UniProt functional annotation for Q9Y580



	UniProt functional annotation for Q9Y580

UniProt code: Q9Y580.

Organism: Homo sapiens (Human).

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

Function: RNA-binding subunit of the trimeric nuclear exosome targeting (NEXT) complex, a complex that functions as an RNA exosome cofactor that directs a subset of non-coding short-lived RNAs for exosomal degradation (PubMed:25189701, PubMed:25578728, PubMed:25525152, PubMed:25852104, PubMed:27871484). NEXT is involved in surveillance and turnover of aberrant transcripts and non-coding RNAs (PubMed:25189701, PubMed:27871484, PubMed:25852104). Binds preferentially polyuridine sequences and associates with newly synthesized RNAs, including pre- mRNAs and short-lived exosome substrates such as promoter upstream transcripts (PROMPTs), enhancer RNAs (eRNAs), and 3'-extended products from small nuclear RNAs (snRNAs) (PubMed:25189701, PubMed:25578728, PubMed:25525152, PubMed:25852104). Participates in several biological processes including DNA damage response (DDR) and stress response (PubMed:25525152, PubMed:30824372). During stress response, activation of the p38MAPK-MK2 pathway decreases RBM7-RNA-binding and subsequently the RNA exosome degradation activities, thereby modulating the turnover of non-coding transcriptome (PubMed:25525152). Participates in DNA damage response (DDR), through its interaction with MEPCE and LARP7, the core subunits of 7SK snRNP complex, that release the positive transcription elongation factor b (P-TEFb) complex from the 7SK snRNP. In turn, activation of P-TEFb complex induces the transcription of P- TEFb-dependent DDR genes to promote cell viability (PubMed:30824372). {ECO:0000269|PubMed:25189701, ECO:0000269|PubMed:25525152, ECO:0000269|PubMed:25578728, ECO:0000269|PubMed:25852104, ECO:0000269|PubMed:27871484, ECO:0000269|PubMed:30824372}.

Subunit: Component of the nuclear exosome targeting (NEXT) complex composed of MTREX, ZCCHC8, and RBM7 that directs a subset of non-coding short-lived RNAs for exosomal degradation (PubMed:27905398, PubMed:27871484, PubMed:25189701). Interacts with ZCCHC8 and SF3B2/SAP145 (PubMed:27905398, PubMed:27871484, PubMed:16263084). Binds to MTREX through ZCCHC8 (PubMed:27871484). Interacts with YWHAE and YWHAZ; these interactions are stress-dependent and RBM7 phosphorylation dependent; release RNA from the NEXT complex and may affect RNA targeting to the nuclear RNA exosomome for degradation (PubMed:25189701). Interacts with MEPCE and LARP7, the core subunits of 7SK snRNP; upon genotoxic stress this interaction is enhanced, triggering the release of inactive P-TEFb complex from the core and P- TEFb complex activation (PubMed:30824372). {ECO:0000269|PubMed:16263084, ECO:0000269|PubMed:25189701, ECO:0000269|PubMed:27871484, ECO:0000269|PubMed:27905398, ECO:0000269|PubMed:30824372}.

Subcellular location: Nucleus, nucleoplasm {ECO:0000269|PubMed:21855801, ECO:0000269|PubMed:25852104}. Nucleus {ECO:0000250|UniProtKB:Q9CQT2}. Note=Excluded from the nucleolus. {ECO:0000269|PubMed:21855801}.

Tissue specificity: Ubiquitous.

Domain: The RRM domain mediates RNA binding; the RNA must have four nucleotides for efficient binding (PubMed:25852104). Mediates the interaction of NEXT complex with promoter upstream transcripts (PROMPTs) and potentially aberrant forms of other non coding RNAs, such as snRNAs (PubMed:25852104). The RRM domain exhibits specificity for polyuridine sequences (PubMed:25852104). {ECO:0000269|PubMed:25852104}.

Ptm: Phosphorylated at Ser-136 by MAPK14/p38-alpha-activated MAPKAPK2/MK2; this phosphorylation is stress-dependent; this phosphorylation decreases its RNA-binding capacity therefore affecting RNA nuclear exosome-mediated degradation (PubMed:25525152, PubMed:25189701). This phosphorylation mediates YWHAE and YWHAZ interactions (PubMed:25189701). {ECO:0000269|PubMed:25189701, ECO:0000269|PubMed:25525152}.

