ESRP1 (epithelial splicing regulatory protein 1, also RBM35A) is an epithelium-specific RNA-binding protein with three RNA-recognition motifs that regulates alternative pre-mRNA splicing. It binds GU-rich/UGG-containing cis-elements in target pre-mRNAs, such as the ISE/ISS-3 element in FGFR2 intron 8, and acts in a position-dependent manner: binding downstream of an alternative exon promotes its inclusion, whereas binding within or upstream promotes skipping. Together with its paralog ESRP2 it drives an epithelial splicing program (FGFR2-IIIb, CD44, CTNND1, ENAH and hundreds of other events in genes for cell-cell adhesion, polarity and migration) that is lost when ESRP expression falls during the epithelial-to-mesenchymal transition; it has also been reported to influence alternative polyadenylation. ESRP1 acts in the nucleus (nucleoplasm). Loss of Esrp1 in mice causes cleft lip and palate and other epithelial developmental defects, and biallelic ESRP1 mutations in humans cause autosomal recessive sensorineural hearing loss (DFNB109) through defective splicing in cochlear development.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003676 nucleic acid binding | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro-based IEA (RRM / RNA-binding domain superfamily) assigning generic nucleic acid binding. ESRP1 has three RRMs and binds RNA sequence-specifically. Reason: True but uninformative: ESRP1 is an RNA-binding protein whose sequence-specific binding of GU-rich/UGG-containing pre-mRNA elements is directly demonstrated, and the more specific sequence-specific mRNA binding (GO:1990825) and pre-mRNA intronic binding (GO:0097157) asserted in this review entail this term. Supporting Evidence: file:human/ESRP1/ESRP1-uniprot.txt DR SMART; SM00360; RRM; 3. PMID:19285943 Crosslinking of overexpressed Esrp1 and Esrp2 was observed with the wild-type, but not the functional mutant of this sequence, suggesting that they bind specific GU-rich sequence motifs |
| GO:0003723 RNA binding | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO (IPR000504 RRM domain) IEA for RNA binding. ESRP1 has three RRM domains and directly binds RNA. Reason: Correct (ESRP1 binds RNA via its RRMs; PAINT also places RNA binding at PTN000360053) but entailed by the more specific sequence-specific mRNA binding (GO:1990825) proposed as the replacement for the mRNA binding rows and by the NEW pre-mRNA intronic binding row. Supporting Evidence: file:human/ESRP1/ESRP1-uniprot.txt DR SMART; SM00360; RRM; 3. PMID:19285943 Crosslinking of overexpressed Esrp1 and Esrp2 was observed with the wild-type, but not the functional mutant of this sequence, suggesting that they bind specific GU-rich sequence motifs PMID:19285943 Immunoreactive bands of the expected size for ESRP1 and ESRP2 were identified in pulldowns from the wild-type, but not the mutant 3X ISE/ISS-3 sequence |
| GO:0003729 mRNA binding | IBA GO_REF:0000033 | MODIFY | Summary: IBA from PAINT node PTN001018050 (Eumetazoa ESRP clade; IBD seeded by Drosophila fusilli, human ESRP1 and ESRP2). Human ESRP1 is inside the clade and is itself an experimental seed. ESRP1 binds specific GU-rich/UGG-containing sequences in target pre-mRNAs: UV-crosslinking to the FGFR2 ISE/ISS-3 element is lost when GU/UG dinucleotides are mutated, and endogenous human ESRP1 is pulled down from KATO III nuclear extract by wild-type but not mutant ISE/ISS-3 RNA. Reason: The node placement is sound: ESRP1, ESRP2 (PTHR13976:SF30) and fusilli (SF25) form the ESRP clade, ESRP1 is a seed, and fusilli can substitute for the mammalian protein in FGFR2 splicing. Because the binding is sequence-specific (GU-rich motif), refine to sequence-specific mRNA binding (GO:1990825), a descendant of mRNA binding; actions kept consistent with the IDA row. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001018050 SUPPORTS TRANSFER Eumetazoan ESRP-clade node seeded by fusilli, ESRP1 and ESRP2; ESRP1 is inside the clade and is itself a seed. The inherited term is correct; the MODIFY only refines it to sequence-specific mRNA binding. Proposed replacements: sequence-specific mRNA binding Supporting Evidence: PMID:19285943 Crosslinking of overexpressed Esrp1 and Esrp2 was observed with the wild-type, but not the functional mutant of this sequence, suggesting that they bind specific GU-rich sequence motifs PMID:19285943 Our demonstration that D. Melanogaster Fusilli can regulate endogenous FGFR2 splicing provides the first evidence that this fly protein is a splicing factor file:human/ESRP1/ESRP1-uniprot.txt DR InterPro; IPR050666; ESRP. |
