a mechanism for degrading transcripts
with premature termination codons arising from errors in transcription
or splicing, from mutated genes, or from genes that are physiologically
regulated by NMD. UPF3A (605530) and UPF3B are components of an
exon-junction complex that promotes NMD and regulates translation
efficiency (summary by Kunz et al., 2006).
CLONING
By searching sequence databases for homologs of the yeast Upf2 and Upf3
genes, followed by RT-PCR, Lykke-Andersen et al. (2000) isolated cDNAs
encoding 3 human proteins, which they named UPF2 (605529), UPF3A, and
UPF3B. The predicted UPF2, UPF3A, and UPF3B proteins contain 1,272, 476,
and 470 amino acids, respectively.
Using comparative genomics and RACE, Serin et al. (2001) isolated cDNAs
encoding UPF3A, which they called UPF3, and UPF3B, which they called
UPF3X. UPF3B encodes a 483-amino acid protein and a 470-amino acid
splice variant that lacks exon 8. Northern blot analysis revealed
expression of a 2.4-kb UPF3B transcript in HeLa cells. RT-PCR detected
variable UPF3B expression in all tissues examined, with highest
expression in testis and fetal brain. Epitope-tagged UPF3B was expressed
in the nucleus of transfected HeLa cells.
GENE FUNCTION
Using mutation and Western blot analyses, Serin et al. (2001) showed
that the central-to-C-terminal portion of UPF2 interacted with the
N-terminal nuclear export signal of UPF3B.
Lykke-Andersen et al. (2000) found that UPF2, UPF3A, and UPF3B were
complexed with UPF1 (RENT1; 601430) while in HeLa cell extracts. In
intact cells, UPF3A and UPF3B were found to be nucleocytoplasmic
shuttling proteins, while UPF2 was perinuclear, and UPF1 was
cytoplasmic. UPF3A and UPF3B associated selectively with spliced
beta-globin (141900) mRNA in vivo, and tethering of any UPF protein to
the 3-prime untranslated region of beta-globin mRNA elicited NMD. These
data suggested that assembly of a dynamic human UPF complex initiates in
the nucleus at mRNA exon-exon junctions and triggers NMD in the
cytoplasm when recognized downstream of a translation termination site.
By immunoprecipitation and immunoblot analyses of nucleoplasmic
fractions, Kim et al. (2001) showed that UPF3A and UPF3B are associated
in an RNase-resistant manner with Y14 (RBM8A; 605313), as well as with
the mRNA export factors ALY (604171) and TAP (NXF1; 602647), in
mRNA-protein complexes. UPF3 proteins appeared to bind immediately
upstream of exon-exon junctions. Kim et al. (2001) concluded that UPF3
proteins facilitate the export of spliced mRNAs by recruiting mRNA
export proteins. They proposed that UPF3 functions in NMD and travels
with the mRNA to the cytoplasm, where a leading translating ribosome
displaces the UPF3-Y14 complexes from the mRNA.
Using a reporter gene assay to quantify mRNA stability against NMD, Kunz
et al. (2006) showed that UPF3B caused NMD, whereas both isoforms of
UPF3A, UPF3AL and UPF3AS, had only weak NMD activity. Mutation analysis
revealed that the C termini of UPF3A and UPF3B were largely responsible
for NMD activity. The elevated NMD activity of UPF3B was due to the
presence of arg419, which is lacking in UPF3A. Immunoprecipitation
analysis revealed that NMD activity also required interaction of UPF3AL,
UPF3AS, or UPF3B with Magoh (602603), but not with UPF2. All UPF3
isoforms that showed at least partial NMD activity coprecipitated with
Magoh and also with EIF4AIII (EIF4A3; 608546) and BTZ (CASCS; 606504).
UPF3AS, UPF3AL, and, more potently, UPF3B also stimulated translation of
a reporter mRNA, and this stimulation was independent of their
C-terminal domains or interaction with Magoh, EIF4AIII, or BTZ. Deletion
of the N-terminal RRM domain, including the UPF2-interacting site,
significantly decreased translational activity of UPF3B.
