Q92900 · RENT1_HUMAN
- ProteinRegulator of nonsense transcripts 1
- GeneUPF1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1129 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Is recruited to mRNAs upon translation termination and undergoes a cycle of phosphorylation and dephosphorylation; its phosphorylation appears to be a key step in NMD (PubMed:11544179, PubMed:25220460).
Recruited by release factors to stalled ribosomes together with the SMG1C protein kinase complex to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex (PubMed:19417104).
In EJC-dependent NMD, the SURF complex associates with the exon junction complex (EJC) (located 50-55 or more nucleotides downstream from the termination codon) through UPF2 and allows the formation of an UPF1-UPF2-UPF3 surveillance complex which is believed to activate NMD (PubMed:21419344).
Phosphorylated UPF1 is recognized by EST1B/SMG5, SMG6 and SMG7 which are thought to provide a link to the mRNA degradation machinery involving exonucleolytic and endonucleolytic pathways, and to serve as adapters to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation and allowing the recycling of NMD factors (PubMed:12554878).
UPF1 can also activate NMD without UPF2 or UPF3, and in the absence of the NMD-enhancing downstream EJC indicative for alternative NMD pathways (PubMed:18447585).
Plays a role in replication-dependent histone mRNA degradation at the end of phase S; the function is independent of UPF2 (PubMed:16086026, PubMed:18172165).
For the recognition of premature termination codons (PTC) and initiation of NMD a competitive interaction between UPF1 and PABPC1 with the ribosome-bound release factors is proposed (PubMed:18447585, PubMed:25220460).
The ATPase activity of UPF1 is required for disassembly of mRNPs undergoing NMD (PubMed:21145460).
Together with UPF2 and dependent on TDRD6, mediates the degradation of mRNA harboring long 3'UTR by inducing the NMD machinery (By similarity).
Also capable of unwinding double-stranded DNA and translocating on single-stranded DNA (PubMed:30218034).
Catalytic activity
- ATP + H2O = ADP + H+ + phosphateThis reaction proceeds in the forward direction.
- ATP + H2O = ADP + H+ + phosphateThis reaction proceeds in the forward direction.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 123 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 126 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 137 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 140 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 145 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 155 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 159 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 165 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 183 | Zn2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 186 | Zn2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 209 | Zn2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 213 | Zn2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 486 | ATP (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 506-510 | ATP (UniProtKB | ChEBI) | ||||
Sequence: GTGKT | ||||||
Binding site | 676 | ATP (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 713 | ATP (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 844 | ATP (UniProtKB | ChEBI) | ||||
Sequence: E |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameRegulator of nonsense transcripts 1
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ92900
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_056207 | 69 | in dbSNP:rs17339451 | |||