| GO:0003729 mRNA binding | IDA PMID:19285943 ESRP1 and ESRP2 are epithelial cell-type-specific regulators... | MODIFY | Summary: IDA from Warzecha et al. 2009. ESRP1 binds specific GU-rich/UGG-containing sequences in target pre-mRNAs: UV-crosslinking to the FGFR2 ISE/ISS-3 element is lost when GU/UG dinucleotides are mutated, and endogenous human ESRP1 is pulled down from KATO III nuclear extract by wild-type but not mutant ISE/ISS-3 RNA. Reason: The binding is established in human cells for endogenous ESRP1 and is sequence-specific, so the more precise descendant sequence-specific mRNA binding (GO:1990825; is_a GO:0003729, verified) is warranted. The bound element lies in FGFR2 intron 8, which is also captured by the NEW pre-mRNA intronic binding row. Proposed replacements: sequence-specific mRNA binding Supporting Evidence: PMID:19285943 Crosslinking of overexpressed Esrp1 and Esrp2 was observed with the wild-type, but not the functional mutant of this sequence, suggesting that they bind specific GU-rich sequence motifs PMID:19285943 Immunoreactive bands of the expected size for ESRP1 and ESRP2 were identified in pulldowns from the wild-type, but not the mutant 3X ISE/ISS-3 sequence |
| GO:0003729 mRNA binding | IEA GO_REF:0000117 | MODIFY | Summary: ARBA machine-learning IEA for mRNA binding; the claim agrees with direct experimental evidence on ESRP1. ESRP1 binds specific GU-rich/UGG-containing sequences in target pre-mRNAs: UV-crosslinking to the FGFR2 ISE/ISS-3 element is lost when GU/UG dinucleotides are mutated, and endogenous human ESRP1 is pulled down from KATO III nuclear extract by wild-type but not mutant ISE/ISS-3 RNA. Reason: The term is correct, but the evidence supports the more specific sequence-specific mRNA binding (GO:1990825); MODIFY for consistency with the IDA and IBA rows. Support rests on the publication, not the ARBA rule. Proposed replacements: sequence-specific mRNA binding Supporting Evidence: PMID:19285943 Crosslinking of overexpressed Esrp1 and Esrp2 was observed with the wild-type, but not the functional mutant of this sequence, suggesting that they bind specific GU-rich sequence motifs PMID:19285943 Immunoreactive bands of the expected size for ESRP1 and ESRP2 were identified in pulldowns from the wild-type, but not the mutant 3X ISE/ISS-3 sequence |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:25416956) reporting an interaction with UniProtKB:P54253. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32296183) reporting an interaction with UniProtKB:P54253. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32296183) reporting an interaction with UniProtKB:P86480. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32296183) reporting an interaction with UniProtKB:Q03989. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32296183) reporting an interaction with UniProtKB:Q15038. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32296183) reporting an interaction with UniProtKB:Q3LI72. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32296183) reporting an interaction with UniProtKB:Q6ZRY4. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32296183) reporting an interaction with UniProtKB:Q71SY5. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32296183) reporting an interaction with UniProtKB:Q8TDS5. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32296183) reporting an interaction with UniProtKB:Q96G42. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:O14645. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:O14901. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:O60333-2. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:O76024. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:P00488. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:P02489. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:P02766. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:P04792. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:P08670. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:P10809. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:P13637. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:P16284. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:P22607. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:P28329-3. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:P34741. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:P46379-2. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:P48643. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:P54253. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:Q13148. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:Q13393. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:Q14203-5. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:Q86V38. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:Q92876. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:Q9UMX0. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:Q9Y3C5. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:32814053) reporting an interaction with UniProtKB:Q9Y649. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:33961781) reporting an interaction with UniProtKB:Q6ZRY4. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: High-throughput binary interactome/Y2H screen IPI (PMID:40205054) reporting an interaction with UniProtKB:Q6ZRY4. ESRP1 appears as a frequent prey/bait in these screens (e.g. ATXN1, TARDBP, RBPMS2). Reason: Bare protein binding is uninformative under the repository protein-binding policy. The interaction is not disputed, but the screen establishes no specific molecular function (no adaptor, regulator or complex role) for ESRP1, whose established activity is sequence-specific RNA binding in splicing regulation. |
| GO:0005634 nucleus | IDA PMID:19285943 ESRP1 and ESRP2 are epithelial cell-type-specific regulators... | MODIFY | Summary: IDA from Warzecha et al. 2009 (also UniProt subcellular location Nucleus, ECO:0000269 PubMed:19285943). Endogenous ESRP1 was recovered from KATO III nuclear extract bound to ISE/ISS-3 RNA, consistent with nuclear action on pre-mRNA. Reason: Nuclear localization is correct, and ESRP1 already carries the more specific nucleoplasm (GO:0005654, part_of nucleus) by IBA (PTN000360053), HPA immunofluorescence and Reactome. Nucleoplasm is where an intronic pre-mRNA splicing regulator acts, so refine to it. Not a REMOVE; the family-level nucleus assessment (PTHR13976 review, scope UNRESOLVED) is not contradicted for ESRP1. Proposed replacements: nucleoplasm Supporting Evidence: PMID:19285943 To determine whether endogenous Esrp1 and Esrp2 protein binds to this sequence we carried out RNA affinity pulldown experiments using FGFR2-IIIb expressing KATO III cells, for which preparation of bulk nuclear extracts is feasible file:human/ESRP1/ESRP1-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19285943}. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | MODIFY | Summary: UniProt SubCell keyword mapping (SL-0191 Nucleus); derived from the curated nuclear location based on PMID:19285943. Reason: Nuclear localization is correct, and ESRP1 already carries the more specific nucleoplasm (GO:0005654, part_of nucleus) by IBA (PTN000360053), HPA immunofluorescence and Reactome. Nucleoplasm is where an intronic pre-mRNA splicing regulator acts, so refine to it. Not a REMOVE; the family-level nucleus assessment (PTHR13976 review, scope UNRESOLVED) is not contradicted for ESRP1. Proposed replacements: nucleoplasm Supporting Evidence: PMID:19285943 To determine whether endogenous Esrp1 and Esrp2 protein binds to this sequence we carried out RNA affinity pulldown experiments using FGFR2-IIIb expressing KATO III cells, for which preparation of bulk nuclear extracts is feasible |
