id: O14595 gene_symbol: CTDSP2 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: CTDSP2 (SCP2, OS4, NIF2) is a small nuclear protein phosphatase of the FCP/SCP branch of the haloacid dehalogenase (HAD) superfamily. Its C-terminal FCP1-homology domain uses a Mg2+-dependent DXDX(T/V) motif, with Asp107 forming a phosphoaspartyl intermediate, to hydrolyse phosphoserine on protein substrates. Like its paralogs CTDSP1 and CTDSPL, it dephosphorylates the C-terminal heptad repeats of the RNA polymerase II largest subunit with a preference for phospho-Ser5, and it is recruited to promoters by transcription factors such as the androgen receptor and REST, where it restrains promoter clearance and contributes to silencing of neuronal genes in non-neuronal cells. CTDSP2 also removes the activating C-terminal phosphates from Smad1 in the nucleus, terminating BMP signalling. CTDSP2 is a FOXO target gene, and its intron hosts miR-26a-2. existing_annotations: - term: id: GO:0004722 label: protein serine/threonine phosphatase activity evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: enables supporting_entities: - RHEA:20629 - RHEA:47004 - EC:3.1.3.16 review: summary: Protein serine/threonine phosphatase activity is correct and is the most precise existing term that covers both known substrate classes (RNA polymerase II CTD and Smad1 C-terminal phosphoserines). action: ACCEPT reason: CTDSP2 carries the FCP1-homology HAD-family catalytic domain (residues 97-255) with the DXDX(T/V) nucleophile Asp107 and proton donor Asp109, and SCP-family enzymes dephosphorylate phosphoserine in the RNA polymerase II CTD heptad repeats (PMID:12721286). Human SCP2 also dephosphorylates the C-terminal SSXS phosphoserines of Smad1 (PMID:16882717), a non-CTD protein substrate for which GO has no substrate-specific child term. GO:0008420 (is_a this term) captures the CTD activity; this broader term remains as precise as warranted for the Smad1 activity, so it is not refined away. supported_by: - &id006 reference_id: file:human/CTDSP2/CTDSP2-uniprot.txt record_section: ["FT:ACT_SITE"] supporting_text: /note="4-aspartylphosphate intermediate" - &id007 reference_id: file:human/CTDSP2/CTDSP2-uniprot.txt record_section: ["FT:ACT_SITE"] supporting_text: /note="Proton donor" - &id005 reference_id: PMID:12721286 supporting_text: This study describes a family of small CTD phosphatases (SCPs) that preferentially catalyze the dephosphorylation of Ser5 within the consensus repeat. - &id001 reference_id: PMID:16882717 supporting_text: In Xenopus embryos, SCP2/Os4 and human SCP1, 2, and 3 cause selective dephosphorylation of Smad1 compared with Smad2, inhibiting BMP- and Smad1-dependent transcription - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16724108 qualifier: enables supporting_entities: - UniProtKB:P10275 review: summary: Binding to androgen receptor (AR) is a characterised, functional interaction through which CTDSP2 is recruited to AR target promoters. action: MODIFY reason: Per the GO:0005515 policy, bare protein binding is replaced by an informative term where the paper supports one. PMID:16724108 identified SCP2 as an AR interactor, showed AR- and androgen-dependent recruitment to the PSA promoter, and found that SCP2 attenuates AR transcriptional activity. Nuclear androgen receptor binding (GO:0050681) captures this. supported_by: - reference_id: PMID:16724108 supporting_text: Small carboxyl-terminal domain (CTD) phosphatase 2 (SCP2) was identified and verified as a protein that interacts with the androgen receptor (AR). - &id003 reference_id: PMID:16724108 supporting_text: Silencing SCP2 and SCP1 by short hairpin RNAs increased androgen-dependent transcription of the PSA gene proposed_replacement_terms: - id: GO:0050681 label: nuclear androgen receptor binding - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16882717 qualifier: enables supporting_entities: - UniProtKB:Q15797 review: summary: Smad1 is a substrate of CTDSP2; the interaction reflects enzyme-substrate engagement. action: MODIFY reason: Per the GO:0005515 policy, the bare binding row is replaced by the informative activity that the cited paper supports. PMID:16882717 