UniProt functional annotation for Q92900



	UniProt functional annotation for Q92900

UniProt code: Q92900.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: RNA-dependent helicase and ATPase required for nonsense- mediated decay (NMD) of mRNAs containing premature stop codons. 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. Recruited by release factors to stalled ribosomes together with the SMG1C protein kinase complex to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. 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. 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. UPF1 can also activate NMD without UPF2 or UPF3, and in the absence of the NMD-enhancing downstream EJC indicative for alternative NMD pathways. Plays a role in replication-dependent histone mRNA degradation at the end of phase S; the function is independent of UPF2. 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. The ATPase activity of UPF1 is required for disassembly of mRNPs undergoing NMD. Essential for embryonic viability. Together with UPF2 and dependent on TDRD6, mediates the degradation of mRNA hardoring long 3'UTR by inducing the NMD machinery (By similarity). {ECO:0000250|UniProtKB:Q9EPU0, ECO:0000269|PubMed:11163187, ECO:0000269|PubMed:16086026, ECO:0000269|PubMed:18172165, ECO:0000269|PubMed:21145460, ECO:0000269|PubMed:21419344, ECO:0000269|PubMed:24726324}.

Subunit: Found in a post-splicing messenger ribonucleoprotein (mRNP) complex (PubMed:21419344). 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). Interacts with UPF2 (PubMed:11163187, PubMed:11073994, PubMed:11113196, 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 (By similarity). {ECO:0000250|UniProtKB:Q9EPU0, ECO:0000269|PubMed:11073994, ECO:0000269|PubMed:11113196, ECO:0000269|PubMed:11163187, ECO:0000269|PubMed:11546874, ECO:0000269|PubMed:12554878, ECO:0000269|PubMed:15721257, ECO:0000269|PubMed:16086026, ECO:0000269|PubMed:16452507, ECO:0000269|PubMed:17932509, ECO:0000269|PubMed:18362360, ECO:0000269|PubMed:18447585, ECO:0000269|PubMed:19150429, ECO:0000269|PubMed:19417104, ECO:0000269|PubMed:19556969, ECO:0000269|PubMed:19864460, ECO:0000269|PubMed:21419344, ECO:0000269|PubMed:24726324, ECO:0000269|PubMed:26000482, ECO:0000269|PubMed:27974568}.

Subunit: (Microbial infection) Interacts with human T-cell leukemia virus 1/HTLV-1 protein Tax; this interaction inhibits the host nonsense-mediated mRNA decay (NMD). {ECO:0000269|PubMed:29382845}.

Subcellular location: Cytoplasm. Cytoplasm, P-body. Nucleus. Note=Hyperphosphorylated form is targeted to the P-body, while unphosphorylated protein is distributed throughout the cytoplasm. Localized in the chromatoid bodies of round spermatids (By similarity). {ECO:0000250|UniProtKB:Q9EPU0}.

Tissue specificity: Ubiquitous.

Domain: The [ST]-Q motif constitutes a recognition sequence for kinases from the PI3/PI4-kinase family.

Ptm: Phosphorylated by SMG1; required for formation of mRNA surveillance complexes. {ECO:0000269|PubMed:11331269, ECO:0000269|PubMed:11544179, ECO:0000269|PubMed:14636577, ECO:0000269|PubMed:16452507, ECO:0000269|PubMed:19150429}.

Similarity: Belongs to the DNA2/NAM7 helicase family. {ECO:0000305}.

Sequence caution: Sequence=BAA19664.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		RNA-dependent helicase and ATPase required for nonsense- mediated decay (NMD) of mRNAs containing premature stop codons. 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. Recruited by release factors to stalled ribosomes together with the SMG1C protein kinase complex to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. 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. 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. UPF1 can also activate NMD without UPF2 or UPF3, and in the absence of the NMD-enhancing downstream EJC indicative for alternative NMD pathways. Plays a role in replication-dependent histone mRNA degradation at the end of phase S; the function is independent of UPF2. 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. The ATPase activity of UPF1 is required for disassembly of mRNPs undergoing NMD. Essential for embryonic viability. Together with UPF2 and dependent on TDRD6, mediates the degradation of mRNA hardoring long 3'UTR by inducing the NMD machinery (By similarity). {ECO:0000250\|UniProtKB:Q9EPU0, ECO:0000269\|PubMed:11163187, ECO:0000269\|PubMed:16086026, ECO:0000269\|PubMed:18172165, ECO:0000269\|PubMed:21145460, ECO:0000269\|PubMed:21419344, ECO:0000269\|PubMed:24726324}.


Subunit:		Found in a post-splicing messenger ribonucleoprotein (mRNP) complex (PubMed:21419344). 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). Interacts with UPF2 (PubMed:11163187, PubMed:11073994, PubMed:11113196, 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 (By similarity). {ECO:0000250\|UniProtKB:Q9EPU0, ECO:0000269\|PubMed:11073994, ECO:0000269\|PubMed:11113196, ECO:0000269\|PubMed:11163187, ECO:0000269\|PubMed:11546874, ECO:0000269\|PubMed:12554878, ECO:0000269\|PubMed:15721257, ECO:0000269\|PubMed:16086026, ECO:0000269\|PubMed:16452507, ECO:0000269\|PubMed:17932509, ECO:0000269\|PubMed:18362360, ECO:0000269\|PubMed:18447585, ECO:0000269\|PubMed:19150429, ECO:0000269\|PubMed:19417104, ECO:0000269\|PubMed:19556969, ECO:0000269\|PubMed:19864460, ECO:0000269\|PubMed:21419344, ECO:0000269\|PubMed:24726324, ECO:0000269\|PubMed:26000482, ECO:0000269\|PubMed:27974568}.
Subunit:		(Microbial infection) Interacts with human T-cell leukemia virus 1/HTLV-1 protein Tax; this interaction inhibits the host nonsense-mediated mRNA decay (NMD). {ECO:0000269\|PubMed:29382845}.
Subcellular location:		Cytoplasm. Cytoplasm, P-body. Nucleus. Note=Hyperphosphorylated form is targeted to the P-body, while unphosphorylated protein is distributed throughout the cytoplasm. Localized in the chromatoid bodies of round spermatids (By similarity). {ECO:0000250\|UniProtKB:Q9EPU0}.
Tissue specificity:		Ubiquitous.
Domain:		The [ST]-Q motif constitutes a recognition sequence for kinases from the PI3/PI4-kinase family.
Ptm:		Phosphorylated by SMG1; required for formation of mRNA surveillance complexes. {ECO:0000269\|PubMed:11331269, ECO:0000269\|PubMed:11544179, ECO:0000269\|PubMed:14636577, ECO:0000269\|PubMed:16452507, ECO:0000269\|PubMed:19150429}.
Similarity:		Belongs to the DNA2/NAM7 helicase family. {ECO:0000305}.
Sequence caution:		Sequence=BAA19664.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};