In lymphoblastoid cells from 3 individuals with X-linked mental
retardation (MRXS14; 300676) and mutations in the UPF3B gene (e.g.,
300298.0001) resulting in undetectable full-length UPF3B protein, Chan
et al. (2009) observed upregulation of UPF3AL protein, but not UPF3AL
mRNA. Using overexpression and knockdown studies with HeLa and mouse
LM-TK cells, Chan et al. (2009) found that UPF3AL and UPF3B competed for
binding to UPF2, with UPF3B showing higher binding affinity for UPF2. In
the absence of UPF3B, UPF2 bound and stabilized UPF3AL against
proteolytic degradation. Microarray analysis identified 44 transcripts,
most of which showed NMD-inducing features, that were significantly
upregulated in response to depletion of both UPF3A and UPF3B, but not in
response to depletion of UPF3A or UPF3B alone, suggesting redundancy of
function.
Using chromatin immunoprecipitation and luciferase expression studies,
Leoyklang et al. (2013) demonstrated that the transcriptional regulator
SATB2 (608148) binds to the UPF3B promoter and activates UPF3B gene
transcription. Leoyklang et al. (2013) chose to study this interaction
because patients with mutation in the SATB2 gene (see Glass syndrome;
612313) have overlapping features with patients carrying mutations in
the UPF3B gene.
GENE STRUCTURE
By analysis of a PAC clone, Serin et al. (2001) determined that the
UPF3B gene contains 11 exons and spans 18.9 kb.
MAPPING
Scott (2001) mapped the UPF3B gene to Xq25-q26 based on sequence
similarity between the UPF3B sequence (GenBank GENBANK AY013251), an X
chromosome clone (GenBank GENBANK AC002477), and a genomic contig
(GenBank GENBANK NT_025333).
MOLECULAR GENETICS
In affected members of 4 unrelated families with X-linked syndromic
mental retardation (MRXS14; 300676), Tarpey et al. (2007) identified
hemizygous mutations in the UPF3B gene (300298.0001-300298.0004). The
phenotype was variable, but commonly included mild to severe mental
retardation, autistic features, slender build, poor musculature, long
face, high-arched palate, and pectus deformities.
Tarpey et al. (2009) sequenced the coding exons of the X chromosome in
208 families with X-linked mental retardation. They identified 3
separate nonrecurring truncating mutations in UPF3B that segregated
absolutely with the phenotype. In addition to the X-linked mental
retardation, affected family members had elements of the Opitz-Kaveggia
(305450) and Lujan-Fryns (309520) syndromes.
By exome sequencing of a Chinese family with nonsyndromic X-linked
mental retardation, Xu et al. (2013) identified a hemizygous mutation in
the UPF3B gene (R430X; 300298.0003).
*FIELD* AV
.0001
MENTAL RETARDATION, X-LINKED, SYNDROMIC 14
UPF3B, 4-BP DEL, 674GAAA
In 2 brothers with X-linked syndromic mental retardation (MRXS14;
300676), Tarpey et al. (2007) identified a hemizygous 4-bp deletion
(674delGAAA) in exon 7 of the UPF3B gene, resulting in a frameshift and
premature termination of the protein. The family had originally been
reported by Graham et al. (1998) as having Opitz-Kaveggia syndrome
(305450). Clinical features included macrocephaly, long, thin face,
widow's peak, upslanting palpebral fissures, long fingers, broad thumbs,
and severe mental retardation associated with dysgenesis of the corpus
callosum. Further studies showed that nonsense-mediated decay of mutant
mRNA was only partially compromised.
.0002
MENTAL RETARDATION, X-LINKED, SYNDROMIC 14
UPF3B, 2-BP DEL, 867AG
In 2 Australian brothers with MRXS14 (300676), Tarpey et al. (2007)
identified a hemizygous 2-bp deletion (867delAG) in exon 9 of the UPF3B
gene, resulting in a frameshift and premature termination of the
protein. Although the patients had originally been diagnosed with
Lujan-Fryns syndrome (309520), review showed that unaffected family
members were also tall. The patients had severe mental retardation,
long, thin face with high-arched palate, narrow chest, and poorly
developed musculature. One patient exhibited psychotic behavior. Further
studies showed that nonsense-mediated decay of mutant mRNA was only
partially compromised.
.0003
MENTAL RETARDATION, X-LINKED, SYNDROMIC 14
UPF3B, ARG430TER
In affected members of a 4-generation family with MRXS14 (300676),
Tarpey et al. (2007) identified a hemizygous 1288C-T transition in exon
10 of the UPF3B gene, resulting in an arg430-to-ter (R430X)
substitution. The family had originally been diagnosed with Lujan-Fryns
syndrome (309520). Affected males had severe mental retardation, long,
thin face and body habitus, high-arched palate, and stereotypical
behaviors.