shows that human SCP2 dephosphorylates the BMP-receptor-phosphorylated C-terminus of Smad1, so the interaction is best represented as the protein serine/threonine phosphatase activity acting on Smad1. supported_by: - *id001 - &id010 reference_id: PMID:16882717 supporting_text: In human cells, RNAi-mediated depletion of SCP1 and SCP2 increases the extent and duration of Smad1 phosphorylation in response to BMP proposed_replacement_terms: - id: GO:0004722 label: protein serine/threonine phosphatase activity - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:22458338 qualifier: enables supporting_entities: - UniProtKB:P14079 review: summary: High-throughput interaction with HTLV-1 Tax (host-pathogen yeast two-hybrid screen); uninformative about CTDSP2 function. action: REMOVE reason: Bare GO:0005515 is removed under the repository protein-binding policy because it conveys no functional information. Removal does not dispute the reported interaction with HTLV-1 Tax (host-pathogen yeast two-hybrid screen); no study links this partner to CTDSP2 catalytic or regulatory activity, so there is no more informative MF to substitute. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25416956 qualifier: enables supporting_entities: - UniProtKB:Q99618 review: summary: High-throughput interaction with CDCA3 (proteome-scale binary interactome screens); uninformative about CTDSP2 function. action: REMOVE reason: Bare GO:0005515 is removed under the repository protein-binding policy because it conveys no functional information. Removal does not dispute the reported interaction with CDCA3 (proteome-scale binary interactome screens); no study links this partner to CTDSP2 catalytic or regulatory activity, so there is no more informative MF to substitute. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:27880917 qualifier: enables supporting_entities: - UniProtKB:Q99618 review: summary: High-throughput interaction with CDCA3 (proteome-scale binary interactome screens); uninformative about CTDSP2 function. action: REMOVE reason: Bare GO:0005515 is removed under the repository protein-binding policy because it conveys no functional information. Removal does not dispute the reported interaction with CDCA3 (proteome-scale binary interactome screens); no study links this partner to CTDSP2 catalytic or regulatory activity, so there is no more informative MF to substitute. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:28514442 qualifier: enables supporting_entities: - UniProtKB:Q99618 review: summary: High-throughput interaction with CDCA3 (proteome-scale binary interactome screens); uninformative about CTDSP2 function. action: REMOVE reason: Bare GO:0005515 is removed under the repository protein-binding policy because it conveys no functional information. Removal does not dispute the reported interaction with CDCA3 (proteome-scale binary interactome screens); no study links this partner to CTDSP2 catalytic or regulatory activity, so there is no more informative MF to substitute. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables supporting_entities: - UniProtKB:O15049 review: summary: High-throughput interaction with N4BP3 (proteome-scale binary interactome screen); uninformative about CTDSP2 function. action: REMOVE reason: Bare GO:0005515 is removed under the repository protein-binding policy because it conveys no functional information. Removal does not dispute the reported interaction with N4BP3 (proteome-scale binary interactome screen); no study links this partner to CTDSP2 catalytic or regulatory activity, so there is no more informative MF to substitute. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables supporting_entities: - UniProtKB:P80188 review: summary: High-throughput interaction with LCN2 (proteome-scale binary interactome screen); uninformative about CTDSP2 function. action: REMOVE reason: Bare GO:0005515 is removed under the repository protein-binding policy because it conveys no functional information. Removal does not dispute the reported interaction with LCN2 (proteome-scale binary interactome screen); no study links this partner to CTDSP2 catalytic or regulatory activity, so there is no more informative MF to substitute. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables supporting_entities: - UniProtKB:Q99618 review: summary: High-throughput interaction with CDCA3 (proteome-scale binary interactome screens); uninformative about CTDSP2 function. action: REMOVE reason: Bare GO:0005515 is removed under the repository protein-binding policy because it conveys no functional information. Removal does not dispute the reported interaction with CDCA3 (proteome-scale binary interactome screens); no study links this partner to CTDSP2 catalytic or regulatory activity, so there is no more informative MF to substitute. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:33961781 qualifier: enables supporting_entities: - UniProtKB:Q99618 review: summary: High-throughput interaction with CDCA3 (proteome-scale binary interactome screens); uninformative about CTDSP2 function. action: REMOVE reason: Bare GO:0005515 is removed under the repository protein-binding policy because it conveys no functional information. Removal does not dispute the reported interaction with CDCA3 (proteome-scale binary interactome screens); no study links this partner to CTDSP2 catalytic or regulatory activity, so there is no more informative MF to substitute. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:40205054 qualifier: enables supporting_entities: - UniProtKB:Q99618 review: summary: High-throughput interaction with CDCA3 (proteome-scale binary interactome screens); uninformative about CTDSP2 function. action: REMOVE reason: Bare GO:0005515 is removed under the repository protein-binding policy because it conveys no functional information. Removal does not dispute the reported interaction with CDCA3 (proteome-scale binary interactome screens); no study links this partner to CTDSP2 catalytic or regulatory activity, so there is no more informative MF to substitute. - term: id: GO:0005634 label: nucleus evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in supporting_entities: - UniProtKB-SubCell:SL-0191 review: summary: Nuclear localization is supported and is where CTDSP2 meets its substrates. action: ACCEPT reason: UniProt records nuclear localization (by similarity) and the SCP family is described as nuclear phosphatases that dephosphorylate Smad1 and RNA polymerase II CTD; CTDSP2 is recruited to AR- and REST-bound promoters. Accept as the core location. supported_by: - &id002 reference_id: PMID:16882717 supporting_text: identifying the SCP (small C-terminal domain phosphatase) family of nuclear phosphatases as mediators of Smad1 dephosphorylation - reference_id: file:human/CTDSP2/CTDSP2-uniprot.txt record_section: ["CC:SUBCELLULAR LOCATION"] supporting_text: 'SUBCELLULAR LOCATION: Nucleus' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-1791130 qualifier: located_in review: summary: Nucleoplasm is consistent with chromatin-associated CTD and Smad1 dephosphorylation. action: ACCEPT reason: The Reactome TAS comes from the generic "Expression of CTDSP2" event, which itself says nothing about compartment beyond placing the product in the nucleoplasm. The location is nevertheless consistent with recruitment of CTDSP2 to promoters (PMID:16724108, PMID:15681389) and with the nuclear SCP family (PMID:16882717). Accepted as a refinement of nucleus. supported_by: - *id002 - &id004 reference_id: PMID:15681389 supporting_text: We show that REST/NRSF recruits SCPs to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells. - term: id: GO:0006357 label: regulation of transcription by RNA polymerase II evidence_type: IEA original_reference_id: GO_REF:0000108 qualifier: involved_in supporting_entities: - GO:0008420 review: summary: CTDSP2 regulates RNA polymerase II transcription, and the evidence indicates the direction is negative. action: MODIFY reason: This IEA is a logical inference from GO:0008420 and is correct but less specific than the evidence. CTDSP2 attenuates androgen- and glucocorticoid-receptor-dependent transcription and its silencing increases PSA transcription with earlier Ser5 CTD phosphorylation (PMID:16724108); SCPs recruited by REST silence RE-1-containing neuronal genes (PMID:15681389); UniProt summarizes