| GO:0005654 nucleoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PAINT node PTN000360053 (ESRP/hnRNP H/F clade), seeded by experimental nucleoplasm annotations including human ESRP1 itself. Reason: Nucleoplasm is the compartment where ESRP1 binds intronic elements of target pre-mRNAs and regulates splicing; supported by nuclear-extract binding of endogenous ESRP1, HPA imaging and Reactome, and inherited at the PAINT node of which ESRP1 is a seed. Supporting Evidence: PMID:19285943 To determine whether endogenous Esrp1 and Esrp2 protein binds to this sequence we carried out RNA affinity pulldown experiments using FGFR2-IIIb expressing KATO III cells, for which preparation of bulk nuclear extracts is feasible Reactome:R-HSA-6803527 ESRP1 and ESRP2 are RNA-binding mRNA splicing factors that promote epithelial-specific IIIb splicing by binding to the ISE/ISS-3 sequence |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Human Protein Atlas immunofluorescence (GO_REF:0000052) localizing ESRP1 to the nucleoplasm. Reason: Nucleoplasm is the compartment where ESRP1 binds intronic elements of target pre-mRNAs and regulates splicing; supported by nuclear-extract binding of endogenous ESRP1, HPA imaging and Reactome, and inherited at the PAINT node of which ESRP1 is a seed. Supporting Evidence: PMID:19285943 To determine whether endogenous Esrp1 and Esrp2 protein binds to this sequence we carried out RNA affinity pulldown experiments using FGFR2-IIIb expressing KATO III cells, for which preparation of bulk nuclear extracts is feasible Reactome:R-HSA-6803527 ESRP1 and ESRP2 are RNA-binding mRNA splicing factors that promote epithelial-specific IIIb splicing by binding to the ISE/ISS-3 sequence |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6803527 | ACCEPT | Summary: Reactome TAS: ESRP1 binds FGFR2 pre-mRNA in the nucleoplasm to promote exon IIIb inclusion (R-HSA-6803527). Reason: Nucleoplasm is the compartment where ESRP1 binds intronic elements of target pre-mRNAs and regulates splicing; supported by nuclear-extract binding of endogenous ESRP1, HPA imaging and Reactome, and inherited at the PAINT node of which ESRP1 is a seed. Supporting Evidence: PMID:19285943 To determine whether endogenous Esrp1 and Esrp2 protein binds to this sequence we carried out RNA affinity pulldown experiments using FGFR2-IIIb expressing KATO III cells, for which preparation of bulk nuclear extracts is feasible Reactome:R-HSA-6803527 ESRP1 and ESRP2 are RNA-binding mRNA splicing factors that promote epithelial-specific IIIb splicing by binding to the ISE/ISS-3 sequence |
| GO:0016604 nuclear body | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Human Protein Atlas immunofluorescence (GO_REF:0000052) reporting ESRP1 in nuclear bodies in addition to nucleoplasm. Reason: Single high-throughput imaging observation without functional characterisation of which nuclear body is involved; plausible for a splicing regulator but not part of the established mechanism, which acts on pre-mRNA in the nucleoplasm. |
| GO:0042669 regulation of inner ear auditory receptor cell fate specification | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS transfer from mouse Esrp1 (Q3US41; same PANTHER subfamily PTHR13976:SF37, a 1:1 ortholog). The mouse annotation reflects Esrp1-/- embryos with altered cochlear morphogenesis, hair cell differentiation and cell fate specification (Rohacek et al. 2017). Reason: The ortholog relationship is sound, but the underlying claim is a knockout developmental phenotype downstream of ESRP1-dependent splicing of many transcripts (e.g. Fgfr2), not participation in auditory receptor cell fate specification. The direct activity is regulation of alternative splicing; inner-ear defects (and human DFNB109 deafness) are consequences of losing that splicing program. Supporting Evidence: PMID:29107558 we evaluated Esrp1−/− mouse embryos and uncovered alterations in cochlear morphogenesis, auditory hair cell differentiation, and cell fate specification PMID:29107558 Patient derived induced pluripotent stem cells (iPSCs) showed alterations in alternative splicing, consistent with a loss of ESRP1 function |
