ID REN3A_HUMAN Reviewed; 476 AA. AC Q9H1J1; A2A366; Q5T8C3; Q5T8C9; Q7Z6N3; Q86YK1; Q9BZI8; DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 1. DT 28-JAN-2026, entry version 186. DE RecName: Full=Regulator of nonsense transcripts 3A; DE AltName: Full=Nonsense mRNA reducing factor 3A; DE AltName: Full=Up-frameshift suppressor 3 homolog A; DE Short=hUpf3; GN Name=UPF3A; Synonyms=RENT3A, UPF3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION IN NONSENSE-MEDIATED MRNA RP 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 bound RT downstream of a termination codon."; RL Cell 103:1121-1131(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057823; DOI=10.1038/nature02379; RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L., RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., RA Frankish A.G., Frankland J., French L., Garner P., Garnett J., RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., RA Rogers J., Ross M.T.; RT "The DNA sequence and analysis of human chromosome 13."; RL Nature 428:522-528(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). RC TISSUE=Brain, and Eye; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 25-476 (ISOFORM 1), INTERACTION WITH UPF2, RP SUBCELLULAR 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 Saccharomyces RT cerevisiae Upf2 protein and Upf3 protein (Caenorhabditis elegans SMG-4)."; RL Mol. Cell. Biol. 21:209-223(2001). RN [6] RP INTERACTION WITH RBM8A, IDENTIFICATION IN A POST-SPLICING MRNP COMPLEX, RP 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-dependent RT exon-exon junction complex."; RL Science 293:1832-1836(2001). RN [7] RP IDENTIFICATION IN A POST-SPLICING MRNP COMPLEX, AND ASSOCIATION WITH THE RP 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 [8] RP PROBABLE INTERACTION WITH SMG1. 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 LACK OF ACTIVITY IN NMD, FUNCTION IN TRANSLATION STIMULATION, PROTEIN RP INTERACTION, AND MUTAGENESIS OF ALA-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 [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-341, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [11] RP INTERACTION WITH DHX34. RX PubMed=25220460; DOI=10.1016/j.celrep.2014.08.020; RA Hug N., Caceres J.F.; RT "The RNA helicase DHX34 activates NMD by promoting a transition from the RT surveillance to the decay-inducing complex."; RL Cell Rep. 8:1845-1856(2014). RN [12] RP STRUCTURE BY NMR OF 70-155. RG Northeast structural genomics consortium (NESG); RT "Solution NMR structure of nonsense mRNA reducing factor 3A from H. RT sapiens, northeast structural genomics consortium target HR4714B."; RL Submitted (AUG-2010) to the PDB data bank. CC -!- FUNCTION: Involved in nonsense-mediated decay (NMD) of mRNAs containing CC premature stop codons by associating with the nuclear exon junction CC complex (EJC) and serving as link between the EJC core and NMD CC machinery. Recruits UPF2 at the cytoplasmic side of the nuclear CC envelope and the subsequent formation of an UPF1-UPF2-UPF3 surveillance CC complex (including UPF1 bound to release factors at the stalled CC ribosome) is believed to activate NMD. However, UPF3A is shown to be CC only marginally active in NMD as compared to UPF3B. Binds spliced mRNA CC upstream of exon-exon junctions. In vitro, weakly stimulates CC translation. {ECO:0000269|PubMed:11163187, CC ECO:0000269|PubMed:16601204}. CC -!- SUBUNIT: Found in a post-splicing messenger ribonucleoprotein (mRNP) CC complex. Associates with the exon junction complex (EJC). Interacts CC with UPF2 and RBM8A. Interacts with DHX34; the interaction is RNA- CC independent (PubMed:25220460). {ECO:0000269|PubMed:11113196, CC ECO:0000269|PubMed:11163187, ECO:0000269|PubMed:11546873, CC ECO:0000269|PubMed:11546874, ECO:0000269|PubMed:25220460}. CC -!