CTDSP2 as a negative regulator of RNA polymerase II transcription. CTDSP2 does the work in these processes by dephosphorylating the polymerase CTD, so negative regulation of transcription by RNA polymerase II is the supported refinement. supported_by: - *id003 - &id009 reference_id: PMID:16724108 supporting_text: Ser 5 phosphorylation of the RNA polymerase II CTD, a process necessary for initiation of transcription elongation, occurred significantly earlier in SCP2-silenced than parental LNCaP cells. - *id004 - reference_id: file:human/CTDSP2/CTDSP2-uniprot.txt record_section: ["CC:FUNCTION"] supporting_text: Negatively regulates RNA polymerase II transcription proposed_replacement_terms: - id: GO:0000122 label: negative regulation of transcription by RNA polymerase II - term: id: GO:0006470 label: protein dephosphorylation evidence_type: IDA original_reference_id: PMID:12721286 qualifier: involved_in review: summary: CTDSP2 directly dephosphorylates protein substrates (RNA polymerase II CTD, Smad1). action: ACCEPT reason: Protein dephosphorylation is the process directly executed by the catalytic activity. The more specific process term for CTD dephosphorylation (GO:0070940) is obsolete, so this is as precise as GO allows. supported_by: - *id005 - *id001 - term: id: GO:0008420 label: RNA polymerase II CTD heptapeptide repeat phosphatase activity evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables supporting_entities: - PANTHER:PTN000954535 - UniProtKB:O14595 - UniProtKB:Q9GZU7 review: summary: RNA polymerase II CTD heptapeptide repeat phosphatase activity is the defining catalytic activity of the small CTD phosphatases. action: ACCEPT reason: The PAINT IBD for GO:0008420 sits at PANTHER node PTN000954535, seeded by experimental annotations of human CTDSP2 (O14595) and CTDSP1 (Q9GZU7); CTDSP2 descends from that node (PTHR12210 subfamily SF187, whereas CTDSP1 is SF139 and CTDSPL SF43, all inside the SCP clade). The target appearing in its own WITH/FROM is the expected marker that it has its own experimental grounding (PMID:12721286), not circularity. The catalytic Asp107/Asp109 DXDX(T/V) motif is intact, so there is no evidence of loss in this lineage. PAINT propagated only the MF from this node and no process or location terms; that restraint is respected here. supported_by: - &id008 reference_id: file:human/CTDSP2/CTDSP2-uniprot.txt record_section: ["CC:FUNCTION"] supporting_text: Preferentially catalyzes the dephosphorylation of 'Ser-5' within the tandem 7 residue repeats in the C-terminal domain (CTD) of the largest RNA polymerase II subunit POLR2A. - *id005 - *id006 - *id007 - term: id: GO:0008420 label: RNA polymerase II CTD heptapeptide repeat phosphatase activity evidence_type: IDA original_reference_id: PMID:12721286 qualifier: enables review: summary: RNA polymerase II CTD heptapeptide repeat phosphatase activity is the defining catalytic activity of the small CTD phosphatases. action: ACCEPT reason: Yeo et al. (2003) describe the SCP family as RNAPII CTD phosphatases that prefer phospho-Ser5; UniProt cites this paper (ECO:0000269) for the CTDSP2 Ser5 CTD phosphatase function. The cached abstract foregrounds SCP1 and full text is not available locally, so the experimental annotation of CTDSP2 is deferred to the curator who read the full paper. Independent CTDSP2-specific support comes from AR-dependent transcription, where SCP2 silencing caused earlier Ser5 CTD phosphorylation at the PSA promoter (PMID:16724108). supported_by: - *id005 - *id008 - *id009 - term: id: GO:0008420 label: RNA polymerase II CTD heptapeptide repeat phosphatase activity evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: enables supporting_entities: - ARBA:ARBA00085272 - InterPro:IPR040078 review: summary: RNA polymerase II CTD heptapeptide repeat phosphatase activity is the defining catalytic activity of the small CTD phosphatases. action: ACCEPT reason: The ARBA/InterPro (IPR040078 RNA polymerase II CTD phosphatase) electronic mapping agrees with the experimental and phylogenetic annotation of this activity; consistent with the IDA and IBA rows. supported_by: - *id008 - *id005 - *id006 - *id007 - term: id: GO:0016791 label: phosphatase activity evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: enables supporting_entities: - InterPro:IPR011948 review: summary: Correct but very general; CTDSP2 is a protein serine phosphatase acting on RNA polymerase II CTD and Smad1. action: MODIFY reason: 'The InterPro (Dullard-like phosphatase, IPR011948) mapping is correct but less specific than the evidence supports. Replace with the specific activities supported for CTDSP2 and already carried by the gene: RNA polymerase II CTD heptapeptide repeat phosphatase activity (GO:0008420) and protein serine/threonine phosphatase activity (GO:0004722) for the Smad1 C-terminal phosphatase activity.' supported_by: - *id006 - *id005 - *id001 proposed_replacement_terms: - id: GO:0008420 label: RNA polymerase II CTD heptapeptide repeat phosphatase activity - id: GO:0004722 label: protein serine/threonine phosphatase activity - term: id: GO:0030514 label: negative regulation of BMP signaling pathway evidence_type: IDA original_reference_id: PMID:16882717 review: summary: CTDSP2 terminates BMP signaling by dephosphorylating the receptor-phosphorylated C-terminus of Smad1 in the nucleus. action: NEW reason: 'Participation test: CTDSP2 itself performs the inactivating step (removal of the activating C-terminal phosphates of Smad1), so this is not a substrate or necessity claim. Human SCP2 selectively dephosphorylated Smad1 and inhibited BMP/Smad1-dependent transcription, and SCP1/SCP2 depletion prolonged BMP-induced Smad1 phosphorylation in human cells. The only GOA row from this paper is an IntAct IPI, so the absence of a process annotation reflects absent GO curation rather than a curator decision. Comparator check: the Smad2/3 C-terminal phosphatase PPM1A carries the analogous negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512, IDA, PMID:16751101), while no SCP paralog yet carries the BMP term; flagged as a suggested question. Part of the loss-of-function data combine SCP1 and SCP2 knockdown.' supported_by: - *id001 - *id010 references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt findings: [] - id: GO_REF:0000108 title: Automatic assignment of GO terms using logical inference, based on on inter-ontology links findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: PMID:12721286 title: A novel RNA polymerase II C-terminal domain phosphatase that preferentially dephosphorylates serine 5. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Abstract-only in cache; establishes SCP-family Ser5 CTD phosphatase activity; UniProt cites it (ECO:0000269) for CTDSP2 function. - id: PMID:16724108 title: Small carboxyl-terminal domain phosphatase 2 attenuates androgen-dependent transcription. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: 'CTDSP2-specific: AR interaction, promoter recruitment, attenuation of AR/GR transcription, earlier Ser5 CTD phosphorylation on SCP2 silencing.' - id: PMID:16882717 title: 'Unique players in the BMP pathway: small C-terminal domain phosphatases dephosphorylate Smad1 to attenuate BMP signaling.' findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Smad1 C-terminal dephosphorylation by SCP2; some loss-of-function experiments deplete SCP1 and SCP2 together. - id: PMID:22458338 title: Host-pathogen interactome mapping for HTLV-1 and -2 retroviruses. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: High-throughput interactome screen; the bare protein-binding rows it supports are removed under the GO:0005515 policy. Retained as the source of those GOA rows. - id: PMID:25416956 title: A proteome-scale map of the human interactome network. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: High-throughput interactome screen; the bare protein-binding rows it supports are removed under the GO:0005515 policy. Retained as the source of those GOA rows. - id: PMID:27880917 title: Phenotypic and Interaction Profiling of the Human Phosphatases Identifies Diverse Mitotic Regulators. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: High-throughput interactome screen; the bare protein-binding rows it supports are removed under the GO:0005515 policy. Retained as the source of those GOA rows. - id: PMID:28514442 title: Architecture of the human interactome defines protein communities and disease networks. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: High-throughput interactome screen; the bare protein-binding rows it supports are removed under the GO:0005515 policy. Retained as the source of those GOA rows. - id: PMID:32296183 title: A reference map of the human binary protein interactome. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: High-throughput interactome screen; the bare protein-binding rows it supports are removed under the GO:0005515 policy. Retained as the source of those GOA rows. - id: PMID:33961781 title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: High-throughput interactome screen; the bare protein-binding rows it supports are removed under the GO:0005515 policy. Retained as the source of those GOA rows. - id: PMID:40205054 title: Multimodal cell maps as a foundation for structural and functional genomics. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: High-throughput interactome screen; the bare protein-binding rows it supports are removed under the GO:0005515 policy. Retained as the source of those GOA rows. - id: Reactome:R-HSA-1791130 title: Expression of CTDSP2 findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: Generic gene-expression event; source of the nucleoplasm TAS only. - id: file:human/CTDSP2/CTDSP2-uniprot.txt title: 'UniProtKB O14595: human CTDSP2 sequence and curated catalytic features' findings: [] - id: PMID:15681389 title: Small CTD phosphatases function in silencing neuronal gene expression. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: REST recruits SCP1-3 to RE-1 neuronal genes; family-level, cited by UniProt for CTDSP2. - id: PMID:25990325 title: FOXO target gene CTDSP2 regulates cell cycle progression through Ras and p21(Cip1/Waf1). findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: CTDSP2 as FOXO target; cell-cycle arrest on overexpression, dependent on phosphatase activity. Overexpression phenotypes, not used for process annotation. - id: PMID:22210897 title: MicroRNA-26a/b and their host genes cooperate to inhibit the G1/S transition by activating the pRb protein. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: miR-26a/b host gene co-regulation with CTDSP family; G1/S effects are combined miRNA+host gene gain/loss of function and are not used for annotation. core_functions: - description: Mg2+-dependent, aspartate-nucleophile dephosphorylation of phospho-Ser5 in the RNA polymerase II CTD heptad repeats at promoters, restraining promoter clearance and repressing transcription of target genes (for example AR- and REST-regulated genes). molecular_function: id: GO:0008420 label: RNA polymerase II CTD heptapeptide repeat phosphatase activity locations: - id: GO:0005654 label: nucleoplasm directly_involved_in: - id: GO:0000122 label: negative regulation of transcription by RNA polymerase II - id: GO:0006470 label: protein dephosphorylation supported_by: - *id005 - *id008 - *id009 - *id004 - *id006 - description: Dephosphorylation of the receptor-phosphorylated C-terminal serines of Smad1 in the nucleus, terminating BMP-Smad1 signalling. molecular_function: id: GO:0004722 label: protein serine/threonine phosphatase activity locations: - id: GO:0005634 label: nucleus directly_involved_in: - id: GO:0030514 label: negative regulation of BMP signaling pathway - id: GO:0006470 label: protein dephosphorylation supported_by: - *id001 - *id010 - *id002 suggested_questions: - question: None of the SCP paralogs (CTDSP1, CTDSP2, CTDSPL) carries a BMP-signalling process annotation despite PMID:16882717; should GO curators annotate negative regulation of BMP signaling pathway to the family, and is it inherited from the SCP ancestral node? - question: Which genes in non-neuronal cells depend specifically on CTDSP2 rather than on redundant CTDSP1/CTDSPL for CTD Ser5 dephosphorylation? suggested_experiments: - description: CTDSP2-only knockout (versus CTDSP1/CTDSPL single and compound knockouts) in a BMP-responsive cell line, with phospho-Smad1 kinetics and catalytic-dead (D107A) rescue, to separate CTDSP2-specific from redundant SCP activity.