By exome sequencing of a Chinese family with nonsyndromic X-linked
mental retardation, Xu et al. (2013) identified a hemizygous R430X
mutation in the UPF3B gene. The mutation was validated by Sanger
sequencing and segregated with the disorder. X-chromosome inactivation
studies in 3 carrier mothers showed that only 18%, 17%, and 13% of
lymphocytes, respectively, expressed the mutant allele. PCR analysis of
patient cells showed decreased levels of mutant mRNA in the patients,
suggesting that it undergoes nonsense-mediated mRNA decay. Patient cells
showed higher expression of the GADD45B gene (604948), a component of
the classical nonsense-mediated decay pathway, compared to controls,
suggesting that the UPF3B mutation caused dysregulation of this pathway.
.0004
MENTAL RETARDATION, X-LINKED, SYNDROMIC 14
UPF3B, TYR160ASP
In affected members of a family with MRXS14 (300676), Tarpey et al.
(2007) identified a hemizygous 478T-G transversion in exon 5 of the
UPF3B gene, resulting in a tyr160-to-asp (Y160D) substitution. One of
the patients was diagnosed with 'high-functioning autism.' Other
affected family members had long facies and mental retardation.
*FIELD* RF
1. Chan, W.-K.; Bhalla, A. D.; Le Hir, H.; Nguyen, L. S.; Huang, L.;
Gecz, J.; Wilkinson, M. F.: A UPF3-mediated regulatory switch that
maintains RNA surveillance. Nature Struct. Molec. Biol. 16: 747-753,
2009.
2. Graham, J. M., Jr.; Tackels, D.; Dibbern, K.; Superneau, D.; Rogers,
C.; Corning, K.; Schwartz, C. E.: FG syndrome: report of three new
families with linkage to Xq12-q22.1. Am. J. Med. Genet. 80: 145-156,
1998.
3. Kim, V. N.; Kataoka, N.; Dreyfuss, G.: Role of the nonsense-mediated
decay factor hUpf3 in the splicing-dependent exon-exon junction complex. Science 293:
1832-1836, 2001.
4. Kunz, J. B.; Neu-Yilik, G.; Hentze, M. W.; Kulozik, A. E.; Gehring,
N. H.: Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA decay
and translation. RNA 12: 1015-1022, 2006.
5. Leoyklang, P.; Suphapeetiporn, K.; Srichomthong, C.; Tongkobpetch,
S.; Fietze, S.; Dorward, H.; Cullinane, A. R.; Gahl, W. A.; Huizing,
M.; Shotelersuk, V.: Disorders with similar clinical phenotypes reveal
underlying genetic interaction: SATB2 acts as an activator of the
UPF3B gene. Hum. Genet. 132: 1383-1393, 2013.
6. Lykke-Andersen, J.; Shu, M.-D.; Steitz, J. A.: Human Upf proteins
target an mRNA for nonsense-mediated decay when bound downstream of
a termination codon. Cell 103: 1121-1131, 2000.
7. Scott, A. F.: Personal Communication. Baltimore, Md. 2/9/2001.
8. Serin, G.; Gersappe, A.; Black, J. D.; Aronoff, R.; Maquat, L.
E.: Identification and characterization of human orthologues to Saccharomyces
cerevisiae Upf2 protein and Upf3 protein (Caenorhabditis elegans SMG-4). Molec.
Cell. Biol. 21: 209-223, 2001.
9. Tarpey, P. S.; Raymond, F. L.; Nguyen, L. S.; Rodriguez, J.; Hackett,
A.; Vandeleur, L.; Smith, R.; Shoubridge, C.; Edkins, S.; Stevens,
C.; O'Meara, S.; Tofts, C.; and 45 others: Mutations in UPF3B,
a member of the nonsense-mediated mRNA decay complex, cause syndromic
and nonsyndromic mental retardation. Nature Genet. 39: 1127-1133,
2007.
10. Tarpey, P. S.; Smith, R.; Pleasance, E.; Whibley, A.; Edkins,
S.; Hardy, C.; O'Meara, S.; Latimer, C.; Dicks, E.; Menzies, A.; Stephens,
P.; Blow, M.; and 67 others: A systematic, large-scale resequencing
screen of X-chromosome coding exons in mental retardation. Nature
Genet. 41: 535-543, 2009.
