UniProt functional annotation for Q13148



	UniProt functional annotation for Q13148

UniProt code: Q13148.

Organism: Homo sapiens (Human).

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

Function: RNA-binding protein that is involved in various steps of RNA biogenesis and processing (PubMed:23519609). Preferentially binds, via its two RNA recognition motifs RRM1 and RRM2, to GU-repeats on RNA molecules predominantly localized within long introns and in the 3'UTR of mRNAs (PubMed:23519609, PubMed:24240615, PubMed:24464995). In turn, regulates the splicing of many non-coding and protein-coding RNAs including proteins involved in neuronal survival, as well as mRNAs that encode proteins relevant for neurodegenerative diseases (PubMed:21358640, PubMed:29438978). Plays a role in maintaining mitochondrial homeostasis by regulating the processing of mitochondrial transcripts (PubMed:28794432). Regulates also mRNA stability by recruiting CNOT7/CAF1 deadenylase on mRNA 3'UTR leading to poly(A) tail deadenylation and thus shortening (PubMed:30520513). In response to oxidative insult, associates with stalled ribosomes localized to stress granules (SGs) and contributes to cell survival (PubMed:23398327, PubMed:19765185). Participates also in the normal skeletal muscle formation and regeneration, forming cytoplasmic myo-granules and binding mRNAs that encode sarcomeric proteins (PubMed:30464263). Plays a role in the maintenance of the circadian clock periodicity via stabilization of the CRY1 and CRY2 proteins in a FBXL3-dependent manner (PubMed:27123980). Negatively regulates the expression of CDK6 (PubMed:19760257). Regulates the expression of HDAC6, ATG7 and VCP in a PPIA/CYPA-dependent manner (PubMed:25678563). {ECO:0000269|PubMed:11285240, ECO:0000269|PubMed:17481916, ECO:0000269|PubMed:19760257, ECO:0000269|PubMed:19765185, ECO:0000269|PubMed:21358640, ECO:0000269|PubMed:23398327, ECO:0000269|PubMed:23519609, ECO:0000269|PubMed:24240615, ECO:0000269|PubMed:24464995, ECO:0000269|PubMed:25678563, ECO:0000269|PubMed:27123980, ECO:0000269|PubMed:28794432, ECO:0000269|PubMed:29438978, ECO:0000269|PubMed:30464263, ECO:0000269|PubMed:30520513}.

Subunit: Homodimer (PubMed:20043239, PubMed:24464995). Homooligomer (via its N-terminal domain) (PubMed:28663553, PubMed:29438978). Interacts with BRDT (By similarity). Binds specifically to pyrimidine- rich motifs of TAR DNA and to single stranded TG repeated sequences. Binds to RNA, specifically to UG repeated sequences with a minimun of six contiguous repeats. Interacts with ATXN2; the interaction is RNA- dependent (PubMed:20740007). Interacts with MATR3 (PubMed:24686783). Interacts with UBQLN2 (PubMed:23541532). Interacts with HNRNPA2B1 (PubMed:19429692). Interacts with ZNF106 (By similarity). Interacts with CNOT7/CAF1 (PubMed:30520513). Interacts with CRY2 (PubMed:27123980). Interacts with PPIA/CYPA; the interaction is dependent on RNA-binding activity of TARDBP and PPIase activity of PPIA/CYPA and acetylation of PPIA/CYPA at 'Lys-125' favors the interaction (PubMed:25678563). {ECO:0000250|UniProtKB:Q921F2, ECO:0000269|PubMed:11470789, ECO:0000269|PubMed:19429692, ECO:0000269|PubMed:20043239, ECO:0000269|PubMed:20740007, ECO:0000269|PubMed:23541532, ECO:0000269|PubMed:24464995, ECO:0000269|PubMed:24686783, ECO:0000269|PubMed:25678563, ECO:0000269|PubMed:27123980, ECO:0000269|PubMed:28663553, ECO:0000269|PubMed:29438978, ECO:0000269|PubMed:30520513}.