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-binding subunit of the trimeric nuclear exosome targeting (NEXT) complex, a complex that functions as an RNA exosome cofactor that directs a subset of non-coding short-lived RNAs for exosomal degradation (PubMed:25189701, PubMed:25578728, PubMed:25525152, PubMed:25852104, PubMed:27871484). NEXT is involved in surveillance and turnover of aberrant transcripts and non-coding RNAs (PubMed:25189701, PubMed:27871484, PubMed:25852104). Binds preferentially polyuridine sequences and associates with newly synthesized RNAs, including pre- mRNAs and short-lived exosome substrates such as promoter upstream transcripts (PROMPTs), enhancer RNAs (eRNAs), and 3'-extended products from small nuclear RNAs (snRNAs) (PubMed:25189701, PubMed:25578728, PubMed:25525152, PubMed:25852104). Participates in several biological processes including DNA damage response (DDR) and stress response (PubMed:25525152, PubMed:30824372). During stress response, activation of the p38MAPK-MK2 pathway decreases RBM7-RNA-binding and subsequently the RNA exosome degradation activities, thereby modulating the turnover of non-coding transcriptome (PubMed:25525152). Participates in DNA damage response (DDR), through its interaction with MEPCE and LARP7, the core subunits of 7SK snRNP complex, that release the positive transcription elongation factor b (P-TEFb) complex from the 7SK snRNP. In turn, activation of P-TEFb complex induces the transcription of P- TEFb-dependent DDR genes to promote cell viability (PubMed:30824372). {ECO:0000269\|PubMed:25189701, ECO:0000269\|PubMed:25525152, ECO:0000269\|PubMed:25578728, ECO:0000269\|PubMed:25852104, ECO:0000269\|PubMed:27871484, ECO:0000269\|PubMed:30824372}.


Subunit:		Component of the nuclear exosome targeting (NEXT) complex composed of MTREX, ZCCHC8, and RBM7 that directs a subset of non-coding short-lived RNAs for exosomal degradation (PubMed:27905398, PubMed:27871484, PubMed:25189701). Interacts with ZCCHC8 and SF3B2/SAP145 (PubMed:27905398, PubMed:27871484, PubMed:16263084). Binds to MTREX through ZCCHC8 (PubMed:27871484). Interacts with YWHAE and YWHAZ; these interactions are stress-dependent and RBM7 phosphorylation dependent; release RNA from the NEXT complex and may affect RNA targeting to the nuclear RNA exosomome for degradation (PubMed:25189701). Interacts with MEPCE and LARP7, the core subunits of 7SK snRNP; upon genotoxic stress this interaction is enhanced, triggering the release of inactive P-TEFb complex from the core and P- TEFb complex activation (PubMed:30824372). {ECO:0000269\|PubMed:16263084, ECO:0000269\|PubMed:25189701, ECO:0000269\|PubMed:27871484, ECO:0000269\|PubMed:27905398, ECO:0000269\|PubMed:30824372}.
Subcellular location:		Nucleus, nucleoplasm {ECO:0000269\|PubMed:21855801, ECO:0000269\|PubMed:25852104}. Nucleus {ECO:0000250\|UniProtKB:Q9CQT2}. Note=Excluded from the nucleolus. {ECO:0000269\|PubMed:21855801}.
Tissue specificity:		Ubiquitous.
Domain:		The RRM domain mediates RNA binding; the RNA must have four nucleotides for efficient binding (PubMed:25852104). Mediates the interaction of NEXT complex with promoter upstream transcripts (PROMPTs) and potentially aberrant forms of other non coding RNAs, such as snRNAs (PubMed:25852104). The RRM domain exhibits specificity for polyuridine sequences (PubMed:25852104). {ECO:0000269\|PubMed:25852104}.
Ptm:		Phosphorylated at Ser-136 by MAPK14/p38-alpha-activated MAPKAPK2/MK2; this phosphorylation is stress-dependent; this phosphorylation decreases its RNA-binding capacity therefore affecting RNA nuclear exosome-mediated degradation (PubMed:25525152, PubMed:25189701). This phosphorylation mediates YWHAE and YWHAZ interactions (PubMed:25189701). {ECO:0000269\|PubMed:25189701, ECO:0000269\|PubMed:25525152}.