UniProt functional annotation for O95453



	UniProt functional annotation for O95453

UniProt code: O95453.

Organism: Homo sapiens (Human).

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

Function: 3'-exoribonuclease that has a preference for poly(A) tails of mRNAs, thereby efficiently degrading poly(A) tails. Exonucleolytic degradation of the poly(A) tail is often the first step in the decay of eukaryotic mRNAs and is also used to silence certain maternal mRNAs translationally during oocyte maturation and early embryonic development. Interacts with both the 3'-end poly(A) tail and the 5'-end cap structure during degradation, the interaction with the cap structure being required for an efficient degradation of poly(A) tails. Involved in nonsense-mediated mRNA decay, a critical process of selective degradation of mRNAs that contain premature stop codons. Also involved in degradation of inherently unstable mRNAs that contain AU- rich elements (AREs) in their 3'-UTR, possibly via its interaction with KHSRP. Probably mediates the removal of poly(A) tails of AREs mRNAs, which constitutes the first step of destabilization (PubMed:10882133, PubMed:11359775, PubMed:12748283, PubMed:15175153, PubMed:9736620). Also able to recognize and trim poly(A) tails of microRNAs such as MIR21 and H/ACA box snoRNAs (small nucleolar RNAs) leading to microRNAs degradation or snoRNA increased stability (PubMed:25049417, PubMed:22442037). {ECO:0000269|PubMed:10882133, ECO:0000269|PubMed:11359775, ECO:0000269|PubMed:12748283, ECO:0000269|PubMed:15175153, ECO:0000269|PubMed:22442037, ECO:0000269|PubMed:25049417, ECO:0000269|PubMed:9736620}.

Catalytic activity: Reaction=Exonucleolytic cleavage of poly(A) to 5'-AMP.; EC=3.1.13.4; Evidence={ECO:0000269|PubMed:10801819, ECO:0000269|PubMed:9736620};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:11359775, ECO:0000269|PubMed:15358788}; Note=Divalent metal cations. Mg(2+) is the most probable. {ECO:0000269|PubMed:11359775, ECO:0000269|PubMed:15358788};

Subunit: Homodimer (PubMed:10801819, PubMed:16281054). Found in a mRNA decay complex with RENT1, RENT2 and RENT3B (PubMed:14527413). Interacts with KHSRP (PubMed:15175153). Interacts with CELF1/CUGBP1 (PubMed:16601207). Interacts with ZC3HAV1 in an RNA-independent manner (PubMed:21876179). Interacts with DHX36 (PubMed:14731398). {ECO:0000269|PubMed:10801819, ECO:0000269|PubMed:14527413, ECO:0000269|PubMed:14731398, ECO:0000269|PubMed:15175153, ECO:0000269|PubMed:16281054, ECO:0000269|PubMed:16601207, ECO:0000269|PubMed:21876179}.

Subcellular location: Nucleus {ECO:0000269|PubMed:9736620}. Cytoplasm {ECO:0000269|PubMed:9736620}. Nucleus, nucleolus {ECO:0000269|PubMed:12429849, ECO:0000269|PubMed:22442037}. Note=Some nuclear fraction is nucleolar.

Tissue specificity: Ubiquitous. {ECO:0000269|PubMed:10640832, ECO:0000269|PubMed:9736620}.

Ptm: Phosphorylation by MAPKAPK2, preventing GADD45A mRNA degradation after genotoxic stress. {ECO:0000269|PubMed:20932473}.

Disease: Dyskeratosis congenita, autosomal recessive, 6 (DKCB6) [MIM:616353]: A form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. {ECO:0000269|PubMed:25893599}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Pulmonary fibrosis, and/or bone marrow failure, telomere- related, 4 (PFBMFT4) [MIM:616371]: A disease associated with shortened telomeres. Pulmonary fibrosis is the most common manifestation. Other manifestations include aplastic anemia due to bone marrow failure, hepatic fibrosis, and increased cancer risk, particularly myelodysplastic syndrome and acute myeloid leukemia. Phenotype, age at onset, and severity are determined by telomere length. {ECO:0000269|PubMed:25848748}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: [Isoform 2]: Non canonical splice junctions. {ECO:0000305}.