Subcellular location: Nucleus {ECO:0000269|PubMed:17023659, ECO:0000269|PubMed:17481916, ECO:0000269|PubMed:18957508, ECO:0000269|PubMed:19765185, ECO:0000269|PubMed:25678563, ECO:0000269|PubMed:28663553, ECO:0000269|PubMed:29438978}. Cytoplasm {ECO:0000269|PubMed:18957508, ECO:0000269|PubMed:23398327, ECO:0000269|PubMed:30464263}. Cytoplasm, Stress granule {ECO:0000269|PubMed:19765185, ECO:0000269|PubMed:23398327}. Note=Continuously travels in and out of the nucleus (PubMed:18957508). Localizes to stress granules in response to oxidative stress (PubMed:19765185). {ECO:0000269|PubMed:18957508, ECO:0000269|PubMed:19765185}.

Tissue specificity: Ubiquitously expressed. In particular, expression is high in pancreas, placenta, lung, genital tract and spleen.

Domain: Consists of an N-terminal domain (NTD) and two tandem RNA recognition motifs, RRM1 and RRM2, followed by a C-terminal glycine- rich region.

Domain: Contains a nuclear localization sequence and is mostly nuclear; however, its nuclear export sequence permits it to transport mRNAs to the cytoplasm and even to synapses as part of neuronal granules. {ECO:0000269|PubMed:18957508}.

Ptm: Hyperphosphorylated in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU. Phosphorylated upon cellular stress. {ECO:0000269|PubMed:23398327}.

Ptm: Ubiquitinated in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU. {ECO:0000269|PubMed:17023659, ECO:0000269|PubMed:17481916}.

Ptm: Cleaved to generate C-terminal fragments in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU.

Disease: Amyotrophic lateral sclerosis 10 (ALS10) [MIM:612069]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. {ECO:0000269|PubMed:18288693, ECO:0000269|PubMed:18309045, ECO:0000269|PubMed:18372902, ECO:0000269|PubMed:18396105, ECO:0000269|PubMed:18438952, ECO:0000269|PubMed:19224587, ECO:0000269|PubMed:19350673, ECO:0000269|PubMed:19655382, ECO:0000269|PubMed:19695877, ECO:0000269|PubMed:19760257, ECO:0000269|PubMed:20740007, ECO:0000269|PubMed:21220647, ECO:0000269|PubMed:21418058, ECO:0000269|PubMed:22456481, ECO:0000269|PubMed:25678563}. Note=The disease is caused by variants affecting the gene represented in this entry.

Sequence caution: Sequence=ABO32290.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305}; Sequence=ABO32292.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; 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-binding protein that is involved in various steps of RNA biogenesis and processing (PubMed:23519609). Preferentially binds, via its two RNA recognition motifs RRM1 and RRM2, to GU-repeats on RNA molecules predominantly localized within long introns and in the 3'UTR of mRNAs (PubMed:23519609, PubMed:24240615, PubMed:24464995). In turn, regulates the splicing of many non-coding and protein-coding RNAs including proteins involved in neuronal survival, as well as mRNAs that encode proteins relevant for neurodegenerative diseases (PubMed:21358640, PubMed:29438978). Plays a role in maintaining mitochondrial homeostasis by regulating the processing of mitochondrial transcripts (PubMed:28794432). Regulates also mRNA stability by recruiting CNOT7/CAF1 deadenylase on mRNA 3'UTR leading to poly(A) tail deadenylation and thus shortening (PubMed:30520513). In response to oxidative insult, associates with stalled ribosomes localized to stress granules (SGs) and contributes to cell survival (PubMed:23398327, PubMed:19765185). Participates also in the normal skeletal muscle formation and regeneration, forming cytoplasmic myo-granules and binding mRNAs that encode sarcomeric proteins (PubMed:30464263). Plays a role in the maintenance of the circadian clock periodicity via stabilization of the CRY1 and CRY2 proteins in a FBXL3-dependent manner (PubMed:27123980). Negatively regulates the expression of CDK6 (PubMed:19760257). Regulates the expression of HDAC6, ATG7 and VCP in a PPIA/CYPA-dependent manner (PubMed:25678563). {ECO:0000269\|PubMed:11285240, ECO:0000269\|PubMed:17481916, ECO:0000269\|PubMed:19760257, ECO:0000269\|PubMed:19765185, ECO:0000269\|PubMed:21358640, ECO:0000269\|PubMed:23398327, ECO:0000269\|PubMed:23519609, ECO:0000269\|PubMed:24240615, ECO:0000269\|PubMed:24464995, ECO:0000269\|PubMed:25678563, ECO:0000269\|PubMed:27123980, ECO:0000269\|PubMed:28794432, ECO:0000269\|PubMed:29438978, ECO:0000269\|PubMed:30464263, ECO:0000269\|PubMed:30520513}.


