| Domain/Region | Location (amino acid positions if available) | Function | Key Features | Supporting Evidence |
|---|---|---|---|---|
| RRM1 (RNA recognition motif 1) | Exact residue positions not provided in retrieved sources; one of three conserved RRMs | Contributes to RNA binding and ESRP1 splicing activity | Shares 89% sequence identity with the corresponding ESRP2 RRM; combined point mutations in RRM1 and RRM2 suppress binding to key targets including **Fgfr2** and **Enah**, indicating functional importance for target recognition | (pqac-00000005) |
| RRM2 (RNA recognition motif 2) | Exact residue positions not provided; central RRM | Major determinant of RNA recognition and splicing regulation | Shares 68% sequence identity with the corresponding ESRP2 RRM; point mutation in ESRP2 RRM2 reduced binding to **FGFR2** pre-mRNA; X-ray structure of ESRP1 qRRM2 showed binding to **GGU** motifs, with guanines inserted into aromatic pockets | (pqac-00000005, pqac-00000003) |
| RRM3 (RNA recognition motif 3) | Exact residue positions not provided; C-terminal-most RRM among the three RRMs | Supports RNA binding and splicing activity | Shares 76% sequence identity with the corresponding ESRP2 RRM; evidence indicates RRM2 and RRM3 are essential for recognition and/or interaction with pre-mRNA targets | (pqac-00000005) |
| Three-RRM module (overall RNA-binding core) | Distributed across the ESRP1 polypeptide; exact coordinates not given | Binds cis-regulatory elements in target pre-mRNAs to control exon inclusion or exclusion | Highly conserved across orthologs in flies (**fusilli**), worms (**sym-2**), chicken, and mammals; ESRP proteins are epithelial-specific RNA-binding proteins with strongest conservation in the three RRMs | (pqac-00000005, pqac-00000008) |
| DNAQ-like exonuclease domain | N-terminal region; exact residue positions not provided | Putative structural/regulatory region; specific molecular role not yet characterized | Reported in both ESRP paralogs; present outside the canonical RRMs, but its precise function remains unknown in current literature | (pqac-00000005) |
| DAZAP2-like domain | C-terminal region of ESRP1; exact residue positions not provided | Putative paralog-specific structural/regulatory region | Present in ESRP1 but not ESRP2; contrasted with a FAM70 domain in ESRP2; specific function remains uncharacterized | (pqac-00000005) |
| Putative nuclear localization sequence (pNLS) | Exact residue positions not provided | Promotes nuclear localization for pre-mRNA splicing function | Supports existence of nuclear ESRP1 isoforms; literature also supports distinct cytoplasmic ESRP1 isoforms with non-splicing roles | (pqac-00000005, pqac-00000004) |
| Alternative splice region controlling nuclear vs cytoplasmic isoforms | 5' alternative splice site at the terminus of exon 12 | Determines production of nuclear versus cytoplasmic ESRP1 isoforms | Isoform choice changes intracellular distribution; supports functional partitioning between nuclear splicing regulation and cytoplasmic post-transcriptional regulation | (pqac-00000005) |
| qRRM2 RNA-binding surface | Structural feature within RRM2; residue-level coordinates not provided in retrieved text | Sequence-specific recognition of ESRP1 target motifs | Crystal structure revealed recognition of **GGU**-containing RNA; explains biochemical specificity for **UGG/GGU-rich** motifs used in ESRP-dependent regulation | (pqac-00000003, pqac-00000005) |
| UTR-binding/post-transcriptional interaction regions | Not mapped to a specific domain in retrieved sources | May mediate functions beyond splicing, including translation control, mRNA stability, or alternative polyadenylation | ESRP1 binds broadly in 3' and 5' UTRs; cytoplasmic ESRP1 appears to regulate CTNND1 protein abundance, indicating additional post-transcriptional roles beyond nuclear splicing | (pqac-00000004, pqac-00000005) |
| Family-level ortholog architecture | Whole protein | Supports conserved epithelial splicing regulatory function across animals | Orthologs identified in fly (**fusilli**), worm (**sym-2**), chicken, and mammals; the RRM architecture is especially conserved, supporting functional inference for poorly characterized vertebrate orthologs such as the ghost shark protein | (pqac-00000005, pqac-00000008) |


*Table: This table summarizes the known and inferred structural organization of ESRP1, emphasizing conserved RNA-binding domains, paralog-specific regions, and localization features. It is useful for annotating the ghost shark ESRP1 ortholog because direct species-specific literature is lacking but domain-level function is strongly conserved.*