Sequence: A → S | ||||||
Mutagenesis | 126 | Abolishes ability to interact with UPF2/RENT2 and copurifies with greater amounts of SMG1, SMG8 and SMG9. Increases interaction with DHX34. No effect on interaction with SMG1-DHX34-UPF1 complex. | ||||
Sequence: C → S | ||||||
Mutagenesis | 181-184 | Abolishes interaction with UPF2. Decreases interaction with DHX34. | ||||
Sequence: LECY → VRVD | ||||||
Mutagenesis | 204-205 | Abolishes interaction with UPF2. No effect on interaction with DHX34. | ||||
Sequence: VV → DI | ||||||
Mutagenesis | 506 | Decreases interaction with DHX34; when associated with E-508. | ||||
Sequence: G → R | ||||||
Mutagenesis | 506-508 | Prevents dephosphorylation and targets the protein to the P-body. | ||||
Sequence: GTG → RTE | ||||||
Mutagenesis | 508 | Decreases interaction with DHX34; when associated with R-506. | ||||
Sequence: G → E | ||||||
Mutagenesis | 509 | Inhibits histone mRNA degradation, ATPase activity and ATP binding. No effect on interaction with DHX34. | ||||
Sequence: K → A | ||||||
Mutagenesis | 610-611 | Impairs RNA binding. | ||||
Sequence: KR → AA | ||||||
Mutagenesis | 615 | Impairs RNA binding. | ||||
Sequence: R → A | ||||||
Mutagenesis | 647-648 | Loss of ATPase activity and helicase activity. | ||||
Sequence: DE → AA | ||||||
Mutagenesis | 647-648 | Loss of ATPase activity and helicase activity. Inhibits ZC3H12A-mediated IL6 mRNA degradation. | ||||
Sequence: DE → AA | ||||||
Mutagenesis | 676 | Impairs ATPase activity, no effect on ATP binding. | ||||
Sequence: Q → A | ||||||
Mutagenesis | 714 | Impairs ATPase activity and ATP binding. | ||||
Sequence: R → A | ||||||
Mutagenesis | 843 | Inhibits histone mRNA degradation. | ||||
Sequence: R → A | ||||||
Mutagenesis | 843 | Abolishes NMD. | ||||
Sequence: R → C | ||||||
Mutagenesis | 876 | Impairs ATPase activity and ATP binding. | ||||
Sequence: R → A | ||||||
Mutagenesis | 1084 | Impairs association with UPF2, SMG1 and SMG7 and impairs phosphorylation; when associated with A-1089, A-1107 and A-1127. | ||||
Sequence: S → A | ||||||
Mutagenesis | 1089 | Impairs association with UPF2, SMG1 and SMG7 and impairs phosphorylation; when associated with A-1084, A-1107 and A-1127. | ||||
Sequence: S → A | ||||||
Mutagenesis | 1089 | Still phosphorylated but with less efficiency. | ||||
Sequence: S → A | ||||||
Mutagenesis | 1107 | Impairs association with UPF2, SMG1 and SMG7 and impairs phosphorylation; when associated with A-1084, A-1089 and A-1127. | ||||
Sequence: S → A | ||||||
Mutagenesis | 1107 | Impairs phosphorylation. | ||||
Sequence: S → A | ||||||
Mutagenesis | 1108 | Impairs phosphorylation. | ||||
Sequence: Q → N | ||||||
Mutagenesis | 1127 | Impairs association with UPF2, SMG1 and SMG7 and impairs phosphorylation; when associated with A-1084, A-1089 and A-1107. | ||||
Sequence: S → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 769 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000080716 | 1-1129 | UniProt | Regulator of nonsense transcripts 1 | |||