Subunit:		Homodimer (PubMed:20043239, PubMed:24464995). Homooligomer (via its N-terminal domain) (PubMed:28663553, PubMed:29438978). Interacts with BRDT (By similarity). Binds specifically to pyrimidine- rich motifs of TAR DNA and to single stranded TG repeated sequences. Binds to RNA, specifically to UG repeated sequences with a minimun of six contiguous repeats. Interacts with ATXN2; the interaction is RNA- dependent (PubMed:20740007). Interacts with MATR3 (PubMed:24686783). Interacts with UBQLN2 (PubMed:23541532). Interacts with HNRNPA2B1 (PubMed:19429692). Interacts with ZNF106 (By similarity). Interacts with CNOT7/CAF1 (PubMed:30520513). Interacts with CRY2 (PubMed:27123980). Interacts with PPIA/CYPA; the interaction is dependent on RNA-binding activity of TARDBP and PPIase activity of PPIA/CYPA and acetylation of PPIA/CYPA at 'Lys-125' favors the interaction (PubMed:25678563). {ECO:0000250\|UniProtKB:Q921F2, ECO:0000269\|PubMed:11470789, ECO:0000269\|PubMed:19429692, ECO:0000269\|PubMed:20043239, ECO:0000269\|PubMed:20740007, ECO:0000269\|PubMed:23541532, ECO:0000269\|PubMed:24464995, ECO:0000269\|PubMed:24686783, ECO:0000269\|PubMed:25678563, ECO:0000269\|PubMed:27123980, ECO:0000269\|PubMed:28663553, ECO:0000269\|PubMed:29438978, ECO:0000269\|PubMed:30520513}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:17023659, ECO:0000269\|PubMed:17481916, ECO:0000269\|PubMed:18957508, ECO:0000269\|PubMed:19765185, ECO:0000269\|PubMed:25678563, ECO:0000269\|PubMed:28663553, ECO:0000269\|PubMed:29438978}. Cytoplasm {ECO:0000269\|PubMed:18957508, ECO:0000269\|PubMed:23398327, ECO:0000269\|PubMed:30464263}. Cytoplasm, Stress granule {ECO:0000269\|PubMed:19765185, ECO:0000269\|PubMed:23398327}. Note=Continuously travels in and out of the nucleus (PubMed:18957508). Localizes to stress granules in response to oxidative stress (PubMed:19765185). {ECO:0000269\|PubMed:18957508, ECO:0000269\|PubMed:19765185}.
Tissue specificity:		Ubiquitously expressed. In particular, expression is high in pancreas, placenta, lung, genital tract and spleen.
Domain:		Consists of an N-terminal domain (NTD) and two tandem RNA recognition motifs, RRM1 and RRM2, followed by a C-terminal glycine- rich region.
Domain:		Contains a nuclear localization sequence and is mostly nuclear; however, its nuclear export sequence permits it to transport mRNAs to the cytoplasm and even to synapses as part of neuronal granules. {ECO:0000269\|PubMed:18957508}.
Ptm:		Hyperphosphorylated in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU. Phosphorylated upon cellular stress. {ECO:0000269\|PubMed:23398327}.
Ptm:		Ubiquitinated in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU. {ECO:0000269\|PubMed:17023659, ECO:0000269\|PubMed:17481916}.
Ptm:		Cleaved to generate C-terminal fragments in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU.
Disease:		Amyotrophic lateral sclerosis 10 (ALS10) [MIM:612069]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. {ECO:0000269\|PubMed:18288693, ECO:0000269\|PubMed:18309045, ECO:0000269\|PubMed:18372902, ECO:0000269\|PubMed:18396105, ECO:0000269\|PubMed:18438952, ECO:0000269\|PubMed:19224587, ECO:0000269\|PubMed:19350673, ECO:0000269\|PubMed:19655382, ECO:0000269\|PubMed:19695877, ECO:0000269\|PubMed:19760257, ECO:0000269\|PubMed:20740007, ECO:0000269\|PubMed:21220647, ECO:0000269\|PubMed:21418058, ECO:0000269\|PubMed:22456481, ECO:0000269\|PubMed:25678563}. Note=The disease is caused by variants affecting the gene represented in this entry.
Sequence caution:		Sequence=ABO32290.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305}; Sequence=ABO32292.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};