REN3A_HUMAN
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 03-AUG-2022, entry version 170.
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}.
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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_023011.3. [Q9H1J1-1]
DR RefSeq; NP_542418.1; NM_080687.2. [Q9H1J1-2]
DR PDB; 2L08; NMR; -; A=70-155.
DR PDBsum; 2L08; -.
DR AlphaFoldDB; Q9H1J1; -.
DR BMRB; Q9H1J1; -.
DR SMR; Q9H1J1; -.
DR BioGRID; 122397; 41.
DR CORUM; Q9H1J1; -.
DR DIP; DIP-31146N; -.
DR IntAct; Q9H1J1; 36.
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 EPD; Q9H1J1; -.
DR jPOST; Q9H1J1; -.
DR MassIVE; Q9H1J1; -.
DR MaxQB; Q9H1J1; -.
DR PaxDb; Q9H1J1; -.
DR PeptideAtlas; Q9H1J1; -.
DR PRIDE; Q9H1J1; -.
DR ProteomicsDB; 80415; -. [Q9H1J1-1]
DR ProteomicsDB; 80416; -. [Q9H1J1-2]
DR ProteomicsDB; 80417; -. [Q9H1J1-3]
DR TopDownProteomics; Q9H1J1-2; -. [Q9H1J1-2]
DR Antibodypedia; 11926; 87 antibodies from 28 providers.
DR DNASU; 65110; -.
DR Ensembl; ENST00000351487.5; ENSP00000329592.5; ENSG00000169062.15. [Q9H1J1-2]
DR Ensembl; ENST00000375299.8; ENSP00000364448.3; ENSG00000169062.15. [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 CTD; 65110; -.
DR DisGeNET; 65110; -.
DR GeneCards; UPF3A; -.
DR HGNC; HGNC:20332; UPF3A.
DR HPA; ENSG00000169062; Low tissue specificity.
DR MIM; 605530; gene.
DR neXtProt; NX_Q9H1J1; -.
DR OpenTargets; ENSG00000169062; -.
DR PharmGKB; PA134961553; -.
DR VEuPathDB; HostDB:ENSG00000169062; -.
DR eggNOG; KOG1295; Eukaryota.
DR GeneTree; ENSGT00390000017146; -.
DR HOGENOM; CLU_041202_1_0_1; -.
DR InParanoid; Q9H1J1; -.
DR OMA; PYHASKI; -.
DR OrthoDB; 737663at2759; -.
DR PhylomeDB; Q9H1J1; -.
DR TreeFam; TF316034; -.
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 BioGRID-ORCS; 65110; 100 hits in 1048 CRISPR screens.
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 115 other tissues.
DR ExpressionAtlas; Q9H1J1; baseline and differential.
DR Genevisible; Q9H1J1; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0035145; C:exon-exon junction complex; IDA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
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:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0017056; F:structural constituent of nuclear pore; NAS:UniProtKB.
DR GO; GO:0042162; F:telomeric DNA binding; IDA:BHF-UCL.
DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; NAS:UniProtKB.
DR GO; GO:0045727; P:positive regulation of translation; IDA:UniProtKB.
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 InterPro; IPR034978; UPF3A.
DR PANTHER; PTHR13112; PTHR13112; 1.
DR PANTHER; PTHR13112:SF2; PTHR13112:SF2; 1.
DR Pfam; PF03467; Smg4_UPF3; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; mRNA transport;
KW Nonsense-mediated mRNA decay; Nucleus; Phosphoprotein; Reference proteome;
KW 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 32..51
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 250..308
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 328..397
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 414..436
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 450..476
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 70..73
FT /evidence="ECO:0007829|PDB:2L08"
FT HELIX 81..84
FT /evidence="ECO:0007829|PDB:2L08"
FT TURN 85..88
FT /evidence="ECO:0007829|PDB:2L08"
FT STRAND 92..96
FT /evidence="ECO:0007829|PDB:2L08"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:2L08"
FT STRAND 115..119
FT /evidence="ECO:0007829|PDB:2L08"
FT HELIX 121..130
FT /evidence="ECO:0007829|PDB:2L08"
FT STRAND 134..137
FT /evidence="ECO:0007829|PDB:2L08"
FT STRAND 143..150
FT /evidence="ECO:0007829|PDB:2L08"
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