| GO:0043484 regulation of RNA splicing | IBA GO_REF:0000033 | MODIFY | Summary: IBA from PAINT node PTN000360053 (seeds include fusilli, mouse Esrp1, hnRNP H1/F, human ESRP1, ESRP2). Reason: Correct but general. ESRP1 directly regulates alternative mRNA splicing: it binds UGG/GU-rich intronic and exonic elements and enhances or silences specific exons in a position-dependent RNA map, across hundreds of events of all alternative-splicing types. The specific descendant regulation of alternative mRNA splicing, via spliceosome (GO:0000381; is_a chain to GO:0043484 verified) is warranted; all three rows are refined consistently. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000360053 SUPPORTS TRANSFER ESRP/hnRNP H/F node whose seeds include human ESRP1 and mouse Esrp1; the general splicing-regulation term is appropriate at the node, and ESRP1-specific evidence warrants the alternative-splicing refinement. Proposed replacements: regulation of alternative mRNA splicing, via spliceosome Supporting Evidence: PMID:19285943 Two separate combinations of effective siRNAs against ESRP1 and ESRP2 caused a significant switch from exon IIIb to exon IIIc splicing in the endogenous FGFR2 transcript PMID:19285943 Our demonstration that D. Melanogaster Fusilli can regulate endogenous FGFR2 splicing provides the first evidence that this fly protein is a splicing factor PMID:20711167 Mapping of this motif relative to ESRP-regulated exons revealed a trend suggestive of an RNA map of position-dependent ESRP binding in which binding sites in the downstream intron promote exon inclusion and binding within or upstream of an exon promote exon skipping PMID:19829082 The ESRP regulated events encompass all known types of alternative splicing events |
| GO:0043484 regulation of RNA splicing | IDA PMID:19285943 ESRP1 and ESRP2 are epithelial cell-type-specific regulators... | MODIFY | Summary: IDA from Warzecha et al. 2009: ectopic ESRP1 switches endogenous FGFR2 to exon IIIb; ESRP1/2 knockdown in human PNT2 cells switches to IIIc, rescued by RNAi-resistant Esrp1; CD44, CTNND1 and ENAH splicing also regulated. Reason: Correct but general. ESRP1 directly regulates alternative mRNA splicing: it binds UGG/GU-rich intronic and exonic elements and enhances or silences specific exons in a position-dependent RNA map, across hundreds of events of all alternative-splicing types. The specific descendant regulation of alternative mRNA splicing, via spliceosome (GO:0000381; is_a chain to GO:0043484 verified) is warranted; all three rows are refined consistently. Proposed replacements: regulation of alternative mRNA splicing, via spliceosome Supporting Evidence: PMID:19285943 Two separate combinations of effective siRNAs against ESRP1 and ESRP2 caused a significant switch from exon IIIb to exon IIIc splicing in the endogenous FGFR2 transcript PMID:19285943 In contrast to the controls, cells transduced with RNAi resistant cDNAs for Esrp1 maintained predominant FGFR2-IIIb expression PMID:20711167 Mapping of this motif relative to ESRP-regulated exons revealed a trend suggestive of an RNA map of position-dependent ESRP binding in which binding sites in the downstream intron promote exon inclusion and binding within or upstream of an exon promote exon skipping PMID:19829082 The ESRP regulated events encompass all known types of alternative splicing events |
| GO:0043484 regulation of RNA splicing | IEA GO_REF:0000117 | MODIFY | Summary: ARBA machine-learning IEA for regulation of RNA splicing, agreeing with direct experimental evidence. Reason: Correct but general. ESRP1 directly regulates alternative mRNA splicing: it binds UGG/GU-rich intronic and exonic elements and enhances or silences specific exons in a position-dependent RNA map, across hundreds of events of all alternative-splicing types. The specific descendant regulation of alternative mRNA splicing, via spliceosome (GO:0000381; is_a chain to GO:0043484 verified) is warranted; all three rows are refined