11. Xu, X.; Zhang, L.; Tong, P.; Xun, G.; Su, W.; Xiong, Z.; Zhu,
T.; Zheng, Y.; Luo, S.; Pan, Y.; Xia, K.; Hu, Z.: Exome sequencing
identifies UPF3B as the causative gene for a Chinese non-syndrome
mental retardation pedigree. Clin. Genet. 83: 560-564, 2013.
*FIELD* CN
Cassandra L. Kniffin - updated: 1/13/2014
Cassandra L. Kniffin - updated: 6/4/2013
Patricia A. Hartz - updated: 2/14/2011
Ada Hamosh - updated: 10/1/2009
Cassandra L. Kniffin - updated: 9/13/2007
Paul J. Converse - updated: 9/19/2001
*FIELD* CD
Stylianos E. Antonarakis: 2/9/2001
*FIELD* ED
carol: 01/14/2014
ckniffin: 1/13/2014
carol: 9/11/2013
alopez: 6/12/2013
ckniffin: 6/4/2013
mgross: 4/6/2011
terry: 2/14/2011
alopez: 10/7/2009
terry: 10/1/2009
alopez: 9/24/2007
ckniffin: 9/13/2007
mgross: 3/12/2003
mgross: 9/19/2001
mgross: 2/9/2001
MIM
300676
*RECORD*
*FIELD* NO
300676
*FIELD* TI
#300676 MENTAL RETARDATION, X-LINKED, SYNDROMIC 14; MRXS14
*FIELD* TX
A number sign (#) is used with this entry because X-linked syndromic
read moremental retardation-14 (MRXS14) is caused by mutation in the UPF3B gene
(300298), which is involved in nonsense-mediated decay of mRNA
transcripts, on chromosome Xq25-q26. Some patients have nonsyndromic
mental retardation.
CLINICAL FEATURES
Tarpey et al. (2007) reported 4 unrelated families with X-linked mental
retardation. Although the phenotype was variable, common features
included mild to severe mental retardation, autistic features, slender
build, poor musculature, long, thin face, high-arched palate, high nasal
bridge, and pectus deformities. Two families had been diagnosed as
having Lujan-Fryns syndrome (309520) and 1 as having Opitz-Kaveggia
syndrome (OKS; 305450). One of the families had been reported by Graham
et al. (1998).
Xu et al. (2013) reported a large Chinese family in which 3 living males
and 1 deceased male had nonsyndromic mild mental retardation. None of
the affected individuals was known to have additional physical
abnormalities. Carrier females were unaffected.
INHERITANCE
The transmission pattern in the families with mental retardation
reported by Tarpey et al. (2007) and Xu et al. (2013) was consistent
with X-linked recessive inheritance.
MOLECULAR GENETICS
In affected members of 4 unrelated families with X-linked syndromic
mental retardation, Tarpey et al. (2007) identified hemizygous mutations
in the UPF3B gene (300298.0001-300298.0004).
Tarpey et al. (2009) sequenced the coding exons of the X chromosome in
208 families with X-linked mental retardation. They identified 3
separate nonrecurring truncating mutations in UPF3B that segregated
absolutely with the phenotype. In addition to the X-linked mental
retardation, affected family members had elements of the Opitz-Kaveggia
and Lujan-Fryns syndromes.
By exome sequencing of a Chinese family with nonsyndromic X-linked
mental retardation, Xu et al. (2013) identified a hemizygous mutation in
the UPF3B gene (R430X; 300298.0003). X-chromosome inactivation studies
in 3 carrier mothers showed that only 18%, 17%, and 13% of lymphocytes,
respectively, expressed the mutant allele. PCR analysis of patient cells
showed decreased levels of mutant mRNA in the patients, suggesting that
it undergoes nonsense-mediated mRNA decay. Patient cells showed higher
expression of the GADD45B gene (604948), a component of the classical
nonsense-mediated decay pathway compared to controls, suggesting that
the UPF3B mutation caused dysregulation of this pathway.
*FIELD* RF
1. Graham, J. M., Jr.; Tackels, D.; Dibbern, K.; Superneau, D.; Rogers,
C.; Corning, K.; Schwartz, C. E.: FG syndrome: report of three new
families with linkage to Xq12-q22.1. Am. J. Med. Genet. 80: 145-156,
1998.