- INTERACTION: CC Q9H1J1; Q9Y5S9: RBM8A; NbExp=4; IntAct=EBI-521530, EBI-447231; CC Q9H1J1; Q92900: UPF1; NbExp=4; IntAct=EBI-521530, EBI-373471; CC Q9H1J1; Q9HAU5: UPF2; NbExp=5; IntAct=EBI-521530, EBI-372073; CC Q9H1J1; Q9BZI7-2: UPF3B; NbExp=2; IntAct=EBI-521530, EBI-15674130; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11163187}. Cytoplasm CC {ECO:0000269|PubMed:11163187}. Note=Shuttling between the nucleus and CC the cytoplasm. {ECO:0000269|PubMed:11163187}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=hUpf3p, hUPF3L; CC IsoId=Q9H1J1-1; Sequence=Displayed; CC Name=2; Synonyms=hUpf3pdelta, hUPF3S; CC IsoId=Q9H1J1-2; Sequence=VSP_012962; CC Name=3; CC IsoId=Q9H1J1-3; Sequence=VSP_012961; CC -!- TISSUE SPECIFICITY: Isoform 1 is strongly expressed in testis, uterus, CC muscle, fetal brain and spinal cord. Isoform 2 is strongly expressed in CC fetal brain and spinal cord. {ECO:0000269|PubMed:11113196}. CC -!- SIMILARITY: Belongs to the RENT3 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY013250; AAG48510.1; -; mRNA. DR EMBL; AL160396; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471085; EAX09252.1; -; Genomic_DNA. DR EMBL; BC008694; AAH08694.1; -; mRNA. DR EMBL; BC023569; AAH23569.1; -; mRNA. DR EMBL; AF318575; AAG60690.1; -; mRNA. DR CCDS; CCDS9543.1; -. [Q9H1J1-1] DR CCDS; CCDS9544.1; -. [Q9H1J1-2] DR RefSeq; NP_075387.1; NM_023011.4. [Q9H1J1-1] DR RefSeq; NP_542418.1; NM_080687.3. [Q9H1J1-2] DR PDB; 2L08; NMR; -; A=70-155. DR PDB; 7QG6; X-ray; 2.95 A; A/C/E/G=58-206. DR PDBsum; 2L08; -. DR PDBsum; 7QG6; -. DR AlphaFoldDB; Q9H1J1; -. DR BMRB; Q9H1J1; -. DR SMR; Q9H1J1; -. DR BioGRID; 122397; 48. DR CORUM; Q9H1J1; -. DR DIP; DIP-31146N; -. DR FunCoup; Q9H1J1; 3695. DR IntAct; Q9H1J1; 39. DR MINT; Q9H1J1; -. DR STRING; 9606.ENSP00000364448; -. DR GlyGen; Q9H1J1; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9H1J1; -. DR PhosphoSitePlus; Q9H1J1; -. DR BioMuta; UPF3A; -. DR DMDM; 60390646; -. DR jPOST; Q9H1J1; -. DR MassIVE; Q9H1J1; -. DR PaxDb; 9606-ENSP00000364448; -. DR PeptideAtlas; Q9H1J1; -. DR ProteomicsDB; 80415; -. [Q9H1J1-1] DR ProteomicsDB; 80416; -. [Q9H1J1-2] DR ProteomicsDB; 80417; -. [Q9H1J1-3] DR Pumba; Q9H1J1; -. DR TopDownProteomics; Q9H1J1-2; -. [Q9H1J1-2] DR Antibodypedia; 11926; 91 antibodies from 28 providers. DR DNASU; 65110; -. DR Ensembl; ENST00000351487.5; ENSP00000329592.5; ENSG00000169062.16. [Q9H1J1-2] DR Ensembl; ENST00000375299.8; ENSP00000364448.3; ENSG00000169062.16. [Q9H1J1-1] DR GeneID; 65110; -. DR KEGG; hsa:65110; -. DR MANE-Select; ENST00000375299.8; ENSP00000364448.3; NM_023011.4; NP_075387.1. DR UCSC; uc001vup.4; human. [Q9H1J1-1] DR AGR; HGNC:20332; -. DR ClinPGx; PA134961553; -. DR CTD; 65110; -. DR DisGeNET; 65110; -. DR GeneCards; UPF3A; -. DR HGNC; HGNC:20332; UPF3A. DR HPA; ENSG00000169062; Low tissue specificity. DR MIM; 605530; gene. DR OpenTargets; ENSG00000169062; -. DR VEuPathDB; HostDB:ENSG00000169062; -. DR eggNOG; KOG1295; Eukaryota. DR GeneTree; ENSGT00390000017146; -. DR HOGENOM; CLU_041202_1_0_1; -. DR InParanoid; Q9H1J1; -. DR OMA; FSRVYFV; -. DR OrthoDB; 18087at2759; -. DR PAN-GO; Q9H1J1; 4 GO annotations based on evolutionary models. DR PhylomeDB; Q9H1J1; -. DR PathwayCommons; Q9H1J1; -. DR Reactome; R-HSA-9010553; Regulation of expression of SLITs and ROBOs. DR Reactome; R-HSA-975957; Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC). [Q9H1J1-2] DR SignaLink; Q9H1J1; -. DR Agora; ENSG00000169062; -. DR BioGRID-ORCS; 65110; 109 hits in 1128 CRISPR screens. DR CD-CODE; 91857CE7; Nucleolus. DR CD-CODE; DEE660B4; Stress granule. DR ChiTaRS; UPF3A; human. DR EvolutionaryTrace; Q9H1J1; -. DR GeneWiki; UPF3A; -. DR GenomeRNAi; 65110; -. DR Pharos; Q9H1J1; Tbio. DR PRO; PR:Q9H1J1; -. DR Proteomes; UP000005640; Chromosome 13. DR RNAct; Q9H1J1; protein. DR Bgee; ENSG00000169062; Expressed in right hemisphere of cerebellum and 117 other cell types or tissues. DR ExpressionAtlas; Q9H1J1; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0035145; C:exon-exon junction complex; IDA:GO_Central. DR GO; GO:0043005; C:neuron projection; IEA:Ensembl. DR GO; GO:0005730; C:nucleolus; IBA:GO_Central. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; NAS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0003729; F:mRNA binding; IDA:GO_Central. DR GO; GO:0140311; F:protein sequestering activity; IMP:MGI. DR GO; GO:0042162; F:telomeric DNA binding; IDA:BHF-UCL. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW. DR GO; GO:2000623; P:negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IPI:MGI. DR GO; GO:1905746; P:positive regulation of mRNA cis splicing, via spliceosome; IEA:Ensembl. DR GO; GO:0045727; P:positive regulation of translation; IDA:UniProtKB. DR GO; GO:0060816; P:random inactivation of X chromosome; IEA:Ensembl. DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl. DR CDD; cd12727; RRM_like_Smg4_UPF3A; 1. DR FunFam; 3.30.70.330:FF:000067; regulator of nonsense transcripts 3A isoform X2; 1. DR Gene3D; 3.30.70.330; -; 1. DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf. DR InterPro; IPR035979; RBD_domain_sf. DR InterPro; IPR039722; Upf3. DR InterPro; IPR005120; UPF3_dom. DR PANTHER; PTHR13112:SF2; REGULATOR OF NONSENSE TRANSCRIPTS 3A; 1. DR PANTHER; PTHR13112; UPF3 REGULATOR OF NONSENSE TRANSCRIPTS-LIKE PROTEIN; 1. DR Pfam; PF03467; Smg4_UPF3; 1. DR SUPFAM; SSF54928; RNA-binding domain, RBD; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; mRNA transport; KW Nonsense-mediated mRNA decay; Nucleus; Phosphoprotein; KW Proteomics identification; Reference proteome; RNA-binding; Transport. FT CHAIN 1..476 FT /note="Regulator of nonsense transcripts 3A" FT /id="PRO_0000215296" FT REGION 1..63 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 66..140 FT /note="Required for interaction with UPF2" FT REGION 250..476 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 421..434 FT /note="Required for association with EIF4A3 and ECJ core FT components CASC3, MAGOH and RBM8A" FT COMPBIAS 21..38 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 250..304 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 340..401 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 410..437 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 341 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT VAR_SEQ 1..325 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_012961" FT VAR_SEQ 141..173 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_012962" FT VARIANT 64 FT /note="R -> K (in dbSNP:rs3752105)" FT /id="VAR_062143" FT MUTAGEN 432 FT /note="A->R: Increases NMD activity and translation FT stimulation." FT /evidence="ECO:0000269|PubMed:16601204" FT CONFLICT 25 FT /note="K -> M (in Ref. 5; AAG60690)" FT /evidence="ECO:0000305" FT STRAND 69..75 FT /evidence="ECO:0007829|PDB:7QG6" FT HELIX 81..87 FT /evidence="ECO:0007829|PDB:7QG6" FT STRAND 94..100 FT /evidence="ECO:0007829|PDB:7QG6" FT STRAND 104..106 FT /evidence="ECO:0007829|PDB:7QG6" FT STRAND 112..120 FT /evidence="ECO:0007829|PDB:7QG6" FT TURN 121..123 FT /evidence="ECO:0007829|PDB:7QG6" FT HELIX 124..131 FT /evidence="ECO:0007829|PDB:7QG6" FT STRAND 135..137 FT /evidence="ECO:0007829|PDB:7QG6" FT STRAND 143..145 FT /evidence="ECO:0007829|PDB:7QG6" FT STRAND 147..150 FT /evidence="ECO:0007829|PDB:7QG6" FT HELIX 171..173 FT /evidence="ECO:0007829|PDB:7QG6" FT HELIX 175..184 FT /evidence="ECO:0007829|PDB:7QG6" SQ SEQUENCE 476 AA; 54696 MW; 023031890E47C4EB CRC64; MRSEKEGAGG LRAAVAARGP SGREKLSALE VQFHRDSQQQ EAETPPTSSS GCGGGAGKPR EEKRTALSKV VIRRLPPGLT KEQLEEQLRP LPAHDYFEFF AADLSLYPHL YSRAYINFRN PDDILLFRDR FDGYIFLDSK GLEYPAVVEF APFQKIAKKK LRKKDAKTGS IEDDPEYKKF LETYCVEEEK TSANPETLLG EMEAKTRELI ARRTTPLLEY IKNRKLEKQR IREEKREERR RRELEKKRLR EEEKRRRREE ERCKKKETDK QKKIAEKEVR IKLLKKPEKG EEPTTEKPKE RGEEIDTGGG KQESCAPGAV VKARPMEGSL EEPQETSHSG SDKEHRDVER SQEQESEAQR YHVDDGRRHR AHHEPERLSR RSEDEQRWGK GPGQDRGKKG SQDSGAPGEA MERLGRAQRC DDSPAPRKER LANKDRPALQ LYDPGARFRA RECGGNRRIC KAEGSGTGPE KREEAE //