Sequence: MSVEAYGPSSQTLTFLDTEEAELLGADTQGSEFEFTDFTLPSQTQTPPGGPGGPGGGGAGGPGGAGAGAAAGQLDAQVGPEGILQNGAVDDSVAKTSQLLAELNFEEDEEDTYYTKDLPIHACSYCGIHDPACVVYCNTSKKWFCNGRGNTSGSHIVNHLVRAKCKEVTLHKDGPLGETVLECYNCGCRNVFLLGFIPAKADSVVVLLCRQPCASQSSLKDINWDSSQWQPLIQDRCFLSWLVKIPSEQEQLRARQITAQQINKLEELWKENPSATLEDLEKPGVDEEPQHVLLRYEDAYQYQNIFGPLVKLEADYDKKLKESQTQDNITVRWDLGLNKKRIAYFTLPKTDSGNEDLVIIWLRDMRLMQGDEICLRYKGDLAPLWKGIGHVIKVPDNYGDEIAIELRSSVGAPVEVTHNFQVDFVWKSTSFDRMQSALKTFAVDETSVSGYIYHKLLGHEVEDVIIKCQLPKRFTAQGLPDLNHSQVYAVKTVLQRPLSLIQGPPGTGKTVTSATIVYHLARQGNGPVLVCAPSNIAVDQLTEKIHQTGLKVVRLCAKSREAIDSPVSFLALHNQIRNMDSMPELQKLQQLKDETGELSSADEKRYRALKRTAERELLMNADVICCTCVGAGDPRLAKMQFRSILIDESTQATEPECMVPVVLGAKQLILVGDHCQLGPVVMCKKAAKAGLSQSLFERLVVLGIRPIRLQVQYRMHPALSAFPSNIFYEGSLQNGVTAADRVKKGFDFQWPQPDKPMFFYVTQGQEEIASSGTSYLNRTEAANVEKITTKLLKAGAKPDQIGIITPYEGQRSYLVQYMQFSGSLHTKLYQEVEIASVDAFQGREKDFIILSCVRANEHQGIGFLNDPRRLNVALTRARYGVIIVGNPKALSKQPLWNHLLNYYKEQKVLVEGPLNNLRESLMQFSKPRKLVNTINPGARFMTTAMYDAREAIIPGSVYDRSSQGRPSSMYFQTHDQIGMISAGPSHVAAMNIPIPFNLVMPPMPPPGYFGQANGPAAGRGTPKGKTGRGGRQKNRFGLPGPSQTNLPNSQASQDVASQPFSQGALTQGYISMSQPSQMSQPGLSQPELSQDSYLGDEFKSQIDVALSQDSTYQGERAYQHGGVTGLSQY | |||||||
Modified residue (large scale data) | 6 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 10 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 31 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 203 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 488 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 565 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 946 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 956 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 956 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 958 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 1019 | UniProt | Omega-N-methylarginine | ||||
Sequence: R | |||||||
Modified residue | 1089 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1100 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1107 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1107 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1110 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1110 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1111 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 1118 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 1127 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1127 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1129 | PRIDE | Phosphotyrosine | ||||
Sequence: Y |
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Gene expression databases
Organism-specific databases
Interaction
Subunit
Associates with the exon junction complex (EJC) (PubMed:11546874, PubMed:16452507).
Associates with the SGM1C complex; is phosphorylated by the complex kinase component SGM1 (PubMed:19417104).
Part of a complex composed of SMG1, DHX34 and UPF1; within the complex DHX34 acts as a scaffolding protein to facilitate SMG1 phosphorylation of UPF1 (PubMed:26841701).
Interacts with UPF2 (PubMed:11073994, PubMed:11113196, PubMed:11163187, PubMed:19556969).
Interacts with UPF3A and UPF3B (PubMed:11163187).
Interacts with EST1A (PubMed:12554878).
Interacts with SLBP (PubMed:16086026).
Interacts (when hyperphosphorylated) with PNRC2 (PubMed:19150429).
Interacts with AGO1 and AGO2 (PubMed:17932509).
Interacts with GSPT2 (PubMed:18447585).
Interacts with isoform 1 and isoform 5 of ADAR/ADAR1 (PubMed:18362360).
Interacts with SMG7 (PubMed:15721257).
Interacts with ZC3H12A; this interaction occurs in a mRNA translationally active- and termination-dependent manner and is essential for ZC3H12A-mediated degradation of target mRNAs (PubMed:26000482).
Interacts with CPSF6 (PubMed:19864460).
Interacts with MOV10; the interaction is direct and RNA-dependent (PubMed:24726324).
Interacts with SHFL; the interaction increases in the presence of RNA (PubMed:27974568).
Interacts with UPF2 and DDX4; interactions are mediated by TDRD6 (PubMed:25220460).
Interacts with DHX34 and PABPC1/PABP1; the interactions are RNA-independent (PubMed:25220460).
Interacts with RBM46 (By similarity).