Similarity: Belongs to the CAF1 family. {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:		3'-exoribonuclease that has a preference for poly(A) tails of mRNAs, thereby efficiently degrading poly(A) tails. Exonucleolytic degradation of the poly(A) tail is often the first step in the decay of eukaryotic mRNAs and is also used to silence certain maternal mRNAs translationally during oocyte maturation and early embryonic development. Interacts with both the 3'-end poly(A) tail and the 5'-end cap structure during degradation, the interaction with the cap structure being required for an efficient degradation of poly(A) tails. Involved in nonsense-mediated mRNA decay, a critical process of selective degradation of mRNAs that contain premature stop codons. Also involved in degradation of inherently unstable mRNAs that contain AU- rich elements (AREs) in their 3'-UTR, possibly via its interaction with KHSRP. Probably mediates the removal of poly(A) tails of AREs mRNAs, which constitutes the first step of destabilization (PubMed:10882133, PubMed:11359775, PubMed:12748283, PubMed:15175153, PubMed:9736620). Also able to recognize and trim poly(A) tails of microRNAs such as MIR21 and H/ACA box snoRNAs (small nucleolar RNAs) leading to microRNAs degradation or snoRNA increased stability (PubMed:25049417, PubMed:22442037). {ECO:0000269\|PubMed:10882133, ECO:0000269\|PubMed:11359775, ECO:0000269\|PubMed:12748283, ECO:0000269\|PubMed:15175153, ECO:0000269\|PubMed:22442037, ECO:0000269\|PubMed:25049417, ECO:0000269\|PubMed:9736620}.


Catalytic activity:		Reaction=Exonucleolytic cleavage of poly(A) to 5'-AMP.; EC=3.1.13.4; Evidence={ECO:0000269\|PubMed:10801819, ECO:0000269\|PubMed:9736620};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:11359775, ECO:0000269\|PubMed:15358788}; Note=Divalent metal cations. Mg(2+) is the most probable. {ECO:0000269\|PubMed:11359775, ECO:0000269\|PubMed:15358788};
Subunit:		Homodimer (PubMed:10801819, PubMed:16281054). Found in a mRNA decay complex with RENT1, RENT2 and RENT3B (PubMed:14527413). Interacts with KHSRP (PubMed:15175153). Interacts with CELF1/CUGBP1 (PubMed:16601207). Interacts with ZC3HAV1 in an RNA-independent manner (PubMed:21876179). Interacts with DHX36 (PubMed:14731398). {ECO:0000269\|PubMed:10801819, ECO:0000269\|PubMed:14527413, ECO:0000269\|PubMed:14731398, ECO:0000269\|PubMed:15175153, ECO:0000269\|PubMed:16281054, ECO:0000269\|PubMed:16601207, ECO:0000269\|PubMed:21876179}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:9736620}. Cytoplasm {ECO:0000269\|PubMed:9736620}. Nucleus, nucleolus {ECO:0000269\|PubMed:12429849, ECO:0000269\|PubMed:22442037}. Note=Some nuclear fraction is nucleolar.
Tissue specificity:		Ubiquitous. {ECO:0000269\|PubMed:10640832, ECO:0000269\|PubMed:9736620}.
Ptm:		Phosphorylation by MAPKAPK2, preventing GADD45A mRNA degradation after genotoxic stress. {ECO:0000269\|PubMed:20932473}.
Disease:		Dyskeratosis congenita, autosomal recessive, 6 (DKCB6) [MIM:616353]: A form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. {ECO:0000269\|PubMed:25893599}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Pulmonary fibrosis, and/or bone marrow failure, telomere- related, 4 (PFBMFT4) [MIM:616371]: A disease associated with shortened telomeres. Pulmonary fibrosis is the most common manifestation. Other manifestations include aplastic anemia due to bone marrow failure, hepatic fibrosis, and increased cancer risk, particularly myelodysplastic syndrome and acute myeloid leukemia. Phenotype, age at onset, and severity are determined by telomere length. {ECO:0000269\|PubMed:25848748}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		[Isoform 2]: Non canonical splice junctions. {ECO:0000305}.
Similarity:		Belongs to the CAF1 family. {ECO:0000305}.