consistently. Proposed replacements: regulation of alternative mRNA splicing, via spliceosome Supporting Evidence: PMID:19285943 Two separate combinations of effective siRNAs against ESRP1 and ESRP2 caused a significant switch from exon IIIb to exon IIIc splicing in the endogenous FGFR2 transcript PMID:20711167 we identified an extensive ESRP-regulated splicing network of hundreds of alternative splicing events within numerous genes with functions in cell-cell adhesion, polarity, and migration PMID:20711167 Mapping of this motif relative to ESRP-regulated exons revealed a trend suggestive of an RNA map of position-dependent ESRP binding in which binding sites in the downstream intron promote exon inclusion and binding within or upstream of an exon promote exon skipping PMID:19829082 The ESRP regulated events encompass all known types of alternative splicing events |
| GO:1990904 ribonucleoprotein complex | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA from deep PAINT node PTN000359854 (Eukaryota), seeded only by hnRNP H1, hnRNP F and hnRNP H2; no ESRP member is an experimental seed. Reason: ESRP1 lies within the clade, and as a pre-mRNA-bound splicing regulator it is plausibly part of RNP complexes, but there is no ESRP-specific evidence identifying a defined RNP complex. Kept as a non-core inherited cellular-component statement. |
| GO:0097157 pre-mRNA intronic binding | IDA PMID:19285943 ESRP1 and ESRP2 are epithelial cell-type-specific regulators... | NEW | Summary: ESRP1 binds the ISE/ISS-3 auxiliary cis-element in FGFR2 intron 8; binding requires GU/UG dinucleotides and endogenous human ESRP1 is captured by wild-type but not mutant ISE/ISS-3 RNA. Reason: Direct molecular-function evidence for binding an intronic pre-mRNA element, not captured by any existing annotation (GO:0097157 sits under pre-mRNA binding, not under mRNA binding, so it is not redundant with the GO:0003729 rows). Genome-wide motif mapping places functional ESRP binding sites in introns flanking regulated exons. Supporting Evidence: PMID:19285943 Crosslinking of overexpressed Esrp1 and Esrp2 was observed with the wild-type, but not the functional mutant of this sequence, suggesting that they bind specific GU-rich sequence motifs PMID:19285943 Immunoreactive bands of the expected size for ESRP1 and ESRP2 were identified in pulldowns from the wild-type, but not the mutant 3X ISE/ISS-3 sequence PMID:20711167 Mapping of this motif relative to ESRP-regulated exons revealed a trend suggestive of an RNA map of position-dependent ESRP binding in which binding sites in the downstream intron promote exon inclusion and binding within or upstream of an exon promote exon skipping |
Loading supporting content…
Download this section (compressed HTML)Q: Which RRM(s) of ESRP1 confer UGG/GU-rich motif specificity, and do the three RRMs bind cooperatively or recognise distinct sub-motifs?
Q: Do the reported cytoplasmic or 3-prime-end (alternative polyadenylation) activities of ESRP1 reflect direct binding in the cytoplasm, warranting additional location and mRNA-processing annotations, or are they secondary to nuclear splicing changes?
Q: How does ESRP1 enhance versus silence exons mechanistically: which spliceosomal or auxiliary factors (e.g. RBFOX2, hnRNP H/F) does it recruit or antagonise at ISE/ISS-3?
Experiment: Perform eCLIP of endogenous ESRP1 in a human epithelial line (e.g. PNT2 or KATO III) combined with acute degron depletion and RNA-seq, then test position-dependent motif enrichment and rescue with RRM point mutants to separate direct from indirect splicing changes.
Hypothesis: ESRP1 directly binds UGG-rich motifs downstream of exons it promotes and within/upstream of exons it represses in human epithelial cells.
Experiment: Express single and paired RRM constructs for in vitro RNA Bind-n-Seq and structural analysis with ISE/ISS-3 RNA, and test the corresponding RRM mutants for FGFR2 IIIb rescue in ESRP1/2-depleted cells.
Hypothesis: Individual RRMs of ESRP1 have distinct contributions to RNA specificity.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)