2. Tarpey, P. S.; Raymond, F. L.; Nguyen, L. S.; Rodriguez, J.; Hackett,
A.; Vandeleur, L.; Smith, R.; Shoubridge, C.; Edkins, S.; Stevens,
C.; O'Meara, S.; Tofts, C.; and 45 others: Mutations in UPF3B,
a member of the nonsense-mediated mRNA decay complex, cause syndromic
and nonsyndromic mental retardation. Nature Genet. 39: 1127-1133,
2007.
3. Tarpey, P. S.; Smith, R.; Pleasance, E.; Whibley, A.; Edkins, S.;
Hardy, C.; O'Meara, S.; Latimer, C.; Dicks, E.; Menzies, A.; Stephens,
P.; Blow, M.; and 67 others: A systematic, large-scale resequencing
screen of X-chromosome coding exons in mental retardation. Nature
Genet. 41: 535-543, 2009.
4. Xu, X.; Zhang, L.; Tong, P.; Xun, G.; Su, W.; Xiong, Z.; Zhu, T.;
Zheng, Y.; Luo, S.; Pan, Y.; Xia, K.; Hu, Z.: Exome sequencing identifies
UPF3B as the causative gene for a Chinese non-syndrome mental retardation
pedigree. Clin. Genet. 83: 560-564, 2013.
*FIELD* CS
INHERITANCE:
X-linked recessive
GROWTH:
[Height];
Tall, thin habitus
HEAD AND NECK:
[Head];
Macrocephaly;
[Face];
Long, thin face;
Prominent forehead;
Maxillary hypoplasia;
Prominent jaw;
[Nose];
High nasal bridge;
[Mouth];
High-arched palate
CHEST:
[External features];
Pectus excavatum;
Pectus carinatum;
Narrow chest
SKELETAL:
[Spine];
Kyphosis;
Scoliosis;
[Hands];
Long hands;
Long fingers;
[Feet];
Long feet
MUSCLE, SOFT TISSUE:
Poor musculature
NEUROLOGIC:
[Central nervous system];
Mental retardation, mild to severe;
[Behavioral/psychiatric manifestations];
Autistic features
VOICE:
Hypernasal voice
MOLECULAR BASIS:
Caused by mutation in the UPF3, B, yeast homolog gene (UPF3B, 300298.0001)
*FIELD* CD
Cassandra L. Kniffin: 9/13/2007
*FIELD* ED
joanna: 10/11/2007
ckniffin: 9/13/2007
*FIELD* CN
Cassandra L. Kniffin - updated: 6/4/2013
Ada Hamosh - updated: 10/1/2009
*FIELD* CD
Cassandra L. Kniffin: 9/13/2007
*FIELD* ED
carol: 07/02/2013
alopez: 6/12/2013
ckniffin: 6/4/2013
alopez: 10/7/2009
terry: 10/1/2009
alopez: 9/24/2007
ckniffin: 9/13/2007
*RECORD*
*FIELD* NO
300676
*FIELD* TI
#300676 MENTAL RETARDATION, X-LINKED, SYNDROMIC 14; MRXS14
*FIELD* TX
A number sign (#) is used with this entry because X-linked syndromic
read moremental retardation-14 (MRXS14) is caused by mutation in the UPF3B gene
(300298), which is involved in nonsense-mediated decay of mRNA
transcripts, on chromosome Xq25-q26. Some patients have nonsyndromic
mental retardation.
CLINICAL FEATURES
Tarpey et al. (2007) reported 4 unrelated families with X-linked mental
retardation. Although the phenotype was variable, common features
included mild to severe mental retardation, autistic features, slender
build, poor musculature, long, thin face, high-arched palate, high nasal
bridge, and pectus deformities. Two families had been diagnosed as
having Lujan-Fryns syndrome (309520) and 1 as having Opitz-Kaveggia
syndrome (OKS; 305450). One of the families had been reported by Graham
et al. (1998).
Xu et al. (2013) reported a large Chinese family in which 3 living males
and 1 deceased male had nonsyndromic mild mental retardation. None of
the affected individuals was known to have additional physical
abnormalities. Carrier females were unaffected.
INHERITANCE
The transmission pattern in the families with mental retardation
reported by Tarpey et al. (2007) and Xu et al. (2013) was consistent
with X-linked recessive inheritance.
MOLECULAR GENETICS
In affected members of 4 unrelated families with X-linked syndromic
mental retardation, Tarpey et al. (2007) identified hemizygous mutations
in the UPF3B gene (300298.0001-300298.0004).