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain, compositional bias, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-415 | Sufficient for interaction with RENT2 | ||||
Sequence: MSVEAYGPSSQTLTFLDTEEAELLGADTQGSEFEFTDFTLPSQTQTPPGGPGGPGGGGAGGPGGAGAGAAAGQLDAQVGPEGILQNGAVDDSVAKTSQLLAELNFEEDEEDTYYTKDLPIHACSYCGIHDPACVVYCNTSKKWFCNGRGNTSGSHIVNHLVRAKCKEVTLHKDGPLGETVLECYNCGCRNVFLLGFIPAKADSVVVLLCRQPCASQSSLKDINWDSSQWQPLIQDRCFLSWLVKIPSEQEQLRARQITAQQINKLEELWKENPSATLEDLEKPGVDEEPQHVLLRYEDAYQYQNIFGPLVKLEADYDKKLKESQTQDNITVRWDLGLNKKRIAYFTLPKTDSGNEDLVIIWLRDMRLMQGDEICLRYKGDLAPLWKGIGHVIKVPDNYGDEIAIELRSSVGAPVE | ||||||
Region | 39-70 | Disordered | ||||
Sequence: TLPSQTQTPPGGPGGPGGGGAGGPGGAGAGAA | ||||||
Domain | 115-272 | Upf1 CH-rich | ||||
Sequence: TKDLPIHACSYCGIHDPACVVYCNTSKKWFCNGRGNTSGSHIVNHLVRAKCKEVTLHKDGPLGETVLECYNCGCRNVFLLGFIPAKADSVVVLLCRQPCASQSSLKDINWDSSQWQPLIQDRCFLSWLVKIPSEQEQLRARQITAQQINKLEELWKEN | ||||||
Region | 123-155 | C3H | ||||
Sequence: CSYCGIHDPACVVYCNTSKKWFCNGRGNTSGSH | ||||||
Region | 137-165 | CC/SHH/C | ||||
Sequence: CNTSKKWFCNGRGNTSGSHIVNHLVRAKC | ||||||
Region | 183-213 | C4 | ||||
Sequence: CYNCGCRNVFLLGFIPAKADSVVVLLCRQPC | ||||||
Region | 1009-1058 | Disordered | ||||
Sequence: FGQANGPAAGRGTPKGKTGRGGRQKNRFGLPGPSQTNLPNSQASQDVASQ | ||||||
Compositional bias | 1037-1058 | Polar residues | ||||
Sequence: GLPGPSQTNLPNSQASQDVASQ | ||||||
Region | 1073-1096 | Disordered | ||||
Sequence: SQPSQMSQPGLSQPELSQDSYLGD | ||||||
Motif | 1089-1090 | [ST]-Q motif 1 | ||||
Sequence: SQ | ||||||
Motif | 1107-1108 | [ST]-Q motif 2 | ||||
Sequence: SQ | ||||||
Region | 1110-1129 | Disordered | ||||
Sequence: STYQGERAYQHGGVTGLSQY |
Domain
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q92900-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length1,129
- Mass (Da)124,345
- Last updated2001-10-18 v2
- Checksum6CCA6FE42B15BA28
Q92900-2
- Name2
- Differences from canonical
- 353-363: Missing
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A994J773 | A0A994J773_HUMAN | UPF1 | 391 | ||
A0A994J597 | A0A994J597_HUMAN | UPF1 | 346 | ||
A0A994J4L7 | A0A994J4L7_HUMAN | UPF1 | 1113 |
Sequence caution
Features
Showing features for sequence conflict, alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 61 | in Ref. 2; AAC51140 | ||||
Sequence: G → S | ||||||
Alternative sequence | VSP_003393 | 353-363 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 466 | in Ref. 2; AAC51140 | ||||
Sequence: I → T | ||||||
Sequence conflict | 478 | in Ref. 1; AAC50771 | ||||
Sequence: G → A | ||||||
Sequence conflict | 524 | in Ref. 1; AAC50771 | ||||
Sequence: G → D | ||||||
Sequence conflict | 557 | in Ref. 1; AAC50771 | ||||
Sequence: A → P | ||||||
Sequence conflict | 901-902 | in Ref. 1; AAC50771 | ||||
Sequence: NY → IF | ||||||
Compositional bias | 1037-1058 | Polar residues | ||||
Sequence: GLPGPSQTNLPNSQASQDVASQ |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U65533 EMBL· GenBank· DDBJ | AAC50771.1 EMBL· GenBank· DDBJ | mRNA | ||
U59323 EMBL· GenBank· DDBJ | AAC51140.1 EMBL· GenBank· DDBJ | mRNA | ||
D86988 EMBL· GenBank· DDBJ | BAA19664.2 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AF074016 EMBL· GenBank· DDBJ | AAC26788.1 EMBL· GenBank· DDBJ | mRNA | ||
AC003972 EMBL· GenBank· DDBJ | AAB94785.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC039817 EMBL· GenBank· DDBJ | AAH39817.1 EMBL· GenBank· DDBJ | mRNA |