Tarpey et al. (2009) sequenced the coding exons of the X chromosome in
208 families with X-linked mental retardation. They identified 3
separate nonrecurring truncating mutations in UPF3B that segregated
absolutely with the phenotype. In addition to the X-linked mental
retardation, affected family members had elements of the Opitz-Kaveggia
and Lujan-Fryns syndromes.
By exome sequencing of a Chinese family with nonsyndromic X-linked
mental retardation, Xu et al. (2013) identified a hemizygous mutation in
the UPF3B gene (R430X; 300298.0003). X-chromosome inactivation studies
in 3 carrier mothers showed that only 18%, 17%, and 13% of lymphocytes,
respectively, expressed the mutant allele. PCR analysis of patient cells
showed decreased levels of mutant mRNA in the patients, suggesting that
it undergoes nonsense-mediated mRNA decay. Patient cells showed higher
expression of the GADD45B gene (604948), a component of the classical
nonsense-mediated decay pathway compared to controls, suggesting that
the UPF3B mutation caused dysregulation of this pathway.
*FIELD* RF
1. Graham, J. M., Jr.; Tackels, D.; Dibbern, K.; Superneau, D.; Rogers,
C.; Corning, K.; Schwartz, C. E.: FG syndrome: report of three new
families with linkage to Xq12-q22.1. Am. J. Med. Genet. 80: 145-156,
1998.
2. Tarpey, P. S.; Raymond, F. L.; Nguyen, L. S.; Rodriguez, J.; Hackett,
A.; Vandeleur, L.; Smith, R.; Shoubridge, C.; Edkins, S.; Stevens,
C.; O'Meara, S.; Tofts, C.; and 45 others: Mutations in UPF3B,
a member of the nonsense-mediated mRNA decay complex, cause syndromic
and nonsyndromic mental retardation. Nature Genet. 39: 1127-1133,
2007.
3. Tarpey, P. S.; Smith, R.; Pleasance, E.; Whibley, A.; Edkins, S.;
Hardy, C.; O'Meara, S.; Latimer, C.; Dicks, E.; Menzies, A.; Stephens,
P.; Blow, M.; and 67 others: A systematic, large-scale resequencing
screen of X-chromosome coding exons in mental retardation. Nature
Genet. 41: 535-543, 2009.
4. Xu, X.; Zhang, L.; Tong, P.; Xun, G.; Su, W.; Xiong, Z.; Zhu, T.;
Zheng, Y.; Luo, S.; Pan, Y.; Xia, K.; Hu, Z.: Exome sequencing identifies
UPF3B as the causative gene for a Chinese non-syndrome mental retardation
pedigree. Clin. Genet. 83: 560-564, 2013.
*FIELD* CS
INHERITANCE:
X-linked recessive
GROWTH:
[Height];
Tall, thin habitus
HEAD AND NECK:
[Head];
Macrocephaly;
[Face];
Long, thin face;
Prominent forehead;
Maxillary hypoplasia;
Prominent jaw;
[Nose];
High nasal bridge;
[Mouth];
High-arched palate
CHEST:
[External features];
Pectus excavatum;
Pectus carinatum;
Narrow chest
SKELETAL:
[Spine];
Kyphosis;
Scoliosis;
[Hands];
Long hands;
Long fingers;
[Feet];
Long feet
MUSCLE, SOFT TISSUE:
Poor musculature
NEUROLOGIC:
[Central nervous system];
Mental retardation, mild to severe;
[Behavioral/psychiatric manifestations];
Autistic features
VOICE:
Hypernasal voice
MOLECULAR BASIS:
Caused by mutation in the UPF3, B, yeast homolog gene (UPF3B, 300298.0001)
*FIELD* CD
Cassandra L. Kniffin: 9/13/2007
*FIELD* ED
joanna: 10/11/2007
ckniffin: 9/13/2007
*FIELD* CN
Cassandra L. Kniffin - updated: 6/4/2013
Ada Hamosh - updated: 10/1/2009
*FIELD* CD
Cassandra L. Kniffin: 9/13/2007
*FIELD* ED
carol: 07/02/2013
alopez: 6/12/2013
ckniffin: 6/4/2013
alopez: 10/7/2009
terry: 10/1/2009
alopez: 9/24/2007
ckniffin: 9/13/2007